{"mention": "Naloxone", "mention_text": "Naloxone reverses the antihypertensive effect of clonidine.", "entity": "Naloxone", "aliases": "Abello Brand of Naloxone Hydrochloride Boots Bristol Myers Squibb Bristol-Myers Curamed Naloxon Dihydride Endo Hydrobromide Lamepro MRZ 2593 Br 2593-Br 2593Br MRZ-2593 MRZ2593 Nalone ratiopharm Naloxon-ratiopharm (5 beta,9 alpha,13 alpha,14 alpha)-Isomer Naloxonratiopharm Narcan Narcanti SERB United Drug", "definition": "A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.\n    ", "id": "MESH:D009270"}
{"mention": "clonidine", "mention_text": "Naloxone reverses the antihypertensive effect of clonidine.", "entity": "Clonidine", "aliases": "Boehringer Ingelheim Brand of Clonidine Hydrochloride Catapres Catapresan Catapressan Chlophazolin Clofelin Clofenil Dihydrochloride Monohydrobromide Monohydrochloride Clopheline Dixarit Gemiton Hemiton Isoglaucon Klofelin Klofenil M 5041T M-5041T M5041T ST 155 ST-155 ST155", "definition": "An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.\n    ", "id": "MESH:D003000"}
{"mention": "hypertensive", "mention_text": "In unanesthetized, spontaneously hypertensive rats the decrease in blood pressure and heart rate produced by intravenous clonidine, 5 to 20 micrograms/kg, was inhibited or reversed by nalozone, 0.2 to 2 mg/kg. The hypotensive effect of 100 mg/kg alpha-methyldopa was also partially reversed by naloxone. Naloxone alone did not affect either blood pressure or heart rate. In brain membranes from spontaneously hypertensive rats clonidine, 10(-8) to 10(-5) M, did not influence stereoselective binding of [3H]-naloxone (8 nM), and naloxone, 10(-8) to 10(-4) M, did not influence clonidine-suppressible binding of [3H]-dihydroergocryptine (1 nM). These findings indicate that in spontaneously hypertensive rats the effects of central alpha-adrenoceptor stimulation involve activation of opiate receptors. As naloxone and clonidine do not appear to interact with the same receptor site, the observed functional antagonism suggests the release of an endogenous opiate by clonidine or alpha-methyldopa and the possible role of the opiate in the central control of sympathetic tone.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "clonidine", "mention_text": "In unanesthetized, spontaneously hypertensive rats the decrease in blood pressure and heart rate produced by intravenous clonidine, 5 to 20 micrograms/kg, was inhibited or reversed by nalozone, 0.2 to 2 mg/kg. The hypotensive effect of 100 mg/kg alpha-methyldopa was also partially reversed by naloxone. Naloxone alone did not affect either blood pressure or heart rate. In brain membranes from spontaneously hypertensive rats clonidine, 10(-8) to 10(-5) M, did not influence stereoselective binding of [3H]-naloxone (8 nM), and naloxone, 10(-8) to 10(-4) M, did not influence clonidine-suppressible binding of [3H]-dihydroergocryptine (1 nM). These findings indicate that in spontaneously hypertensive rats the effects of central alpha-adrenoceptor stimulation involve activation of opiate receptors. As naloxone and clonidine do not appear to interact with the same receptor site, the observed functional antagonism suggests the release of an endogenous opiate by clonidine or alpha-methyldopa and the possible role of the opiate in the central control of sympathetic tone.", "entity": "Clonidine", "aliases": "Boehringer Ingelheim Brand of Clonidine Hydrochloride Catapres Catapresan Catapressan Chlophazolin Clofelin Clofenil Dihydrochloride Monohydrobromide Monohydrochloride Clopheline Dixarit Gemiton Hemiton Isoglaucon Klofelin Klofenil M 5041T M-5041T M5041T ST 155 ST-155 ST155", "definition": "An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.\n    ", "id": "MESH:D003000"}
{"mention": "hypotensive", "mention_text": "In unanesthetized, spontaneously hypertensive rats the decrease in blood pressure and heart rate produced by intravenous clonidine, 5 to 20 micrograms/kg, was inhibited or reversed by nalozone, 0.2 to 2 mg/kg. The hypotensive effect of 100 mg/kg alpha-methyldopa was also partially reversed by naloxone. Naloxone alone did not affect either blood pressure or heart rate. In brain membranes from spontaneously hypertensive rats clonidine, 10(-8) to 10(-5) M, did not influence stereoselective binding of [3H]-naloxone (8 nM), and naloxone, 10(-8) to 10(-4) M, did not influence clonidine-suppressible binding of [3H]-dihydroergocryptine (1 nM). These findings indicate that in spontaneously hypertensive rats the effects of central alpha-adrenoceptor stimulation involve activation of opiate receptors. As naloxone and clonidine do not appear to interact with the same receptor site, the observed functional antagonism suggests the release of an endogenous opiate by clonidine or alpha-methyldopa and the possible role of the opiate in the central control of sympathetic tone.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "alpha-methyldopa", "mention_text": "In unanesthetized, spontaneously hypertensive rats the decrease in blood pressure and heart rate produced by intravenous clonidine, 5 to 20 micrograms/kg, was inhibited or reversed by nalozone, 0.2 to 2 mg/kg. The hypotensive effect of 100 mg/kg alpha-methyldopa was also partially reversed by naloxone. Naloxone alone did not affect either blood pressure or heart rate. In brain membranes from spontaneously hypertensive rats clonidine, 10(-8) to 10(-5) M, did not influence stereoselective binding of [3H]-naloxone (8 nM), and naloxone, 10(-8) to 10(-4) M, did not influence clonidine-suppressible binding of [3H]-dihydroergocryptine (1 nM). These findings indicate that in spontaneously hypertensive rats the effects of central alpha-adrenoceptor stimulation involve activation of opiate receptors. As naloxone and clonidine do not appear to interact with the same receptor site, the observed functional antagonism suggests the release of an endogenous opiate by clonidine or alpha-methyldopa and the possible role of the opiate in the central control of sympathetic tone.", "entity": "Methyldopa", "aliases": "Aldomet Alphamethyldopa Alphapharm Brand of Methyldopa Apo Apo-Methyldopa Apotex Biopat Cahill May Roberts Clonmel Dopamet Dopegit Dopegyt Dopergit Hydopa Meldopa Merck Sharp & Dohme Nu-Pharm Orion Methyldopate Nu Medopa Pharm Nu-Medopa Rhône Poulenc Rorer Rhône-Poulenc Sembrina alpha Methyl L Dopa alpha-Methyl-L-Dopa alpha-Methyldopa", "definition": "An alpha-2 adrenergic agonist that has both central and peripheral nervous system effects. Its primary clinical use is as an antihypertensive agent.\n    ", "id": "MESH:D008750"}
{"mention": "naloxone", "mention_text": "In unanesthetized, spontaneously hypertensive rats the decrease in blood pressure and heart rate produced by intravenous clonidine, 5 to 20 micrograms/kg, was inhibited or reversed by nalozone, 0.2 to 2 mg/kg. The hypotensive effect of 100 mg/kg alpha-methyldopa was also partially reversed by naloxone. Naloxone alone did not affect either blood pressure or heart rate. In brain membranes from spontaneously hypertensive rats clonidine, 10(-8) to 10(-5) M, did not influence stereoselective binding of [3H]-naloxone (8 nM), and naloxone, 10(-8) to 10(-4) M, did not influence clonidine-suppressible binding of [3H]-dihydroergocryptine (1 nM). These findings indicate that in spontaneously hypertensive rats the effects of central alpha-adrenoceptor stimulation involve activation of opiate receptors. As naloxone and clonidine do not appear to interact with the same receptor site, the observed functional antagonism suggests the release of an endogenous opiate by clonidine or alpha-methyldopa and the possible role of the opiate in the central control of sympathetic tone.", "entity": "Naloxone", "aliases": "Abello Brand of Naloxone Hydrochloride Boots Bristol Myers Squibb Bristol-Myers Curamed Naloxon Dihydride Endo Hydrobromide Lamepro MRZ 2593 Br 2593-Br 2593Br MRZ-2593 MRZ2593 Nalone ratiopharm Naloxon-ratiopharm (5 beta,9 alpha,13 alpha,14 alpha)-Isomer Naloxonratiopharm Narcan Narcanti SERB United Drug", "definition": "A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.\n    ", "id": "MESH:D009270"}
{"mention": "Naloxone", "mention_text": "In unanesthetized, spontaneously hypertensive rats the decrease in blood pressure and heart rate produced by intravenous clonidine, 5 to 20 micrograms/kg, was inhibited or reversed by nalozone, 0.2 to 2 mg/kg. The hypotensive effect of 100 mg/kg alpha-methyldopa was also partially reversed by naloxone. Naloxone alone did not affect either blood pressure or heart rate. In brain membranes from spontaneously hypertensive rats clonidine, 10(-8) to 10(-5) M, did not influence stereoselective binding of [3H]-naloxone (8 nM), and naloxone, 10(-8) to 10(-4) M, did not influence clonidine-suppressible binding of [3H]-dihydroergocryptine (1 nM). These findings indicate that in spontaneously hypertensive rats the effects of central alpha-adrenoceptor stimulation involve activation of opiate receptors. As naloxone and clonidine do not appear to interact with the same receptor site, the observed functional antagonism suggests the release of an endogenous opiate by clonidine or alpha-methyldopa and the possible role of the opiate in the central control of sympathetic tone.", "entity": "Naloxone", "aliases": "Abello Brand of Naloxone Hydrochloride Boots Bristol Myers Squibb Bristol-Myers Curamed Naloxon Dihydride Endo Hydrobromide Lamepro MRZ 2593 Br 2593-Br 2593Br MRZ-2593 MRZ2593 Nalone ratiopharm Naloxon-ratiopharm (5 beta,9 alpha,13 alpha,14 alpha)-Isomer Naloxonratiopharm Narcan Narcanti SERB United Drug", "definition": "A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.\n    ", "id": "MESH:D009270"}
{"mention": "Lidocaine", "mention_text": "Lidocaine-induced cardiac asystole.", "entity": "Lidocaine", "aliases": "2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide 2-2EtN-2MePhAcN Astrazeneca Brand of Lidocaine Dalcaine Jenapharm Lidocanine Hydrochloride Carbonate (2:1) Hydrocarbonate Monoacetate Monohydrochloride Monohydrate Sulfate (1:1) Lignocaine Novocol Octocaine Strathmann Xylesthesin Xylocaine Xylocitin Xyloneural", "definition": "A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.\n    ", "id": "MESH:D008012"}
{"mention": "cardiac asystole", "mention_text": "Lidocaine-induced cardiac asystole.", "entity": "Heart Arrest", "aliases": "Arrest Cardiac Cardiopulmonary Heart Asystole Asystoles", "definition": "Cessation of heart beat or MYOCARDIAL CONTRACTION. If it is treated within a few minutes, heart arrest can be reversed in most cases to normal cardiac rhythm and effective circulation.\n    ", "id": "MESH:D006323"}
{"mention": "lidocaine", "mention_text": "Intravenous administration of a single 50-mg bolus of lidocaine in a 67-year-old man resulted in profound depression of the activity of the sinoatrial and atrioventricular nodal pacemakers. The patient had no apparent associated conditions which might have predisposed him to the development of bradyarrhythmias; and, thus, this probably represented a true idiosyncrasy to lidocaine.", "entity": "Lidocaine", "aliases": "2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide 2-2EtN-2MePhAcN Astrazeneca Brand of Lidocaine Dalcaine Jenapharm Lidocanine Hydrochloride Carbonate (2:1) Hydrocarbonate Monoacetate Monohydrochloride Monohydrate Sulfate (1:1) Lignocaine Novocol Octocaine Strathmann Xylesthesin Xylocaine Xylocitin Xyloneural", "definition": "A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.\n    ", "id": "MESH:D008012"}
{"mention": "depression", "mention_text": "Intravenous administration of a single 50-mg bolus of lidocaine in a 67-year-old man resulted in profound depression of the activity of the sinoatrial and atrioventricular nodal pacemakers. The patient had no apparent associated conditions which might have predisposed him to the development of bradyarrhythmias; and, thus, this probably represented a true idiosyncrasy to lidocaine.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "bradyarrhythmias", "mention_text": "Intravenous administration of a single 50-mg bolus of lidocaine in a 67-year-old man resulted in profound depression of the activity of the sinoatrial and atrioventricular nodal pacemakers. The patient had no apparent associated conditions which might have predisposed him to the development of bradyarrhythmias; and, thus, this probably represented a true idiosyncrasy to lidocaine.", "entity": "Bradycardia", "aliases": "Bradyarrhythmia Bradyarrhythmias Bradycardia Bradycardias", "definition": "Cardiac arrhythmias that are characterized by excessively slow HEART RATE, usually below 50 beats per minute in human adults. They can be classified broadly into SINOATRIAL NODE dysfunction and ATRIOVENTRICULAR BLOCK.\n    ", "id": "MESH:D001919"}
{"mention": "Suxamethonium", "mention_text": "Suxamethonium infusion rate and observed fasciculations. A dose-response study.", "entity": "Succinylcholine", "aliases": "Anectine Bromide Suxamethonium Celocurine Dibromide Succinylcholine Dichloride Diiodide Diperchlorate Ditilin Listenon Lysthenon Myorelaxin Quelicin Succicuran Chloride Di H2O Di-H2O Iodide Succinyldicholine", "definition": "A quaternary skeletal muscle relaxant usually used in the form of its bromide, chloride, or iodide. It is a depolarizing relaxant, acting in about 30 seconds and with a duration of effect averaging three to five minutes. Succinylcholine is used in surgical, anesthetic, and other procedures in which a brief period of muscle relaxation is called for.\n    ", "id": "MESH:D013390"}
{"mention": "fasciculations", "mention_text": "Suxamethonium infusion rate and observed fasciculations. A dose-response study.", "entity": "Fasciculation", "aliases": "Benign Fasciculation Fasciculations Muscular Neural Skeletal Muscle Tongue", "definition": "Involuntary contraction of the muscle fibers innervated by a motor unit. Fasciculations can often by visualized and take the form of a muscle twitch or dimpling under the skin, but usually do not generate sufficient force to move a limb. They may represent a benign condition or occur as a manifestation of MOTOR NEURON DISEASE or PERIPHERAL NERVOUS SYSTEM DISEASES. (Adams et al., Principles of Neurology, 6th ed, p1294)\n    ", "id": "MESH:D005207"}
{"mention": "Suxamethonium chloride", "mention_text": "Suxamethonium chloride (Sch) was administered i.v. to 36 adult males at six rates: 0.25 mg s-1 to 20 mg s-1. The infusion was discontinued either when there was no muscular response to tetanic stimulation of the ulnar nerve or when Sch 120 mg was exceeded. Six additional patients received a 30-mg i.v. bolus dose. Fasciculations in six areas of the body were scored from 0 to 3 and summated as a total fasciculation score. The times to first fasciculation, twitch suppression and tetanus suppression were inversely related to the infusion rates. Fasciculations in the six areas and the total fasciculation score were related directly to the rate of infusion. Total fasciculation scores in the 30-mg bolus group and the 5-mg s-1 and 20-mg s-1 infusion groups were not significantly different.", "entity": "Succinylcholine", "aliases": "Anectine Bromide Suxamethonium Celocurine Dibromide Succinylcholine Dichloride Diiodide Diperchlorate Ditilin Listenon Lysthenon Myorelaxin Quelicin Succicuran Chloride Di H2O Di-H2O Iodide Succinyldicholine", "definition": "A quaternary skeletal muscle relaxant usually used in the form of its bromide, chloride, or iodide. It is a depolarizing relaxant, acting in about 30 seconds and with a duration of effect averaging three to five minutes. Succinylcholine is used in surgical, anesthetic, and other procedures in which a brief period of muscle relaxation is called for.\n    ", "id": "MESH:D013390"}
{"mention": "Sch", "mention_text": "Suxamethonium chloride (Sch) was administered i.v. to 36 adult males at six rates: 0.25 mg s-1 to 20 mg s-1. The infusion was discontinued either when there was no muscular response to tetanic stimulation of the ulnar nerve or when Sch 120 mg was exceeded. Six additional patients received a 30-mg i.v. bolus dose. Fasciculations in six areas of the body were scored from 0 to 3 and summated as a total fasciculation score. The times to first fasciculation, twitch suppression and tetanus suppression were inversely related to the infusion rates. Fasciculations in the six areas and the total fasciculation score were related directly to the rate of infusion. Total fasciculation scores in the 30-mg bolus group and the 5-mg s-1 and 20-mg s-1 infusion groups were not significantly different.", "entity": "Succinylcholine", "aliases": "Anectine Bromide Suxamethonium Celocurine Dibromide Succinylcholine Dichloride Diiodide Diperchlorate Ditilin Listenon Lysthenon Myorelaxin Quelicin Succicuran Chloride Di H2O Di-H2O Iodide Succinyldicholine", "definition": "A quaternary skeletal muscle relaxant usually used in the form of its bromide, chloride, or iodide. It is a depolarizing relaxant, acting in about 30 seconds and with a duration of effect averaging three to five minutes. Succinylcholine is used in surgical, anesthetic, and other procedures in which a brief period of muscle relaxation is called for.\n    ", "id": "MESH:D013390"}
{"mention": "tetanic", "mention_text": "Suxamethonium chloride (Sch) was administered i.v. to 36 adult males at six rates: 0.25 mg s-1 to 20 mg s-1. The infusion was discontinued either when there was no muscular response to tetanic stimulation of the ulnar nerve or when Sch 120 mg was exceeded. Six additional patients received a 30-mg i.v. bolus dose. Fasciculations in six areas of the body were scored from 0 to 3 and summated as a total fasciculation score. The times to first fasciculation, twitch suppression and tetanus suppression were inversely related to the infusion rates. Fasciculations in the six areas and the total fasciculation score were related directly to the rate of infusion. Total fasciculation scores in the 30-mg bolus group and the 5-mg s-1 and 20-mg s-1 infusion groups were not significantly different.", "entity": "Tetany", "aliases": "Neonatal Tetanies Tetany Spasmophilia Spasmophilias Tetanilla Tetanillas", "definition": "A disorder characterized by muscle twitches, cramps, and carpopedal spasm, and when severe, laryngospasm and seizures. This condition is associated with unstable depolarization of axonal membranes, primarily in the peripheral nervous system. Tetany usually results from HYPOCALCEMIA or reduced serum levels of MAGNESIUM that may be associated with HYPERVENTILATION; HYPOPARATHYROIDISM; RICKETS; UREMIA; or other conditions. (From Adams et al., Principles of Neurology, 6th ed, p1490)\n    ", "id": "MESH:D013746"}
{"mention": "Fasciculations", "mention_text": "Suxamethonium chloride (Sch) was administered i.v. to 36 adult males at six rates: 0.25 mg s-1 to 20 mg s-1. The infusion was discontinued either when there was no muscular response to tetanic stimulation of the ulnar nerve or when Sch 120 mg was exceeded. Six additional patients received a 30-mg i.v. bolus dose. Fasciculations in six areas of the body were scored from 0 to 3 and summated as a total fasciculation score. The times to first fasciculation, twitch suppression and tetanus suppression were inversely related to the infusion rates. Fasciculations in the six areas and the total fasciculation score were related directly to the rate of infusion. Total fasciculation scores in the 30-mg bolus group and the 5-mg s-1 and 20-mg s-1 infusion groups were not significantly different.", "entity": "Fasciculation", "aliases": "Benign Fasciculation Fasciculations Muscular Neural Skeletal Muscle Tongue", "definition": "Involuntary contraction of the muscle fibers innervated by a motor unit. Fasciculations can often by visualized and take the form of a muscle twitch or dimpling under the skin, but usually do not generate sufficient force to move a limb. They may represent a benign condition or occur as a manifestation of MOTOR NEURON DISEASE or PERIPHERAL NERVOUS SYSTEM DISEASES. (Adams et al., Principles of Neurology, 6th ed, p1294)\n    ", "id": "MESH:D005207"}
{"mention": "fasciculation", "mention_text": "Suxamethonium chloride (Sch) was administered i.v. to 36 adult males at six rates: 0.25 mg s-1 to 20 mg s-1. The infusion was discontinued either when there was no muscular response to tetanic stimulation of the ulnar nerve or when Sch 120 mg was exceeded. Six additional patients received a 30-mg i.v. bolus dose. Fasciculations in six areas of the body were scored from 0 to 3 and summated as a total fasciculation score. The times to first fasciculation, twitch suppression and tetanus suppression were inversely related to the infusion rates. Fasciculations in the six areas and the total fasciculation score were related directly to the rate of infusion. Total fasciculation scores in the 30-mg bolus group and the 5-mg s-1 and 20-mg s-1 infusion groups were not significantly different.", "entity": "Fasciculation", "aliases": "Benign Fasciculation Fasciculations Muscular Neural Skeletal Muscle Tongue", "definition": "Involuntary contraction of the muscle fibers innervated by a motor unit. Fasciculations can often by visualized and take the form of a muscle twitch or dimpling under the skin, but usually do not generate sufficient force to move a limb. They may represent a benign condition or occur as a manifestation of MOTOR NEURON DISEASE or PERIPHERAL NERVOUS SYSTEM DISEASES. (Adams et al., Principles of Neurology, 6th ed, p1294)\n    ", "id": "MESH:D005207"}
{"mention": "twitch", "mention_text": "Suxamethonium chloride (Sch) was administered i.v. to 36 adult males at six rates: 0.25 mg s-1 to 20 mg s-1. The infusion was discontinued either when there was no muscular response to tetanic stimulation of the ulnar nerve or when Sch 120 mg was exceeded. Six additional patients received a 30-mg i.v. bolus dose. Fasciculations in six areas of the body were scored from 0 to 3 and summated as a total fasciculation score. The times to first fasciculation, twitch suppression and tetanus suppression were inversely related to the infusion rates. Fasciculations in the six areas and the total fasciculation score were related directly to the rate of infusion. Total fasciculation scores in the 30-mg bolus group and the 5-mg s-1 and 20-mg s-1 infusion groups were not significantly different.", "entity": "Tetany", "aliases": "Neonatal Tetanies Tetany Spasmophilia Spasmophilias Tetanilla Tetanillas", "definition": "A disorder characterized by muscle twitches, cramps, and carpopedal spasm, and when severe, laryngospasm and seizures. This condition is associated with unstable depolarization of axonal membranes, primarily in the peripheral nervous system. Tetany usually results from HYPOCALCEMIA or reduced serum levels of MAGNESIUM that may be associated with HYPERVENTILATION; HYPOPARATHYROIDISM; RICKETS; UREMIA; or other conditions. (From Adams et al., Principles of Neurology, 6th ed, p1490)\n    ", "id": "MESH:D013746"}
{"mention": "tetanus", "mention_text": "Suxamethonium chloride (Sch) was administered i.v. to 36 adult males at six rates: 0.25 mg s-1 to 20 mg s-1. The infusion was discontinued either when there was no muscular response to tetanic stimulation of the ulnar nerve or when Sch 120 mg was exceeded. Six additional patients received a 30-mg i.v. bolus dose. Fasciculations in six areas of the body were scored from 0 to 3 and summated as a total fasciculation score. The times to first fasciculation, twitch suppression and tetanus suppression were inversely related to the infusion rates. Fasciculations in the six areas and the total fasciculation score were related directly to the rate of infusion. Total fasciculation scores in the 30-mg bolus group and the 5-mg s-1 and 20-mg s-1 infusion groups were not significantly different.", "entity": "Tetany", "aliases": "Neonatal Tetanies Tetany Spasmophilia Spasmophilias Tetanilla Tetanillas", "definition": "A disorder characterized by muscle twitches, cramps, and carpopedal spasm, and when severe, laryngospasm and seizures. This condition is associated with unstable depolarization of axonal membranes, primarily in the peripheral nervous system. Tetany usually results from HYPOCALCEMIA or reduced serum levels of MAGNESIUM that may be associated with HYPERVENTILATION; HYPOPARATHYROIDISM; RICKETS; UREMIA; or other conditions. (From Adams et al., Principles of Neurology, 6th ed, p1490)\n    ", "id": "MESH:D013746"}
{"mention": "Galanthamine hydrobromide", "mention_text": "Galanthamine hydrobromide, a longer acting anticholinesterase drug, in the treatment of the central effects of scopolamine (Hyoscine).", "entity": "Galantamine", "aliases": "Galantamin Galantamine Galanthamine Hydrobromide Lycoremine Nivalin Nivaline Ortho McNeil Neurologics Brand of Ortho-McNeil Razadyne Reminyl", "definition": "A benzazepine derived from norbelladine. It is found in GALANTHUS and other AMARYLLIDACEAE. It is a cholinesterase inhibitor that has been used to reverse the muscular effects of GALLAMINE TRIETHIODIDE and TUBOCURARINE and has been studied as a treatment for ALZHEIMER DISEASE and other central nervous system disorders.\n    ", "id": "MESH:D005702"}
{"mention": "scopolamine", "mention_text": "Galanthamine hydrobromide, a longer acting anticholinesterase drug, in the treatment of the central effects of scopolamine (Hyoscine).", "entity": "Scopolamine Hydrobromide", "aliases": "Alcon Brand of Scopolamine Hydrobromide Boro Scopol Boro-Scopol BoroScopol Bull Cooper Hamilton Hope Hyoscine Inibisa Isopto Kwells Novartis Consumer Health Renaudin Roche Scoburen Scopace Scopoderm TTS Transderm Scop V Transderm-V Travacalm HO Vorigeno Winzer Borate", "definition": "An alkaloid from SOLANACEAE, especially DATURA and SCOPOLIA. Scopolamine and its quaternary derivatives act as antimuscarinics like ATROPINE, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in URINARY INCONTINENCE, in MOTION SICKNESS, as an antispasmodic, and as a mydriatic and cycloplegic.\n    ", "id": "MESH:D012601"}
{"mention": "Hyoscine", "mention_text": "Galanthamine hydrobromide, a longer acting anticholinesterase drug, in the treatment of the central effects of scopolamine (Hyoscine).", "entity": "Scopolamine Hydrobromide", "aliases": "Alcon Brand of Scopolamine Hydrobromide Boro Scopol Boro-Scopol BoroScopol Bull Cooper Hamilton Hope Hyoscine Inibisa Isopto Kwells Novartis Consumer Health Renaudin Roche Scoburen Scopace Scopoderm TTS Transderm Scop V Transderm-V Travacalm HO Vorigeno Winzer Borate", "definition": "An alkaloid from SOLANACEAE, especially DATURA and SCOPOLIA. Scopolamine and its quaternary derivatives act as antimuscarinics like ATROPINE, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in URINARY INCONTINENCE, in MOTION SICKNESS, as an antispasmodic, and as a mydriatic and cycloplegic.\n    ", "id": "MESH:D012601"}
{"mention": "Galanthamine hydrobromide", "mention_text": "Galanthamine hydrobromide, an anticholinesterase drug capable of penetrating the blood-brain barrier, was used in a patient demonstrating central effects of scopolamine (hyoscine) overdosage. It is longer acting than physostigmine and is used in anaesthesia to reverse the non-depolarizing neuromuscular block. However, studies into the dose necessary to combating scopolamine intoxication are indicated.", "entity": "Galantamine", "aliases": "Galantamin Galantamine Galanthamine Hydrobromide Lycoremine Nivalin Nivaline Ortho McNeil Neurologics Brand of Ortho-McNeil Razadyne Reminyl", "definition": "A benzazepine derived from norbelladine. It is found in GALANTHUS and other AMARYLLIDACEAE. It is a cholinesterase inhibitor that has been used to reverse the muscular effects of GALLAMINE TRIETHIODIDE and TUBOCURARINE and has been studied as a treatment for ALZHEIMER DISEASE and other central nervous system disorders.\n    ", "id": "MESH:D005702"}
{"mention": "scopolamine", "mention_text": "Galanthamine hydrobromide, an anticholinesterase drug capable of penetrating the blood-brain barrier, was used in a patient demonstrating central effects of scopolamine (hyoscine) overdosage. It is longer acting than physostigmine and is used in anaesthesia to reverse the non-depolarizing neuromuscular block. However, studies into the dose necessary to combating scopolamine intoxication are indicated.", "entity": "Scopolamine Hydrobromide", "aliases": "Alcon Brand of Scopolamine Hydrobromide Boro Scopol Boro-Scopol BoroScopol Bull Cooper Hamilton Hope Hyoscine Inibisa Isopto Kwells Novartis Consumer Health Renaudin Roche Scoburen Scopace Scopoderm TTS Transderm Scop V Transderm-V Travacalm HO Vorigeno Winzer Borate", "definition": "An alkaloid from SOLANACEAE, especially DATURA and SCOPOLIA. Scopolamine and its quaternary derivatives act as antimuscarinics like ATROPINE, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in URINARY INCONTINENCE, in MOTION SICKNESS, as an antispasmodic, and as a mydriatic and cycloplegic.\n    ", "id": "MESH:D012601"}
{"mention": "hyoscine", "mention_text": "Galanthamine hydrobromide, an anticholinesterase drug capable of penetrating the blood-brain barrier, was used in a patient demonstrating central effects of scopolamine (hyoscine) overdosage. It is longer acting than physostigmine and is used in anaesthesia to reverse the non-depolarizing neuromuscular block. However, studies into the dose necessary to combating scopolamine intoxication are indicated.", "entity": "Scopolamine Hydrobromide", "aliases": "Alcon Brand of Scopolamine Hydrobromide Boro Scopol Boro-Scopol BoroScopol Bull Cooper Hamilton Hope Hyoscine Inibisa Isopto Kwells Novartis Consumer Health Renaudin Roche Scoburen Scopace Scopoderm TTS Transderm Scop V Transderm-V Travacalm HO Vorigeno Winzer Borate", "definition": "An alkaloid from SOLANACEAE, especially DATURA and SCOPOLIA. Scopolamine and its quaternary derivatives act as antimuscarinics like ATROPINE, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in URINARY INCONTINENCE, in MOTION SICKNESS, as an antispasmodic, and as a mydriatic and cycloplegic.\n    ", "id": "MESH:D012601"}
{"mention": "overdosage", "mention_text": "Galanthamine hydrobromide, an anticholinesterase drug capable of penetrating the blood-brain barrier, was used in a patient demonstrating central effects of scopolamine (hyoscine) overdosage. It is longer acting than physostigmine and is used in anaesthesia to reverse the non-depolarizing neuromuscular block. However, studies into the dose necessary to combating scopolamine intoxication are indicated.", "entity": "Drug Overdose", "aliases": "Drug Overdose Overdoses", "definition": "Accidental or deliberate use of a medication or street drug in excess of normal dosage.\n    ", "id": "MESH:D062787"}
{"mention": "physostigmine", "mention_text": "Galanthamine hydrobromide, an anticholinesterase drug capable of penetrating the blood-brain barrier, was used in a patient demonstrating central effects of scopolamine (hyoscine) overdosage. It is longer acting than physostigmine and is used in anaesthesia to reverse the non-depolarizing neuromuscular block. However, studies into the dose necessary to combating scopolamine intoxication are indicated.", "entity": "Physostigmine", "aliases": "Eserine Physostigmine", "definition": "A cholinesterase inhibitor that is rapidly absorbed through membranes. It can be applied topically to the conjunctiva. It also can cross the blood-brain barrier and is used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity.\n    ", "id": "MESH:D010830"}
{"mention": "lithium", "mention_text": "Effects of uninephrectomy and high protein feeding on lithium-induced chronic renal failure in rats.", "entity": "Lithium", "aliases": "Lithium", "definition": "An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.\n    ", "id": "MESH:D008094"}
{"mention": "chronic renal failure", "mention_text": "Effects of uninephrectomy and high protein feeding on lithium-induced chronic renal failure in rats.", "entity": "Kidney Failure, Chronic", "aliases": "Chronic Kidney Failure Renal Disease End-Stage ESRD End Stage", "definition": "The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.\n    ", "id": "MESH:D007676"}
{"mention": "lithium", "mention_text": "Rats with lithium-induced nephropathy were subjected to high protein (HP) feeding, uninephrectomy (NX) or a combination of these, in an attempt to induce glomerular hyperfiltration and further progression of renal failure. Newborn female Wistar rats were fed a lithium-containing diet (50 mmol/kg) for 8 weeks and then randomized to normal diet, HP diet (40 vs. 19%), NX or HP+NX for another 8 weeks. Corresponding non-lithium pretreated groups were generated. When comparing all lithium treated versus non-lithium-treated groups, lithium caused a reduction in glomerular filtration rate (GFR) without significant changes in effective renal plasma flow (as determined by a marker secreted into the proximal tubules) or lithium clearance. Consequently, lithium pretreatment caused a fall in filtration fraction and an increase in fractional Li excretion. Lithium also caused proteinuria and systolic hypertension in absence of glomerulosclerosis. HP failed to accentuante progression of renal failure and in fact tended to increase GFR and decrease plasma creatinine levels in lithium pretreated rats. NX caused an additive deterioration in GFR which, however, was ameliorated by HP. NX+HP caused a further rise in blood pressure in Li-pretreated rats. The results indicate that Li-induced nephropathy, even when the GFR is only modestly reduced, is associated with proteinuria and arterial systolic hypertension. In this model of chronic renal failure the decline in GFR is not accompanied by a corresponding fall in effective renal plasma flow, which may be the functional expression of the formation of nonfiltrating atubular glomeruli. The fractional reabsorption of tubular fluid by the proximal tubules is reduced, leaving the distal delivery unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Lithium", "aliases": "Lithium", "definition": "An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.\n    ", "id": "MESH:D008094"}
{"mention": "nephropathy", "mention_text": "Rats with lithium-induced nephropathy were subjected to high protein (HP) feeding, uninephrectomy (NX) or a combination of these, in an attempt to induce glomerular hyperfiltration and further progression of renal failure. Newborn female Wistar rats were fed a lithium-containing diet (50 mmol/kg) for 8 weeks and then randomized to normal diet, HP diet (40 vs. 19%), NX or HP+NX for another 8 weeks. Corresponding non-lithium pretreated groups were generated. When comparing all lithium treated versus non-lithium-treated groups, lithium caused a reduction in glomerular filtration rate (GFR) without significant changes in effective renal plasma flow (as determined by a marker secreted into the proximal tubules) or lithium clearance. Consequently, lithium pretreatment caused a fall in filtration fraction and an increase in fractional Li excretion. Lithium also caused proteinuria and systolic hypertension in absence of glomerulosclerosis. HP failed to accentuante progression of renal failure and in fact tended to increase GFR and decrease plasma creatinine levels in lithium pretreated rats. NX caused an additive deterioration in GFR which, however, was ameliorated by HP. NX+HP caused a further rise in blood pressure in Li-pretreated rats. The results indicate that Li-induced nephropathy, even when the GFR is only modestly reduced, is associated with proteinuria and arterial systolic hypertension. In this model of chronic renal failure the decline in GFR is not accompanied by a corresponding fall in effective renal plasma flow, which may be the functional expression of the formation of nonfiltrating atubular glomeruli. The fractional reabsorption of tubular fluid by the proximal tubules is reduced, leaving the distal delivery unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "renal failure", "mention_text": "Rats with lithium-induced nephropathy were subjected to high protein (HP) feeding, uninephrectomy (NX) or a combination of these, in an attempt to induce glomerular hyperfiltration and further progression of renal failure. Newborn female Wistar rats were fed a lithium-containing diet (50 mmol/kg) for 8 weeks and then randomized to normal diet, HP diet (40 vs. 19%), NX or HP+NX for another 8 weeks. Corresponding non-lithium pretreated groups were generated. When comparing all lithium treated versus non-lithium-treated groups, lithium caused a reduction in glomerular filtration rate (GFR) without significant changes in effective renal plasma flow (as determined by a marker secreted into the proximal tubules) or lithium clearance. Consequently, lithium pretreatment caused a fall in filtration fraction and an increase in fractional Li excretion. Lithium also caused proteinuria and systolic hypertension in absence of glomerulosclerosis. HP failed to accentuante progression of renal failure and in fact tended to increase GFR and decrease plasma creatinine levels in lithium pretreated rats. NX caused an additive deterioration in GFR which, however, was ameliorated by HP. NX+HP caused a further rise in blood pressure in Li-pretreated rats. The results indicate that Li-induced nephropathy, even when the GFR is only modestly reduced, is associated with proteinuria and arterial systolic hypertension. In this model of chronic renal failure the decline in GFR is not accompanied by a corresponding fall in effective renal plasma flow, which may be the functional expression of the formation of nonfiltrating atubular glomeruli. The fractional reabsorption of tubular fluid by the proximal tubules is reduced, leaving the distal delivery unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Renal Insufficiency", "aliases": "Failure Kidney Renal Failures Insufficiency Insufficiencies", "definition": "Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.\n    ", "id": "MESH:D051437"}
{"mention": "Li", "mention_text": "Rats with lithium-induced nephropathy were subjected to high protein (HP) feeding, uninephrectomy (NX) or a combination of these, in an attempt to induce glomerular hyperfiltration and further progression of renal failure. Newborn female Wistar rats were fed a lithium-containing diet (50 mmol/kg) for 8 weeks and then randomized to normal diet, HP diet (40 vs. 19%), NX or HP+NX for another 8 weeks. Corresponding non-lithium pretreated groups were generated. When comparing all lithium treated versus non-lithium-treated groups, lithium caused a reduction in glomerular filtration rate (GFR) without significant changes in effective renal plasma flow (as determined by a marker secreted into the proximal tubules) or lithium clearance. Consequently, lithium pretreatment caused a fall in filtration fraction and an increase in fractional Li excretion. Lithium also caused proteinuria and systolic hypertension in absence of glomerulosclerosis. HP failed to accentuante progression of renal failure and in fact tended to increase GFR and decrease plasma creatinine levels in lithium pretreated rats. NX caused an additive deterioration in GFR which, however, was ameliorated by HP. NX+HP caused a further rise in blood pressure in Li-pretreated rats. The results indicate that Li-induced nephropathy, even when the GFR is only modestly reduced, is associated with proteinuria and arterial systolic hypertension. In this model of chronic renal failure the decline in GFR is not accompanied by a corresponding fall in effective renal plasma flow, which may be the functional expression of the formation of nonfiltrating atubular glomeruli. The fractional reabsorption of tubular fluid by the proximal tubules is reduced, leaving the distal delivery unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Lithium", "aliases": "Lithium", "definition": "An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.\n    ", "id": "MESH:D008094"}
{"mention": "Lithium", "mention_text": "Rats with lithium-induced nephropathy were subjected to high protein (HP) feeding, uninephrectomy (NX) or a combination of these, in an attempt to induce glomerular hyperfiltration and further progression of renal failure. Newborn female Wistar rats were fed a lithium-containing diet (50 mmol/kg) for 8 weeks and then randomized to normal diet, HP diet (40 vs. 19%), NX or HP+NX for another 8 weeks. Corresponding non-lithium pretreated groups were generated. When comparing all lithium treated versus non-lithium-treated groups, lithium caused a reduction in glomerular filtration rate (GFR) without significant changes in effective renal plasma flow (as determined by a marker secreted into the proximal tubules) or lithium clearance. Consequently, lithium pretreatment caused a fall in filtration fraction and an increase in fractional Li excretion. Lithium also caused proteinuria and systolic hypertension in absence of glomerulosclerosis. HP failed to accentuante progression of renal failure and in fact tended to increase GFR and decrease plasma creatinine levels in lithium pretreated rats. NX caused an additive deterioration in GFR which, however, was ameliorated by HP. NX+HP caused a further rise in blood pressure in Li-pretreated rats. The results indicate that Li-induced nephropathy, even when the GFR is only modestly reduced, is associated with proteinuria and arterial systolic hypertension. In this model of chronic renal failure the decline in GFR is not accompanied by a corresponding fall in effective renal plasma flow, which may be the functional expression of the formation of nonfiltrating atubular glomeruli. The fractional reabsorption of tubular fluid by the proximal tubules is reduced, leaving the distal delivery unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Lithium", "aliases": "Lithium", "definition": "An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.\n    ", "id": "MESH:D008094"}
{"mention": "proteinuria", "mention_text": "Rats with lithium-induced nephropathy were subjected to high protein (HP) feeding, uninephrectomy (NX) or a combination of these, in an attempt to induce glomerular hyperfiltration and further progression of renal failure. Newborn female Wistar rats were fed a lithium-containing diet (50 mmol/kg) for 8 weeks and then randomized to normal diet, HP diet (40 vs. 19%), NX or HP+NX for another 8 weeks. Corresponding non-lithium pretreated groups were generated. When comparing all lithium treated versus non-lithium-treated groups, lithium caused a reduction in glomerular filtration rate (GFR) without significant changes in effective renal plasma flow (as determined by a marker secreted into the proximal tubules) or lithium clearance. Consequently, lithium pretreatment caused a fall in filtration fraction and an increase in fractional Li excretion. Lithium also caused proteinuria and systolic hypertension in absence of glomerulosclerosis. HP failed to accentuante progression of renal failure and in fact tended to increase GFR and decrease plasma creatinine levels in lithium pretreated rats. NX caused an additive deterioration in GFR which, however, was ameliorated by HP. NX+HP caused a further rise in blood pressure in Li-pretreated rats. The results indicate that Li-induced nephropathy, even when the GFR is only modestly reduced, is associated with proteinuria and arterial systolic hypertension. In this model of chronic renal failure the decline in GFR is not accompanied by a corresponding fall in effective renal plasma flow, which may be the functional expression of the formation of nonfiltrating atubular glomeruli. The fractional reabsorption of tubular fluid by the proximal tubules is reduced, leaving the distal delivery unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "hypertension", "mention_text": "Rats with lithium-induced nephropathy were subjected to high protein (HP) feeding, uninephrectomy (NX) or a combination of these, in an attempt to induce glomerular hyperfiltration and further progression of renal failure. Newborn female Wistar rats were fed a lithium-containing diet (50 mmol/kg) for 8 weeks and then randomized to normal diet, HP diet (40 vs. 19%), NX or HP+NX for another 8 weeks. Corresponding non-lithium pretreated groups were generated. When comparing all lithium treated versus non-lithium-treated groups, lithium caused a reduction in glomerular filtration rate (GFR) without significant changes in effective renal plasma flow (as determined by a marker secreted into the proximal tubules) or lithium clearance. Consequently, lithium pretreatment caused a fall in filtration fraction and an increase in fractional Li excretion. Lithium also caused proteinuria and systolic hypertension in absence of glomerulosclerosis. HP failed to accentuante progression of renal failure and in fact tended to increase GFR and decrease plasma creatinine levels in lithium pretreated rats. NX caused an additive deterioration in GFR which, however, was ameliorated by HP. NX+HP caused a further rise in blood pressure in Li-pretreated rats. The results indicate that Li-induced nephropathy, even when the GFR is only modestly reduced, is associated with proteinuria and arterial systolic hypertension. In this model of chronic renal failure the decline in GFR is not accompanied by a corresponding fall in effective renal plasma flow, which may be the functional expression of the formation of nonfiltrating atubular glomeruli. The fractional reabsorption of tubular fluid by the proximal tubules is reduced, leaving the distal delivery unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "glomerulosclerosis", "mention_text": "Rats with lithium-induced nephropathy were subjected to high protein (HP) feeding, uninephrectomy (NX) or a combination of these, in an attempt to induce glomerular hyperfiltration and further progression of renal failure. Newborn female Wistar rats were fed a lithium-containing diet (50 mmol/kg) for 8 weeks and then randomized to normal diet, HP diet (40 vs. 19%), NX or HP+NX for another 8 weeks. Corresponding non-lithium pretreated groups were generated. When comparing all lithium treated versus non-lithium-treated groups, lithium caused a reduction in glomerular filtration rate (GFR) without significant changes in effective renal plasma flow (as determined by a marker secreted into the proximal tubules) or lithium clearance. Consequently, lithium pretreatment caused a fall in filtration fraction and an increase in fractional Li excretion. Lithium also caused proteinuria and systolic hypertension in absence of glomerulosclerosis. HP failed to accentuante progression of renal failure and in fact tended to increase GFR and decrease plasma creatinine levels in lithium pretreated rats. NX caused an additive deterioration in GFR which, however, was ameliorated by HP. NX+HP caused a further rise in blood pressure in Li-pretreated rats. The results indicate that Li-induced nephropathy, even when the GFR is only modestly reduced, is associated with proteinuria and arterial systolic hypertension. In this model of chronic renal failure the decline in GFR is not accompanied by a corresponding fall in effective renal plasma flow, which may be the functional expression of the formation of nonfiltrating atubular glomeruli. The fractional reabsorption of tubular fluid by the proximal tubules is reduced, leaving the distal delivery unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Glomerulonephritis", "aliases": "Bright Disease Glomerulonephritides Glomerulonephritis", "definition": "Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.\n    ", "id": "MESH:D005921"}
{"mention": "creatinine", "mention_text": "Rats with lithium-induced nephropathy were subjected to high protein (HP) feeding, uninephrectomy (NX) or a combination of these, in an attempt to induce glomerular hyperfiltration and further progression of renal failure. Newborn female Wistar rats were fed a lithium-containing diet (50 mmol/kg) for 8 weeks and then randomized to normal diet, HP diet (40 vs. 19%), NX or HP+NX for another 8 weeks. Corresponding non-lithium pretreated groups were generated. When comparing all lithium treated versus non-lithium-treated groups, lithium caused a reduction in glomerular filtration rate (GFR) without significant changes in effective renal plasma flow (as determined by a marker secreted into the proximal tubules) or lithium clearance. Consequently, lithium pretreatment caused a fall in filtration fraction and an increase in fractional Li excretion. Lithium also caused proteinuria and systolic hypertension in absence of glomerulosclerosis. HP failed to accentuante progression of renal failure and in fact tended to increase GFR and decrease plasma creatinine levels in lithium pretreated rats. NX caused an additive deterioration in GFR which, however, was ameliorated by HP. NX+HP caused a further rise in blood pressure in Li-pretreated rats. The results indicate that Li-induced nephropathy, even when the GFR is only modestly reduced, is associated with proteinuria and arterial systolic hypertension. In this model of chronic renal failure the decline in GFR is not accompanied by a corresponding fall in effective renal plasma flow, which may be the functional expression of the formation of nonfiltrating atubular glomeruli. The fractional reabsorption of tubular fluid by the proximal tubules is reduced, leaving the distal delivery unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Creatinine", "aliases": "Creatinine Sulfate Salt Krebiozen", "definition": "", "id": "MESH:D003404"}
{"mention": "chronic renal failure", "mention_text": "Rats with lithium-induced nephropathy were subjected to high protein (HP) feeding, uninephrectomy (NX) or a combination of these, in an attempt to induce glomerular hyperfiltration and further progression of renal failure. Newborn female Wistar rats were fed a lithium-containing diet (50 mmol/kg) for 8 weeks and then randomized to normal diet, HP diet (40 vs. 19%), NX or HP+NX for another 8 weeks. Corresponding non-lithium pretreated groups were generated. When comparing all lithium treated versus non-lithium-treated groups, lithium caused a reduction in glomerular filtration rate (GFR) without significant changes in effective renal plasma flow (as determined by a marker secreted into the proximal tubules) or lithium clearance. Consequently, lithium pretreatment caused a fall in filtration fraction and an increase in fractional Li excretion. Lithium also caused proteinuria and systolic hypertension in absence of glomerulosclerosis. HP failed to accentuante progression of renal failure and in fact tended to increase GFR and decrease plasma creatinine levels in lithium pretreated rats. NX caused an additive deterioration in GFR which, however, was ameliorated by HP. NX+HP caused a further rise in blood pressure in Li-pretreated rats. The results indicate that Li-induced nephropathy, even when the GFR is only modestly reduced, is associated with proteinuria and arterial systolic hypertension. In this model of chronic renal failure the decline in GFR is not accompanied by a corresponding fall in effective renal plasma flow, which may be the functional expression of the formation of nonfiltrating atubular glomeruli. The fractional reabsorption of tubular fluid by the proximal tubules is reduced, leaving the distal delivery unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Kidney Failure, Chronic", "aliases": "Chronic Kidney Failure Renal Disease End-Stage ESRD End Stage", "definition": "The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.\n    ", "id": "MESH:D007676"}
{"mention": "Crohn's disease", "mention_text": "Treatment of Crohn's disease with fusidic acid: an antibiotic with immunosuppressive properties similar to cyclosporin.", "entity": "Crohn Disease", "aliases": "Colitis Granulomatous Crohn Disease Crohn's Enteritis Crohns Regional Ileitis Terminal Ileocolitis Inflammatory Bowel 1 Ileitides", "definition": "A chronic transmural inflammation that may involve any part of the DIGESTIVE TRACT from MOUTH to ANUS, mostly found in the ILEUM, the CECUM, and the COLON. In Crohn disease, the inflammation, extending through the intestinal wall from the MUCOSA to the serosa, is characteristically asymmetric and segmental. Epithelioid GRANULOMAS may be seen in some patients.\n    ", "id": "MESH:D003424"}
{"mention": "fusidic acid", "mention_text": "Treatment of Crohn's disease with fusidic acid: an antibiotic with immunosuppressive properties similar to cyclosporin.", "entity": "Fusidic Acid", "aliases": "Acid Fusidic Fucithalmic Fusidate Sodium Silver Salt Fusidin Stanicide", "definition": "An antibiotic isolated from the fermentation broth of Fusidium coccineum. (From Merck Index, 11th ed). It acts by inhibiting translocation during protein synthesis.\n    ", "id": "MESH:D005672"}
{"mention": "cyclosporin", "mention_text": "Treatment of Crohn's disease with fusidic acid: an antibiotic with immunosuppressive properties similar to cyclosporin.", "entity": "Cyclosporine", "aliases": "Ciclosporin CsA Neoral CsA-Neoral CsANeoral CyA NOF CyA-NOF Cyclosporin A Cyclosporine OL 27 400 27-400 27400 Sandimmun Sandimmune", "definition": "A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).\n    ", "id": "MESH:D016572"}
{"mention": "cyclosporin", "mention_text": "Fusidic acid is an antibiotic with T-cell specific immunosuppressive effects similar to those of cyclosporin. Because of the need for the development of new treatments for Crohn's disease, a pilot study was undertaken to estimate the pharmacodynamics and tolerability of fusidic acid treatment in chronic active, therapy-resistant patients. Eight Crohn's disease patients were included. Fusidic acid was administered orally in a dose of 500 mg t.d.s. and the treatment was planned to last 8 weeks. The disease activity was primarily measured by a modified individual grading score. Five of 8 patients (63%) improved during fusidic acid treatment: 3 at two weeks and 2 after four weeks. There were no serious clinical side effects, but dose reduction was required in two patients because of nausea. Biochemically, an increase in alkaline phosphatases was noted in 5 of 8 cases (63%), and the greatest increases were seen in those who had elevated levels prior to treatment. All reversed to pre-treatment levels after cessation of treatment. The results of this pilot study suggest that fusidic acid may be of benefit in selected chronic active Crohn's disease patients in whom conventional treatment is ineffective. Because there seems to exist a scientific rationale for the use of fusidic acid at the cytokine level in inflammatory bowel disease, we suggest that the role of this treatment should be further investigated.", "entity": "Cyclosporine", "aliases": "Ciclosporin CsA Neoral CsA-Neoral CsANeoral CyA NOF CyA-NOF Cyclosporin A Cyclosporine OL 27 400 27-400 27400 Sandimmun Sandimmune", "definition": "A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).\n    ", "id": "MESH:D016572"}
{"mention": "Crohn's disease", "mention_text": "Fusidic acid is an antibiotic with T-cell specific immunosuppressive effects similar to those of cyclosporin. Because of the need for the development of new treatments for Crohn's disease, a pilot study was undertaken to estimate the pharmacodynamics and tolerability of fusidic acid treatment in chronic active, therapy-resistant patients. Eight Crohn's disease patients were included. Fusidic acid was administered orally in a dose of 500 mg t.d.s. and the treatment was planned to last 8 weeks. The disease activity was primarily measured by a modified individual grading score. Five of 8 patients (63%) improved during fusidic acid treatment: 3 at two weeks and 2 after four weeks. There were no serious clinical side effects, but dose reduction was required in two patients because of nausea. Biochemically, an increase in alkaline phosphatases was noted in 5 of 8 cases (63%), and the greatest increases were seen in those who had elevated levels prior to treatment. All reversed to pre-treatment levels after cessation of treatment. The results of this pilot study suggest that fusidic acid may be of benefit in selected chronic active Crohn's disease patients in whom conventional treatment is ineffective. Because there seems to exist a scientific rationale for the use of fusidic acid at the cytokine level in inflammatory bowel disease, we suggest that the role of this treatment should be further investigated.", "entity": "Crohn Disease", "aliases": "Colitis Granulomatous Crohn Disease Crohn's Enteritis Crohns Regional Ileitis Terminal Ileocolitis Inflammatory Bowel 1 Ileitides", "definition": "A chronic transmural inflammation that may involve any part of the DIGESTIVE TRACT from MOUTH to ANUS, mostly found in the ILEUM, the CECUM, and the COLON. In Crohn disease, the inflammation, extending through the intestinal wall from the MUCOSA to the serosa, is characteristically asymmetric and segmental. Epithelioid GRANULOMAS may be seen in some patients.\n    ", "id": "MESH:D003424"}
{"mention": "fusidic acid", "mention_text": "Fusidic acid is an antibiotic with T-cell specific immunosuppressive effects similar to those of cyclosporin. Because of the need for the development of new treatments for Crohn's disease, a pilot study was undertaken to estimate the pharmacodynamics and tolerability of fusidic acid treatment in chronic active, therapy-resistant patients. Eight Crohn's disease patients were included. Fusidic acid was administered orally in a dose of 500 mg t.d.s. and the treatment was planned to last 8 weeks. The disease activity was primarily measured by a modified individual grading score. Five of 8 patients (63%) improved during fusidic acid treatment: 3 at two weeks and 2 after four weeks. There were no serious clinical side effects, but dose reduction was required in two patients because of nausea. Biochemically, an increase in alkaline phosphatases was noted in 5 of 8 cases (63%), and the greatest increases were seen in those who had elevated levels prior to treatment. All reversed to pre-treatment levels after cessation of treatment. The results of this pilot study suggest that fusidic acid may be of benefit in selected chronic active Crohn's disease patients in whom conventional treatment is ineffective. Because there seems to exist a scientific rationale for the use of fusidic acid at the cytokine level in inflammatory bowel disease, we suggest that the role of this treatment should be further investigated.", "entity": "Fusidic Acid", "aliases": "Acid Fusidic Fucithalmic Fusidate Sodium Silver Salt Fusidin Stanicide", "definition": "An antibiotic isolated from the fermentation broth of Fusidium coccineum. (From Merck Index, 11th ed). It acts by inhibiting translocation during protein synthesis.\n    ", "id": "MESH:D005672"}
{"mention": "Fusidic acid", "mention_text": "Fusidic acid is an antibiotic with T-cell specific immunosuppressive effects similar to those of cyclosporin. Because of the need for the development of new treatments for Crohn's disease, a pilot study was undertaken to estimate the pharmacodynamics and tolerability of fusidic acid treatment in chronic active, therapy-resistant patients. Eight Crohn's disease patients were included. Fusidic acid was administered orally in a dose of 500 mg t.d.s. and the treatment was planned to last 8 weeks. The disease activity was primarily measured by a modified individual grading score. Five of 8 patients (63%) improved during fusidic acid treatment: 3 at two weeks and 2 after four weeks. There were no serious clinical side effects, but dose reduction was required in two patients because of nausea. Biochemically, an increase in alkaline phosphatases was noted in 5 of 8 cases (63%), and the greatest increases were seen in those who had elevated levels prior to treatment. All reversed to pre-treatment levels after cessation of treatment. The results of this pilot study suggest that fusidic acid may be of benefit in selected chronic active Crohn's disease patients in whom conventional treatment is ineffective. Because there seems to exist a scientific rationale for the use of fusidic acid at the cytokine level in inflammatory bowel disease, we suggest that the role of this treatment should be further investigated.", "entity": "Fusidic Acid", "aliases": "Acid Fusidic Fucithalmic Fusidate Sodium Silver Salt Fusidin Stanicide", "definition": "An antibiotic isolated from the fermentation broth of Fusidium coccineum. (From Merck Index, 11th ed). It acts by inhibiting translocation during protein synthesis.\n    ", "id": "MESH:D005672"}
{"mention": "nausea", "mention_text": "Fusidic acid is an antibiotic with T-cell specific immunosuppressive effects similar to those of cyclosporin. Because of the need for the development of new treatments for Crohn's disease, a pilot study was undertaken to estimate the pharmacodynamics and tolerability of fusidic acid treatment in chronic active, therapy-resistant patients. Eight Crohn's disease patients were included. Fusidic acid was administered orally in a dose of 500 mg t.d.s. and the treatment was planned to last 8 weeks. The disease activity was primarily measured by a modified individual grading score. Five of 8 patients (63%) improved during fusidic acid treatment: 3 at two weeks and 2 after four weeks. There were no serious clinical side effects, but dose reduction was required in two patients because of nausea. Biochemically, an increase in alkaline phosphatases was noted in 5 of 8 cases (63%), and the greatest increases were seen in those who had elevated levels prior to treatment. All reversed to pre-treatment levels after cessation of treatment. The results of this pilot study suggest that fusidic acid may be of benefit in selected chronic active Crohn's disease patients in whom conventional treatment is ineffective. Because there seems to exist a scientific rationale for the use of fusidic acid at the cytokine level in inflammatory bowel disease, we suggest that the role of this treatment should be further investigated.", "entity": "Nausea", "aliases": "Nausea", "definition": "An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.\n    ", "id": "MESH:D009325"}
{"mention": "inflammatory bowel disease", "mention_text": "Fusidic acid is an antibiotic with T-cell specific immunosuppressive effects similar to those of cyclosporin. Because of the need for the development of new treatments for Crohn's disease, a pilot study was undertaken to estimate the pharmacodynamics and tolerability of fusidic acid treatment in chronic active, therapy-resistant patients. Eight Crohn's disease patients were included. Fusidic acid was administered orally in a dose of 500 mg t.d.s. and the treatment was planned to last 8 weeks. The disease activity was primarily measured by a modified individual grading score. Five of 8 patients (63%) improved during fusidic acid treatment: 3 at two weeks and 2 after four weeks. There were no serious clinical side effects, but dose reduction was required in two patients because of nausea. Biochemically, an increase in alkaline phosphatases was noted in 5 of 8 cases (63%), and the greatest increases were seen in those who had elevated levels prior to treatment. All reversed to pre-treatment levels after cessation of treatment. The results of this pilot study suggest that fusidic acid may be of benefit in selected chronic active Crohn's disease patients in whom conventional treatment is ineffective. Because there seems to exist a scientific rationale for the use of fusidic acid at the cytokine level in inflammatory bowel disease, we suggest that the role of this treatment should be further investigated.", "entity": "Inflammatory Bowel Diseases", "aliases": "Bowel Diseases Inflammatory Disease", "definition": "Chronic, non-specific inflammation of the GASTROINTESTINAL TRACT. Etiology may be genetic or environmental. This term includes CROHN DISEASE and ULCERATIVE COLITIS.\n    ", "id": "MESH:D015212"}
{"mention": "myocardial injury", "mention_text": "Electrocardiographic evidence of myocardial injury in psychiatrically hospitalized cocaine abusers.", "entity": "Cardiomyopathies", "aliases": "Cardiomyopathies Primary Secondary Cardiomyopathy Disease Myocardial Diseases Myocardiopathies Myocardiopathy", "definition": "A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).\n    ", "id": "MESH:D009202"}
{"mention": "cocaine", "mention_text": "Electrocardiographic evidence of myocardial injury in psychiatrically hospitalized cocaine abusers.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "cocaine", "mention_text": "The electrocardiograms (ECG) of 99 cocaine-abusing patients were compared with the ECGs of 50 schizophrenic controls. Eleven of the cocaine abusers and none of the controls had ECG evidence of significant myocardial injury defined as myocardial infarction, ischemia, and bundle branch block.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "schizophrenic", "mention_text": "The electrocardiograms (ECG) of 99 cocaine-abusing patients were compared with the ECGs of 50 schizophrenic controls. Eleven of the cocaine abusers and none of the controls had ECG evidence of significant myocardial injury defined as myocardial infarction, ischemia, and bundle branch block.", "entity": "Schizophrenia", "aliases": "Dementia Praecox Disorder Schizophrenic Disorders Schizophrenia Schizophrenias", "definition": "A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior.\n    ", "id": "MESH:D012559"}
{"mention": "myocardial injury", "mention_text": "The electrocardiograms (ECG) of 99 cocaine-abusing patients were compared with the ECGs of 50 schizophrenic controls. Eleven of the cocaine abusers and none of the controls had ECG evidence of significant myocardial injury defined as myocardial infarction, ischemia, and bundle branch block.", "entity": "Cardiomyopathies", "aliases": "Cardiomyopathies Primary Secondary Cardiomyopathy Disease Myocardial Diseases Myocardiopathies Myocardiopathy", "definition": "A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).\n    ", "id": "MESH:D009202"}
{"mention": "myocardial infarction", "mention_text": "The electrocardiograms (ECG) of 99 cocaine-abusing patients were compared with the ECGs of 50 schizophrenic controls. Eleven of the cocaine abusers and none of the controls had ECG evidence of significant myocardial injury defined as myocardial infarction, ischemia, and bundle branch block.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "ischemia", "mention_text": "The electrocardiograms (ECG) of 99 cocaine-abusing patients were compared with the ECGs of 50 schizophrenic controls. Eleven of the cocaine abusers and none of the controls had ECG evidence of significant myocardial injury defined as myocardial infarction, ischemia, and bundle branch block.", "entity": "Ischemia", "aliases": "Ischemia Ischemias", "definition": "A hypoperfusion of the BLOOD through an organ or tissue caused by a PATHOLOGIC CONSTRICTION or obstruction of its BLOOD VESSELS, or an absence of BLOOD CIRCULATION.\n    ", "id": "MESH:D007511"}
{"mention": "bundle branch block", "mention_text": "The electrocardiograms (ECG) of 99 cocaine-abusing patients were compared with the ECGs of 50 schizophrenic controls. Eleven of the cocaine abusers and none of the controls had ECG evidence of significant myocardial injury defined as myocardial infarction, ischemia, and bundle branch block.", "entity": "Bundle-Branch Block", "aliases": "Anterior Fascicular Block Blocks Bundle Branch Bundle-Branch Left Posterior Right", "definition": "A form of heart block in which the electrical stimulation of HEART VENTRICLES is interrupted at either one of the branches of BUNDLE OF HIS thus preventing the simultaneous depolarization of the two ventricles.\n    ", "id": "MESH:D002037"}
{"mention": "Sulpiride", "mention_text": "Sulpiride-induced tardive dystonia.", "entity": "Sulpiride", "aliases": "Aiglonyl Allphar Brand of Sulpiride Almirall Areu Arminol Centrum Deponerton Desisulpid Desitin Digton Dogmatil Dolmatil Dolorgiet Eglonyl Ekilid Erempharma Fumouzer Guastil Hennig Hexal Hoechst Hormosan Krewel Lebopride Meresa Pharmacia Pontiride Psicocen Psicofarma Rosemont Sanofi Synthelabo Sanofi-Synthelabo Spyfarma Sulp Sulperide Sulpitil Sulpivert Sulpor Synédil Tepavil Uriach Vertigo Vertigo-Meresa neogama vertigo vertigo-neogama", "definition": "A dopamine D2-receptor antagonist. It has been used therapeutically as an antidepressant, antipsychotic, and as a digestive aid. (From Merck Index, 11th ed)\n    ", "id": "MESH:D013469"}
{"mention": "tardive dystonia", "mention_text": "Sulpiride-induced tardive dystonia.", "entity": "Dystonia", "aliases": "Diurnal Dystonia Limb Muscle Paroxysmal", "definition": "An attitude or posture due to the co-contraction of agonists and antagonist muscles in one region of the body. It most often affects the large axial muscles of the trunk and limb girdles. Conditions which feature persistent or recurrent episodes of dystonia as a primary manifestation of disease are referred to as DYSTONIC DISORDERS. (Adams et al., Principles of Neurology, 6th ed, p77)\n    ", "id": "MESH:D004421"}
{"mention": "Sulpiride", "mention_text": "Sulpiride is a selective D2-receptor antagonist with antipsychotic and antidepressant properties. Although initially thought to be free of extrapyramidal side effects, sulpiride-induced tardive dyskinesia and parkinsonism have been reported occasionally. We studied a 37-year-old man who developed persistent segmental dystonia within 2 months after starting sulpiride therapy. We could not find any previous reports of sulpiride-induced tardive dystonia.", "entity": "Sulpiride", "aliases": "Aiglonyl Allphar Brand of Sulpiride Almirall Areu Arminol Centrum Deponerton Desisulpid Desitin Digton Dogmatil Dolmatil Dolorgiet Eglonyl Ekilid Erempharma Fumouzer Guastil Hennig Hexal Hoechst Hormosan Krewel Lebopride Meresa Pharmacia Pontiride Psicocen Psicofarma Rosemont Sanofi Synthelabo Sanofi-Synthelabo Spyfarma Sulp Sulperide Sulpitil Sulpivert Sulpor Synédil Tepavil Uriach Vertigo Vertigo-Meresa neogama vertigo vertigo-neogama", "definition": "A dopamine D2-receptor antagonist. It has been used therapeutically as an antidepressant, antipsychotic, and as a digestive aid. (From Merck Index, 11th ed)\n    ", "id": "MESH:D013469"}
{"mention": "antidepressant", "mention_text": "Sulpiride is a selective D2-receptor antagonist with antipsychotic and antidepressant properties. Although initially thought to be free of extrapyramidal side effects, sulpiride-induced tardive dyskinesia and parkinsonism have been reported occasionally. We studied a 37-year-old man who developed persistent segmental dystonia within 2 months after starting sulpiride therapy. We could not find any previous reports of sulpiride-induced tardive dystonia.", "entity": "Antidepressive Agents", "aliases": "Agents Antidepressive Antidepressant Drugs Antidepressants Thymoanaleptics Thymoleptics", "definition": "Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.\n    ", "id": "MESH:D000928"}
{"mention": "sulpiride", "mention_text": "Sulpiride is a selective D2-receptor antagonist with antipsychotic and antidepressant properties. Although initially thought to be free of extrapyramidal side effects, sulpiride-induced tardive dyskinesia and parkinsonism have been reported occasionally. We studied a 37-year-old man who developed persistent segmental dystonia within 2 months after starting sulpiride therapy. We could not find any previous reports of sulpiride-induced tardive dystonia.", "entity": "Sulpiride", "aliases": "Aiglonyl Allphar Brand of Sulpiride Almirall Areu Arminol Centrum Deponerton Desisulpid Desitin Digton Dogmatil Dolmatil Dolorgiet Eglonyl Ekilid Erempharma Fumouzer Guastil Hennig Hexal Hoechst Hormosan Krewel Lebopride Meresa Pharmacia Pontiride Psicocen Psicofarma Rosemont Sanofi Synthelabo Sanofi-Synthelabo Spyfarma Sulp Sulperide Sulpitil Sulpivert Sulpor Synédil Tepavil Uriach Vertigo Vertigo-Meresa neogama vertigo vertigo-neogama", "definition": "A dopamine D2-receptor antagonist. It has been used therapeutically as an antidepressant, antipsychotic, and as a digestive aid. (From Merck Index, 11th ed)\n    ", "id": "MESH:D013469"}
{"mention": "tardive dyskinesia", "mention_text": "Sulpiride is a selective D2-receptor antagonist with antipsychotic and antidepressant properties. Although initially thought to be free of extrapyramidal side effects, sulpiride-induced tardive dyskinesia and parkinsonism have been reported occasionally. We studied a 37-year-old man who developed persistent segmental dystonia within 2 months after starting sulpiride therapy. We could not find any previous reports of sulpiride-induced tardive dystonia.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "parkinsonism", "mention_text": "Sulpiride is a selective D2-receptor antagonist with antipsychotic and antidepressant properties. Although initially thought to be free of extrapyramidal side effects, sulpiride-induced tardive dyskinesia and parkinsonism have been reported occasionally. We studied a 37-year-old man who developed persistent segmental dystonia within 2 months after starting sulpiride therapy. We could not find any previous reports of sulpiride-induced tardive dystonia.", "entity": "Parkinson Disease, Secondary", "aliases": "Atherosclerotic Parkinsonism Parkinson Disease Secondary Vascular Symptomatic", "definition": "Conditions which feature clinical manifestations resembling primary Parkinson disease that are caused by a known or suspected condition. Examples include parkinsonism caused by vascular injury, drugs, trauma, toxin exposure, neoplasms, infections and degenerative or hereditary conditions. Clinical features may include bradykinesia, rigidity, parkinsonian gait, and masked facies. In general, tremor is less prominent in secondary parkinsonism than in the primary form. (From Joynt, Clinical Neurology, 1998, Ch38, pp39-42)\n    ", "id": "MESH:D010302"}
{"mention": "dystonia", "mention_text": "Sulpiride is a selective D2-receptor antagonist with antipsychotic and antidepressant properties. Although initially thought to be free of extrapyramidal side effects, sulpiride-induced tardive dyskinesia and parkinsonism have been reported occasionally. We studied a 37-year-old man who developed persistent segmental dystonia within 2 months after starting sulpiride therapy. We could not find any previous reports of sulpiride-induced tardive dystonia.", "entity": "Dystonia", "aliases": "Diurnal Dystonia Limb Muscle Paroxysmal", "definition": "An attitude or posture due to the co-contraction of agonists and antagonist muscles in one region of the body. It most often affects the large axial muscles of the trunk and limb girdles. Conditions which feature persistent or recurrent episodes of dystonia as a primary manifestation of disease are referred to as DYSTONIC DISORDERS. (Adams et al., Principles of Neurology, 6th ed, p77)\n    ", "id": "MESH:D004421"}
{"mention": "tardive dystonia", "mention_text": "Sulpiride is a selective D2-receptor antagonist with antipsychotic and antidepressant properties. Although initially thought to be free of extrapyramidal side effects, sulpiride-induced tardive dyskinesia and parkinsonism have been reported occasionally. We studied a 37-year-old man who developed persistent segmental dystonia within 2 months after starting sulpiride therapy. We could not find any previous reports of sulpiride-induced tardive dystonia.", "entity": "Dystonia", "aliases": "Diurnal Dystonia Limb Muscle Paroxysmal", "definition": "An attitude or posture due to the co-contraction of agonists and antagonist muscles in one region of the body. It most often affects the large axial muscles of the trunk and limb girdles. Conditions which feature persistent or recurrent episodes of dystonia as a primary manifestation of disease are referred to as DYSTONIC DISORDERS. (Adams et al., Principles of Neurology, 6th ed, p77)\n    ", "id": "MESH:D004421"}
{"mention": "auditory toxicity", "mention_text": "Ocular and auditory toxicity in hemodialyzed patients receiving desferrioxamine.", "entity": "Hearing Disorders", "aliases": "Distorted Hearing Dysacusis Disorder Disorders Paracousis Paracusis", "definition": "Conditions that impair the transmission of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways.\n    ", "id": "MESH:D006311"}
{"mention": "desferrioxamine", "mention_text": "Ocular and auditory toxicity in hemodialyzed patients receiving desferrioxamine.", "entity": "Deferoxamine", "aliases": "B Deferoxamine Desferrioxamine Mesilate Mesylate Methanesulfonate Deferoximine Deferrioxamine Desferal Desferioximine Desferroxamine", "definition": "Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form.\n    ", "id": "MESH:D003676"}
{"mention": "desferrioxamine", "mention_text": "During an 18-month period of study 41 hemodialyzed patients receiving desferrioxamine (10-40 mg/kg BW/3 times weekly) for the first time were monitored for detection of audiovisual toxicity. 6 patients presented clinical symptoms of visual or auditory toxicity. Moreover, detailed ophthalmologic and audiologic studies disclosed abnormalities in 7 more asymptomatic patients. Visual toxicity was of retinal origin and was characterized by a tritan-type dyschromatopsy, sometimes associated with a loss of visual acuity and pigmentary retinal deposits. Auditory toxicity was characterized by a mid- to high-frequency neurosensorial hearing loss and the lesion was of the cochlear type. Desferrioxamine withdrawal resulted in a complete recovery of visual function in 1 patient and partial recovery in 3, and a complete reversal of hearing loss in 3 patients and partial recovery in 3. This toxicity appeared in patients receiving the higher doses of desferrioxamine or coincided with the normalization of ferritin or aluminium serum levels. The data indicate that audiovisual toxicity is not an infrequent complication in hemodialyzed patients receiving desferrioxamine. Periodical audiovisual monitoring should be performed on hemodialyzed patients receiving the drug in order to detect adverse effects as early as possible.", "entity": "Deferoxamine", "aliases": "B Deferoxamine Desferrioxamine Mesilate Mesylate Methanesulfonate Deferoximine Deferrioxamine Desferal Desferioximine Desferroxamine", "definition": "Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form.\n    ", "id": "MESH:D003676"}
{"mention": "auditory toxicity", "mention_text": "During an 18-month period of study 41 hemodialyzed patients receiving desferrioxamine (10-40 mg/kg BW/3 times weekly) for the first time were monitored for detection of audiovisual toxicity. 6 patients presented clinical symptoms of visual or auditory toxicity. Moreover, detailed ophthalmologic and audiologic studies disclosed abnormalities in 7 more asymptomatic patients. Visual toxicity was of retinal origin and was characterized by a tritan-type dyschromatopsy, sometimes associated with a loss of visual acuity and pigmentary retinal deposits. Auditory toxicity was characterized by a mid- to high-frequency neurosensorial hearing loss and the lesion was of the cochlear type. Desferrioxamine withdrawal resulted in a complete recovery of visual function in 1 patient and partial recovery in 3, and a complete reversal of hearing loss in 3 patients and partial recovery in 3. This toxicity appeared in patients receiving the higher doses of desferrioxamine or coincided with the normalization of ferritin or aluminium serum levels. The data indicate that audiovisual toxicity is not an infrequent complication in hemodialyzed patients receiving desferrioxamine. Periodical audiovisual monitoring should be performed on hemodialyzed patients receiving the drug in order to detect adverse effects as early as possible.", "entity": "Hearing Disorders", "aliases": "Distorted Hearing Dysacusis Disorder Disorders Paracousis Paracusis", "definition": "Conditions that impair the transmission of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways.\n    ", "id": "MESH:D006311"}
{"mention": "Visual toxicity", "mention_text": "During an 18-month period of study 41 hemodialyzed patients receiving desferrioxamine (10-40 mg/kg BW/3 times weekly) for the first time were monitored for detection of audiovisual toxicity. 6 patients presented clinical symptoms of visual or auditory toxicity. Moreover, detailed ophthalmologic and audiologic studies disclosed abnormalities in 7 more asymptomatic patients. Visual toxicity was of retinal origin and was characterized by a tritan-type dyschromatopsy, sometimes associated with a loss of visual acuity and pigmentary retinal deposits. Auditory toxicity was characterized by a mid- to high-frequency neurosensorial hearing loss and the lesion was of the cochlear type. Desferrioxamine withdrawal resulted in a complete recovery of visual function in 1 patient and partial recovery in 3, and a complete reversal of hearing loss in 3 patients and partial recovery in 3. This toxicity appeared in patients receiving the higher doses of desferrioxamine or coincided with the normalization of ferritin or aluminium serum levels. The data indicate that audiovisual toxicity is not an infrequent complication in hemodialyzed patients receiving desferrioxamine. Periodical audiovisual monitoring should be performed on hemodialyzed patients receiving the drug in order to detect adverse effects as early as possible.", "entity": "Vision Disorders", "aliases": "Blindness Day Disabilities Vision Disability Disorder Visual Disorders Hemeralopia Hemeralopias Impairment Impairments Macropsia Macropsias Metamorphopsia Metamorphopsias Micropsia Micropsias", "definition": "Visual impairments limiting one or more of the basic functions of the eye: visual acuity, dark adaptation, color vision, or peripheral vision. These may result from EYE DISEASES; OPTIC NERVE DISEASES; VISUAL PATHWAY diseases; OCCIPITAL LOBE diseases; OCULAR MOTILITY DISORDERS; and other conditions (From Newell, Ophthalmology: Principles and Concepts, 7th ed, p132).\n    ", "id": "MESH:D014786"}
{"mention": "a loss of visual acuity", "mention_text": "During an 18-month period of study 41 hemodialyzed patients receiving desferrioxamine (10-40 mg/kg BW/3 times weekly) for the first time were monitored for detection of audiovisual toxicity. 6 patients presented clinical symptoms of visual or auditory toxicity. Moreover, detailed ophthalmologic and audiologic studies disclosed abnormalities in 7 more asymptomatic patients. Visual toxicity was of retinal origin and was characterized by a tritan-type dyschromatopsy, sometimes associated with a loss of visual acuity and pigmentary retinal deposits. Auditory toxicity was characterized by a mid- to high-frequency neurosensorial hearing loss and the lesion was of the cochlear type. Desferrioxamine withdrawal resulted in a complete recovery of visual function in 1 patient and partial recovery in 3, and a complete reversal of hearing loss in 3 patients and partial recovery in 3. This toxicity appeared in patients receiving the higher doses of desferrioxamine or coincided with the normalization of ferritin or aluminium serum levels. The data indicate that audiovisual toxicity is not an infrequent complication in hemodialyzed patients receiving desferrioxamine. Periodical audiovisual monitoring should be performed on hemodialyzed patients receiving the drug in order to detect adverse effects as early as possible.", "entity": "Vision Disorders", "aliases": "Blindness Day Disabilities Vision Disability Disorder Visual Disorders Hemeralopia Hemeralopias Impairment Impairments Macropsia Macropsias Metamorphopsia Metamorphopsias Micropsia Micropsias", "definition": "Visual impairments limiting one or more of the basic functions of the eye: visual acuity, dark adaptation, color vision, or peripheral vision. These may result from EYE DISEASES; OPTIC NERVE DISEASES; VISUAL PATHWAY diseases; OCCIPITAL LOBE diseases; OCULAR MOTILITY DISORDERS; and other conditions (From Newell, Ophthalmology: Principles and Concepts, 7th ed, p132).\n    ", "id": "MESH:D014786"}
{"mention": "pigmentary retinal deposits", "mention_text": "During an 18-month period of study 41 hemodialyzed patients receiving desferrioxamine (10-40 mg/kg BW/3 times weekly) for the first time were monitored for detection of audiovisual toxicity. 6 patients presented clinical symptoms of visual or auditory toxicity. Moreover, detailed ophthalmologic and audiologic studies disclosed abnormalities in 7 more asymptomatic patients. Visual toxicity was of retinal origin and was characterized by a tritan-type dyschromatopsy, sometimes associated with a loss of visual acuity and pigmentary retinal deposits. Auditory toxicity was characterized by a mid- to high-frequency neurosensorial hearing loss and the lesion was of the cochlear type. Desferrioxamine withdrawal resulted in a complete recovery of visual function in 1 patient and partial recovery in 3, and a complete reversal of hearing loss in 3 patients and partial recovery in 3. This toxicity appeared in patients receiving the higher doses of desferrioxamine or coincided with the normalization of ferritin or aluminium serum levels. The data indicate that audiovisual toxicity is not an infrequent complication in hemodialyzed patients receiving desferrioxamine. Periodical audiovisual monitoring should be performed on hemodialyzed patients receiving the drug in order to detect adverse effects as early as possible.", "entity": "Retinal Diseases", "aliases": "Disease Retinal Diseases", "definition": "", "id": "MESH:D012164"}
{"mention": "Auditory toxicity", "mention_text": "During an 18-month period of study 41 hemodialyzed patients receiving desferrioxamine (10-40 mg/kg BW/3 times weekly) for the first time were monitored for detection of audiovisual toxicity. 6 patients presented clinical symptoms of visual or auditory toxicity. Moreover, detailed ophthalmologic and audiologic studies disclosed abnormalities in 7 more asymptomatic patients. Visual toxicity was of retinal origin and was characterized by a tritan-type dyschromatopsy, sometimes associated with a loss of visual acuity and pigmentary retinal deposits. Auditory toxicity was characterized by a mid- to high-frequency neurosensorial hearing loss and the lesion was of the cochlear type. Desferrioxamine withdrawal resulted in a complete recovery of visual function in 1 patient and partial recovery in 3, and a complete reversal of hearing loss in 3 patients and partial recovery in 3. This toxicity appeared in patients receiving the higher doses of desferrioxamine or coincided with the normalization of ferritin or aluminium serum levels. The data indicate that audiovisual toxicity is not an infrequent complication in hemodialyzed patients receiving desferrioxamine. Periodical audiovisual monitoring should be performed on hemodialyzed patients receiving the drug in order to detect adverse effects as early as possible.", "entity": "Hearing Disorders", "aliases": "Distorted Hearing Dysacusis Disorder Disorders Paracousis Paracusis", "definition": "Conditions that impair the transmission of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways.\n    ", "id": "MESH:D006311"}
{"mention": "neurosensorial hearing loss", "mention_text": "During an 18-month period of study 41 hemodialyzed patients receiving desferrioxamine (10-40 mg/kg BW/3 times weekly) for the first time were monitored for detection of audiovisual toxicity. 6 patients presented clinical symptoms of visual or auditory toxicity. Moreover, detailed ophthalmologic and audiologic studies disclosed abnormalities in 7 more asymptomatic patients. Visual toxicity was of retinal origin and was characterized by a tritan-type dyschromatopsy, sometimes associated with a loss of visual acuity and pigmentary retinal deposits. Auditory toxicity was characterized by a mid- to high-frequency neurosensorial hearing loss and the lesion was of the cochlear type. Desferrioxamine withdrawal resulted in a complete recovery of visual function in 1 patient and partial recovery in 3, and a complete reversal of hearing loss in 3 patients and partial recovery in 3. This toxicity appeared in patients receiving the higher doses of desferrioxamine or coincided with the normalization of ferritin or aluminium serum levels. The data indicate that audiovisual toxicity is not an infrequent complication in hemodialyzed patients receiving desferrioxamine. Periodical audiovisual monitoring should be performed on hemodialyzed patients receiving the drug in order to detect adverse effects as early as possible.", "entity": "Hearing Loss, Sensorineural", "aliases": "Cochlear Hearing Loss Sensorineural", "definition": "Hearing loss resulting from damage to the COCHLEA and the sensorineural elements which lie internally beyond the oval and round windows. These elements include the AUDITORY NERVE and its connections in the BRAINSTEM.\n    ", "id": "MESH:D006319"}
{"mention": "Desferrioxamine", "mention_text": "During an 18-month period of study 41 hemodialyzed patients receiving desferrioxamine (10-40 mg/kg BW/3 times weekly) for the first time were monitored for detection of audiovisual toxicity. 6 patients presented clinical symptoms of visual or auditory toxicity. Moreover, detailed ophthalmologic and audiologic studies disclosed abnormalities in 7 more asymptomatic patients. Visual toxicity was of retinal origin and was characterized by a tritan-type dyschromatopsy, sometimes associated with a loss of visual acuity and pigmentary retinal deposits. Auditory toxicity was characterized by a mid- to high-frequency neurosensorial hearing loss and the lesion was of the cochlear type. Desferrioxamine withdrawal resulted in a complete recovery of visual function in 1 patient and partial recovery in 3, and a complete reversal of hearing loss in 3 patients and partial recovery in 3. This toxicity appeared in patients receiving the higher doses of desferrioxamine or coincided with the normalization of ferritin or aluminium serum levels. The data indicate that audiovisual toxicity is not an infrequent complication in hemodialyzed patients receiving desferrioxamine. Periodical audiovisual monitoring should be performed on hemodialyzed patients receiving the drug in order to detect adverse effects as early as possible.", "entity": "Deferoxamine", "aliases": "B Deferoxamine Desferrioxamine Mesilate Mesylate Methanesulfonate Deferoximine Deferrioxamine Desferal Desferioximine Desferroxamine", "definition": "Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form.\n    ", "id": "MESH:D003676"}
{"mention": "hearing loss", "mention_text": "During an 18-month period of study 41 hemodialyzed patients receiving desferrioxamine (10-40 mg/kg BW/3 times weekly) for the first time were monitored for detection of audiovisual toxicity. 6 patients presented clinical symptoms of visual or auditory toxicity. Moreover, detailed ophthalmologic and audiologic studies disclosed abnormalities in 7 more asymptomatic patients. Visual toxicity was of retinal origin and was characterized by a tritan-type dyschromatopsy, sometimes associated with a loss of visual acuity and pigmentary retinal deposits. Auditory toxicity was characterized by a mid- to high-frequency neurosensorial hearing loss and the lesion was of the cochlear type. Desferrioxamine withdrawal resulted in a complete recovery of visual function in 1 patient and partial recovery in 3, and a complete reversal of hearing loss in 3 patients and partial recovery in 3. This toxicity appeared in patients receiving the higher doses of desferrioxamine or coincided with the normalization of ferritin or aluminium serum levels. The data indicate that audiovisual toxicity is not an infrequent complication in hemodialyzed patients receiving desferrioxamine. Periodical audiovisual monitoring should be performed on hemodialyzed patients receiving the drug in order to detect adverse effects as early as possible.", "entity": "Hearing Loss", "aliases": "Hearing Impairment Loss Hypoacuses Hypoacusis", "definition": "A general term for the complete or partial loss of the ability to hear from one or both ears.\n    ", "id": "MESH:D034381"}
{"mention": "toxicity", "mention_text": "During an 18-month period of study 41 hemodialyzed patients receiving desferrioxamine (10-40 mg/kg BW/3 times weekly) for the first time were monitored for detection of audiovisual toxicity. 6 patients presented clinical symptoms of visual or auditory toxicity. Moreover, detailed ophthalmologic and audiologic studies disclosed abnormalities in 7 more asymptomatic patients. Visual toxicity was of retinal origin and was characterized by a tritan-type dyschromatopsy, sometimes associated with a loss of visual acuity and pigmentary retinal deposits. Auditory toxicity was characterized by a mid- to high-frequency neurosensorial hearing loss and the lesion was of the cochlear type. Desferrioxamine withdrawal resulted in a complete recovery of visual function in 1 patient and partial recovery in 3, and a complete reversal of hearing loss in 3 patients and partial recovery in 3. This toxicity appeared in patients receiving the higher doses of desferrioxamine or coincided with the normalization of ferritin or aluminium serum levels. The data indicate that audiovisual toxicity is not an infrequent complication in hemodialyzed patients receiving desferrioxamine. Periodical audiovisual monitoring should be performed on hemodialyzed patients receiving the drug in order to detect adverse effects as early as possible.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "Myasthenia gravis", "mention_text": "Myasthenia gravis presenting as weakness after magnesium administration.", "entity": "Myasthenia Gravis", "aliases": "Generalized Myasthenia Gravis Ocular", "definition": "A disorder of neuromuscular transmission characterized by weakness of cranial and skeletal muscles. Autoantibodies directed against acetylcholine receptors damage the motor endplate portion of the NEUROMUSCULAR JUNCTION, impairing the transmission of impulses to skeletal muscles. Clinical manifestations may include diplopia, ptosis, and weakness of facial, bulbar, respiratory, and proximal limb muscles. The disease may remain limited to the ocular muscles. THYMOMA is commonly associated with this condition. (Adams et al., Principles of Neurology, 6th ed, p1459)\n    ", "id": "MESH:D009157"}
{"mention": "magnesium", "mention_text": "Myasthenia gravis presenting as weakness after magnesium administration.", "entity": "Magnesium", "aliases": "Magnesium", "definition": "A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.\n    ", "id": "MESH:D008274"}
{"mention": "neuromuscular disease", "mention_text": "We studied a patient with no prior history of neuromuscular disease who became virtually quadriplegic after parenteral magnesium administration for preeclampsia. The serum magnesium concentration was 3.0 mEq/L, which is usually well tolerated. The magnesium was stopped and she recovered over a few days. While she was weak, 2-Hz repetitive stimulation revealed a decrement without significant facilitation at rapid rates or after exercise, suggesting postsynaptic neuromuscular blockade. After her strength returned, repetitive stimulation was normal, but single fiber EMG revealed increased jitter and blocking. Her acetylcholine receptor antibody level was markedly elevated. Although paralysis after magnesium administration has been described in patients with known myasthenia gravis, it has not previously been reported to be the initial or only manifestation of the disease. Patients who are unusually sensitive to the neuromuscular effects of magnesium should be suspected of having an underlying disorder of neuromuscular transmission.", "entity": "Neuromuscular Diseases", "aliases": "Amyotonia Congenita Benign Fasciculation-Cramp Syndrome Syndromes Cramp Fasciculation Cramp-Fasciculation Foley Denny Brown Foley-Denny-Brown Neuromuscular Disease Diseases Oppenheim Oppenheim's Oppenheims", "definition": "A general term encompassing lower MOTOR NEURON DISEASE; PERIPHERAL NERVOUS SYSTEM DISEASES; and certain MUSCULAR DISEASES. Manifestations include MUSCLE WEAKNESS; FASCICULATION; muscle ATROPHY; SPASM; MYOKYMIA; MUSCLE HYPERTONIA, myalgias, and MUSCLE HYPOTONIA.\n    ", "id": "MESH:D009468"}
{"mention": "quadriplegic", "mention_text": "We studied a patient with no prior history of neuromuscular disease who became virtually quadriplegic after parenteral magnesium administration for preeclampsia. The serum magnesium concentration was 3.0 mEq/L, which is usually well tolerated. The magnesium was stopped and she recovered over a few days. While she was weak, 2-Hz repetitive stimulation revealed a decrement without significant facilitation at rapid rates or after exercise, suggesting postsynaptic neuromuscular blockade. After her strength returned, repetitive stimulation was normal, but single fiber EMG revealed increased jitter and blocking. Her acetylcholine receptor antibody level was markedly elevated. Although paralysis after magnesium administration has been described in patients with known myasthenia gravis, it has not previously been reported to be the initial or only manifestation of the disease. Patients who are unusually sensitive to the neuromuscular effects of magnesium should be suspected of having an underlying disorder of neuromuscular transmission.", "entity": "Quadriplegia", "aliases": "Flaccid Quadriplegia Quadriplegias Tetraplegia Tetraplegias Locked In Syndrome Locked-In Syndromes Paralysis Spinal Quadriplegic Quadripareses Quadriparesis Spastic", "definition": "Severe or complete loss of motor function in all four limbs which may result from BRAIN DISEASES; SPINAL CORD DISEASES; PERIPHERAL NERVOUS SYSTEM DISEASES; NEUROMUSCULAR DISEASES; or rarely MUSCULAR DISEASES. The locked-in syndrome is characterized by quadriplegia in combination with cranial muscle paralysis. Consciousness is spared and the only retained voluntary motor activity may be limited eye movements. This condition is usually caused by a lesion in the upper BRAIN STEM which injures the descending cortico-spinal and cortico-bulbar tracts.\n    ", "id": "MESH:D011782"}
{"mention": "magnesium", "mention_text": "We studied a patient with no prior history of neuromuscular disease who became virtually quadriplegic after parenteral magnesium administration for preeclampsia. The serum magnesium concentration was 3.0 mEq/L, which is usually well tolerated. The magnesium was stopped and she recovered over a few days. While she was weak, 2-Hz repetitive stimulation revealed a decrement without significant facilitation at rapid rates or after exercise, suggesting postsynaptic neuromuscular blockade. After her strength returned, repetitive stimulation was normal, but single fiber EMG revealed increased jitter and blocking. Her acetylcholine receptor antibody level was markedly elevated. Although paralysis after magnesium administration has been described in patients with known myasthenia gravis, it has not previously been reported to be the initial or only manifestation of the disease. Patients who are unusually sensitive to the neuromuscular effects of magnesium should be suspected of having an underlying disorder of neuromuscular transmission.", "entity": "Magnesium", "aliases": "Magnesium", "definition": "A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.\n    ", "id": "MESH:D008274"}
{"mention": "preeclampsia", "mention_text": "We studied a patient with no prior history of neuromuscular disease who became virtually quadriplegic after parenteral magnesium administration for preeclampsia. The serum magnesium concentration was 3.0 mEq/L, which is usually well tolerated. The magnesium was stopped and she recovered over a few days. While she was weak, 2-Hz repetitive stimulation revealed a decrement without significant facilitation at rapid rates or after exercise, suggesting postsynaptic neuromuscular blockade. After her strength returned, repetitive stimulation was normal, but single fiber EMG revealed increased jitter and blocking. Her acetylcholine receptor antibody level was markedly elevated. Although paralysis after magnesium administration has been described in patients with known myasthenia gravis, it has not previously been reported to be the initial or only manifestation of the disease. Patients who are unusually sensitive to the neuromuscular effects of magnesium should be suspected of having an underlying disorder of neuromuscular transmission.", "entity": "Pre-Eclampsia", "aliases": "EPH Complex Gestosis Toxemia Toxemias Edema Proteinuria Hypertension Edema-Proteinuria-Hypertension Hypertension-Edema-Proteinuria Proteinuria-Edema-Hypertension Pre Eclampsia Pre-Eclampsia Preeclampsia Preeclampsia/Eclampsia 1 Pregnancy Of", "definition": "A complication of PREGNANCY, characterized by a complex of symptoms including maternal HYPERTENSION and PROTEINURIA with or without pathological EDEMA. Symptoms may range between mild and severe. Pre-eclampsia usually occurs after the 20th week of gestation, but may develop before this time in the presence of trophoblastic disease.\n    ", "id": "MESH:D011225"}
{"mention": "postsynaptic neuromuscular blockade", "mention_text": "We studied a patient with no prior history of neuromuscular disease who became virtually quadriplegic after parenteral magnesium administration for preeclampsia. The serum magnesium concentration was 3.0 mEq/L, which is usually well tolerated. The magnesium was stopped and she recovered over a few days. While she was weak, 2-Hz repetitive stimulation revealed a decrement without significant facilitation at rapid rates or after exercise, suggesting postsynaptic neuromuscular blockade. After her strength returned, repetitive stimulation was normal, but single fiber EMG revealed increased jitter and blocking. Her acetylcholine receptor antibody level was markedly elevated. Although paralysis after magnesium administration has been described in patients with known myasthenia gravis, it has not previously been reported to be the initial or only manifestation of the disease. Patients who are unusually sensitive to the neuromuscular effects of magnesium should be suspected of having an underlying disorder of neuromuscular transmission.", "entity": "Neuromuscular Diseases", "aliases": "Amyotonia Congenita Benign Fasciculation-Cramp Syndrome Syndromes Cramp Fasciculation Cramp-Fasciculation Foley Denny Brown Foley-Denny-Brown Neuromuscular Disease Diseases Oppenheim Oppenheim's Oppenheims", "definition": "A general term encompassing lower MOTOR NEURON DISEASE; PERIPHERAL NERVOUS SYSTEM DISEASES; and certain MUSCULAR DISEASES. Manifestations include MUSCLE WEAKNESS; FASCICULATION; muscle ATROPHY; SPASM; MYOKYMIA; MUSCLE HYPERTONIA, myalgias, and MUSCLE HYPOTONIA.\n    ", "id": "MESH:D009468"}
{"mention": "acetylcholine", "mention_text": "We studied a patient with no prior history of neuromuscular disease who became virtually quadriplegic after parenteral magnesium administration for preeclampsia. The serum magnesium concentration was 3.0 mEq/L, which is usually well tolerated. The magnesium was stopped and she recovered over a few days. While she was weak, 2-Hz repetitive stimulation revealed a decrement without significant facilitation at rapid rates or after exercise, suggesting postsynaptic neuromuscular blockade. After her strength returned, repetitive stimulation was normal, but single fiber EMG revealed increased jitter and blocking. Her acetylcholine receptor antibody level was markedly elevated. Although paralysis after magnesium administration has been described in patients with known myasthenia gravis, it has not previously been reported to be the initial or only manifestation of the disease. Patients who are unusually sensitive to the neuromuscular effects of magnesium should be suspected of having an underlying disorder of neuromuscular transmission.", "entity": "Acetylcholine", "aliases": "2-(Acetyloxy)-N,N,N-trimethylethanaminium Acetilcolina Cusi Acetylcholine Bromide Chloride Fluoride Hydroxide Iodide L Tartrate L-Tartrate Perchlorate Picrate (1:1) Sulfate Alcon Brand of Bournonville Bromoacetylcholine Chloroacetylcholine Ciba Vision Iolab Miochol", "definition": "A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.\n    ", "id": "MESH:D000109"}
{"mention": "paralysis", "mention_text": "We studied a patient with no prior history of neuromuscular disease who became virtually quadriplegic after parenteral magnesium administration for preeclampsia. The serum magnesium concentration was 3.0 mEq/L, which is usually well tolerated. The magnesium was stopped and she recovered over a few days. While she was weak, 2-Hz repetitive stimulation revealed a decrement without significant facilitation at rapid rates or after exercise, suggesting postsynaptic neuromuscular blockade. After her strength returned, repetitive stimulation was normal, but single fiber EMG revealed increased jitter and blocking. Her acetylcholine receptor antibody level was markedly elevated. Although paralysis after magnesium administration has been described in patients with known myasthenia gravis, it has not previously been reported to be the initial or only manifestation of the disease. Patients who are unusually sensitive to the neuromuscular effects of magnesium should be suspected of having an underlying disorder of neuromuscular transmission.", "entity": "Paralysis", "aliases": "Palsies Palsy Paralyses Paralysis Todd Todd's Plegia Plegias Todds", "definition": "A general term most often used to describe severe or complete loss of muscle strength due to motor system disease from the level of the cerebral cortex to the muscle fiber. This term may also occasionally refer to a loss of sensory function. (From Adams et al., Principles of Neurology, 6th ed, p45)\n    ", "id": "MESH:D010243"}
{"mention": "myasthenia gravis", "mention_text": "We studied a patient with no prior history of neuromuscular disease who became virtually quadriplegic after parenteral magnesium administration for preeclampsia. The serum magnesium concentration was 3.0 mEq/L, which is usually well tolerated. The magnesium was stopped and she recovered over a few days. While she was weak, 2-Hz repetitive stimulation revealed a decrement without significant facilitation at rapid rates or after exercise, suggesting postsynaptic neuromuscular blockade. After her strength returned, repetitive stimulation was normal, but single fiber EMG revealed increased jitter and blocking. Her acetylcholine receptor antibody level was markedly elevated. Although paralysis after magnesium administration has been described in patients with known myasthenia gravis, it has not previously been reported to be the initial or only manifestation of the disease. Patients who are unusually sensitive to the neuromuscular effects of magnesium should be suspected of having an underlying disorder of neuromuscular transmission.", "entity": "Myasthenia Gravis", "aliases": "Generalized Myasthenia Gravis Ocular", "definition": "A disorder of neuromuscular transmission characterized by weakness of cranial and skeletal muscles. Autoantibodies directed against acetylcholine receptors damage the motor endplate portion of the NEUROMUSCULAR JUNCTION, impairing the transmission of impulses to skeletal muscles. Clinical manifestations may include diplopia, ptosis, and weakness of facial, bulbar, respiratory, and proximal limb muscles. The disease may remain limited to the ocular muscles. THYMOMA is commonly associated with this condition. (Adams et al., Principles of Neurology, 6th ed, p1459)\n    ", "id": "MESH:D009157"}
{"mention": "disorder of neuromuscular transmission", "mention_text": "We studied a patient with no prior history of neuromuscular disease who became virtually quadriplegic after parenteral magnesium administration for preeclampsia. The serum magnesium concentration was 3.0 mEq/L, which is usually well tolerated. The magnesium was stopped and she recovered over a few days. While she was weak, 2-Hz repetitive stimulation revealed a decrement without significant facilitation at rapid rates or after exercise, suggesting postsynaptic neuromuscular blockade. After her strength returned, repetitive stimulation was normal, but single fiber EMG revealed increased jitter and blocking. Her acetylcholine receptor antibody level was markedly elevated. Although paralysis after magnesium administration has been described in patients with known myasthenia gravis, it has not previously been reported to be the initial or only manifestation of the disease. Patients who are unusually sensitive to the neuromuscular effects of magnesium should be suspected of having an underlying disorder of neuromuscular transmission.", "entity": "Neuromuscular Junction Diseases", "aliases": "Neuromuscular Junction Disease Diseases Disorder Disorders Toxic Transmission", "definition": "Conditions characterized by impaired transmission of impulses at the NEUROMUSCULAR JUNCTION. This may result from disorders that affect receptor function, pre- or postsynaptic membrane function, or ACETYLCHOLINESTERASE activity. The majority of diseases in this category are associated with autoimmune, toxic, or inherited conditions.\n    ", "id": "MESH:D020511"}
{"mention": "Chloroacetaldehyde", "mention_text": "Chloroacetaldehyde and its contribution to urotoxicity during treatment with cyclophosphamide or ifosfamide. An experimental study/short communication.", "entity": "chloroacetaldehyde", "aliases": "2-chloroacetaldehyde chloroacetaldehyde hydrate", "definition": "", "id": "MESH:C004656"}
{"mention": "cyclophosphamide", "mention_text": "Chloroacetaldehyde and its contribution to urotoxicity during treatment with cyclophosphamide or ifosfamide. An experimental study/short communication.", "entity": "Cyclophosphamide", "aliases": "Anhydrous Cyclophosphamide B 518 B-518 B518 Monohydrate (R)-Isomer (S)-Isomer Cyclophosphane Cytophosphan Cytophosphane Cytoxan Endoxan NSC 26271 NSC-26271 NSC26271 Neosar Procytox Sendoxan", "definition": "Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.\n    ", "id": "MESH:D003520"}
{"mention": "ifosfamide", "mention_text": "Chloroacetaldehyde and its contribution to urotoxicity during treatment with cyclophosphamide or ifosfamide. An experimental study/short communication.", "entity": "Ifosfamide", "aliases": "Asta Z 4942 Holoxan Ifosfamide Iphosphamide Iso Endoxan Iso-Endoxan Isofosfamide Isophosphamide NSC 109,724 109724 NSC-109,724 NSC-109724 NSC109,724 NSC109724", "definition": "Positional isomer of CYCLOPHOSPHAMIDE which is active as an alkylating agent and an immunosuppressive agent.\n    ", "id": "MESH:D007069"}
{"mention": "chloroacetaldehyde", "mention_text": "Based on clinical data, indicating that chloroacetaldehyde (CAA) is an important metabolite of oxazaphosphorine cytostatics, an experimental study was carried out in order to elucidate the role of CAA in the development of hemorrhagic cystitis. The data demonstrate that CAA after i.v. administration does not contribute to bladder damage. When instilled directly into the bladder, CAA exerts urotoxic effects, it is, however, susceptible to detoxification with mesna.", "entity": "chloroacetaldehyde", "aliases": "2-chloroacetaldehyde chloroacetaldehyde hydrate", "definition": "", "id": "MESH:C004656"}
{"mention": "CAA", "mention_text": "Based on clinical data, indicating that chloroacetaldehyde (CAA) is an important metabolite of oxazaphosphorine cytostatics, an experimental study was carried out in order to elucidate the role of CAA in the development of hemorrhagic cystitis. The data demonstrate that CAA after i.v. administration does not contribute to bladder damage. When instilled directly into the bladder, CAA exerts urotoxic effects, it is, however, susceptible to detoxification with mesna.", "entity": "chloroacetaldehyde", "aliases": "2-chloroacetaldehyde chloroacetaldehyde hydrate", "definition": "", "id": "MESH:C004656"}
{"mention": "hemorrhagic", "mention_text": "Based on clinical data, indicating that chloroacetaldehyde (CAA) is an important metabolite of oxazaphosphorine cytostatics, an experimental study was carried out in order to elucidate the role of CAA in the development of hemorrhagic cystitis. The data demonstrate that CAA after i.v. administration does not contribute to bladder damage. When instilled directly into the bladder, CAA exerts urotoxic effects, it is, however, susceptible to detoxification with mesna.", "entity": "Hemorrhage", "aliases": "Bleeding Hemorrhage Hemorrhages", "definition": "Bleeding or escape of blood from a vessel.\n    ", "id": "MESH:D006470"}
{"mention": "cystitis", "mention_text": "Based on clinical data, indicating that chloroacetaldehyde (CAA) is an important metabolite of oxazaphosphorine cytostatics, an experimental study was carried out in order to elucidate the role of CAA in the development of hemorrhagic cystitis. The data demonstrate that CAA after i.v. administration does not contribute to bladder damage. When instilled directly into the bladder, CAA exerts urotoxic effects, it is, however, susceptible to detoxification with mesna.", "entity": "Cystitis", "aliases": "Cystitides Cystitis", "definition": "Inflammation of the URINARY BLADDER, either from bacterial or non-bacterial causes. Cystitis is usually associated with painful urination (dysuria), increased frequency, urgency, and suprapubic pain.\n    ", "id": "MESH:D003556"}
{"mention": "bladder damage", "mention_text": "Based on clinical data, indicating that chloroacetaldehyde (CAA) is an important metabolite of oxazaphosphorine cytostatics, an experimental study was carried out in order to elucidate the role of CAA in the development of hemorrhagic cystitis. The data demonstrate that CAA after i.v. administration does not contribute to bladder damage. When instilled directly into the bladder, CAA exerts urotoxic effects, it is, however, susceptible to detoxification with mesna.", "entity": "Urinary Bladder Diseases", "aliases": "Bladder Disease Diseases Urinary", "definition": "Pathological processes of the URINARY BLADDER.\n    ", "id": "MESH:D001745"}
{"mention": "mesna", "mention_text": "Based on clinical data, indicating that chloroacetaldehyde (CAA) is an important metabolite of oxazaphosphorine cytostatics, an experimental study was carried out in order to elucidate the role of CAA in the development of hemorrhagic cystitis. The data demonstrate that CAA after i.v. administration does not contribute to bladder damage. When instilled directly into the bladder, CAA exerts urotoxic effects, it is, however, susceptible to detoxification with mesna.", "entity": "Mesna", "aliases": "2 Mercaptoethanesulfonate 2-Mercaptoethanesulfonate 2-Mercaptoethanesulphonate Sodium ASTA D 7093 Medica Brand of Mesna ASTA-D ASTAD Bristol Myers Squibb Bristol-Myers Coenzyme M Kendrick MESNA cell MESNA-cell Sanfer Mesnex Mesnum Mistabron Mistabronco Mitexan Mucofluid UCB 3983 UCB-3983 UCB3983 Uromitexan Ziken pharm", "definition": "A sulfhydryl compound used to prevent urothelial toxicity by inactivating metabolites from ANTINEOPLASTIC AGENTS, such as IFOSFAMIDE or CYCLOPHOSPHAMIDE.\n    ", "id": "MESH:D015080"}
{"mention": "pain", "mention_text": "Source of pain and primitive dysfunction in migraine: an identical site?", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "migraine", "mention_text": "Source of pain and primitive dysfunction in migraine: an identical site?", "entity": "Migraine Disorders", "aliases": "Abdominal Migraine Migraines Acute Confusional Cervical Syndrome Syndromes Disorder Disorders Headache Sick Headaches Hemicrania Variant Variants Status Migrainosus", "definition": "A class of disabling primary headache disorders, characterized by recurrent unilateral pulsatile headaches. The two major subtypes are common migraine (without aura) and classic migraine (with aura or neurological symptoms). (International Classification of Headache Disorders, 2nd ed. Cephalalgia 2004: suppl 1)\n    ", "id": "MESH:D008881"}
{"mention": "migraine", "mention_text": "Twenty common migraine patients received a one sided frontotemporal application of nitroglycerin (10 patients) or placebo ointment (10 patients) in a double blind study. Early onset migraine attacks were induced by nitroglycerin in seven out of 10 patients versus no patient in the placebo group. Subsequently 20 migraine patients, who developed an early onset attack with frontotemporal nitroglycerin, received the drug in a second induction test at other body areas. No early onset migraine was observed. Thus the migraine-inducing effect of nitroglycerin seems to depend on direct stimulation of the habitual site of pain, suggesting that the frontotemporal region is of crucial importance in the development of a migraine crisis. This is not consistent with a CNS origin of migraine attack.", "entity": "Migraine Disorders", "aliases": "Abdominal Migraine Migraines Acute Confusional Cervical Syndrome Syndromes Disorder Disorders Headache Sick Headaches Hemicrania Variant Variants Status Migrainosus", "definition": "A class of disabling primary headache disorders, characterized by recurrent unilateral pulsatile headaches. The two major subtypes are common migraine (without aura) and classic migraine (with aura or neurological symptoms). (International Classification of Headache Disorders, 2nd ed. Cephalalgia 2004: suppl 1)\n    ", "id": "MESH:D008881"}
{"mention": "nitroglycerin", "mention_text": "Twenty common migraine patients received a one sided frontotemporal application of nitroglycerin (10 patients) or placebo ointment (10 patients) in a double blind study. Early onset migraine attacks were induced by nitroglycerin in seven out of 10 patients versus no patient in the placebo group. Subsequently 20 migraine patients, who developed an early onset attack with frontotemporal nitroglycerin, received the drug in a second induction test at other body areas. No early onset migraine was observed. Thus the migraine-inducing effect of nitroglycerin seems to depend on direct stimulation of the habitual site of pain, suggesting that the frontotemporal region is of crucial importance in the development of a migraine crisis. This is not consistent with a CNS origin of migraine attack.", "entity": "Nitroglycerin", "aliases": "Anginine Dynamite Gilustenon Glyceryl Trinitrate Nitrangin Nitro Bid Dur Nitro-Bid Nitro-Dur NitroBid NitroDur Nitrocard Nitroderm TTS Nitroglycerin Nitroglyn Nitrol Nitrolan Nitrong Nitrospan Nitrostat Perlinganit Susadrin Sustac Sustak Sustonit Transderm Tridil Trinitrin Trinitrolong", "definition": "A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives.\n    ", "id": "MESH:D005996"}
{"mention": "pain", "mention_text": "Twenty common migraine patients received a one sided frontotemporal application of nitroglycerin (10 patients) or placebo ointment (10 patients) in a double blind study. Early onset migraine attacks were induced by nitroglycerin in seven out of 10 patients versus no patient in the placebo group. Subsequently 20 migraine patients, who developed an early onset attack with frontotemporal nitroglycerin, received the drug in a second induction test at other body areas. No early onset migraine was observed. Thus the migraine-inducing effect of nitroglycerin seems to depend on direct stimulation of the habitual site of pain, suggesting that the frontotemporal region is of crucial importance in the development of a migraine crisis. This is not consistent with a CNS origin of migraine attack.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "Clotiazepam", "mention_text": "Clotiazepam-induced acute hepatitis.", "entity": "clotiazepam", "aliases": "Y 6047 Y-6047 Y6047 clotiazepam", "definition": "", "id": "MESH:C084599"}
{"mention": "hepatitis", "mention_text": "Clotiazepam-induced acute hepatitis.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "hepatitis", "mention_text": "We report the case of a patient who developed acute hepatitis with extensive hepatocellular necrosis, 7 months after the onset of administration of clotiazepam, a thienodiazepine derivative. Clotiazepam withdrawal was followed by prompt recovery. The administration of several benzodiazepines, chemically related to clotiazepam, did not interfere with recovery and did not induce any relapse of hepatitis. This observation shows that clotiazepam can induce acute hepatitis and suggests that there is no cross hepatotoxicity between clotiazepam and several benzodiazepines.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "extensive hepatocellular necrosis", "mention_text": "We report the case of a patient who developed acute hepatitis with extensive hepatocellular necrosis, 7 months after the onset of administration of clotiazepam, a thienodiazepine derivative. Clotiazepam withdrawal was followed by prompt recovery. The administration of several benzodiazepines, chemically related to clotiazepam, did not interfere with recovery and did not induce any relapse of hepatitis. This observation shows that clotiazepam can induce acute hepatitis and suggests that there is no cross hepatotoxicity between clotiazepam and several benzodiazepines.", "entity": "Massive Hepatic Necrosis", "aliases": "Acute Yellow Atrophies Atrophy of Liver Hepatic Necrosis Massive", "definition": "Extensive and rapid death of parenchymal cells in the LIVER, often due to exposure to toxic materials. It is characterized by a soft, flabby, yellow-brown wrinkled, and shrunken liver. It was called \"acute yellow atrophy\".\n    ", "id": "MESH:D047508"}
{"mention": "clotiazepam", "mention_text": "We report the case of a patient who developed acute hepatitis with extensive hepatocellular necrosis, 7 months after the onset of administration of clotiazepam, a thienodiazepine derivative. Clotiazepam withdrawal was followed by prompt recovery. The administration of several benzodiazepines, chemically related to clotiazepam, did not interfere with recovery and did not induce any relapse of hepatitis. This observation shows that clotiazepam can induce acute hepatitis and suggests that there is no cross hepatotoxicity between clotiazepam and several benzodiazepines.", "entity": "clotiazepam", "aliases": "Y 6047 Y-6047 Y6047 clotiazepam", "definition": "", "id": "MESH:C084599"}
{"mention": "thienodiazepine", "mention_text": "We report the case of a patient who developed acute hepatitis with extensive hepatocellular necrosis, 7 months after the onset of administration of clotiazepam, a thienodiazepine derivative. Clotiazepam withdrawal was followed by prompt recovery. The administration of several benzodiazepines, chemically related to clotiazepam, did not interfere with recovery and did not induce any relapse of hepatitis. This observation shows that clotiazepam can induce acute hepatitis and suggests that there is no cross hepatotoxicity between clotiazepam and several benzodiazepines.", "entity": "thienodiazepine substance", "aliases": "Bay g 5653 thienodiazepine substance", "definition": "", "id": "MESH:C013295"}
{"mention": "Clotiazepam", "mention_text": "We report the case of a patient who developed acute hepatitis with extensive hepatocellular necrosis, 7 months after the onset of administration of clotiazepam, a thienodiazepine derivative. Clotiazepam withdrawal was followed by prompt recovery. The administration of several benzodiazepines, chemically related to clotiazepam, did not interfere with recovery and did not induce any relapse of hepatitis. This observation shows that clotiazepam can induce acute hepatitis and suggests that there is no cross hepatotoxicity between clotiazepam and several benzodiazepines.", "entity": "clotiazepam", "aliases": "Y 6047 Y-6047 Y6047 clotiazepam", "definition": "", "id": "MESH:C084599"}
{"mention": "benzodiazepines", "mention_text": "We report the case of a patient who developed acute hepatitis with extensive hepatocellular necrosis, 7 months after the onset of administration of clotiazepam, a thienodiazepine derivative. Clotiazepam withdrawal was followed by prompt recovery. The administration of several benzodiazepines, chemically related to clotiazepam, did not interfere with recovery and did not induce any relapse of hepatitis. This observation shows that clotiazepam can induce acute hepatitis and suggests that there is no cross hepatotoxicity between clotiazepam and several benzodiazepines.", "entity": "Benzodiazepines", "aliases": "Benzodiazepine Compounds Benzodiazepines", "definition": "A group of two-ring heterocyclic compounds consisting of a benzene ring fused to a diazepine ring.\n    ", "id": "MESH:D001569"}
{"mention": "hepatotoxicity", "mention_text": "We report the case of a patient who developed acute hepatitis with extensive hepatocellular necrosis, 7 months after the onset of administration of clotiazepam, a thienodiazepine derivative. Clotiazepam withdrawal was followed by prompt recovery. The administration of several benzodiazepines, chemically related to clotiazepam, did not interfere with recovery and did not induce any relapse of hepatitis. This observation shows that clotiazepam can induce acute hepatitis and suggests that there is no cross hepatotoxicity between clotiazepam and several benzodiazepines.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "hypertension", "mention_text": "Arterial hypertension as a complication of prolonged ketoconazole treatment.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "ketoconazole", "mention_text": "Arterial hypertension as a complication of prolonged ketoconazole treatment.", "entity": "Ketoconazole", "aliases": "Janssen Brand of Ketoconazole Nizoral R 41400 R-41400 R41,400 R41400", "definition": "Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.\n    ", "id": "MESH:D007654"}
{"mention": "Cushing's syndrome", "mention_text": "Two of 14 patients with Cushing's syndrome treated on a long-term basis with ketoconazole developed sustained hypertension. In both cases normal plasma and urinary free cortisol levels had been achieved following ketoconazole therapy, yet continuous blood pressure monitoring demonstrated hypertension 31 (patient 1) and 52 weeks (patient 2) after treatment. In patient 1, plasma levels of deoxycorticosterone and 11-deoxycortisol were elevated. In patient 2, in addition to an increase in both deoxycorticosterone and 11-deoxycortisol levels, plasma aldosterone values were raised, with a concomitant suppression of renin levels. Our findings show that long-term treatment with high doses of ketoconazole may induce enzyme blockade leading to mineralocorticoid-related hypertension.", "entity": "Cushing Syndrome", "aliases": "Cushing Syndrome Cushing's Hypercortisolism", "definition": "A condition caused by prolonged exposure to excess levels of cortisol (HYDROCORTISONE) or other GLUCOCORTICOIDS from endogenous or exogenous sources. It is characterized by upper body OBESITY; OSTEOPOROSIS; HYPERTENSION; DIABETES MELLITUS; HIRSUTISM; AMENORRHEA; and excess body fluid. Endogenous Cushing syndrome or spontaneous hypercortisolism is divided into two groups, those due to an excess of ADRENOCORTICOTROPIN and those that are ACTH-independent.\n    ", "id": "MESH:D003480"}
{"mention": "ketoconazole", "mention_text": "Two of 14 patients with Cushing's syndrome treated on a long-term basis with ketoconazole developed sustained hypertension. In both cases normal plasma and urinary free cortisol levels had been achieved following ketoconazole therapy, yet continuous blood pressure monitoring demonstrated hypertension 31 (patient 1) and 52 weeks (patient 2) after treatment. In patient 1, plasma levels of deoxycorticosterone and 11-deoxycortisol were elevated. In patient 2, in addition to an increase in both deoxycorticosterone and 11-deoxycortisol levels, plasma aldosterone values were raised, with a concomitant suppression of renin levels. Our findings show that long-term treatment with high doses of ketoconazole may induce enzyme blockade leading to mineralocorticoid-related hypertension.", "entity": "Ketoconazole", "aliases": "Janssen Brand of Ketoconazole Nizoral R 41400 R-41400 R41,400 R41400", "definition": "Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.\n    ", "id": "MESH:D007654"}
{"mention": "hypertension", "mention_text": "Two of 14 patients with Cushing's syndrome treated on a long-term basis with ketoconazole developed sustained hypertension. In both cases normal plasma and urinary free cortisol levels had been achieved following ketoconazole therapy, yet continuous blood pressure monitoring demonstrated hypertension 31 (patient 1) and 52 weeks (patient 2) after treatment. In patient 1, plasma levels of deoxycorticosterone and 11-deoxycortisol were elevated. In patient 2, in addition to an increase in both deoxycorticosterone and 11-deoxycortisol levels, plasma aldosterone values were raised, with a concomitant suppression of renin levels. Our findings show that long-term treatment with high doses of ketoconazole may induce enzyme blockade leading to mineralocorticoid-related hypertension.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "cortisol", "mention_text": "Two of 14 patients with Cushing's syndrome treated on a long-term basis with ketoconazole developed sustained hypertension. In both cases normal plasma and urinary free cortisol levels had been achieved following ketoconazole therapy, yet continuous blood pressure monitoring demonstrated hypertension 31 (patient 1) and 52 weeks (patient 2) after treatment. In patient 1, plasma levels of deoxycorticosterone and 11-deoxycortisol were elevated. In patient 2, in addition to an increase in both deoxycorticosterone and 11-deoxycortisol levels, plasma aldosterone values were raised, with a concomitant suppression of renin levels. Our findings show that long-term treatment with high doses of ketoconazole may induce enzyme blockade leading to mineralocorticoid-related hypertension.", "entity": "Hydrocortisone", "aliases": "11 Epicortisol 11-Epicortisol Cortifair Cortisol Cortril Hydrocortisone (11 alpha)-Isomer (9 beta,10 alpha,11", "definition": "The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.\n    ", "id": "MESH:D006854"}
{"mention": "deoxycorticosterone", "mention_text": "Two of 14 patients with Cushing's syndrome treated on a long-term basis with ketoconazole developed sustained hypertension. In both cases normal plasma and urinary free cortisol levels had been achieved following ketoconazole therapy, yet continuous blood pressure monitoring demonstrated hypertension 31 (patient 1) and 52 weeks (patient 2) after treatment. In patient 1, plasma levels of deoxycorticosterone and 11-deoxycortisol were elevated. In patient 2, in addition to an increase in both deoxycorticosterone and 11-deoxycortisol levels, plasma aldosterone values were raised, with a concomitant suppression of renin levels. Our findings show that long-term treatment with high doses of ketoconazole may induce enzyme blockade leading to mineralocorticoid-related hypertension.", "entity": "Desoxycorticosterone", "aliases": "11 Decorticosterone 11-Decorticosterone 21 Hydroxy 4 pregnene 3,20 dione Hydroxyprogesterone 21-Hydroxy-4-pregnene-3,20-dione 21-Hydroxyprogesterone Cortexone Deoxycorticosterone Desoxycorticosterone Desoxycortone", "definition": "A steroid metabolite that is the 11-deoxy derivative of CORTICOSTERONE and the 21-hydroxy derivative of PROGESTERONE\n    ", "id": "MESH:D003900"}
{"mention": "11-deoxycortisol", "mention_text": "Two of 14 patients with Cushing's syndrome treated on a long-term basis with ketoconazole developed sustained hypertension. In both cases normal plasma and urinary free cortisol levels had been achieved following ketoconazole therapy, yet continuous blood pressure monitoring demonstrated hypertension 31 (patient 1) and 52 weeks (patient 2) after treatment. In patient 1, plasma levels of deoxycorticosterone and 11-deoxycortisol were elevated. In patient 2, in addition to an increase in both deoxycorticosterone and 11-deoxycortisol levels, plasma aldosterone values were raised, with a concomitant suppression of renin levels. Our findings show that long-term treatment with high doses of ketoconazole may induce enzyme blockade leading to mineralocorticoid-related hypertension.", "entity": "Cortodoxone", "aliases": "11 Deoxycortisol Desoxycortisol Desoxycortisone 11-Deoxycortisol 11-Desoxycortisol 11-Desoxycortisone Cortexolone Cortodoxone Reichstein Substance S Reichstein's Reichsteins", "definition": "17,21-Dihydroxypregn-4-ene-3,20-dione. A 17-hydroxycorticosteroid with glucocorticoid and anti-inflammatory activities.\n    ", "id": "MESH:D003350"}
{"mention": "aldosterone", "mention_text": "Two of 14 patients with Cushing's syndrome treated on a long-term basis with ketoconazole developed sustained hypertension. In both cases normal plasma and urinary free cortisol levels had been achieved following ketoconazole therapy, yet continuous blood pressure monitoring demonstrated hypertension 31 (patient 1) and 52 weeks (patient 2) after treatment. In patient 1, plasma levels of deoxycorticosterone and 11-deoxycortisol were elevated. In patient 2, in addition to an increase in both deoxycorticosterone and 11-deoxycortisol levels, plasma aldosterone values were raised, with a concomitant suppression of renin levels. Our findings show that long-term treatment with high doses of ketoconazole may induce enzyme blockade leading to mineralocorticoid-related hypertension.", "entity": "Aldosterone", "aliases": "Aldosterone (+-)-Isomer (11 beta,17 alpha)-Isomer", "definition": "A hormone secreted by the ADRENAL CORTEX that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium.\n    ", "id": "MESH:D000450"}
{"mention": "angiotensin", "mention_text": "Effects of an inhibitor of angiotensin converting enzyme (Captopril) on pulmonary and renal insufficiency due to intravascular coagulation in the rat.", "entity": "Angiotensins", "aliases": "Angiotensin Angiotensins", "definition": "Oligopeptides which are important in the regulation of blood pressure (VASOCONSTRICTION) and fluid homeostasis via the RENIN-ANGIOTENSIN SYSTEM. These include angiotensins derived naturally from precursor ANGIOTENSINOGEN, and those synthesized.\n    ", "id": "MESH:D000809"}
{"mention": "Captopril", "mention_text": "Effects of an inhibitor of angiotensin converting enzyme (Captopril) on pulmonary and renal insufficiency due to intravascular coagulation in the rat.", "entity": "Captopril", "aliases": "(S)-1-(3-Mercapto-2-methyl-1-oxopropyl)-L-proline Capoten Captopril Lopirin SQ 14,225 14,534 14225 14534 SQ-14,225 SQ-14,534 SQ-14225 SQ-14534 SQ14,225 SQ14,534 SQ14225 SQ14534", "definition": "A potent and specific inhibitor of PEPTIDYL-DIPEPTIDASE A. It blocks the conversion of ANGIOTENSIN I to ANGIOTENSIN II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the RENIN-ANGIOTENSIN SYSTEM and inhibits pressure responses to exogenous angiotensin.\n    ", "id": "MESH:D002216"}
{"mention": "renal insufficiency", "mention_text": "Effects of an inhibitor of angiotensin converting enzyme (Captopril) on pulmonary and renal insufficiency due to intravascular coagulation in the rat.", "entity": "Renal Insufficiency", "aliases": "Failure Kidney Renal Failures Insufficiency Insufficiencies", "definition": "Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.\n    ", "id": "MESH:D051437"}
{"mention": "intravascular coagulation", "mention_text": "Effects of an inhibitor of angiotensin converting enzyme (Captopril) on pulmonary and renal insufficiency due to intravascular coagulation in the rat.", "entity": "Disseminated Intravascular Coagulation", "aliases": "Coagulation Disseminated Intravascular Coagulations Coagulopathies Consumption Coagulopathy", "definition": "A disorder characterized by procoagulant substances entering the general circulation causing a systemic thrombotic process. The activation of the clotting mechanism may arise from any of a number of disorders. A majority of the patients manifest skin lesions, sometimes leading to PURPURA FULMINANS.\n    ", "id": "MESH:D004211"}
{"mention": "intravascular coagulation", "mention_text": "Induction of intravascular coagulation and inhibition of fibrinolysis by injection of thrombin and tranexamic acid (AMCA) in the rat gives rise to pulmonary and renal insufficiency resembling that occurring after trauma or sepsis in man. Injection of Captopril (1 mg/kg), an inhibitor of angiotensin converting enzyme (ACE), reduced both pulmonary and renal insufficiency in this rat model. The lung weights were lower and PaO2 was improved in rats given this enzyme-blocking agent. The contents of albumin in the lungs were not changed, indicating that Captopril did not influence the extravasation of protein. Renal damage as reflected by an increase in serum urea and in kidney weight was prevented by Captopril. The amount of fibrin in the kidneys was also considerably lower than in animals which received thrombin and AMCA alone. It is suggested that the effects of Captopril on the lungs may be attributable to a vasodilatory effect due to a reduction in the circulating level of Angiotension II and an increase in prostacyclin (secondary to an increase in bradykinin). Captopril may, by the same mechanism, reduce the increase in glomerular filtration that is known to occur after an injection of thrombin, thereby diminishing the aggregation of fibrin monomers in the glomeruli, with the result that less fibrin will be deposited and thus less kidney damage will be produced.", "entity": "Disseminated Intravascular Coagulation", "aliases": "Coagulation Disseminated Intravascular Coagulations Coagulopathies Consumption Coagulopathy", "definition": "A disorder characterized by procoagulant substances entering the general circulation causing a systemic thrombotic process. The activation of the clotting mechanism may arise from any of a number of disorders. A majority of the patients manifest skin lesions, sometimes leading to PURPURA FULMINANS.\n    ", "id": "MESH:D004211"}
{"mention": "tranexamic acid", "mention_text": "Induction of intravascular coagulation and inhibition of fibrinolysis by injection of thrombin and tranexamic acid (AMCA) in the rat gives rise to pulmonary and renal insufficiency resembling that occurring after trauma or sepsis in man. Injection of Captopril (1 mg/kg), an inhibitor of angiotensin converting enzyme (ACE), reduced both pulmonary and renal insufficiency in this rat model. The lung weights were lower and PaO2 was improved in rats given this enzyme-blocking agent. The contents of albumin in the lungs were not changed, indicating that Captopril did not influence the extravasation of protein. Renal damage as reflected by an increase in serum urea and in kidney weight was prevented by Captopril. The amount of fibrin in the kidneys was also considerably lower than in animals which received thrombin and AMCA alone. It is suggested that the effects of Captopril on the lungs may be attributable to a vasodilatory effect due to a reduction in the circulating level of Angiotension II and an increase in prostacyclin (secondary to an increase in bradykinin). Captopril may, by the same mechanism, reduce the increase in glomerular filtration that is known to occur after an injection of thrombin, thereby diminishing the aggregation of fibrin monomers in the glomeruli, with the result that less fibrin will be deposited and thus less kidney damage will be produced.", "entity": "Tranexamic Acid", "aliases": "AMCA AMCHA Abbott Brand of Tranexamic Acid Amchafibrin Anvitoff Cyklokapron Exacyl Fides Ecopharma KABI 2161 Pfizer Pharmygiène Sanofi Synthelabo Spotof Transamin Ugurol t-AMCHA trans-4-(Aminomethyl)cyclohexanecarboxylic", "definition": "Antifibrinolytic hemostatic used in severe hemorrhage.\n    ", "id": "MESH:D014148"}
{"mention": "AMCA", "mention_text": "Induction of intravascular coagulation and inhibition of fibrinolysis by injection of thrombin and tranexamic acid (AMCA) in the rat gives rise to pulmonary and renal insufficiency resembling that occurring after trauma or sepsis in man. Injection of Captopril (1 mg/kg), an inhibitor of angiotensin converting enzyme (ACE), reduced both pulmonary and renal insufficiency in this rat model. The lung weights were lower and PaO2 was improved in rats given this enzyme-blocking agent. The contents of albumin in the lungs were not changed, indicating that Captopril did not influence the extravasation of protein. Renal damage as reflected by an increase in serum urea and in kidney weight was prevented by Captopril. The amount of fibrin in the kidneys was also considerably lower than in animals which received thrombin and AMCA alone. It is suggested that the effects of Captopril on the lungs may be attributable to a vasodilatory effect due to a reduction in the circulating level of Angiotension II and an increase in prostacyclin (secondary to an increase in bradykinin). Captopril may, by the same mechanism, reduce the increase in glomerular filtration that is known to occur after an injection of thrombin, thereby diminishing the aggregation of fibrin monomers in the glomeruli, with the result that less fibrin will be deposited and thus less kidney damage will be produced.", "entity": "Tranexamic Acid", "aliases": "AMCA AMCHA Abbott Brand of Tranexamic Acid Amchafibrin Anvitoff Cyklokapron Exacyl Fides Ecopharma KABI 2161 Pfizer Pharmygiène Sanofi Synthelabo Spotof Transamin Ugurol t-AMCHA trans-4-(Aminomethyl)cyclohexanecarboxylic", "definition": "Antifibrinolytic hemostatic used in severe hemorrhage.\n    ", "id": "MESH:D014148"}
{"mention": "renal insufficiency", "mention_text": "Induction of intravascular coagulation and inhibition of fibrinolysis by injection of thrombin and tranexamic acid (AMCA) in the rat gives rise to pulmonary and renal insufficiency resembling that occurring after trauma or sepsis in man. Injection of Captopril (1 mg/kg), an inhibitor of angiotensin converting enzyme (ACE), reduced both pulmonary and renal insufficiency in this rat model. The lung weights were lower and PaO2 was improved in rats given this enzyme-blocking agent. The contents of albumin in the lungs were not changed, indicating that Captopril did not influence the extravasation of protein. Renal damage as reflected by an increase in serum urea and in kidney weight was prevented by Captopril. The amount of fibrin in the kidneys was also considerably lower than in animals which received thrombin and AMCA alone. It is suggested that the effects of Captopril on the lungs may be attributable to a vasodilatory effect due to a reduction in the circulating level of Angiotension II and an increase in prostacyclin (secondary to an increase in bradykinin). Captopril may, by the same mechanism, reduce the increase in glomerular filtration that is known to occur after an injection of thrombin, thereby diminishing the aggregation of fibrin monomers in the glomeruli, with the result that less fibrin will be deposited and thus less kidney damage will be produced.", "entity": "Renal Insufficiency", "aliases": "Failure Kidney Renal Failures Insufficiency Insufficiencies", "definition": "Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.\n    ", "id": "MESH:D051437"}
{"mention": "trauma", "mention_text": "Induction of intravascular coagulation and inhibition of fibrinolysis by injection of thrombin and tranexamic acid (AMCA) in the rat gives rise to pulmonary and renal insufficiency resembling that occurring after trauma or sepsis in man. Injection of Captopril (1 mg/kg), an inhibitor of angiotensin converting enzyme (ACE), reduced both pulmonary and renal insufficiency in this rat model. The lung weights were lower and PaO2 was improved in rats given this enzyme-blocking agent. The contents of albumin in the lungs were not changed, indicating that Captopril did not influence the extravasation of protein. Renal damage as reflected by an increase in serum urea and in kidney weight was prevented by Captopril. The amount of fibrin in the kidneys was also considerably lower than in animals which received thrombin and AMCA alone. It is suggested that the effects of Captopril on the lungs may be attributable to a vasodilatory effect due to a reduction in the circulating level of Angiotension II and an increase in prostacyclin (secondary to an increase in bradykinin). Captopril may, by the same mechanism, reduce the increase in glomerular filtration that is known to occur after an injection of thrombin, thereby diminishing the aggregation of fibrin monomers in the glomeruli, with the result that less fibrin will be deposited and thus less kidney damage will be produced.", "entity": "Wounds and Injuries", "aliases": "Injuries and Wounds Injury Trauma Traumas Wound", "definition": "Damage inflicted on the body as the direct or indirect result of an external force, with or without disruption of structural continuity.\n    ", "id": "MESH:D014947"}
{"mention": "sepsis", "mention_text": "Induction of intravascular coagulation and inhibition of fibrinolysis by injection of thrombin and tranexamic acid (AMCA) in the rat gives rise to pulmonary and renal insufficiency resembling that occurring after trauma or sepsis in man. Injection of Captopril (1 mg/kg), an inhibitor of angiotensin converting enzyme (ACE), reduced both pulmonary and renal insufficiency in this rat model. The lung weights were lower and PaO2 was improved in rats given this enzyme-blocking agent. The contents of albumin in the lungs were not changed, indicating that Captopril did not influence the extravasation of protein. Renal damage as reflected by an increase in serum urea and in kidney weight was prevented by Captopril. The amount of fibrin in the kidneys was also considerably lower than in animals which received thrombin and AMCA alone. It is suggested that the effects of Captopril on the lungs may be attributable to a vasodilatory effect due to a reduction in the circulating level of Angiotension II and an increase in prostacyclin (secondary to an increase in bradykinin). Captopril may, by the same mechanism, reduce the increase in glomerular filtration that is known to occur after an injection of thrombin, thereby diminishing the aggregation of fibrin monomers in the glomeruli, with the result that less fibrin will be deposited and thus less kidney damage will be produced.", "entity": "Sepsis", "aliases": "Blood Poisoning Poisonings Pyaemia Pyaemias Pyemia Pyemias Pyohemia Pyohemias Sepsis Severe Septicemia Septicemias", "definition": "Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by HYPOTENSION despite adequate fluid infusion, it is called SEPTIC SHOCK.\n    ", "id": "MESH:D018805"}
{"mention": "Captopril", "mention_text": "Induction of intravascular coagulation and inhibition of fibrinolysis by injection of thrombin and tranexamic acid (AMCA) in the rat gives rise to pulmonary and renal insufficiency resembling that occurring after trauma or sepsis in man. Injection of Captopril (1 mg/kg), an inhibitor of angiotensin converting enzyme (ACE), reduced both pulmonary and renal insufficiency in this rat model. The lung weights were lower and PaO2 was improved in rats given this enzyme-blocking agent. The contents of albumin in the lungs were not changed, indicating that Captopril did not influence the extravasation of protein. Renal damage as reflected by an increase in serum urea and in kidney weight was prevented by Captopril. The amount of fibrin in the kidneys was also considerably lower than in animals which received thrombin and AMCA alone. It is suggested that the effects of Captopril on the lungs may be attributable to a vasodilatory effect due to a reduction in the circulating level of Angiotension II and an increase in prostacyclin (secondary to an increase in bradykinin). Captopril may, by the same mechanism, reduce the increase in glomerular filtration that is known to occur after an injection of thrombin, thereby diminishing the aggregation of fibrin monomers in the glomeruli, with the result that less fibrin will be deposited and thus less kidney damage will be produced.", "entity": "Captopril", "aliases": "(S)-1-(3-Mercapto-2-methyl-1-oxopropyl)-L-proline Capoten Captopril Lopirin SQ 14,225 14,534 14225 14534 SQ-14,225 SQ-14,534 SQ-14225 SQ-14534 SQ14,225 SQ14,534 SQ14225 SQ14534", "definition": "A potent and specific inhibitor of PEPTIDYL-DIPEPTIDASE A. It blocks the conversion of ANGIOTENSIN I to ANGIOTENSIN II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the RENIN-ANGIOTENSIN SYSTEM and inhibits pressure responses to exogenous angiotensin.\n    ", "id": "MESH:D002216"}
{"mention": "angiotensin", "mention_text": "Induction of intravascular coagulation and inhibition of fibrinolysis by injection of thrombin and tranexamic acid (AMCA) in the rat gives rise to pulmonary and renal insufficiency resembling that occurring after trauma or sepsis in man. Injection of Captopril (1 mg/kg), an inhibitor of angiotensin converting enzyme (ACE), reduced both pulmonary and renal insufficiency in this rat model. The lung weights were lower and PaO2 was improved in rats given this enzyme-blocking agent. The contents of albumin in the lungs were not changed, indicating that Captopril did not influence the extravasation of protein. Renal damage as reflected by an increase in serum urea and in kidney weight was prevented by Captopril. The amount of fibrin in the kidneys was also considerably lower than in animals which received thrombin and AMCA alone. It is suggested that the effects of Captopril on the lungs may be attributable to a vasodilatory effect due to a reduction in the circulating level of Angiotension II and an increase in prostacyclin (secondary to an increase in bradykinin). Captopril may, by the same mechanism, reduce the increase in glomerular filtration that is known to occur after an injection of thrombin, thereby diminishing the aggregation of fibrin monomers in the glomeruli, with the result that less fibrin will be deposited and thus less kidney damage will be produced.", "entity": "Angiotensins", "aliases": "Angiotensin Angiotensins", "definition": "Oligopeptides which are important in the regulation of blood pressure (VASOCONSTRICTION) and fluid homeostasis via the RENIN-ANGIOTENSIN SYSTEM. These include angiotensins derived naturally from precursor ANGIOTENSINOGEN, and those synthesized.\n    ", "id": "MESH:D000809"}
{"mention": "Renal damage", "mention_text": "Induction of intravascular coagulation and inhibition of fibrinolysis by injection of thrombin and tranexamic acid (AMCA) in the rat gives rise to pulmonary and renal insufficiency resembling that occurring after trauma or sepsis in man. Injection of Captopril (1 mg/kg), an inhibitor of angiotensin converting enzyme (ACE), reduced both pulmonary and renal insufficiency in this rat model. The lung weights were lower and PaO2 was improved in rats given this enzyme-blocking agent. The contents of albumin in the lungs were not changed, indicating that Captopril did not influence the extravasation of protein. Renal damage as reflected by an increase in serum urea and in kidney weight was prevented by Captopril. The amount of fibrin in the kidneys was also considerably lower than in animals which received thrombin and AMCA alone. It is suggested that the effects of Captopril on the lungs may be attributable to a vasodilatory effect due to a reduction in the circulating level of Angiotension II and an increase in prostacyclin (secondary to an increase in bradykinin). Captopril may, by the same mechanism, reduce the increase in glomerular filtration that is known to occur after an injection of thrombin, thereby diminishing the aggregation of fibrin monomers in the glomeruli, with the result that less fibrin will be deposited and thus less kidney damage will be produced.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "urea", "mention_text": "Induction of intravascular coagulation and inhibition of fibrinolysis by injection of thrombin and tranexamic acid (AMCA) in the rat gives rise to pulmonary and renal insufficiency resembling that occurring after trauma or sepsis in man. Injection of Captopril (1 mg/kg), an inhibitor of angiotensin converting enzyme (ACE), reduced both pulmonary and renal insufficiency in this rat model. The lung weights were lower and PaO2 was improved in rats given this enzyme-blocking agent. The contents of albumin in the lungs were not changed, indicating that Captopril did not influence the extravasation of protein. Renal damage as reflected by an increase in serum urea and in kidney weight was prevented by Captopril. The amount of fibrin in the kidneys was also considerably lower than in animals which received thrombin and AMCA alone. It is suggested that the effects of Captopril on the lungs may be attributable to a vasodilatory effect due to a reduction in the circulating level of Angiotension II and an increase in prostacyclin (secondary to an increase in bradykinin). Captopril may, by the same mechanism, reduce the increase in glomerular filtration that is known to occur after an injection of thrombin, thereby diminishing the aggregation of fibrin monomers in the glomeruli, with the result that less fibrin will be deposited and thus less kidney damage will be produced.", "entity": "Urea", "aliases": "Basodexan Carbamide Carmol Urea", "definition": "A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids.\n    ", "id": "MESH:D014508"}
{"mention": "Angiotension II", "mention_text": "Induction of intravascular coagulation and inhibition of fibrinolysis by injection of thrombin and tranexamic acid (AMCA) in the rat gives rise to pulmonary and renal insufficiency resembling that occurring after trauma or sepsis in man. Injection of Captopril (1 mg/kg), an inhibitor of angiotensin converting enzyme (ACE), reduced both pulmonary and renal insufficiency in this rat model. The lung weights were lower and PaO2 was improved in rats given this enzyme-blocking agent. The contents of albumin in the lungs were not changed, indicating that Captopril did not influence the extravasation of protein. Renal damage as reflected by an increase in serum urea and in kidney weight was prevented by Captopril. The amount of fibrin in the kidneys was also considerably lower than in animals which received thrombin and AMCA alone. It is suggested that the effects of Captopril on the lungs may be attributable to a vasodilatory effect due to a reduction in the circulating level of Angiotension II and an increase in prostacyclin (secondary to an increase in bradykinin). Captopril may, by the same mechanism, reduce the increase in glomerular filtration that is known to occur after an injection of thrombin, thereby diminishing the aggregation of fibrin monomers in the glomeruli, with the result that less fibrin will be deposited and thus less kidney damage will be produced.", "entity": "Angiotensin II", "aliases": "5 L Isoleucine Angiotensin II 5-L-Isoleucine ANG-(1-8)Octapeptide Ile(5)- Isoleucine(5)- Val(5)- Valine(5)- Angiotensin-(1-8) Octapeptide Isoleucine(5)-Angiotensin Isoleucyl(5)-Angiotensin Valyl(5)-Angiotensin", "definition": "An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.\n    ", "id": "MESH:D000804"}
{"mention": "prostacyclin", "mention_text": "Induction of intravascular coagulation and inhibition of fibrinolysis by injection of thrombin and tranexamic acid (AMCA) in the rat gives rise to pulmonary and renal insufficiency resembling that occurring after trauma or sepsis in man. Injection of Captopril (1 mg/kg), an inhibitor of angiotensin converting enzyme (ACE), reduced both pulmonary and renal insufficiency in this rat model. The lung weights were lower and PaO2 was improved in rats given this enzyme-blocking agent. The contents of albumin in the lungs were not changed, indicating that Captopril did not influence the extravasation of protein. Renal damage as reflected by an increase in serum urea and in kidney weight was prevented by Captopril. The amount of fibrin in the kidneys was also considerably lower than in animals which received thrombin and AMCA alone. It is suggested that the effects of Captopril on the lungs may be attributable to a vasodilatory effect due to a reduction in the circulating level of Angiotension II and an increase in prostacyclin (secondary to an increase in bradykinin). Captopril may, by the same mechanism, reduce the increase in glomerular filtration that is known to occur after an injection of thrombin, thereby diminishing the aggregation of fibrin monomers in the glomeruli, with the result that less fibrin will be deposited and thus less kidney damage will be produced.", "entity": "Epoprostenol", "aliases": "Epoprostanol Epoprostenol Sodium Salt (5Z,9alpha,11alpha,13E,15S)-Isomer Flolan PGI2 PGX Prostacyclin Prostaglandin I(2) I2", "definition": "A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY).\n    ", "id": "MESH:D011464"}
{"mention": "bradykinin", "mention_text": "Induction of intravascular coagulation and inhibition of fibrinolysis by injection of thrombin and tranexamic acid (AMCA) in the rat gives rise to pulmonary and renal insufficiency resembling that occurring after trauma or sepsis in man. Injection of Captopril (1 mg/kg), an inhibitor of angiotensin converting enzyme (ACE), reduced both pulmonary and renal insufficiency in this rat model. The lung weights were lower and PaO2 was improved in rats given this enzyme-blocking agent. The contents of albumin in the lungs were not changed, indicating that Captopril did not influence the extravasation of protein. Renal damage as reflected by an increase in serum urea and in kidney weight was prevented by Captopril. The amount of fibrin in the kidneys was also considerably lower than in animals which received thrombin and AMCA alone. It is suggested that the effects of Captopril on the lungs may be attributable to a vasodilatory effect due to a reduction in the circulating level of Angiotension II and an increase in prostacyclin (secondary to an increase in bradykinin). Captopril may, by the same mechanism, reduce the increase in glomerular filtration that is known to occur after an injection of thrombin, thereby diminishing the aggregation of fibrin monomers in the glomeruli, with the result that less fibrin will be deposited and thus less kidney damage will be produced.", "entity": "Bradykinin", "aliases": "Arg Pro Pro Gly Phe Ser Pro Phe Arg Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg Bradykinin Acetate (9-D-Arg)-Isomer Diacetate Hydrochloride Triacetate (1-D-Arg)-Isomer (2-D-Pro)-Isomer (2-D-Pro-3-D-Pro-7-D-Pro)-Isomer (2-D-Pro-7-D-Pro)-Isomer (3-D-Pro)-Isomer (3-D-Pro-7-D-Pro)-Isomer (5-D-Phe)-Isomer (5-D-Phe-8-D-Phe)-Isomer (6-D-Ser)-Isomer (7-D-Pro)-Isomer (8-D-Phe)-Isomer", "definition": "A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.\n    ", "id": "MESH:D001920"}
{"mention": "kidney damage", "mention_text": "Induction of intravascular coagulation and inhibition of fibrinolysis by injection of thrombin and tranexamic acid (AMCA) in the rat gives rise to pulmonary and renal insufficiency resembling that occurring after trauma or sepsis in man. Injection of Captopril (1 mg/kg), an inhibitor of angiotensin converting enzyme (ACE), reduced both pulmonary and renal insufficiency in this rat model. The lung weights were lower and PaO2 was improved in rats given this enzyme-blocking agent. The contents of albumin in the lungs were not changed, indicating that Captopril did not influence the extravasation of protein. Renal damage as reflected by an increase in serum urea and in kidney weight was prevented by Captopril. The amount of fibrin in the kidneys was also considerably lower than in animals which received thrombin and AMCA alone. It is suggested that the effects of Captopril on the lungs may be attributable to a vasodilatory effect due to a reduction in the circulating level of Angiotension II and an increase in prostacyclin (secondary to an increase in bradykinin). Captopril may, by the same mechanism, reduce the increase in glomerular filtration that is known to occur after an injection of thrombin, thereby diminishing the aggregation of fibrin monomers in the glomeruli, with the result that less fibrin will be deposited and thus less kidney damage will be produced.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "labetalol", "mention_text": "A randomized comparison of labetalol and nitroprusside for induced hypotension.", "entity": "Labetalol", "aliases": "AH 5158 AH-5158 AH5158 Albetol Alphapharm Brand of Labetalol Hydrochloride Apo Apo-Labetalol ApoLabetalol Apotex Celltech Dilevalol Faro Glaxo Wellcome GlaxoSmithKline Kern (R,R)-Isomer Labetolol Leiras Normodyne Presolol R,R R,R-Labetalol SCH 19927 SCH-19927 SCH19927 Schering Shire Sigma Trandate", "definition": "A salicylamide derivative that is a non-cardioselective blocker of BETA-ADRENERGIC RECEPTORS and ALPHA-1 ADRENERGIC RECEPTORS.\n    ", "id": "MESH:D007741"}
{"mention": "nitroprusside", "mention_text": "A randomized comparison of labetalol and nitroprusside for induced hypotension.", "entity": "Nitroprusside", "aliases": "Abbott Brand of Sodium Nitroprusside Bayer Cyanonitrosylferrate Disodium Salt Faulding Fides Ecopharma Ketostix Naniprus Nipride Nipruton Nitriate Nitroferricyanide Nitropress Nitroprussiat Dihydrate Roche SERB", "definition": "A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.\n    ", "id": "MESH:D009599"}
{"mention": "hypotension", "mention_text": "A randomized comparison of labetalol and nitroprusside for induced hypotension.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "labetalol", "mention_text": "In a randomized study, labetalol-induced hypotension and nitroprusside-induced hypotension were compared in 20 patients (10 in each group) scheduled for major orthopedic procedures. Each patient was subjected to an identical anesthetic protocol and similar drug-induced reductions in mean arterial blood pressure (BP) (50 to 55 mmHg). Nitroprusside infusion was associated with a significant (p less than 0.05) increase in heart rate and cardiac output; rebound hypertension was observed in three patients after discontinuation of nitroprusside. Labetalol administration was not associated with any of these findings. Arterial PO2 decreased in both groups. It was concluded that labetalol offers advantages over nitroprusside.", "entity": "Labetalol", "aliases": "AH 5158 AH-5158 AH5158 Albetol Alphapharm Brand of Labetalol Hydrochloride Apo Apo-Labetalol ApoLabetalol Apotex Celltech Dilevalol Faro Glaxo Wellcome GlaxoSmithKline Kern (R,R)-Isomer Labetolol Leiras Normodyne Presolol R,R R,R-Labetalol SCH 19927 SCH-19927 SCH19927 Schering Shire Sigma Trandate", "definition": "A salicylamide derivative that is a non-cardioselective blocker of BETA-ADRENERGIC RECEPTORS and ALPHA-1 ADRENERGIC RECEPTORS.\n    ", "id": "MESH:D007741"}
{"mention": "hypotension", "mention_text": "In a randomized study, labetalol-induced hypotension and nitroprusside-induced hypotension were compared in 20 patients (10 in each group) scheduled for major orthopedic procedures. Each patient was subjected to an identical anesthetic protocol and similar drug-induced reductions in mean arterial blood pressure (BP) (50 to 55 mmHg). Nitroprusside infusion was associated with a significant (p less than 0.05) increase in heart rate and cardiac output; rebound hypertension was observed in three patients after discontinuation of nitroprusside. Labetalol administration was not associated with any of these findings. Arterial PO2 decreased in both groups. It was concluded that labetalol offers advantages over nitroprusside.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "nitroprusside", "mention_text": "In a randomized study, labetalol-induced hypotension and nitroprusside-induced hypotension were compared in 20 patients (10 in each group) scheduled for major orthopedic procedures. Each patient was subjected to an identical anesthetic protocol and similar drug-induced reductions in mean arterial blood pressure (BP) (50 to 55 mmHg). Nitroprusside infusion was associated with a significant (p less than 0.05) increase in heart rate and cardiac output; rebound hypertension was observed in three patients after discontinuation of nitroprusside. Labetalol administration was not associated with any of these findings. Arterial PO2 decreased in both groups. It was concluded that labetalol offers advantages over nitroprusside.", "entity": "Nitroprusside", "aliases": "Abbott Brand of Sodium Nitroprusside Bayer Cyanonitrosylferrate Disodium Salt Faulding Fides Ecopharma Ketostix Naniprus Nipride Nipruton Nitriate Nitroferricyanide Nitropress Nitroprussiat Dihydrate Roche SERB", "definition": "A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.\n    ", "id": "MESH:D009599"}
{"mention": "reductions in mean arterial blood pressure", "mention_text": "In a randomized study, labetalol-induced hypotension and nitroprusside-induced hypotension were compared in 20 patients (10 in each group) scheduled for major orthopedic procedures. Each patient was subjected to an identical anesthetic protocol and similar drug-induced reductions in mean arterial blood pressure (BP) (50 to 55 mmHg). Nitroprusside infusion was associated with a significant (p less than 0.05) increase in heart rate and cardiac output; rebound hypertension was observed in three patients after discontinuation of nitroprusside. Labetalol administration was not associated with any of these findings. Arterial PO2 decreased in both groups. It was concluded that labetalol offers advantages over nitroprusside.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "increase in heart rate and cardiac output", "mention_text": "In a randomized study, labetalol-induced hypotension and nitroprusside-induced hypotension were compared in 20 patients (10 in each group) scheduled for major orthopedic procedures. Each patient was subjected to an identical anesthetic protocol and similar drug-induced reductions in mean arterial blood pressure (BP) (50 to 55 mmHg). Nitroprusside infusion was associated with a significant (p less than 0.05) increase in heart rate and cardiac output; rebound hypertension was observed in three patients after discontinuation of nitroprusside. Labetalol administration was not associated with any of these findings. Arterial PO2 decreased in both groups. It was concluded that labetalol offers advantages over nitroprusside.", "entity": "Cardiac Output, High", "aliases": "Cardiac Output High Outputs", "definition": "A state of elevated cardiac output due to conditions of either increased hemodynamic demand or reduced cardiac oxygen output. These conditions may include ANEMIA; ARTERIOVENOUS FISTULA; THYROTOXICOSIS; PREGNANCY; EXERCISE; FEVER; and ANOXIA. In time, compensatory changes of the heart can lead to pathological form of high cardiac output and eventual HEART FAILURE.\n    ", "id": "MESH:D016534"}
{"mention": "hypertension", "mention_text": "In a randomized study, labetalol-induced hypotension and nitroprusside-induced hypotension were compared in 20 patients (10 in each group) scheduled for major orthopedic procedures. Each patient was subjected to an identical anesthetic protocol and similar drug-induced reductions in mean arterial blood pressure (BP) (50 to 55 mmHg). Nitroprusside infusion was associated with a significant (p less than 0.05) increase in heart rate and cardiac output; rebound hypertension was observed in three patients after discontinuation of nitroprusside. Labetalol administration was not associated with any of these findings. Arterial PO2 decreased in both groups. It was concluded that labetalol offers advantages over nitroprusside.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "Labetalol", "mention_text": "In a randomized study, labetalol-induced hypotension and nitroprusside-induced hypotension were compared in 20 patients (10 in each group) scheduled for major orthopedic procedures. Each patient was subjected to an identical anesthetic protocol and similar drug-induced reductions in mean arterial blood pressure (BP) (50 to 55 mmHg). Nitroprusside infusion was associated with a significant (p less than 0.05) increase in heart rate and cardiac output; rebound hypertension was observed in three patients after discontinuation of nitroprusside. Labetalol administration was not associated with any of these findings. Arterial PO2 decreased in both groups. It was concluded that labetalol offers advantages over nitroprusside.", "entity": "Labetalol", "aliases": "AH 5158 AH-5158 AH5158 Albetol Alphapharm Brand of Labetalol Hydrochloride Apo Apo-Labetalol ApoLabetalol Apotex Celltech Dilevalol Faro Glaxo Wellcome GlaxoSmithKline Kern (R,R)-Isomer Labetolol Leiras Normodyne Presolol R,R R,R-Labetalol SCH 19927 SCH-19927 SCH19927 Schering Shire Sigma Trandate", "definition": "A salicylamide derivative that is a non-cardioselective blocker of BETA-ADRENERGIC RECEPTORS and ALPHA-1 ADRENERGIC RECEPTORS.\n    ", "id": "MESH:D007741"}
{"mention": "PO2", "mention_text": "In a randomized study, labetalol-induced hypotension and nitroprusside-induced hypotension were compared in 20 patients (10 in each group) scheduled for major orthopedic procedures. Each patient was subjected to an identical anesthetic protocol and similar drug-induced reductions in mean arterial blood pressure (BP) (50 to 55 mmHg). Nitroprusside infusion was associated with a significant (p less than 0.05) increase in heart rate and cardiac output; rebound hypertension was observed in three patients after discontinuation of nitroprusside. Labetalol administration was not associated with any of these findings. Arterial PO2 decreased in both groups. It was concluded that labetalol offers advantages over nitroprusside.", "entity": "PO-2", "aliases": "PO-2", "definition": "", "id": "MESH:C093415"}
{"mention": "carbamazepine", "mention_text": "Chronic carbamazepine treatment in the rat: efficacy, toxicity, and effect on plasma and tissue folate concentrations.", "entity": "Carbamazepine", "aliases": "Amizepine Carbamazepine Acetate Anhydrous Dihydrate Hydrochloride L-Tartrate (4:1) Phosphate Sulfate (2:1) Carbazepin Epitol Finlepsin Neurotol Tegretol", "definition": "An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of PHENYTOIN; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar.\n    ", "id": "MESH:D002220"}
{"mention": "toxicity", "mention_text": "Chronic carbamazepine treatment in the rat: efficacy, toxicity, and effect on plasma and tissue folate concentrations.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "folate", "mention_text": "Chronic carbamazepine treatment in the rat: efficacy, toxicity, and effect on plasma and tissue folate concentrations.", "entity": "Folic Acid", "aliases": "B9 Vitamin Folacin Folate Folic Acid (D)-Isomer (DL)-Isomer Calcium Salt (1:1) Monopotassium Monosodium Potassium Sodium Folvite Pteroylglutamic M", "definition": "A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses (POACEAE). Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia.\n    ", "id": "MESH:D005492"}
{"mention": "Folate", "mention_text": "Folate depletion has often been a problem in chronic antiepileptic drug (AED) therapy. Carbamazepine (CBZ), a commonly used AED, has been implicated in some clinical studies. A rat model was developed to examine the effects of chronic CBZ treatment on folate concentrations in the rat. In the course of developing this model, a common vehicle, propylene glycol, by itself in high doses, was found to exhibit protective properties against induced seizures and inhibited weight gain. Seizures induced by hexafluorodiethyl ether (HFDE) were also found to be a more sensitive measure of protection by CBZ than seizures induced by maximal electroshock (MES). Oral administration of CBZ as an aqueous suspension every 8 h at a dose of 250 mg/kg was continuously protective against HFDE-induced seizures and was minimally toxic as measured by weight gain over 8 weeks of treatment. The CBZ levels measured in plasma and brain of these animals, however, were below those normally considered protective. This treatment with CBZ had no apparent adverse effect on folate concentrations in the rat, and, indeed, the folate concentration increased in liver after 6 weeks of treatment and in plasma at 8 weeks of treatment.", "entity": "Folic Acid", "aliases": "B9 Vitamin Folacin Folate Folic Acid (D)-Isomer (DL)-Isomer Calcium Salt (1:1) Monopotassium Monosodium Potassium Sodium Folvite Pteroylglutamic M", "definition": "A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses (POACEAE). Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia.\n    ", "id": "MESH:D005492"}
{"mention": "Carbamazepine", "mention_text": "Folate depletion has often been a problem in chronic antiepileptic drug (AED) therapy. Carbamazepine (CBZ), a commonly used AED, has been implicated in some clinical studies. A rat model was developed to examine the effects of chronic CBZ treatment on folate concentrations in the rat. In the course of developing this model, a common vehicle, propylene glycol, by itself in high doses, was found to exhibit protective properties against induced seizures and inhibited weight gain. Seizures induced by hexafluorodiethyl ether (HFDE) were also found to be a more sensitive measure of protection by CBZ than seizures induced by maximal electroshock (MES). Oral administration of CBZ as an aqueous suspension every 8 h at a dose of 250 mg/kg was continuously protective against HFDE-induced seizures and was minimally toxic as measured by weight gain over 8 weeks of treatment. The CBZ levels measured in plasma and brain of these animals, however, were below those normally considered protective. This treatment with CBZ had no apparent adverse effect on folate concentrations in the rat, and, indeed, the folate concentration increased in liver after 6 weeks of treatment and in plasma at 8 weeks of treatment.", "entity": "Carbamazepine", "aliases": "Amizepine Carbamazepine Acetate Anhydrous Dihydrate Hydrochloride L-Tartrate (4:1) Phosphate Sulfate (2:1) Carbazepin Epitol Finlepsin Neurotol Tegretol", "definition": "An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of PHENYTOIN; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar.\n    ", "id": "MESH:D002220"}
{"mention": "CBZ", "mention_text": "Folate depletion has often been a problem in chronic antiepileptic drug (AED) therapy. Carbamazepine (CBZ), a commonly used AED, has been implicated in some clinical studies. A rat model was developed to examine the effects of chronic CBZ treatment on folate concentrations in the rat. In the course of developing this model, a common vehicle, propylene glycol, by itself in high doses, was found to exhibit protective properties against induced seizures and inhibited weight gain. Seizures induced by hexafluorodiethyl ether (HFDE) were also found to be a more sensitive measure of protection by CBZ than seizures induced by maximal electroshock (MES). Oral administration of CBZ as an aqueous suspension every 8 h at a dose of 250 mg/kg was continuously protective against HFDE-induced seizures and was minimally toxic as measured by weight gain over 8 weeks of treatment. The CBZ levels measured in plasma and brain of these animals, however, were below those normally considered protective. This treatment with CBZ had no apparent adverse effect on folate concentrations in the rat, and, indeed, the folate concentration increased in liver after 6 weeks of treatment and in plasma at 8 weeks of treatment.", "entity": "Carbamazepine", "aliases": "Amizepine Carbamazepine Acetate Anhydrous Dihydrate Hydrochloride L-Tartrate (4:1) Phosphate Sulfate (2:1) Carbazepin Epitol Finlepsin Neurotol Tegretol", "definition": "An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of PHENYTOIN; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar.\n    ", "id": "MESH:D002220"}
{"mention": "folate", "mention_text": "Folate depletion has often been a problem in chronic antiepileptic drug (AED) therapy. Carbamazepine (CBZ), a commonly used AED, has been implicated in some clinical studies. A rat model was developed to examine the effects of chronic CBZ treatment on folate concentrations in the rat. In the course of developing this model, a common vehicle, propylene glycol, by itself in high doses, was found to exhibit protective properties against induced seizures and inhibited weight gain. Seizures induced by hexafluorodiethyl ether (HFDE) were also found to be a more sensitive measure of protection by CBZ than seizures induced by maximal electroshock (MES). Oral administration of CBZ as an aqueous suspension every 8 h at a dose of 250 mg/kg was continuously protective against HFDE-induced seizures and was minimally toxic as measured by weight gain over 8 weeks of treatment. The CBZ levels measured in plasma and brain of these animals, however, were below those normally considered protective. This treatment with CBZ had no apparent adverse effect on folate concentrations in the rat, and, indeed, the folate concentration increased in liver after 6 weeks of treatment and in plasma at 8 weeks of treatment.", "entity": "Folic Acid", "aliases": "B9 Vitamin Folacin Folate Folic Acid (D)-Isomer (DL)-Isomer Calcium Salt (1:1) Monopotassium Monosodium Potassium Sodium Folvite Pteroylglutamic M", "definition": "A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses (POACEAE). Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia.\n    ", "id": "MESH:D005492"}
{"mention": "propylene glycol", "mention_text": "Folate depletion has often been a problem in chronic antiepileptic drug (AED) therapy. Carbamazepine (CBZ), a commonly used AED, has been implicated in some clinical studies. A rat model was developed to examine the effects of chronic CBZ treatment on folate concentrations in the rat. In the course of developing this model, a common vehicle, propylene glycol, by itself in high doses, was found to exhibit protective properties against induced seizures and inhibited weight gain. Seizures induced by hexafluorodiethyl ether (HFDE) were also found to be a more sensitive measure of protection by CBZ than seizures induced by maximal electroshock (MES). Oral administration of CBZ as an aqueous suspension every 8 h at a dose of 250 mg/kg was continuously protective against HFDE-induced seizures and was minimally toxic as measured by weight gain over 8 weeks of treatment. The CBZ levels measured in plasma and brain of these animals, however, were below those normally considered protective. This treatment with CBZ had no apparent adverse effect on folate concentrations in the rat, and, indeed, the folate concentration increased in liver after 6 weeks of treatment and in plasma at 8 weeks of treatment.", "entity": "Propylene Glycol", "aliases": "1,2 Propanediol 1,2-Propanediol Glycol Propylene Monohydrate Propan-1,2-Diol Sodium Salt (+-)-Isomer (R)-Isomer (S)-Isomer", "definition": "A clear, colorless, viscous organic solvent and diluent used in pharmaceutical preparations.\n    ", "id": "MESH:D019946"}
{"mention": "seizures", "mention_text": "Folate depletion has often been a problem in chronic antiepileptic drug (AED) therapy. Carbamazepine (CBZ), a commonly used AED, has been implicated in some clinical studies. A rat model was developed to examine the effects of chronic CBZ treatment on folate concentrations in the rat. In the course of developing this model, a common vehicle, propylene glycol, by itself in high doses, was found to exhibit protective properties against induced seizures and inhibited weight gain. Seizures induced by hexafluorodiethyl ether (HFDE) were also found to be a more sensitive measure of protection by CBZ than seizures induced by maximal electroshock (MES). Oral administration of CBZ as an aqueous suspension every 8 h at a dose of 250 mg/kg was continuously protective against HFDE-induced seizures and was minimally toxic as measured by weight gain over 8 weeks of treatment. The CBZ levels measured in plasma and brain of these animals, however, were below those normally considered protective. This treatment with CBZ had no apparent adverse effect on folate concentrations in the rat, and, indeed, the folate concentration increased in liver after 6 weeks of treatment and in plasma at 8 weeks of treatment.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "weight gain", "mention_text": "Folate depletion has often been a problem in chronic antiepileptic drug (AED) therapy. Carbamazepine (CBZ), a commonly used AED, has been implicated in some clinical studies. A rat model was developed to examine the effects of chronic CBZ treatment on folate concentrations in the rat. In the course of developing this model, a common vehicle, propylene glycol, by itself in high doses, was found to exhibit protective properties against induced seizures and inhibited weight gain. Seizures induced by hexafluorodiethyl ether (HFDE) were also found to be a more sensitive measure of protection by CBZ than seizures induced by maximal electroshock (MES). Oral administration of CBZ as an aqueous suspension every 8 h at a dose of 250 mg/kg was continuously protective against HFDE-induced seizures and was minimally toxic as measured by weight gain over 8 weeks of treatment. The CBZ levels measured in plasma and brain of these animals, however, were below those normally considered protective. This treatment with CBZ had no apparent adverse effect on folate concentrations in the rat, and, indeed, the folate concentration increased in liver after 6 weeks of treatment and in plasma at 8 weeks of treatment.", "entity": "Weight Gain", "aliases": "Gain Weight Gains", "definition": "Increase in BODY WEIGHT over existing weight.\n    ", "id": "MESH:D015430"}
{"mention": "Seizures", "mention_text": "Folate depletion has often been a problem in chronic antiepileptic drug (AED) therapy. Carbamazepine (CBZ), a commonly used AED, has been implicated in some clinical studies. A rat model was developed to examine the effects of chronic CBZ treatment on folate concentrations in the rat. In the course of developing this model, a common vehicle, propylene glycol, by itself in high doses, was found to exhibit protective properties against induced seizures and inhibited weight gain. Seizures induced by hexafluorodiethyl ether (HFDE) were also found to be a more sensitive measure of protection by CBZ than seizures induced by maximal electroshock (MES). Oral administration of CBZ as an aqueous suspension every 8 h at a dose of 250 mg/kg was continuously protective against HFDE-induced seizures and was minimally toxic as measured by weight gain over 8 weeks of treatment. The CBZ levels measured in plasma and brain of these animals, however, were below those normally considered protective. This treatment with CBZ had no apparent adverse effect on folate concentrations in the rat, and, indeed, the folate concentration increased in liver after 6 weeks of treatment and in plasma at 8 weeks of treatment.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "hexafluorodiethyl ether", "mention_text": "Folate depletion has often been a problem in chronic antiepileptic drug (AED) therapy. Carbamazepine (CBZ), a commonly used AED, has been implicated in some clinical studies. A rat model was developed to examine the effects of chronic CBZ treatment on folate concentrations in the rat. In the course of developing this model, a common vehicle, propylene glycol, by itself in high doses, was found to exhibit protective properties against induced seizures and inhibited weight gain. Seizures induced by hexafluorodiethyl ether (HFDE) were also found to be a more sensitive measure of protection by CBZ than seizures induced by maximal electroshock (MES). Oral administration of CBZ as an aqueous suspension every 8 h at a dose of 250 mg/kg was continuously protective against HFDE-induced seizures and was minimally toxic as measured by weight gain over 8 weeks of treatment. The CBZ levels measured in plasma and brain of these animals, however, were below those normally considered protective. This treatment with CBZ had no apparent adverse effect on folate concentrations in the rat, and, indeed, the folate concentration increased in liver after 6 weeks of treatment and in plasma at 8 weeks of treatment.", "entity": "Flurothyl", "aliases": "Fluorothyl Flurothyl Flurotyl Indoklon", "definition": "A convulsant primarily used in experimental animals. It was formerly used to induce convulsions as a alternative to electroshock therapy.\n    ", "id": "MESH:D005481"}
{"mention": "HFDE", "mention_text": "Folate depletion has often been a problem in chronic antiepileptic drug (AED) therapy. Carbamazepine (CBZ), a commonly used AED, has been implicated in some clinical studies. A rat model was developed to examine the effects of chronic CBZ treatment on folate concentrations in the rat. In the course of developing this model, a common vehicle, propylene glycol, by itself in high doses, was found to exhibit protective properties against induced seizures and inhibited weight gain. Seizures induced by hexafluorodiethyl ether (HFDE) were also found to be a more sensitive measure of protection by CBZ than seizures induced by maximal electroshock (MES). Oral administration of CBZ as an aqueous suspension every 8 h at a dose of 250 mg/kg was continuously protective against HFDE-induced seizures and was minimally toxic as measured by weight gain over 8 weeks of treatment. The CBZ levels measured in plasma and brain of these animals, however, were below those normally considered protective. This treatment with CBZ had no apparent adverse effect on folate concentrations in the rat, and, indeed, the folate concentration increased in liver after 6 weeks of treatment and in plasma at 8 weeks of treatment.", "entity": "Flurothyl", "aliases": "Fluorothyl Flurothyl Flurotyl Indoklon", "definition": "A convulsant primarily used in experimental animals. It was formerly used to induce convulsions as a alternative to electroshock therapy.\n    ", "id": "MESH:D005481"}
{"mention": "sodium", "mention_text": "In six conscious, trained dogs, maintained on a normal sodium intake of 2 to 4 mEq/kg/day, sympathetic activity was assessed as the release rate of norepinephrine and epinephrine during 15-minute i.v. infusions of human alpha-atrial natriuretic factor. Mean arterial pressure (as a percentage of control +/- SEM) during randomized infusions of 0.03, 0.1, 0.3, or 1.0 microgram/kg/min was 99 +/- 1, 95 +/- 1 (p less than 0.05), 93 +/- 1 (p less than 0.01), or 79 +/- 6% (p less than 0.001), respectively, but no tachycardia and no augmentation of the norepinephrine release rate (up to 0.3 microgram/kg/min) were observed, which is in contrast to comparable hypotension induced by hydralazine or nitroglycerin. The release rate of epinephrine (control, 6.7 +/- 0.6 ng/kg/min) declined immediately during infusions of atrial natriuretic factor to a minimum of 49 +/- 5% of control (p less than 0.001) during 0.1 microgram/kg/min and to 63 +/- 5% (0.1 greater than p greater than 0.05) or 95 +/- 13% (not significant) during 0.3 or 1.0 microgram/kg/min. Steady state arterial plasma concentrations of atrial natriuretic factor were 39 +/- 10 pg/ml (n = 6) during infusions of saline and 284 +/- 24 pg/ml (n = 6) and 1520 +/- 300 pg/ml (n = 9) during 0.03 and 0.1 microgram/kg/min infusions of the factor.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Sodium", "aliases": "Ion Level Sodium", "definition": "A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.\n    ", "id": "MESH:D012964"}
{"mention": "norepinephrine", "mention_text": "In six conscious, trained dogs, maintained on a normal sodium intake of 2 to 4 mEq/kg/day, sympathetic activity was assessed as the release rate of norepinephrine and epinephrine during 15-minute i.v. infusions of human alpha-atrial natriuretic factor. Mean arterial pressure (as a percentage of control +/- SEM) during randomized infusions of 0.03, 0.1, 0.3, or 1.0 microgram/kg/min was 99 +/- 1, 95 +/- 1 (p less than 0.05), 93 +/- 1 (p less than 0.01), or 79 +/- 6% (p less than 0.001), respectively, but no tachycardia and no augmentation of the norepinephrine release rate (up to 0.3 microgram/kg/min) were observed, which is in contrast to comparable hypotension induced by hydralazine or nitroglycerin. The release rate of epinephrine (control, 6.7 +/- 0.6 ng/kg/min) declined immediately during infusions of atrial natriuretic factor to a minimum of 49 +/- 5% of control (p less than 0.001) during 0.1 microgram/kg/min and to 63 +/- 5% (0.1 greater than p greater than 0.05) or 95 +/- 13% (not significant) during 0.3 or 1.0 microgram/kg/min. Steady state arterial plasma concentrations of atrial natriuretic factor were 39 +/- 10 pg/ml (n = 6) during infusions of saline and 284 +/- 24 pg/ml (n = 6) and 1520 +/- 300 pg/ml (n = 9) during 0.03 and 0.1 microgram/kg/min infusions of the factor.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Norepinephrine", "aliases": "Abbott Brand of Levophed Bitartrate Arterenol Aventis Norepinephrine Hydrochloride Noradrenaline Levarterenol Levonor Levonorepinephrine Noradrénaline tartrate renaudin Norepinephrin d-Tartrate (1:1) (+)-Isomer (+,-)-Isomer l-Tartrate Monohydrate (1:2) Renaudin", "definition": "Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.\n    ", "id": "MESH:D009638"}
{"mention": "epinephrine", "mention_text": "In six conscious, trained dogs, maintained on a normal sodium intake of 2 to 4 mEq/kg/day, sympathetic activity was assessed as the release rate of norepinephrine and epinephrine during 15-minute i.v. infusions of human alpha-atrial natriuretic factor. Mean arterial pressure (as a percentage of control +/- SEM) during randomized infusions of 0.03, 0.1, 0.3, or 1.0 microgram/kg/min was 99 +/- 1, 95 +/- 1 (p less than 0.05), 93 +/- 1 (p less than 0.01), or 79 +/- 6% (p less than 0.001), respectively, but no tachycardia and no augmentation of the norepinephrine release rate (up to 0.3 microgram/kg/min) were observed, which is in contrast to comparable hypotension induced by hydralazine or nitroglycerin. The release rate of epinephrine (control, 6.7 +/- 0.6 ng/kg/min) declined immediately during infusions of atrial natriuretic factor to a minimum of 49 +/- 5% of control (p less than 0.001) during 0.1 microgram/kg/min and to 63 +/- 5% (0.1 greater than p greater than 0.05) or 95 +/- 13% (not significant) during 0.3 or 1.0 microgram/kg/min. Steady state arterial plasma concentrations of atrial natriuretic factor were 39 +/- 10 pg/ml (n = 6) during infusions of saline and 284 +/- 24 pg/ml (n = 6) and 1520 +/- 300 pg/ml (n = 9) during 0.03 and 0.1 microgram/kg/min infusions of the factor.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Epinephrine", "aliases": "4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-benzenediol Acetate Epinephrine Adrenaline Acid Tartrate Bitartrate Hydrochloride Allergan Brand of Epifrin Hydrogen Epitrate Lyophrin Medihaler-Epi", "definition": "The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.\n    ", "id": "MESH:D004837"}
{"mention": "tachycardia", "mention_text": "In six conscious, trained dogs, maintained on a normal sodium intake of 2 to 4 mEq/kg/day, sympathetic activity was assessed as the release rate of norepinephrine and epinephrine during 15-minute i.v. infusions of human alpha-atrial natriuretic factor. Mean arterial pressure (as a percentage of control +/- SEM) during randomized infusions of 0.03, 0.1, 0.3, or 1.0 microgram/kg/min was 99 +/- 1, 95 +/- 1 (p less than 0.05), 93 +/- 1 (p less than 0.01), or 79 +/- 6% (p less than 0.001), respectively, but no tachycardia and no augmentation of the norepinephrine release rate (up to 0.3 microgram/kg/min) were observed, which is in contrast to comparable hypotension induced by hydralazine or nitroglycerin. The release rate of epinephrine (control, 6.7 +/- 0.6 ng/kg/min) declined immediately during infusions of atrial natriuretic factor to a minimum of 49 +/- 5% of control (p less than 0.001) during 0.1 microgram/kg/min and to 63 +/- 5% (0.1 greater than p greater than 0.05) or 95 +/- 13% (not significant) during 0.3 or 1.0 microgram/kg/min. Steady state arterial plasma concentrations of atrial natriuretic factor were 39 +/- 10 pg/ml (n = 6) during infusions of saline and 284 +/- 24 pg/ml (n = 6) and 1520 +/- 300 pg/ml (n = 9) during 0.03 and 0.1 microgram/kg/min infusions of the factor.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Tachycardia", "aliases": "Tachyarrhythmia Tachyarrhythmias Tachycardia Tachycardias", "definition": "Abnormally rapid heartbeat, usually with a HEART RATE above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia.\n    ", "id": "MESH:D013610"}
{"mention": "hypotension", "mention_text": "In six conscious, trained dogs, maintained on a normal sodium intake of 2 to 4 mEq/kg/day, sympathetic activity was assessed as the release rate of norepinephrine and epinephrine during 15-minute i.v. infusions of human alpha-atrial natriuretic factor. Mean arterial pressure (as a percentage of control +/- SEM) during randomized infusions of 0.03, 0.1, 0.3, or 1.0 microgram/kg/min was 99 +/- 1, 95 +/- 1 (p less than 0.05), 93 +/- 1 (p less than 0.01), or 79 +/- 6% (p less than 0.001), respectively, but no tachycardia and no augmentation of the norepinephrine release rate (up to 0.3 microgram/kg/min) were observed, which is in contrast to comparable hypotension induced by hydralazine or nitroglycerin. The release rate of epinephrine (control, 6.7 +/- 0.6 ng/kg/min) declined immediately during infusions of atrial natriuretic factor to a minimum of 49 +/- 5% of control (p less than 0.001) during 0.1 microgram/kg/min and to 63 +/- 5% (0.1 greater than p greater than 0.05) or 95 +/- 13% (not significant) during 0.3 or 1.0 microgram/kg/min. Steady state arterial plasma concentrations of atrial natriuretic factor were 39 +/- 10 pg/ml (n = 6) during infusions of saline and 284 +/- 24 pg/ml (n = 6) and 1520 +/- 300 pg/ml (n = 9) during 0.03 and 0.1 microgram/kg/min infusions of the factor.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "hydralazine", "mention_text": "In six conscious, trained dogs, maintained on a normal sodium intake of 2 to 4 mEq/kg/day, sympathetic activity was assessed as the release rate of norepinephrine and epinephrine during 15-minute i.v. infusions of human alpha-atrial natriuretic factor. Mean arterial pressure (as a percentage of control +/- SEM) during randomized infusions of 0.03, 0.1, 0.3, or 1.0 microgram/kg/min was 99 +/- 1, 95 +/- 1 (p less than 0.05), 93 +/- 1 (p less than 0.01), or 79 +/- 6% (p less than 0.001), respectively, but no tachycardia and no augmentation of the norepinephrine release rate (up to 0.3 microgram/kg/min) were observed, which is in contrast to comparable hypotension induced by hydralazine or nitroglycerin. The release rate of epinephrine (control, 6.7 +/- 0.6 ng/kg/min) declined immediately during infusions of atrial natriuretic factor to a minimum of 49 +/- 5% of control (p less than 0.001) during 0.1 microgram/kg/min and to 63 +/- 5% (0.1 greater than p greater than 0.05) or 95 +/- 13% (not significant) during 0.3 or 1.0 microgram/kg/min. Steady state arterial plasma concentrations of atrial natriuretic factor were 39 +/- 10 pg/ml (n = 6) during infusions of saline and 284 +/- 24 pg/ml (n = 6) and 1520 +/- 300 pg/ml (n = 9) during 0.03 and 0.1 microgram/kg/min infusions of the factor.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Hydralazine", "aliases": "Apresoline Apressin Apressoline Hydralazine Hydrochloride mono mono-Hydrochloride Hydrallazin Hydrazinophthalazine Nepresol", "definition": "A direct-acting vasodilator that is used as an antihypertensive agent.\n    ", "id": "MESH:D006830"}
{"mention": "nitroglycerin", "mention_text": "In six conscious, trained dogs, maintained on a normal sodium intake of 2 to 4 mEq/kg/day, sympathetic activity was assessed as the release rate of norepinephrine and epinephrine during 15-minute i.v. infusions of human alpha-atrial natriuretic factor. Mean arterial pressure (as a percentage of control +/- SEM) during randomized infusions of 0.03, 0.1, 0.3, or 1.0 microgram/kg/min was 99 +/- 1, 95 +/- 1 (p less than 0.05), 93 +/- 1 (p less than 0.01), or 79 +/- 6% (p less than 0.001), respectively, but no tachycardia and no augmentation of the norepinephrine release rate (up to 0.3 microgram/kg/min) were observed, which is in contrast to comparable hypotension induced by hydralazine or nitroglycerin. The release rate of epinephrine (control, 6.7 +/- 0.6 ng/kg/min) declined immediately during infusions of atrial natriuretic factor to a minimum of 49 +/- 5% of control (p less than 0.001) during 0.1 microgram/kg/min and to 63 +/- 5% (0.1 greater than p greater than 0.05) or 95 +/- 13% (not significant) during 0.3 or 1.0 microgram/kg/min. Steady state arterial plasma concentrations of atrial natriuretic factor were 39 +/- 10 pg/ml (n = 6) during infusions of saline and 284 +/- 24 pg/ml (n = 6) and 1520 +/- 300 pg/ml (n = 9) during 0.03 and 0.1 microgram/kg/min infusions of the factor.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Nitroglycerin", "aliases": "Anginine Dynamite Gilustenon Glyceryl Trinitrate Nitrangin Nitro Bid Dur Nitro-Bid Nitro-Dur NitroBid NitroDur Nitrocard Nitroderm TTS Nitroglycerin Nitroglyn Nitrol Nitrolan Nitrong Nitrospan Nitrostat Perlinganit Susadrin Sustac Sustak Sustonit Transderm Tridil Trinitrin Trinitrolong", "definition": "A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives.\n    ", "id": "MESH:D005996"}
{"mention": "Death", "mention_text": "Death from chemotherapy in gestational trophoblastic disease.", "entity": "Death", "aliases": "Cardiac Death Determination of Near-Death Experience", "definition": "Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.\n    ", "id": "MESH:D003643"}
{"mention": "gestational trophoblastic disease", "mention_text": "Death from chemotherapy in gestational trophoblastic disease.", "entity": "Gestational Trophoblastic Disease", "aliases": "Disease Gestational Trophoblastic Diseases Neoplasia Neoplasm Neoplasms", "definition": "A group of diseases arising from pregnancy that are commonly associated with hyperplasia of trophoblasts (TROPHOBLAST) and markedly elevated human CHORIONIC GONADOTROPIN. They include HYDATIDIFORM MOLE, invasive mole (HYDATIDIFORM MOLE, INVASIVE), placental-site trophoblastic tumor (TROPHOBLASTIC TUMOR, PLACENTAL SITE), and CHORIOCARCINOMA. These neoplasms have varying propensities for invasion and spread.\n    ", "id": "MESH:D031901"}
{"mention": "choriocarcinoma", "mention_text": "Multiple cytotoxic drug administration is the generally accepted treatment of patients with a high-risk stage of choriocarcinoma. Based on this principle a 27-year old woman, classified as being in the high-risk group (Goldstein and Berkowitz score: 11), was treated with multiple cytotoxic drugs. The multiple drug schema consisted of: Etoposide 16.213, Methotrexate, Cyclophosphamide, Actomycin-D, and Cisplatin. On the first day of the schedule, moderate high doses of Methotrexate, Etoposide and Cyclophosphamide were administered. Within 8 hours after initiation of therapy the patient died with a clinical picture resembling massive pulmonary obstruction due to choriocarcinomic tissue plugs, probably originating from the uterus. Formation of these plugs was probably due to extensive tumor necrosis at the level of the walls of the major uterine veins, which resulted in an open exchange of tumor plugs to the vascular spaces; decrease in tumor tissue coherence secondary to chemotherapy may have further contributed to the formation of tumor emboli. In view of the close time association between the start of chemotherapy and the acute onset of massive embolism other explanations, such as spontaneous necrosis, must be considered less likely. Patients with large pelvic tumor loads are, according to existing classifications, at high risk to die and to develop drug resistance. Notwithstanding these facts our findings suggest that these patients might benefit from relatively mild initial treatment, especially true for patients not previously exposed to this drug. Close observation of the response status both clinically and with beta-hCG values may indicate whether and when more agressive combination chemotherapy should be started.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Choriocarcinoma", "aliases": "Choriocarcinoma Choriocarcinomas", "definition": "A malignant metastatic form of trophoblastic tumors. Unlike the HYDATIDIFORM MOLE, choriocarcinoma contains no CHORIONIC VILLI but rather sheets of undifferentiated cytotrophoblasts and syncytiotrophoblasts (TROPHOBLASTS). It is characterized by the large amounts of CHORIONIC GONADOTROPIN produced. Tissue origins can be determined by DNA analyses: placental (fetal) origin or non-placental origin (CHORIOCARCINOMA, NON-GESTATIONAL).\n    ", "id": "MESH:D002822"}
{"mention": "Etoposide", "mention_text": "Multiple cytotoxic drug administration is the generally accepted treatment of patients with a high-risk stage of choriocarcinoma. Based on this principle a 27-year old woman, classified as being in the high-risk group (Goldstein and Berkowitz score: 11), was treated with multiple cytotoxic drugs. The multiple drug schema consisted of: Etoposide 16.213, Methotrexate, Cyclophosphamide, Actomycin-D, and Cisplatin. On the first day of the schedule, moderate high doses of Methotrexate, Etoposide and Cyclophosphamide were administered. Within 8 hours after initiation of therapy the patient died with a clinical picture resembling massive pulmonary obstruction due to choriocarcinomic tissue plugs, probably originating from the uterus. Formation of these plugs was probably due to extensive tumor necrosis at the level of the walls of the major uterine veins, which resulted in an open exchange of tumor plugs to the vascular spaces; decrease in tumor tissue coherence secondary to chemotherapy may have further contributed to the formation of tumor emboli. In view of the close time association between the start of chemotherapy and the acute onset of massive embolism other explanations, such as spontaneous necrosis, must be considered less likely. Patients with large pelvic tumor loads are, according to existing classifications, at high risk to die and to develop drug resistance. Notwithstanding these facts our findings suggest that these patients might benefit from relatively mild initial treatment, especially true for patients not previously exposed to this drug. Close observation of the response status both clinically and with beta-hCG values may indicate whether and when more agressive combination chemotherapy should be started.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Etoposide", "aliases": "Baxter Brand of Etoposide Oncology Bristol Myers Squibb Bristol-Myers Celltop Demethyl Epipodophyllotoxin Ethylidine Glucoside Eposide Eposin Eto GRY Eto-GRY Etomedac Etopos Pierre Fabre Teva (5S)-Isomer (5a alpha)-Isomer alpha,9 alpha D Glucopyranosyl Isomer alpha-D-Glucopyranosyl Etoposido Ferrer Farma Exitop Gry Lastet Lemery Medac NSC 141540 NSC-141540 NSC141540 Novartis Onkoposid Onkoworks Pharmachemie Prasfarma Riboposid Sanfer Tedec Meiji Toposar VP 16 213 16-213 16213 VP-16 VP16 Vepesid ", "definition": "A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.\n    ", "id": "MESH:D005047"}
{"mention": "Methotrexate", "mention_text": "Multiple cytotoxic drug administration is the generally accepted treatment of patients with a high-risk stage of choriocarcinoma. Based on this principle a 27-year old woman, classified as being in the high-risk group (Goldstein and Berkowitz score: 11), was treated with multiple cytotoxic drugs. The multiple drug schema consisted of: Etoposide 16.213, Methotrexate, Cyclophosphamide, Actomycin-D, and Cisplatin. On the first day of the schedule, moderate high doses of Methotrexate, Etoposide and Cyclophosphamide were administered. Within 8 hours after initiation of therapy the patient died with a clinical picture resembling massive pulmonary obstruction due to choriocarcinomic tissue plugs, probably originating from the uterus. Formation of these plugs was probably due to extensive tumor necrosis at the level of the walls of the major uterine veins, which resulted in an open exchange of tumor plugs to the vascular spaces; decrease in tumor tissue coherence secondary to chemotherapy may have further contributed to the formation of tumor emboli. In view of the close time association between the start of chemotherapy and the acute onset of massive embolism other explanations, such as spontaneous necrosis, must be considered less likely. Patients with large pelvic tumor loads are, according to existing classifications, at high risk to die and to develop drug resistance. Notwithstanding these facts our findings suggest that these patients might benefit from relatively mild initial treatment, especially true for patients not previously exposed to this drug. Close observation of the response status both clinically and with beta-hCG values may indicate whether and when more agressive combination chemotherapy should be started.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Methotrexate", "aliases": "Amethopterin Dicesium Salt Methotrexate Hydrate Sodium (D)-Isomer (DL)-Isomer Disodium Mexate", "definition": "An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.\n    ", "id": "MESH:D008727"}
{"mention": "Cyclophosphamide", "mention_text": "Multiple cytotoxic drug administration is the generally accepted treatment of patients with a high-risk stage of choriocarcinoma. Based on this principle a 27-year old woman, classified as being in the high-risk group (Goldstein and Berkowitz score: 11), was treated with multiple cytotoxic drugs. The multiple drug schema consisted of: Etoposide 16.213, Methotrexate, Cyclophosphamide, Actomycin-D, and Cisplatin. On the first day of the schedule, moderate high doses of Methotrexate, Etoposide and Cyclophosphamide were administered. Within 8 hours after initiation of therapy the patient died with a clinical picture resembling massive pulmonary obstruction due to choriocarcinomic tissue plugs, probably originating from the uterus. Formation of these plugs was probably due to extensive tumor necrosis at the level of the walls of the major uterine veins, which resulted in an open exchange of tumor plugs to the vascular spaces; decrease in tumor tissue coherence secondary to chemotherapy may have further contributed to the formation of tumor emboli. In view of the close time association between the start of chemotherapy and the acute onset of massive embolism other explanations, such as spontaneous necrosis, must be considered less likely. Patients with large pelvic tumor loads are, according to existing classifications, at high risk to die and to develop drug resistance. Notwithstanding these facts our findings suggest that these patients might benefit from relatively mild initial treatment, especially true for patients not previously exposed to this drug. Close observation of the response status both clinically and with beta-hCG values may indicate whether and when more agressive combination chemotherapy should be started.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Cyclophosphamide", "aliases": "Anhydrous Cyclophosphamide B 518 B-518 B518 Monohydrate (R)-Isomer (S)-Isomer Cyclophosphane Cytophosphan Cytophosphane Cytoxan Endoxan NSC 26271 NSC-26271 NSC26271 Neosar Procytox Sendoxan", "definition": "Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.\n    ", "id": "MESH:D003520"}
{"mention": "Actomycin-D", "mention_text": "Multiple cytotoxic drug administration is the generally accepted treatment of patients with a high-risk stage of choriocarcinoma. Based on this principle a 27-year old woman, classified as being in the high-risk group (Goldstein and Berkowitz score: 11), was treated with multiple cytotoxic drugs. The multiple drug schema consisted of: Etoposide 16.213, Methotrexate, Cyclophosphamide, Actomycin-D, and Cisplatin. On the first day of the schedule, moderate high doses of Methotrexate, Etoposide and Cyclophosphamide were administered. Within 8 hours after initiation of therapy the patient died with a clinical picture resembling massive pulmonary obstruction due to choriocarcinomic tissue plugs, probably originating from the uterus. Formation of these plugs was probably due to extensive tumor necrosis at the level of the walls of the major uterine veins, which resulted in an open exchange of tumor plugs to the vascular spaces; decrease in tumor tissue coherence secondary to chemotherapy may have further contributed to the formation of tumor emboli. In view of the close time association between the start of chemotherapy and the acute onset of massive embolism other explanations, such as spontaneous necrosis, must be considered less likely. Patients with large pelvic tumor loads are, according to existing classifications, at high risk to die and to develop drug resistance. Notwithstanding these facts our findings suggest that these patients might benefit from relatively mild initial treatment, especially true for patients not previously exposed to this drug. Close observation of the response status both clinically and with beta-hCG values may indicate whether and when more agressive combination chemotherapy should be started.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Dactinomycin", "aliases": "Ac-De Actinomycin D Cosmegen Lyovac Dactinomycin Lemery Brand of Lyovac-Cosmegen MSD Meractinomycin Merck Frosst Sharp & Dohme", "definition": "A compound composed of a two CYCLIC PEPTIDES attached to a phenoxazine that is derived from STREPTOMYCES parvullus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. (From AMA Drug Evaluations Annual, 1993, p2015)\n    ", "id": "MESH:D003609"}
{"mention": "Cisplatin", "mention_text": "Multiple cytotoxic drug administration is the generally accepted treatment of patients with a high-risk stage of choriocarcinoma. Based on this principle a 27-year old woman, classified as being in the high-risk group (Goldstein and Berkowitz score: 11), was treated with multiple cytotoxic drugs. The multiple drug schema consisted of: Etoposide 16.213, Methotrexate, Cyclophosphamide, Actomycin-D, and Cisplatin. On the first day of the schedule, moderate high doses of Methotrexate, Etoposide and Cyclophosphamide were administered. Within 8 hours after initiation of therapy the patient died with a clinical picture resembling massive pulmonary obstruction due to choriocarcinomic tissue plugs, probably originating from the uterus. Formation of these plugs was probably due to extensive tumor necrosis at the level of the walls of the major uterine veins, which resulted in an open exchange of tumor plugs to the vascular spaces; decrease in tumor tissue coherence secondary to chemotherapy may have further contributed to the formation of tumor emboli. In view of the close time association between the start of chemotherapy and the acute onset of massive embolism other explanations, such as spontaneous necrosis, must be considered less likely. Patients with large pelvic tumor loads are, according to existing classifications, at high risk to die and to develop drug resistance. Notwithstanding these facts our findings suggest that these patients might benefit from relatively mild initial treatment, especially true for patients not previously exposed to this drug. Close observation of the response status both clinically and with beta-hCG values may indicate whether and when more agressive combination chemotherapy should be started.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Cisplatin", "aliases": "Biocisplatinum Cisplatin Diamminodichloride Platinum Dichlorodiammineplatinum NSC-119875 Platidiam Platino Platinol cis Diamminedichloroplatinum cis-Diamminedichloroplatinum cis-Diamminedichloroplatinum(II) cis-Dichlorodiammineplatinum(II) cis-Platinum", "definition": "An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.\n    ", "id": "MESH:D002945"}
{"mention": "pulmonary obstruction", "mention_text": "Multiple cytotoxic drug administration is the generally accepted treatment of patients with a high-risk stage of choriocarcinoma. Based on this principle a 27-year old woman, classified as being in the high-risk group (Goldstein and Berkowitz score: 11), was treated with multiple cytotoxic drugs. The multiple drug schema consisted of: Etoposide 16.213, Methotrexate, Cyclophosphamide, Actomycin-D, and Cisplatin. On the first day of the schedule, moderate high doses of Methotrexate, Etoposide and Cyclophosphamide were administered. Within 8 hours after initiation of therapy the patient died with a clinical picture resembling massive pulmonary obstruction due to choriocarcinomic tissue plugs, probably originating from the uterus. Formation of these plugs was probably due to extensive tumor necrosis at the level of the walls of the major uterine veins, which resulted in an open exchange of tumor plugs to the vascular spaces; decrease in tumor tissue coherence secondary to chemotherapy may have further contributed to the formation of tumor emboli. In view of the close time association between the start of chemotherapy and the acute onset of massive embolism other explanations, such as spontaneous necrosis, must be considered less likely. Patients with large pelvic tumor loads are, according to existing classifications, at high risk to die and to develop drug resistance. Notwithstanding these facts our findings suggest that these patients might benefit from relatively mild initial treatment, especially true for patients not previously exposed to this drug. Close observation of the response status both clinically and with beta-hCG values may indicate whether and when more agressive combination chemotherapy should be started.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Pulmonary Embolism", "aliases": "Embolism Pulmonary Embolisms Thromboembolism Thromboembolisms", "definition": "Blocking of the PULMONARY ARTERY or one of its branches by an EMBOLUS.\n    ", "id": "MESH:D011655"}
{"mention": "tumor", "mention_text": "Multiple cytotoxic drug administration is the generally accepted treatment of patients with a high-risk stage of choriocarcinoma. Based on this principle a 27-year old woman, classified as being in the high-risk group (Goldstein and Berkowitz score: 11), was treated with multiple cytotoxic drugs. The multiple drug schema consisted of: Etoposide 16.213, Methotrexate, Cyclophosphamide, Actomycin-D, and Cisplatin. On the first day of the schedule, moderate high doses of Methotrexate, Etoposide and Cyclophosphamide were administered. Within 8 hours after initiation of therapy the patient died with a clinical picture resembling massive pulmonary obstruction due to choriocarcinomic tissue plugs, probably originating from the uterus. Formation of these plugs was probably due to extensive tumor necrosis at the level of the walls of the major uterine veins, which resulted in an open exchange of tumor plugs to the vascular spaces; decrease in tumor tissue coherence secondary to chemotherapy may have further contributed to the formation of tumor emboli. In view of the close time association between the start of chemotherapy and the acute onset of massive embolism other explanations, such as spontaneous necrosis, must be considered less likely. Patients with large pelvic tumor loads are, according to existing classifications, at high risk to die and to develop drug resistance. Notwithstanding these facts our findings suggest that these patients might benefit from relatively mild initial treatment, especially true for patients not previously exposed to this drug. Close observation of the response status both clinically and with beta-hCG values may indicate whether and when more agressive combination chemotherapy should be started.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "necrosis", "mention_text": "Multiple cytotoxic drug administration is the generally accepted treatment of patients with a high-risk stage of choriocarcinoma. Based on this principle a 27-year old woman, classified as being in the high-risk group (Goldstein and Berkowitz score: 11), was treated with multiple cytotoxic drugs. The multiple drug schema consisted of: Etoposide 16.213, Methotrexate, Cyclophosphamide, Actomycin-D, and Cisplatin. On the first day of the schedule, moderate high doses of Methotrexate, Etoposide and Cyclophosphamide were administered. Within 8 hours after initiation of therapy the patient died with a clinical picture resembling massive pulmonary obstruction due to choriocarcinomic tissue plugs, probably originating from the uterus. Formation of these plugs was probably due to extensive tumor necrosis at the level of the walls of the major uterine veins, which resulted in an open exchange of tumor plugs to the vascular spaces; decrease in tumor tissue coherence secondary to chemotherapy may have further contributed to the formation of tumor emboli. In view of the close time association between the start of chemotherapy and the acute onset of massive embolism other explanations, such as spontaneous necrosis, must be considered less likely. Patients with large pelvic tumor loads are, according to existing classifications, at high risk to die and to develop drug resistance. Notwithstanding these facts our findings suggest that these patients might benefit from relatively mild initial treatment, especially true for patients not previously exposed to this drug. Close observation of the response status both clinically and with beta-hCG values may indicate whether and when more agressive combination chemotherapy should be started.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Necrosis", "aliases": "Necroses Necrosis", "definition": "The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. Distinguish it from APOPTOSIS which is a normal, regulated cellular process.\n    ", "id": "MESH:D009336"}
{"mention": "embolism", "mention_text": "Multiple cytotoxic drug administration is the generally accepted treatment of patients with a high-risk stage of choriocarcinoma. Based on this principle a 27-year old woman, classified as being in the high-risk group (Goldstein and Berkowitz score: 11), was treated with multiple cytotoxic drugs. The multiple drug schema consisted of: Etoposide 16.213, Methotrexate, Cyclophosphamide, Actomycin-D, and Cisplatin. On the first day of the schedule, moderate high doses of Methotrexate, Etoposide and Cyclophosphamide were administered. Within 8 hours after initiation of therapy the patient died with a clinical picture resembling massive pulmonary obstruction due to choriocarcinomic tissue plugs, probably originating from the uterus. Formation of these plugs was probably due to extensive tumor necrosis at the level of the walls of the major uterine veins, which resulted in an open exchange of tumor plugs to the vascular spaces; decrease in tumor tissue coherence secondary to chemotherapy may have further contributed to the formation of tumor emboli. In view of the close time association between the start of chemotherapy and the acute onset of massive embolism other explanations, such as spontaneous necrosis, must be considered less likely. Patients with large pelvic tumor loads are, according to existing classifications, at high risk to die and to develop drug resistance. Notwithstanding these facts our findings suggest that these patients might benefit from relatively mild initial treatment, especially true for patients not previously exposed to this drug. Close observation of the response status both clinically and with beta-hCG values may indicate whether and when more agressive combination chemotherapy should be started.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Embolism", "aliases": "Embolism Embolisms Embolus", "definition": "Blocking of a blood vessel by an embolus which can be a blood clot or other undissolved material in the blood stream.\n    ", "id": "MESH:D004617"}
{"mention": "pelvic tumor", "mention_text": "Multiple cytotoxic drug administration is the generally accepted treatment of patients with a high-risk stage of choriocarcinoma. Based on this principle a 27-year old woman, classified as being in the high-risk group (Goldstein and Berkowitz score: 11), was treated with multiple cytotoxic drugs. The multiple drug schema consisted of: Etoposide 16.213, Methotrexate, Cyclophosphamide, Actomycin-D, and Cisplatin. On the first day of the schedule, moderate high doses of Methotrexate, Etoposide and Cyclophosphamide were administered. Within 8 hours after initiation of therapy the patient died with a clinical picture resembling massive pulmonary obstruction due to choriocarcinomic tissue plugs, probably originating from the uterus. Formation of these plugs was probably due to extensive tumor necrosis at the level of the walls of the major uterine veins, which resulted in an open exchange of tumor plugs to the vascular spaces; decrease in tumor tissue coherence secondary to chemotherapy may have further contributed to the formation of tumor emboli. In view of the close time association between the start of chemotherapy and the acute onset of massive embolism other explanations, such as spontaneous necrosis, must be considered less likely. Patients with large pelvic tumor loads are, according to existing classifications, at high risk to die and to develop drug resistance. Notwithstanding these facts our findings suggest that these patients might benefit from relatively mild initial treatment, especially true for patients not previously exposed to this drug. Close observation of the response status both clinically and with beta-hCG values may indicate whether and when more agressive combination chemotherapy should be started.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Pelvic Neoplasms", "aliases": "Cancer of Pelvis the Pelvic Cancers Neoplasm Neoplasms", "definition": "Tumors or cancer of the pelvic region.\n    ", "id": "MESH:D010386"}
{"mention": "Sexual dysfunction", "mention_text": "Sexual dysfunction among patients with arthritis.", "entity": "Sexual Dysfunction, Physiological", "aliases": "Physiological Sexual Disorder Disorders Dysfunction Dysfunctions Sex", "definition": "Physiological disturbances in normal sexual performance in either the male or the female.\n    ", "id": "MESH:D012735"}
{"mention": "arthritis", "mention_text": "Sexual dysfunction among patients with arthritis.", "entity": "Arthritis", "aliases": "Arthritides Arthritis Polyarthritides Polyarthritis", "definition": "", "id": "MESH:D001168"}
{"mention": "arthritis", "mention_text": "The relationship of arthritis and sexual dysfunction was investigated among 169 patients with rheumatoid arthritis, osteoarthritis and spondyloarthropathy, 130 of whom were pair-matched to controls. Assessments of marital happiness and depressed mood were also made using the CES-D and the Azrin Marital Happiness Scale (AMHS). Sexual dysfunctions were found to be common among patients and controls, the majority in both groups reporting one or more dysfunctions. Impotence was more common among male patients than controls and was found to be associated with co-morbidity and the taking of methotrexate. Depressed mood was more common among patients and was associated with certain sexual difficulties, but not with impotence. Marital unhappiness, as indicated by AMHS scores, was not associated with arthritis but was associated with sexual dysfunction, sexual dissatisfaction and being female.", "entity": "Arthritis", "aliases": "Arthritides Arthritis Polyarthritides Polyarthritis", "definition": "", "id": "MESH:D001168"}
{"mention": "sexual dysfunction", "mention_text": "The relationship of arthritis and sexual dysfunction was investigated among 169 patients with rheumatoid arthritis, osteoarthritis and spondyloarthropathy, 130 of whom were pair-matched to controls. Assessments of marital happiness and depressed mood were also made using the CES-D and the Azrin Marital Happiness Scale (AMHS). Sexual dysfunctions were found to be common among patients and controls, the majority in both groups reporting one or more dysfunctions. Impotence was more common among male patients than controls and was found to be associated with co-morbidity and the taking of methotrexate. Depressed mood was more common among patients and was associated with certain sexual difficulties, but not with impotence. Marital unhappiness, as indicated by AMHS scores, was not associated with arthritis but was associated with sexual dysfunction, sexual dissatisfaction and being female.", "entity": "Sexual Dysfunction, Physiological", "aliases": "Physiological Sexual Disorder Disorders Dysfunction Dysfunctions Sex", "definition": "Physiological disturbances in normal sexual performance in either the male or the female.\n    ", "id": "MESH:D012735"}
{"mention": "rheumatoid arthritis", "mention_text": "The relationship of arthritis and sexual dysfunction was investigated among 169 patients with rheumatoid arthritis, osteoarthritis and spondyloarthropathy, 130 of whom were pair-matched to controls. Assessments of marital happiness and depressed mood were also made using the CES-D and the Azrin Marital Happiness Scale (AMHS). Sexual dysfunctions were found to be common among patients and controls, the majority in both groups reporting one or more dysfunctions. Impotence was more common among male patients than controls and was found to be associated with co-morbidity and the taking of methotrexate. Depressed mood was more common among patients and was associated with certain sexual difficulties, but not with impotence. Marital unhappiness, as indicated by AMHS scores, was not associated with arthritis but was associated with sexual dysfunction, sexual dissatisfaction and being female.", "entity": "Arthritis, Rheumatoid", "aliases": "Arthritis Rheumatoid", "definition": "A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.\n    ", "id": "MESH:D001172"}
{"mention": "osteoarthritis", "mention_text": "The relationship of arthritis and sexual dysfunction was investigated among 169 patients with rheumatoid arthritis, osteoarthritis and spondyloarthropathy, 130 of whom were pair-matched to controls. Assessments of marital happiness and depressed mood were also made using the CES-D and the Azrin Marital Happiness Scale (AMHS). Sexual dysfunctions were found to be common among patients and controls, the majority in both groups reporting one or more dysfunctions. Impotence was more common among male patients than controls and was found to be associated with co-morbidity and the taking of methotrexate. Depressed mood was more common among patients and was associated with certain sexual difficulties, but not with impotence. Marital unhappiness, as indicated by AMHS scores, was not associated with arthritis but was associated with sexual dysfunction, sexual dissatisfaction and being female.", "entity": "Osteoarthritis", "aliases": "Arthritides Degenerative Arthritis Osteoarthritides Osteoarthritis Osteoarthroses Osteoarthrosis Deformans", "definition": "A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans.\n    ", "id": "MESH:D010003"}
{"mention": "spondyloarthropathy", "mention_text": "The relationship of arthritis and sexual dysfunction was investigated among 169 patients with rheumatoid arthritis, osteoarthritis and spondyloarthropathy, 130 of whom were pair-matched to controls. Assessments of marital happiness and depressed mood were also made using the CES-D and the Azrin Marital Happiness Scale (AMHS). Sexual dysfunctions were found to be common among patients and controls, the majority in both groups reporting one or more dysfunctions. Impotence was more common among male patients than controls and was found to be associated with co-morbidity and the taking of methotrexate. Depressed mood was more common among patients and was associated with certain sexual difficulties, but not with impotence. Marital unhappiness, as indicated by AMHS scores, was not associated with arthritis but was associated with sexual dysfunction, sexual dissatisfaction and being female.", "entity": "Spondylarthropathies", "aliases": "Bechterew Syndrome Marie Strumpell Spondylitis Marie-Strumpell Spondylarthropathies Spondylarthropathy Spondyloarthropathies Spondyloarthropathy", "definition": "Heterogeneous group of arthritic diseases sharing clinical and radiologic features. They are associated with the HLA-B27 ANTIGEN and some with a triggering infection. Most involve the axial joints in the SPINE, particularly the SACROILIAC JOINT, but can also involve asymmetric peripheral joints. Subsets include ANKYLOSING SPONDYLITIS; REACTIVE ARTHRITIS; PSORIATIC ARTHRITIS; and others.\n    ", "id": "MESH:D025242"}
{"mention": "depressed mood", "mention_text": "The relationship of arthritis and sexual dysfunction was investigated among 169 patients with rheumatoid arthritis, osteoarthritis and spondyloarthropathy, 130 of whom were pair-matched to controls. Assessments of marital happiness and depressed mood were also made using the CES-D and the Azrin Marital Happiness Scale (AMHS). Sexual dysfunctions were found to be common among patients and controls, the majority in both groups reporting one or more dysfunctions. Impotence was more common among male patients than controls and was found to be associated with co-morbidity and the taking of methotrexate. Depressed mood was more common among patients and was associated with certain sexual difficulties, but not with impotence. Marital unhappiness, as indicated by AMHS scores, was not associated with arthritis but was associated with sexual dysfunction, sexual dissatisfaction and being female.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "Sexual dysfunctions", "mention_text": "The relationship of arthritis and sexual dysfunction was investigated among 169 patients with rheumatoid arthritis, osteoarthritis and spondyloarthropathy, 130 of whom were pair-matched to controls. Assessments of marital happiness and depressed mood were also made using the CES-D and the Azrin Marital Happiness Scale (AMHS). Sexual dysfunctions were found to be common among patients and controls, the majority in both groups reporting one or more dysfunctions. Impotence was more common among male patients than controls and was found to be associated with co-morbidity and the taking of methotrexate. Depressed mood was more common among patients and was associated with certain sexual difficulties, but not with impotence. Marital unhappiness, as indicated by AMHS scores, was not associated with arthritis but was associated with sexual dysfunction, sexual dissatisfaction and being female.", "entity": "Sexual Dysfunction, Physiological", "aliases": "Physiological Sexual Disorder Disorders Dysfunction Dysfunctions Sex", "definition": "Physiological disturbances in normal sexual performance in either the male or the female.\n    ", "id": "MESH:D012735"}
{"mention": "Impotence", "mention_text": "The relationship of arthritis and sexual dysfunction was investigated among 169 patients with rheumatoid arthritis, osteoarthritis and spondyloarthropathy, 130 of whom were pair-matched to controls. Assessments of marital happiness and depressed mood were also made using the CES-D and the Azrin Marital Happiness Scale (AMHS). Sexual dysfunctions were found to be common among patients and controls, the majority in both groups reporting one or more dysfunctions. Impotence was more common among male patients than controls and was found to be associated with co-morbidity and the taking of methotrexate. Depressed mood was more common among patients and was associated with certain sexual difficulties, but not with impotence. Marital unhappiness, as indicated by AMHS scores, was not associated with arthritis but was associated with sexual dysfunction, sexual dissatisfaction and being female.", "entity": "Erectile Dysfunction", "aliases": "Dysfunction Erectile Impotence Male Sexual", "definition": "The inability in the male to have a PENILE ERECTION due to psychological or organ dysfunction.\n    ", "id": "MESH:D007172"}
{"mention": "methotrexate", "mention_text": "The relationship of arthritis and sexual dysfunction was investigated among 169 patients with rheumatoid arthritis, osteoarthritis and spondyloarthropathy, 130 of whom were pair-matched to controls. Assessments of marital happiness and depressed mood were also made using the CES-D and the Azrin Marital Happiness Scale (AMHS). Sexual dysfunctions were found to be common among patients and controls, the majority in both groups reporting one or more dysfunctions. Impotence was more common among male patients than controls and was found to be associated with co-morbidity and the taking of methotrexate. Depressed mood was more common among patients and was associated with certain sexual difficulties, but not with impotence. Marital unhappiness, as indicated by AMHS scores, was not associated with arthritis but was associated with sexual dysfunction, sexual dissatisfaction and being female.", "entity": "Methotrexate", "aliases": "Amethopterin Dicesium Salt Methotrexate Hydrate Sodium (D)-Isomer (DL)-Isomer Disodium Mexate", "definition": "An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.\n    ", "id": "MESH:D008727"}
{"mention": "Depressed mood", "mention_text": "The relationship of arthritis and sexual dysfunction was investigated among 169 patients with rheumatoid arthritis, osteoarthritis and spondyloarthropathy, 130 of whom were pair-matched to controls. Assessments of marital happiness and depressed mood were also made using the CES-D and the Azrin Marital Happiness Scale (AMHS). Sexual dysfunctions were found to be common among patients and controls, the majority in both groups reporting one or more dysfunctions. Impotence was more common among male patients than controls and was found to be associated with co-morbidity and the taking of methotrexate. Depressed mood was more common among patients and was associated with certain sexual difficulties, but not with impotence. Marital unhappiness, as indicated by AMHS scores, was not associated with arthritis but was associated with sexual dysfunction, sexual dissatisfaction and being female.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "impotence", "mention_text": "The relationship of arthritis and sexual dysfunction was investigated among 169 patients with rheumatoid arthritis, osteoarthritis and spondyloarthropathy, 130 of whom were pair-matched to controls. Assessments of marital happiness and depressed mood were also made using the CES-D and the Azrin Marital Happiness Scale (AMHS). Sexual dysfunctions were found to be common among patients and controls, the majority in both groups reporting one or more dysfunctions. Impotence was more common among male patients than controls and was found to be associated with co-morbidity and the taking of methotrexate. Depressed mood was more common among patients and was associated with certain sexual difficulties, but not with impotence. Marital unhappiness, as indicated by AMHS scores, was not associated with arthritis but was associated with sexual dysfunction, sexual dissatisfaction and being female.", "entity": "Erectile Dysfunction", "aliases": "Dysfunction Erectile Impotence Male Sexual", "definition": "The inability in the male to have a PENILE ERECTION due to psychological or organ dysfunction.\n    ", "id": "MESH:D007172"}
{"mention": "paracetamol", "mention_text": "Does paracetamol cause urothelial cancer or renal papillary necrosis?", "entity": "Acetaminophen", "aliases": "APAP Acamol Acephen Acetaco Acetamidophenol Acetaminophen Acetominophen Algotropyl Anacin 3 Anacin-3 Anacin3 Datril Hydroxyacetanilide N-(4-Hydroxyphenyl)acetanilide N-Acetyl-p-aminophenol Panadol Paracetamol Tylenol p-Acetamidophenol p-Hydroxyacetanilide", "definition": "Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.\n    ", "id": "MESH:D000082"}
{"mention": "urothelial cancer", "mention_text": "Does paracetamol cause urothelial cancer or renal papillary necrosis?", "entity": "Urethral Neoplasms", "aliases": "Cancer of Urethra the Urethral Cancers Neoplasm Neoplasms", "definition": "Cancer or tumors of the URETHRA. Benign epithelial tumors of the urethra usually consist of squamous and transitional cells. Primary urethral carcinomas are rare and typically of squamous cells. Urethral carcinoma is the only urological malignancy that is more common in females than in males.\n    ", "id": "MESH:D014523"}
{"mention": "renal papillary necrosis", "mention_text": "Does paracetamol cause urothelial cancer or renal papillary necrosis?", "entity": "Kidney Papillary Necrosis", "aliases": "Kidney Papillary Necrosis Renal Medullary Necrotizing Papillitides Papillitis", "definition": "A complication of kidney diseases characterized by cell death involving KIDNEY PAPILLA in the KIDNEY MEDULLA. Damages to this area may hinder the kidney to concentrate urine resulting in POLYURIA. Sloughed off necrotic tissue may block KIDNEY PELVIS or URETER. Necrosis of multiple renal papillae can lead to KIDNEY FAILURE.\n    ", "id": "MESH:D007681"}
{"mention": "renal papillary necrosis", "mention_text": "The risk of developing renal papillary necrosis or cancer of the renal pelvis, ureter or bladder associated with consumption of either phenacetin or paracetamol was calculated from data acquired by questionnaire from 381 cases and 808 controls. The risk of renal papillary necrosis was increased nearly 20-fold by consumption of phenacetin, which also increased the risk for cancer of the renal pelvis and bladder but not for ureteric cancer. By contrast, we were unable to substantiate an increased risk from paracetamol consumption for renal papillary necrosis or any of these cancers although there was a suggestion of an association with cancer of the ureter.", "entity": "Kidney Papillary Necrosis", "aliases": "Kidney Papillary Necrosis Renal Medullary Necrotizing Papillitides Papillitis", "definition": "A complication of kidney diseases characterized by cell death involving KIDNEY PAPILLA in the KIDNEY MEDULLA. Damages to this area may hinder the kidney to concentrate urine resulting in POLYURIA. Sloughed off necrotic tissue may block KIDNEY PELVIS or URETER. Necrosis of multiple renal papillae can lead to KIDNEY FAILURE.\n    ", "id": "MESH:D007681"}
{"mention": "cancer of the renal pelvis", "mention_text": "The risk of developing renal papillary necrosis or cancer of the renal pelvis, ureter or bladder associated with consumption of either phenacetin or paracetamol was calculated from data acquired by questionnaire from 381 cases and 808 controls. The risk of renal papillary necrosis was increased nearly 20-fold by consumption of phenacetin, which also increased the risk for cancer of the renal pelvis and bladder but not for ureteric cancer. By contrast, we were unable to substantiate an increased risk from paracetamol consumption for renal papillary necrosis or any of these cancers although there was a suggestion of an association with cancer of the ureter.", "entity": "Kidney Neoplasms", "aliases": "Cancer of Kidney the Renal Cancers Neoplasm Neoplasms", "definition": "Tumors or cancers of the KIDNEY.\n    ", "id": "MESH:D007680"}
{"mention": "phenacetin", "mention_text": "The risk of developing renal papillary necrosis or cancer of the renal pelvis, ureter or bladder associated with consumption of either phenacetin or paracetamol was calculated from data acquired by questionnaire from 381 cases and 808 controls. The risk of renal papillary necrosis was increased nearly 20-fold by consumption of phenacetin, which also increased the risk for cancer of the renal pelvis and bladder but not for ureteric cancer. By contrast, we were unable to substantiate an increased risk from paracetamol consumption for renal papillary necrosis or any of these cancers although there was a suggestion of an association with cancer of the ureter.", "entity": "Phenacetin", "aliases": "Acetophenetidin Phenacetin", "definition": "A phenylacetamide that was formerly used in ANALGESICS but nephropathy and METHEMOGLOBINEMIA led to its withdrawal from the market. (From Smith and Reynard, Textbook of Pharmacology,1991, p431)\n    ", "id": "MESH:D010615"}
{"mention": "paracetamol", "mention_text": "The risk of developing renal papillary necrosis or cancer of the renal pelvis, ureter or bladder associated with consumption of either phenacetin or paracetamol was calculated from data acquired by questionnaire from 381 cases and 808 controls. The risk of renal papillary necrosis was increased nearly 20-fold by consumption of phenacetin, which also increased the risk for cancer of the renal pelvis and bladder but not for ureteric cancer. By contrast, we were unable to substantiate an increased risk from paracetamol consumption for renal papillary necrosis or any of these cancers although there was a suggestion of an association with cancer of the ureter.", "entity": "Acetaminophen", "aliases": "APAP Acamol Acephen Acetaco Acetamidophenol Acetaminophen Acetominophen Algotropyl Anacin 3 Anacin-3 Anacin3 Datril Hydroxyacetanilide N-(4-Hydroxyphenyl)acetanilide N-Acetyl-p-aminophenol Panadol Paracetamol Tylenol p-Acetamidophenol p-Hydroxyacetanilide", "definition": "Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.\n    ", "id": "MESH:D000082"}
{"mention": "ureteric cancer", "mention_text": "The risk of developing renal papillary necrosis or cancer of the renal pelvis, ureter or bladder associated with consumption of either phenacetin or paracetamol was calculated from data acquired by questionnaire from 381 cases and 808 controls. The risk of renal papillary necrosis was increased nearly 20-fold by consumption of phenacetin, which also increased the risk for cancer of the renal pelvis and bladder but not for ureteric cancer. By contrast, we were unable to substantiate an increased risk from paracetamol consumption for renal papillary necrosis or any of these cancers although there was a suggestion of an association with cancer of the ureter.", "entity": "Ureteral Neoplasms", "aliases": "Cancer of Ureter the Ureteral Cancers Neoplasm Neoplasms Of", "definition": "Cancer or tumors of the URETER which may cause obstruction leading to hydroureter, HYDRONEPHROSIS, and PYELONEPHRITIS. HEMATURIA is a common symptom.\n    ", "id": "MESH:D014516"}
{"mention": "cancers", "mention_text": "The risk of developing renal papillary necrosis or cancer of the renal pelvis, ureter or bladder associated with consumption of either phenacetin or paracetamol was calculated from data acquired by questionnaire from 381 cases and 808 controls. The risk of renal papillary necrosis was increased nearly 20-fold by consumption of phenacetin, which also increased the risk for cancer of the renal pelvis and bladder but not for ureteric cancer. By contrast, we were unable to substantiate an increased risk from paracetamol consumption for renal papillary necrosis or any of these cancers although there was a suggestion of an association with cancer of the ureter.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "cancer of the ureter", "mention_text": "The risk of developing renal papillary necrosis or cancer of the renal pelvis, ureter or bladder associated with consumption of either phenacetin or paracetamol was calculated from data acquired by questionnaire from 381 cases and 808 controls. The risk of renal papillary necrosis was increased nearly 20-fold by consumption of phenacetin, which also increased the risk for cancer of the renal pelvis and bladder but not for ureteric cancer. By contrast, we were unable to substantiate an increased risk from paracetamol consumption for renal papillary necrosis or any of these cancers although there was a suggestion of an association with cancer of the ureter.", "entity": "Ureteral Neoplasms", "aliases": "Cancer of Ureter the Ureteral Cancers Neoplasm Neoplasms Of", "definition": "Cancer or tumors of the URETER which may cause obstruction leading to hydroureter, HYDRONEPHROSIS, and PYELONEPHRITIS. HEMATURIA is a common symptom.\n    ", "id": "MESH:D014516"}
{"mention": "Dapsone", "mention_text": "Dapsone-associated Heinz body hemolytic anemia in a Cambodian woman with hemoglobin E trait.", "entity": "Dapsone", "aliases": "4,4' Diaminophenyl Sulfone 4,4'-Diaminophenyl Avlosulfone DADPS Dapsoderm-X Dapson-Fatol Dapsone Diaminodiphenylsulfone Diaphenylsulfone Disulone Fatol Brand of Mex-America Orsade Sulfona Sulfonyldianiline", "definition": "A sulfone active against a wide range of bacteria but mainly employed for its actions against MYCOBACTERIUM LEPRAE. Its mechanism of action is probably similar to that of the SULFONAMIDES which involves inhibition of folic acid synthesis in susceptible organisms. It is also used with PYRIMETHAMINE in the treatment of malaria. (From Martindale, The Extra Pharmacopoeia, 30th ed, p157-8)\n    ", "id": "MESH:D003622"}
{"mention": "hemolytic anemia", "mention_text": "Dapsone-associated Heinz body hemolytic anemia in a Cambodian woman with hemoglobin E trait.", "entity": "Anemia, Hemolytic", "aliases": "Acquired Hemolytic Anemia Microangiopathic", "definition": "A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES).\n    ", "id": "MESH:D000743"}
{"mention": "leprosy", "mention_text": "A Cambodian woman with hemoglobin E trait (AE) and leprosy developed a Heinz body hemolytic anemia while taking a dose of dapsone (50 mg/day) not usually associated with clinical hemolysis. Her red blood cells (RBCs) had increased incubated Heinz body formation, decreased reduced glutathione (GSH), and decreased GSH stability. The pentose phosphate shunt activity of the dapsone-exposed AE RBCs was increased compared to normal RBCs. Although the AE RBCs from an individual not taking dapsone had increased incubated Heinz body formation, the GSH content and GSH stability were normal. The pentose phosphate shunt activity of the non-dapsone-exposed AE RBCs was decreased compared to normal RBCs. Thus, AE RBCs appear to have an increased sensitivity to oxidant stress both in vitro and in vivo, since dapsone does not cause hemolytic anemia at this dose in hematologically normal individuals. Given the influx of Southeast Asians into the United States, oxidant medications should be used with caution, especially if an infection is present, in individuals of ethnic backgrounds that have an increased prevalence of hemoglobin E.", "entity": "Leprosy", "aliases": "Disease Hansen Hansen's Hansens Leprosies Leprosy", "definition": "A chronic granulomatous infection caused by MYCOBACTERIUM LEPRAE. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid.\n    ", "id": "MESH:D007918"}
{"mention": "hemolytic anemia", "mention_text": "A Cambodian woman with hemoglobin E trait (AE) and leprosy developed a Heinz body hemolytic anemia while taking a dose of dapsone (50 mg/day) not usually associated with clinical hemolysis. Her red blood cells (RBCs) had increased incubated Heinz body formation, decreased reduced glutathione (GSH), and decreased GSH stability. The pentose phosphate shunt activity of the dapsone-exposed AE RBCs was increased compared to normal RBCs. Although the AE RBCs from an individual not taking dapsone had increased incubated Heinz body formation, the GSH content and GSH stability were normal. The pentose phosphate shunt activity of the non-dapsone-exposed AE RBCs was decreased compared to normal RBCs. Thus, AE RBCs appear to have an increased sensitivity to oxidant stress both in vitro and in vivo, since dapsone does not cause hemolytic anemia at this dose in hematologically normal individuals. Given the influx of Southeast Asians into the United States, oxidant medications should be used with caution, especially if an infection is present, in individuals of ethnic backgrounds that have an increased prevalence of hemoglobin E.", "entity": "Anemia, Hemolytic", "aliases": "Acquired Hemolytic Anemia Microangiopathic", "definition": "A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES).\n    ", "id": "MESH:D000743"}
{"mention": "dapsone", "mention_text": "A Cambodian woman with hemoglobin E trait (AE) and leprosy developed a Heinz body hemolytic anemia while taking a dose of dapsone (50 mg/day) not usually associated with clinical hemolysis. Her red blood cells (RBCs) had increased incubated Heinz body formation, decreased reduced glutathione (GSH), and decreased GSH stability. The pentose phosphate shunt activity of the dapsone-exposed AE RBCs was increased compared to normal RBCs. Although the AE RBCs from an individual not taking dapsone had increased incubated Heinz body formation, the GSH content and GSH stability were normal. The pentose phosphate shunt activity of the non-dapsone-exposed AE RBCs was decreased compared to normal RBCs. Thus, AE RBCs appear to have an increased sensitivity to oxidant stress both in vitro and in vivo, since dapsone does not cause hemolytic anemia at this dose in hematologically normal individuals. Given the influx of Southeast Asians into the United States, oxidant medications should be used with caution, especially if an infection is present, in individuals of ethnic backgrounds that have an increased prevalence of hemoglobin E.", "entity": "Dapsone", "aliases": "4,4' Diaminophenyl Sulfone 4,4'-Diaminophenyl Avlosulfone DADPS Dapsoderm-X Dapson-Fatol Dapsone Diaminodiphenylsulfone Diaphenylsulfone Disulone Fatol Brand of Mex-America Orsade Sulfona Sulfonyldianiline", "definition": "A sulfone active against a wide range of bacteria but mainly employed for its actions against MYCOBACTERIUM LEPRAE. Its mechanism of action is probably similar to that of the SULFONAMIDES which involves inhibition of folic acid synthesis in susceptible organisms. It is also used with PYRIMETHAMINE in the treatment of malaria. (From Martindale, The Extra Pharmacopoeia, 30th ed, p157-8)\n    ", "id": "MESH:D003622"}
{"mention": "hemolysis", "mention_text": "A Cambodian woman with hemoglobin E trait (AE) and leprosy developed a Heinz body hemolytic anemia while taking a dose of dapsone (50 mg/day) not usually associated with clinical hemolysis. Her red blood cells (RBCs) had increased incubated Heinz body formation, decreased reduced glutathione (GSH), and decreased GSH stability. The pentose phosphate shunt activity of the dapsone-exposed AE RBCs was increased compared to normal RBCs. Although the AE RBCs from an individual not taking dapsone had increased incubated Heinz body formation, the GSH content and GSH stability were normal. The pentose phosphate shunt activity of the non-dapsone-exposed AE RBCs was decreased compared to normal RBCs. Thus, AE RBCs appear to have an increased sensitivity to oxidant stress both in vitro and in vivo, since dapsone does not cause hemolytic anemia at this dose in hematologically normal individuals. Given the influx of Southeast Asians into the United States, oxidant medications should be used with caution, especially if an infection is present, in individuals of ethnic backgrounds that have an increased prevalence of hemoglobin E.", "entity": "Hemolysis", "aliases": "Hemolysis", "definition": "The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.\n    ", "id": "MESH:D006461"}
{"mention": "glutathione", "mention_text": "A Cambodian woman with hemoglobin E trait (AE) and leprosy developed a Heinz body hemolytic anemia while taking a dose of dapsone (50 mg/day) not usually associated with clinical hemolysis. Her red blood cells (RBCs) had increased incubated Heinz body formation, decreased reduced glutathione (GSH), and decreased GSH stability. The pentose phosphate shunt activity of the dapsone-exposed AE RBCs was increased compared to normal RBCs. Although the AE RBCs from an individual not taking dapsone had increased incubated Heinz body formation, the GSH content and GSH stability were normal. The pentose phosphate shunt activity of the non-dapsone-exposed AE RBCs was decreased compared to normal RBCs. Thus, AE RBCs appear to have an increased sensitivity to oxidant stress both in vitro and in vivo, since dapsone does not cause hemolytic anemia at this dose in hematologically normal individuals. Given the influx of Southeast Asians into the United States, oxidant medications should be used with caution, especially if an infection is present, in individuals of ethnic backgrounds that have an increased prevalence of hemoglobin E.", "entity": "Glutathione", "aliases": "Glutathione Reduced gamma L Glu L Cys Gly Glutamyl Cysteinylglycine gamma-L-Glu-L-Cys-Gly gamma-L-Glutamyl-L-Cysteinylglycine", "definition": "A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.\n    ", "id": "MESH:D005978"}
{"mention": "GSH", "mention_text": "A Cambodian woman with hemoglobin E trait (AE) and leprosy developed a Heinz body hemolytic anemia while taking a dose of dapsone (50 mg/day) not usually associated with clinical hemolysis. Her red blood cells (RBCs) had increased incubated Heinz body formation, decreased reduced glutathione (GSH), and decreased GSH stability. The pentose phosphate shunt activity of the dapsone-exposed AE RBCs was increased compared to normal RBCs. Although the AE RBCs from an individual not taking dapsone had increased incubated Heinz body formation, the GSH content and GSH stability were normal. The pentose phosphate shunt activity of the non-dapsone-exposed AE RBCs was decreased compared to normal RBCs. Thus, AE RBCs appear to have an increased sensitivity to oxidant stress both in vitro and in vivo, since dapsone does not cause hemolytic anemia at this dose in hematologically normal individuals. Given the influx of Southeast Asians into the United States, oxidant medications should be used with caution, especially if an infection is present, in individuals of ethnic backgrounds that have an increased prevalence of hemoglobin E.", "entity": "Glutathione", "aliases": "Glutathione Reduced gamma L Glu L Cys Gly Glutamyl Cysteinylglycine gamma-L-Glu-L-Cys-Gly gamma-L-Glutamyl-L-Cysteinylglycine", "definition": "A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.\n    ", "id": "MESH:D005978"}
{"mention": "pentose phosphate", "mention_text": "A Cambodian woman with hemoglobin E trait (AE) and leprosy developed a Heinz body hemolytic anemia while taking a dose of dapsone (50 mg/day) not usually associated with clinical hemolysis. Her red blood cells (RBCs) had increased incubated Heinz body formation, decreased reduced glutathione (GSH), and decreased GSH stability. The pentose phosphate shunt activity of the dapsone-exposed AE RBCs was increased compared to normal RBCs. Although the AE RBCs from an individual not taking dapsone had increased incubated Heinz body formation, the GSH content and GSH stability were normal. The pentose phosphate shunt activity of the non-dapsone-exposed AE RBCs was decreased compared to normal RBCs. Thus, AE RBCs appear to have an increased sensitivity to oxidant stress both in vitro and in vivo, since dapsone does not cause hemolytic anemia at this dose in hematologically normal individuals. Given the influx of Southeast Asians into the United States, oxidant medications should be used with caution, especially if an infection is present, in individuals of ethnic backgrounds that have an increased prevalence of hemoglobin E.", "entity": "Pentosephosphates", "aliases": "Pentosephosphates", "definition": "", "id": "MESH:D010428"}
{"mention": "infection", "mention_text": "A Cambodian woman with hemoglobin E trait (AE) and leprosy developed a Heinz body hemolytic anemia while taking a dose of dapsone (50 mg/day) not usually associated with clinical hemolysis. Her red blood cells (RBCs) had increased incubated Heinz body formation, decreased reduced glutathione (GSH), and decreased GSH stability. The pentose phosphate shunt activity of the dapsone-exposed AE RBCs was increased compared to normal RBCs. Although the AE RBCs from an individual not taking dapsone had increased incubated Heinz body formation, the GSH content and GSH stability were normal. The pentose phosphate shunt activity of the non-dapsone-exposed AE RBCs was decreased compared to normal RBCs. Thus, AE RBCs appear to have an increased sensitivity to oxidant stress both in vitro and in vivo, since dapsone does not cause hemolytic anemia at this dose in hematologically normal individuals. Given the influx of Southeast Asians into the United States, oxidant medications should be used with caution, especially if an infection is present, in individuals of ethnic backgrounds that have an increased prevalence of hemoglobin E.", "entity": "Infection", "aliases": "Infection Infections", "definition": "Invasion of the host organism by microorganisms that can cause pathological conditions or diseases.\n    ", "id": "MESH:D007239"}
{"mention": "metoprolol", "mention_text": "Severe complications of antianginal drug therapy in a patient identified as a poor metabolizer of metoprolol, propafenone, diltiazem, and sparteine.", "entity": "Metoprolol", "aliases": "AstraZeneca Brand of Metaoprolol Tartrate Seloken Beloc Duriles Beloc-Duriles BelocDuriles Betaloc Astra Betaloc-Astra BetalocAstra Betalok CGP 2175 CGP-2175 CGP2175 H 93 26 93-26 9326 Leiras Metoprolol Succinate or Metoprolol Lopressor Novartis Metprolol Spesicor Spesikor", "definition": "A selective adrenergic beta-1 blocking agent that is commonly used to treat ANGINA PECTORIS; HYPERTENSION; and CARDIAC ARRHYTHMIAS.\n    ", "id": "MESH:D008790"}
{"mention": "propafenone", "mention_text": "Severe complications of antianginal drug therapy in a patient identified as a poor metabolizer of metoprolol, propafenone, diltiazem, and sparteine.", "entity": "Propafenone", "aliases": "Abbott Brand of Propafenone Hydrochloride Aliud Alpharma Apo-Propafenone Apotex Arythmol Azupharma Baxarytmon Cuxafenon Fenoprain Hexal Juta Jutanorm Kendrick Knoll Merck dura Nistaken Norfenon Pintoform Prolecofen Propafenon AL Minden (R)-Isomer (S)-Isomer (+-)-Isomer Propamerck Q-Pharm Rythmol Rytmo-Puren Rytmogenat Rytmonorm SA 79 SA-79 SA79 TAD", "definition": "An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity.\n    ", "id": "MESH:D011405"}
{"mention": "diltiazem", "mention_text": "Severe complications of antianginal drug therapy in a patient identified as a poor metabolizer of metoprolol, propafenone, diltiazem, and sparteine.", "entity": "Diltiazem", "aliases": "Aldizem Biovail Brand of Diltiazem Hydrochloride CRD 401 CRD-401 CRD401 Cardil Cardizem Dilacor XR Dilren Malate Dilzem Tiazac Watson Pharmaceuticals Diltazem", "definition": "A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of CALCIUM ion on membrane functions.\n    ", "id": "MESH:D004110"}
{"mention": "sparteine", "mention_text": "Severe complications of antianginal drug therapy in a patient identified as a poor metabolizer of metoprolol, propafenone, diltiazem, and sparteine.", "entity": "Sparteine", "aliases": "Anhydrous Sparteine Sulfate D-sparteine Depasan Retard Genisteine Alkaloid L-Sparteine Pachycarpine (1:1) Pentahydrate (7S-(7alpha,7aalpha,14alpha,14abeta))-Isomer Hydrochloride (7R-(7alpha,7aalpha,14alpha,14abeta))-Isomer Hydroiodide Monohydrochloride Monohydroiodide (7S-(7alpha,7aalpha,14alpha,14aalpha))-Isomer (+)-Isomer (-)-Isomer (7R-(7alpha,7abeta,14alpha,14abeta))-Isomer (7S-(7alpha,7abeta,14alpha,14abeta))-Isomer alpha Isosparteine alpha-Isosparteine beta beta-Isosparteine", "definition": "A quinolizidine alkaloid isolated from several FABACEAE including LUPINUS; SPARTIUM; and CYTISUS. It has been used as an oxytocic and an anti-arrhythmia agent. It has also been of interest as an indicator of CYP2D6 genotype.\n    ", "id": "MESH:D013034"}
{"mention": "coronary artery disease", "mention_text": "A 47-year-old patient suffering from coronary artery disease was admitted to the CCU in shock with III. AV block, severe hypotension, and impairment of ventricular function. One week prior to admission a therapy with standard doses of metoprolol (100 mg t.i.d. and then 100 mg b.i.d.) had been initiated. Two days before admission diltiazem (60 mg b.i.d.) was prescribed in addition. Analyses of a blood sample revealed unusually high plasma concentrations of metoprolol (greater than 3000 ng/ml) and diltiazem (526 ng/ml). The patient recovered within 1 week following discontinuation of antianginal therapy. Three months later the patient was exposed to a single dose of metoprolol, diltiazem, propafenone (since he had received this drug in the past), and sparteine (as a probe for the debrisoquine/sparteine type polymorphism of oxidative drug metabolism). It was found that he was a poor metabolizer of all four drugs, indicating that their metabolism is under the same genetic control. Therefore, patients belonging to the poor-metabolizer phenotype of sparteine/debrisoquine polymorphism in drug metabolism, which constitutes 6.4% of the German population, may experience adverse drug reactions when treated with standard doses of one of these drugs alone. Moreover, the coadministration of these frequently used drugs is expected to be especially harmful in this subgroup of patients.", "entity": "Coronary Artery Disease", "aliases": "Arterioscleroses Coronary Arteriosclerosis Artery Disease Diseases Atheroscleroses Atherosclerosis", "definition": "Pathological processes of CORONARY ARTERIES that may derive from a congenital abnormality, atherosclerotic, or non-atherosclerotic cause.\n    ", "id": "MESH:D003324"}
{"mention": "shock", "mention_text": "A 47-year-old patient suffering from coronary artery disease was admitted to the CCU in shock with III. AV block, severe hypotension, and impairment of ventricular function. One week prior to admission a therapy with standard doses of metoprolol (100 mg t.i.d. and then 100 mg b.i.d.) had been initiated. Two days before admission diltiazem (60 mg b.i.d.) was prescribed in addition. Analyses of a blood sample revealed unusually high plasma concentrations of metoprolol (greater than 3000 ng/ml) and diltiazem (526 ng/ml). The patient recovered within 1 week following discontinuation of antianginal therapy. Three months later the patient was exposed to a single dose of metoprolol, diltiazem, propafenone (since he had received this drug in the past), and sparteine (as a probe for the debrisoquine/sparteine type polymorphism of oxidative drug metabolism). It was found that he was a poor metabolizer of all four drugs, indicating that their metabolism is under the same genetic control. Therefore, patients belonging to the poor-metabolizer phenotype of sparteine/debrisoquine polymorphism in drug metabolism, which constitutes 6.4% of the German population, may experience adverse drug reactions when treated with standard doses of one of these drugs alone. Moreover, the coadministration of these frequently used drugs is expected to be especially harmful in this subgroup of patients.", "entity": "Shock", "aliases": "Circulatory Collapse Failure Hypovolemic Shock", "definition": "A pathological condition manifested by failure to perfuse or oxygenate vital organs.\n    ", "id": "MESH:D012769"}
{"mention": "AV block", "mention_text": "A 47-year-old patient suffering from coronary artery disease was admitted to the CCU in shock with III. AV block, severe hypotension, and impairment of ventricular function. One week prior to admission a therapy with standard doses of metoprolol (100 mg t.i.d. and then 100 mg b.i.d.) had been initiated. Two days before admission diltiazem (60 mg b.i.d.) was prescribed in addition. Analyses of a blood sample revealed unusually high plasma concentrations of metoprolol (greater than 3000 ng/ml) and diltiazem (526 ng/ml). The patient recovered within 1 week following discontinuation of antianginal therapy. Three months later the patient was exposed to a single dose of metoprolol, diltiazem, propafenone (since he had received this drug in the past), and sparteine (as a probe for the debrisoquine/sparteine type polymorphism of oxidative drug metabolism). It was found that he was a poor metabolizer of all four drugs, indicating that their metabolism is under the same genetic control. Therefore, patients belonging to the poor-metabolizer phenotype of sparteine/debrisoquine polymorphism in drug metabolism, which constitutes 6.4% of the German population, may experience adverse drug reactions when treated with standard doses of one of these drugs alone. Moreover, the coadministration of these frequently used drugs is expected to be especially harmful in this subgroup of patients.", "entity": "Atrioventricular Block", "aliases": "AV Block Blocks Atrioventricular Conduction", "definition": "Impaired impulse conduction from HEART ATRIA to HEART VENTRICLES. AV block can mean delayed or completely blocked impulse conduction.\n    ", "id": "MESH:D054537"}
{"mention": "hypotension", "mention_text": "A 47-year-old patient suffering from coronary artery disease was admitted to the CCU in shock with III. AV block, severe hypotension, and impairment of ventricular function. One week prior to admission a therapy with standard doses of metoprolol (100 mg t.i.d. and then 100 mg b.i.d.) had been initiated. Two days before admission diltiazem (60 mg b.i.d.) was prescribed in addition. Analyses of a blood sample revealed unusually high plasma concentrations of metoprolol (greater than 3000 ng/ml) and diltiazem (526 ng/ml). The patient recovered within 1 week following discontinuation of antianginal therapy. Three months later the patient was exposed to a single dose of metoprolol, diltiazem, propafenone (since he had received this drug in the past), and sparteine (as a probe for the debrisoquine/sparteine type polymorphism of oxidative drug metabolism). It was found that he was a poor metabolizer of all four drugs, indicating that their metabolism is under the same genetic control. Therefore, patients belonging to the poor-metabolizer phenotype of sparteine/debrisoquine polymorphism in drug metabolism, which constitutes 6.4% of the German population, may experience adverse drug reactions when treated with standard doses of one of these drugs alone. Moreover, the coadministration of these frequently used drugs is expected to be especially harmful in this subgroup of patients.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "impairment of ventricular function", "mention_text": "A 47-year-old patient suffering from coronary artery disease was admitted to the CCU in shock with III. AV block, severe hypotension, and impairment of ventricular function. One week prior to admission a therapy with standard doses of metoprolol (100 mg t.i.d. and then 100 mg b.i.d.) had been initiated. Two days before admission diltiazem (60 mg b.i.d.) was prescribed in addition. Analyses of a blood sample revealed unusually high plasma concentrations of metoprolol (greater than 3000 ng/ml) and diltiazem (526 ng/ml). The patient recovered within 1 week following discontinuation of antianginal therapy. Three months later the patient was exposed to a single dose of metoprolol, diltiazem, propafenone (since he had received this drug in the past), and sparteine (as a probe for the debrisoquine/sparteine type polymorphism of oxidative drug metabolism). It was found that he was a poor metabolizer of all four drugs, indicating that their metabolism is under the same genetic control. Therefore, patients belonging to the poor-metabolizer phenotype of sparteine/debrisoquine polymorphism in drug metabolism, which constitutes 6.4% of the German population, may experience adverse drug reactions when treated with standard doses of one of these drugs alone. Moreover, the coadministration of these frequently used drugs is expected to be especially harmful in this subgroup of patients.", "entity": "Ventricular Dysfunction", "aliases": "Dysfunction Ventricular Dysfunctions", "definition": "A condition in which HEART VENTRICLES exhibit impaired function.\n    ", "id": "MESH:D018754"}
{"mention": "metoprolol", "mention_text": "A 47-year-old patient suffering from coronary artery disease was admitted to the CCU in shock with III. AV block, severe hypotension, and impairment of ventricular function. One week prior to admission a therapy with standard doses of metoprolol (100 mg t.i.d. and then 100 mg b.i.d.) had been initiated. Two days before admission diltiazem (60 mg b.i.d.) was prescribed in addition. Analyses of a blood sample revealed unusually high plasma concentrations of metoprolol (greater than 3000 ng/ml) and diltiazem (526 ng/ml). The patient recovered within 1 week following discontinuation of antianginal therapy. Three months later the patient was exposed to a single dose of metoprolol, diltiazem, propafenone (since he had received this drug in the past), and sparteine (as a probe for the debrisoquine/sparteine type polymorphism of oxidative drug metabolism). It was found that he was a poor metabolizer of all four drugs, indicating that their metabolism is under the same genetic control. Therefore, patients belonging to the poor-metabolizer phenotype of sparteine/debrisoquine polymorphism in drug metabolism, which constitutes 6.4% of the German population, may experience adverse drug reactions when treated with standard doses of one of these drugs alone. Moreover, the coadministration of these frequently used drugs is expected to be especially harmful in this subgroup of patients.", "entity": "Metoprolol", "aliases": "AstraZeneca Brand of Metaoprolol Tartrate Seloken Beloc Duriles Beloc-Duriles BelocDuriles Betaloc Astra Betaloc-Astra BetalocAstra Betalok CGP 2175 CGP-2175 CGP2175 H 93 26 93-26 9326 Leiras Metoprolol Succinate or Metoprolol Lopressor Novartis Metprolol Spesicor Spesikor", "definition": "A selective adrenergic beta-1 blocking agent that is commonly used to treat ANGINA PECTORIS; HYPERTENSION; and CARDIAC ARRHYTHMIAS.\n    ", "id": "MESH:D008790"}
{"mention": "diltiazem", "mention_text": "A 47-year-old patient suffering from coronary artery disease was admitted to the CCU in shock with III. AV block, severe hypotension, and impairment of ventricular function. One week prior to admission a therapy with standard doses of metoprolol (100 mg t.i.d. and then 100 mg b.i.d.) had been initiated. Two days before admission diltiazem (60 mg b.i.d.) was prescribed in addition. Analyses of a blood sample revealed unusually high plasma concentrations of metoprolol (greater than 3000 ng/ml) and diltiazem (526 ng/ml). The patient recovered within 1 week following discontinuation of antianginal therapy. Three months later the patient was exposed to a single dose of metoprolol, diltiazem, propafenone (since he had received this drug in the past), and sparteine (as a probe for the debrisoquine/sparteine type polymorphism of oxidative drug metabolism). It was found that he was a poor metabolizer of all four drugs, indicating that their metabolism is under the same genetic control. Therefore, patients belonging to the poor-metabolizer phenotype of sparteine/debrisoquine polymorphism in drug metabolism, which constitutes 6.4% of the German population, may experience adverse drug reactions when treated with standard doses of one of these drugs alone. Moreover, the coadministration of these frequently used drugs is expected to be especially harmful in this subgroup of patients.", "entity": "Diltiazem", "aliases": "Aldizem Biovail Brand of Diltiazem Hydrochloride CRD 401 CRD-401 CRD401 Cardil Cardizem Dilacor XR Dilren Malate Dilzem Tiazac Watson Pharmaceuticals Diltazem", "definition": "A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of CALCIUM ion on membrane functions.\n    ", "id": "MESH:D004110"}
{"mention": "propafenone", "mention_text": "A 47-year-old patient suffering from coronary artery disease was admitted to the CCU in shock with III. AV block, severe hypotension, and impairment of ventricular function. One week prior to admission a therapy with standard doses of metoprolol (100 mg t.i.d. and then 100 mg b.i.d.) had been initiated. Two days before admission diltiazem (60 mg b.i.d.) was prescribed in addition. Analyses of a blood sample revealed unusually high plasma concentrations of metoprolol (greater than 3000 ng/ml) and diltiazem (526 ng/ml). The patient recovered within 1 week following discontinuation of antianginal therapy. Three months later the patient was exposed to a single dose of metoprolol, diltiazem, propafenone (since he had received this drug in the past), and sparteine (as a probe for the debrisoquine/sparteine type polymorphism of oxidative drug metabolism). It was found that he was a poor metabolizer of all four drugs, indicating that their metabolism is under the same genetic control. Therefore, patients belonging to the poor-metabolizer phenotype of sparteine/debrisoquine polymorphism in drug metabolism, which constitutes 6.4% of the German population, may experience adverse drug reactions when treated with standard doses of one of these drugs alone. Moreover, the coadministration of these frequently used drugs is expected to be especially harmful in this subgroup of patients.", "entity": "Propafenone", "aliases": "Abbott Brand of Propafenone Hydrochloride Aliud Alpharma Apo-Propafenone Apotex Arythmol Azupharma Baxarytmon Cuxafenon Fenoprain Hexal Juta Jutanorm Kendrick Knoll Merck dura Nistaken Norfenon Pintoform Prolecofen Propafenon AL Minden (R)-Isomer (S)-Isomer (+-)-Isomer Propamerck Q-Pharm Rythmol Rytmo-Puren Rytmogenat Rytmonorm SA 79 SA-79 SA79 TAD", "definition": "An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity.\n    ", "id": "MESH:D011405"}
{"mention": "sparteine", "mention_text": "A 47-year-old patient suffering from coronary artery disease was admitted to the CCU in shock with III. AV block, severe hypotension, and impairment of ventricular function. One week prior to admission a therapy with standard doses of metoprolol (100 mg t.i.d. and then 100 mg b.i.d.) had been initiated. Two days before admission diltiazem (60 mg b.i.d.) was prescribed in addition. Analyses of a blood sample revealed unusually high plasma concentrations of metoprolol (greater than 3000 ng/ml) and diltiazem (526 ng/ml). The patient recovered within 1 week following discontinuation of antianginal therapy. Three months later the patient was exposed to a single dose of metoprolol, diltiazem, propafenone (since he had received this drug in the past), and sparteine (as a probe for the debrisoquine/sparteine type polymorphism of oxidative drug metabolism). It was found that he was a poor metabolizer of all four drugs, indicating that their metabolism is under the same genetic control. Therefore, patients belonging to the poor-metabolizer phenotype of sparteine/debrisoquine polymorphism in drug metabolism, which constitutes 6.4% of the German population, may experience adverse drug reactions when treated with standard doses of one of these drugs alone. Moreover, the coadministration of these frequently used drugs is expected to be especially harmful in this subgroup of patients.", "entity": "Sparteine", "aliases": "Anhydrous Sparteine Sulfate D-sparteine Depasan Retard Genisteine Alkaloid L-Sparteine Pachycarpine (1:1) Pentahydrate (7S-(7alpha,7aalpha,14alpha,14abeta))-Isomer Hydrochloride (7R-(7alpha,7aalpha,14alpha,14abeta))-Isomer Hydroiodide Monohydrochloride Monohydroiodide (7S-(7alpha,7aalpha,14alpha,14aalpha))-Isomer (+)-Isomer (-)-Isomer (7R-(7alpha,7abeta,14alpha,14abeta))-Isomer (7S-(7alpha,7abeta,14alpha,14abeta))-Isomer alpha Isosparteine alpha-Isosparteine beta beta-Isosparteine", "definition": "A quinolizidine alkaloid isolated from several FABACEAE including LUPINUS; SPARTIUM; and CYTISUS. It has been used as an oxytocic and an anti-arrhythmia agent. It has also been of interest as an indicator of CYP2D6 genotype.\n    ", "id": "MESH:D013034"}
{"mention": "debrisoquine", "mention_text": "A 47-year-old patient suffering from coronary artery disease was admitted to the CCU in shock with III. AV block, severe hypotension, and impairment of ventricular function. One week prior to admission a therapy with standard doses of metoprolol (100 mg t.i.d. and then 100 mg b.i.d.) had been initiated. Two days before admission diltiazem (60 mg b.i.d.) was prescribed in addition. Analyses of a blood sample revealed unusually high plasma concentrations of metoprolol (greater than 3000 ng/ml) and diltiazem (526 ng/ml). The patient recovered within 1 week following discontinuation of antianginal therapy. Three months later the patient was exposed to a single dose of metoprolol, diltiazem, propafenone (since he had received this drug in the past), and sparteine (as a probe for the debrisoquine/sparteine type polymorphism of oxidative drug metabolism). It was found that he was a poor metabolizer of all four drugs, indicating that their metabolism is under the same genetic control. Therefore, patients belonging to the poor-metabolizer phenotype of sparteine/debrisoquine polymorphism in drug metabolism, which constitutes 6.4% of the German population, may experience adverse drug reactions when treated with standard doses of one of these drugs alone. Moreover, the coadministration of these frequently used drugs is expected to be especially harmful in this subgroup of patients.", "entity": "Debrisoquin", "aliases": "Debrisoquin Debrisoquine Tendor", "definition": "An adrenergic neuron-blocking drug similar in effects to GUANETHIDINE. It is also noteworthy in being a substrate for a polymorphic cytochrome P-450 enzyme. Persons with certain isoforms of this enzyme are unable to properly metabolize this and many other clinically important drugs. They are commonly referred to as having a debrisoquin 4-hydroxylase polymorphism.\n    ", "id": "MESH:D003647"}
{"mention": "adverse drug reactions", "mention_text": "A 47-year-old patient suffering from coronary artery disease was admitted to the CCU in shock with III. AV block, severe hypotension, and impairment of ventricular function. One week prior to admission a therapy with standard doses of metoprolol (100 mg t.i.d. and then 100 mg b.i.d.) had been initiated. Two days before admission diltiazem (60 mg b.i.d.) was prescribed in addition. Analyses of a blood sample revealed unusually high plasma concentrations of metoprolol (greater than 3000 ng/ml) and diltiazem (526 ng/ml). The patient recovered within 1 week following discontinuation of antianginal therapy. Three months later the patient was exposed to a single dose of metoprolol, diltiazem, propafenone (since he had received this drug in the past), and sparteine (as a probe for the debrisoquine/sparteine type polymorphism of oxidative drug metabolism). It was found that he was a poor metabolizer of all four drugs, indicating that their metabolism is under the same genetic control. Therefore, patients belonging to the poor-metabolizer phenotype of sparteine/debrisoquine polymorphism in drug metabolism, which constitutes 6.4% of the German population, may experience adverse drug reactions when treated with standard doses of one of these drugs alone. Moreover, the coadministration of these frequently used drugs is expected to be especially harmful in this subgroup of patients.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "Triazolam", "mention_text": "Triazolam-induced brief episodes of secondary mania in a depressed patient.", "entity": "Triazolam", "aliases": "Apo Triazo Apo-Triazo Apotex Brand of Triazolam Gen Gen-Triazolam Genpharm Gerard Halcion Pfizer Trilam U 33,030 U-33,030 U33,030", "definition": "A short-acting benzodiazepine used in the treatment of insomnia. Some countries temporarily withdrew triazolam from the market because of concerns about adverse reactions, mostly psychological, associated with higher dose ranges. Its use at lower doses with appropriate care and labeling has been reaffirmed by the FDA and most other countries.\n    ", "id": "MESH:D014229"}
{"mention": "mania", "mention_text": "Triazolam-induced brief episodes of secondary mania in a depressed patient.", "entity": "Bipolar Disorder", "aliases": "Affective Psychosis Bipolar Depression Disorder Disorders Manic Mania Manias Depressive State States Manic-Depressive Psychoses", "definition": "A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.\n    ", "id": "MESH:D001714"}
{"mention": "depressed", "mention_text": "Triazolam-induced brief episodes of secondary mania in a depressed patient.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "triazolam", "mention_text": "Large doses of triazolam repeatedly induced brief episodes of mania in a depressed elderly woman. Features of organic mental disorder (delirium) were not present. Manic excitement was coincident with the duration of action of triazolam. The possible contribution of the triazolo group to changes in affective status is discussed.", "entity": "Triazolam", "aliases": "Apo Triazo Apo-Triazo Apotex Brand of Triazolam Gen Gen-Triazolam Genpharm Gerard Halcion Pfizer Trilam U 33,030 U-33,030 U33,030", "definition": "A short-acting benzodiazepine used in the treatment of insomnia. Some countries temporarily withdrew triazolam from the market because of concerns about adverse reactions, mostly psychological, associated with higher dose ranges. Its use at lower doses with appropriate care and labeling has been reaffirmed by the FDA and most other countries.\n    ", "id": "MESH:D014229"}
{"mention": "mania", "mention_text": "Large doses of triazolam repeatedly induced brief episodes of mania in a depressed elderly woman. Features of organic mental disorder (delirium) were not present. Manic excitement was coincident with the duration of action of triazolam. The possible contribution of the triazolo group to changes in affective status is discussed.", "entity": "Bipolar Disorder", "aliases": "Affective Psychosis Bipolar Depression Disorder Disorders Manic Mania Manias Depressive State States Manic-Depressive Psychoses", "definition": "A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.\n    ", "id": "MESH:D001714"}
{"mention": "depressed", "mention_text": "Large doses of triazolam repeatedly induced brief episodes of mania in a depressed elderly woman. Features of organic mental disorder (delirium) were not present. Manic excitement was coincident with the duration of action of triazolam. The possible contribution of the triazolo group to changes in affective status is discussed.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "organic mental disorder", "mention_text": "Large doses of triazolam repeatedly induced brief episodes of mania in a depressed elderly woman. Features of organic mental disorder (delirium) were not present. Manic excitement was coincident with the duration of action of triazolam. The possible contribution of the triazolo group to changes in affective status is discussed.", "entity": "Delirium, Dementia, Amnestic, Cognitive Disorders", "aliases": "Clerambault Syndrome Delirium Dementia Amnestic Cognitive Disorders Organic Mental Kandinsky Disorder Nonpsychotic Brain Psychotic Psychoses Traumatic", "definition": "Cognitive disorders including delirium, dementia, and other cognitive disorders. These may be the result of substance use, trauma, or other causes.\n    ", "id": "MESH:D019965"}
{"mention": "delirium", "mention_text": "Large doses of triazolam repeatedly induced brief episodes of mania in a depressed elderly woman. Features of organic mental disorder (delirium) were not present. Manic excitement was coincident with the duration of action of triazolam. The possible contribution of the triazolo group to changes in affective status is discussed.", "entity": "Delirium", "aliases": "Delirium of Mixed Origin Subacute Deliriums", "definition": "A disorder characterized by CONFUSION; inattentiveness; disorientation; ILLUSIONS; HALLUCINATIONS; agitation; and in some instances autonomic nervous system overactivity. It may result from toxic/metabolic conditions or structural brain lesions. (From Adams et al., Principles of Neurology, 6th ed, pp411-2)\n    ", "id": "MESH:D003693"}
{"mention": "Manic", "mention_text": "Large doses of triazolam repeatedly induced brief episodes of mania in a depressed elderly woman. Features of organic mental disorder (delirium) were not present. Manic excitement was coincident with the duration of action of triazolam. The possible contribution of the triazolo group to changes in affective status is discussed.", "entity": "Bipolar Disorder", "aliases": "Affective Psychosis Bipolar Depression Disorder Disorders Manic Mania Manias Depressive State States Manic-Depressive Psychoses", "definition": "A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.\n    ", "id": "MESH:D001714"}
{"mention": "triazolo", "mention_text": "Large doses of triazolam repeatedly induced brief episodes of mania in a depressed elderly woman. Features of organic mental disorder (delirium) were not present. Manic excitement was coincident with the duration of action of triazolam. The possible contribution of the triazolo group to changes in affective status is discussed.", "entity": "Triazolam", "aliases": "Apo Triazo Apo-Triazo Apotex Brand of Triazolam Gen Gen-Triazolam Genpharm Gerard Halcion Pfizer Trilam U 33,030 U-33,030 U33,030", "definition": "A short-acting benzodiazepine used in the treatment of insomnia. Some countries temporarily withdrew triazolam from the market because of concerns about adverse reactions, mostly psychological, associated with higher dose ranges. Its use at lower doses with appropriate care and labeling has been reaffirmed by the FDA and most other countries.\n    ", "id": "MESH:D014229"}
{"mention": "muscular rigidity", "mention_text": "On the mechanisms of the development of tolerance to the muscular rigidity produced by morphine in rats.", "entity": "Muscle Rigidity", "aliases": "Catatonic Rigidity Cogwheel Rigidities Extensor Extrapyramidal Gegenhalten Gegenhaltens Muscle Muscular Nuchal", "definition": "Continuous involuntary sustained muscle contraction which is often a manifestation of BASAL GANGLIA DISEASES. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from MUSCLE SPASTICITY. (From Adams et al., Principles of Neurology, 6th ed, p73)\n    ", "id": "MESH:D009127"}
{"mention": "morphine", "mention_text": "On the mechanisms of the development of tolerance to the muscular rigidity produced by morphine in rats.", "entity": "Morphine", "aliases": "Chloride Morphine Contin MS Duramorph Morphia Sulfate (2:1) Anhydrous Pentahydrate Oramorph SR SDZ 202 250 202-250 202250 SDZ202 SDZ202-250 SDZ202250", "definition": "The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.\n    ", "id": "MESH:D009020"}
{"mention": "muscular rigidity", "mention_text": "The development of tolerance to the muscular rigidity produced by morphine was studied in rats. Saline-pretreated controls given a test dose of morphine (20 mg/kg i.p.) showed a pronounced rigidity recorded as tonic activity in the electromyogram. Rats treated for 11 days with morphine and withdrawn for 36-40 h showed differences in the development of tolerance: about half of the animals showed a rigidity after the test dose of morphine that was not significantly less than in the controls and were akinetic (A group). The other rats showed a strong decrease in the rigidity and the occurrence of stereotyped (S) licking and/or gnawing in presence of akinetic or hyperkinetic (K) behaviour (AS/KS group), suggesting signs of dopaminergic activation. The rigidity was considerably decreased in both groups after 20 days' treatment. In a further series of experiments, haloperidol (0.2 mg/kg i.p.) was used in order to block the dopaminergic activation and to estimate the real degree of the tolerance to the rigidity without any dopaminergic interference. Haloperidol enhanced the rigidity in the A group. However, the level in the AS/KS group remained considerably lower than in the A group. The results suggest that rigidity, which is assumed to be due to an action of morphine in the striatum, can be antagonized by another process leading to dopaminergic activation in the striatum. Nevertheless, there occurs some real tolerance to this effect. The rapid alternations of rigidity and the signs of dopaminergic activation observed in the animals of the AS/KS group might be due to rapid shifts in the predominance of various DA-innervated structures.", "entity": "Muscle Rigidity", "aliases": "Catatonic Rigidity Cogwheel Rigidities Extensor Extrapyramidal Gegenhalten Gegenhaltens Muscle Muscular Nuchal", "definition": "Continuous involuntary sustained muscle contraction which is often a manifestation of BASAL GANGLIA DISEASES. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from MUSCLE SPASTICITY. (From Adams et al., Principles of Neurology, 6th ed, p73)\n    ", "id": "MESH:D009127"}
{"mention": "morphine", "mention_text": "The development of tolerance to the muscular rigidity produced by morphine was studied in rats. Saline-pretreated controls given a test dose of morphine (20 mg/kg i.p.) showed a pronounced rigidity recorded as tonic activity in the electromyogram. Rats treated for 11 days with morphine and withdrawn for 36-40 h showed differences in the development of tolerance: about half of the animals showed a rigidity after the test dose of morphine that was not significantly less than in the controls and were akinetic (A group). The other rats showed a strong decrease in the rigidity and the occurrence of stereotyped (S) licking and/or gnawing in presence of akinetic or hyperkinetic (K) behaviour (AS/KS group), suggesting signs of dopaminergic activation. The rigidity was considerably decreased in both groups after 20 days' treatment. In a further series of experiments, haloperidol (0.2 mg/kg i.p.) was used in order to block the dopaminergic activation and to estimate the real degree of the tolerance to the rigidity without any dopaminergic interference. Haloperidol enhanced the rigidity in the A group. However, the level in the AS/KS group remained considerably lower than in the A group. The results suggest that rigidity, which is assumed to be due to an action of morphine in the striatum, can be antagonized by another process leading to dopaminergic activation in the striatum. Nevertheless, there occurs some real tolerance to this effect. The rapid alternations of rigidity and the signs of dopaminergic activation observed in the animals of the AS/KS group might be due to rapid shifts in the predominance of various DA-innervated structures.", "entity": "Morphine", "aliases": "Chloride Morphine Contin MS Duramorph Morphia Sulfate (2:1) Anhydrous Pentahydrate Oramorph SR SDZ 202 250 202-250 202250 SDZ202 SDZ202-250 SDZ202250", "definition": "The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.\n    ", "id": "MESH:D009020"}
{"mention": "rigidity", "mention_text": "The development of tolerance to the muscular rigidity produced by morphine was studied in rats. Saline-pretreated controls given a test dose of morphine (20 mg/kg i.p.) showed a pronounced rigidity recorded as tonic activity in the electromyogram. Rats treated for 11 days with morphine and withdrawn for 36-40 h showed differences in the development of tolerance: about half of the animals showed a rigidity after the test dose of morphine that was not significantly less than in the controls and were akinetic (A group). The other rats showed a strong decrease in the rigidity and the occurrence of stereotyped (S) licking and/or gnawing in presence of akinetic or hyperkinetic (K) behaviour (AS/KS group), suggesting signs of dopaminergic activation. The rigidity was considerably decreased in both groups after 20 days' treatment. In a further series of experiments, haloperidol (0.2 mg/kg i.p.) was used in order to block the dopaminergic activation and to estimate the real degree of the tolerance to the rigidity without any dopaminergic interference. Haloperidol enhanced the rigidity in the A group. However, the level in the AS/KS group remained considerably lower than in the A group. The results suggest that rigidity, which is assumed to be due to an action of morphine in the striatum, can be antagonized by another process leading to dopaminergic activation in the striatum. Nevertheless, there occurs some real tolerance to this effect. The rapid alternations of rigidity and the signs of dopaminergic activation observed in the animals of the AS/KS group might be due to rapid shifts in the predominance of various DA-innervated structures.", "entity": "Muscle Rigidity", "aliases": "Catatonic Rigidity Cogwheel Rigidities Extensor Extrapyramidal Gegenhalten Gegenhaltens Muscle Muscular Nuchal", "definition": "Continuous involuntary sustained muscle contraction which is often a manifestation of BASAL GANGLIA DISEASES. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from MUSCLE SPASTICITY. (From Adams et al., Principles of Neurology, 6th ed, p73)\n    ", "id": "MESH:D009127"}
{"mention": "akinetic", "mention_text": "The development of tolerance to the muscular rigidity produced by morphine was studied in rats. Saline-pretreated controls given a test dose of morphine (20 mg/kg i.p.) showed a pronounced rigidity recorded as tonic activity in the electromyogram. Rats treated for 11 days with morphine and withdrawn for 36-40 h showed differences in the development of tolerance: about half of the animals showed a rigidity after the test dose of morphine that was not significantly less than in the controls and were akinetic (A group). The other rats showed a strong decrease in the rigidity and the occurrence of stereotyped (S) licking and/or gnawing in presence of akinetic or hyperkinetic (K) behaviour (AS/KS group), suggesting signs of dopaminergic activation. The rigidity was considerably decreased in both groups after 20 days' treatment. In a further series of experiments, haloperidol (0.2 mg/kg i.p.) was used in order to block the dopaminergic activation and to estimate the real degree of the tolerance to the rigidity without any dopaminergic interference. Haloperidol enhanced the rigidity in the A group. However, the level in the AS/KS group remained considerably lower than in the A group. The results suggest that rigidity, which is assumed to be due to an action of morphine in the striatum, can be antagonized by another process leading to dopaminergic activation in the striatum. Nevertheless, there occurs some real tolerance to this effect. The rapid alternations of rigidity and the signs of dopaminergic activation observed in the animals of the AS/KS group might be due to rapid shifts in the predominance of various DA-innervated structures.", "entity": "Hypokinesia", "aliases": "Antiorthostatic Hypokinesia Hypokinesias Bradykinesia Bradykinesias Hypodynamia", "definition": "Slow or diminished movement of body musculature. It may be associated with BASAL GANGLIA DISEASES; MENTAL DISORDERS; prolonged inactivity due to illness; and other conditions.\n    ", "id": "MESH:D018476"}
{"mention": "hyperkinetic", "mention_text": "The development of tolerance to the muscular rigidity produced by morphine was studied in rats. Saline-pretreated controls given a test dose of morphine (20 mg/kg i.p.) showed a pronounced rigidity recorded as tonic activity in the electromyogram. Rats treated for 11 days with morphine and withdrawn for 36-40 h showed differences in the development of tolerance: about half of the animals showed a rigidity after the test dose of morphine that was not significantly less than in the controls and were akinetic (A group). The other rats showed a strong decrease in the rigidity and the occurrence of stereotyped (S) licking and/or gnawing in presence of akinetic or hyperkinetic (K) behaviour (AS/KS group), suggesting signs of dopaminergic activation. The rigidity was considerably decreased in both groups after 20 days' treatment. In a further series of experiments, haloperidol (0.2 mg/kg i.p.) was used in order to block the dopaminergic activation and to estimate the real degree of the tolerance to the rigidity without any dopaminergic interference. Haloperidol enhanced the rigidity in the A group. However, the level in the AS/KS group remained considerably lower than in the A group. The results suggest that rigidity, which is assumed to be due to an action of morphine in the striatum, can be antagonized by another process leading to dopaminergic activation in the striatum. Nevertheless, there occurs some real tolerance to this effect. The rapid alternations of rigidity and the signs of dopaminergic activation observed in the animals of the AS/KS group might be due to rapid shifts in the predominance of various DA-innervated structures.", "entity": "Hyperkinesis", "aliases": "Generalized Hyperkinesia Hyperkinesias Hyperactivity Motor Hyperkinesis Hyperkinetic Movement Movements", "definition": "Excessive movement of muscles of the body as a whole, which may be associated with organic or psychological disorders.\n    ", "id": "MESH:D006948"}
{"mention": "haloperidol", "mention_text": "The development of tolerance to the muscular rigidity produced by morphine was studied in rats. Saline-pretreated controls given a test dose of morphine (20 mg/kg i.p.) showed a pronounced rigidity recorded as tonic activity in the electromyogram. Rats treated for 11 days with morphine and withdrawn for 36-40 h showed differences in the development of tolerance: about half of the animals showed a rigidity after the test dose of morphine that was not significantly less than in the controls and were akinetic (A group). The other rats showed a strong decrease in the rigidity and the occurrence of stereotyped (S) licking and/or gnawing in presence of akinetic or hyperkinetic (K) behaviour (AS/KS group), suggesting signs of dopaminergic activation. The rigidity was considerably decreased in both groups after 20 days' treatment. In a further series of experiments, haloperidol (0.2 mg/kg i.p.) was used in order to block the dopaminergic activation and to estimate the real degree of the tolerance to the rigidity without any dopaminergic interference. Haloperidol enhanced the rigidity in the A group. However, the level in the AS/KS group remained considerably lower than in the A group. The results suggest that rigidity, which is assumed to be due to an action of morphine in the striatum, can be antagonized by another process leading to dopaminergic activation in the striatum. Nevertheless, there occurs some real tolerance to this effect. The rapid alternations of rigidity and the signs of dopaminergic activation observed in the animals of the AS/KS group might be due to rapid shifts in the predominance of various DA-innervated structures.", "entity": "Haloperidol", "aliases": "Haldol Haloperidol", "definition": "A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)\n    ", "id": "MESH:D006220"}
{"mention": "Haloperidol", "mention_text": "The development of tolerance to the muscular rigidity produced by morphine was studied in rats. Saline-pretreated controls given a test dose of morphine (20 mg/kg i.p.) showed a pronounced rigidity recorded as tonic activity in the electromyogram. Rats treated for 11 days with morphine and withdrawn for 36-40 h showed differences in the development of tolerance: about half of the animals showed a rigidity after the test dose of morphine that was not significantly less than in the controls and were akinetic (A group). The other rats showed a strong decrease in the rigidity and the occurrence of stereotyped (S) licking and/or gnawing in presence of akinetic or hyperkinetic (K) behaviour (AS/KS group), suggesting signs of dopaminergic activation. The rigidity was considerably decreased in both groups after 20 days' treatment. In a further series of experiments, haloperidol (0.2 mg/kg i.p.) was used in order to block the dopaminergic activation and to estimate the real degree of the tolerance to the rigidity without any dopaminergic interference. Haloperidol enhanced the rigidity in the A group. However, the level in the AS/KS group remained considerably lower than in the A group. The results suggest that rigidity, which is assumed to be due to an action of morphine in the striatum, can be antagonized by another process leading to dopaminergic activation in the striatum. Nevertheless, there occurs some real tolerance to this effect. The rapid alternations of rigidity and the signs of dopaminergic activation observed in the animals of the AS/KS group might be due to rapid shifts in the predominance of various DA-innervated structures.", "entity": "Haloperidol", "aliases": "Haldol Haloperidol", "definition": "A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)\n    ", "id": "MESH:D006220"}
{"mention": "Compression neuropathy", "mention_text": "Compression neuropathy of the radial nerve due to pentazocine-induced fibrous myopathy.", "entity": "Nerve Compression Syndromes", "aliases": "Compression Syndrome Nerve Syndromes Entrapment Neuropathies Entrapments External Internal Neuropathy", "definition": "Mechanical compression of nerves or nerve roots from internal or external causes. These may result in a conduction block to nerve impulses (due to MYELIN SHEATH dysfunction) or axonal loss. The nerve and nerve sheath injuries may be caused by ISCHEMIA; INFLAMMATION; or a direct mechanical effect.\n    ", "id": "MESH:D009408"}
{"mention": "neuropathy of the radial nerve", "mention_text": "Compression neuropathy of the radial nerve due to pentazocine-induced fibrous myopathy.", "entity": "Radial Neuropathy", "aliases": "Crutch Palsies Palsy Lesion Radial Nerve Superficial Lesions Disease Diseases Neuropathies Neuropathy Saturday Night", "definition": "Disease involving the RADIAL NERVE. Clinical features include weakness of elbow extension, elbow flexion, supination of the forearm, wrist and finger extension, and thumb abduction. Sensation may be impaired over regions of the dorsal forearm. Common sites of compression or traumatic injury include the AXILLA and radial groove of the HUMERUS.\n    ", "id": "MESH:D020425"}
{"mention": "pentazocine", "mention_text": "Compression neuropathy of the radial nerve due to pentazocine-induced fibrous myopathy.", "entity": "Pentazocine", "aliases": "Fortral Hydrochloride Pentazocine Lactate Lexir Talwin", "definition": "The first mixed agonist-antagonist analgesic to be marketed. It is an agonist at the kappa and sigma opioid receptors and has a weak antagonist action at the mu receptor. (From AMA Drug Evaluations Annual, 1991, p97)\n    ", "id": "MESH:D010423"}
{"mention": "pentazocine", "mention_text": "Fibrous myopathy is a common, well-known side effect of repeated pentazocine injection. However, compression neuropathy due to fibrotic muscle affected by pentazocine-induced myopathy has not previously been reported. In a 37-year-old woman with documented pentazocine-induced fibrous myopathy of triceps and deltoid muscles bilaterally and a three-week history of right wrist drop, electrodiagnostic examination showed a severe but partial lesion of the right radial nerve distal to the branches to the triceps, in addition to the fibrous myopathy. Surgery revealed the right radial nerve to be severely compressed by the densely fibrotic lateral head of the triceps. Decompression and neurolysis were performed with good subsequent recovery of function.", "entity": "Pentazocine", "aliases": "Fortral Hydrochloride Pentazocine Lactate Lexir Talwin", "definition": "The first mixed agonist-antagonist analgesic to be marketed. It is an agonist at the kappa and sigma opioid receptors and has a weak antagonist action at the mu receptor. (From AMA Drug Evaluations Annual, 1991, p97)\n    ", "id": "MESH:D010423"}
{"mention": "compression neuropathy", "mention_text": "Fibrous myopathy is a common, well-known side effect of repeated pentazocine injection. However, compression neuropathy due to fibrotic muscle affected by pentazocine-induced myopathy has not previously been reported. In a 37-year-old woman with documented pentazocine-induced fibrous myopathy of triceps and deltoid muscles bilaterally and a three-week history of right wrist drop, electrodiagnostic examination showed a severe but partial lesion of the right radial nerve distal to the branches to the triceps, in addition to the fibrous myopathy. Surgery revealed the right radial nerve to be severely compressed by the densely fibrotic lateral head of the triceps. Decompression and neurolysis were performed with good subsequent recovery of function.", "entity": "Nerve Compression Syndromes", "aliases": "Compression Syndrome Nerve Syndromes Entrapment Neuropathies Entrapments External Internal Neuropathy", "definition": "Mechanical compression of nerves or nerve roots from internal or external causes. These may result in a conduction block to nerve impulses (due to MYELIN SHEATH dysfunction) or axonal loss. The nerve and nerve sheath injuries may be caused by ISCHEMIA; INFLAMMATION; or a direct mechanical effect.\n    ", "id": "MESH:D009408"}
{"mention": "myopathy", "mention_text": "Fibrous myopathy is a common, well-known side effect of repeated pentazocine injection. However, compression neuropathy due to fibrotic muscle affected by pentazocine-induced myopathy has not previously been reported. In a 37-year-old woman with documented pentazocine-induced fibrous myopathy of triceps and deltoid muscles bilaterally and a three-week history of right wrist drop, electrodiagnostic examination showed a severe but partial lesion of the right radial nerve distal to the branches to the triceps, in addition to the fibrous myopathy. Surgery revealed the right radial nerve to be severely compressed by the densely fibrotic lateral head of the triceps. Decompression and neurolysis were performed with good subsequent recovery of function.", "entity": "Muscular Diseases", "aliases": "Muscle Disorder Disorders Muscular Disease Diseases Myopathic Condition Conditions Myopathies Myopathy", "definition": "Acquired, familial, and congenital disorders of SKELETAL MUSCLE and SMOOTH MUSCLE.\n    ", "id": "MESH:D009135"}
{"mention": "acute renal failure", "mention_text": "Recurrent reversible acute renal failure from amphotericin.", "entity": "Acute Kidney Injury", "aliases": "Acute Kidney Failure Failures Injuries Injury Insufficiencies Insufficiency Renal", "definition": "Abrupt reduction in kidney function. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions.\n    ", "id": "MESH:D058186"}
{"mention": "amphotericin", "mention_text": "Recurrent reversible acute renal failure from amphotericin.", "entity": "Amphotericin B", "aliases": "Amphocil Amphotericin B Cholesterol Dispersion Colloidal Fungizone", "definition": "Macrolide antifungal antibiotic produced by Streptomyces nodosus obtained from soil of the Orinoco river region of Venezuela.\n    ", "id": "MESH:D000666"}
{"mention": "cirrhosis", "mention_text": "A patient with cryptogenic cirrhosis and disseminated sporotrichosis developed acute renal failure immediately following the administration of amphotericin B on four separate occasions. The abruptness of the renal failure and its reversibility within days suggests that there was a functional component to the renal dysfunction. We propose that amphotericin, in the setting of reduced effective arterial volume, may activate tubuloglomerular feedback, thereby contributing to acute renal failure.", "entity": "Fibrosis", "aliases": "Cirrhosis Fibroses Fibrosis", "definition": "Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.\n    ", "id": "MESH:D005355"}
{"mention": "sporotrichosis", "mention_text": "A patient with cryptogenic cirrhosis and disseminated sporotrichosis developed acute renal failure immediately following the administration of amphotericin B on four separate occasions. The abruptness of the renal failure and its reversibility within days suggests that there was a functional component to the renal dysfunction. We propose that amphotericin, in the setting of reduced effective arterial volume, may activate tubuloglomerular feedback, thereby contributing to acute renal failure.", "entity": "Sporotrichosis", "aliases": "Sporotrichoses Sporotrichosis", "definition": "The commonest and least serious of the deep mycoses, characterized by nodular lesions of the cutaneous and subcutaneous tissues. It is caused by inhalation of contaminated dust or by infection of a wound.\n    ", "id": "MESH:D013174"}
{"mention": "acute renal failure", "mention_text": "A patient with cryptogenic cirrhosis and disseminated sporotrichosis developed acute renal failure immediately following the administration of amphotericin B on four separate occasions. The abruptness of the renal failure and its reversibility within days suggests that there was a functional component to the renal dysfunction. We propose that amphotericin, in the setting of reduced effective arterial volume, may activate tubuloglomerular feedback, thereby contributing to acute renal failure.", "entity": "Acute Kidney Injury", "aliases": "Acute Kidney Failure Failures Injuries Injury Insufficiencies Insufficiency Renal", "definition": "Abrupt reduction in kidney function. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions.\n    ", "id": "MESH:D058186"}
{"mention": "amphotericin B", "mention_text": "A patient with cryptogenic cirrhosis and disseminated sporotrichosis developed acute renal failure immediately following the administration of amphotericin B on four separate occasions. The abruptness of the renal failure and its reversibility within days suggests that there was a functional component to the renal dysfunction. We propose that amphotericin, in the setting of reduced effective arterial volume, may activate tubuloglomerular feedback, thereby contributing to acute renal failure.", "entity": "Amphotericin B", "aliases": "Amphocil Amphotericin B Cholesterol Dispersion Colloidal Fungizone", "definition": "Macrolide antifungal antibiotic produced by Streptomyces nodosus obtained from soil of the Orinoco river region of Venezuela.\n    ", "id": "MESH:D000666"}
{"mention": "renal failure", "mention_text": "A patient with cryptogenic cirrhosis and disseminated sporotrichosis developed acute renal failure immediately following the administration of amphotericin B on four separate occasions. The abruptness of the renal failure and its reversibility within days suggests that there was a functional component to the renal dysfunction. We propose that amphotericin, in the setting of reduced effective arterial volume, may activate tubuloglomerular feedback, thereby contributing to acute renal failure.", "entity": "Renal Insufficiency", "aliases": "Failure Kidney Renal Failures Insufficiency Insufficiencies", "definition": "Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.\n    ", "id": "MESH:D051437"}
{"mention": "renal dysfunction", "mention_text": "A patient with cryptogenic cirrhosis and disseminated sporotrichosis developed acute renal failure immediately following the administration of amphotericin B on four separate occasions. The abruptness of the renal failure and its reversibility within days suggests that there was a functional component to the renal dysfunction. We propose that amphotericin, in the setting of reduced effective arterial volume, may activate tubuloglomerular feedback, thereby contributing to acute renal failure.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "amphotericin", "mention_text": "A patient with cryptogenic cirrhosis and disseminated sporotrichosis developed acute renal failure immediately following the administration of amphotericin B on four separate occasions. The abruptness of the renal failure and its reversibility within days suggests that there was a functional component to the renal dysfunction. We propose that amphotericin, in the setting of reduced effective arterial volume, may activate tubuloglomerular feedback, thereby contributing to acute renal failure.", "entity": "Amphotericin B", "aliases": "Amphocil Amphotericin B Cholesterol Dispersion Colloidal Fungizone", "definition": "Macrolide antifungal antibiotic produced by Streptomyces nodosus obtained from soil of the Orinoco river region of Venezuela.\n    ", "id": "MESH:D000666"}
{"mention": "pericardial effusion", "mention_text": "Pneumonitis with pleural and pericardial effusion and neuropathy during amiodarone therapy.", "entity": "Pericardial Effusion", "aliases": "Chylopericardium Chylopericardiums Effusion Pericardial Effusions Hemopericardium", "definition": "Fluid accumulation within the PERICARDIUM. Serous effusions are associated with pericardial diseases. Hemopericardium is associated with trauma. Lipid-containing effusion (chylopericardium) results from leakage of THORACIC DUCT. Severe cases can lead to CARDIAC TAMPONADE.\n    ", "id": "MESH:D010490"}
{"mention": "neuropathy", "mention_text": "Pneumonitis with pleural and pericardial effusion and neuropathy during amiodarone therapy.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "amiodarone", "mention_text": "Pneumonitis with pleural and pericardial effusion and neuropathy during amiodarone therapy.", "entity": "Amiodarone", "aliases": "ASTA Medica Brand of Amiodarone Hydrochloride Alphapharm Amiobeta Amiodarex Amiodarona Amiohexal Aratac Armstrong Berenguer Infale Betapharm Braxan Corbionax Cordarex Cordarone G Gam Hexal Kordaron L 3428 L-3428 L3428 Leurquin Ortacrone Pharma Investi Rytmarone SKF 33134 A 33134-A 33134A Sanofi Winthrop Tachydaron Trangorex Wyeth", "definition": "An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.\n    ", "id": "MESH:D000638"}
{"mention": "sinuatrial disease", "mention_text": "A patient with sinuatrial disease and implanted pacemaker was treated with amiodarone (maximum dose 1000 mg, maintenance dose 800 mg daily) for 10 months, for control of supraventricular tachyarrhythmias. He developed pneumonitis, pleural and pericardial effusions, and a predominantly proximal motor neuropathy. Immediate but gradual improvement followed withdrawal of amiodarone and treatment with prednisolone. Review of this and previously reported cases indicates the need for early diagnosis of amiodarone pneumonitis, immediate withdrawal of amiodarone, and prompt but continued steroid therapy to ensure full recovery.", "entity": "Cardiovascular Diseases", "aliases": "Cardiovascular Disease Diseases", "definition": "Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.\n    ", "id": "MESH:D002318"}
{"mention": "amiodarone", "mention_text": "A patient with sinuatrial disease and implanted pacemaker was treated with amiodarone (maximum dose 1000 mg, maintenance dose 800 mg daily) for 10 months, for control of supraventricular tachyarrhythmias. He developed pneumonitis, pleural and pericardial effusions, and a predominantly proximal motor neuropathy. Immediate but gradual improvement followed withdrawal of amiodarone and treatment with prednisolone. Review of this and previously reported cases indicates the need for early diagnosis of amiodarone pneumonitis, immediate withdrawal of amiodarone, and prompt but continued steroid therapy to ensure full recovery.", "entity": "Amiodarone", "aliases": "ASTA Medica Brand of Amiodarone Hydrochloride Alphapharm Amiobeta Amiodarex Amiodarona Amiohexal Aratac Armstrong Berenguer Infale Betapharm Braxan Corbionax Cordarex Cordarone G Gam Hexal Kordaron L 3428 L-3428 L3428 Leurquin Ortacrone Pharma Investi Rytmarone SKF 33134 A 33134-A 33134A Sanofi Winthrop Tachydaron Trangorex Wyeth", "definition": "An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.\n    ", "id": "MESH:D000638"}
{"mention": "supraventricular tachyarrhythmias", "mention_text": "A patient with sinuatrial disease and implanted pacemaker was treated with amiodarone (maximum dose 1000 mg, maintenance dose 800 mg daily) for 10 months, for control of supraventricular tachyarrhythmias. He developed pneumonitis, pleural and pericardial effusions, and a predominantly proximal motor neuropathy. Immediate but gradual improvement followed withdrawal of amiodarone and treatment with prednisolone. Review of this and previously reported cases indicates the need for early diagnosis of amiodarone pneumonitis, immediate withdrawal of amiodarone, and prompt but continued steroid therapy to ensure full recovery.", "entity": "Tachycardia, Supraventricular", "aliases": "Supraventricular Tachycardia Tachycardias", "definition": "A generic expression for any tachycardia that originates above the BUNDLE OF HIS.\n    ", "id": "MESH:D013617"}
{"mention": "pneumonitis", "mention_text": "A patient with sinuatrial disease and implanted pacemaker was treated with amiodarone (maximum dose 1000 mg, maintenance dose 800 mg daily) for 10 months, for control of supraventricular tachyarrhythmias. He developed pneumonitis, pleural and pericardial effusions, and a predominantly proximal motor neuropathy. Immediate but gradual improvement followed withdrawal of amiodarone and treatment with prednisolone. Review of this and previously reported cases indicates the need for early diagnosis of amiodarone pneumonitis, immediate withdrawal of amiodarone, and prompt but continued steroid therapy to ensure full recovery.", "entity": "Pneumonia", "aliases": "Experimental Lung Inflammation Inflammations Pulmonary Lobar Pneumonia Pneumonias Pneumonitides Pneumonitis", "definition": "Inflammation of any part, segment or lobe, of the lung parenchyma.\n    ", "id": "MESH:D011014"}
{"mention": "pericardial effusions", "mention_text": "A patient with sinuatrial disease and implanted pacemaker was treated with amiodarone (maximum dose 1000 mg, maintenance dose 800 mg daily) for 10 months, for control of supraventricular tachyarrhythmias. He developed pneumonitis, pleural and pericardial effusions, and a predominantly proximal motor neuropathy. Immediate but gradual improvement followed withdrawal of amiodarone and treatment with prednisolone. Review of this and previously reported cases indicates the need for early diagnosis of amiodarone pneumonitis, immediate withdrawal of amiodarone, and prompt but continued steroid therapy to ensure full recovery.", "entity": "Pericardial Effusion", "aliases": "Chylopericardium Chylopericardiums Effusion Pericardial Effusions Hemopericardium", "definition": "Fluid accumulation within the PERICARDIUM. Serous effusions are associated with pericardial diseases. Hemopericardium is associated with trauma. Lipid-containing effusion (chylopericardium) results from leakage of THORACIC DUCT. Severe cases can lead to CARDIAC TAMPONADE.\n    ", "id": "MESH:D010490"}
{"mention": "proximal motor neuropathy", "mention_text": "A patient with sinuatrial disease and implanted pacemaker was treated with amiodarone (maximum dose 1000 mg, maintenance dose 800 mg daily) for 10 months, for control of supraventricular tachyarrhythmias. He developed pneumonitis, pleural and pericardial effusions, and a predominantly proximal motor neuropathy. Immediate but gradual improvement followed withdrawal of amiodarone and treatment with prednisolone. Review of this and previously reported cases indicates the need for early diagnosis of amiodarone pneumonitis, immediate withdrawal of amiodarone, and prompt but continued steroid therapy to ensure full recovery.", "entity": "Neuromuscular Diseases", "aliases": "Amyotonia Congenita Benign Fasciculation-Cramp Syndrome Syndromes Cramp Fasciculation Cramp-Fasciculation Foley Denny Brown Foley-Denny-Brown Neuromuscular Disease Diseases Oppenheim Oppenheim's Oppenheims", "definition": "A general term encompassing lower MOTOR NEURON DISEASE; PERIPHERAL NERVOUS SYSTEM DISEASES; and certain MUSCULAR DISEASES. Manifestations include MUSCLE WEAKNESS; FASCICULATION; muscle ATROPHY; SPASM; MYOKYMIA; MUSCLE HYPERTONIA, myalgias, and MUSCLE HYPOTONIA.\n    ", "id": "MESH:D009468"}
{"mention": "prednisolone", "mention_text": "A patient with sinuatrial disease and implanted pacemaker was treated with amiodarone (maximum dose 1000 mg, maintenance dose 800 mg daily) for 10 months, for control of supraventricular tachyarrhythmias. He developed pneumonitis, pleural and pericardial effusions, and a predominantly proximal motor neuropathy. Immediate but gradual improvement followed withdrawal of amiodarone and treatment with prednisolone. Review of this and previously reported cases indicates the need for early diagnosis of amiodarone pneumonitis, immediate withdrawal of amiodarone, and prompt but continued steroid therapy to ensure full recovery.", "entity": "Prednisolone", "aliases": "Di Adreson F Di-Adreson-F DiAdresonF Predate Prednisolone Predonine", "definition": "A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states.\n    ", "id": "MESH:D011239"}
{"mention": "steroid", "mention_text": "A patient with sinuatrial disease and implanted pacemaker was treated with amiodarone (maximum dose 1000 mg, maintenance dose 800 mg daily) for 10 months, for control of supraventricular tachyarrhythmias. He developed pneumonitis, pleural and pericardial effusions, and a predominantly proximal motor neuropathy. Immediate but gradual improvement followed withdrawal of amiodarone and treatment with prednisolone. Review of this and previously reported cases indicates the need for early diagnosis of amiodarone pneumonitis, immediate withdrawal of amiodarone, and prompt but continued steroid therapy to ensure full recovery.", "entity": "Steroids", "aliases": "Catatoxic Steroids", "definition": "A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)\n    ", "id": "MESH:D013256"}
{"mention": "Indomethacin", "mention_text": "Indomethacin-induced renal insufficiency: recurrence on rechallenge.", "entity": "Indomethacin", "aliases": "Amuno Hydrochloride Indomethacin Indocid Indocin Indomet 140 Indometacin Metindol Osmosin", "definition": "A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes.\n    ", "id": "MESH:D007213"}
{"mention": "renal insufficiency", "mention_text": "Indomethacin-induced renal insufficiency: recurrence on rechallenge.", "entity": "Renal Insufficiency", "aliases": "Failure Kidney Renal Failures Insufficiency Insufficiencies", "definition": "Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.\n    ", "id": "MESH:D051437"}
{"mention": "renal failure", "mention_text": "We have reported a case of acute oliguric renal failure with hyperkalemia in a patient with cirrhosis, ascites, and cor pulmonale after indomethacin therapy. Prompt restoration of renal function followed drug withdrawal, while re-exposure to a single dose of indomethacin caused recurrence of acute reversible oliguria. Our case supports the hypothesis that endogenous renal prostaglandins play a role in the maintenance of renal blood flow when circulating plasma volume is diminished. Since nonsteroidal anti-inflammatory agents interfere with this compensatory mechanism and may cause acute renal failure, they should be used with caution in such patients.", "entity": "Renal Insufficiency", "aliases": "Failure Kidney Renal Failures Insufficiency Insufficiencies", "definition": "Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.\n    ", "id": "MESH:D051437"}
{"mention": "hyperkalemia", "mention_text": "We have reported a case of acute oliguric renal failure with hyperkalemia in a patient with cirrhosis, ascites, and cor pulmonale after indomethacin therapy. Prompt restoration of renal function followed drug withdrawal, while re-exposure to a single dose of indomethacin caused recurrence of acute reversible oliguria. Our case supports the hypothesis that endogenous renal prostaglandins play a role in the maintenance of renal blood flow when circulating plasma volume is diminished. Since nonsteroidal anti-inflammatory agents interfere with this compensatory mechanism and may cause acute renal failure, they should be used with caution in such patients.", "entity": "Hyperkalemia", "aliases": "Hyperkalemia Hyperkalemias Hyperpotassemia Hyperpotassemias", "definition": "Abnormally high potassium concentration in the blood, most often due to defective renal excretion. It is characterized clinically by electrocardiographic abnormalities (elevated T waves and depressed P waves, and eventually by atrial asystole). In severe cases, weakness and flaccid paralysis may occur. (Dorland, 27th ed)\n    ", "id": "MESH:D006947"}
{"mention": "cirrhosis", "mention_text": "We have reported a case of acute oliguric renal failure with hyperkalemia in a patient with cirrhosis, ascites, and cor pulmonale after indomethacin therapy. Prompt restoration of renal function followed drug withdrawal, while re-exposure to a single dose of indomethacin caused recurrence of acute reversible oliguria. Our case supports the hypothesis that endogenous renal prostaglandins play a role in the maintenance of renal blood flow when circulating plasma volume is diminished. Since nonsteroidal anti-inflammatory agents interfere with this compensatory mechanism and may cause acute renal failure, they should be used with caution in such patients.", "entity": "Fibrosis", "aliases": "Cirrhosis Fibroses Fibrosis", "definition": "Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.\n    ", "id": "MESH:D005355"}
{"mention": "ascites", "mention_text": "We have reported a case of acute oliguric renal failure with hyperkalemia in a patient with cirrhosis, ascites, and cor pulmonale after indomethacin therapy. Prompt restoration of renal function followed drug withdrawal, while re-exposure to a single dose of indomethacin caused recurrence of acute reversible oliguria. Our case supports the hypothesis that endogenous renal prostaglandins play a role in the maintenance of renal blood flow when circulating plasma volume is diminished. Since nonsteroidal anti-inflammatory agents interfere with this compensatory mechanism and may cause acute renal failure, they should be used with caution in such patients.", "entity": "Ascites", "aliases": "Ascites", "definition": "Accumulation or retention of free fluid within the peritoneal cavity.\n    ", "id": "MESH:D001201"}
{"mention": "cor pulmonale", "mention_text": "We have reported a case of acute oliguric renal failure with hyperkalemia in a patient with cirrhosis, ascites, and cor pulmonale after indomethacin therapy. Prompt restoration of renal function followed drug withdrawal, while re-exposure to a single dose of indomethacin caused recurrence of acute reversible oliguria. Our case supports the hypothesis that endogenous renal prostaglandins play a role in the maintenance of renal blood flow when circulating plasma volume is diminished. Since nonsteroidal anti-inflammatory agents interfere with this compensatory mechanism and may cause acute renal failure, they should be used with caution in such patients.", "entity": "Pulmonary Heart Disease", "aliases": "Cor Pulmonale Disease Pulmonary Heart Diseases", "definition": "Hypertrophy and dilation of the RIGHT VENTRICLE of the heart that is caused by PULMONARY HYPERTENSION. This condition is often associated with pulmonary parenchymal or vascular diseases, such as CHRONIC OBSTRUCTIVE PULMONARY DISEASE and PULMONARY EMBOLISM.\n    ", "id": "MESH:D011660"}
{"mention": "indomethacin", "mention_text": "We have reported a case of acute oliguric renal failure with hyperkalemia in a patient with cirrhosis, ascites, and cor pulmonale after indomethacin therapy. Prompt restoration of renal function followed drug withdrawal, while re-exposure to a single dose of indomethacin caused recurrence of acute reversible oliguria. Our case supports the hypothesis that endogenous renal prostaglandins play a role in the maintenance of renal blood flow when circulating plasma volume is diminished. Since nonsteroidal anti-inflammatory agents interfere with this compensatory mechanism and may cause acute renal failure, they should be used with caution in such patients.", "entity": "Indomethacin", "aliases": "Amuno Hydrochloride Indomethacin Indocid Indocin Indomet 140 Indometacin Metindol Osmosin", "definition": "A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes.\n    ", "id": "MESH:D007213"}
{"mention": "oliguria", "mention_text": "We have reported a case of acute oliguric renal failure with hyperkalemia in a patient with cirrhosis, ascites, and cor pulmonale after indomethacin therapy. Prompt restoration of renal function followed drug withdrawal, while re-exposure to a single dose of indomethacin caused recurrence of acute reversible oliguria. Our case supports the hypothesis that endogenous renal prostaglandins play a role in the maintenance of renal blood flow when circulating plasma volume is diminished. Since nonsteroidal anti-inflammatory agents interfere with this compensatory mechanism and may cause acute renal failure, they should be used with caution in such patients.", "entity": "Oliguria", "aliases": "Oliguria Oligurias", "definition": "Decreased URINE output that is below the normal range. Oliguria can be defined as urine output of less than or equal to 0.5 or 1 ml/kg/hr depending on the age.\n    ", "id": "MESH:D009846"}
{"mention": "prostaglandins", "mention_text": "We have reported a case of acute oliguric renal failure with hyperkalemia in a patient with cirrhosis, ascites, and cor pulmonale after indomethacin therapy. Prompt restoration of renal function followed drug withdrawal, while re-exposure to a single dose of indomethacin caused recurrence of acute reversible oliguria. Our case supports the hypothesis that endogenous renal prostaglandins play a role in the maintenance of renal blood flow when circulating plasma volume is diminished. Since nonsteroidal anti-inflammatory agents interfere with this compensatory mechanism and may cause acute renal failure, they should be used with caution in such patients.", "entity": "Prostaglandins", "aliases": "Prostaglandins Prostanoids", "definition": "A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes.\n    ", "id": "MESH:D011453"}
{"mention": "acute renal failure", "mention_text": "We have reported a case of acute oliguric renal failure with hyperkalemia in a patient with cirrhosis, ascites, and cor pulmonale after indomethacin therapy. Prompt restoration of renal function followed drug withdrawal, while re-exposure to a single dose of indomethacin caused recurrence of acute reversible oliguria. Our case supports the hypothesis that endogenous renal prostaglandins play a role in the maintenance of renal blood flow when circulating plasma volume is diminished. Since nonsteroidal anti-inflammatory agents interfere with this compensatory mechanism and may cause acute renal failure, they should be used with caution in such patients.", "entity": "Acute Kidney Injury", "aliases": "Acute Kidney Failure Failures Injuries Injury Insufficiencies Insufficiency Renal", "definition": "Abrupt reduction in kidney function. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions.\n    ", "id": "MESH:D058186"}
{"mention": "flunitrazepam", "mention_text": "Comparison of the subjective effects and plasma concentrations following oral and i.m. administration of flunitrazepam in volunteers.", "entity": "Flunitrazepam", "aliases": "1A Brand of Flunitrazepam Fluni Pharma Flunibeta Flunimerck Fluninoc Teva neuraxpharm ratiopharm Flunitrazepam-Teva Flunitrazepam-neuraxpharm Flunitrazepam-ratiopharm Fluridrazepam Hexal Merck dura Narcozep RO-5-4200 RO54200 Roche Rohipnol Rohypnol betapharm ct Arzneimittel ct-Arzneimittel flunizep von", "definition": "A benzodiazepine with pharmacologic actions similar to those of DIAZEPAM that can cause ANTEROGRADE AMNESIA. Some reports indicate that it is used as a date rape drug and suggest that it may precipitate violent behavior. The United States Government has banned the importation of this drug.\n    ", "id": "MESH:D005445"}
{"mention": "Flunitrazepam", "mention_text": "Flunitrazepam 0.5, 1.0 or 2.0 mg was given by the oral or i.m. routes to groups of volunteers and its effects compared. Plasma concentrations of the drug were estimated by gas-liquid chromatography, in a smaller number of the subjects. The most striking effect was sedation which increased with the dose, 2 mg producing deep sleep although the subjects could still be aroused. The effects of i.m. administration were apparent earlier and sometimes lasted longer than those following oral administration. Dizziness was less marked than sedation, but increased with the dose. There was pain on i.m. injection of flunitrazepam significantly more often than with isotonic saline. Plasma concentrations varied with dose and route and corresponded qualitatively with the subjective effects. The drug was still present in measurable quantities after 24 h even with the smallest dose.", "entity": "Flunitrazepam", "aliases": "1A Brand of Flunitrazepam Fluni Pharma Flunibeta Flunimerck Fluninoc Teva neuraxpharm ratiopharm Flunitrazepam-Teva Flunitrazepam-neuraxpharm Flunitrazepam-ratiopharm Fluridrazepam Hexal Merck dura Narcozep RO-5-4200 RO54200 Roche Rohipnol Rohypnol betapharm ct Arzneimittel ct-Arzneimittel flunizep von", "definition": "A benzodiazepine with pharmacologic actions similar to those of DIAZEPAM that can cause ANTEROGRADE AMNESIA. Some reports indicate that it is used as a date rape drug and suggest that it may precipitate violent behavior. The United States Government has banned the importation of this drug.\n    ", "id": "MESH:D005445"}
{"mention": "Dizziness", "mention_text": "Flunitrazepam 0.5, 1.0 or 2.0 mg was given by the oral or i.m. routes to groups of volunteers and its effects compared. Plasma concentrations of the drug were estimated by gas-liquid chromatography, in a smaller number of the subjects. The most striking effect was sedation which increased with the dose, 2 mg producing deep sleep although the subjects could still be aroused. The effects of i.m. administration were apparent earlier and sometimes lasted longer than those following oral administration. Dizziness was less marked than sedation, but increased with the dose. There was pain on i.m. injection of flunitrazepam significantly more often than with isotonic saline. Plasma concentrations varied with dose and route and corresponded qualitatively with the subjective effects. The drug was still present in measurable quantities after 24 h even with the smallest dose.", "entity": "Dizziness", "aliases": "Dizziness Dizzyness Light Headedness Light-Headedness Lightheadedness Orthostasis", "definition": "An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness.\n    ", "id": "MESH:D004244"}
{"mention": "pain", "mention_text": "Flunitrazepam 0.5, 1.0 or 2.0 mg was given by the oral or i.m. routes to groups of volunteers and its effects compared. Plasma concentrations of the drug were estimated by gas-liquid chromatography, in a smaller number of the subjects. The most striking effect was sedation which increased with the dose, 2 mg producing deep sleep although the subjects could still be aroused. The effects of i.m. administration were apparent earlier and sometimes lasted longer than those following oral administration. Dizziness was less marked than sedation, but increased with the dose. There was pain on i.m. injection of flunitrazepam significantly more often than with isotonic saline. Plasma concentrations varied with dose and route and corresponded qualitatively with the subjective effects. The drug was still present in measurable quantities after 24 h even with the smallest dose.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "flunitrazepam", "mention_text": "Flunitrazepam 0.5, 1.0 or 2.0 mg was given by the oral or i.m. routes to groups of volunteers and its effects compared. Plasma concentrations of the drug were estimated by gas-liquid chromatography, in a smaller number of the subjects. The most striking effect was sedation which increased with the dose, 2 mg producing deep sleep although the subjects could still be aroused. The effects of i.m. administration were apparent earlier and sometimes lasted longer than those following oral administration. Dizziness was less marked than sedation, but increased with the dose. There was pain on i.m. injection of flunitrazepam significantly more often than with isotonic saline. Plasma concentrations varied with dose and route and corresponded qualitatively with the subjective effects. The drug was still present in measurable quantities after 24 h even with the smallest dose.", "entity": "Flunitrazepam", "aliases": "1A Brand of Flunitrazepam Fluni Pharma Flunibeta Flunimerck Fluninoc Teva neuraxpharm ratiopharm Flunitrazepam-Teva Flunitrazepam-neuraxpharm Flunitrazepam-ratiopharm Fluridrazepam Hexal Merck dura Narcozep RO-5-4200 RO54200 Roche Rohipnol Rohypnol betapharm ct Arzneimittel ct-Arzneimittel flunizep von", "definition": "A benzodiazepine with pharmacologic actions similar to those of DIAZEPAM that can cause ANTEROGRADE AMNESIA. Some reports indicate that it is used as a date rape drug and suggest that it may precipitate violent behavior. The United States Government has banned the importation of this drug.\n    ", "id": "MESH:D005445"}
{"mention": "timolol", "mention_text": "Changes in heart size during long-term timolol treatment after myocardial infarction.", "entity": "Timolol", "aliases": "(S)-1-((1,1-Dimethylethyl)amino)-3-((4-(4-morpholinyl)-1,2,5-thiadazol-3-yl)oxy)-2-propanol Blocadren Hemihydrate Timolol L 714,465 L-714,465 L714,465 MK 950 MK-950 MK950 Optimol Timacar Maleate (1:1) Salt Timoptic Timoptol", "definition": "A beta-adrenergic antagonist similar in action to PROPRANOLOL. The levo-isomer is the more active. Timolol has been proposed as an antihypertensive, antiarrhythmic, antiangina, and antiglaucoma agent. It is also used in the treatment of MIGRAINE DISORDERS and tremor.\n    ", "id": "MESH:D013999"}
{"mention": "myocardial infarction", "mention_text": "Changes in heart size during long-term timolol treatment after myocardial infarction.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "timolol", "mention_text": "The effect of long-term timolol treatment on heart size after myocardial infarction was evaluated by X-ray in a double-blind study including 241 patients (placebo 126, timolol 115). The follow-up period was 12 months. The timolol-treated patients showed a small but significant increase in heart size from baseline in contrast to a decrease in the placebo group. These differences may be caused by timolol-induced bradycardia and a compensatory increase in end-diastolic volume. The timolol-related increase in heart size was observed only in patients with normal and borderline heart size. In patients with cardiomegaly, the increase in heart size was similar in both groups. After re-infarction, heart size increased in the placebo group and remained unchanged in the timolol group.", "entity": "Timolol", "aliases": "(S)-1-((1,1-Dimethylethyl)amino)-3-((4-(4-morpholinyl)-1,2,5-thiadazol-3-yl)oxy)-2-propanol Blocadren Hemihydrate Timolol L 714,465 L-714,465 L714,465 MK 950 MK-950 MK950 Optimol Timacar Maleate (1:1) Salt Timoptic Timoptol", "definition": "A beta-adrenergic antagonist similar in action to PROPRANOLOL. The levo-isomer is the more active. Timolol has been proposed as an antihypertensive, antiarrhythmic, antiangina, and antiglaucoma agent. It is also used in the treatment of MIGRAINE DISORDERS and tremor.\n    ", "id": "MESH:D013999"}
{"mention": "myocardial infarction", "mention_text": "The effect of long-term timolol treatment on heart size after myocardial infarction was evaluated by X-ray in a double-blind study including 241 patients (placebo 126, timolol 115). The follow-up period was 12 months. The timolol-treated patients showed a small but significant increase in heart size from baseline in contrast to a decrease in the placebo group. These differences may be caused by timolol-induced bradycardia and a compensatory increase in end-diastolic volume. The timolol-related increase in heart size was observed only in patients with normal and borderline heart size. In patients with cardiomegaly, the increase in heart size was similar in both groups. After re-infarction, heart size increased in the placebo group and remained unchanged in the timolol group.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "bradycardia", "mention_text": "The effect of long-term timolol treatment on heart size after myocardial infarction was evaluated by X-ray in a double-blind study including 241 patients (placebo 126, timolol 115). The follow-up period was 12 months. The timolol-treated patients showed a small but significant increase in heart size from baseline in contrast to a decrease in the placebo group. These differences may be caused by timolol-induced bradycardia and a compensatory increase in end-diastolic volume. The timolol-related increase in heart size was observed only in patients with normal and borderline heart size. In patients with cardiomegaly, the increase in heart size was similar in both groups. After re-infarction, heart size increased in the placebo group and remained unchanged in the timolol group.", "entity": "Bradycardia", "aliases": "Bradyarrhythmia Bradyarrhythmias Bradycardia Bradycardias", "definition": "Cardiac arrhythmias that are characterized by excessively slow HEART RATE, usually below 50 beats per minute in human adults. They can be classified broadly into SINOATRIAL NODE dysfunction and ATRIOVENTRICULAR BLOCK.\n    ", "id": "MESH:D001919"}
{"mention": "cardiomegaly", "mention_text": "The effect of long-term timolol treatment on heart size after myocardial infarction was evaluated by X-ray in a double-blind study including 241 patients (placebo 126, timolol 115). The follow-up period was 12 months. The timolol-treated patients showed a small but significant increase in heart size from baseline in contrast to a decrease in the placebo group. These differences may be caused by timolol-induced bradycardia and a compensatory increase in end-diastolic volume. The timolol-related increase in heart size was observed only in patients with normal and borderline heart size. In patients with cardiomegaly, the increase in heart size was similar in both groups. After re-infarction, heart size increased in the placebo group and remained unchanged in the timolol group.", "entity": "Cardiomegaly", "aliases": "Cardiac Hypertrophy Cardiomegaly Enlarged Heart Enlargement", "definition": "Enlargement of the HEART, usually indicated by a cardiothoracic ratio above 0.50. Heart enlargement may involve the right, the left, or both HEART VENTRICLES or HEART ATRIA. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (HEART FAILURE) or several forms of CARDIOMYOPATHIES.\n    ", "id": "MESH:D006332"}
{"mention": "infarction", "mention_text": "The effect of long-term timolol treatment on heart size after myocardial infarction was evaluated by X-ray in a double-blind study including 241 patients (placebo 126, timolol 115). The follow-up period was 12 months. The timolol-treated patients showed a small but significant increase in heart size from baseline in contrast to a decrease in the placebo group. These differences may be caused by timolol-induced bradycardia and a compensatory increase in end-diastolic volume. The timolol-related increase in heart size was observed only in patients with normal and borderline heart size. In patients with cardiomegaly, the increase in heart size was similar in both groups. After re-infarction, heart size increased in the placebo group and remained unchanged in the timolol group.", "entity": "Infarction", "aliases": "Infarction Infarctions", "definition": "Formation of an infarct, which is NECROSIS in tissue due to local ISCHEMIA resulting from obstruction of BLOOD CIRCULATION, most commonly by a THROMBUS or EMBOLUS.\n    ", "id": "MESH:D007238"}
{"mention": "Vitamin D3", "mention_text": "Vitamin D3 toxicity in dairy cows.", "entity": "Cholecalciferol", "aliases": "(3 beta,5Z,7E)-9,10-Secocholesta-5,7,10(19)-trien-3-ol Calciol Cholecalciferol Cholecalciferols Vitamin D 3 D3", "definition": "Derivative of 7-dehydroxycholesterol formed by ULTRAVIOLET RAYS breaking of the C9-C10 bond. It differs from ERGOCALCIFEROL in having a single bond between C22 and C23 and lacking a methyl group at C24.\n    ", "id": "MESH:D002762"}
{"mention": "toxicity", "mention_text": "Vitamin D3 toxicity in dairy cows.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "vitamin D3", "mention_text": "Large parenteral doses of vitamin D3 (15 to 17.5 x 10(6) IU vitamin D3) were associated with prolonged hypercalcemia, hyperphosphatemia, and large increases of vitamin D3 and its metabolites in the blood plasma of nonlactating nonpregnant and pregnant Jersey cows. Calcium concentrations 1 day postpartum were higher in cows treated with vitamin D3 about 32 days prepartum (8.8 mg/100 ml) than in control cows (5.5 mg/100 ml). None of the cows treated with vitamin D3 showed signs of milk fever during the peripartal period; however, 22% of the control cows developed clinical signs of milk fever during this period. Signs of vitamin D3 toxicity were not observed in nonlactating nonpregnant cows; however, pregnant cows commonly developed severe signs of vitamin D3 toxicity and 10 of 17 cows died. There was widespread metastatic calcification in the cows that died. Because of the extreme toxicity of vitamin D3 in pregnant Jersey cows and the low margin of safety between doses of vitamin D3 that prevent milk fever and doses that induce milk fever, we concluded that vitamin D3 cannot be used practically to prevent milk fever when injected several weeks prepartum.", "entity": "Cholecalciferol", "aliases": "(3 beta,5Z,7E)-9,10-Secocholesta-5,7,10(19)-trien-3-ol Calciol Cholecalciferol Cholecalciferols Vitamin D 3 D3", "definition": "Derivative of 7-dehydroxycholesterol formed by ULTRAVIOLET RAYS breaking of the C9-C10 bond. It differs from ERGOCALCIFEROL in having a single bond between C22 and C23 and lacking a methyl group at C24.\n    ", "id": "MESH:D002762"}
{"mention": "hypercalcemia", "mention_text": "Large parenteral doses of vitamin D3 (15 to 17.5 x 10(6) IU vitamin D3) were associated with prolonged hypercalcemia, hyperphosphatemia, and large increases of vitamin D3 and its metabolites in the blood plasma of nonlactating nonpregnant and pregnant Jersey cows. Calcium concentrations 1 day postpartum were higher in cows treated with vitamin D3 about 32 days prepartum (8.8 mg/100 ml) than in control cows (5.5 mg/100 ml). None of the cows treated with vitamin D3 showed signs of milk fever during the peripartal period; however, 22% of the control cows developed clinical signs of milk fever during this period. Signs of vitamin D3 toxicity were not observed in nonlactating nonpregnant cows; however, pregnant cows commonly developed severe signs of vitamin D3 toxicity and 10 of 17 cows died. There was widespread metastatic calcification in the cows that died. Because of the extreme toxicity of vitamin D3 in pregnant Jersey cows and the low margin of safety between doses of vitamin D3 that prevent milk fever and doses that induce milk fever, we concluded that vitamin D3 cannot be used practically to prevent milk fever when injected several weeks prepartum.", "entity": "Hypercalcemia", "aliases": "Hypercalcemia Hypercalcemias Milk Alkali Syndrome Milk-Alkali", "definition": "Abnormally high level of calcium in the blood.\n    ", "id": "MESH:D006934"}
{"mention": "hyperphosphatemia", "mention_text": "Large parenteral doses of vitamin D3 (15 to 17.5 x 10(6) IU vitamin D3) were associated with prolonged hypercalcemia, hyperphosphatemia, and large increases of vitamin D3 and its metabolites in the blood plasma of nonlactating nonpregnant and pregnant Jersey cows. Calcium concentrations 1 day postpartum were higher in cows treated with vitamin D3 about 32 days prepartum (8.8 mg/100 ml) than in control cows (5.5 mg/100 ml). None of the cows treated with vitamin D3 showed signs of milk fever during the peripartal period; however, 22% of the control cows developed clinical signs of milk fever during this period. Signs of vitamin D3 toxicity were not observed in nonlactating nonpregnant cows; however, pregnant cows commonly developed severe signs of vitamin D3 toxicity and 10 of 17 cows died. There was widespread metastatic calcification in the cows that died. Because of the extreme toxicity of vitamin D3 in pregnant Jersey cows and the low margin of safety between doses of vitamin D3 that prevent milk fever and doses that induce milk fever, we concluded that vitamin D3 cannot be used practically to prevent milk fever when injected several weeks prepartum.", "entity": "Hyperphosphatemia", "aliases": "Hyperphosphatemia Hyperphosphatemias", "definition": "A condition of abnormally high level of PHOSPHATES in the blood, usually significantly above the normal range of 0.84-1.58 mmol per liter of serum.\n    ", "id": "MESH:D054559"}
{"mention": "Calcium", "mention_text": "Large parenteral doses of vitamin D3 (15 to 17.5 x 10(6) IU vitamin D3) were associated with prolonged hypercalcemia, hyperphosphatemia, and large increases of vitamin D3 and its metabolites in the blood plasma of nonlactating nonpregnant and pregnant Jersey cows. Calcium concentrations 1 day postpartum were higher in cows treated with vitamin D3 about 32 days prepartum (8.8 mg/100 ml) than in control cows (5.5 mg/100 ml). None of the cows treated with vitamin D3 showed signs of milk fever during the peripartal period; however, 22% of the control cows developed clinical signs of milk fever during this period. Signs of vitamin D3 toxicity were not observed in nonlactating nonpregnant cows; however, pregnant cows commonly developed severe signs of vitamin D3 toxicity and 10 of 17 cows died. There was widespread metastatic calcification in the cows that died. Because of the extreme toxicity of vitamin D3 in pregnant Jersey cows and the low margin of safety between doses of vitamin D3 that prevent milk fever and doses that induce milk fever, we concluded that vitamin D3 cannot be used practically to prevent milk fever when injected several weeks prepartum.", "entity": "Calcium", "aliases": "Blood Coagulation Factor IV Calcium", "definition": "A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.\n    ", "id": "MESH:D002118"}
{"mention": "milk fever", "mention_text": "Large parenteral doses of vitamin D3 (15 to 17.5 x 10(6) IU vitamin D3) were associated with prolonged hypercalcemia, hyperphosphatemia, and large increases of vitamin D3 and its metabolites in the blood plasma of nonlactating nonpregnant and pregnant Jersey cows. Calcium concentrations 1 day postpartum were higher in cows treated with vitamin D3 about 32 days prepartum (8.8 mg/100 ml) than in control cows (5.5 mg/100 ml). None of the cows treated with vitamin D3 showed signs of milk fever during the peripartal period; however, 22% of the control cows developed clinical signs of milk fever during this period. Signs of vitamin D3 toxicity were not observed in nonlactating nonpregnant cows; however, pregnant cows commonly developed severe signs of vitamin D3 toxicity and 10 of 17 cows died. There was widespread metastatic calcification in the cows that died. Because of the extreme toxicity of vitamin D3 in pregnant Jersey cows and the low margin of safety between doses of vitamin D3 that prevent milk fever and doses that induce milk fever, we concluded that vitamin D3 cannot be used practically to prevent milk fever when injected several weeks prepartum.", "entity": "Parturient Paresis", "aliases": "Animal Milk Fever Pareses Parturient Paresis", "definition": "A disease of pregnant and lactating cows and ewes leading to generalized paresis and death. The disease, which is characterized by hypocalcemia, occurs at or shortly after parturition in cows and within weeks before or after parturition in ewes.\n    ", "id": "MESH:D010319"}
{"mention": "toxicity", "mention_text": "Large parenteral doses of vitamin D3 (15 to 17.5 x 10(6) IU vitamin D3) were associated with prolonged hypercalcemia, hyperphosphatemia, and large increases of vitamin D3 and its metabolites in the blood plasma of nonlactating nonpregnant and pregnant Jersey cows. Calcium concentrations 1 day postpartum were higher in cows treated with vitamin D3 about 32 days prepartum (8.8 mg/100 ml) than in control cows (5.5 mg/100 ml). None of the cows treated with vitamin D3 showed signs of milk fever during the peripartal period; however, 22% of the control cows developed clinical signs of milk fever during this period. Signs of vitamin D3 toxicity were not observed in nonlactating nonpregnant cows; however, pregnant cows commonly developed severe signs of vitamin D3 toxicity and 10 of 17 cows died. There was widespread metastatic calcification in the cows that died. Because of the extreme toxicity of vitamin D3 in pregnant Jersey cows and the low margin of safety between doses of vitamin D3 that prevent milk fever and doses that induce milk fever, we concluded that vitamin D3 cannot be used practically to prevent milk fever when injected several weeks prepartum.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "Diseases of peripheral nerves", "mention_text": "Diseases of peripheral nerves as seen in the Nigerian African.", "entity": "Peripheral Nervous System Diseases", "aliases": "Nerve Disease Peripheral Diseases Neuropathy PNS (Peripheral Nervous System) System Disorders Neuropathies", "definition": "Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.\n    ", "id": "MESH:D010523"}
{"mention": "peripheral nerve disease", "mention_text": "The anatomical and aetiological diagnoses of peripheral nerve disease excluding its primary benign and malignant disorders, as seen in 358 Nigerians are presented. There is a male preponderance and the peak incidence is in the fourth decade. Sensori-motor neuropathy was the commonest presentation (50%). Guillain-Barr   syndrome was the commonest identifiable cause (15.6%), accounting for half of the cases with motor neuropathy. Peripheral neuropathy due to nutritional deficiency of thiamine and riboflavin was common (10.1%) and presented mainly as sensory and sensori-motor neuropathy. Diabetes mellitus was the major cause of autonomic neuropathy. Isoniazid was the most frequent agent in drug-induced neuropathy. Migraine (20%) was not an uncommon cause of cranial neuropathy although malignancies arising from the reticuloendothelial system or related structures of the head and neck were more frequent (26%). In 26.5% of all the cases, the aetiology of the neuropathy was undetermined. Heredofamilial and connective tissue disorders were rare. Some of the factors related to the clinical presentation and pathogenesis of the neuropathies are briefly discussed.", "entity": "Peripheral Nervous System Diseases", "aliases": "Nerve Disease Peripheral Diseases Neuropathy PNS (Peripheral Nervous System) System Disorders Neuropathies", "definition": "Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.\n    ", "id": "MESH:D010523"}
{"mention": "Sensori-motor neuropathy", "mention_text": "The anatomical and aetiological diagnoses of peripheral nerve disease excluding its primary benign and malignant disorders, as seen in 358 Nigerians are presented. There is a male preponderance and the peak incidence is in the fourth decade. Sensori-motor neuropathy was the commonest presentation (50%). Guillain-Barr   syndrome was the commonest identifiable cause (15.6%), accounting for half of the cases with motor neuropathy. Peripheral neuropathy due to nutritional deficiency of thiamine and riboflavin was common (10.1%) and presented mainly as sensory and sensori-motor neuropathy. Diabetes mellitus was the major cause of autonomic neuropathy. Isoniazid was the most frequent agent in drug-induced neuropathy. Migraine (20%) was not an uncommon cause of cranial neuropathy although malignancies arising from the reticuloendothelial system or related structures of the head and neck were more frequent (26%). In 26.5% of all the cases, the aetiology of the neuropathy was undetermined. Heredofamilial and connective tissue disorders were rare. Some of the factors related to the clinical presentation and pathogenesis of the neuropathies are briefly discussed.", "entity": "Peripheral Nervous System Diseases", "aliases": "Nerve Disease Peripheral Diseases Neuropathy PNS (Peripheral Nervous System) System Disorders Neuropathies", "definition": "Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.\n    ", "id": "MESH:D010523"}
{"mention": "Guillain-Barr   syndrome", "mention_text": "The anatomical and aetiological diagnoses of peripheral nerve disease excluding its primary benign and malignant disorders, as seen in 358 Nigerians are presented. There is a male preponderance and the peak incidence is in the fourth decade. Sensori-motor neuropathy was the commonest presentation (50%). Guillain-Barr   syndrome was the commonest identifiable cause (15.6%), accounting for half of the cases with motor neuropathy. Peripheral neuropathy due to nutritional deficiency of thiamine and riboflavin was common (10.1%) and presented mainly as sensory and sensori-motor neuropathy. Diabetes mellitus was the major cause of autonomic neuropathy. Isoniazid was the most frequent agent in drug-induced neuropathy. Migraine (20%) was not an uncommon cause of cranial neuropathy although malignancies arising from the reticuloendothelial system or related structures of the head and neck were more frequent (26%). In 26.5% of all the cases, the aetiology of the neuropathy was undetermined. Heredofamilial and connective tissue disorders were rare. Some of the factors related to the clinical presentation and pathogenesis of the neuropathies are briefly discussed.", "entity": "Guillain-Barre Syndrome", "aliases": "Acute Autoimmune Neuropathies Neuropathy Infectious Polyneuritis Inflammatory Demyelinating Polyneuropathy Polyradiculoneuropathy Polyneuropathies Polyradiculoneuropathies Guillain Barre Syndrome Guillain-Barre Familial Guillain-Barré Guillaine Guillaine-Barre Acutes Landry Landry-Guillain-Barre", "definition": "An acute inflammatory autoimmune neuritis caused by T cell- mediated cellular immune response directed towards peripheral myelin. Demyelination occurs in peripheral nerves and nerve roots. The process is often preceded by a viral or bacterial infection, surgery, immunization, lymphoma, or exposure to toxins. Common clinical manifestations include progressive weakness, loss of sensation, and loss of deep tendon reflexes. Weakness of respiratory muscles and autonomic dysfunction may occur. (From Adams et al., Principles of Neurology, 6th ed, pp1312-1314)\n    ", "id": "MESH:D020275"}
{"mention": "motor neuropathy", "mention_text": "The anatomical and aetiological diagnoses of peripheral nerve disease excluding its primary benign and malignant disorders, as seen in 358 Nigerians are presented. There is a male preponderance and the peak incidence is in the fourth decade. Sensori-motor neuropathy was the commonest presentation (50%). Guillain-Barr   syndrome was the commonest identifiable cause (15.6%), accounting for half of the cases with motor neuropathy. Peripheral neuropathy due to nutritional deficiency of thiamine and riboflavin was common (10.1%) and presented mainly as sensory and sensori-motor neuropathy. Diabetes mellitus was the major cause of autonomic neuropathy. Isoniazid was the most frequent agent in drug-induced neuropathy. Migraine (20%) was not an uncommon cause of cranial neuropathy although malignancies arising from the reticuloendothelial system or related structures of the head and neck were more frequent (26%). In 26.5% of all the cases, the aetiology of the neuropathy was undetermined. Heredofamilial and connective tissue disorders were rare. Some of the factors related to the clinical presentation and pathogenesis of the neuropathies are briefly discussed.", "entity": "Peripheral Nervous System Diseases", "aliases": "Nerve Disease Peripheral Diseases Neuropathy PNS (Peripheral Nervous System) System Disorders Neuropathies", "definition": "Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.\n    ", "id": "MESH:D010523"}
{"mention": "Peripheral neuropathy", "mention_text": "The anatomical and aetiological diagnoses of peripheral nerve disease excluding its primary benign and malignant disorders, as seen in 358 Nigerians are presented. There is a male preponderance and the peak incidence is in the fourth decade. Sensori-motor neuropathy was the commonest presentation (50%). Guillain-Barr   syndrome was the commonest identifiable cause (15.6%), accounting for half of the cases with motor neuropathy. Peripheral neuropathy due to nutritional deficiency of thiamine and riboflavin was common (10.1%) and presented mainly as sensory and sensori-motor neuropathy. Diabetes mellitus was the major cause of autonomic neuropathy. Isoniazid was the most frequent agent in drug-induced neuropathy. Migraine (20%) was not an uncommon cause of cranial neuropathy although malignancies arising from the reticuloendothelial system or related structures of the head and neck were more frequent (26%). In 26.5% of all the cases, the aetiology of the neuropathy was undetermined. Heredofamilial and connective tissue disorders were rare. Some of the factors related to the clinical presentation and pathogenesis of the neuropathies are briefly discussed.", "entity": "Peripheral Nervous System Diseases", "aliases": "Nerve Disease Peripheral Diseases Neuropathy PNS (Peripheral Nervous System) System Disorders Neuropathies", "definition": "Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.\n    ", "id": "MESH:D010523"}
{"mention": "nutritional deficiency", "mention_text": "The anatomical and aetiological diagnoses of peripheral nerve disease excluding its primary benign and malignant disorders, as seen in 358 Nigerians are presented. There is a male preponderance and the peak incidence is in the fourth decade. Sensori-motor neuropathy was the commonest presentation (50%). Guillain-Barr   syndrome was the commonest identifiable cause (15.6%), accounting for half of the cases with motor neuropathy. Peripheral neuropathy due to nutritional deficiency of thiamine and riboflavin was common (10.1%) and presented mainly as sensory and sensori-motor neuropathy. Diabetes mellitus was the major cause of autonomic neuropathy. Isoniazid was the most frequent agent in drug-induced neuropathy. Migraine (20%) was not an uncommon cause of cranial neuropathy although malignancies arising from the reticuloendothelial system or related structures of the head and neck were more frequent (26%). In 26.5% of all the cases, the aetiology of the neuropathy was undetermined. Heredofamilial and connective tissue disorders were rare. Some of the factors related to the clinical presentation and pathogenesis of the neuropathies are briefly discussed.", "entity": "Malnutrition", "aliases": "Malnutrition Nutritional Deficiencies Deficiency Undernutrition", "definition": "An imbalanced nutritional status resulted from insufficient intake of nutrients to meet normal physiological requirement.\n    ", "id": "MESH:D044342"}
{"mention": "thiamine", "mention_text": "The anatomical and aetiological diagnoses of peripheral nerve disease excluding its primary benign and malignant disorders, as seen in 358 Nigerians are presented. There is a male preponderance and the peak incidence is in the fourth decade. Sensori-motor neuropathy was the commonest presentation (50%). Guillain-Barr   syndrome was the commonest identifiable cause (15.6%), accounting for half of the cases with motor neuropathy. Peripheral neuropathy due to nutritional deficiency of thiamine and riboflavin was common (10.1%) and presented mainly as sensory and sensori-motor neuropathy. Diabetes mellitus was the major cause of autonomic neuropathy. Isoniazid was the most frequent agent in drug-induced neuropathy. Migraine (20%) was not an uncommon cause of cranial neuropathy although malignancies arising from the reticuloendothelial system or related structures of the head and neck were more frequent (26%). In 26.5% of all the cases, the aetiology of the neuropathy was undetermined. Heredofamilial and connective tissue disorders were rare. Some of the factors related to the clinical presentation and pathogenesis of the neuropathies are briefly discussed.", "entity": "Thiamine", "aliases": "Aneurin Mononitrate Thiamine Vitamin B 1 B1", "definition": "3-((4-Amino-2-methyl-5-pyrimidinyl)methyl)-5-(2- hydroxyethyl)-4-methylthiazolium chloride.\n    ", "id": "MESH:D013831"}
{"mention": "riboflavin", "mention_text": "The anatomical and aetiological diagnoses of peripheral nerve disease excluding its primary benign and malignant disorders, as seen in 358 Nigerians are presented. There is a male preponderance and the peak incidence is in the fourth decade. Sensori-motor neuropathy was the commonest presentation (50%). Guillain-Barr   syndrome was the commonest identifiable cause (15.6%), accounting for half of the cases with motor neuropathy. Peripheral neuropathy due to nutritional deficiency of thiamine and riboflavin was common (10.1%) and presented mainly as sensory and sensori-motor neuropathy. Diabetes mellitus was the major cause of autonomic neuropathy. Isoniazid was the most frequent agent in drug-induced neuropathy. Migraine (20%) was not an uncommon cause of cranial neuropathy although malignancies arising from the reticuloendothelial system or related structures of the head and neck were more frequent (26%). In 26.5% of all the cases, the aetiology of the neuropathy was undetermined. Heredofamilial and connective tissue disorders were rare. Some of the factors related to the clinical presentation and pathogenesis of the neuropathies are briefly discussed.", "entity": "Riboflavin", "aliases": "Riboflavin Vitamin B 2 B2 G", "definition": "Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FLAVIN MONONUCLEOTIDE and FLAVIN-ADENINE DINUCLEOTIDE.\n    ", "id": "MESH:D012256"}
{"mention": "sensori-motor neuropathy", "mention_text": "The anatomical and aetiological diagnoses of peripheral nerve disease excluding its primary benign and malignant disorders, as seen in 358 Nigerians are presented. There is a male preponderance and the peak incidence is in the fourth decade. Sensori-motor neuropathy was the commonest presentation (50%). Guillain-Barr   syndrome was the commonest identifiable cause (15.6%), accounting for half of the cases with motor neuropathy. Peripheral neuropathy due to nutritional deficiency of thiamine and riboflavin was common (10.1%) and presented mainly as sensory and sensori-motor neuropathy. Diabetes mellitus was the major cause of autonomic neuropathy. Isoniazid was the most frequent agent in drug-induced neuropathy. Migraine (20%) was not an uncommon cause of cranial neuropathy although malignancies arising from the reticuloendothelial system or related structures of the head and neck were more frequent (26%). In 26.5% of all the cases, the aetiology of the neuropathy was undetermined. Heredofamilial and connective tissue disorders were rare. Some of the factors related to the clinical presentation and pathogenesis of the neuropathies are briefly discussed.", "entity": "Peripheral Nervous System Diseases", "aliases": "Nerve Disease Peripheral Diseases Neuropathy PNS (Peripheral Nervous System) System Disorders Neuropathies", "definition": "Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.\n    ", "id": "MESH:D010523"}
{"mention": "Diabetes mellitus", "mention_text": "The anatomical and aetiological diagnoses of peripheral nerve disease excluding its primary benign and malignant disorders, as seen in 358 Nigerians are presented. There is a male preponderance and the peak incidence is in the fourth decade. Sensori-motor neuropathy was the commonest presentation (50%). Guillain-Barr   syndrome was the commonest identifiable cause (15.6%), accounting for half of the cases with motor neuropathy. Peripheral neuropathy due to nutritional deficiency of thiamine and riboflavin was common (10.1%) and presented mainly as sensory and sensori-motor neuropathy. Diabetes mellitus was the major cause of autonomic neuropathy. Isoniazid was the most frequent agent in drug-induced neuropathy. Migraine (20%) was not an uncommon cause of cranial neuropathy although malignancies arising from the reticuloendothelial system or related structures of the head and neck were more frequent (26%). In 26.5% of all the cases, the aetiology of the neuropathy was undetermined. Heredofamilial and connective tissue disorders were rare. Some of the factors related to the clinical presentation and pathogenesis of the neuropathies are briefly discussed.", "entity": "Diabetes Mellitus", "aliases": "Diabetes Mellitus", "definition": "A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.\n    ", "id": "MESH:D003920"}
{"mention": "autonomic neuropathy", "mention_text": "The anatomical and aetiological diagnoses of peripheral nerve disease excluding its primary benign and malignant disorders, as seen in 358 Nigerians are presented. There is a male preponderance and the peak incidence is in the fourth decade. Sensori-motor neuropathy was the commonest presentation (50%). Guillain-Barr   syndrome was the commonest identifiable cause (15.6%), accounting for half of the cases with motor neuropathy. Peripheral neuropathy due to nutritional deficiency of thiamine and riboflavin was common (10.1%) and presented mainly as sensory and sensori-motor neuropathy. Diabetes mellitus was the major cause of autonomic neuropathy. Isoniazid was the most frequent agent in drug-induced neuropathy. Migraine (20%) was not an uncommon cause of cranial neuropathy although malignancies arising from the reticuloendothelial system or related structures of the head and neck were more frequent (26%). In 26.5% of all the cases, the aetiology of the neuropathy was undetermined. Heredofamilial and connective tissue disorders were rare. Some of the factors related to the clinical presentation and pathogenesis of the neuropathies are briefly discussed.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "Isoniazid", "mention_text": "The anatomical and aetiological diagnoses of peripheral nerve disease excluding its primary benign and malignant disorders, as seen in 358 Nigerians are presented. There is a male preponderance and the peak incidence is in the fourth decade. Sensori-motor neuropathy was the commonest presentation (50%). Guillain-Barr   syndrome was the commonest identifiable cause (15.6%), accounting for half of the cases with motor neuropathy. Peripheral neuropathy due to nutritional deficiency of thiamine and riboflavin was common (10.1%) and presented mainly as sensory and sensori-motor neuropathy. Diabetes mellitus was the major cause of autonomic neuropathy. Isoniazid was the most frequent agent in drug-induced neuropathy. Migraine (20%) was not an uncommon cause of cranial neuropathy although malignancies arising from the reticuloendothelial system or related structures of the head and neck were more frequent (26%). In 26.5% of all the cases, the aetiology of the neuropathy was undetermined. Heredofamilial and connective tissue disorders were rare. Some of the factors related to the clinical presentation and pathogenesis of the neuropathies are briefly discussed.", "entity": "Isoniazid", "aliases": "Acid Vanillylidenehydrazide Isonicotinic Ftivazide Hydrazide Isonex Isoniazid Phthivazid Phthivazide Tubazide", "definition": "Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis.\n    ", "id": "MESH:D007538"}
{"mention": "neuropathy", "mention_text": "The anatomical and aetiological diagnoses of peripheral nerve disease excluding its primary benign and malignant disorders, as seen in 358 Nigerians are presented. There is a male preponderance and the peak incidence is in the fourth decade. Sensori-motor neuropathy was the commonest presentation (50%). Guillain-Barr   syndrome was the commonest identifiable cause (15.6%), accounting for half of the cases with motor neuropathy. Peripheral neuropathy due to nutritional deficiency of thiamine and riboflavin was common (10.1%) and presented mainly as sensory and sensori-motor neuropathy. Diabetes mellitus was the major cause of autonomic neuropathy. Isoniazid was the most frequent agent in drug-induced neuropathy. Migraine (20%) was not an uncommon cause of cranial neuropathy although malignancies arising from the reticuloendothelial system or related structures of the head and neck were more frequent (26%). In 26.5% of all the cases, the aetiology of the neuropathy was undetermined. Heredofamilial and connective tissue disorders were rare. Some of the factors related to the clinical presentation and pathogenesis of the neuropathies are briefly discussed.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "Migraine", "mention_text": "The anatomical and aetiological diagnoses of peripheral nerve disease excluding its primary benign and malignant disorders, as seen in 358 Nigerians are presented. There is a male preponderance and the peak incidence is in the fourth decade. Sensori-motor neuropathy was the commonest presentation (50%). Guillain-Barr   syndrome was the commonest identifiable cause (15.6%), accounting for half of the cases with motor neuropathy. Peripheral neuropathy due to nutritional deficiency of thiamine and riboflavin was common (10.1%) and presented mainly as sensory and sensori-motor neuropathy. Diabetes mellitus was the major cause of autonomic neuropathy. Isoniazid was the most frequent agent in drug-induced neuropathy. Migraine (20%) was not an uncommon cause of cranial neuropathy although malignancies arising from the reticuloendothelial system or related structures of the head and neck were more frequent (26%). In 26.5% of all the cases, the aetiology of the neuropathy was undetermined. Heredofamilial and connective tissue disorders were rare. Some of the factors related to the clinical presentation and pathogenesis of the neuropathies are briefly discussed.", "entity": "Migraine Disorders", "aliases": "Abdominal Migraine Migraines Acute Confusional Cervical Syndrome Syndromes Disorder Disorders Headache Sick Headaches Hemicrania Variant Variants Status Migrainosus", "definition": "A class of disabling primary headache disorders, characterized by recurrent unilateral pulsatile headaches. The two major subtypes are common migraine (without aura) and classic migraine (with aura or neurological symptoms). (International Classification of Headache Disorders, 2nd ed. Cephalalgia 2004: suppl 1)\n    ", "id": "MESH:D008881"}
{"mention": "cranial neuropathy", "mention_text": "The anatomical and aetiological diagnoses of peripheral nerve disease excluding its primary benign and malignant disorders, as seen in 358 Nigerians are presented. There is a male preponderance and the peak incidence is in the fourth decade. Sensori-motor neuropathy was the commonest presentation (50%). Guillain-Barr   syndrome was the commonest identifiable cause (15.6%), accounting for half of the cases with motor neuropathy. Peripheral neuropathy due to nutritional deficiency of thiamine and riboflavin was common (10.1%) and presented mainly as sensory and sensori-motor neuropathy. Diabetes mellitus was the major cause of autonomic neuropathy. Isoniazid was the most frequent agent in drug-induced neuropathy. Migraine (20%) was not an uncommon cause of cranial neuropathy although malignancies arising from the reticuloendothelial system or related structures of the head and neck were more frequent (26%). In 26.5% of all the cases, the aetiology of the neuropathy was undetermined. Heredofamilial and connective tissue disorders were rare. Some of the factors related to the clinical presentation and pathogenesis of the neuropathies are briefly discussed.", "entity": "Cranial Nerve Diseases", "aliases": "Cranial Nerve Disease Diseases Disorder Disorders Palsies Palsy Neuropathies Multiple Neuropathy Nervus Cranialis", "definition": "Disorders of one or more of the twelve cranial nerves. With the exception of the optic and olfactory nerves, this includes disorders of the brain stem nuclei from which the cranial nerves originate or terminate.\n    ", "id": "MESH:D003389"}
{"mention": "malignancies", "mention_text": "The anatomical and aetiological diagnoses of peripheral nerve disease excluding its primary benign and malignant disorders, as seen in 358 Nigerians are presented. There is a male preponderance and the peak incidence is in the fourth decade. Sensori-motor neuropathy was the commonest presentation (50%). Guillain-Barr   syndrome was the commonest identifiable cause (15.6%), accounting for half of the cases with motor neuropathy. Peripheral neuropathy due to nutritional deficiency of thiamine and riboflavin was common (10.1%) and presented mainly as sensory and sensori-motor neuropathy. Diabetes mellitus was the major cause of autonomic neuropathy. Isoniazid was the most frequent agent in drug-induced neuropathy. Migraine (20%) was not an uncommon cause of cranial neuropathy although malignancies arising from the reticuloendothelial system or related structures of the head and neck were more frequent (26%). In 26.5% of all the cases, the aetiology of the neuropathy was undetermined. Heredofamilial and connective tissue disorders were rare. Some of the factors related to the clinical presentation and pathogenesis of the neuropathies are briefly discussed.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "connective tissue disorders", "mention_text": "The anatomical and aetiological diagnoses of peripheral nerve disease excluding its primary benign and malignant disorders, as seen in 358 Nigerians are presented. There is a male preponderance and the peak incidence is in the fourth decade. Sensori-motor neuropathy was the commonest presentation (50%). Guillain-Barr   syndrome was the commonest identifiable cause (15.6%), accounting for half of the cases with motor neuropathy. Peripheral neuropathy due to nutritional deficiency of thiamine and riboflavin was common (10.1%) and presented mainly as sensory and sensori-motor neuropathy. Diabetes mellitus was the major cause of autonomic neuropathy. Isoniazid was the most frequent agent in drug-induced neuropathy. Migraine (20%) was not an uncommon cause of cranial neuropathy although malignancies arising from the reticuloendothelial system or related structures of the head and neck were more frequent (26%). In 26.5% of all the cases, the aetiology of the neuropathy was undetermined. Heredofamilial and connective tissue disorders were rare. Some of the factors related to the clinical presentation and pathogenesis of the neuropathies are briefly discussed.", "entity": "Connective Tissue Diseases", "aliases": "Connective Tissue Disease Diseases", "definition": "A heterogeneous group of disorders, some hereditary, others acquired, characterized by abnormal structure or function of one or more of the elements of connective tissue, i.e., collagen, elastin, or the mucopolysaccharides.\n    ", "id": "MESH:D003240"}
{"mention": "neuropathies", "mention_text": "The anatomical and aetiological diagnoses of peripheral nerve disease excluding its primary benign and malignant disorders, as seen in 358 Nigerians are presented. There is a male preponderance and the peak incidence is in the fourth decade. Sensori-motor neuropathy was the commonest presentation (50%). Guillain-Barr   syndrome was the commonest identifiable cause (15.6%), accounting for half of the cases with motor neuropathy. Peripheral neuropathy due to nutritional deficiency of thiamine and riboflavin was common (10.1%) and presented mainly as sensory and sensori-motor neuropathy. Diabetes mellitus was the major cause of autonomic neuropathy. Isoniazid was the most frequent agent in drug-induced neuropathy. Migraine (20%) was not an uncommon cause of cranial neuropathy although malignancies arising from the reticuloendothelial system or related structures of the head and neck were more frequent (26%). In 26.5% of all the cases, the aetiology of the neuropathy was undetermined. Heredofamilial and connective tissue disorders were rare. Some of the factors related to the clinical presentation and pathogenesis of the neuropathies are briefly discussed.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "dothiepin hydrochloride", "mention_text": "A double-blind study of the efficacy and safety of dothiepin hydrochloride in the treatment of major depressive disorder.", "entity": "Dothiepin", "aliases": "Dosulepin Dothiepin Hydrochloride Prothiaden", "definition": "A tricyclic antidepressant with some tranquilizing action.\n    ", "id": "MESH:D004308"}
{"mention": "depressive disorder", "mention_text": "A double-blind study of the efficacy and safety of dothiepin hydrochloride in the treatment of major depressive disorder.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "dothiepin", "mention_text": "In a 6-week double-blind parallel treatment study, dothiepin and amitriptyline were compared to placebo in the treatment of 33 depressed outpatients. Dothiepin and amitriptyline were equally effective in alleviating the symptoms of depressive illness, and both were significantly superior to placebo. The overall incidence of side effects and the frequency and severity of blurred vision, dry mouth, and drowsiness were significantly less with dothiepin than with amitriptyline. Dothiepin also produced fewer CNS and cardiovascular effects. There were no clinically important changes in laboratory parameters. Dothiepin thus was found to be an effective antidepressant drug associated with fewer side effects than amitriptyline in the treatment of depressed outpatients.", "entity": "Dothiepin", "aliases": "Dosulepin Dothiepin Hydrochloride Prothiaden", "definition": "A tricyclic antidepressant with some tranquilizing action.\n    ", "id": "MESH:D004308"}
{"mention": "amitriptyline", "mention_text": "In a 6-week double-blind parallel treatment study, dothiepin and amitriptyline were compared to placebo in the treatment of 33 depressed outpatients. Dothiepin and amitriptyline were equally effective in alleviating the symptoms of depressive illness, and both were significantly superior to placebo. The overall incidence of side effects and the frequency and severity of blurred vision, dry mouth, and drowsiness were significantly less with dothiepin than with amitriptyline. Dothiepin also produced fewer CNS and cardiovascular effects. There were no clinically important changes in laboratory parameters. Dothiepin thus was found to be an effective antidepressant drug associated with fewer side effects than amitriptyline in the treatment of depressed outpatients.", "entity": "Amitriptyline", "aliases": "APS Brand of Amitriptyline Hydrochloride Alphapharm Amineurin Amitrip Amitriptylin Desitin RPh beta neuraxpharm Amitriptylin-neuraxpharm Amitriptylinneuraxpharm Amitrol Amrad Anapsique Apo Apo-Amitriptyline ApoAmitriptyline Apotex Bayer Betapharm Cahill May Roberts Embonate DDSA Damilen Domical Douglas Elavil Endep Goldshield Hexal Krewel Laroxyl Lentizol Lundbeck Merck Sharp & Dohme Neuro Novoprotect Parke Davis Protea Psicofarma Rhône Poulenc Rorer Rhône-Poulenc Roche Rodleben Saroten Sarotex ", "definition": "Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antagonize cholinergic and alpha-1 adrenergic responses to bioactive amines.\n    ", "id": "MESH:D000639"}
{"mention": "depressed", "mention_text": "In a 6-week double-blind parallel treatment study, dothiepin and amitriptyline were compared to placebo in the treatment of 33 depressed outpatients. Dothiepin and amitriptyline were equally effective in alleviating the symptoms of depressive illness, and both were significantly superior to placebo. The overall incidence of side effects and the frequency and severity of blurred vision, dry mouth, and drowsiness were significantly less with dothiepin than with amitriptyline. Dothiepin also produced fewer CNS and cardiovascular effects. There were no clinically important changes in laboratory parameters. Dothiepin thus was found to be an effective antidepressant drug associated with fewer side effects than amitriptyline in the treatment of depressed outpatients.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "Dothiepin", "mention_text": "In a 6-week double-blind parallel treatment study, dothiepin and amitriptyline were compared to placebo in the treatment of 33 depressed outpatients. Dothiepin and amitriptyline were equally effective in alleviating the symptoms of depressive illness, and both were significantly superior to placebo. The overall incidence of side effects and the frequency and severity of blurred vision, dry mouth, and drowsiness were significantly less with dothiepin than with amitriptyline. Dothiepin also produced fewer CNS and cardiovascular effects. There were no clinically important changes in laboratory parameters. Dothiepin thus was found to be an effective antidepressant drug associated with fewer side effects than amitriptyline in the treatment of depressed outpatients.", "entity": "Dothiepin", "aliases": "Dosulepin Dothiepin Hydrochloride Prothiaden", "definition": "A tricyclic antidepressant with some tranquilizing action.\n    ", "id": "MESH:D004308"}
{"mention": "depressive illness", "mention_text": "In a 6-week double-blind parallel treatment study, dothiepin and amitriptyline were compared to placebo in the treatment of 33 depressed outpatients. Dothiepin and amitriptyline were equally effective in alleviating the symptoms of depressive illness, and both were significantly superior to placebo. The overall incidence of side effects and the frequency and severity of blurred vision, dry mouth, and drowsiness were significantly less with dothiepin than with amitriptyline. Dothiepin also produced fewer CNS and cardiovascular effects. There were no clinically important changes in laboratory parameters. Dothiepin thus was found to be an effective antidepressant drug associated with fewer side effects than amitriptyline in the treatment of depressed outpatients.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "blurred vision", "mention_text": "In a 6-week double-blind parallel treatment study, dothiepin and amitriptyline were compared to placebo in the treatment of 33 depressed outpatients. Dothiepin and amitriptyline were equally effective in alleviating the symptoms of depressive illness, and both were significantly superior to placebo. The overall incidence of side effects and the frequency and severity of blurred vision, dry mouth, and drowsiness were significantly less with dothiepin than with amitriptyline. Dothiepin also produced fewer CNS and cardiovascular effects. There were no clinically important changes in laboratory parameters. Dothiepin thus was found to be an effective antidepressant drug associated with fewer side effects than amitriptyline in the treatment of depressed outpatients.", "entity": "Vision Disorders", "aliases": "Blindness Day Disabilities Vision Disability Disorder Visual Disorders Hemeralopia Hemeralopias Impairment Impairments Macropsia Macropsias Metamorphopsia Metamorphopsias Micropsia Micropsias", "definition": "Visual impairments limiting one or more of the basic functions of the eye: visual acuity, dark adaptation, color vision, or peripheral vision. These may result from EYE DISEASES; OPTIC NERVE DISEASES; VISUAL PATHWAY diseases; OCCIPITAL LOBE diseases; OCULAR MOTILITY DISORDERS; and other conditions (From Newell, Ophthalmology: Principles and Concepts, 7th ed, p132).\n    ", "id": "MESH:D014786"}
{"mention": "dry mouth", "mention_text": "In a 6-week double-blind parallel treatment study, dothiepin and amitriptyline were compared to placebo in the treatment of 33 depressed outpatients. Dothiepin and amitriptyline were equally effective in alleviating the symptoms of depressive illness, and both were significantly superior to placebo. The overall incidence of side effects and the frequency and severity of blurred vision, dry mouth, and drowsiness were significantly less with dothiepin than with amitriptyline. Dothiepin also produced fewer CNS and cardiovascular effects. There were no clinically important changes in laboratory parameters. Dothiepin thus was found to be an effective antidepressant drug associated with fewer side effects than amitriptyline in the treatment of depressed outpatients.", "entity": "Xerostomia", "aliases": "Asialia Asialias Dryness Mouth Hyposalivation Hyposalivations Xerostomia Xerostomias", "definition": "Decreased salivary flow.\n    ", "id": "MESH:D014987"}
{"mention": "antidepressant", "mention_text": "In a 6-week double-blind parallel treatment study, dothiepin and amitriptyline were compared to placebo in the treatment of 33 depressed outpatients. Dothiepin and amitriptyline were equally effective in alleviating the symptoms of depressive illness, and both were significantly superior to placebo. The overall incidence of side effects and the frequency and severity of blurred vision, dry mouth, and drowsiness were significantly less with dothiepin than with amitriptyline. Dothiepin also produced fewer CNS and cardiovascular effects. There were no clinically important changes in laboratory parameters. Dothiepin thus was found to be an effective antidepressant drug associated with fewer side effects than amitriptyline in the treatment of depressed outpatients.", "entity": "Antidepressive Agents", "aliases": "Agents Antidepressive Antidepressant Drugs Antidepressants Thymoanaleptics Thymoleptics", "definition": "Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.\n    ", "id": "MESH:D000928"}
{"mention": "diazepam", "mention_text": "Behavioral effects of diazepam and propranolol in patients with panic disorder and agoraphobia.", "entity": "Diazepam", "aliases": "7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one Apaurin Diazemuls Diazepam Faustan Relanium Seduxen Sibazon Stesolid Valium", "definition": "A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity.\n    ", "id": "MESH:D003975"}
{"mention": "propranolol", "mention_text": "Behavioral effects of diazepam and propranolol in patients with panic disorder and agoraphobia.", "entity": "Propranolol", "aliases": "AY 20694 AY-20694 AY20694 Anaprilin Anapriline Avlocardyl Betadren Dexpropranolol Dociton Hydrochloride Propranolol Inderal Obsidan Obzidan Propanolol Rexigen", "definition": "A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.\n    ", "id": "MESH:D011433"}
{"mention": "panic disorder", "mention_text": "Behavioral effects of diazepam and propranolol in patients with panic disorder and agoraphobia.", "entity": "Panic Disorder", "aliases": "Attack Panic Attacks Disorder Disorders", "definition": "A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait.\n    ", "id": "MESH:D016584"}
{"mention": "agoraphobia", "mention_text": "Behavioral effects of diazepam and propranolol in patients with panic disorder and agoraphobia.", "entity": "Agoraphobia", "aliases": "Agoraphobia Agoraphobias", "definition": "Obsessive, persistent, intense fear of open places.\n    ", "id": "MESH:D000379"}
{"mention": "diazepam", "mention_text": "The effects of oral doses of diazepam (single dose of 10 mg and a median dose of 30 mg/day for 2 weeks) and propranolol (single dose of 80 mg and a median dose of 240 mg/day for 2 weeks) on psychological performance of patients with panic disorders and agoraphobia were investigated in a double-blind, randomized and crossover design. Both drugs impaired immediate free recall but the decrease was greater for diazepam than propranolol. Delayed free recall was also impaired but the two drugs did not differ. Patients tapped faster after propranolol than diazepam and they were more sedated after diazepam than propranolol. After 2 weeks of treatment, patients tested 5-8 h after the last dose of medication did not show any decrement of performance. These results are similar to those previously found in healthy subjects. Accumulation of drugs was not reflected in prolonged behavioral impairment.", "entity": "Diazepam", "aliases": "7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one Apaurin Diazemuls Diazepam Faustan Relanium Seduxen Sibazon Stesolid Valium", "definition": "A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity.\n    ", "id": "MESH:D003975"}
{"mention": "propranolol", "mention_text": "The effects of oral doses of diazepam (single dose of 10 mg and a median dose of 30 mg/day for 2 weeks) and propranolol (single dose of 80 mg and a median dose of 240 mg/day for 2 weeks) on psychological performance of patients with panic disorders and agoraphobia were investigated in a double-blind, randomized and crossover design. Both drugs impaired immediate free recall but the decrease was greater for diazepam than propranolol. Delayed free recall was also impaired but the two drugs did not differ. Patients tapped faster after propranolol than diazepam and they were more sedated after diazepam than propranolol. After 2 weeks of treatment, patients tested 5-8 h after the last dose of medication did not show any decrement of performance. These results are similar to those previously found in healthy subjects. Accumulation of drugs was not reflected in prolonged behavioral impairment.", "entity": "Propranolol", "aliases": "AY 20694 AY-20694 AY20694 Anaprilin Anapriline Avlocardyl Betadren Dexpropranolol Dociton Hydrochloride Propranolol Inderal Obsidan Obzidan Propanolol Rexigen", "definition": "A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.\n    ", "id": "MESH:D011433"}
{"mention": "panic disorders", "mention_text": "The effects of oral doses of diazepam (single dose of 10 mg and a median dose of 30 mg/day for 2 weeks) and propranolol (single dose of 80 mg and a median dose of 240 mg/day for 2 weeks) on psychological performance of patients with panic disorders and agoraphobia were investigated in a double-blind, randomized and crossover design. Both drugs impaired immediate free recall but the decrease was greater for diazepam than propranolol. Delayed free recall was also impaired but the two drugs did not differ. Patients tapped faster after propranolol than diazepam and they were more sedated after diazepam than propranolol. After 2 weeks of treatment, patients tested 5-8 h after the last dose of medication did not show any decrement of performance. These results are similar to those previously found in healthy subjects. Accumulation of drugs was not reflected in prolonged behavioral impairment.", "entity": "Panic Disorder", "aliases": "Attack Panic Attacks Disorder Disorders", "definition": "A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait.\n    ", "id": "MESH:D016584"}
{"mention": "agoraphobia", "mention_text": "The effects of oral doses of diazepam (single dose of 10 mg and a median dose of 30 mg/day for 2 weeks) and propranolol (single dose of 80 mg and a median dose of 240 mg/day for 2 weeks) on psychological performance of patients with panic disorders and agoraphobia were investigated in a double-blind, randomized and crossover design. Both drugs impaired immediate free recall but the decrease was greater for diazepam than propranolol. Delayed free recall was also impaired but the two drugs did not differ. Patients tapped faster after propranolol than diazepam and they were more sedated after diazepam than propranolol. After 2 weeks of treatment, patients tested 5-8 h after the last dose of medication did not show any decrement of performance. These results are similar to those previously found in healthy subjects. Accumulation of drugs was not reflected in prolonged behavioral impairment.", "entity": "Agoraphobia", "aliases": "Agoraphobia Agoraphobias", "definition": "Obsessive, persistent, intense fear of open places.\n    ", "id": "MESH:D000379"}
{"mention": "impaired immediate free recall", "mention_text": "The effects of oral doses of diazepam (single dose of 10 mg and a median dose of 30 mg/day for 2 weeks) and propranolol (single dose of 80 mg and a median dose of 240 mg/day for 2 weeks) on psychological performance of patients with panic disorders and agoraphobia were investigated in a double-blind, randomized and crossover design. Both drugs impaired immediate free recall but the decrease was greater for diazepam than propranolol. Delayed free recall was also impaired but the two drugs did not differ. Patients tapped faster after propranolol than diazepam and they were more sedated after diazepam than propranolol. After 2 weeks of treatment, patients tested 5-8 h after the last dose of medication did not show any decrement of performance. These results are similar to those previously found in healthy subjects. Accumulation of drugs was not reflected in prolonged behavioral impairment.", "entity": "Memory Disorders", "aliases": "Age Related Memory Disorders Age-Related Disorder Cognitive Retention Deficit Deficits Semantic Spatial Loss Losses", "definition": "Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions.\n    ", "id": "MESH:D008569"}
{"mention": "Delayed free recall was also impaired", "mention_text": "The effects of oral doses of diazepam (single dose of 10 mg and a median dose of 30 mg/day for 2 weeks) and propranolol (single dose of 80 mg and a median dose of 240 mg/day for 2 weeks) on psychological performance of patients with panic disorders and agoraphobia were investigated in a double-blind, randomized and crossover design. Both drugs impaired immediate free recall but the decrease was greater for diazepam than propranolol. Delayed free recall was also impaired but the two drugs did not differ. Patients tapped faster after propranolol than diazepam and they were more sedated after diazepam than propranolol. After 2 weeks of treatment, patients tested 5-8 h after the last dose of medication did not show any decrement of performance. These results are similar to those previously found in healthy subjects. Accumulation of drugs was not reflected in prolonged behavioral impairment.", "entity": "Memory Disorders", "aliases": "Age Related Memory Disorders Age-Related Disorder Cognitive Retention Deficit Deficits Semantic Spatial Loss Losses", "definition": "Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions.\n    ", "id": "MESH:D008569"}
{"mention": "behavioral impairment", "mention_text": "The effects of oral doses of diazepam (single dose of 10 mg and a median dose of 30 mg/day for 2 weeks) and propranolol (single dose of 80 mg and a median dose of 240 mg/day for 2 weeks) on psychological performance of patients with panic disorders and agoraphobia were investigated in a double-blind, randomized and crossover design. Both drugs impaired immediate free recall but the decrease was greater for diazepam than propranolol. Delayed free recall was also impaired but the two drugs did not differ. Patients tapped faster after propranolol than diazepam and they were more sedated after diazepam than propranolol. After 2 weeks of treatment, patients tested 5-8 h after the last dose of medication did not show any decrement of performance. These results are similar to those previously found in healthy subjects. Accumulation of drugs was not reflected in prolonged behavioral impairment.", "entity": "Mental Disorders", "aliases": "Behavior Disorders Diagnosis Psychiatric Disorder Mental", "definition": "Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.\n    ", "id": "MESH:D001523"}
{"mention": "aspirin", "mention_text": "Effect of aspirin on N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide-induced epithelial proliferation in the urinary bladder and forestomach of the rat.", "entity": "Aspirin", "aliases": "2-(Acetyloxy)benzoic Acid Acetylsalicylic Acetysal Acylpyrin Aloxiprimum Aspirin Colfarit Dispril Easprin Ecotrin Endosprin Magnecyl Micristin Polopirin Polopiryna Solprin Solupsan Zorprin", "definition": "The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)\n    ", "id": "MESH:D001241"}
{"mention": "N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide", "mention_text": "Effect of aspirin on N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide-induced epithelial proliferation in the urinary bladder and forestomach of the rat.", "entity": "FANFT", "aliases": "FANFT N-4-(5-Nitro-2-furyl)-2-thiazolylformamide", "definition": "A potent nitrofuran derivative tumor initiator. It causes bladder tumors in all animals studied and is mutagenic to many bacteria.\n    ", "id": "MESH:D005200"}
{"mention": "aspirin", "mention_text": "The co-administration of aspirin with N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (FANFT) to rats resulted in a reduced incidence of FANFT-induced bladder carcinomas but a concomitant induction of forestomach tumors. An autoradiographic study was performed on male F-344 rats fed diet containing FANFT at a level of 0.2% and/or aspirin at a level of 0.5% to evaluate the effect of aspirin on the increased cell proliferation induced by FANFT in the forestomach and bladder. FANFT-induced cell proliferation in the bladder was significantly suppressed by aspirin co-administration after 4 weeks but not after 12 weeks. In the forestomach, and also in the liver, aspirin did not affect the FANFT-induced increase in labeling index. The present results are consistent with the carcinogenicity experiment suggesting that different mechanisms are involved in FANFT carcinogenesis in the bladder and forestomach, and that aspirin's effect on FANFT in the forestomach is not due to an irritant effect associated with increased cell proliferation. Also, there appears to be an adaptation by the rats to the chronic ingestion of aspirin.", "entity": "Aspirin", "aliases": "2-(Acetyloxy)benzoic Acid Acetylsalicylic Acetysal Acylpyrin Aloxiprimum Aspirin Colfarit Dispril Easprin Ecotrin Endosprin Magnecyl Micristin Polopirin Polopiryna Solprin Solupsan Zorprin", "definition": "The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)\n    ", "id": "MESH:D001241"}
{"mention": "N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide", "mention_text": "The co-administration of aspirin with N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (FANFT) to rats resulted in a reduced incidence of FANFT-induced bladder carcinomas but a concomitant induction of forestomach tumors. An autoradiographic study was performed on male F-344 rats fed diet containing FANFT at a level of 0.2% and/or aspirin at a level of 0.5% to evaluate the effect of aspirin on the increased cell proliferation induced by FANFT in the forestomach and bladder. FANFT-induced cell proliferation in the bladder was significantly suppressed by aspirin co-administration after 4 weeks but not after 12 weeks. In the forestomach, and also in the liver, aspirin did not affect the FANFT-induced increase in labeling index. The present results are consistent with the carcinogenicity experiment suggesting that different mechanisms are involved in FANFT carcinogenesis in the bladder and forestomach, and that aspirin's effect on FANFT in the forestomach is not due to an irritant effect associated with increased cell proliferation. Also, there appears to be an adaptation by the rats to the chronic ingestion of aspirin.", "entity": "FANFT", "aliases": "FANFT N-4-(5-Nitro-2-furyl)-2-thiazolylformamide", "definition": "A potent nitrofuran derivative tumor initiator. It causes bladder tumors in all animals studied and is mutagenic to many bacteria.\n    ", "id": "MESH:D005200"}
{"mention": "FANFT", "mention_text": "The co-administration of aspirin with N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (FANFT) to rats resulted in a reduced incidence of FANFT-induced bladder carcinomas but a concomitant induction of forestomach tumors. An autoradiographic study was performed on male F-344 rats fed diet containing FANFT at a level of 0.2% and/or aspirin at a level of 0.5% to evaluate the effect of aspirin on the increased cell proliferation induced by FANFT in the forestomach and bladder. FANFT-induced cell proliferation in the bladder was significantly suppressed by aspirin co-administration after 4 weeks but not after 12 weeks. In the forestomach, and also in the liver, aspirin did not affect the FANFT-induced increase in labeling index. The present results are consistent with the carcinogenicity experiment suggesting that different mechanisms are involved in FANFT carcinogenesis in the bladder and forestomach, and that aspirin's effect on FANFT in the forestomach is not due to an irritant effect associated with increased cell proliferation. Also, there appears to be an adaptation by the rats to the chronic ingestion of aspirin.", "entity": "FANFT", "aliases": "FANFT N-4-(5-Nitro-2-furyl)-2-thiazolylformamide", "definition": "A potent nitrofuran derivative tumor initiator. It causes bladder tumors in all animals studied and is mutagenic to many bacteria.\n    ", "id": "MESH:D005200"}
{"mention": "bladder carcinomas", "mention_text": "The co-administration of aspirin with N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (FANFT) to rats resulted in a reduced incidence of FANFT-induced bladder carcinomas but a concomitant induction of forestomach tumors. An autoradiographic study was performed on male F-344 rats fed diet containing FANFT at a level of 0.2% and/or aspirin at a level of 0.5% to evaluate the effect of aspirin on the increased cell proliferation induced by FANFT in the forestomach and bladder. FANFT-induced cell proliferation in the bladder was significantly suppressed by aspirin co-administration after 4 weeks but not after 12 weeks. In the forestomach, and also in the liver, aspirin did not affect the FANFT-induced increase in labeling index. The present results are consistent with the carcinogenicity experiment suggesting that different mechanisms are involved in FANFT carcinogenesis in the bladder and forestomach, and that aspirin's effect on FANFT in the forestomach is not due to an irritant effect associated with increased cell proliferation. Also, there appears to be an adaptation by the rats to the chronic ingestion of aspirin.", "entity": "Urinary Bladder Neoplasms", "aliases": "Bladder Cancer Cancers Neoplasm Neoplasms Tumor Tumors of the Urinary Malignant", "definition": "Tumors or cancer of the URINARY BLADDER.\n    ", "id": "MESH:D001749"}
{"mention": "forestomach tumors", "mention_text": "The co-administration of aspirin with N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (FANFT) to rats resulted in a reduced incidence of FANFT-induced bladder carcinomas but a concomitant induction of forestomach tumors. An autoradiographic study was performed on male F-344 rats fed diet containing FANFT at a level of 0.2% and/or aspirin at a level of 0.5% to evaluate the effect of aspirin on the increased cell proliferation induced by FANFT in the forestomach and bladder. FANFT-induced cell proliferation in the bladder was significantly suppressed by aspirin co-administration after 4 weeks but not after 12 weeks. In the forestomach, and also in the liver, aspirin did not affect the FANFT-induced increase in labeling index. The present results are consistent with the carcinogenicity experiment suggesting that different mechanisms are involved in FANFT carcinogenesis in the bladder and forestomach, and that aspirin's effect on FANFT in the forestomach is not due to an irritant effect associated with increased cell proliferation. Also, there appears to be an adaptation by the rats to the chronic ingestion of aspirin.", "entity": "Stomach Neoplasms", "aliases": "Cancer of Stomach the Gastric Cancers Familial Diffuse Neoplasm Neoplasms", "definition": "Tumors or cancer of the STOMACH.\n    ", "id": "MESH:D013274"}
{"mention": "carcinogenesis", "mention_text": "The co-administration of aspirin with N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (FANFT) to rats resulted in a reduced incidence of FANFT-induced bladder carcinomas but a concomitant induction of forestomach tumors. An autoradiographic study was performed on male F-344 rats fed diet containing FANFT at a level of 0.2% and/or aspirin at a level of 0.5% to evaluate the effect of aspirin on the increased cell proliferation induced by FANFT in the forestomach and bladder. FANFT-induced cell proliferation in the bladder was significantly suppressed by aspirin co-administration after 4 weeks but not after 12 weeks. In the forestomach, and also in the liver, aspirin did not affect the FANFT-induced increase in labeling index. The present results are consistent with the carcinogenicity experiment suggesting that different mechanisms are involved in FANFT carcinogenesis in the bladder and forestomach, and that aspirin's effect on FANFT in the forestomach is not due to an irritant effect associated with increased cell proliferation. Also, there appears to be an adaptation by the rats to the chronic ingestion of aspirin.", "entity": "Carcinogenesis", "aliases": "Carcinogeneses Carcinogenesis Oncogeneses Oncogenesis Tumorigeneses Tumorigenesis", "definition": "The origin, production or development of cancer through genotypic and phenotypic changes which upset the normal balance between cell proliferation and cell death. Carcinogenesis generally requires a constellation of steps, which may occur quickly or over a period of many years.\n    ", "id": "MESH:D063646"}
{"mention": "hypotension", "mention_text": "Provocation of postural hypotension by nitroglycerin in diabetic autonomic neuropathy?", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "nitroglycerin", "mention_text": "Provocation of postural hypotension by nitroglycerin in diabetic autonomic neuropathy?", "entity": "Nitroglycerin", "aliases": "Anginine Dynamite Gilustenon Glyceryl Trinitrate Nitrangin Nitro Bid Dur Nitro-Bid Nitro-Dur NitroBid NitroDur Nitrocard Nitroderm TTS Nitroglycerin Nitroglyn Nitrol Nitrolan Nitrong Nitrospan Nitrostat Perlinganit Susadrin Sustac Sustak Sustonit Transderm Tridil Trinitrin Trinitrolong", "definition": "A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives.\n    ", "id": "MESH:D005996"}
{"mention": "diabetic autonomic neuropathy", "mention_text": "Provocation of postural hypotension by nitroglycerin in diabetic autonomic neuropathy?", "entity": "Diabetic Neuropathies", "aliases": "Amyotrophies Diabetic Amyotrophy Asymmetric Proximal Motor Neuropathy Polyneuropathies Polyneuropathy Autonomic Neuropathies Mononeuropathies Mononeuropathy Simplex Simplices Neuralgia Neuralgias Painful Symmetric", "definition": "Peripheral, autonomic, and cranial nerve disorders that are associated with DIABETES MELLITUS. These conditions usually result from diabetic microvascular injury involving small blood vessels that supply nerves (VASA NERVORUM). Relatively common conditions which may be associated with diabetic neuropathy include third nerve palsy (see OCULOMOTOR NERVE DISEASES); MONONEUROPATHY; mononeuropathy multiplex; diabetic amyotrophy; a painful POLYNEUROPATHY; autonomic neuropathy; and thoracoabdominal neuropathy. (From Adams et al., Principles of Neurology, 6th ed, p1325)\n    ", "id": "MESH:D003929"}
{"mention": "nitroglycerin", "mention_text": "The effect of nitroglycerin on heart rate and systolic blood pressure was compared in 5 normal subjects, 12 diabetic subjects without autonomic neuropathy, and 5 diabetic subjects with autonomic neuropathy. The magnitude and time course of the increase in heart rate and the decrease in systolic blood pressure after nitroglycerin were similar in the normal and diabetic subjects without autonomic neuropathy, whereas a lesser increase in heart rate and a greater decrease in systolic blood pressure occurred in the diabetic subjects with autonomic neuropathy. It is therefore suggested that caution should be exercised when prescribing vasodilator drugs in diabetic patients, particularly those with autonomic neuropathy.", "entity": "Nitroglycerin", "aliases": "Anginine Dynamite Gilustenon Glyceryl Trinitrate Nitrangin Nitro Bid Dur Nitro-Bid Nitro-Dur NitroBid NitroDur Nitrocard Nitroderm TTS Nitroglycerin Nitroglyn Nitrol Nitrolan Nitrong Nitrospan Nitrostat Perlinganit Susadrin Sustac Sustak Sustonit Transderm Tridil Trinitrin Trinitrolong", "definition": "A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives.\n    ", "id": "MESH:D005996"}
{"mention": "diabetic", "mention_text": "The effect of nitroglycerin on heart rate and systolic blood pressure was compared in 5 normal subjects, 12 diabetic subjects without autonomic neuropathy, and 5 diabetic subjects with autonomic neuropathy. The magnitude and time course of the increase in heart rate and the decrease in systolic blood pressure after nitroglycerin were similar in the normal and diabetic subjects without autonomic neuropathy, whereas a lesser increase in heart rate and a greater decrease in systolic blood pressure occurred in the diabetic subjects with autonomic neuropathy. It is therefore suggested that caution should be exercised when prescribing vasodilator drugs in diabetic patients, particularly those with autonomic neuropathy.", "entity": "Diabetes Mellitus", "aliases": "Diabetes Mellitus", "definition": "A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.\n    ", "id": "MESH:D003920"}
{"mention": "autonomic neuropathy", "mention_text": "The effect of nitroglycerin on heart rate and systolic blood pressure was compared in 5 normal subjects, 12 diabetic subjects without autonomic neuropathy, and 5 diabetic subjects with autonomic neuropathy. The magnitude and time course of the increase in heart rate and the decrease in systolic blood pressure after nitroglycerin were similar in the normal and diabetic subjects without autonomic neuropathy, whereas a lesser increase in heart rate and a greater decrease in systolic blood pressure occurred in the diabetic subjects with autonomic neuropathy. It is therefore suggested that caution should be exercised when prescribing vasodilator drugs in diabetic patients, particularly those with autonomic neuropathy.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "estrogen", "mention_text": "Characterization of estrogen-induced adenohypophyseal tumors in the Fischer 344 rat.", "entity": "Estrogens", "aliases": "Agents Estrogenic Agonists Estrogen Receptor Compounds Effects Effect Estrogens", "definition": "Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds.\n    ", "id": "MESH:D004967"}
{"mention": "adenohypophyseal tumors", "mention_text": "Characterization of estrogen-induced adenohypophyseal tumors in the Fischer 344 rat.", "entity": "Pituitary Neoplasms", "aliases": "Adenoma Pituitary Adenomas Cancer of the Cancers Carcinoma Carcinomas Neoplasm Neoplasms Tumor Tumors", "definition": "Neoplasms which arise from or metastasize to the PITUITARY GLAND. The majority of pituitary neoplasms are adenomas, which are divided into non-secreting and secreting forms. Hormone producing forms are further classified by the type of hormone they secrete. Pituitary adenomas may also be characterized by their staining properties (see ADENOMA, BASOPHIL; ADENOMA, ACIDOPHIL; and ADENOMA, CHROMOPHOBE). Pituitary tumors may compress adjacent structures, including the HYPOTHALAMUS, several CRANIAL NERVES, and the OPTIC CHIASM. Chiasmal compression may result in bitemporal HEMIANOPSIA.\n    ", "id": "MESH:D010911"}
{"mention": "Pituitary tumors", "mention_text": "Pituitary tumors were induced in F344 female rats by chronic treatment with diethylstilbestrol (DES, 8-10 mg) implanted subcutaneously in silastic capsules. Over a range of 1-150 days of DES treatment, pairs of control and DES-treated rats were sacrificed, and their pituitaries dissociated enzymatically into single-cell preparations. The cell populations were examined regarding total cell recovery correlated with gland weight, intracellular prolactin (PRL) content and subsequent release in primary culture, immunocytochemical PRL staining, density and/or size alterations via separation on Ficoll-Hypaque and by unit gravity sedimentation, and cell cycle analysis, after acriflavine DNA staining, by laser flow cytometry. Total cell yields from DES-treated pituitaries increased from 1.3 times control yields at 8 days of treatment to 58.9 times control values by day 150. Intracellular PRL content ranged from 1.9 to 9.4 times control levels, and PRL release in vitro was significantly and consistently higher than controls, after at least 8 days of DES exposure. Beyond 8 days of DES exposure, the immunochemically PRL-positive proportion of cells increased to over 50% of the total population. Increased density and/or size and PRL content were indicated for the majority of the PRL cell population in both types of separation protocols. All these effects of DES were more pronounced among previously ovariectomized animals. The data extend the findings of other investigators, further establishing the DES-induced tumor as a model for study of PRL cellular control mechanisms.", "entity": "Pituitary Neoplasms", "aliases": "Adenoma Pituitary Adenomas Cancer of the Cancers Carcinoma Carcinomas Neoplasm Neoplasms Tumor Tumors", "definition": "Neoplasms which arise from or metastasize to the PITUITARY GLAND. The majority of pituitary neoplasms are adenomas, which are divided into non-secreting and secreting forms. Hormone producing forms are further classified by the type of hormone they secrete. Pituitary adenomas may also be characterized by their staining properties (see ADENOMA, BASOPHIL; ADENOMA, ACIDOPHIL; and ADENOMA, CHROMOPHOBE). Pituitary tumors may compress adjacent structures, including the HYPOTHALAMUS, several CRANIAL NERVES, and the OPTIC CHIASM. Chiasmal compression may result in bitemporal HEMIANOPSIA.\n    ", "id": "MESH:D010911"}
{"mention": "diethylstilbestrol", "mention_text": "Pituitary tumors were induced in F344 female rats by chronic treatment with diethylstilbestrol (DES, 8-10 mg) implanted subcutaneously in silastic capsules. Over a range of 1-150 days of DES treatment, pairs of control and DES-treated rats were sacrificed, and their pituitaries dissociated enzymatically into single-cell preparations. The cell populations were examined regarding total cell recovery correlated with gland weight, intracellular prolactin (PRL) content and subsequent release in primary culture, immunocytochemical PRL staining, density and/or size alterations via separation on Ficoll-Hypaque and by unit gravity sedimentation, and cell cycle analysis, after acriflavine DNA staining, by laser flow cytometry. Total cell yields from DES-treated pituitaries increased from 1.3 times control yields at 8 days of treatment to 58.9 times control values by day 150. Intracellular PRL content ranged from 1.9 to 9.4 times control levels, and PRL release in vitro was significantly and consistently higher than controls, after at least 8 days of DES exposure. Beyond 8 days of DES exposure, the immunochemically PRL-positive proportion of cells increased to over 50% of the total population. Increased density and/or size and PRL content were indicated for the majority of the PRL cell population in both types of separation protocols. All these effects of DES were more pronounced among previously ovariectomized animals. The data extend the findings of other investigators, further establishing the DES-induced tumor as a model for study of PRL cellular control mechanisms.", "entity": "Diethylstilbestrol", "aliases": "APS Brand of Diethylstilbestrol Agostilben Apstil Co Pharma Co-Pharma (Z)-Isomer Disodium Salt Distilbène Estrogen Stilbene Gerda Stilbestrol Tampovagan", "definition": "A synthetic nonsteroidal estrogen used in the treatment of menopausal and postmenopausal disorders. It was also used formerly as a growth promoter in animals. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), diethylstilbestrol has been listed as a known carcinogen. (Merck, 11th ed)\n    ", "id": "MESH:D004054"}
{"mention": "DES", "mention_text": "Pituitary tumors were induced in F344 female rats by chronic treatment with diethylstilbestrol (DES, 8-10 mg) implanted subcutaneously in silastic capsules. Over a range of 1-150 days of DES treatment, pairs of control and DES-treated rats were sacrificed, and their pituitaries dissociated enzymatically into single-cell preparations. The cell populations were examined regarding total cell recovery correlated with gland weight, intracellular prolactin (PRL) content and subsequent release in primary culture, immunocytochemical PRL staining, density and/or size alterations via separation on Ficoll-Hypaque and by unit gravity sedimentation, and cell cycle analysis, after acriflavine DNA staining, by laser flow cytometry. Total cell yields from DES-treated pituitaries increased from 1.3 times control yields at 8 days of treatment to 58.9 times control values by day 150. Intracellular PRL content ranged from 1.9 to 9.4 times control levels, and PRL release in vitro was significantly and consistently higher than controls, after at least 8 days of DES exposure. Beyond 8 days of DES exposure, the immunochemically PRL-positive proportion of cells increased to over 50% of the total population. Increased density and/or size and PRL content were indicated for the majority of the PRL cell population in both types of separation protocols. All these effects of DES were more pronounced among previously ovariectomized animals. The data extend the findings of other investigators, further establishing the DES-induced tumor as a model for study of PRL cellular control mechanisms.", "entity": "Diethylstilbestrol", "aliases": "APS Brand of Diethylstilbestrol Agostilben Apstil Co Pharma Co-Pharma (Z)-Isomer Disodium Salt Distilbène Estrogen Stilbene Gerda Stilbestrol Tampovagan", "definition": "A synthetic nonsteroidal estrogen used in the treatment of menopausal and postmenopausal disorders. It was also used formerly as a growth promoter in animals. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), diethylstilbestrol has been listed as a known carcinogen. (Merck, 11th ed)\n    ", "id": "MESH:D004054"}
{"mention": "acriflavine", "mention_text": "Pituitary tumors were induced in F344 female rats by chronic treatment with diethylstilbestrol (DES, 8-10 mg) implanted subcutaneously in silastic capsules. Over a range of 1-150 days of DES treatment, pairs of control and DES-treated rats were sacrificed, and their pituitaries dissociated enzymatically into single-cell preparations. The cell populations were examined regarding total cell recovery correlated with gland weight, intracellular prolactin (PRL) content and subsequent release in primary culture, immunocytochemical PRL staining, density and/or size alterations via separation on Ficoll-Hypaque and by unit gravity sedimentation, and cell cycle analysis, after acriflavine DNA staining, by laser flow cytometry. Total cell yields from DES-treated pituitaries increased from 1.3 times control yields at 8 days of treatment to 58.9 times control values by day 150. Intracellular PRL content ranged from 1.9 to 9.4 times control levels, and PRL release in vitro was significantly and consistently higher than controls, after at least 8 days of DES exposure. Beyond 8 days of DES exposure, the immunochemically PRL-positive proportion of cells increased to over 50% of the total population. Increased density and/or size and PRL content were indicated for the majority of the PRL cell population in both types of separation protocols. All these effects of DES were more pronounced among previously ovariectomized animals. The data extend the findings of other investigators, further establishing the DES-induced tumor as a model for study of PRL cellular control mechanisms.", "entity": "Acriflavine", "aliases": "2,8-Diamino-10-Methylacridinium Chloride Mixture With 2,8-Diaminoacridine Acriflavine Xanthacridinum", "definition": "3,6-Diamino-10-methylacridinium chloride mixt. with 3,6-acridinediamine. Fluorescent dye used as a local antiseptic and also as a biological stain. It intercalates into nucleic acids thereby inhibiting bacterial and viral replication.\n    ", "id": "MESH:D000167"}
{"mention": "tumor", "mention_text": "Pituitary tumors were induced in F344 female rats by chronic treatment with diethylstilbestrol (DES, 8-10 mg) implanted subcutaneously in silastic capsules. Over a range of 1-150 days of DES treatment, pairs of control and DES-treated rats were sacrificed, and their pituitaries dissociated enzymatically into single-cell preparations. The cell populations were examined regarding total cell recovery correlated with gland weight, intracellular prolactin (PRL) content and subsequent release in primary culture, immunocytochemical PRL staining, density and/or size alterations via separation on Ficoll-Hypaque and by unit gravity sedimentation, and cell cycle analysis, after acriflavine DNA staining, by laser flow cytometry. Total cell yields from DES-treated pituitaries increased from 1.3 times control yields at 8 days of treatment to 58.9 times control values by day 150. Intracellular PRL content ranged from 1.9 to 9.4 times control levels, and PRL release in vitro was significantly and consistently higher than controls, after at least 8 days of DES exposure. Beyond 8 days of DES exposure, the immunochemically PRL-positive proportion of cells increased to over 50% of the total population. Increased density and/or size and PRL content were indicated for the majority of the PRL cell population in both types of separation protocols. All these effects of DES were more pronounced among previously ovariectomized animals. The data extend the findings of other investigators, further establishing the DES-induced tumor as a model for study of PRL cellular control mechanisms.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "Triamterene", "mention_text": "Triamterene nephrolithiasis complicating dyazide therapy.", "entity": "Triamterene", "aliases": "Dyrenium Dytac Goldshield Brand of Triamterene Jorba SmithKline Beecham Urocaudal Wellspring", "definition": "A pteridinetriamine compound that inhibits SODIUM reabsorption through SODIUM CHANNELS in renal EPITHELIAL CELLS.\n    ", "id": "MESH:D014223"}
{"mention": "nephrolithiasis", "mention_text": "Triamterene nephrolithiasis complicating dyazide therapy.", "entity": "Nephrolithiasis", "aliases": "Nephrolithiasis", "definition": "Formation of stones in the KIDNEY.\n    ", "id": "MESH:D053040"}
{"mention": "dyazide", "mention_text": "Triamterene nephrolithiasis complicating dyazide therapy.", "entity": "hydrochlorothiazide-triamterene", "aliases": "Dyazide Maxzide Slimin Triampur (combination) compositum hydrochlorathiazide-triamterene hydrochlorothiazide-triamterene", "definition": "", "id": "MESH:C020743"}
{"mention": "triamterene", "mention_text": "A case of triamterene nephrolithiasis is reported in a man after 4 years of hydrochlorothiazide-triamterene therapy for hypertension. The stone passed spontaneously and was found to contain a triamterene metabolite admixed with uric acid salts. Factors affecting triamterene nephrolithiasis are discussed and 2 previously reported cases are reviewed.", "entity": "Triamterene", "aliases": "Dyrenium Dytac Goldshield Brand of Triamterene Jorba SmithKline Beecham Urocaudal Wellspring", "definition": "A pteridinetriamine compound that inhibits SODIUM reabsorption through SODIUM CHANNELS in renal EPITHELIAL CELLS.\n    ", "id": "MESH:D014223"}
{"mention": "nephrolithiasis", "mention_text": "A case of triamterene nephrolithiasis is reported in a man after 4 years of hydrochlorothiazide-triamterene therapy for hypertension. The stone passed spontaneously and was found to contain a triamterene metabolite admixed with uric acid salts. Factors affecting triamterene nephrolithiasis are discussed and 2 previously reported cases are reviewed.", "entity": "Nephrolithiasis", "aliases": "Nephrolithiasis", "definition": "Formation of stones in the KIDNEY.\n    ", "id": "MESH:D053040"}
{"mention": "hydrochlorothiazide-triamterene", "mention_text": "A case of triamterene nephrolithiasis is reported in a man after 4 years of hydrochlorothiazide-triamterene therapy for hypertension. The stone passed spontaneously and was found to contain a triamterene metabolite admixed with uric acid salts. Factors affecting triamterene nephrolithiasis are discussed and 2 previously reported cases are reviewed.", "entity": "hydrochlorothiazide-triamterene", "aliases": "Dyazide Maxzide Slimin Triampur (combination) compositum hydrochlorathiazide-triamterene hydrochlorothiazide-triamterene", "definition": "", "id": "MESH:C020743"}
{"mention": "hypertension", "mention_text": "A case of triamterene nephrolithiasis is reported in a man after 4 years of hydrochlorothiazide-triamterene therapy for hypertension. The stone passed spontaneously and was found to contain a triamterene metabolite admixed with uric acid salts. Factors affecting triamterene nephrolithiasis are discussed and 2 previously reported cases are reviewed.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "adriamycin", "mention_text": "Metabolic involvement in adriamycin cardiotoxicity.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "cardiotoxicity", "mention_text": "Metabolic involvement in adriamycin cardiotoxicity.", "entity": "Cardiotoxicity", "aliases": "Cardiac Toxicities Toxicity Cardiotoxicities Cardiotoxicity", "definition": "Damage to the heart or its function secondary to exposure to toxic substances such as drugs used in CHEMOTHERAPY; IMMUNOTHERAPY; or RADIATION.\n    ", "id": "MESH:D066126"}
{"mention": "cardiotoxic", "mention_text": "The cardiotoxic effects of adriamycin were studied in mammalian myocardial cells in culture as a model system. Adriamycin inhibited cell growth and the rhythmic contractions characteristic of myocardial cells in culture. A possible involvement of energy metabolism was suggested previously, and in this study the adenylate energy charge and phosphorylcreatine mole fraction were determined in the adriamycin-treated cells. The adenylate energy charge was found to be significantly decreased, while the phophorylcreatine mole fraction was unchanged. Such disparity suggests an inhibition of creatine phosphokinase. The addition of 1 mM adenosine to the myocardial cell cultures markedly increases the ATP concentration through a pathway reportedly leading to a compartmentalized ATP pool. In the adriamycin-treated cells, the addition of adenosine increased the adenylate charge and, concomitant with this inrcease, the cells' functional integrity, in terms of percentage of beating cells and rate of contractions, was maintained.", "entity": "Cardiotoxicity", "aliases": "Cardiac Toxicities Toxicity Cardiotoxicities Cardiotoxicity", "definition": "Damage to the heart or its function secondary to exposure to toxic substances such as drugs used in CHEMOTHERAPY; IMMUNOTHERAPY; or RADIATION.\n    ", "id": "MESH:D066126"}
{"mention": "adriamycin", "mention_text": "The cardiotoxic effects of adriamycin were studied in mammalian myocardial cells in culture as a model system. Adriamycin inhibited cell growth and the rhythmic contractions characteristic of myocardial cells in culture. A possible involvement of energy metabolism was suggested previously, and in this study the adenylate energy charge and phosphorylcreatine mole fraction were determined in the adriamycin-treated cells. The adenylate energy charge was found to be significantly decreased, while the phophorylcreatine mole fraction was unchanged. Such disparity suggests an inhibition of creatine phosphokinase. The addition of 1 mM adenosine to the myocardial cell cultures markedly increases the ATP concentration through a pathway reportedly leading to a compartmentalized ATP pool. In the adriamycin-treated cells, the addition of adenosine increased the adenylate charge and, concomitant with this inrcease, the cells' functional integrity, in terms of percentage of beating cells and rate of contractions, was maintained.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "Adriamycin", "mention_text": "The cardiotoxic effects of adriamycin were studied in mammalian myocardial cells in culture as a model system. Adriamycin inhibited cell growth and the rhythmic contractions characteristic of myocardial cells in culture. A possible involvement of energy metabolism was suggested previously, and in this study the adenylate energy charge and phosphorylcreatine mole fraction were determined in the adriamycin-treated cells. The adenylate energy charge was found to be significantly decreased, while the phophorylcreatine mole fraction was unchanged. Such disparity suggests an inhibition of creatine phosphokinase. The addition of 1 mM adenosine to the myocardial cell cultures markedly increases the ATP concentration through a pathway reportedly leading to a compartmentalized ATP pool. In the adriamycin-treated cells, the addition of adenosine increased the adenylate charge and, concomitant with this inrcease, the cells' functional integrity, in terms of percentage of beating cells and rate of contractions, was maintained.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "phosphorylcreatine", "mention_text": "The cardiotoxic effects of adriamycin were studied in mammalian myocardial cells in culture as a model system. Adriamycin inhibited cell growth and the rhythmic contractions characteristic of myocardial cells in culture. A possible involvement of energy metabolism was suggested previously, and in this study the adenylate energy charge and phosphorylcreatine mole fraction were determined in the adriamycin-treated cells. The adenylate energy charge was found to be significantly decreased, while the phophorylcreatine mole fraction was unchanged. Such disparity suggests an inhibition of creatine phosphokinase. The addition of 1 mM adenosine to the myocardial cell cultures markedly increases the ATP concentration through a pathway reportedly leading to a compartmentalized ATP pool. In the adriamycin-treated cells, the addition of adenosine increased the adenylate charge and, concomitant with this inrcease, the cells' functional integrity, in terms of percentage of beating cells and rate of contractions, was maintained.", "entity": "Phosphocreatine", "aliases": "Creatine Phosphate Disodium Salt Phosphocreatine Neoton Phosphorylcreatine", "definition": "An endogenous substance found mainly in skeletal muscle of vertebrates. It has been tried in the treatment of cardiac disorders and has been added to cardioplegic solutions. (Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1996)\n    ", "id": "MESH:D010725"}
{"mention": "phophorylcreatine", "mention_text": "The cardiotoxic effects of adriamycin were studied in mammalian myocardial cells in culture as a model system. Adriamycin inhibited cell growth and the rhythmic contractions characteristic of myocardial cells in culture. A possible involvement of energy metabolism was suggested previously, and in this study the adenylate energy charge and phosphorylcreatine mole fraction were determined in the adriamycin-treated cells. The adenylate energy charge was found to be significantly decreased, while the phophorylcreatine mole fraction was unchanged. Such disparity suggests an inhibition of creatine phosphokinase. The addition of 1 mM adenosine to the myocardial cell cultures markedly increases the ATP concentration through a pathway reportedly leading to a compartmentalized ATP pool. In the adriamycin-treated cells, the addition of adenosine increased the adenylate charge and, concomitant with this inrcease, the cells' functional integrity, in terms of percentage of beating cells and rate of contractions, was maintained.", "entity": "Phosphocreatine", "aliases": "Creatine Phosphate Disodium Salt Phosphocreatine Neoton Phosphorylcreatine", "definition": "An endogenous substance found mainly in skeletal muscle of vertebrates. It has been tried in the treatment of cardiac disorders and has been added to cardioplegic solutions. (Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1996)\n    ", "id": "MESH:D010725"}
{"mention": "creatine", "mention_text": "The cardiotoxic effects of adriamycin were studied in mammalian myocardial cells in culture as a model system. Adriamycin inhibited cell growth and the rhythmic contractions characteristic of myocardial cells in culture. A possible involvement of energy metabolism was suggested previously, and in this study the adenylate energy charge and phosphorylcreatine mole fraction were determined in the adriamycin-treated cells. The adenylate energy charge was found to be significantly decreased, while the phophorylcreatine mole fraction was unchanged. Such disparity suggests an inhibition of creatine phosphokinase. The addition of 1 mM adenosine to the myocardial cell cultures markedly increases the ATP concentration through a pathway reportedly leading to a compartmentalized ATP pool. In the adriamycin-treated cells, the addition of adenosine increased the adenylate charge and, concomitant with this inrcease, the cells' functional integrity, in terms of percentage of beating cells and rate of contractions, was maintained.", "entity": "Creatine", "aliases": "Creatine", "definition": "An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as CREATININE in the urine.\n    ", "id": "MESH:D003401"}
{"mention": "adenosine", "mention_text": "The cardiotoxic effects of adriamycin were studied in mammalian myocardial cells in culture as a model system. Adriamycin inhibited cell growth and the rhythmic contractions characteristic of myocardial cells in culture. A possible involvement of energy metabolism was suggested previously, and in this study the adenylate energy charge and phosphorylcreatine mole fraction were determined in the adriamycin-treated cells. The adenylate energy charge was found to be significantly decreased, while the phophorylcreatine mole fraction was unchanged. Such disparity suggests an inhibition of creatine phosphokinase. The addition of 1 mM adenosine to the myocardial cell cultures markedly increases the ATP concentration through a pathway reportedly leading to a compartmentalized ATP pool. In the adriamycin-treated cells, the addition of adenosine increased the adenylate charge and, concomitant with this inrcease, the cells' functional integrity, in terms of percentage of beating cells and rate of contractions, was maintained.", "entity": "Adenosine", "aliases": "Adenocard Adenoscan Adenosine", "definition": "A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.\n    ", "id": "MESH:D000241"}
{"mention": "ATP", "mention_text": "The cardiotoxic effects of adriamycin were studied in mammalian myocardial cells in culture as a model system. Adriamycin inhibited cell growth and the rhythmic contractions characteristic of myocardial cells in culture. A possible involvement of energy metabolism was suggested previously, and in this study the adenylate energy charge and phosphorylcreatine mole fraction were determined in the adriamycin-treated cells. The adenylate energy charge was found to be significantly decreased, while the phophorylcreatine mole fraction was unchanged. Such disparity suggests an inhibition of creatine phosphokinase. The addition of 1 mM adenosine to the myocardial cell cultures markedly increases the ATP concentration through a pathway reportedly leading to a compartmentalized ATP pool. In the adriamycin-treated cells, the addition of adenosine increased the adenylate charge and, concomitant with this inrcease, the cells' functional integrity, in terms of percentage of beating cells and rate of contractions, was maintained.", "entity": "Adenosine Triphosphate", "aliases": "ATP MgCl2 ATP-MgCl2 Adenosine Triphosphate Calcium Salt Chromium Ammonium Magnesium Chloride Manganese Adenylpyrophosphate Atriphos CaATP Cr(H2O)4 CrATP MgATP MnATP Striadyne", "definition": "An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.\n    ", "id": "MESH:D000255"}
{"mention": "neurotoxic", "mention_text": "Age-dependent sensitivity of the rat to neurotoxic effects of streptomycin.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "streptomycin", "mention_text": "Age-dependent sensitivity of the rat to neurotoxic effects of streptomycin.", "entity": "Streptomycin", "aliases": "CEPA Brand of Streptomycin Sulfate Clariana Estreptomicina Normon Fatol Grünenthal Panpharma Sanavita Strepto Hefa Strepto-Fatol Strepto-Hefa (2:3) Salt Sulphate Streptomycine Wernigerode", "definition": "An antibiotic produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis.\n    ", "id": "MESH:D013307"}
{"mention": "Streptomycin", "mention_text": "Streptomycin sulfate (300 mg/kg s.c.) was injected for various periods into preweanling rats and for 3 weeks into weanling rats. Beginning at 8 days of age, body movement and hearing were examined for 6 and up to 17 weeks, respectively. Abnormal movements and deafness occurred only in rats treated during the preweaning period; within this period the greatest sensitivities for these abnormalities occurred from 2 to 11-17 and 5 to 11 days of age, respectively, indicating that the cochlea is more sensitive to streptomycin than the site (vestibular or central) responsible for the dyskinesias.", "entity": "Streptomycin", "aliases": "CEPA Brand of Streptomycin Sulfate Clariana Estreptomicina Normon Fatol Grünenthal Panpharma Sanavita Strepto Hefa Strepto-Fatol Strepto-Hefa (2:3) Salt Sulphate Streptomycine Wernigerode", "definition": "An antibiotic produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis.\n    ", "id": "MESH:D013307"}
{"mention": "Abnormal movements", "mention_text": "Streptomycin sulfate (300 mg/kg s.c.) was injected for various periods into preweanling rats and for 3 weeks into weanling rats. Beginning at 8 days of age, body movement and hearing were examined for 6 and up to 17 weeks, respectively. Abnormal movements and deafness occurred only in rats treated during the preweaning period; within this period the greatest sensitivities for these abnormalities occurred from 2 to 11-17 and 5 to 11 days of age, respectively, indicating that the cochlea is more sensitive to streptomycin than the site (vestibular or central) responsible for the dyskinesias.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "deafness", "mention_text": "Streptomycin sulfate (300 mg/kg s.c.) was injected for various periods into preweanling rats and for 3 weeks into weanling rats. Beginning at 8 days of age, body movement and hearing were examined for 6 and up to 17 weeks, respectively. Abnormal movements and deafness occurred only in rats treated during the preweaning period; within this period the greatest sensitivities for these abnormalities occurred from 2 to 11-17 and 5 to 11 days of age, respectively, indicating that the cochlea is more sensitive to streptomycin than the site (vestibular or central) responsible for the dyskinesias.", "entity": "Deafness", "aliases": "Acquired Deafness Bilateral Complete Hearing Loss Deaf Mutism Deaf-Mutism Prelingual Extreme", "definition": "A general term for the complete loss of the ability to hear from both ears.\n    ", "id": "MESH:D003638"}
{"mention": "streptomycin", "mention_text": "Streptomycin sulfate (300 mg/kg s.c.) was injected for various periods into preweanling rats and for 3 weeks into weanling rats. Beginning at 8 days of age, body movement and hearing were examined for 6 and up to 17 weeks, respectively. Abnormal movements and deafness occurred only in rats treated during the preweaning period; within this period the greatest sensitivities for these abnormalities occurred from 2 to 11-17 and 5 to 11 days of age, respectively, indicating that the cochlea is more sensitive to streptomycin than the site (vestibular or central) responsible for the dyskinesias.", "entity": "Streptomycin", "aliases": "CEPA Brand of Streptomycin Sulfate Clariana Estreptomicina Normon Fatol Grünenthal Panpharma Sanavita Strepto Hefa Strepto-Fatol Strepto-Hefa (2:3) Salt Sulphate Streptomycine Wernigerode", "definition": "An antibiotic produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis.\n    ", "id": "MESH:D013307"}
{"mention": "dyskinesias", "mention_text": "Streptomycin sulfate (300 mg/kg s.c.) was injected for various periods into preweanling rats and for 3 weeks into weanling rats. Beginning at 8 days of age, body movement and hearing were examined for 6 and up to 17 weeks, respectively. Abnormal movements and deafness occurred only in rats treated during the preweaning period; within this period the greatest sensitivities for these abnormalities occurred from 2 to 11-17 and 5 to 11 days of age, respectively, indicating that the cochlea is more sensitive to streptomycin than the site (vestibular or central) responsible for the dyskinesias.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "glomerulonephritis", "mention_text": "Crescentic fibrillary glomerulonephritis associated with intermittent rifampin therapy for pulmonary tuberculosis.", "entity": "Glomerulonephritis", "aliases": "Bright Disease Glomerulonephritides Glomerulonephritis", "definition": "Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.\n    ", "id": "MESH:D005921"}
{"mention": "rifampin", "mention_text": "Crescentic fibrillary glomerulonephritis associated with intermittent rifampin therapy for pulmonary tuberculosis.", "entity": "Rifampin", "aliases": "Benemycin Rifadin Rifampicin Rifampin Rimactan Rimactane Tubocin", "definition": "A semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1160)\n    ", "id": "MESH:D012293"}
{"mention": "pulmonary tuberculosis", "mention_text": "Crescentic fibrillary glomerulonephritis associated with intermittent rifampin therapy for pulmonary tuberculosis.", "entity": "Tuberculosis, Pulmonary", "aliases": "Consumption Pulmonary Consumptions Phthises Phthisis Tuberculoses Tuberculosis", "definition": "MYCOBACTERIUM infections of the lung.\n    ", "id": "MESH:D014397"}
{"mention": "glomerulonephritis", "mention_text": "This case study reveals an unusual finding of rapidly proliferative crescentic glomerulonephritis in a patient treated with rifampin who had no other identifiable causes for developing this disease. This patient underwent a 10-month regimen of rifampin and isoniazid for pulmonary tuberculosis and was discovered to have developed signs of severe renal failure five weeks after completion of therapy. Renal biopsy revealed severe glomerulonephritis with crescents, electron dense fibrillar deposits and moderate lymphocytic interstitial infiltrate. Other possible causes of rapidly progressive glomerulonephritis were investigated and ruled out. This report documents the unusual occurrence of rapidly progressive glomerulonephritis with crescents and fibrillar glomerulonephritis in a patient treated with rifampin.", "entity": "Glomerulonephritis", "aliases": "Bright Disease Glomerulonephritides Glomerulonephritis", "definition": "Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.\n    ", "id": "MESH:D005921"}
{"mention": "rifampin", "mention_text": "This case study reveals an unusual finding of rapidly proliferative crescentic glomerulonephritis in a patient treated with rifampin who had no other identifiable causes for developing this disease. This patient underwent a 10-month regimen of rifampin and isoniazid for pulmonary tuberculosis and was discovered to have developed signs of severe renal failure five weeks after completion of therapy. Renal biopsy revealed severe glomerulonephritis with crescents, electron dense fibrillar deposits and moderate lymphocytic interstitial infiltrate. Other possible causes of rapidly progressive glomerulonephritis were investigated and ruled out. This report documents the unusual occurrence of rapidly progressive glomerulonephritis with crescents and fibrillar glomerulonephritis in a patient treated with rifampin.", "entity": "Rifampin", "aliases": "Benemycin Rifadin Rifampicin Rifampin Rimactan Rimactane Tubocin", "definition": "A semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1160)\n    ", "id": "MESH:D012293"}
{"mention": "isoniazid", "mention_text": "This case study reveals an unusual finding of rapidly proliferative crescentic glomerulonephritis in a patient treated with rifampin who had no other identifiable causes for developing this disease. This patient underwent a 10-month regimen of rifampin and isoniazid for pulmonary tuberculosis and was discovered to have developed signs of severe renal failure five weeks after completion of therapy. Renal biopsy revealed severe glomerulonephritis with crescents, electron dense fibrillar deposits and moderate lymphocytic interstitial infiltrate. Other possible causes of rapidly progressive glomerulonephritis were investigated and ruled out. This report documents the unusual occurrence of rapidly progressive glomerulonephritis with crescents and fibrillar glomerulonephritis in a patient treated with rifampin.", "entity": "Isoniazid", "aliases": "Acid Vanillylidenehydrazide Isonicotinic Ftivazide Hydrazide Isonex Isoniazid Phthivazid Phthivazide Tubazide", "definition": "Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis.\n    ", "id": "MESH:D007538"}
{"mention": "pulmonary tuberculosis", "mention_text": "This case study reveals an unusual finding of rapidly proliferative crescentic glomerulonephritis in a patient treated with rifampin who had no other identifiable causes for developing this disease. This patient underwent a 10-month regimen of rifampin and isoniazid for pulmonary tuberculosis and was discovered to have developed signs of severe renal failure five weeks after completion of therapy. Renal biopsy revealed severe glomerulonephritis with crescents, electron dense fibrillar deposits and moderate lymphocytic interstitial infiltrate. Other possible causes of rapidly progressive glomerulonephritis were investigated and ruled out. This report documents the unusual occurrence of rapidly progressive glomerulonephritis with crescents and fibrillar glomerulonephritis in a patient treated with rifampin.", "entity": "Tuberculosis, Pulmonary", "aliases": "Consumption Pulmonary Consumptions Phthises Phthisis Tuberculoses Tuberculosis", "definition": "MYCOBACTERIUM infections of the lung.\n    ", "id": "MESH:D014397"}
{"mention": "renal failure", "mention_text": "This case study reveals an unusual finding of rapidly proliferative crescentic glomerulonephritis in a patient treated with rifampin who had no other identifiable causes for developing this disease. This patient underwent a 10-month regimen of rifampin and isoniazid for pulmonary tuberculosis and was discovered to have developed signs of severe renal failure five weeks after completion of therapy. Renal biopsy revealed severe glomerulonephritis with crescents, electron dense fibrillar deposits and moderate lymphocytic interstitial infiltrate. Other possible causes of rapidly progressive glomerulonephritis were investigated and ruled out. This report documents the unusual occurrence of rapidly progressive glomerulonephritis with crescents and fibrillar glomerulonephritis in a patient treated with rifampin.", "entity": "Renal Insufficiency", "aliases": "Failure Kidney Renal Failures Insufficiency Insufficiencies", "definition": "Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.\n    ", "id": "MESH:D051437"}
{"mention": "puromycin aminonucleoside", "mention_text": "Time course of lipid peroxidation in puromycin aminonucleoside-induced nephropathy.", "entity": "Puromycin Aminonucleoside", "aliases": "3' Amino 3' deoxy N,N dimethyladenosine 3'-Amino-3'-deoxy-N,N-dimethyladenosine Aminonucleoside Puromycin", "definition": "PUROMYCIN derivative that lacks the methoxyphenylalanyl group on the amine of the sugar ring. It is an antibiotic with antineoplastic properties and can cause nephrosis.\n    ", "id": "MESH:D011692"}
{"mention": "nephropathy", "mention_text": "Time course of lipid peroxidation in puromycin aminonucleoside-induced nephropathy.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "oxygen", "mention_text": "Reactive oxygen species have been implicated in the pathogenesis of acute puromycin aminonucleoside (PAN)-induced nephropathy, with antioxidants significantly reducing the proteinuria. The temporal relationship between lipid peroxidation in the kidney and proteinuria was examined in this study. Rats were treated with a single IV injection of puromycin aminonucleoside, (PAN, 7.5 mg/kg) and 24 hour urine samples were obtained prior to sacrifice on days 3,5,7,10,17,27,41 (N = 5-10 per group). The kidneys were removed, flushed with ice cold TRIS buffer. Kidney cortices from each animal were used to prepare homogenates. Tissue lipid peroxidation was measured in whole homogenates as well as in lipid extracts from homogenates as thiobarbituric acid reactive substances. Proteinuria was evident at day 5, peaked at day 7 and persisted to day 27. Lipid peroxidation in homogenates was maximal at day 3 and declined rapidly to control levels by day 17. This study supports the role of lipid peroxidation in mediating the proteinuric injury in PAN nephropathy.", "entity": "Oxygen", "aliases": "Dioxygen Oxygen", "definition": "An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.\n    ", "id": "MESH:D010100"}
{"mention": "puromycin aminonucleoside", "mention_text": "Reactive oxygen species have been implicated in the pathogenesis of acute puromycin aminonucleoside (PAN)-induced nephropathy, with antioxidants significantly reducing the proteinuria. The temporal relationship between lipid peroxidation in the kidney and proteinuria was examined in this study. Rats were treated with a single IV injection of puromycin aminonucleoside, (PAN, 7.5 mg/kg) and 24 hour urine samples were obtained prior to sacrifice on days 3,5,7,10,17,27,41 (N = 5-10 per group). The kidneys were removed, flushed with ice cold TRIS buffer. Kidney cortices from each animal were used to prepare homogenates. Tissue lipid peroxidation was measured in whole homogenates as well as in lipid extracts from homogenates as thiobarbituric acid reactive substances. Proteinuria was evident at day 5, peaked at day 7 and persisted to day 27. Lipid peroxidation in homogenates was maximal at day 3 and declined rapidly to control levels by day 17. This study supports the role of lipid peroxidation in mediating the proteinuric injury in PAN nephropathy.", "entity": "Puromycin Aminonucleoside", "aliases": "3' Amino 3' deoxy N,N dimethyladenosine 3'-Amino-3'-deoxy-N,N-dimethyladenosine Aminonucleoside Puromycin", "definition": "PUROMYCIN derivative that lacks the methoxyphenylalanyl group on the amine of the sugar ring. It is an antibiotic with antineoplastic properties and can cause nephrosis.\n    ", "id": "MESH:D011692"}
{"mention": "PAN", "mention_text": "Reactive oxygen species have been implicated in the pathogenesis of acute puromycin aminonucleoside (PAN)-induced nephropathy, with antioxidants significantly reducing the proteinuria. The temporal relationship between lipid peroxidation in the kidney and proteinuria was examined in this study. Rats were treated with a single IV injection of puromycin aminonucleoside, (PAN, 7.5 mg/kg) and 24 hour urine samples were obtained prior to sacrifice on days 3,5,7,10,17,27,41 (N = 5-10 per group). The kidneys were removed, flushed with ice cold TRIS buffer. Kidney cortices from each animal were used to prepare homogenates. Tissue lipid peroxidation was measured in whole homogenates as well as in lipid extracts from homogenates as thiobarbituric acid reactive substances. Proteinuria was evident at day 5, peaked at day 7 and persisted to day 27. Lipid peroxidation in homogenates was maximal at day 3 and declined rapidly to control levels by day 17. This study supports the role of lipid peroxidation in mediating the proteinuric injury in PAN nephropathy.", "entity": "Puromycin Aminonucleoside", "aliases": "3' Amino 3' deoxy N,N dimethyladenosine 3'-Amino-3'-deoxy-N,N-dimethyladenosine Aminonucleoside Puromycin", "definition": "PUROMYCIN derivative that lacks the methoxyphenylalanyl group on the amine of the sugar ring. It is an antibiotic with antineoplastic properties and can cause nephrosis.\n    ", "id": "MESH:D011692"}
{"mention": "nephropathy", "mention_text": "Reactive oxygen species have been implicated in the pathogenesis of acute puromycin aminonucleoside (PAN)-induced nephropathy, with antioxidants significantly reducing the proteinuria. The temporal relationship between lipid peroxidation in the kidney and proteinuria was examined in this study. Rats were treated with a single IV injection of puromycin aminonucleoside, (PAN, 7.5 mg/kg) and 24 hour urine samples were obtained prior to sacrifice on days 3,5,7,10,17,27,41 (N = 5-10 per group). The kidneys were removed, flushed with ice cold TRIS buffer. Kidney cortices from each animal were used to prepare homogenates. Tissue lipid peroxidation was measured in whole homogenates as well as in lipid extracts from homogenates as thiobarbituric acid reactive substances. Proteinuria was evident at day 5, peaked at day 7 and persisted to day 27. Lipid peroxidation in homogenates was maximal at day 3 and declined rapidly to control levels by day 17. This study supports the role of lipid peroxidation in mediating the proteinuric injury in PAN nephropathy.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "proteinuria", "mention_text": "Reactive oxygen species have been implicated in the pathogenesis of acute puromycin aminonucleoside (PAN)-induced nephropathy, with antioxidants significantly reducing the proteinuria. The temporal relationship between lipid peroxidation in the kidney and proteinuria was examined in this study. Rats were treated with a single IV injection of puromycin aminonucleoside, (PAN, 7.5 mg/kg) and 24 hour urine samples were obtained prior to sacrifice on days 3,5,7,10,17,27,41 (N = 5-10 per group). The kidneys were removed, flushed with ice cold TRIS buffer. Kidney cortices from each animal were used to prepare homogenates. Tissue lipid peroxidation was measured in whole homogenates as well as in lipid extracts from homogenates as thiobarbituric acid reactive substances. Proteinuria was evident at day 5, peaked at day 7 and persisted to day 27. Lipid peroxidation in homogenates was maximal at day 3 and declined rapidly to control levels by day 17. This study supports the role of lipid peroxidation in mediating the proteinuric injury in PAN nephropathy.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "thiobarbituric acid", "mention_text": "Reactive oxygen species have been implicated in the pathogenesis of acute puromycin aminonucleoside (PAN)-induced nephropathy, with antioxidants significantly reducing the proteinuria. The temporal relationship between lipid peroxidation in the kidney and proteinuria was examined in this study. Rats were treated with a single IV injection of puromycin aminonucleoside, (PAN, 7.5 mg/kg) and 24 hour urine samples were obtained prior to sacrifice on days 3,5,7,10,17,27,41 (N = 5-10 per group). The kidneys were removed, flushed with ice cold TRIS buffer. Kidney cortices from each animal were used to prepare homogenates. Tissue lipid peroxidation was measured in whole homogenates as well as in lipid extracts from homogenates as thiobarbituric acid reactive substances. Proteinuria was evident at day 5, peaked at day 7 and persisted to day 27. Lipid peroxidation in homogenates was maximal at day 3 and declined rapidly to control levels by day 17. This study supports the role of lipid peroxidation in mediating the proteinuric injury in PAN nephropathy.", "entity": "thiobarbituric acid", "aliases": "2-mercaptobarbituric acid 2-thiobarbituric thiobarbiturate thiobarbituric monosodium salt", "definition": "", "id": "MESH:C029684"}
{"mention": "Proteinuria", "mention_text": "Reactive oxygen species have been implicated in the pathogenesis of acute puromycin aminonucleoside (PAN)-induced nephropathy, with antioxidants significantly reducing the proteinuria. The temporal relationship between lipid peroxidation in the kidney and proteinuria was examined in this study. Rats were treated with a single IV injection of puromycin aminonucleoside, (PAN, 7.5 mg/kg) and 24 hour urine samples were obtained prior to sacrifice on days 3,5,7,10,17,27,41 (N = 5-10 per group). The kidneys were removed, flushed with ice cold TRIS buffer. Kidney cortices from each animal were used to prepare homogenates. Tissue lipid peroxidation was measured in whole homogenates as well as in lipid extracts from homogenates as thiobarbituric acid reactive substances. Proteinuria was evident at day 5, peaked at day 7 and persisted to day 27. Lipid peroxidation in homogenates was maximal at day 3 and declined rapidly to control levels by day 17. This study supports the role of lipid peroxidation in mediating the proteinuric injury in PAN nephropathy.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "proteinuric injury", "mention_text": "Reactive oxygen species have been implicated in the pathogenesis of acute puromycin aminonucleoside (PAN)-induced nephropathy, with antioxidants significantly reducing the proteinuria. The temporal relationship between lipid peroxidation in the kidney and proteinuria was examined in this study. Rats were treated with a single IV injection of puromycin aminonucleoside, (PAN, 7.5 mg/kg) and 24 hour urine samples were obtained prior to sacrifice on days 3,5,7,10,17,27,41 (N = 5-10 per group). The kidneys were removed, flushed with ice cold TRIS buffer. Kidney cortices from each animal were used to prepare homogenates. Tissue lipid peroxidation was measured in whole homogenates as well as in lipid extracts from homogenates as thiobarbituric acid reactive substances. Proteinuria was evident at day 5, peaked at day 7 and persisted to day 27. Lipid peroxidation in homogenates was maximal at day 3 and declined rapidly to control levels by day 17. This study supports the role of lipid peroxidation in mediating the proteinuric injury in PAN nephropathy.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "Clomipramine", "mention_text": "Clomipramine-induced sleep disturbance does not impair its prolactin-releasing action.", "entity": "Clomipramine", "aliases": "Anafranil Chlomipramine Chlorimipramine Clomipramine Hydrochloride Maleate (1:1) Monohydrochloride Hydiphen", "definition": "A tricyclic antidepressant similar to IMIPRAMINE that selectively inhibits the uptake of serotonin in the brain. It is readily absorbed from the gastrointestinal tract and demethylated in the liver to form its primary active metabolite, desmethylclomipramine.\n    ", "id": "MESH:D002997"}
{"mention": "sleep disturbance", "mention_text": "Clomipramine-induced sleep disturbance does not impair its prolactin-releasing action.", "entity": "Sleep Disorders", "aliases": "Long Sleeper Syndrome Syndromes Neurogenic Tachypnea Sleep-Related Tachypneas Phenotype Short Sleep Phenotypes Disorders Related Subwakefullness", "definition": "Conditions characterized by disturbances of usual sleep patterns or behaviors. Sleep disorders may be divided into three major categories: DYSSOMNIAS (i.e. disorders characterized by insomnia or hypersomnia), PARASOMNIAS (abnormal sleep behaviors), and sleep disorders secondary to medical or psychiatric disorders. (From Thorpy, Sleep Disorders Medicine, 1994, p187)\n    ", "id": "MESH:D012893"}
{"mention": "sleep disturbance", "mention_text": "The present study was undertaken to examine the role of sleep disturbance, induced by clomipramine administration, on the secretory rate of prolactin (PRL) in addition to the direct drug effect. Two groups of supine subjects were studied under placebo-controlled conditions, one during the night, when sleeping (n = 7) and the other at daytime, when awake (n = 6). Each subject received a single 50 mg dose of clomipramine given orally 2 hours before blood collection. Plasma PRL concentrations were analysed at 10 min intervals and underlying secretory rates calculated by a deconvolution procedure. For both experiments the drug intake led to significant increases in PRL secretion, acting preferentially on tonic secretion as pulse amplitude and frequency did not differ significantly from corresponding control values. During the night clomipramine ingestion altered the complete sleep architecture in that it suppressed REM sleep and the sleep cycles and induced increased wakefulness. As the relative increase in PRL secretion expressed as a percentage of the mean did not significantly differ between the night and day time studies (46 +/- 19% vs 34 +/- 10%), it can be concluded that the observed sleep disturbance did not interfere with the drug action per se. The presence of REM sleep was shown not to be a determining factor either for secretory pulse amplitude and frequency, as, for both, mean nocturnal values were similar with and without prior clomipramine ingestion.", "entity": "Sleep Disorders", "aliases": "Long Sleeper Syndrome Syndromes Neurogenic Tachypnea Sleep-Related Tachypneas Phenotype Short Sleep Phenotypes Disorders Related Subwakefullness", "definition": "Conditions characterized by disturbances of usual sleep patterns or behaviors. Sleep disorders may be divided into three major categories: DYSSOMNIAS (i.e. disorders characterized by insomnia or hypersomnia), PARASOMNIAS (abnormal sleep behaviors), and sleep disorders secondary to medical or psychiatric disorders. (From Thorpy, Sleep Disorders Medicine, 1994, p187)\n    ", "id": "MESH:D012893"}
{"mention": "clomipramine", "mention_text": "The present study was undertaken to examine the role of sleep disturbance, induced by clomipramine administration, on the secretory rate of prolactin (PRL) in addition to the direct drug effect. Two groups of supine subjects were studied under placebo-controlled conditions, one during the night, when sleeping (n = 7) and the other at daytime, when awake (n = 6). Each subject received a single 50 mg dose of clomipramine given orally 2 hours before blood collection. Plasma PRL concentrations were analysed at 10 min intervals and underlying secretory rates calculated by a deconvolution procedure. For both experiments the drug intake led to significant increases in PRL secretion, acting preferentially on tonic secretion as pulse amplitude and frequency did not differ significantly from corresponding control values. During the night clomipramine ingestion altered the complete sleep architecture in that it suppressed REM sleep and the sleep cycles and induced increased wakefulness. As the relative increase in PRL secretion expressed as a percentage of the mean did not significantly differ between the night and day time studies (46 +/- 19% vs 34 +/- 10%), it can be concluded that the observed sleep disturbance did not interfere with the drug action per se. The presence of REM sleep was shown not to be a determining factor either for secretory pulse amplitude and frequency, as, for both, mean nocturnal values were similar with and without prior clomipramine ingestion.", "entity": "Clomipramine", "aliases": "Anafranil Chlomipramine Chlorimipramine Clomipramine Hydrochloride Maleate (1:1) Monohydrochloride Hydiphen", "definition": "A tricyclic antidepressant similar to IMIPRAMINE that selectively inhibits the uptake of serotonin in the brain. It is readily absorbed from the gastrointestinal tract and demethylated in the liver to form its primary active metabolite, desmethylclomipramine.\n    ", "id": "MESH:D002997"}
{"mention": "Angioedema", "mention_text": "Angioedema following the intravenous administration of metoprolol.", "entity": "Angioedema", "aliases": "Angioedema Angioedemas Angioneurotic Edema Edemas Quincke's Giant Urticaria Urticarias Quincke Quinckes", "definition": "Swelling involving the deep DERMIS, subcutaneous, or submucosal tissues, representing localized EDEMA. Angioedema often occurs in the face, lips, tongue, and larynx.\n    ", "id": "MESH:D000799"}
{"mention": "metoprolol", "mention_text": "Angioedema following the intravenous administration of metoprolol.", "entity": "Metoprolol", "aliases": "AstraZeneca Brand of Metaoprolol Tartrate Seloken Beloc Duriles Beloc-Duriles BelocDuriles Betaloc Astra Betaloc-Astra BetalocAstra Betalok CGP 2175 CGP-2175 CGP2175 H 93 26 93-26 9326 Leiras Metoprolol Succinate or Metoprolol Lopressor Novartis Metprolol Spesicor Spesikor", "definition": "A selective adrenergic beta-1 blocking agent that is commonly used to treat ANGINA PECTORIS; HYPERTENSION; and CARDIAC ARRHYTHMIAS.\n    ", "id": "MESH:D008790"}
{"mention": "pulmonary edema", "mention_text": "A 72-year-old woman was admitted to the hospital with \"flash\" pulmonary edema, preceded by chest pain, requiring intubation. Her medical history included coronary artery disease with previous myocardial infarctions, hypertension, and diabetes mellitus. A history of angioedema secondary to lisinopril therapy was elicited. Current medications did not include angiotensin-converting enzyme inhibitors or beta-blockers. She had no previous beta-blocking drug exposure. During the first day of hospitalization (while intubated), intravenous metoprolol was given, resulting in severe angioedema. The angioedema resolved after therapy with intravenous steroids and diphenhydramine hydrochloride.", "entity": "Pulmonary Edema", "aliases": "Edema Pulmonary Edemas Lung Wet Lungs", "definition": "Excessive accumulation of extravascular fluid in the lung, an indication of a serious underlying disease or disorder. Pulmonary edema prevents efficient PULMONARY GAS EXCHANGE in the PULMONARY ALVEOLI, and can be life-threatening.\n    ", "id": "MESH:D011654"}
{"mention": "chest pain", "mention_text": "A 72-year-old woman was admitted to the hospital with \"flash\" pulmonary edema, preceded by chest pain, requiring intubation. Her medical history included coronary artery disease with previous myocardial infarctions, hypertension, and diabetes mellitus. A history of angioedema secondary to lisinopril therapy was elicited. Current medications did not include angiotensin-converting enzyme inhibitors or beta-blockers. She had no previous beta-blocking drug exposure. During the first day of hospitalization (while intubated), intravenous metoprolol was given, resulting in severe angioedema. The angioedema resolved after therapy with intravenous steroids and diphenhydramine hydrochloride.", "entity": "Chest Pain", "aliases": "Chest Pain Pains", "definition": "Pressure, burning, or numbness in the chest.\n    ", "id": "MESH:D002637"}
{"mention": "coronary artery disease", "mention_text": "A 72-year-old woman was admitted to the hospital with \"flash\" pulmonary edema, preceded by chest pain, requiring intubation. Her medical history included coronary artery disease with previous myocardial infarctions, hypertension, and diabetes mellitus. A history of angioedema secondary to lisinopril therapy was elicited. Current medications did not include angiotensin-converting enzyme inhibitors or beta-blockers. She had no previous beta-blocking drug exposure. During the first day of hospitalization (while intubated), intravenous metoprolol was given, resulting in severe angioedema. The angioedema resolved after therapy with intravenous steroids and diphenhydramine hydrochloride.", "entity": "Coronary Artery Disease", "aliases": "Arterioscleroses Coronary Arteriosclerosis Artery Disease Diseases Atheroscleroses Atherosclerosis", "definition": "Pathological processes of CORONARY ARTERIES that may derive from a congenital abnormality, atherosclerotic, or non-atherosclerotic cause.\n    ", "id": "MESH:D003324"}
{"mention": "myocardial infarctions", "mention_text": "A 72-year-old woman was admitted to the hospital with \"flash\" pulmonary edema, preceded by chest pain, requiring intubation. Her medical history included coronary artery disease with previous myocardial infarctions, hypertension, and diabetes mellitus. A history of angioedema secondary to lisinopril therapy was elicited. Current medications did not include angiotensin-converting enzyme inhibitors or beta-blockers. She had no previous beta-blocking drug exposure. During the first day of hospitalization (while intubated), intravenous metoprolol was given, resulting in severe angioedema. The angioedema resolved after therapy with intravenous steroids and diphenhydramine hydrochloride.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "hypertension", "mention_text": "A 72-year-old woman was admitted to the hospital with \"flash\" pulmonary edema, preceded by chest pain, requiring intubation. Her medical history included coronary artery disease with previous myocardial infarctions, hypertension, and diabetes mellitus. A history of angioedema secondary to lisinopril therapy was elicited. Current medications did not include angiotensin-converting enzyme inhibitors or beta-blockers. She had no previous beta-blocking drug exposure. During the first day of hospitalization (while intubated), intravenous metoprolol was given, resulting in severe angioedema. The angioedema resolved after therapy with intravenous steroids and diphenhydramine hydrochloride.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "diabetes mellitus", "mention_text": "A 72-year-old woman was admitted to the hospital with \"flash\" pulmonary edema, preceded by chest pain, requiring intubation. Her medical history included coronary artery disease with previous myocardial infarctions, hypertension, and diabetes mellitus. A history of angioedema secondary to lisinopril therapy was elicited. Current medications did not include angiotensin-converting enzyme inhibitors or beta-blockers. She had no previous beta-blocking drug exposure. During the first day of hospitalization (while intubated), intravenous metoprolol was given, resulting in severe angioedema. The angioedema resolved after therapy with intravenous steroids and diphenhydramine hydrochloride.", "entity": "Diabetes Mellitus", "aliases": "Diabetes Mellitus", "definition": "A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.\n    ", "id": "MESH:D003920"}
{"mention": "angioedema", "mention_text": "A 72-year-old woman was admitted to the hospital with \"flash\" pulmonary edema, preceded by chest pain, requiring intubation. Her medical history included coronary artery disease with previous myocardial infarctions, hypertension, and diabetes mellitus. A history of angioedema secondary to lisinopril therapy was elicited. Current medications did not include angiotensin-converting enzyme inhibitors or beta-blockers. She had no previous beta-blocking drug exposure. During the first day of hospitalization (while intubated), intravenous metoprolol was given, resulting in severe angioedema. The angioedema resolved after therapy with intravenous steroids and diphenhydramine hydrochloride.", "entity": "Angioedema", "aliases": "Angioedema Angioedemas Angioneurotic Edema Edemas Quincke's Giant Urticaria Urticarias Quincke Quinckes", "definition": "Swelling involving the deep DERMIS, subcutaneous, or submucosal tissues, representing localized EDEMA. Angioedema often occurs in the face, lips, tongue, and larynx.\n    ", "id": "MESH:D000799"}
{"mention": "lisinopril", "mention_text": "A 72-year-old woman was admitted to the hospital with \"flash\" pulmonary edema, preceded by chest pain, requiring intubation. Her medical history included coronary artery disease with previous myocardial infarctions, hypertension, and diabetes mellitus. A history of angioedema secondary to lisinopril therapy was elicited. Current medications did not include angiotensin-converting enzyme inhibitors or beta-blockers. She had no previous beta-blocking drug exposure. During the first day of hospitalization (while intubated), intravenous metoprolol was given, resulting in severe angioedema. The angioedema resolved after therapy with intravenous steroids and diphenhydramine hydrochloride.", "entity": "Lisinopril", "aliases": "Lisinopril Maleate (1:1) Sulfate (1:2) Lysinopril MK-521 Prinivil Zestril", "definition": "One of the ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACE inhibitors), orally active, that has been used in the treatment of hypertension and congestive heart failure.\n    ", "id": "MESH:D017706"}
{"mention": "angiotensin", "mention_text": "A 72-year-old woman was admitted to the hospital with \"flash\" pulmonary edema, preceded by chest pain, requiring intubation. Her medical history included coronary artery disease with previous myocardial infarctions, hypertension, and diabetes mellitus. A history of angioedema secondary to lisinopril therapy was elicited. Current medications did not include angiotensin-converting enzyme inhibitors or beta-blockers. She had no previous beta-blocking drug exposure. During the first day of hospitalization (while intubated), intravenous metoprolol was given, resulting in severe angioedema. The angioedema resolved after therapy with intravenous steroids and diphenhydramine hydrochloride.", "entity": "Angiotensins", "aliases": "Angiotensin Angiotensins", "definition": "Oligopeptides which are important in the regulation of blood pressure (VASOCONSTRICTION) and fluid homeostasis via the RENIN-ANGIOTENSIN SYSTEM. These include angiotensins derived naturally from precursor ANGIOTENSINOGEN, and those synthesized.\n    ", "id": "MESH:D000809"}
{"mention": "metoprolol", "mention_text": "A 72-year-old woman was admitted to the hospital with \"flash\" pulmonary edema, preceded by chest pain, requiring intubation. Her medical history included coronary artery disease with previous myocardial infarctions, hypertension, and diabetes mellitus. A history of angioedema secondary to lisinopril therapy was elicited. Current medications did not include angiotensin-converting enzyme inhibitors or beta-blockers. She had no previous beta-blocking drug exposure. During the first day of hospitalization (while intubated), intravenous metoprolol was given, resulting in severe angioedema. The angioedema resolved after therapy with intravenous steroids and diphenhydramine hydrochloride.", "entity": "Metoprolol", "aliases": "AstraZeneca Brand of Metaoprolol Tartrate Seloken Beloc Duriles Beloc-Duriles BelocDuriles Betaloc Astra Betaloc-Astra BetalocAstra Betalok CGP 2175 CGP-2175 CGP2175 H 93 26 93-26 9326 Leiras Metoprolol Succinate or Metoprolol Lopressor Novartis Metprolol Spesicor Spesikor", "definition": "A selective adrenergic beta-1 blocking agent that is commonly used to treat ANGINA PECTORIS; HYPERTENSION; and CARDIAC ARRHYTHMIAS.\n    ", "id": "MESH:D008790"}
{"mention": "steroids", "mention_text": "A 72-year-old woman was admitted to the hospital with \"flash\" pulmonary edema, preceded by chest pain, requiring intubation. Her medical history included coronary artery disease with previous myocardial infarctions, hypertension, and diabetes mellitus. A history of angioedema secondary to lisinopril therapy was elicited. Current medications did not include angiotensin-converting enzyme inhibitors or beta-blockers. She had no previous beta-blocking drug exposure. During the first day of hospitalization (while intubated), intravenous metoprolol was given, resulting in severe angioedema. The angioedema resolved after therapy with intravenous steroids and diphenhydramine hydrochloride.", "entity": "Steroids", "aliases": "Catatoxic Steroids", "definition": "A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)\n    ", "id": "MESH:D013256"}
{"mention": "diphenhydramine", "mention_text": "A 72-year-old woman was admitted to the hospital with \"flash\" pulmonary edema, preceded by chest pain, requiring intubation. Her medical history included coronary artery disease with previous myocardial infarctions, hypertension, and diabetes mellitus. A history of angioedema secondary to lisinopril therapy was elicited. Current medications did not include angiotensin-converting enzyme inhibitors or beta-blockers. She had no previous beta-blocking drug exposure. During the first day of hospitalization (while intubated), intravenous metoprolol was given, resulting in severe angioedema. The angioedema resolved after therapy with intravenous steroids and diphenhydramine hydrochloride.", "entity": "Diphenhydramine", "aliases": "2-Diphenylmethoxy-N,N-dimethylethylamine Allerdryl Benadryl Benhydramin Benylin Benzhydramine Citrate Diphenhydramine Dimedrol (1:1) Hydrochloride Diphenylhydramin Diphenylhydramine Dormin", "definition": "A histamine H1 antagonist used as an antiemetic, antitussive, for dermatoses and pruritus, for hypersensitivity reactions, as a hypnotic, an antiparkinson, and as an ingredient in common cold preparations. It has some undesired antimuscarinic and sedative effects.\n    ", "id": "MESH:D004155"}
{"mention": "coniine", "mention_text": "Effect of coniine on the developing chick embryo.", "entity": "coniine", "aliases": "cicutine conicine coniine hydrobromide (S)-isomer hydrochloride (+-)-isomer koniin", "definition": "", "id": "MESH:C007112"}
{"mention": "Coniine", "mention_text": "Coniine, an alkaloid from Conium maculatum (poison hemlock), has been shown to be teratogenic in livestock. The major teratogenic outcome is arthrogryposis, presumably due to nicotinic receptor blockade. However, coniine has failed to produce arthrogryposis in rats or mice and is only weakly teratogenic in rabbits. The purpose of this study was to evaluate and compare the effects of coniine and nicotine in the developing chick. Concentrations of coniine and nicotine sulfate were 0.015%, 0.03%, 0.075%, 0.15%, 0.75%, 1.5%, 3%, and 6% and 1%, 5%, and 10%, respectively. Both compounds caused deformations and lethality in a dose-dependent manner. All concentrations of nicotine sulfate caused some lethality but a no effect level for coniine lethality was 0.75%. The deformations caused by both coniine and nicotine sulfate were excessive flexion or extension of one or more toes. No histopathological alterations or differences in bone formation were seen in the limbs or toes of any chicks from any group; however, extensive cranial hemorrhage occurred in all nicotine sulfate-treated chicks. There was a statistically significant (P < or = 0.01) decrease in movement in coniine and nicotine sulfate treated chicks as determined by ultrasound. Control chicks were in motion an average of 33.67% of the time, while coniine-treated chicks were only moving 8.95% of a 5-min interval, and no movement was observed for nicotine sulfate treated chicks. In summary, the chick embryo provides a reliable and simple experimental animal model of coniine-induced arthrogryposis. Data from this model support a mechanism involving nicotinic receptor blockade with subsequent decreased fetal movement.", "entity": "coniine", "aliases": "cicutine conicine coniine hydrobromide (S)-isomer hydrochloride (+-)-isomer koniin", "definition": "", "id": "MESH:C007112"}
{"mention": "arthrogryposis", "mention_text": "Coniine, an alkaloid from Conium maculatum (poison hemlock), has been shown to be teratogenic in livestock. The major teratogenic outcome is arthrogryposis, presumably due to nicotinic receptor blockade. However, coniine has failed to produce arthrogryposis in rats or mice and is only weakly teratogenic in rabbits. The purpose of this study was to evaluate and compare the effects of coniine and nicotine in the developing chick. Concentrations of coniine and nicotine sulfate were 0.015%, 0.03%, 0.075%, 0.15%, 0.75%, 1.5%, 3%, and 6% and 1%, 5%, and 10%, respectively. Both compounds caused deformations and lethality in a dose-dependent manner. All concentrations of nicotine sulfate caused some lethality but a no effect level for coniine lethality was 0.75%. The deformations caused by both coniine and nicotine sulfate were excessive flexion or extension of one or more toes. No histopathological alterations or differences in bone formation were seen in the limbs or toes of any chicks from any group; however, extensive cranial hemorrhage occurred in all nicotine sulfate-treated chicks. There was a statistically significant (P < or = 0.01) decrease in movement in coniine and nicotine sulfate treated chicks as determined by ultrasound. Control chicks were in motion an average of 33.67% of the time, while coniine-treated chicks were only moving 8.95% of a 5-min interval, and no movement was observed for nicotine sulfate treated chicks. In summary, the chick embryo provides a reliable and simple experimental animal model of coniine-induced arthrogryposis. Data from this model support a mechanism involving nicotinic receptor blockade with subsequent decreased fetal movement.", "entity": "Arthrogryposis", "aliases": "Amyoplasia Congenita Arthrogryposes Congenital Multiple Arthrogryposis Multiplex (AMC) Congenitas Arthromyodysplasia Arthromyodysplasias Fibrous Ankylosis of Joints Guerin Stern Syndrome Guerin-Stern Guérin Guérin-Stern Myodystrophia Fetalis Deformans Otto Rocher Sheldon Rocher-Sheldon Rossi", "definition": "Persistent flexure or contracture of a joint. \n    ", "id": "MESH:D001176"}
{"mention": "coniine", "mention_text": "Coniine, an alkaloid from Conium maculatum (poison hemlock), has been shown to be teratogenic in livestock. The major teratogenic outcome is arthrogryposis, presumably due to nicotinic receptor blockade. However, coniine has failed to produce arthrogryposis in rats or mice and is only weakly teratogenic in rabbits. The purpose of this study was to evaluate and compare the effects of coniine and nicotine in the developing chick. Concentrations of coniine and nicotine sulfate were 0.015%, 0.03%, 0.075%, 0.15%, 0.75%, 1.5%, 3%, and 6% and 1%, 5%, and 10%, respectively. Both compounds caused deformations and lethality in a dose-dependent manner. All concentrations of nicotine sulfate caused some lethality but a no effect level for coniine lethality was 0.75%. The deformations caused by both coniine and nicotine sulfate were excessive flexion or extension of one or more toes. No histopathological alterations or differences in bone formation were seen in the limbs or toes of any chicks from any group; however, extensive cranial hemorrhage occurred in all nicotine sulfate-treated chicks. There was a statistically significant (P < or = 0.01) decrease in movement in coniine and nicotine sulfate treated chicks as determined by ultrasound. Control chicks were in motion an average of 33.67% of the time, while coniine-treated chicks were only moving 8.95% of a 5-min interval, and no movement was observed for nicotine sulfate treated chicks. In summary, the chick embryo provides a reliable and simple experimental animal model of coniine-induced arthrogryposis. Data from this model support a mechanism involving nicotinic receptor blockade with subsequent decreased fetal movement.", "entity": "coniine", "aliases": "cicutine conicine coniine hydrobromide (S)-isomer hydrochloride (+-)-isomer koniin", "definition": "", "id": "MESH:C007112"}
{"mention": "nicotine", "mention_text": "Coniine, an alkaloid from Conium maculatum (poison hemlock), has been shown to be teratogenic in livestock. The major teratogenic outcome is arthrogryposis, presumably due to nicotinic receptor blockade. However, coniine has failed to produce arthrogryposis in rats or mice and is only weakly teratogenic in rabbits. The purpose of this study was to evaluate and compare the effects of coniine and nicotine in the developing chick. Concentrations of coniine and nicotine sulfate were 0.015%, 0.03%, 0.075%, 0.15%, 0.75%, 1.5%, 3%, and 6% and 1%, 5%, and 10%, respectively. Both compounds caused deformations and lethality in a dose-dependent manner. All concentrations of nicotine sulfate caused some lethality but a no effect level for coniine lethality was 0.75%. The deformations caused by both coniine and nicotine sulfate were excessive flexion or extension of one or more toes. No histopathological alterations or differences in bone formation were seen in the limbs or toes of any chicks from any group; however, extensive cranial hemorrhage occurred in all nicotine sulfate-treated chicks. There was a statistically significant (P < or = 0.01) decrease in movement in coniine and nicotine sulfate treated chicks as determined by ultrasound. Control chicks were in motion an average of 33.67% of the time, while coniine-treated chicks were only moving 8.95% of a 5-min interval, and no movement was observed for nicotine sulfate treated chicks. In summary, the chick embryo provides a reliable and simple experimental animal model of coniine-induced arthrogryposis. Data from this model support a mechanism involving nicotinic receptor blockade with subsequent decreased fetal movement.", "entity": "Nicotine", "aliases": "Bitartrate Nicotine Tartrate", "definition": "Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.\n    ", "id": "MESH:D009538"}
{"mention": "deformations", "mention_text": "Coniine, an alkaloid from Conium maculatum (poison hemlock), has been shown to be teratogenic in livestock. The major teratogenic outcome is arthrogryposis, presumably due to nicotinic receptor blockade. However, coniine has failed to produce arthrogryposis in rats or mice and is only weakly teratogenic in rabbits. The purpose of this study was to evaluate and compare the effects of coniine and nicotine in the developing chick. Concentrations of coniine and nicotine sulfate were 0.015%, 0.03%, 0.075%, 0.15%, 0.75%, 1.5%, 3%, and 6% and 1%, 5%, and 10%, respectively. Both compounds caused deformations and lethality in a dose-dependent manner. All concentrations of nicotine sulfate caused some lethality but a no effect level for coniine lethality was 0.75%. The deformations caused by both coniine and nicotine sulfate were excessive flexion or extension of one or more toes. No histopathological alterations or differences in bone formation were seen in the limbs or toes of any chicks from any group; however, extensive cranial hemorrhage occurred in all nicotine sulfate-treated chicks. There was a statistically significant (P < or = 0.01) decrease in movement in coniine and nicotine sulfate treated chicks as determined by ultrasound. Control chicks were in motion an average of 33.67% of the time, while coniine-treated chicks were only moving 8.95% of a 5-min interval, and no movement was observed for nicotine sulfate treated chicks. In summary, the chick embryo provides a reliable and simple experimental animal model of coniine-induced arthrogryposis. Data from this model support a mechanism involving nicotinic receptor blockade with subsequent decreased fetal movement.", "entity": "Musculoskeletal Diseases", "aliases": "Disease Musculoskeletal Diseases", "definition": "Diseases of the muscles and their associated ligaments and other connective tissue and of the bones and cartilage viewed collectively.\n    ", "id": "MESH:D009140"}
{"mention": "excessive flexion or extension of one or more toes", "mention_text": "Coniine, an alkaloid from Conium maculatum (poison hemlock), has been shown to be teratogenic in livestock. The major teratogenic outcome is arthrogryposis, presumably due to nicotinic receptor blockade. However, coniine has failed to produce arthrogryposis in rats or mice and is only weakly teratogenic in rabbits. The purpose of this study was to evaluate and compare the effects of coniine and nicotine in the developing chick. Concentrations of coniine and nicotine sulfate were 0.015%, 0.03%, 0.075%, 0.15%, 0.75%, 1.5%, 3%, and 6% and 1%, 5%, and 10%, respectively. Both compounds caused deformations and lethality in a dose-dependent manner. All concentrations of nicotine sulfate caused some lethality but a no effect level for coniine lethality was 0.75%. The deformations caused by both coniine and nicotine sulfate were excessive flexion or extension of one or more toes. No histopathological alterations or differences in bone formation were seen in the limbs or toes of any chicks from any group; however, extensive cranial hemorrhage occurred in all nicotine sulfate-treated chicks. There was a statistically significant (P < or = 0.01) decrease in movement in coniine and nicotine sulfate treated chicks as determined by ultrasound. Control chicks were in motion an average of 33.67% of the time, while coniine-treated chicks were only moving 8.95% of a 5-min interval, and no movement was observed for nicotine sulfate treated chicks. In summary, the chick embryo provides a reliable and simple experimental animal model of coniine-induced arthrogryposis. Data from this model support a mechanism involving nicotinic receptor blockade with subsequent decreased fetal movement.", "entity": "Musculoskeletal Diseases", "aliases": "Disease Musculoskeletal Diseases", "definition": "Diseases of the muscles and their associated ligaments and other connective tissue and of the bones and cartilage viewed collectively.\n    ", "id": "MESH:D009140"}
{"mention": "cranial hemorrhage", "mention_text": "Coniine, an alkaloid from Conium maculatum (poison hemlock), has been shown to be teratogenic in livestock. The major teratogenic outcome is arthrogryposis, presumably due to nicotinic receptor blockade. However, coniine has failed to produce arthrogryposis in rats or mice and is only weakly teratogenic in rabbits. The purpose of this study was to evaluate and compare the effects of coniine and nicotine in the developing chick. Concentrations of coniine and nicotine sulfate were 0.015%, 0.03%, 0.075%, 0.15%, 0.75%, 1.5%, 3%, and 6% and 1%, 5%, and 10%, respectively. Both compounds caused deformations and lethality in a dose-dependent manner. All concentrations of nicotine sulfate caused some lethality but a no effect level for coniine lethality was 0.75%. The deformations caused by both coniine and nicotine sulfate were excessive flexion or extension of one or more toes. No histopathological alterations or differences in bone formation were seen in the limbs or toes of any chicks from any group; however, extensive cranial hemorrhage occurred in all nicotine sulfate-treated chicks. There was a statistically significant (P < or = 0.01) decrease in movement in coniine and nicotine sulfate treated chicks as determined by ultrasound. Control chicks were in motion an average of 33.67% of the time, while coniine-treated chicks were only moving 8.95% of a 5-min interval, and no movement was observed for nicotine sulfate treated chicks. In summary, the chick embryo provides a reliable and simple experimental animal model of coniine-induced arthrogryposis. Data from this model support a mechanism involving nicotinic receptor blockade with subsequent decreased fetal movement.", "entity": "Cerebral Hemorrhage", "aliases": "Brain Hemorrhage Cerebral Hemorrhages Parenchymal Cerebrum Intracerebral", "definition": "Bleeding into one or both CEREBRAL HEMISPHERES including the BASAL GANGLIA and the CEREBRAL CORTEX. It is often associated with HYPERTENSION and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D002543"}
{"mention": "prostaglandin E1", "mention_text": "Epidural blood flow during prostaglandin E1 or trimethaphan induced hypotension.", "entity": "Alprostadil", "aliases": "Abbott Brand of Alprostadil Allphar Astra AstraZeneca Caverject Edex Hoyer Janssen Lipo PGE1 Lipo-PGE1 Minprog Muse PGE1alpha Paladin Pharmacia 1 2 Prostaglandin E1 E1alpha Prostavasin Prostin VR Prostine Schwarz Pharma Sugiran Vasaprostan Viridal Vivus", "definition": "A potent vasodilator agent that increases peripheral blood flow.\n    ", "id": "MESH:D000527"}
{"mention": "trimethaphan", "mention_text": "Epidural blood flow during prostaglandin E1 or trimethaphan induced hypotension.", "entity": "Trimethaphan", "aliases": "Thimethaphan Trimetaphan Trimethaphan", "definition": "A nicotinic antagonist that has been used as a ganglionic blocker in hypertension, as an adjunct to anesthesia, and to induce hypotension during surgery.\n    ", "id": "MESH:D014294"}
{"mention": "hypotension", "mention_text": "Epidural blood flow during prostaglandin E1 or trimethaphan induced hypotension.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "prostaglandin E1", "mention_text": "To evaluate the effect of prostaglandin E1 (PGE1) or trimethaphan (TMP) induced hypotension on epidural blood flow (EBF) during spinal surgery, EBF was measured using the heat clearance method in 30 patients who underwent postero-lateral interbody fusion under isoflurane anaesthesia. An initial dose of 0.1 microgram.kg-1.min-1 of PGE1 (15 patients), or 10 micrograms.kg-1.min-1 of TMP (15 patients) was administered intravenously after the dural opening and the dose was adjusted to maintain the mean arterial blood pressure (MAP) at about 60 mmHg. The hypotensive drug was discontinued at the completion of the operative procedure. After starting PGE1 or TMP, MAP and rate pressure product (RPP) decreased significantly compared with preinfusion values (P < 0.01), and the degree of hypotension due to PGE1 remained constant until 60 min after its discontinuation. Heart rate (HR) did not change in either group. EBFF did not change during PGE1 infusion whereas in the TMP group, EBF decreased significantly at 30 and 60 min after the start of TMP (preinfusion: 45.9 +/- 13.9 ml/100g/min. 30 min: 32.3 +/- 9.9 ml/100 g/min (P < 0.05). 60 min: 30 +/- 7.5 ml/100 g/min (P < 0.05)). These results suggest that PGE1 may be preferable to TMP for hypotensive anaesthesia in spinal surgery because TMP decreased EBF.", "entity": "Alprostadil", "aliases": "Abbott Brand of Alprostadil Allphar Astra AstraZeneca Caverject Edex Hoyer Janssen Lipo PGE1 Lipo-PGE1 Minprog Muse PGE1alpha Paladin Pharmacia 1 2 Prostaglandin E1 E1alpha Prostavasin Prostin VR Prostine Schwarz Pharma Sugiran Vasaprostan Viridal Vivus", "definition": "A potent vasodilator agent that increases peripheral blood flow.\n    ", "id": "MESH:D000527"}
{"mention": "PGE1", "mention_text": "To evaluate the effect of prostaglandin E1 (PGE1) or trimethaphan (TMP) induced hypotension on epidural blood flow (EBF) during spinal surgery, EBF was measured using the heat clearance method in 30 patients who underwent postero-lateral interbody fusion under isoflurane anaesthesia. An initial dose of 0.1 microgram.kg-1.min-1 of PGE1 (15 patients), or 10 micrograms.kg-1.min-1 of TMP (15 patients) was administered intravenously after the dural opening and the dose was adjusted to maintain the mean arterial blood pressure (MAP) at about 60 mmHg. The hypotensive drug was discontinued at the completion of the operative procedure. After starting PGE1 or TMP, MAP and rate pressure product (RPP) decreased significantly compared with preinfusion values (P < 0.01), and the degree of hypotension due to PGE1 remained constant until 60 min after its discontinuation. Heart rate (HR) did not change in either group. EBFF did not change during PGE1 infusion whereas in the TMP group, EBF decreased significantly at 30 and 60 min after the start of TMP (preinfusion: 45.9 +/- 13.9 ml/100g/min. 30 min: 32.3 +/- 9.9 ml/100 g/min (P < 0.05). 60 min: 30 +/- 7.5 ml/100 g/min (P < 0.05)). These results suggest that PGE1 may be preferable to TMP for hypotensive anaesthesia in spinal surgery because TMP decreased EBF.", "entity": "Alprostadil", "aliases": "Abbott Brand of Alprostadil Allphar Astra AstraZeneca Caverject Edex Hoyer Janssen Lipo PGE1 Lipo-PGE1 Minprog Muse PGE1alpha Paladin Pharmacia 1 2 Prostaglandin E1 E1alpha Prostavasin Prostin VR Prostine Schwarz Pharma Sugiran Vasaprostan Viridal Vivus", "definition": "A potent vasodilator agent that increases peripheral blood flow.\n    ", "id": "MESH:D000527"}
{"mention": "trimethaphan", "mention_text": "To evaluate the effect of prostaglandin E1 (PGE1) or trimethaphan (TMP) induced hypotension on epidural blood flow (EBF) during spinal surgery, EBF was measured using the heat clearance method in 30 patients who underwent postero-lateral interbody fusion under isoflurane anaesthesia. An initial dose of 0.1 microgram.kg-1.min-1 of PGE1 (15 patients), or 10 micrograms.kg-1.min-1 of TMP (15 patients) was administered intravenously after the dural opening and the dose was adjusted to maintain the mean arterial blood pressure (MAP) at about 60 mmHg. The hypotensive drug was discontinued at the completion of the operative procedure. After starting PGE1 or TMP, MAP and rate pressure product (RPP) decreased significantly compared with preinfusion values (P < 0.01), and the degree of hypotension due to PGE1 remained constant until 60 min after its discontinuation. Heart rate (HR) did not change in either group. EBFF did not change during PGE1 infusion whereas in the TMP group, EBF decreased significantly at 30 and 60 min after the start of TMP (preinfusion: 45.9 +/- 13.9 ml/100g/min. 30 min: 32.3 +/- 9.9 ml/100 g/min (P < 0.05). 60 min: 30 +/- 7.5 ml/100 g/min (P < 0.05)). These results suggest that PGE1 may be preferable to TMP for hypotensive anaesthesia in spinal surgery because TMP decreased EBF.", "entity": "Trimethaphan", "aliases": "Thimethaphan Trimetaphan Trimethaphan", "definition": "A nicotinic antagonist that has been used as a ganglionic blocker in hypertension, as an adjunct to anesthesia, and to induce hypotension during surgery.\n    ", "id": "MESH:D014294"}
{"mention": "TMP", "mention_text": "To evaluate the effect of prostaglandin E1 (PGE1) or trimethaphan (TMP) induced hypotension on epidural blood flow (EBF) during spinal surgery, EBF was measured using the heat clearance method in 30 patients who underwent postero-lateral interbody fusion under isoflurane anaesthesia. An initial dose of 0.1 microgram.kg-1.min-1 of PGE1 (15 patients), or 10 micrograms.kg-1.min-1 of TMP (15 patients) was administered intravenously after the dural opening and the dose was adjusted to maintain the mean arterial blood pressure (MAP) at about 60 mmHg. The hypotensive drug was discontinued at the completion of the operative procedure. After starting PGE1 or TMP, MAP and rate pressure product (RPP) decreased significantly compared with preinfusion values (P < 0.01), and the degree of hypotension due to PGE1 remained constant until 60 min after its discontinuation. Heart rate (HR) did not change in either group. EBFF did not change during PGE1 infusion whereas in the TMP group, EBF decreased significantly at 30 and 60 min after the start of TMP (preinfusion: 45.9 +/- 13.9 ml/100g/min. 30 min: 32.3 +/- 9.9 ml/100 g/min (P < 0.05). 60 min: 30 +/- 7.5 ml/100 g/min (P < 0.05)). These results suggest that PGE1 may be preferable to TMP for hypotensive anaesthesia in spinal surgery because TMP decreased EBF.", "entity": "Trimethaphan", "aliases": "Thimethaphan Trimetaphan Trimethaphan", "definition": "A nicotinic antagonist that has been used as a ganglionic blocker in hypertension, as an adjunct to anesthesia, and to induce hypotension during surgery.\n    ", "id": "MESH:D014294"}
{"mention": "hypotension", "mention_text": "To evaluate the effect of prostaglandin E1 (PGE1) or trimethaphan (TMP) induced hypotension on epidural blood flow (EBF) during spinal surgery, EBF was measured using the heat clearance method in 30 patients who underwent postero-lateral interbody fusion under isoflurane anaesthesia. An initial dose of 0.1 microgram.kg-1.min-1 of PGE1 (15 patients), or 10 micrograms.kg-1.min-1 of TMP (15 patients) was administered intravenously after the dural opening and the dose was adjusted to maintain the mean arterial blood pressure (MAP) at about 60 mmHg. The hypotensive drug was discontinued at the completion of the operative procedure. After starting PGE1 or TMP, MAP and rate pressure product (RPP) decreased significantly compared with preinfusion values (P < 0.01), and the degree of hypotension due to PGE1 remained constant until 60 min after its discontinuation. Heart rate (HR) did not change in either group. EBFF did not change during PGE1 infusion whereas in the TMP group, EBF decreased significantly at 30 and 60 min after the start of TMP (preinfusion: 45.9 +/- 13.9 ml/100g/min. 30 min: 32.3 +/- 9.9 ml/100 g/min (P < 0.05). 60 min: 30 +/- 7.5 ml/100 g/min (P < 0.05)). These results suggest that PGE1 may be preferable to TMP for hypotensive anaesthesia in spinal surgery because TMP decreased EBF.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "isoflurane", "mention_text": "To evaluate the effect of prostaglandin E1 (PGE1) or trimethaphan (TMP) induced hypotension on epidural blood flow (EBF) during spinal surgery, EBF was measured using the heat clearance method in 30 patients who underwent postero-lateral interbody fusion under isoflurane anaesthesia. An initial dose of 0.1 microgram.kg-1.min-1 of PGE1 (15 patients), or 10 micrograms.kg-1.min-1 of TMP (15 patients) was administered intravenously after the dural opening and the dose was adjusted to maintain the mean arterial blood pressure (MAP) at about 60 mmHg. The hypotensive drug was discontinued at the completion of the operative procedure. After starting PGE1 or TMP, MAP and rate pressure product (RPP) decreased significantly compared with preinfusion values (P < 0.01), and the degree of hypotension due to PGE1 remained constant until 60 min after its discontinuation. Heart rate (HR) did not change in either group. EBFF did not change during PGE1 infusion whereas in the TMP group, EBF decreased significantly at 30 and 60 min after the start of TMP (preinfusion: 45.9 +/- 13.9 ml/100g/min. 30 min: 32.3 +/- 9.9 ml/100 g/min (P < 0.05). 60 min: 30 +/- 7.5 ml/100 g/min (P < 0.05)). These results suggest that PGE1 may be preferable to TMP for hypotensive anaesthesia in spinal surgery because TMP decreased EBF.", "entity": "Isoflurane", "aliases": "Isoflurane", "definition": "A stable, non-explosive inhalation anesthetic, relatively free from significant side effects.\n    ", "id": "MESH:D007530"}
{"mention": "hypotensive", "mention_text": "To evaluate the effect of prostaglandin E1 (PGE1) or trimethaphan (TMP) induced hypotension on epidural blood flow (EBF) during spinal surgery, EBF was measured using the heat clearance method in 30 patients who underwent postero-lateral interbody fusion under isoflurane anaesthesia. An initial dose of 0.1 microgram.kg-1.min-1 of PGE1 (15 patients), or 10 micrograms.kg-1.min-1 of TMP (15 patients) was administered intravenously after the dural opening and the dose was adjusted to maintain the mean arterial blood pressure (MAP) at about 60 mmHg. The hypotensive drug was discontinued at the completion of the operative procedure. After starting PGE1 or TMP, MAP and rate pressure product (RPP) decreased significantly compared with preinfusion values (P < 0.01), and the degree of hypotension due to PGE1 remained constant until 60 min after its discontinuation. Heart rate (HR) did not change in either group. EBFF did not change during PGE1 infusion whereas in the TMP group, EBF decreased significantly at 30 and 60 min after the start of TMP (preinfusion: 45.9 +/- 13.9 ml/100g/min. 30 min: 32.3 +/- 9.9 ml/100 g/min (P < 0.05). 60 min: 30 +/- 7.5 ml/100 g/min (P < 0.05)). These results suggest that PGE1 may be preferable to TMP for hypotensive anaesthesia in spinal surgery because TMP decreased EBF.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "axonal damage", "mention_text": "Immunohistochemical studies with antibodies to neurofilament proteins on axonal damage in experimental focal lesions in rat.", "entity": "Basal Ganglia Diseases", "aliases": "Basal Ganglia Disease Diseases Disorder Disorders Extrapyramidal Lenticulostriate", "definition": "Diseases of the BASAL GANGLIA including the PUTAMEN; GLOBUS PALLIDUS; claustrum; AMYGDALA; and CAUDATE NUCLEUS. DYSKINESIAS (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include CEREBROVASCULAR DISORDERS; NEURODEGENERATIVE DISEASES; and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D001480"}
{"mention": "axonal injury", "mention_text": "Immunohistochemistry with monoclonal antibodies against neurofilament (NF) proteins of middle and high molecular weight class, NF-M and NF-H, was used to study axonal injury in the borderzone of focal lesions in rats. Focal injury in the cortex was produced by infusion of lactate at acid pH or by stab caused by needle insertion. Infarcts in substantia nigra pars reticulata were evoked by prolonged pilocarpine-induced status epilepticus. Immunohistochemical staining for NFs showed characteristic terminal clubs of axons in the borderzone of lesions. Differences in the labelling pattern occurred with different antibodies which apparently depended on molecular weight class of NFs and phosphorylation state. These immunohistochemical changes of NFs can serve as a marker for axonal damage in various experimental traumatic or ischemic lesions.", "entity": "Basal Ganglia Diseases", "aliases": "Basal Ganglia Disease Diseases Disorder Disorders Extrapyramidal Lenticulostriate", "definition": "Diseases of the BASAL GANGLIA including the PUTAMEN; GLOBUS PALLIDUS; claustrum; AMYGDALA; and CAUDATE NUCLEUS. DYSKINESIAS (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include CEREBROVASCULAR DISORDERS; NEURODEGENERATIVE DISEASES; and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D001480"}
{"mention": "injury in the cortex", "mention_text": "Immunohistochemistry with monoclonal antibodies against neurofilament (NF) proteins of middle and high molecular weight class, NF-M and NF-H, was used to study axonal injury in the borderzone of focal lesions in rats. Focal injury in the cortex was produced by infusion of lactate at acid pH or by stab caused by needle insertion. Infarcts in substantia nigra pars reticulata were evoked by prolonged pilocarpine-induced status epilepticus. Immunohistochemical staining for NFs showed characteristic terminal clubs of axons in the borderzone of lesions. Differences in the labelling pattern occurred with different antibodies which apparently depended on molecular weight class of NFs and phosphorylation state. These immunohistochemical changes of NFs can serve as a marker for axonal damage in various experimental traumatic or ischemic lesions.", "entity": "Basal Ganglia Diseases", "aliases": "Basal Ganglia Disease Diseases Disorder Disorders Extrapyramidal Lenticulostriate", "definition": "Diseases of the BASAL GANGLIA including the PUTAMEN; GLOBUS PALLIDUS; claustrum; AMYGDALA; and CAUDATE NUCLEUS. DYSKINESIAS (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include CEREBROVASCULAR DISORDERS; NEURODEGENERATIVE DISEASES; and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D001480"}
{"mention": "lactate", "mention_text": "Immunohistochemistry with monoclonal antibodies against neurofilament (NF) proteins of middle and high molecular weight class, NF-M and NF-H, was used to study axonal injury in the borderzone of focal lesions in rats. Focal injury in the cortex was produced by infusion of lactate at acid pH or by stab caused by needle insertion. Infarcts in substantia nigra pars reticulata were evoked by prolonged pilocarpine-induced status epilepticus. Immunohistochemical staining for NFs showed characteristic terminal clubs of axons in the borderzone of lesions. Differences in the labelling pattern occurred with different antibodies which apparently depended on molecular weight class of NFs and phosphorylation state. These immunohistochemical changes of NFs can serve as a marker for axonal damage in various experimental traumatic or ischemic lesions.", "entity": "Lactic Acid", "aliases": "2 Hydroxypropanoic Acid Hydroxypropionic 2-Hydroxypropanoic 2-Hydroxypropionic Ammonium Lactate D Lactic D-Lactic L L-Lactic Propanoic 2-Hydroxy- (2R)- (2S)- Sarcolactic", "definition": "A normal intermediate in the fermentation (oxidation, metabolism) of sugar. The concentrated form is used internally to prevent gastrointestinal fermentation. (From Stedman, 26th ed)\n    ", "id": "MESH:D019344"}
{"mention": "Infarcts in substantia nigra pars reticulata", "mention_text": "Immunohistochemistry with monoclonal antibodies against neurofilament (NF) proteins of middle and high molecular weight class, NF-M and NF-H, was used to study axonal injury in the borderzone of focal lesions in rats. Focal injury in the cortex was produced by infusion of lactate at acid pH or by stab caused by needle insertion. Infarcts in substantia nigra pars reticulata were evoked by prolonged pilocarpine-induced status epilepticus. Immunohistochemical staining for NFs showed characteristic terminal clubs of axons in the borderzone of lesions. Differences in the labelling pattern occurred with different antibodies which apparently depended on molecular weight class of NFs and phosphorylation state. These immunohistochemical changes of NFs can serve as a marker for axonal damage in various experimental traumatic or ischemic lesions.", "entity": "Cerebral Infarction", "aliases": "Anterior Choroidal Artery Infarction Cerebral Left Hemisphere Right Infarctions Subcortical Posterior", "definition": "The formation of an area of NECROSIS in the CEREBRUM caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., INFARCTION, ANTERIOR CEREBRAL ARTERY), and etiology (e.g., embolic infarction).\n    ", "id": "MESH:D002544"}
{"mention": "pilocarpine", "mention_text": "Immunohistochemistry with monoclonal antibodies against neurofilament (NF) proteins of middle and high molecular weight class, NF-M and NF-H, was used to study axonal injury in the borderzone of focal lesions in rats. Focal injury in the cortex was produced by infusion of lactate at acid pH or by stab caused by needle insertion. Infarcts in substantia nigra pars reticulata were evoked by prolonged pilocarpine-induced status epilepticus. Immunohistochemical staining for NFs showed characteristic terminal clubs of axons in the borderzone of lesions. Differences in the labelling pattern occurred with different antibodies which apparently depended on molecular weight class of NFs and phosphorylation state. These immunohistochemical changes of NFs can serve as a marker for axonal damage in various experimental traumatic or ischemic lesions.", "entity": "Pilocarpine", "aliases": "Hydrochloride Pilocarpine Isopilocarpine Isoptocarpine Nitrate Ocusert Mononitrate (3S-cis)-Isomer Monohydrochloride Salagen", "definition": "A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma.\n    ", "id": "MESH:D010862"}
{"mention": "status epilepticus", "mention_text": "Immunohistochemistry with monoclonal antibodies against neurofilament (NF) proteins of middle and high molecular weight class, NF-M and NF-H, was used to study axonal injury in the borderzone of focal lesions in rats. Focal injury in the cortex was produced by infusion of lactate at acid pH or by stab caused by needle insertion. Infarcts in substantia nigra pars reticulata were evoked by prolonged pilocarpine-induced status epilepticus. Immunohistochemical staining for NFs showed characteristic terminal clubs of axons in the borderzone of lesions. Differences in the labelling pattern occurred with different antibodies which apparently depended on molecular weight class of NFs and phosphorylation state. These immunohistochemical changes of NFs can serve as a marker for axonal damage in various experimental traumatic or ischemic lesions.", "entity": "Status Epilepticus", "aliases": "Absence Status Complex Partial Epilepticus Electrographic Generalized Convulsive Grand Mal Non Non-Convulsive Petit Simple Subclinical", "definition": "A prolonged seizure or seizures repeated frequently enough to prevent recovery between episodes occurring over a period of 20-30 minutes. The most common subtype is generalized tonic-clonic status epilepticus, a potentially fatal condition associated with neuronal injury and respiratory and metabolic dysfunction. Nonconvulsive forms include petit mal status and complex partial status, which may manifest as behavioral disturbances. Simple partial status epilepticus consists of persistent motor, sensory, or autonomic seizures that do not impair cognition (see also EPILEPSIA PARTIALIS CONTINUA). Subclinical status epilepticus generally refers to seizures occurring in an unresponsive or comatose individual in the absence of overt signs of seizure activity. (From N Engl J Med 1998 Apr 2;338(14):970-6; Neurologia 1997 Dec;12 Suppl 6:25-30)\n    ", "id": "MESH:D013226"}
{"mention": "axonal damage", "mention_text": "Immunohistochemistry with monoclonal antibodies against neurofilament (NF) proteins of middle and high molecular weight class, NF-M and NF-H, was used to study axonal injury in the borderzone of focal lesions in rats. Focal injury in the cortex was produced by infusion of lactate at acid pH or by stab caused by needle insertion. Infarcts in substantia nigra pars reticulata were evoked by prolonged pilocarpine-induced status epilepticus. Immunohistochemical staining for NFs showed characteristic terminal clubs of axons in the borderzone of lesions. Differences in the labelling pattern occurred with different antibodies which apparently depended on molecular weight class of NFs and phosphorylation state. These immunohistochemical changes of NFs can serve as a marker for axonal damage in various experimental traumatic or ischemic lesions.", "entity": "Basal Ganglia Diseases", "aliases": "Basal Ganglia Disease Diseases Disorder Disorders Extrapyramidal Lenticulostriate", "definition": "Diseases of the BASAL GANGLIA including the PUTAMEN; GLOBUS PALLIDUS; claustrum; AMYGDALA; and CAUDATE NUCLEUS. DYSKINESIAS (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include CEREBROVASCULAR DISORDERS; NEURODEGENERATIVE DISEASES; and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D001480"}
{"mention": "traumatic", "mention_text": "Immunohistochemistry with monoclonal antibodies against neurofilament (NF) proteins of middle and high molecular weight class, NF-M and NF-H, was used to study axonal injury in the borderzone of focal lesions in rats. Focal injury in the cortex was produced by infusion of lactate at acid pH or by stab caused by needle insertion. Infarcts in substantia nigra pars reticulata were evoked by prolonged pilocarpine-induced status epilepticus. Immunohistochemical staining for NFs showed characteristic terminal clubs of axons in the borderzone of lesions. Differences in the labelling pattern occurred with different antibodies which apparently depended on molecular weight class of NFs and phosphorylation state. These immunohistochemical changes of NFs can serve as a marker for axonal damage in various experimental traumatic or ischemic lesions.", "entity": "Wounds and Injuries", "aliases": "Injuries and Wounds Injury Trauma Traumas Wound", "definition": "Damage inflicted on the body as the direct or indirect result of an external force, with or without disruption of structural continuity.\n    ", "id": "MESH:D014947"}
{"mention": "Parkinson disability", "mention_text": "Increase of Parkinson disability after fluoxetine medication.", "entity": "Movement Disorders", "aliases": "Dyskinesia Syndrome Syndromes Lingual-Facial-Buccal Linguofacial Oral Oral-facial Orofacial Tardive Dyskinesias Dystonia Dystonias Etat Marbre Lingual Facial Buccal Movement Disorder Disorders facial Status Marmoratus", "definition": "Syndromes which feature DYSKINESIAS as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions.\n    ", "id": "MESH:D009069"}
{"mention": "fluoxetine", "mention_text": "Increase of Parkinson disability after fluoxetine medication.", "entity": "Fluoxetine", "aliases": "Fluoxetin Fluoxetine Hydrochloride Lilly 110140 Lilly-110140 Lilly110140 N-Methyl-gamma-(4-(trifluoromethyl)phenoxy)benzenepropanamine Prozac Sarafem", "definition": "The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants.\n    ", "id": "MESH:D005473"}
{"mention": "Depression", "mention_text": "Depression is a major clinical feature of Parkinson's disease. We report the increased amount of motor disability in four patients with idiopathic Parkinson's disease after exposure to the antidepressant fluoxetine. The possibility of a clinically relevant dopamine-antagonistic capacity of fluoxetine in Parkinson's disease patients must be considered.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "Parkinson's disease", "mention_text": "Depression is a major clinical feature of Parkinson's disease. We report the increased amount of motor disability in four patients with idiopathic Parkinson's disease after exposure to the antidepressant fluoxetine. The possibility of a clinically relevant dopamine-antagonistic capacity of fluoxetine in Parkinson's disease patients must be considered.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "motor disability", "mention_text": "Depression is a major clinical feature of Parkinson's disease. We report the increased amount of motor disability in four patients with idiopathic Parkinson's disease after exposure to the antidepressant fluoxetine. The possibility of a clinically relevant dopamine-antagonistic capacity of fluoxetine in Parkinson's disease patients must be considered.", "entity": "Movement Disorders", "aliases": "Dyskinesia Syndrome Syndromes Lingual-Facial-Buccal Linguofacial Oral Oral-facial Orofacial Tardive Dyskinesias Dystonia Dystonias Etat Marbre Lingual Facial Buccal Movement Disorder Disorders facial Status Marmoratus", "definition": "Syndromes which feature DYSKINESIAS as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions.\n    ", "id": "MESH:D009069"}
{"mention": "idiopathic Parkinson's disease", "mention_text": "Depression is a major clinical feature of Parkinson's disease. We report the increased amount of motor disability in four patients with idiopathic Parkinson's disease after exposure to the antidepressant fluoxetine. The possibility of a clinically relevant dopamine-antagonistic capacity of fluoxetine in Parkinson's disease patients must be considered.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "antidepressant", "mention_text": "Depression is a major clinical feature of Parkinson's disease. We report the increased amount of motor disability in four patients with idiopathic Parkinson's disease after exposure to the antidepressant fluoxetine. The possibility of a clinically relevant dopamine-antagonistic capacity of fluoxetine in Parkinson's disease patients must be considered.", "entity": "Antidepressive Agents", "aliases": "Agents Antidepressive Antidepressant Drugs Antidepressants Thymoanaleptics Thymoleptics", "definition": "Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.\n    ", "id": "MESH:D000928"}
{"mention": "fluoxetine", "mention_text": "Depression is a major clinical feature of Parkinson's disease. We report the increased amount of motor disability in four patients with idiopathic Parkinson's disease after exposure to the antidepressant fluoxetine. The possibility of a clinically relevant dopamine-antagonistic capacity of fluoxetine in Parkinson's disease patients must be considered.", "entity": "Fluoxetine", "aliases": "Fluoxetin Fluoxetine Hydrochloride Lilly 110140 Lilly-110140 Lilly110140 N-Methyl-gamma-(4-(trifluoromethyl)phenoxy)benzenepropanamine Prozac Sarafem", "definition": "The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants.\n    ", "id": "MESH:D005473"}
{"mention": "dopamine", "mention_text": "Depression is a major clinical feature of Parkinson's disease. We report the increased amount of motor disability in four patients with idiopathic Parkinson's disease after exposure to the antidepressant fluoxetine. The possibility of a clinically relevant dopamine-antagonistic capacity of fluoxetine in Parkinson's disease patients must be considered.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "Acetaminophen", "mention_text": "Acetaminophen-induced hypotension.", "entity": "Acetaminophen", "aliases": "APAP Acamol Acephen Acetaco Acetamidophenol Acetaminophen Acetominophen Algotropyl Anacin 3 Anacin-3 Anacin3 Datril Hydroxyacetanilide N-(4-Hydroxyphenyl)acetanilide N-Acetyl-p-aminophenol Panadol Paracetamol Tylenol p-Acetamidophenol p-Hydroxyacetanilide", "definition": "Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.\n    ", "id": "MESH:D000082"}
{"mention": "hypotension", "mention_text": "Acetaminophen-induced hypotension.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "acetaminophen", "mention_text": "Through 30 years of widespread use, acetaminophen has been shown to be a remarkably safe medication in therapeutic dosages. The potential for acetaminophen to produce cardiovascular toxicities is very low. However, acetaminophen has been demonstrated to produce symptoms of anaphylaxis, including hypotension, in sensitive individuals. This article describes two critically ill patients in whom transient episodes of hypotension reproducibly developed after administration of acetaminophen. Other symptoms of allergic reactions were not clinically detectable. The hypotensive episodes were severe enough to require vasopressor administration. The reports illustrate the need for clinicians to consider acetaminophen in patients with hypotension of unknown origin.", "entity": "Acetaminophen", "aliases": "APAP Acamol Acephen Acetaco Acetamidophenol Acetaminophen Acetominophen Algotropyl Anacin 3 Anacin-3 Anacin3 Datril Hydroxyacetanilide N-(4-Hydroxyphenyl)acetanilide N-Acetyl-p-aminophenol Panadol Paracetamol Tylenol p-Acetamidophenol p-Hydroxyacetanilide", "definition": "Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.\n    ", "id": "MESH:D000082"}
{"mention": "cardiovascular toxicities", "mention_text": "Through 30 years of widespread use, acetaminophen has been shown to be a remarkably safe medication in therapeutic dosages. The potential for acetaminophen to produce cardiovascular toxicities is very low. However, acetaminophen has been demonstrated to produce symptoms of anaphylaxis, including hypotension, in sensitive individuals. This article describes two critically ill patients in whom transient episodes of hypotension reproducibly developed after administration of acetaminophen. Other symptoms of allergic reactions were not clinically detectable. The hypotensive episodes were severe enough to require vasopressor administration. The reports illustrate the need for clinicians to consider acetaminophen in patients with hypotension of unknown origin.", "entity": "Cardiovascular Diseases", "aliases": "Cardiovascular Disease Diseases", "definition": "Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.\n    ", "id": "MESH:D002318"}
{"mention": "anaphylaxis", "mention_text": "Through 30 years of widespread use, acetaminophen has been shown to be a remarkably safe medication in therapeutic dosages. The potential for acetaminophen to produce cardiovascular toxicities is very low. However, acetaminophen has been demonstrated to produce symptoms of anaphylaxis, including hypotension, in sensitive individuals. This article describes two critically ill patients in whom transient episodes of hypotension reproducibly developed after administration of acetaminophen. Other symptoms of allergic reactions were not clinically detectable. The hypotensive episodes were severe enough to require vasopressor administration. The reports illustrate the need for clinicians to consider acetaminophen in patients with hypotension of unknown origin.", "entity": "Anaphylaxis", "aliases": "Anaphylactic Reaction Reactions Shock Anaphylaxis", "definition": "An acute hypersensitivity reaction due to exposure to a previously encountered ANTIGEN. The reaction may include rapidly progressing URTICARIA, respiratory distress, vascular collapse, systemic SHOCK, and death.\n    ", "id": "MESH:D000707"}
{"mention": "hypotension", "mention_text": "Through 30 years of widespread use, acetaminophen has been shown to be a remarkably safe medication in therapeutic dosages. The potential for acetaminophen to produce cardiovascular toxicities is very low. However, acetaminophen has been demonstrated to produce symptoms of anaphylaxis, including hypotension, in sensitive individuals. This article describes two critically ill patients in whom transient episodes of hypotension reproducibly developed after administration of acetaminophen. Other symptoms of allergic reactions were not clinically detectable. The hypotensive episodes were severe enough to require vasopressor administration. The reports illustrate the need for clinicians to consider acetaminophen in patients with hypotension of unknown origin.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "critically ill", "mention_text": "Through 30 years of widespread use, acetaminophen has been shown to be a remarkably safe medication in therapeutic dosages. The potential for acetaminophen to produce cardiovascular toxicities is very low. However, acetaminophen has been demonstrated to produce symptoms of anaphylaxis, including hypotension, in sensitive individuals. This article describes two critically ill patients in whom transient episodes of hypotension reproducibly developed after administration of acetaminophen. Other symptoms of allergic reactions were not clinically detectable. The hypotensive episodes were severe enough to require vasopressor administration. The reports illustrate the need for clinicians to consider acetaminophen in patients with hypotension of unknown origin.", "entity": "Critical Illness", "aliases": "Critical Illness Illnesses Critically Ill", "definition": "A disease or state in which death is possible or imminent.\n    ", "id": "MESH:D016638"}
{"mention": "allergic reactions", "mention_text": "Through 30 years of widespread use, acetaminophen has been shown to be a remarkably safe medication in therapeutic dosages. The potential for acetaminophen to produce cardiovascular toxicities is very low. However, acetaminophen has been demonstrated to produce symptoms of anaphylaxis, including hypotension, in sensitive individuals. This article describes two critically ill patients in whom transient episodes of hypotension reproducibly developed after administration of acetaminophen. Other symptoms of allergic reactions were not clinically detectable. The hypotensive episodes were severe enough to require vasopressor administration. The reports illustrate the need for clinicians to consider acetaminophen in patients with hypotension of unknown origin.", "entity": "Drug Hypersensitivity", "aliases": "Allergies Drug Allergy Hypersensitivities Hypersensitivity", "definition": "Immunologically mediated adverse reactions to medicinal substances used legally or illegally.\n    ", "id": "MESH:D004342"}
{"mention": "hypotensive", "mention_text": "Through 30 years of widespread use, acetaminophen has been shown to be a remarkably safe medication in therapeutic dosages. The potential for acetaminophen to produce cardiovascular toxicities is very low. However, acetaminophen has been demonstrated to produce symptoms of anaphylaxis, including hypotension, in sensitive individuals. This article describes two critically ill patients in whom transient episodes of hypotension reproducibly developed after administration of acetaminophen. Other symptoms of allergic reactions were not clinically detectable. The hypotensive episodes were severe enough to require vasopressor administration. The reports illustrate the need for clinicians to consider acetaminophen in patients with hypotension of unknown origin.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "hepatitis", "mention_text": "Acute hepatitis, autoimmune hemolytic anemia, and erythroblastocytopenia induced by ceftriaxone.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "autoimmune hemolytic anemia", "mention_text": "Acute hepatitis, autoimmune hemolytic anemia, and erythroblastocytopenia induced by ceftriaxone.", "entity": "Anemia, Hemolytic, Autoimmune", "aliases": "Acquired Autoimmune Hemolytic Anemia Agglutinin Disease Cold Diseases Antibody Idiopathic Anemias", "definition": "Acquired hemolytic anemia due to the presence of AUTOANTIBODIES which agglutinate or lyse the patient's own RED BLOOD CELLS.\n    ", "id": "MESH:D000744"}
{"mention": "ceftriaxone", "mention_text": "Acute hepatitis, autoimmune hemolytic anemia, and erythroblastocytopenia induced by ceftriaxone.", "entity": "Ceftriaxone", "aliases": "Anhydrous Ceftriaxone Sodium Benaxona Boehringer Mannheim Brand of Cefatriaxone Cefaxona Ceftrex Ceftriaxon Curamed Hexal Ceftriaxona Andreu LDP Torlan Irex Disodium Salt Hemiheptahydrate Columbia Fustery Galen Hoffman La Roche Hoffman-La Inibsa Lendacin Longacef Longaceph Pisa Ro 13 9904 13-9904 139904 Ro-13-9904 Ro13 Ro13-9904 Ro139904 Rocefalin Rocefin Rocephin Rocephine Syntex Tacex Terbac", "definition": "A broad-spectrum cephalosporin antibiotic with a very long half-life and high penetrability to meninges, eyes and inner ears.\n    ", "id": "MESH:D002443"}
{"mention": "hepatitis", "mention_text": "An 80-yr-old man developed acute hepatitis shortly after ingesting oral ceftriaxone. Although the transaminases gradually returned to baseline after withholding the beta lactam antibiotic, there was a gradual increase in serum bilirubin and a decrease in hemoglobin concentration caused by an autoimmune hemolytic anemia and erythroblastocytopenia. These responded to systemic steroids and immunoglobulins. Despite the widespread use of these agents this triad of side effects has not previously been reported in connection with beta lactam antibiotics.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "ceftriaxone", "mention_text": "An 80-yr-old man developed acute hepatitis shortly after ingesting oral ceftriaxone. Although the transaminases gradually returned to baseline after withholding the beta lactam antibiotic, there was a gradual increase in serum bilirubin and a decrease in hemoglobin concentration caused by an autoimmune hemolytic anemia and erythroblastocytopenia. These responded to systemic steroids and immunoglobulins. Despite the widespread use of these agents this triad of side effects has not previously been reported in connection with beta lactam antibiotics.", "entity": "Ceftriaxone", "aliases": "Anhydrous Ceftriaxone Sodium Benaxona Boehringer Mannheim Brand of Cefatriaxone Cefaxona Ceftrex Ceftriaxon Curamed Hexal Ceftriaxona Andreu LDP Torlan Irex Disodium Salt Hemiheptahydrate Columbia Fustery Galen Hoffman La Roche Hoffman-La Inibsa Lendacin Longacef Longaceph Pisa Ro 13 9904 13-9904 139904 Ro-13-9904 Ro13 Ro13-9904 Ro139904 Rocefalin Rocefin Rocephin Rocephine Syntex Tacex Terbac", "definition": "A broad-spectrum cephalosporin antibiotic with a very long half-life and high penetrability to meninges, eyes and inner ears.\n    ", "id": "MESH:D002443"}
{"mention": "beta lactam", "mention_text": "An 80-yr-old man developed acute hepatitis shortly after ingesting oral ceftriaxone. Although the transaminases gradually returned to baseline after withholding the beta lactam antibiotic, there was a gradual increase in serum bilirubin and a decrease in hemoglobin concentration caused by an autoimmune hemolytic anemia and erythroblastocytopenia. These responded to systemic steroids and immunoglobulins. Despite the widespread use of these agents this triad of side effects has not previously been reported in connection with beta lactam antibiotics.", "entity": "beta-Lactams", "aliases": "4-Thia-1-Azabicyclo(3.2.0)Heptanes 4-Thia-1-Azabicyclo(4.2.0)Octanes beta Lactams beta-Lactams", "definition": "Four-membered cyclic AMIDES, best known for the PENICILLINS based on a bicyclo-thiazolidine, as well as the CEPHALOSPORINS based on a bicyclo-thiazine, and including monocyclic MONOBACTAMS. The BETA-LACTAMASES hydrolyze the beta lactam ring, accounting for BETA-LACTAM RESISTANCE of infective bacteria.\n    ", "id": "MESH:D047090"}
{"mention": "bilirubin", "mention_text": "An 80-yr-old man developed acute hepatitis shortly after ingesting oral ceftriaxone. Although the transaminases gradually returned to baseline after withholding the beta lactam antibiotic, there was a gradual increase in serum bilirubin and a decrease in hemoglobin concentration caused by an autoimmune hemolytic anemia and erythroblastocytopenia. These responded to systemic steroids and immunoglobulins. Despite the widespread use of these agents this triad of side effects has not previously been reported in connection with beta lactam antibiotics.", "entity": "Bilirubin", "aliases": "Bilirubin IX alpha (15E)-Isomer (4E)-Isomer (4E,15E)-Isomer Calcium Salt Disodium Monosodium Bilirubinate Hematoidin delta delta-Bilirubin", "definition": "A bile pigment that is a degradation product of HEME.\n    ", "id": "MESH:D001663"}
{"mention": "autoimmune hemolytic anemia", "mention_text": "An 80-yr-old man developed acute hepatitis shortly after ingesting oral ceftriaxone. Although the transaminases gradually returned to baseline after withholding the beta lactam antibiotic, there was a gradual increase in serum bilirubin and a decrease in hemoglobin concentration caused by an autoimmune hemolytic anemia and erythroblastocytopenia. These responded to systemic steroids and immunoglobulins. Despite the widespread use of these agents this triad of side effects has not previously been reported in connection with beta lactam antibiotics.", "entity": "Anemia, Hemolytic, Autoimmune", "aliases": "Acquired Autoimmune Hemolytic Anemia Agglutinin Disease Cold Diseases Antibody Idiopathic Anemias", "definition": "Acquired hemolytic anemia due to the presence of AUTOANTIBODIES which agglutinate or lyse the patient's own RED BLOOD CELLS.\n    ", "id": "MESH:D000744"}
{"mention": "steroids", "mention_text": "An 80-yr-old man developed acute hepatitis shortly after ingesting oral ceftriaxone. Although the transaminases gradually returned to baseline after withholding the beta lactam antibiotic, there was a gradual increase in serum bilirubin and a decrease in hemoglobin concentration caused by an autoimmune hemolytic anemia and erythroblastocytopenia. These responded to systemic steroids and immunoglobulins. Despite the widespread use of these agents this triad of side effects has not previously been reported in connection with beta lactam antibiotics.", "entity": "Steroids", "aliases": "Catatoxic Steroids", "definition": "A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)\n    ", "id": "MESH:D013256"}
{"mention": "extrapyramidal symptoms", "mention_text": "Adverse effects of antipsychotics often lead to noncompliance. Thus, clinicians should address patients' concerns about adverse effects and attempt to choose medications that will improve their patients' quality of life as well as overall health. The side effect profiles of the atypical antipsychotics are more advantageous than those of the conventional neuroleptics. Conventional agents are associated with unwanted central nervous system effects, including extrapyramidal symptoms (EPS), tardive dyskinesia, sedation, and possible impairment of some cognitive measures, as well as cardiac effects, orthostatic hypotension, hepatic changes, anticholinergic side effects, sexual dysfunction, and weight gain. The newer atypical agents have a lower risk of EPS, but are associated in varying degrees with sedation, cardiovascular effects, anticholinergic effects, weight gain, sexual dysfunction, hepatic effects, lowered seizure threshold (primarily clozapine), and agranulocytosis (clozapine only). Since the incidence and severity of specific adverse effects differ among the various atypicals, the clinician should carefully consider which side effects are most likely to lead to the individual's dissatisfaction and noncompliance before choosing an antipsychotic for a particular patient.", "entity": "Basal Ganglia Diseases", "aliases": "Basal Ganglia Disease Diseases Disorder Disorders Extrapyramidal Lenticulostriate", "definition": "Diseases of the BASAL GANGLIA including the PUTAMEN; GLOBUS PALLIDUS; claustrum; AMYGDALA; and CAUDATE NUCLEUS. DYSKINESIAS (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include CEREBROVASCULAR DISORDERS; NEURODEGENERATIVE DISEASES; and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D001480"}
{"mention": "EPS", "mention_text": "Adverse effects of antipsychotics often lead to noncompliance. Thus, clinicians should address patients' concerns about adverse effects and attempt to choose medications that will improve their patients' quality of life as well as overall health. The side effect profiles of the atypical antipsychotics are more advantageous than those of the conventional neuroleptics. Conventional agents are associated with unwanted central nervous system effects, including extrapyramidal symptoms (EPS), tardive dyskinesia, sedation, and possible impairment of some cognitive measures, as well as cardiac effects, orthostatic hypotension, hepatic changes, anticholinergic side effects, sexual dysfunction, and weight gain. The newer atypical agents have a lower risk of EPS, but are associated in varying degrees with sedation, cardiovascular effects, anticholinergic effects, weight gain, sexual dysfunction, hepatic effects, lowered seizure threshold (primarily clozapine), and agranulocytosis (clozapine only). Since the incidence and severity of specific adverse effects differ among the various atypicals, the clinician should carefully consider which side effects are most likely to lead to the individual's dissatisfaction and noncompliance before choosing an antipsychotic for a particular patient.", "entity": "Basal Ganglia Diseases", "aliases": "Basal Ganglia Disease Diseases Disorder Disorders Extrapyramidal Lenticulostriate", "definition": "Diseases of the BASAL GANGLIA including the PUTAMEN; GLOBUS PALLIDUS; claustrum; AMYGDALA; and CAUDATE NUCLEUS. DYSKINESIAS (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include CEREBROVASCULAR DISORDERS; NEURODEGENERATIVE DISEASES; and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D001480"}
{"mention": "tardive dyskinesia", "mention_text": "Adverse effects of antipsychotics often lead to noncompliance. Thus, clinicians should address patients' concerns about adverse effects and attempt to choose medications that will improve their patients' quality of life as well as overall health. The side effect profiles of the atypical antipsychotics are more advantageous than those of the conventional neuroleptics. Conventional agents are associated with unwanted central nervous system effects, including extrapyramidal symptoms (EPS), tardive dyskinesia, sedation, and possible impairment of some cognitive measures, as well as cardiac effects, orthostatic hypotension, hepatic changes, anticholinergic side effects, sexual dysfunction, and weight gain. The newer atypical agents have a lower risk of EPS, but are associated in varying degrees with sedation, cardiovascular effects, anticholinergic effects, weight gain, sexual dysfunction, hepatic effects, lowered seizure threshold (primarily clozapine), and agranulocytosis (clozapine only). Since the incidence and severity of specific adverse effects differ among the various atypicals, the clinician should carefully consider which side effects are most likely to lead to the individual's dissatisfaction and noncompliance before choosing an antipsychotic for a particular patient.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "orthostatic hypotension", "mention_text": "Adverse effects of antipsychotics often lead to noncompliance. Thus, clinicians should address patients' concerns about adverse effects and attempt to choose medications that will improve their patients' quality of life as well as overall health. The side effect profiles of the atypical antipsychotics are more advantageous than those of the conventional neuroleptics. Conventional agents are associated with unwanted central nervous system effects, including extrapyramidal symptoms (EPS), tardive dyskinesia, sedation, and possible impairment of some cognitive measures, as well as cardiac effects, orthostatic hypotension, hepatic changes, anticholinergic side effects, sexual dysfunction, and weight gain. The newer atypical agents have a lower risk of EPS, but are associated in varying degrees with sedation, cardiovascular effects, anticholinergic effects, weight gain, sexual dysfunction, hepatic effects, lowered seizure threshold (primarily clozapine), and agranulocytosis (clozapine only). Since the incidence and severity of specific adverse effects differ among the various atypicals, the clinician should carefully consider which side effects are most likely to lead to the individual's dissatisfaction and noncompliance before choosing an antipsychotic for a particular patient.", "entity": "Hypotension, Orthostatic", "aliases": "Hypotension Orthostatic Postural", "definition": "A significant drop in BLOOD PRESSURE after assuming a standing position. Orthostatic hypotension is a finding, and defined as a 20-mm Hg decrease in systolic pressure or a 10-mm Hg decrease in diastolic pressure 3 minutes after the person has risen from supine to standing. Symptoms generally include DIZZINESS, blurred vision, and SYNCOPE.\n    ", "id": "MESH:D007024"}
{"mention": "sexual dysfunction", "mention_text": "Adverse effects of antipsychotics often lead to noncompliance. Thus, clinicians should address patients' concerns about adverse effects and attempt to choose medications that will improve their patients' quality of life as well as overall health. The side effect profiles of the atypical antipsychotics are more advantageous than those of the conventional neuroleptics. Conventional agents are associated with unwanted central nervous system effects, including extrapyramidal symptoms (EPS), tardive dyskinesia, sedation, and possible impairment of some cognitive measures, as well as cardiac effects, orthostatic hypotension, hepatic changes, anticholinergic side effects, sexual dysfunction, and weight gain. The newer atypical agents have a lower risk of EPS, but are associated in varying degrees with sedation, cardiovascular effects, anticholinergic effects, weight gain, sexual dysfunction, hepatic effects, lowered seizure threshold (primarily clozapine), and agranulocytosis (clozapine only). Since the incidence and severity of specific adverse effects differ among the various atypicals, the clinician should carefully consider which side effects are most likely to lead to the individual's dissatisfaction and noncompliance before choosing an antipsychotic for a particular patient.", "entity": "Sexual Dysfunction, Physiological", "aliases": "Physiological Sexual Disorder Disorders Dysfunction Dysfunctions Sex", "definition": "Physiological disturbances in normal sexual performance in either the male or the female.\n    ", "id": "MESH:D012735"}
{"mention": "weight gain", "mention_text": "Adverse effects of antipsychotics often lead to noncompliance. Thus, clinicians should address patients' concerns about adverse effects and attempt to choose medications that will improve their patients' quality of life as well as overall health. The side effect profiles of the atypical antipsychotics are more advantageous than those of the conventional neuroleptics. Conventional agents are associated with unwanted central nervous system effects, including extrapyramidal symptoms (EPS), tardive dyskinesia, sedation, and possible impairment of some cognitive measures, as well as cardiac effects, orthostatic hypotension, hepatic changes, anticholinergic side effects, sexual dysfunction, and weight gain. The newer atypical agents have a lower risk of EPS, but are associated in varying degrees with sedation, cardiovascular effects, anticholinergic effects, weight gain, sexual dysfunction, hepatic effects, lowered seizure threshold (primarily clozapine), and agranulocytosis (clozapine only). Since the incidence and severity of specific adverse effects differ among the various atypicals, the clinician should carefully consider which side effects are most likely to lead to the individual's dissatisfaction and noncompliance before choosing an antipsychotic for a particular patient.", "entity": "Weight Gain", "aliases": "Gain Weight Gains", "definition": "Increase in BODY WEIGHT over existing weight.\n    ", "id": "MESH:D015430"}
{"mention": "seizure", "mention_text": "Adverse effects of antipsychotics often lead to noncompliance. Thus, clinicians should address patients' concerns about adverse effects and attempt to choose medications that will improve their patients' quality of life as well as overall health. The side effect profiles of the atypical antipsychotics are more advantageous than those of the conventional neuroleptics. Conventional agents are associated with unwanted central nervous system effects, including extrapyramidal symptoms (EPS), tardive dyskinesia, sedation, and possible impairment of some cognitive measures, as well as cardiac effects, orthostatic hypotension, hepatic changes, anticholinergic side effects, sexual dysfunction, and weight gain. The newer atypical agents have a lower risk of EPS, but are associated in varying degrees with sedation, cardiovascular effects, anticholinergic effects, weight gain, sexual dysfunction, hepatic effects, lowered seizure threshold (primarily clozapine), and agranulocytosis (clozapine only). Since the incidence and severity of specific adverse effects differ among the various atypicals, the clinician should carefully consider which side effects are most likely to lead to the individual's dissatisfaction and noncompliance before choosing an antipsychotic for a particular patient.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "clozapine", "mention_text": "Adverse effects of antipsychotics often lead to noncompliance. Thus, clinicians should address patients' concerns about adverse effects and attempt to choose medications that will improve their patients' quality of life as well as overall health. The side effect profiles of the atypical antipsychotics are more advantageous than those of the conventional neuroleptics. Conventional agents are associated with unwanted central nervous system effects, including extrapyramidal symptoms (EPS), tardive dyskinesia, sedation, and possible impairment of some cognitive measures, as well as cardiac effects, orthostatic hypotension, hepatic changes, anticholinergic side effects, sexual dysfunction, and weight gain. The newer atypical agents have a lower risk of EPS, but are associated in varying degrees with sedation, cardiovascular effects, anticholinergic effects, weight gain, sexual dysfunction, hepatic effects, lowered seizure threshold (primarily clozapine), and agranulocytosis (clozapine only). Since the incidence and severity of specific adverse effects differ among the various atypicals, the clinician should carefully consider which side effects are most likely to lead to the individual's dissatisfaction and noncompliance before choosing an antipsychotic for a particular patient.", "entity": "Clozapine", "aliases": "Clozapine Clozaril Leponex", "definition": "A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.\n    ", "id": "MESH:D003024"}
{"mention": "agranulocytosis", "mention_text": "Adverse effects of antipsychotics often lead to noncompliance. Thus, clinicians should address patients' concerns about adverse effects and attempt to choose medications that will improve their patients' quality of life as well as overall health. The side effect profiles of the atypical antipsychotics are more advantageous than those of the conventional neuroleptics. Conventional agents are associated with unwanted central nervous system effects, including extrapyramidal symptoms (EPS), tardive dyskinesia, sedation, and possible impairment of some cognitive measures, as well as cardiac effects, orthostatic hypotension, hepatic changes, anticholinergic side effects, sexual dysfunction, and weight gain. The newer atypical agents have a lower risk of EPS, but are associated in varying degrees with sedation, cardiovascular effects, anticholinergic effects, weight gain, sexual dysfunction, hepatic effects, lowered seizure threshold (primarily clozapine), and agranulocytosis (clozapine only). Since the incidence and severity of specific adverse effects differ among the various atypicals, the clinician should carefully consider which side effects are most likely to lead to the individual's dissatisfaction and noncompliance before choosing an antipsychotic for a particular patient.", "entity": "Agranulocytosis", "aliases": "Agranulocytoses Agranulocytosis Granulocytopenia Granulocytopenias", "definition": "A decrease in the number of GRANULOCYTES; (BASOPHILS; EOSINOPHILS; and NEUTROPHILS).\n    ", "id": "MESH:D000380"}
{"mention": "tetrandrine", "mention_text": "Effects of tetrandrine and fangchinoline on experimental thrombosis in mice and human platelet aggregation.", "entity": "tetrandrine", "aliases": "6,6',7,12-tetramethoxy-2,2'-dimethyl-1 beta-berbaman NSC-77037 d-tetrandrine hanjisong isotetrandrine dihydrochloride tetradrine tetrandrine (1beta)-isomer (1'beta)-isomer", "definition": "", "id": "MESH:C009438"}
{"mention": "fangchinoline", "mention_text": "Effects of tetrandrine and fangchinoline on experimental thrombosis in mice and human platelet aggregation.", "entity": "fangchinoline", "aliases": "(1beta)-isomer of fangchinoline 7-O-demethyl-tetrandrine 7-O-demethyltetrandrine isofangchinoline limacine thaligine thalrugosine", "definition": "", "id": "MESH:C060802"}
{"mention": "thrombosis", "mention_text": "Effects of tetrandrine and fangchinoline on experimental thrombosis in mice and human platelet aggregation.", "entity": "Thrombosis", "aliases": "Thromboses Thrombosis Thrombus", "definition": "Formation and development of a thrombus or blood clot in the blood vessel.\n    ", "id": "MESH:D013927"}
{"mention": "platelet aggregation", "mention_text": "Effects of tetrandrine and fangchinoline on experimental thrombosis in mice and human platelet aggregation.", "entity": "Blood Platelet Disorders", "aliases": "Blood Platelet Disorder Disorders Thrombocytopathies Thrombocytopathy", "definition": "Disorders caused by abnormalities in platelet count or function.\n    ", "id": "MESH:D001791"}
{"mention": "Tetrandrine", "mention_text": "Tetrandrine (TET) and fangchinoline (FAN) are two naturally occurring analogues with a bisbenzylisoquinoline structure. The present study was undertaken to investigate the effects of TET and FAN on the experimental thrombosis induced by collagen plus epinephrine (EP) in mice, and platelet aggregation and blood coagulation in vitro. In the in vivo study, the administration (50 mg/kg, i.p.) of TET and FAN in mice showed the inhibition of thrombosis by 55% and 35%, respectively, while acetylsalicylic acid (ASA, 50 mg/kg, i.p.), a positive control, showed only 30% inhibition. In the vitro human platelet aggregations induced by the agonists used in tests, TET and FAN showed the inhibitions dose dependently. In addition, neither TET nor FAN showed any anticoagulation activities in the measurement of the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) using human-citrated plasma. These results suggest that antithrombosis of TET and FAN in mice may be mainly related to the antiplatelet aggregation activities.", "entity": "tetrandrine", "aliases": "6,6',7,12-tetramethoxy-2,2'-dimethyl-1 beta-berbaman NSC-77037 d-tetrandrine hanjisong isotetrandrine dihydrochloride tetradrine tetrandrine (1beta)-isomer (1'beta)-isomer", "definition": "", "id": "MESH:C009438"}
{"mention": "TET", "mention_text": "Tetrandrine (TET) and fangchinoline (FAN) are two naturally occurring analogues with a bisbenzylisoquinoline structure. The present study was undertaken to investigate the effects of TET and FAN on the experimental thrombosis induced by collagen plus epinephrine (EP) in mice, and platelet aggregation and blood coagulation in vitro. In the in vivo study, the administration (50 mg/kg, i.p.) of TET and FAN in mice showed the inhibition of thrombosis by 55% and 35%, respectively, while acetylsalicylic acid (ASA, 50 mg/kg, i.p.), a positive control, showed only 30% inhibition. In the vitro human platelet aggregations induced by the agonists used in tests, TET and FAN showed the inhibitions dose dependently. In addition, neither TET nor FAN showed any anticoagulation activities in the measurement of the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) using human-citrated plasma. These results suggest that antithrombosis of TET and FAN in mice may be mainly related to the antiplatelet aggregation activities.", "entity": "tetrandrine", "aliases": "6,6',7,12-tetramethoxy-2,2'-dimethyl-1 beta-berbaman NSC-77037 d-tetrandrine hanjisong isotetrandrine dihydrochloride tetradrine tetrandrine (1beta)-isomer (1'beta)-isomer", "definition": "", "id": "MESH:C009438"}
{"mention": "fangchinoline", "mention_text": "Tetrandrine (TET) and fangchinoline (FAN) are two naturally occurring analogues with a bisbenzylisoquinoline structure. The present study was undertaken to investigate the effects of TET and FAN on the experimental thrombosis induced by collagen plus epinephrine (EP) in mice, and platelet aggregation and blood coagulation in vitro. In the in vivo study, the administration (50 mg/kg, i.p.) of TET and FAN in mice showed the inhibition of thrombosis by 55% and 35%, respectively, while acetylsalicylic acid (ASA, 50 mg/kg, i.p.), a positive control, showed only 30% inhibition. In the vitro human platelet aggregations induced by the agonists used in tests, TET and FAN showed the inhibitions dose dependently. In addition, neither TET nor FAN showed any anticoagulation activities in the measurement of the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) using human-citrated plasma. These results suggest that antithrombosis of TET and FAN in mice may be mainly related to the antiplatelet aggregation activities.", "entity": "fangchinoline", "aliases": "(1beta)-isomer of fangchinoline 7-O-demethyl-tetrandrine 7-O-demethyltetrandrine isofangchinoline limacine thaligine thalrugosine", "definition": "", "id": "MESH:C060802"}
{"mention": "FAN", "mention_text": "Tetrandrine (TET) and fangchinoline (FAN) are two naturally occurring analogues with a bisbenzylisoquinoline structure. The present study was undertaken to investigate the effects of TET and FAN on the experimental thrombosis induced by collagen plus epinephrine (EP) in mice, and platelet aggregation and blood coagulation in vitro. In the in vivo study, the administration (50 mg/kg, i.p.) of TET and FAN in mice showed the inhibition of thrombosis by 55% and 35%, respectively, while acetylsalicylic acid (ASA, 50 mg/kg, i.p.), a positive control, showed only 30% inhibition. In the vitro human platelet aggregations induced by the agonists used in tests, TET and FAN showed the inhibitions dose dependently. In addition, neither TET nor FAN showed any anticoagulation activities in the measurement of the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) using human-citrated plasma. These results suggest that antithrombosis of TET and FAN in mice may be mainly related to the antiplatelet aggregation activities.", "entity": "fangchinoline", "aliases": "(1beta)-isomer of fangchinoline 7-O-demethyl-tetrandrine 7-O-demethyltetrandrine isofangchinoline limacine thaligine thalrugosine", "definition": "", "id": "MESH:C060802"}
{"mention": "bisbenzylisoquinoline", "mention_text": "Tetrandrine (TET) and fangchinoline (FAN) are two naturally occurring analogues with a bisbenzylisoquinoline structure. The present study was undertaken to investigate the effects of TET and FAN on the experimental thrombosis induced by collagen plus epinephrine (EP) in mice, and platelet aggregation and blood coagulation in vitro. In the in vivo study, the administration (50 mg/kg, i.p.) of TET and FAN in mice showed the inhibition of thrombosis by 55% and 35%, respectively, while acetylsalicylic acid (ASA, 50 mg/kg, i.p.), a positive control, showed only 30% inhibition. In the vitro human platelet aggregations induced by the agonists used in tests, TET and FAN showed the inhibitions dose dependently. In addition, neither TET nor FAN showed any anticoagulation activities in the measurement of the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) using human-citrated plasma. These results suggest that antithrombosis of TET and FAN in mice may be mainly related to the antiplatelet aggregation activities.", "entity": "Benzylisoquinolines", "aliases": "Benzyl Isoquinolines Benzyl-Isoquinolines Benzylisoquinolines Bis Bis-Benzyl-Isoquinolines Bis-Benzylisoquinolines Bisbenzylisoquinolines", "definition": "ISOQUINOLINES with a benzyl substituent.\n    ", "id": "MESH:D044182"}
{"mention": "thrombosis", "mention_text": "Tetrandrine (TET) and fangchinoline (FAN) are two naturally occurring analogues with a bisbenzylisoquinoline structure. The present study was undertaken to investigate the effects of TET and FAN on the experimental thrombosis induced by collagen plus epinephrine (EP) in mice, and platelet aggregation and blood coagulation in vitro. In the in vivo study, the administration (50 mg/kg, i.p.) of TET and FAN in mice showed the inhibition of thrombosis by 55% and 35%, respectively, while acetylsalicylic acid (ASA, 50 mg/kg, i.p.), a positive control, showed only 30% inhibition. In the vitro human platelet aggregations induced by the agonists used in tests, TET and FAN showed the inhibitions dose dependently. In addition, neither TET nor FAN showed any anticoagulation activities in the measurement of the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) using human-citrated plasma. These results suggest that antithrombosis of TET and FAN in mice may be mainly related to the antiplatelet aggregation activities.", "entity": "Thrombosis", "aliases": "Thromboses Thrombosis Thrombus", "definition": "Formation and development of a thrombus or blood clot in the blood vessel.\n    ", "id": "MESH:D013927"}
{"mention": "epinephrine", "mention_text": "Tetrandrine (TET) and fangchinoline (FAN) are two naturally occurring analogues with a bisbenzylisoquinoline structure. The present study was undertaken to investigate the effects of TET and FAN on the experimental thrombosis induced by collagen plus epinephrine (EP) in mice, and platelet aggregation and blood coagulation in vitro. In the in vivo study, the administration (50 mg/kg, i.p.) of TET and FAN in mice showed the inhibition of thrombosis by 55% and 35%, respectively, while acetylsalicylic acid (ASA, 50 mg/kg, i.p.), a positive control, showed only 30% inhibition. In the vitro human platelet aggregations induced by the agonists used in tests, TET and FAN showed the inhibitions dose dependently. In addition, neither TET nor FAN showed any anticoagulation activities in the measurement of the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) using human-citrated plasma. These results suggest that antithrombosis of TET and FAN in mice may be mainly related to the antiplatelet aggregation activities.", "entity": "Epinephrine", "aliases": "4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-benzenediol Acetate Epinephrine Adrenaline Acid Tartrate Bitartrate Hydrochloride Allergan Brand of Epifrin Hydrogen Epitrate Lyophrin Medihaler-Epi", "definition": "The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.\n    ", "id": "MESH:D004837"}
{"mention": "EP", "mention_text": "Tetrandrine (TET) and fangchinoline (FAN) are two naturally occurring analogues with a bisbenzylisoquinoline structure. The present study was undertaken to investigate the effects of TET and FAN on the experimental thrombosis induced by collagen plus epinephrine (EP) in mice, and platelet aggregation and blood coagulation in vitro. In the in vivo study, the administration (50 mg/kg, i.p.) of TET and FAN in mice showed the inhibition of thrombosis by 55% and 35%, respectively, while acetylsalicylic acid (ASA, 50 mg/kg, i.p.), a positive control, showed only 30% inhibition. In the vitro human platelet aggregations induced by the agonists used in tests, TET and FAN showed the inhibitions dose dependently. In addition, neither TET nor FAN showed any anticoagulation activities in the measurement of the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) using human-citrated plasma. These results suggest that antithrombosis of TET and FAN in mice may be mainly related to the antiplatelet aggregation activities.", "entity": "Epinephrine", "aliases": "4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-benzenediol Acetate Epinephrine Adrenaline Acid Tartrate Bitartrate Hydrochloride Allergan Brand of Epifrin Hydrogen Epitrate Lyophrin Medihaler-Epi", "definition": "The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.\n    ", "id": "MESH:D004837"}
{"mention": "platelet aggregation", "mention_text": "Tetrandrine (TET) and fangchinoline (FAN) are two naturally occurring analogues with a bisbenzylisoquinoline structure. The present study was undertaken to investigate the effects of TET and FAN on the experimental thrombosis induced by collagen plus epinephrine (EP) in mice, and platelet aggregation and blood coagulation in vitro. In the in vivo study, the administration (50 mg/kg, i.p.) of TET and FAN in mice showed the inhibition of thrombosis by 55% and 35%, respectively, while acetylsalicylic acid (ASA, 50 mg/kg, i.p.), a positive control, showed only 30% inhibition. In the vitro human platelet aggregations induced by the agonists used in tests, TET and FAN showed the inhibitions dose dependently. In addition, neither TET nor FAN showed any anticoagulation activities in the measurement of the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) using human-citrated plasma. These results suggest that antithrombosis of TET and FAN in mice may be mainly related to the antiplatelet aggregation activities.", "entity": "Blood Platelet Disorders", "aliases": "Blood Platelet Disorder Disorders Thrombocytopathies Thrombocytopathy", "definition": "Disorders caused by abnormalities in platelet count or function.\n    ", "id": "MESH:D001791"}
{"mention": "blood coagulation", "mention_text": "Tetrandrine (TET) and fangchinoline (FAN) are two naturally occurring analogues with a bisbenzylisoquinoline structure. The present study was undertaken to investigate the effects of TET and FAN on the experimental thrombosis induced by collagen plus epinephrine (EP) in mice, and platelet aggregation and blood coagulation in vitro. In the in vivo study, the administration (50 mg/kg, i.p.) of TET and FAN in mice showed the inhibition of thrombosis by 55% and 35%, respectively, while acetylsalicylic acid (ASA, 50 mg/kg, i.p.), a positive control, showed only 30% inhibition. In the vitro human platelet aggregations induced by the agonists used in tests, TET and FAN showed the inhibitions dose dependently. In addition, neither TET nor FAN showed any anticoagulation activities in the measurement of the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) using human-citrated plasma. These results suggest that antithrombosis of TET and FAN in mice may be mainly related to the antiplatelet aggregation activities.", "entity": "Blood Coagulation Disorders", "aliases": "Blood Coagulation Disorder Disorders", "definition": "Hemorrhagic and thrombotic disorders that occur as a consequence of abnormalities in blood coagulation due to a variety of factors such as COAGULATION PROTEIN DISORDERS; BLOOD PLATELET DISORDERS; BLOOD PROTEIN DISORDERS or nutritional conditions.\n    ", "id": "MESH:D001778"}
{"mention": "acetylsalicylic acid", "mention_text": "Tetrandrine (TET) and fangchinoline (FAN) are two naturally occurring analogues with a bisbenzylisoquinoline structure. The present study was undertaken to investigate the effects of TET and FAN on the experimental thrombosis induced by collagen plus epinephrine (EP) in mice, and platelet aggregation and blood coagulation in vitro. In the in vivo study, the administration (50 mg/kg, i.p.) of TET and FAN in mice showed the inhibition of thrombosis by 55% and 35%, respectively, while acetylsalicylic acid (ASA, 50 mg/kg, i.p.), a positive control, showed only 30% inhibition. In the vitro human platelet aggregations induced by the agonists used in tests, TET and FAN showed the inhibitions dose dependently. In addition, neither TET nor FAN showed any anticoagulation activities in the measurement of the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) using human-citrated plasma. These results suggest that antithrombosis of TET and FAN in mice may be mainly related to the antiplatelet aggregation activities.", "entity": "Aspirin", "aliases": "2-(Acetyloxy)benzoic Acid Acetylsalicylic Acetysal Acylpyrin Aloxiprimum Aspirin Colfarit Dispril Easprin Ecotrin Endosprin Magnecyl Micristin Polopirin Polopiryna Solprin Solupsan Zorprin", "definition": "The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)\n    ", "id": "MESH:D001241"}
{"mention": "ASA", "mention_text": "Tetrandrine (TET) and fangchinoline (FAN) are two naturally occurring analogues with a bisbenzylisoquinoline structure. The present study was undertaken to investigate the effects of TET and FAN on the experimental thrombosis induced by collagen plus epinephrine (EP) in mice, and platelet aggregation and blood coagulation in vitro. In the in vivo study, the administration (50 mg/kg, i.p.) of TET and FAN in mice showed the inhibition of thrombosis by 55% and 35%, respectively, while acetylsalicylic acid (ASA, 50 mg/kg, i.p.), a positive control, showed only 30% inhibition. In the vitro human platelet aggregations induced by the agonists used in tests, TET and FAN showed the inhibitions dose dependently. In addition, neither TET nor FAN showed any anticoagulation activities in the measurement of the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) using human-citrated plasma. These results suggest that antithrombosis of TET and FAN in mice may be mainly related to the antiplatelet aggregation activities.", "entity": "Aspirin", "aliases": "2-(Acetyloxy)benzoic Acid Acetylsalicylic Acetysal Acylpyrin Aloxiprimum Aspirin Colfarit Dispril Easprin Ecotrin Endosprin Magnecyl Micristin Polopirin Polopiryna Solprin Solupsan Zorprin", "definition": "The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)\n    ", "id": "MESH:D001241"}
{"mention": "platelet aggregations", "mention_text": "Tetrandrine (TET) and fangchinoline (FAN) are two naturally occurring analogues with a bisbenzylisoquinoline structure. The present study was undertaken to investigate the effects of TET and FAN on the experimental thrombosis induced by collagen plus epinephrine (EP) in mice, and platelet aggregation and blood coagulation in vitro. In the in vivo study, the administration (50 mg/kg, i.p.) of TET and FAN in mice showed the inhibition of thrombosis by 55% and 35%, respectively, while acetylsalicylic acid (ASA, 50 mg/kg, i.p.), a positive control, showed only 30% inhibition. In the vitro human platelet aggregations induced by the agonists used in tests, TET and FAN showed the inhibitions dose dependently. In addition, neither TET nor FAN showed any anticoagulation activities in the measurement of the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) using human-citrated plasma. These results suggest that antithrombosis of TET and FAN in mice may be mainly related to the antiplatelet aggregation activities.", "entity": "Blood Platelet Disorders", "aliases": "Blood Platelet Disorder Disorders Thrombocytopathies Thrombocytopathy", "definition": "Disorders caused by abnormalities in platelet count or function.\n    ", "id": "MESH:D001791"}
{"mention": "Gemcitabine", "mention_text": "Gemcitabine plus vinorelbine in nonsmall cell lung carcinoma patients age 70 years or older or patients who cannot receive cisplatin. Oncopaz Cooperative Group.", "entity": "gemcitabine", "aliases": "2',2'-DFDC 2',2'-difluoro-2'-deoxycytidine 2',2'-difluorodeoxycytidine 2'-deoxy-2',2''-difluorocytidine-5'-O-monophosphate 2'-deoxy-2'-difluorocytidine Gemzar LY 188011 LY-188011 dFdCyd gemcitabine hydrochloride (D-threo-pentafuranosyl)-isomer (alpha-D-threo-pentofuranosyl)-isomer (beta-D-threo-pentafuranosyl)-isomer", "definition": "", "id": "MESH:C056507"}
{"mention": "vinorelbine", "mention_text": "Gemcitabine plus vinorelbine in nonsmall cell lung carcinoma patients age 70 years or older or patients who cannot receive cisplatin. Oncopaz Cooperative Group.", "entity": "vinorelbine", "aliases": "5'-nor-anhydrovinblastine KW 2307 KW-2307 Navelbine vinorelbine tartrate", "definition": "", "id": "MESH:C030852"}
{"mention": "nonsmall cell lung carcinoma", "mention_text": "Gemcitabine plus vinorelbine in nonsmall cell lung carcinoma patients age 70 years or older or patients who cannot receive cisplatin. Oncopaz Cooperative Group.", "entity": "Carcinoma, Non-Small-Cell Lung", "aliases": "Carcinoma Non Small Cell Lung Non-Small Non-Small-Cell Carcinomas Cancer Nonsmall", "definition": "A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.\n    ", "id": "MESH:D002289"}
{"mention": "cisplatin", "mention_text": "Gemcitabine plus vinorelbine in nonsmall cell lung carcinoma patients age 70 years or older or patients who cannot receive cisplatin. Oncopaz Cooperative Group.", "entity": "Cisplatin", "aliases": "Biocisplatinum Cisplatin Diamminodichloride Platinum Dichlorodiammineplatinum NSC-119875 Platidiam Platino Platinol cis Diamminedichloroplatinum cis-Diamminedichloroplatinum cis-Diamminedichloroplatinum(II) cis-Dichlorodiammineplatinum(II) cis-Platinum", "definition": "An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.\n    ", "id": "MESH:D002945"}
{"mention": "nonsmall cell lung carcinoma", "mention_text": "BACKGROUND: Although the prevalence of nonsmall cell lung carcinoma (NSCLC) is high among elderly patients, few data are available regarding the efficacy and toxicity of chemotherapy in this group of patients. Recent reports indicate that single agent therapy with vinorelbine (VNB) or gemcitabine (GEM) may obtain a response rate of 20-30% in elderly patients, with acceptable toxicity and improvement in symptoms and quality of life. In the current study the efficacy and toxicity of the combination of GEM and VNB in elderly patients with advanced NSCLC or those with some contraindication to receiving cisplatin were assessed. METHODS: Forty-nine patients with advanced NSCLC were included, 38 of whom were age >/= 70 years and 11 were age < 70 years but who had some contraindication to receiving cisplatin. All patients were evaluable for response and toxicity. Treatment was comprised of VNB, 25 mg/m(2), plus GEM, 1000 mg/m(2), both on Days 1, 8, and 15 every 28 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: One hundred sixty-five courses were administered, with a median of 3. 6 courses per patient. The overall response rate was 26% (95% confidence interval, 15-41%). Two patients attained a complete response (4%) and 11 patients (22%) achieved a partial response. Eastern Cooperative Oncology Group performance status improved in 35% of those patients with an initial value > 0, whereas relief of at least 1 symptom without worsening of other symptoms was noted in 27 patients (55%). The median time to progression was 16 weeks and the 1-year survival rate was 33%. Toxicity was mild. Six patients (12%) had World Health Organization Grade 3-4 neutropenia, 2 patients (4%) had Grade 3-4 thrombocytopenia, and 2 patients (4%) had Grade 3 neurotoxicity. Three patients with severe neutropenia (6%) died of sepsis. The median age of those patients developing Grade 3-4 neutropenia was significantly higher than that of the remaining patients (75 years vs. 72 years; P = 0.047). CONCLUSIONS: The combination of GEM and VNB is moderately active and well tolerated except in patients age >/= 75 years. This age group had an increased risk of myelosuppression. Therefore the prophylactic use of granulocyte-colony stimulating factor should be considered with this treatment. New chemotherapy combinations with higher activity and lower toxicity are needed for elderly patients with advanced NSCLC.", "entity": "Carcinoma, Non-Small-Cell Lung", "aliases": "Carcinoma Non Small Cell Lung Non-Small Non-Small-Cell Carcinomas Cancer Nonsmall", "definition": "A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.\n    ", "id": "MESH:D002289"}
{"mention": "NSCLC", "mention_text": "BACKGROUND: Although the prevalence of nonsmall cell lung carcinoma (NSCLC) is high among elderly patients, few data are available regarding the efficacy and toxicity of chemotherapy in this group of patients. Recent reports indicate that single agent therapy with vinorelbine (VNB) or gemcitabine (GEM) may obtain a response rate of 20-30% in elderly patients, with acceptable toxicity and improvement in symptoms and quality of life. In the current study the efficacy and toxicity of the combination of GEM and VNB in elderly patients with advanced NSCLC or those with some contraindication to receiving cisplatin were assessed. METHODS: Forty-nine patients with advanced NSCLC were included, 38 of whom were age >/= 70 years and 11 were age < 70 years but who had some contraindication to receiving cisplatin. All patients were evaluable for response and toxicity. Treatment was comprised of VNB, 25 mg/m(2), plus GEM, 1000 mg/m(2), both on Days 1, 8, and 15 every 28 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: One hundred sixty-five courses were administered, with a median of 3. 6 courses per patient. The overall response rate was 26% (95% confidence interval, 15-41%). Two patients attained a complete response (4%) and 11 patients (22%) achieved a partial response. Eastern Cooperative Oncology Group performance status improved in 35% of those patients with an initial value > 0, whereas relief of at least 1 symptom without worsening of other symptoms was noted in 27 patients (55%). The median time to progression was 16 weeks and the 1-year survival rate was 33%. Toxicity was mild. Six patients (12%) had World Health Organization Grade 3-4 neutropenia, 2 patients (4%) had Grade 3-4 thrombocytopenia, and 2 patients (4%) had Grade 3 neurotoxicity. Three patients with severe neutropenia (6%) died of sepsis. The median age of those patients developing Grade 3-4 neutropenia was significantly higher than that of the remaining patients (75 years vs. 72 years; P = 0.047). CONCLUSIONS: The combination of GEM and VNB is moderately active and well tolerated except in patients age >/= 75 years. This age group had an increased risk of myelosuppression. Therefore the prophylactic use of granulocyte-colony stimulating factor should be considered with this treatment. New chemotherapy combinations with higher activity and lower toxicity are needed for elderly patients with advanced NSCLC.", "entity": "Carcinoma, Non-Small-Cell Lung", "aliases": "Carcinoma Non Small Cell Lung Non-Small Non-Small-Cell Carcinomas Cancer Nonsmall", "definition": "A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.\n    ", "id": "MESH:D002289"}
{"mention": "toxicity", "mention_text": "BACKGROUND: Although the prevalence of nonsmall cell lung carcinoma (NSCLC) is high among elderly patients, few data are available regarding the efficacy and toxicity of chemotherapy in this group of patients. Recent reports indicate that single agent therapy with vinorelbine (VNB) or gemcitabine (GEM) may obtain a response rate of 20-30% in elderly patients, with acceptable toxicity and improvement in symptoms and quality of life. In the current study the efficacy and toxicity of the combination of GEM and VNB in elderly patients with advanced NSCLC or those with some contraindication to receiving cisplatin were assessed. METHODS: Forty-nine patients with advanced NSCLC were included, 38 of whom were age >/= 70 years and 11 were age < 70 years but who had some contraindication to receiving cisplatin. All patients were evaluable for response and toxicity. Treatment was comprised of VNB, 25 mg/m(2), plus GEM, 1000 mg/m(2), both on Days 1, 8, and 15 every 28 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: One hundred sixty-five courses were administered, with a median of 3. 6 courses per patient. The overall response rate was 26% (95% confidence interval, 15-41%). Two patients attained a complete response (4%) and 11 patients (22%) achieved a partial response. Eastern Cooperative Oncology Group performance status improved in 35% of those patients with an initial value > 0, whereas relief of at least 1 symptom without worsening of other symptoms was noted in 27 patients (55%). The median time to progression was 16 weeks and the 1-year survival rate was 33%. Toxicity was mild. Six patients (12%) had World Health Organization Grade 3-4 neutropenia, 2 patients (4%) had Grade 3-4 thrombocytopenia, and 2 patients (4%) had Grade 3 neurotoxicity. Three patients with severe neutropenia (6%) died of sepsis. The median age of those patients developing Grade 3-4 neutropenia was significantly higher than that of the remaining patients (75 years vs. 72 years; P = 0.047). CONCLUSIONS: The combination of GEM and VNB is moderately active and well tolerated except in patients age >/= 75 years. This age group had an increased risk of myelosuppression. Therefore the prophylactic use of granulocyte-colony stimulating factor should be considered with this treatment. New chemotherapy combinations with higher activity and lower toxicity are needed for elderly patients with advanced NSCLC.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "vinorelbine", "mention_text": "BACKGROUND: Although the prevalence of nonsmall cell lung carcinoma (NSCLC) is high among elderly patients, few data are available regarding the efficacy and toxicity of chemotherapy in this group of patients. Recent reports indicate that single agent therapy with vinorelbine (VNB) or gemcitabine (GEM) may obtain a response rate of 20-30% in elderly patients, with acceptable toxicity and improvement in symptoms and quality of life. In the current study the efficacy and toxicity of the combination of GEM and VNB in elderly patients with advanced NSCLC or those with some contraindication to receiving cisplatin were assessed. METHODS: Forty-nine patients with advanced NSCLC were included, 38 of whom were age >/= 70 years and 11 were age < 70 years but who had some contraindication to receiving cisplatin. All patients were evaluable for response and toxicity. Treatment was comprised of VNB, 25 mg/m(2), plus GEM, 1000 mg/m(2), both on Days 1, 8, and 15 every 28 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: One hundred sixty-five courses were administered, with a median of 3. 6 courses per patient. The overall response rate was 26% (95% confidence interval, 15-41%). Two patients attained a complete response (4%) and 11 patients (22%) achieved a partial response. Eastern Cooperative Oncology Group performance status improved in 35% of those patients with an initial value > 0, whereas relief of at least 1 symptom without worsening of other symptoms was noted in 27 patients (55%). The median time to progression was 16 weeks and the 1-year survival rate was 33%. Toxicity was mild. Six patients (12%) had World Health Organization Grade 3-4 neutropenia, 2 patients (4%) had Grade 3-4 thrombocytopenia, and 2 patients (4%) had Grade 3 neurotoxicity. Three patients with severe neutropenia (6%) died of sepsis. The median age of those patients developing Grade 3-4 neutropenia was significantly higher than that of the remaining patients (75 years vs. 72 years; P = 0.047). CONCLUSIONS: The combination of GEM and VNB is moderately active and well tolerated except in patients age >/= 75 years. This age group had an increased risk of myelosuppression. Therefore the prophylactic use of granulocyte-colony stimulating factor should be considered with this treatment. New chemotherapy combinations with higher activity and lower toxicity are needed for elderly patients with advanced NSCLC.", "entity": "vinorelbine", "aliases": "5'-nor-anhydrovinblastine KW 2307 KW-2307 Navelbine vinorelbine tartrate", "definition": "", "id": "MESH:C030852"}
{"mention": "VNB", "mention_text": "BACKGROUND: Although the prevalence of nonsmall cell lung carcinoma (NSCLC) is high among elderly patients, few data are available regarding the efficacy and toxicity of chemotherapy in this group of patients. Recent reports indicate that single agent therapy with vinorelbine (VNB) or gemcitabine (GEM) may obtain a response rate of 20-30% in elderly patients, with acceptable toxicity and improvement in symptoms and quality of life. In the current study the efficacy and toxicity of the combination of GEM and VNB in elderly patients with advanced NSCLC or those with some contraindication to receiving cisplatin were assessed. METHODS: Forty-nine patients with advanced NSCLC were included, 38 of whom were age >/= 70 years and 11 were age < 70 years but who had some contraindication to receiving cisplatin. All patients were evaluable for response and toxicity. Treatment was comprised of VNB, 25 mg/m(2), plus GEM, 1000 mg/m(2), both on Days 1, 8, and 15 every 28 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: One hundred sixty-five courses were administered, with a median of 3. 6 courses per patient. The overall response rate was 26% (95% confidence interval, 15-41%). Two patients attained a complete response (4%) and 11 patients (22%) achieved a partial response. Eastern Cooperative Oncology Group performance status improved in 35% of those patients with an initial value > 0, whereas relief of at least 1 symptom without worsening of other symptoms was noted in 27 patients (55%). The median time to progression was 16 weeks and the 1-year survival rate was 33%. Toxicity was mild. Six patients (12%) had World Health Organization Grade 3-4 neutropenia, 2 patients (4%) had Grade 3-4 thrombocytopenia, and 2 patients (4%) had Grade 3 neurotoxicity. Three patients with severe neutropenia (6%) died of sepsis. The median age of those patients developing Grade 3-4 neutropenia was significantly higher than that of the remaining patients (75 years vs. 72 years; P = 0.047). CONCLUSIONS: The combination of GEM and VNB is moderately active and well tolerated except in patients age >/= 75 years. This age group had an increased risk of myelosuppression. Therefore the prophylactic use of granulocyte-colony stimulating factor should be considered with this treatment. New chemotherapy combinations with higher activity and lower toxicity are needed for elderly patients with advanced NSCLC.", "entity": "vinorelbine", "aliases": "5'-nor-anhydrovinblastine KW 2307 KW-2307 Navelbine vinorelbine tartrate", "definition": "", "id": "MESH:C030852"}
{"mention": "gemcitabine", "mention_text": "BACKGROUND: Although the prevalence of nonsmall cell lung carcinoma (NSCLC) is high among elderly patients, few data are available regarding the efficacy and toxicity of chemotherapy in this group of patients. Recent reports indicate that single agent therapy with vinorelbine (VNB) or gemcitabine (GEM) may obtain a response rate of 20-30% in elderly patients, with acceptable toxicity and improvement in symptoms and quality of life. In the current study the efficacy and toxicity of the combination of GEM and VNB in elderly patients with advanced NSCLC or those with some contraindication to receiving cisplatin were assessed. METHODS: Forty-nine patients with advanced NSCLC were included, 38 of whom were age >/= 70 years and 11 were age < 70 years but who had some contraindication to receiving cisplatin. All patients were evaluable for response and toxicity. Treatment was comprised of VNB, 25 mg/m(2), plus GEM, 1000 mg/m(2), both on Days 1, 8, and 15 every 28 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: One hundred sixty-five courses were administered, with a median of 3. 6 courses per patient. The overall response rate was 26% (95% confidence interval, 15-41%). Two patients attained a complete response (4%) and 11 patients (22%) achieved a partial response. Eastern Cooperative Oncology Group performance status improved in 35% of those patients with an initial value > 0, whereas relief of at least 1 symptom without worsening of other symptoms was noted in 27 patients (55%). The median time to progression was 16 weeks and the 1-year survival rate was 33%. Toxicity was mild. Six patients (12%) had World Health Organization Grade 3-4 neutropenia, 2 patients (4%) had Grade 3-4 thrombocytopenia, and 2 patients (4%) had Grade 3 neurotoxicity. Three patients with severe neutropenia (6%) died of sepsis. The median age of those patients developing Grade 3-4 neutropenia was significantly higher than that of the remaining patients (75 years vs. 72 years; P = 0.047). CONCLUSIONS: The combination of GEM and VNB is moderately active and well tolerated except in patients age >/= 75 years. This age group had an increased risk of myelosuppression. Therefore the prophylactic use of granulocyte-colony stimulating factor should be considered with this treatment. New chemotherapy combinations with higher activity and lower toxicity are needed for elderly patients with advanced NSCLC.", "entity": "gemcitabine", "aliases": "2',2'-DFDC 2',2'-difluoro-2'-deoxycytidine 2',2'-difluorodeoxycytidine 2'-deoxy-2',2''-difluorocytidine-5'-O-monophosphate 2'-deoxy-2'-difluorocytidine Gemzar LY 188011 LY-188011 dFdCyd gemcitabine hydrochloride (D-threo-pentafuranosyl)-isomer (alpha-D-threo-pentofuranosyl)-isomer (beta-D-threo-pentafuranosyl)-isomer", "definition": "", "id": "MESH:C056507"}
{"mention": "GEM", "mention_text": "BACKGROUND: Although the prevalence of nonsmall cell lung carcinoma (NSCLC) is high among elderly patients, few data are available regarding the efficacy and toxicity of chemotherapy in this group of patients. Recent reports indicate that single agent therapy with vinorelbine (VNB) or gemcitabine (GEM) may obtain a response rate of 20-30% in elderly patients, with acceptable toxicity and improvement in symptoms and quality of life. In the current study the efficacy and toxicity of the combination of GEM and VNB in elderly patients with advanced NSCLC or those with some contraindication to receiving cisplatin were assessed. METHODS: Forty-nine patients with advanced NSCLC were included, 38 of whom were age >/= 70 years and 11 were age < 70 years but who had some contraindication to receiving cisplatin. All patients were evaluable for response and toxicity. Treatment was comprised of VNB, 25 mg/m(2), plus GEM, 1000 mg/m(2), both on Days 1, 8, and 15 every 28 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: One hundred sixty-five courses were administered, with a median of 3. 6 courses per patient. The overall response rate was 26% (95% confidence interval, 15-41%). Two patients attained a complete response (4%) and 11 patients (22%) achieved a partial response. Eastern Cooperative Oncology Group performance status improved in 35% of those patients with an initial value > 0, whereas relief of at least 1 symptom without worsening of other symptoms was noted in 27 patients (55%). The median time to progression was 16 weeks and the 1-year survival rate was 33%. Toxicity was mild. Six patients (12%) had World Health Organization Grade 3-4 neutropenia, 2 patients (4%) had Grade 3-4 thrombocytopenia, and 2 patients (4%) had Grade 3 neurotoxicity. Three patients with severe neutropenia (6%) died of sepsis. The median age of those patients developing Grade 3-4 neutropenia was significantly higher than that of the remaining patients (75 years vs. 72 years; P = 0.047). CONCLUSIONS: The combination of GEM and VNB is moderately active and well tolerated except in patients age >/= 75 years. This age group had an increased risk of myelosuppression. Therefore the prophylactic use of granulocyte-colony stimulating factor should be considered with this treatment. New chemotherapy combinations with higher activity and lower toxicity are needed for elderly patients with advanced NSCLC.", "entity": "gemcitabine", "aliases": "2',2'-DFDC 2',2'-difluoro-2'-deoxycytidine 2',2'-difluorodeoxycytidine 2'-deoxy-2',2''-difluorocytidine-5'-O-monophosphate 2'-deoxy-2'-difluorocytidine Gemzar LY 188011 LY-188011 dFdCyd gemcitabine hydrochloride (D-threo-pentafuranosyl)-isomer (alpha-D-threo-pentofuranosyl)-isomer (beta-D-threo-pentafuranosyl)-isomer", "definition": "", "id": "MESH:C056507"}
{"mention": "cisplatin", "mention_text": "BACKGROUND: Although the prevalence of nonsmall cell lung carcinoma (NSCLC) is high among elderly patients, few data are available regarding the efficacy and toxicity of chemotherapy in this group of patients. Recent reports indicate that single agent therapy with vinorelbine (VNB) or gemcitabine (GEM) may obtain a response rate of 20-30% in elderly patients, with acceptable toxicity and improvement in symptoms and quality of life. In the current study the efficacy and toxicity of the combination of GEM and VNB in elderly patients with advanced NSCLC or those with some contraindication to receiving cisplatin were assessed. METHODS: Forty-nine patients with advanced NSCLC were included, 38 of whom were age >/= 70 years and 11 were age < 70 years but who had some contraindication to receiving cisplatin. All patients were evaluable for response and toxicity. Treatment was comprised of VNB, 25 mg/m(2), plus GEM, 1000 mg/m(2), both on Days 1, 8, and 15 every 28 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: One hundred sixty-five courses were administered, with a median of 3. 6 courses per patient. The overall response rate was 26% (95% confidence interval, 15-41%). Two patients attained a complete response (4%) and 11 patients (22%) achieved a partial response. Eastern Cooperative Oncology Group performance status improved in 35% of those patients with an initial value > 0, whereas relief of at least 1 symptom without worsening of other symptoms was noted in 27 patients (55%). The median time to progression was 16 weeks and the 1-year survival rate was 33%. Toxicity was mild. Six patients (12%) had World Health Organization Grade 3-4 neutropenia, 2 patients (4%) had Grade 3-4 thrombocytopenia, and 2 patients (4%) had Grade 3 neurotoxicity. Three patients with severe neutropenia (6%) died of sepsis. The median age of those patients developing Grade 3-4 neutropenia was significantly higher than that of the remaining patients (75 years vs. 72 years; P = 0.047). CONCLUSIONS: The combination of GEM and VNB is moderately active and well tolerated except in patients age >/= 75 years. This age group had an increased risk of myelosuppression. Therefore the prophylactic use of granulocyte-colony stimulating factor should be considered with this treatment. New chemotherapy combinations with higher activity and lower toxicity are needed for elderly patients with advanced NSCLC.", "entity": "Cisplatin", "aliases": "Biocisplatinum Cisplatin Diamminodichloride Platinum Dichlorodiammineplatinum NSC-119875 Platidiam Platino Platinol cis Diamminedichloroplatinum cis-Diamminedichloroplatinum cis-Diamminedichloroplatinum(II) cis-Dichlorodiammineplatinum(II) cis-Platinum", "definition": "An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.\n    ", "id": "MESH:D002945"}
{"mention": "Toxicity", "mention_text": "BACKGROUND: Although the prevalence of nonsmall cell lung carcinoma (NSCLC) is high among elderly patients, few data are available regarding the efficacy and toxicity of chemotherapy in this group of patients. Recent reports indicate that single agent therapy with vinorelbine (VNB) or gemcitabine (GEM) may obtain a response rate of 20-30% in elderly patients, with acceptable toxicity and improvement in symptoms and quality of life. In the current study the efficacy and toxicity of the combination of GEM and VNB in elderly patients with advanced NSCLC or those with some contraindication to receiving cisplatin were assessed. METHODS: Forty-nine patients with advanced NSCLC were included, 38 of whom were age >/= 70 years and 11 were age < 70 years but who had some contraindication to receiving cisplatin. All patients were evaluable for response and toxicity. Treatment was comprised of VNB, 25 mg/m(2), plus GEM, 1000 mg/m(2), both on Days 1, 8, and 15 every 28 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: One hundred sixty-five courses were administered, with a median of 3. 6 courses per patient. The overall response rate was 26% (95% confidence interval, 15-41%). Two patients attained a complete response (4%) and 11 patients (22%) achieved a partial response. Eastern Cooperative Oncology Group performance status improved in 35% of those patients with an initial value > 0, whereas relief of at least 1 symptom without worsening of other symptoms was noted in 27 patients (55%). The median time to progression was 16 weeks and the 1-year survival rate was 33%. Toxicity was mild. Six patients (12%) had World Health Organization Grade 3-4 neutropenia, 2 patients (4%) had Grade 3-4 thrombocytopenia, and 2 patients (4%) had Grade 3 neurotoxicity. Three patients with severe neutropenia (6%) died of sepsis. The median age of those patients developing Grade 3-4 neutropenia was significantly higher than that of the remaining patients (75 years vs. 72 years; P = 0.047). CONCLUSIONS: The combination of GEM and VNB is moderately active and well tolerated except in patients age >/= 75 years. This age group had an increased risk of myelosuppression. Therefore the prophylactic use of granulocyte-colony stimulating factor should be considered with this treatment. New chemotherapy combinations with higher activity and lower toxicity are needed for elderly patients with advanced NSCLC.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "neutropenia", "mention_text": "BACKGROUND: Although the prevalence of nonsmall cell lung carcinoma (NSCLC) is high among elderly patients, few data are available regarding the efficacy and toxicity of chemotherapy in this group of patients. Recent reports indicate that single agent therapy with vinorelbine (VNB) or gemcitabine (GEM) may obtain a response rate of 20-30% in elderly patients, with acceptable toxicity and improvement in symptoms and quality of life. In the current study the efficacy and toxicity of the combination of GEM and VNB in elderly patients with advanced NSCLC or those with some contraindication to receiving cisplatin were assessed. METHODS: Forty-nine patients with advanced NSCLC were included, 38 of whom were age >/= 70 years and 11 were age < 70 years but who had some contraindication to receiving cisplatin. All patients were evaluable for response and toxicity. Treatment was comprised of VNB, 25 mg/m(2), plus GEM, 1000 mg/m(2), both on Days 1, 8, and 15 every 28 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: One hundred sixty-five courses were administered, with a median of 3. 6 courses per patient. The overall response rate was 26% (95% confidence interval, 15-41%). Two patients attained a complete response (4%) and 11 patients (22%) achieved a partial response. Eastern Cooperative Oncology Group performance status improved in 35% of those patients with an initial value > 0, whereas relief of at least 1 symptom without worsening of other symptoms was noted in 27 patients (55%). The median time to progression was 16 weeks and the 1-year survival rate was 33%. Toxicity was mild. Six patients (12%) had World Health Organization Grade 3-4 neutropenia, 2 patients (4%) had Grade 3-4 thrombocytopenia, and 2 patients (4%) had Grade 3 neurotoxicity. Three patients with severe neutropenia (6%) died of sepsis. The median age of those patients developing Grade 3-4 neutropenia was significantly higher than that of the remaining patients (75 years vs. 72 years; P = 0.047). CONCLUSIONS: The combination of GEM and VNB is moderately active and well tolerated except in patients age >/= 75 years. This age group had an increased risk of myelosuppression. Therefore the prophylactic use of granulocyte-colony stimulating factor should be considered with this treatment. New chemotherapy combinations with higher activity and lower toxicity are needed for elderly patients with advanced NSCLC.", "entity": "Neutropenia", "aliases": "Neutropenia Neutropenias", "definition": "A decrease in the number of NEUTROPHILS found in the blood.\n    ", "id": "MESH:D009503"}
{"mention": "thrombocytopenia", "mention_text": "BACKGROUND: Although the prevalence of nonsmall cell lung carcinoma (NSCLC) is high among elderly patients, few data are available regarding the efficacy and toxicity of chemotherapy in this group of patients. Recent reports indicate that single agent therapy with vinorelbine (VNB) or gemcitabine (GEM) may obtain a response rate of 20-30% in elderly patients, with acceptable toxicity and improvement in symptoms and quality of life. In the current study the efficacy and toxicity of the combination of GEM and VNB in elderly patients with advanced NSCLC or those with some contraindication to receiving cisplatin were assessed. METHODS: Forty-nine patients with advanced NSCLC were included, 38 of whom were age >/= 70 years and 11 were age < 70 years but who had some contraindication to receiving cisplatin. All patients were evaluable for response and toxicity. Treatment was comprised of VNB, 25 mg/m(2), plus GEM, 1000 mg/m(2), both on Days 1, 8, and 15 every 28 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: One hundred sixty-five courses were administered, with a median of 3. 6 courses per patient. The overall response rate was 26% (95% confidence interval, 15-41%). Two patients attained a complete response (4%) and 11 patients (22%) achieved a partial response. Eastern Cooperative Oncology Group performance status improved in 35% of those patients with an initial value > 0, whereas relief of at least 1 symptom without worsening of other symptoms was noted in 27 patients (55%). The median time to progression was 16 weeks and the 1-year survival rate was 33%. Toxicity was mild. Six patients (12%) had World Health Organization Grade 3-4 neutropenia, 2 patients (4%) had Grade 3-4 thrombocytopenia, and 2 patients (4%) had Grade 3 neurotoxicity. Three patients with severe neutropenia (6%) died of sepsis. The median age of those patients developing Grade 3-4 neutropenia was significantly higher than that of the remaining patients (75 years vs. 72 years; P = 0.047). CONCLUSIONS: The combination of GEM and VNB is moderately active and well tolerated except in patients age >/= 75 years. This age group had an increased risk of myelosuppression. Therefore the prophylactic use of granulocyte-colony stimulating factor should be considered with this treatment. New chemotherapy combinations with higher activity and lower toxicity are needed for elderly patients with advanced NSCLC.", "entity": "Thrombocytopenia", "aliases": "Thrombocytopenia Thrombocytopenias Thrombopenia Thrombopenias", "definition": "A subnormal level of BLOOD PLATELETS.\n    ", "id": "MESH:D013921"}
{"mention": "neurotoxicity", "mention_text": "BACKGROUND: Although the prevalence of nonsmall cell lung carcinoma (NSCLC) is high among elderly patients, few data are available regarding the efficacy and toxicity of chemotherapy in this group of patients. Recent reports indicate that single agent therapy with vinorelbine (VNB) or gemcitabine (GEM) may obtain a response rate of 20-30% in elderly patients, with acceptable toxicity and improvement in symptoms and quality of life. In the current study the efficacy and toxicity of the combination of GEM and VNB in elderly patients with advanced NSCLC or those with some contraindication to receiving cisplatin were assessed. METHODS: Forty-nine patients with advanced NSCLC were included, 38 of whom were age >/= 70 years and 11 were age < 70 years but who had some contraindication to receiving cisplatin. All patients were evaluable for response and toxicity. Treatment was comprised of VNB, 25 mg/m(2), plus GEM, 1000 mg/m(2), both on Days 1, 8, and 15 every 28 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: One hundred sixty-five courses were administered, with a median of 3. 6 courses per patient. The overall response rate was 26% (95% confidence interval, 15-41%). Two patients attained a complete response (4%) and 11 patients (22%) achieved a partial response. Eastern Cooperative Oncology Group performance status improved in 35% of those patients with an initial value > 0, whereas relief of at least 1 symptom without worsening of other symptoms was noted in 27 patients (55%). The median time to progression was 16 weeks and the 1-year survival rate was 33%. Toxicity was mild. Six patients (12%) had World Health Organization Grade 3-4 neutropenia, 2 patients (4%) had Grade 3-4 thrombocytopenia, and 2 patients (4%) had Grade 3 neurotoxicity. Three patients with severe neutropenia (6%) died of sepsis. The median age of those patients developing Grade 3-4 neutropenia was significantly higher than that of the remaining patients (75 years vs. 72 years; P = 0.047). CONCLUSIONS: The combination of GEM and VNB is moderately active and well tolerated except in patients age >/= 75 years. This age group had an increased risk of myelosuppression. Therefore the prophylactic use of granulocyte-colony stimulating factor should be considered with this treatment. New chemotherapy combinations with higher activity and lower toxicity are needed for elderly patients with advanced NSCLC.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "sepsis", "mention_text": "BACKGROUND: Although the prevalence of nonsmall cell lung carcinoma (NSCLC) is high among elderly patients, few data are available regarding the efficacy and toxicity of chemotherapy in this group of patients. Recent reports indicate that single agent therapy with vinorelbine (VNB) or gemcitabine (GEM) may obtain a response rate of 20-30% in elderly patients, with acceptable toxicity and improvement in symptoms and quality of life. In the current study the efficacy and toxicity of the combination of GEM and VNB in elderly patients with advanced NSCLC or those with some contraindication to receiving cisplatin were assessed. METHODS: Forty-nine patients with advanced NSCLC were included, 38 of whom were age >/= 70 years and 11 were age < 70 years but who had some contraindication to receiving cisplatin. All patients were evaluable for response and toxicity. Treatment was comprised of VNB, 25 mg/m(2), plus GEM, 1000 mg/m(2), both on Days 1, 8, and 15 every 28 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: One hundred sixty-five courses were administered, with a median of 3. 6 courses per patient. The overall response rate was 26% (95% confidence interval, 15-41%). Two patients attained a complete response (4%) and 11 patients (22%) achieved a partial response. Eastern Cooperative Oncology Group performance status improved in 35% of those patients with an initial value > 0, whereas relief of at least 1 symptom without worsening of other symptoms was noted in 27 patients (55%). The median time to progression was 16 weeks and the 1-year survival rate was 33%. Toxicity was mild. Six patients (12%) had World Health Organization Grade 3-4 neutropenia, 2 patients (4%) had Grade 3-4 thrombocytopenia, and 2 patients (4%) had Grade 3 neurotoxicity. Three patients with severe neutropenia (6%) died of sepsis. The median age of those patients developing Grade 3-4 neutropenia was significantly higher than that of the remaining patients (75 years vs. 72 years; P = 0.047). CONCLUSIONS: The combination of GEM and VNB is moderately active and well tolerated except in patients age >/= 75 years. This age group had an increased risk of myelosuppression. Therefore the prophylactic use of granulocyte-colony stimulating factor should be considered with this treatment. New chemotherapy combinations with higher activity and lower toxicity are needed for elderly patients with advanced NSCLC.", "entity": "Sepsis", "aliases": "Blood Poisoning Poisonings Pyaemia Pyaemias Pyemia Pyemias Pyohemia Pyohemias Sepsis Severe Septicemia Septicemias", "definition": "Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by HYPOTENSION despite adequate fluid infusion, it is called SEPTIC SHOCK.\n    ", "id": "MESH:D018805"}
{"mention": "myelosuppression", "mention_text": "BACKGROUND: Although the prevalence of nonsmall cell lung carcinoma (NSCLC) is high among elderly patients, few data are available regarding the efficacy and toxicity of chemotherapy in this group of patients. Recent reports indicate that single agent therapy with vinorelbine (VNB) or gemcitabine (GEM) may obtain a response rate of 20-30% in elderly patients, with acceptable toxicity and improvement in symptoms and quality of life. In the current study the efficacy and toxicity of the combination of GEM and VNB in elderly patients with advanced NSCLC or those with some contraindication to receiving cisplatin were assessed. METHODS: Forty-nine patients with advanced NSCLC were included, 38 of whom were age >/= 70 years and 11 were age < 70 years but who had some contraindication to receiving cisplatin. All patients were evaluable for response and toxicity. Treatment was comprised of VNB, 25 mg/m(2), plus GEM, 1000 mg/m(2), both on Days 1, 8, and 15 every 28 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: One hundred sixty-five courses were administered, with a median of 3. 6 courses per patient. The overall response rate was 26% (95% confidence interval, 15-41%). Two patients attained a complete response (4%) and 11 patients (22%) achieved a partial response. Eastern Cooperative Oncology Group performance status improved in 35% of those patients with an initial value > 0, whereas relief of at least 1 symptom without worsening of other symptoms was noted in 27 patients (55%). The median time to progression was 16 weeks and the 1-year survival rate was 33%. Toxicity was mild. Six patients (12%) had World Health Organization Grade 3-4 neutropenia, 2 patients (4%) had Grade 3-4 thrombocytopenia, and 2 patients (4%) had Grade 3 neurotoxicity. Three patients with severe neutropenia (6%) died of sepsis. The median age of those patients developing Grade 3-4 neutropenia was significantly higher than that of the remaining patients (75 years vs. 72 years; P = 0.047). CONCLUSIONS: The combination of GEM and VNB is moderately active and well tolerated except in patients age >/= 75 years. This age group had an increased risk of myelosuppression. Therefore the prophylactic use of granulocyte-colony stimulating factor should be considered with this treatment. New chemotherapy combinations with higher activity and lower toxicity are needed for elderly patients with advanced NSCLC.", "entity": "Bone Marrow Diseases", "aliases": "Bone Marrow Disease Diseases", "definition": "", "id": "MESH:D001855"}
{"mention": "Warfarin", "mention_text": "Warfarin-induced artery calcification is accelerated by growth and vitamin D.", "entity": "Warfarin", "aliases": "4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one Aldo Brand of Warfarin Sodium Aldocumar Antigen Apo-Warfarin Apotex Bailly Boots Bristol-Myers Squibb Coumadin Coumadine Estedi Gen-Warfarin Genpharm Goldshield Marevan Potassium Tedicumar Warfant", "definition": "An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.\n    ", "id": "MESH:D014859"}
{"mention": "artery calcification", "mention_text": "Warfarin-induced artery calcification is accelerated by growth and vitamin D.", "entity": "Vascular Calcification", "aliases": "Calcification Vascular Calcifications Calcinoses Calcinosis", "definition": "Deposition of calcium into the blood vessel structures. Excessive calcification of the vessels are associated with ATHEROSCLEROTIC PLAQUES formation particularly after MYOCARDIAL INFARCTION (see MONCKEBERG MEDIAL CALCIFIC SCLEROSIS) and chronic kidney diseases which in turn increase VASCULAR STIFFNESS.\n    ", "id": "MESH:D061205"}
{"mention": "vitamin D", "mention_text": "Warfarin-induced artery calcification is accelerated by growth and vitamin D.", "entity": "Vitamin D", "aliases": "Vitamin D", "definition": "A vitamin that includes both CHOLECALCIFEROLS and ERGOCALCIFEROLS, which have the common effect of preventing or curing RICKETS in animals. It can also be viewed as a hormone since it can be formed in SKIN by action of ULTRAVIOLET RAYS upon the precursors, 7-dehydrocholesterol and ERGOSTEROL, and acts on VITAMIN D RECEPTORS to regulate CALCIUM in opposition to PARATHYROID HORMONE.\n    ", "id": "MESH:D014807"}
{"mention": "vitamin D", "mention_text": "The present studies demonstrate that growth and vitamin D treatment enhance the extent of artery calcification in rats given sufficient doses of Warfarin to inhibit gamma-carboxylation of matrix Gla protein, a calcification inhibitor known to be expressed by smooth muscle cells and macrophages in the artery wall. The first series of experiments examined the influence of age and growth status on artery calcification in Warfarin-treated rats. Treatment for 2 weeks with Warfarin caused massive focal calcification of the artery media in 20-day-old rats and less extensive focal calcification in 42-day-old rats. In contrast, no artery calcification could be detected in 10-month-old adult rats even after 4 weeks of Warfarin treatment. To directly examine the importance of growth to Warfarin-induced artery calcification in animals of the same age, 20-day-old rats were fed for 2 weeks either an ad libitum diet or a 6-g/d restricted diet that maintains weight but prevents growth. Concurrent treatment of both dietary groups with Warfarin produced massive focal calcification of the artery media in the ad libitum-fed rats but no detectable artery calcification in the restricted-diet, growth-inhibited group. Although the explanation for the association between artery calcification and growth status cannot be determined from the present study, there was a relationship between higher serum phosphate and susceptibility to artery calcification, with 30% higher levels of serum phosphate in young, ad libitum-fed rats compared with either of the groups that was resistant to Warfarin-induced artery calcification, ie, the 10-month-old rats and the restricted-diet, growth-inhibited young rats. This observation suggests that increased susceptibility to Warfarin-induced artery calcification could be related to higher serum phosphate levels. The second set of experiments examined the possible synergy between vitamin D and Warfarin in artery calcification. High doses of vitamin D are known to cause calcification of the artery media in as little as 3 to 4 days. High doses of the vitamin K antagonist Warfarin are also known to cause calcification of the artery media, but at treatment times of 2 weeks or longer yet not at 1 week. In the current study, we investigated the synergy between these 2 treatments and found that concurrent Warfarin administration dramatically increased the extent of calcification in the media of vitamin D-treated rats at 3 and 4 days. There was a close parallel between the effect of vitamin D dose on artery calcification and the effect of vitamin D dose on the elevation of serum calcium, which suggests that vitamin D may induce artery calcification through its effect on serum calcium. Because Warfarin treatment had no effect on the elevation in serum calcium produced by vitamin D, the synergy between Warfarin and vitamin D is probably best explained by the hypothesis that Warfarin inhibits the activity of matrix Gla protein as a calcification inhibitor. High levels of matrix Gla protein are found at sites of artery calcification in rats treated with vitamin D plus Warfarin, and chemical analysis showed that the protein that accumulated was indeed not gamma-carboxylated. These observations indicate that although the gamma-carboxyglutamate residues of matrix Gla protein are apparently required for its function as a calcification inhibitor, they are not required for its accumulation at calcification sites.", "entity": "Vitamin D", "aliases": "Vitamin D", "definition": "A vitamin that includes both CHOLECALCIFEROLS and ERGOCALCIFEROLS, which have the common effect of preventing or curing RICKETS in animals. It can also be viewed as a hormone since it can be formed in SKIN by action of ULTRAVIOLET RAYS upon the precursors, 7-dehydrocholesterol and ERGOSTEROL, and acts on VITAMIN D RECEPTORS to regulate CALCIUM in opposition to PARATHYROID HORMONE.\n    ", "id": "MESH:D014807"}
{"mention": "artery calcification", "mention_text": "The present studies demonstrate that growth and vitamin D treatment enhance the extent of artery calcification in rats given sufficient doses of Warfarin to inhibit gamma-carboxylation of matrix Gla protein, a calcification inhibitor known to be expressed by smooth muscle cells and macrophages in the artery wall. The first series of experiments examined the influence of age and growth status on artery calcification in Warfarin-treated rats. Treatment for 2 weeks with Warfarin caused massive focal calcification of the artery media in 20-day-old rats and less extensive focal calcification in 42-day-old rats. In contrast, no artery calcification could be detected in 10-month-old adult rats even after 4 weeks of Warfarin treatment. To directly examine the importance of growth to Warfarin-induced artery calcification in animals of the same age, 20-day-old rats were fed for 2 weeks either an ad libitum diet or a 6-g/d restricted diet that maintains weight but prevents growth. Concurrent treatment of both dietary groups with Warfarin produced massive focal calcification of the artery media in the ad libitum-fed rats but no detectable artery calcification in the restricted-diet, growth-inhibited group. Although the explanation for the association between artery calcification and growth status cannot be determined from the present study, there was a relationship between higher serum phosphate and susceptibility to artery calcification, with 30% higher levels of serum phosphate in young, ad libitum-fed rats compared with either of the groups that was resistant to Warfarin-induced artery calcification, ie, the 10-month-old rats and the restricted-diet, growth-inhibited young rats. This observation suggests that increased susceptibility to Warfarin-induced artery calcification could be related to higher serum phosphate levels. The second set of experiments examined the possible synergy between vitamin D and Warfarin in artery calcification. High doses of vitamin D are known to cause calcification of the artery media in as little as 3 to 4 days. High doses of the vitamin K antagonist Warfarin are also known to cause calcification of the artery media, but at treatment times of 2 weeks or longer yet not at 1 week. In the current study, we investigated the synergy between these 2 treatments and found that concurrent Warfarin administration dramatically increased the extent of calcification in the media of vitamin D-treated rats at 3 and 4 days. There was a close parallel between the effect of vitamin D dose on artery calcification and the effect of vitamin D dose on the elevation of serum calcium, which suggests that vitamin D may induce artery calcification through its effect on serum calcium. Because Warfarin treatment had no effect on the elevation in serum calcium produced by vitamin D, the synergy between Warfarin and vitamin D is probably best explained by the hypothesis that Warfarin inhibits the activity of matrix Gla protein as a calcification inhibitor. High levels of matrix Gla protein are found at sites of artery calcification in rats treated with vitamin D plus Warfarin, and chemical analysis showed that the protein that accumulated was indeed not gamma-carboxylated. These observations indicate that although the gamma-carboxyglutamate residues of matrix Gla protein are apparently required for its function as a calcification inhibitor, they are not required for its accumulation at calcification sites.", "entity": "Vascular Calcification", "aliases": "Calcification Vascular Calcifications Calcinoses Calcinosis", "definition": "Deposition of calcium into the blood vessel structures. Excessive calcification of the vessels are associated with ATHEROSCLEROTIC PLAQUES formation particularly after MYOCARDIAL INFARCTION (see MONCKEBERG MEDIAL CALCIFIC SCLEROSIS) and chronic kidney diseases which in turn increase VASCULAR STIFFNESS.\n    ", "id": "MESH:D061205"}
{"mention": "Warfarin", "mention_text": "The present studies demonstrate that growth and vitamin D treatment enhance the extent of artery calcification in rats given sufficient doses of Warfarin to inhibit gamma-carboxylation of matrix Gla protein, a calcification inhibitor known to be expressed by smooth muscle cells and macrophages in the artery wall. The first series of experiments examined the influence of age and growth status on artery calcification in Warfarin-treated rats. Treatment for 2 weeks with Warfarin caused massive focal calcification of the artery media in 20-day-old rats and less extensive focal calcification in 42-day-old rats. In contrast, no artery calcification could be detected in 10-month-old adult rats even after 4 weeks of Warfarin treatment. To directly examine the importance of growth to Warfarin-induced artery calcification in animals of the same age, 20-day-old rats were fed for 2 weeks either an ad libitum diet or a 6-g/d restricted diet that maintains weight but prevents growth. Concurrent treatment of both dietary groups with Warfarin produced massive focal calcification of the artery media in the ad libitum-fed rats but no detectable artery calcification in the restricted-diet, growth-inhibited group. Although the explanation for the association between artery calcification and growth status cannot be determined from the present study, there was a relationship between higher serum phosphate and susceptibility to artery calcification, with 30% higher levels of serum phosphate in young, ad libitum-fed rats compared with either of the groups that was resistant to Warfarin-induced artery calcification, ie, the 10-month-old rats and the restricted-diet, growth-inhibited young rats. This observation suggests that increased susceptibility to Warfarin-induced artery calcification could be related to higher serum phosphate levels. The second set of experiments examined the possible synergy between vitamin D and Warfarin in artery calcification. High doses of vitamin D are known to cause calcification of the artery media in as little as 3 to 4 days. High doses of the vitamin K antagonist Warfarin are also known to cause calcification of the artery media, but at treatment times of 2 weeks or longer yet not at 1 week. In the current study, we investigated the synergy between these 2 treatments and found that concurrent Warfarin administration dramatically increased the extent of calcification in the media of vitamin D-treated rats at 3 and 4 days. There was a close parallel between the effect of vitamin D dose on artery calcification and the effect of vitamin D dose on the elevation of serum calcium, which suggests that vitamin D may induce artery calcification through its effect on serum calcium. Because Warfarin treatment had no effect on the elevation in serum calcium produced by vitamin D, the synergy between Warfarin and vitamin D is probably best explained by the hypothesis that Warfarin inhibits the activity of matrix Gla protein as a calcification inhibitor. High levels of matrix Gla protein are found at sites of artery calcification in rats treated with vitamin D plus Warfarin, and chemical analysis showed that the protein that accumulated was indeed not gamma-carboxylated. These observations indicate that although the gamma-carboxyglutamate residues of matrix Gla protein are apparently required for its function as a calcification inhibitor, they are not required for its accumulation at calcification sites.", "entity": "Warfarin", "aliases": "4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one Aldo Brand of Warfarin Sodium Aldocumar Antigen Apo-Warfarin Apotex Bailly Boots Bristol-Myers Squibb Coumadin Coumadine Estedi Gen-Warfarin Genpharm Goldshield Marevan Potassium Tedicumar Warfant", "definition": "An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.\n    ", "id": "MESH:D014859"}
{"mention": "calcification", "mention_text": "The present studies demonstrate that growth and vitamin D treatment enhance the extent of artery calcification in rats given sufficient doses of Warfarin to inhibit gamma-carboxylation of matrix Gla protein, a calcification inhibitor known to be expressed by smooth muscle cells and macrophages in the artery wall. The first series of experiments examined the influence of age and growth status on artery calcification in Warfarin-treated rats. Treatment for 2 weeks with Warfarin caused massive focal calcification of the artery media in 20-day-old rats and less extensive focal calcification in 42-day-old rats. In contrast, no artery calcification could be detected in 10-month-old adult rats even after 4 weeks of Warfarin treatment. To directly examine the importance of growth to Warfarin-induced artery calcification in animals of the same age, 20-day-old rats were fed for 2 weeks either an ad libitum diet or a 6-g/d restricted diet that maintains weight but prevents growth. Concurrent treatment of both dietary groups with Warfarin produced massive focal calcification of the artery media in the ad libitum-fed rats but no detectable artery calcification in the restricted-diet, growth-inhibited group. Although the explanation for the association between artery calcification and growth status cannot be determined from the present study, there was a relationship between higher serum phosphate and susceptibility to artery calcification, with 30% higher levels of serum phosphate in young, ad libitum-fed rats compared with either of the groups that was resistant to Warfarin-induced artery calcification, ie, the 10-month-old rats and the restricted-diet, growth-inhibited young rats. This observation suggests that increased susceptibility to Warfarin-induced artery calcification could be related to higher serum phosphate levels. The second set of experiments examined the possible synergy between vitamin D and Warfarin in artery calcification. High doses of vitamin D are known to cause calcification of the artery media in as little as 3 to 4 days. High doses of the vitamin K antagonist Warfarin are also known to cause calcification of the artery media, but at treatment times of 2 weeks or longer yet not at 1 week. In the current study, we investigated the synergy between these 2 treatments and found that concurrent Warfarin administration dramatically increased the extent of calcification in the media of vitamin D-treated rats at 3 and 4 days. There was a close parallel between the effect of vitamin D dose on artery calcification and the effect of vitamin D dose on the elevation of serum calcium, which suggests that vitamin D may induce artery calcification through its effect on serum calcium. Because Warfarin treatment had no effect on the elevation in serum calcium produced by vitamin D, the synergy between Warfarin and vitamin D is probably best explained by the hypothesis that Warfarin inhibits the activity of matrix Gla protein as a calcification inhibitor. High levels of matrix Gla protein are found at sites of artery calcification in rats treated with vitamin D plus Warfarin, and chemical analysis showed that the protein that accumulated was indeed not gamma-carboxylated. These observations indicate that although the gamma-carboxyglutamate residues of matrix Gla protein are apparently required for its function as a calcification inhibitor, they are not required for its accumulation at calcification sites.", "entity": "Calcinosis", "aliases": "Calcification Pathologic Calcinoses Tumoral Calcinosis", "definition": "Pathologic deposition of calcium salts in tissues.\n    ", "id": "MESH:D002114"}
{"mention": "calcification of the artery", "mention_text": "The present studies demonstrate that growth and vitamin D treatment enhance the extent of artery calcification in rats given sufficient doses of Warfarin to inhibit gamma-carboxylation of matrix Gla protein, a calcification inhibitor known to be expressed by smooth muscle cells and macrophages in the artery wall. The first series of experiments examined the influence of age and growth status on artery calcification in Warfarin-treated rats. Treatment for 2 weeks with Warfarin caused massive focal calcification of the artery media in 20-day-old rats and less extensive focal calcification in 42-day-old rats. In contrast, no artery calcification could be detected in 10-month-old adult rats even after 4 weeks of Warfarin treatment. To directly examine the importance of growth to Warfarin-induced artery calcification in animals of the same age, 20-day-old rats were fed for 2 weeks either an ad libitum diet or a 6-g/d restricted diet that maintains weight but prevents growth. Concurrent treatment of both dietary groups with Warfarin produced massive focal calcification of the artery media in the ad libitum-fed rats but no detectable artery calcification in the restricted-diet, growth-inhibited group. Although the explanation for the association between artery calcification and growth status cannot be determined from the present study, there was a relationship between higher serum phosphate and susceptibility to artery calcification, with 30% higher levels of serum phosphate in young, ad libitum-fed rats compared with either of the groups that was resistant to Warfarin-induced artery calcification, ie, the 10-month-old rats and the restricted-diet, growth-inhibited young rats. This observation suggests that increased susceptibility to Warfarin-induced artery calcification could be related to higher serum phosphate levels. The second set of experiments examined the possible synergy between vitamin D and Warfarin in artery calcification. High doses of vitamin D are known to cause calcification of the artery media in as little as 3 to 4 days. High doses of the vitamin K antagonist Warfarin are also known to cause calcification of the artery media, but at treatment times of 2 weeks or longer yet not at 1 week. In the current study, we investigated the synergy between these 2 treatments and found that concurrent Warfarin administration dramatically increased the extent of calcification in the media of vitamin D-treated rats at 3 and 4 days. There was a close parallel between the effect of vitamin D dose on artery calcification and the effect of vitamin D dose on the elevation of serum calcium, which suggests that vitamin D may induce artery calcification through its effect on serum calcium. Because Warfarin treatment had no effect on the elevation in serum calcium produced by vitamin D, the synergy between Warfarin and vitamin D is probably best explained by the hypothesis that Warfarin inhibits the activity of matrix Gla protein as a calcification inhibitor. High levels of matrix Gla protein are found at sites of artery calcification in rats treated with vitamin D plus Warfarin, and chemical analysis showed that the protein that accumulated was indeed not gamma-carboxylated. These observations indicate that although the gamma-carboxyglutamate residues of matrix Gla protein are apparently required for its function as a calcification inhibitor, they are not required for its accumulation at calcification sites.", "entity": "Vascular Calcification", "aliases": "Calcification Vascular Calcifications Calcinoses Calcinosis", "definition": "Deposition of calcium into the blood vessel structures. Excessive calcification of the vessels are associated with ATHEROSCLEROTIC PLAQUES formation particularly after MYOCARDIAL INFARCTION (see MONCKEBERG MEDIAL CALCIFIC SCLEROSIS) and chronic kidney diseases which in turn increase VASCULAR STIFFNESS.\n    ", "id": "MESH:D061205"}
{"mention": "phosphate", "mention_text": "The present studies demonstrate that growth and vitamin D treatment enhance the extent of artery calcification in rats given sufficient doses of Warfarin to inhibit gamma-carboxylation of matrix Gla protein, a calcification inhibitor known to be expressed by smooth muscle cells and macrophages in the artery wall. The first series of experiments examined the influence of age and growth status on artery calcification in Warfarin-treated rats. Treatment for 2 weeks with Warfarin caused massive focal calcification of the artery media in 20-day-old rats and less extensive focal calcification in 42-day-old rats. In contrast, no artery calcification could be detected in 10-month-old adult rats even after 4 weeks of Warfarin treatment. To directly examine the importance of growth to Warfarin-induced artery calcification in animals of the same age, 20-day-old rats were fed for 2 weeks either an ad libitum diet or a 6-g/d restricted diet that maintains weight but prevents growth. Concurrent treatment of both dietary groups with Warfarin produced massive focal calcification of the artery media in the ad libitum-fed rats but no detectable artery calcification in the restricted-diet, growth-inhibited group. Although the explanation for the association between artery calcification and growth status cannot be determined from the present study, there was a relationship between higher serum phosphate and susceptibility to artery calcification, with 30% higher levels of serum phosphate in young, ad libitum-fed rats compared with either of the groups that was resistant to Warfarin-induced artery calcification, ie, the 10-month-old rats and the restricted-diet, growth-inhibited young rats. This observation suggests that increased susceptibility to Warfarin-induced artery calcification could be related to higher serum phosphate levels. The second set of experiments examined the possible synergy between vitamin D and Warfarin in artery calcification. High doses of vitamin D are known to cause calcification of the artery media in as little as 3 to 4 days. High doses of the vitamin K antagonist Warfarin are also known to cause calcification of the artery media, but at treatment times of 2 weeks or longer yet not at 1 week. In the current study, we investigated the synergy between these 2 treatments and found that concurrent Warfarin administration dramatically increased the extent of calcification in the media of vitamin D-treated rats at 3 and 4 days. There was a close parallel between the effect of vitamin D dose on artery calcification and the effect of vitamin D dose on the elevation of serum calcium, which suggests that vitamin D may induce artery calcification through its effect on serum calcium. Because Warfarin treatment had no effect on the elevation in serum calcium produced by vitamin D, the synergy between Warfarin and vitamin D is probably best explained by the hypothesis that Warfarin inhibits the activity of matrix Gla protein as a calcification inhibitor. High levels of matrix Gla protein are found at sites of artery calcification in rats treated with vitamin D plus Warfarin, and chemical analysis showed that the protein that accumulated was indeed not gamma-carboxylated. These observations indicate that although the gamma-carboxyglutamate residues of matrix Gla protein are apparently required for its function as a calcification inhibitor, they are not required for its accumulation at calcification sites.", "entity": "Phosphates", "aliases": "Inorganic Phosphates Orthophosphate", "definition": "Inorganic salts of phosphoric acid.\n    ", "id": "MESH:D010710"}
{"mention": "vitamin K", "mention_text": "The present studies demonstrate that growth and vitamin D treatment enhance the extent of artery calcification in rats given sufficient doses of Warfarin to inhibit gamma-carboxylation of matrix Gla protein, a calcification inhibitor known to be expressed by smooth muscle cells and macrophages in the artery wall. The first series of experiments examined the influence of age and growth status on artery calcification in Warfarin-treated rats. Treatment for 2 weeks with Warfarin caused massive focal calcification of the artery media in 20-day-old rats and less extensive focal calcification in 42-day-old rats. In contrast, no artery calcification could be detected in 10-month-old adult rats even after 4 weeks of Warfarin treatment. To directly examine the importance of growth to Warfarin-induced artery calcification in animals of the same age, 20-day-old rats were fed for 2 weeks either an ad libitum diet or a 6-g/d restricted diet that maintains weight but prevents growth. Concurrent treatment of both dietary groups with Warfarin produced massive focal calcification of the artery media in the ad libitum-fed rats but no detectable artery calcification in the restricted-diet, growth-inhibited group. Although the explanation for the association between artery calcification and growth status cannot be determined from the present study, there was a relationship between higher serum phosphate and susceptibility to artery calcification, with 30% higher levels of serum phosphate in young, ad libitum-fed rats compared with either of the groups that was resistant to Warfarin-induced artery calcification, ie, the 10-month-old rats and the restricted-diet, growth-inhibited young rats. This observation suggests that increased susceptibility to Warfarin-induced artery calcification could be related to higher serum phosphate levels. The second set of experiments examined the possible synergy between vitamin D and Warfarin in artery calcification. High doses of vitamin D are known to cause calcification of the artery media in as little as 3 to 4 days. High doses of the vitamin K antagonist Warfarin are also known to cause calcification of the artery media, but at treatment times of 2 weeks or longer yet not at 1 week. In the current study, we investigated the synergy between these 2 treatments and found that concurrent Warfarin administration dramatically increased the extent of calcification in the media of vitamin D-treated rats at 3 and 4 days. There was a close parallel between the effect of vitamin D dose on artery calcification and the effect of vitamin D dose on the elevation of serum calcium, which suggests that vitamin D may induce artery calcification through its effect on serum calcium. Because Warfarin treatment had no effect on the elevation in serum calcium produced by vitamin D, the synergy between Warfarin and vitamin D is probably best explained by the hypothesis that Warfarin inhibits the activity of matrix Gla protein as a calcification inhibitor. High levels of matrix Gla protein are found at sites of artery calcification in rats treated with vitamin D plus Warfarin, and chemical analysis showed that the protein that accumulated was indeed not gamma-carboxylated. These observations indicate that although the gamma-carboxyglutamate residues of matrix Gla protein are apparently required for its function as a calcification inhibitor, they are not required for its accumulation at calcification sites.", "entity": "Vitamin K", "aliases": "Vitamin K", "definition": "A lipid cofactor that is required for normal blood clotting. Several forms of vitamin K have been identified: VITAMIN K 1 (phytomenadione) derived from plants, VITAMIN K 2 (menaquinone) from bacteria, and synthetic naphthoquinone provitamins, VITAMIN K 3 (menadione). Vitamin K 3 provitamins, after being alkylated in vivo, exhibit the antifibrinolytic activity of vitamin K. Green leafy vegetables, liver, cheese, butter, and egg yolk are good sources of vitamin K.\n    ", "id": "MESH:D014812"}
{"mention": "calcium", "mention_text": "The present studies demonstrate that growth and vitamin D treatment enhance the extent of artery calcification in rats given sufficient doses of Warfarin to inhibit gamma-carboxylation of matrix Gla protein, a calcification inhibitor known to be expressed by smooth muscle cells and macrophages in the artery wall. The first series of experiments examined the influence of age and growth status on artery calcification in Warfarin-treated rats. Treatment for 2 weeks with Warfarin caused massive focal calcification of the artery media in 20-day-old rats and less extensive focal calcification in 42-day-old rats. In contrast, no artery calcification could be detected in 10-month-old adult rats even after 4 weeks of Warfarin treatment. To directly examine the importance of growth to Warfarin-induced artery calcification in animals of the same age, 20-day-old rats were fed for 2 weeks either an ad libitum diet or a 6-g/d restricted diet that maintains weight but prevents growth. Concurrent treatment of both dietary groups with Warfarin produced massive focal calcification of the artery media in the ad libitum-fed rats but no detectable artery calcification in the restricted-diet, growth-inhibited group. Although the explanation for the association between artery calcification and growth status cannot be determined from the present study, there was a relationship between higher serum phosphate and susceptibility to artery calcification, with 30% higher levels of serum phosphate in young, ad libitum-fed rats compared with either of the groups that was resistant to Warfarin-induced artery calcification, ie, the 10-month-old rats and the restricted-diet, growth-inhibited young rats. This observation suggests that increased susceptibility to Warfarin-induced artery calcification could be related to higher serum phosphate levels. The second set of experiments examined the possible synergy between vitamin D and Warfarin in artery calcification. High doses of vitamin D are known to cause calcification of the artery media in as little as 3 to 4 days. High doses of the vitamin K antagonist Warfarin are also known to cause calcification of the artery media, but at treatment times of 2 weeks or longer yet not at 1 week. In the current study, we investigated the synergy between these 2 treatments and found that concurrent Warfarin administration dramatically increased the extent of calcification in the media of vitamin D-treated rats at 3 and 4 days. There was a close parallel between the effect of vitamin D dose on artery calcification and the effect of vitamin D dose on the elevation of serum calcium, which suggests that vitamin D may induce artery calcification through its effect on serum calcium. Because Warfarin treatment had no effect on the elevation in serum calcium produced by vitamin D, the synergy between Warfarin and vitamin D is probably best explained by the hypothesis that Warfarin inhibits the activity of matrix Gla protein as a calcification inhibitor. High levels of matrix Gla protein are found at sites of artery calcification in rats treated with vitamin D plus Warfarin, and chemical analysis showed that the protein that accumulated was indeed not gamma-carboxylated. These observations indicate that although the gamma-carboxyglutamate residues of matrix Gla protein are apparently required for its function as a calcification inhibitor, they are not required for its accumulation at calcification sites.", "entity": "Calcium", "aliases": "Blood Coagulation Factor IV Calcium", "definition": "A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.\n    ", "id": "MESH:D002118"}
{"mention": "gamma-carboxylated", "mention_text": "The present studies demonstrate that growth and vitamin D treatment enhance the extent of artery calcification in rats given sufficient doses of Warfarin to inhibit gamma-carboxylation of matrix Gla protein, a calcification inhibitor known to be expressed by smooth muscle cells and macrophages in the artery wall. The first series of experiments examined the influence of age and growth status on artery calcification in Warfarin-treated rats. Treatment for 2 weeks with Warfarin caused massive focal calcification of the artery media in 20-day-old rats and less extensive focal calcification in 42-day-old rats. In contrast, no artery calcification could be detected in 10-month-old adult rats even after 4 weeks of Warfarin treatment. To directly examine the importance of growth to Warfarin-induced artery calcification in animals of the same age, 20-day-old rats were fed for 2 weeks either an ad libitum diet or a 6-g/d restricted diet that maintains weight but prevents growth. Concurrent treatment of both dietary groups with Warfarin produced massive focal calcification of the artery media in the ad libitum-fed rats but no detectable artery calcification in the restricted-diet, growth-inhibited group. Although the explanation for the association between artery calcification and growth status cannot be determined from the present study, there was a relationship between higher serum phosphate and susceptibility to artery calcification, with 30% higher levels of serum phosphate in young, ad libitum-fed rats compared with either of the groups that was resistant to Warfarin-induced artery calcification, ie, the 10-month-old rats and the restricted-diet, growth-inhibited young rats. This observation suggests that increased susceptibility to Warfarin-induced artery calcification could be related to higher serum phosphate levels. The second set of experiments examined the possible synergy between vitamin D and Warfarin in artery calcification. High doses of vitamin D are known to cause calcification of the artery media in as little as 3 to 4 days. High doses of the vitamin K antagonist Warfarin are also known to cause calcification of the artery media, but at treatment times of 2 weeks or longer yet not at 1 week. In the current study, we investigated the synergy between these 2 treatments and found that concurrent Warfarin administration dramatically increased the extent of calcification in the media of vitamin D-treated rats at 3 and 4 days. There was a close parallel between the effect of vitamin D dose on artery calcification and the effect of vitamin D dose on the elevation of serum calcium, which suggests that vitamin D may induce artery calcification through its effect on serum calcium. Because Warfarin treatment had no effect on the elevation in serum calcium produced by vitamin D, the synergy between Warfarin and vitamin D is probably best explained by the hypothesis that Warfarin inhibits the activity of matrix Gla protein as a calcification inhibitor. High levels of matrix Gla protein are found at sites of artery calcification in rats treated with vitamin D plus Warfarin, and chemical analysis showed that the protein that accumulated was indeed not gamma-carboxylated. These observations indicate that although the gamma-carboxyglutamate residues of matrix Gla protein are apparently required for its function as a calcification inhibitor, they are not required for its accumulation at calcification sites.", "entity": "1-Carboxyglutamic Acid", "aliases": "1 Carboxyglutamic Acid 1-Carboxyglutamic 3-Amino-1,1,3-propanetricarboxylic gamma Carboxyglutamate gamma-Carboxyglutamate gamma-Carboxyglutamic", "definition": "Found in various tissues, particularly in four blood-clotting proteins including prothrombin, in kidney protein, in bone protein, and in the protein present in various ectopic calcifications.\n    ", "id": "MESH:D015055"}
{"mention": "gamma-carboxyglutamate", "mention_text": "The present studies demonstrate that growth and vitamin D treatment enhance the extent of artery calcification in rats given sufficient doses of Warfarin to inhibit gamma-carboxylation of matrix Gla protein, a calcification inhibitor known to be expressed by smooth muscle cells and macrophages in the artery wall. The first series of experiments examined the influence of age and growth status on artery calcification in Warfarin-treated rats. Treatment for 2 weeks with Warfarin caused massive focal calcification of the artery media in 20-day-old rats and less extensive focal calcification in 42-day-old rats. In contrast, no artery calcification could be detected in 10-month-old adult rats even after 4 weeks of Warfarin treatment. To directly examine the importance of growth to Warfarin-induced artery calcification in animals of the same age, 20-day-old rats were fed for 2 weeks either an ad libitum diet or a 6-g/d restricted diet that maintains weight but prevents growth. Concurrent treatment of both dietary groups with Warfarin produced massive focal calcification of the artery media in the ad libitum-fed rats but no detectable artery calcification in the restricted-diet, growth-inhibited group. Although the explanation for the association between artery calcification and growth status cannot be determined from the present study, there was a relationship between higher serum phosphate and susceptibility to artery calcification, with 30% higher levels of serum phosphate in young, ad libitum-fed rats compared with either of the groups that was resistant to Warfarin-induced artery calcification, ie, the 10-month-old rats and the restricted-diet, growth-inhibited young rats. This observation suggests that increased susceptibility to Warfarin-induced artery calcification could be related to higher serum phosphate levels. The second set of experiments examined the possible synergy between vitamin D and Warfarin in artery calcification. High doses of vitamin D are known to cause calcification of the artery media in as little as 3 to 4 days. High doses of the vitamin K antagonist Warfarin are also known to cause calcification of the artery media, but at treatment times of 2 weeks or longer yet not at 1 week. In the current study, we investigated the synergy between these 2 treatments and found that concurrent Warfarin administration dramatically increased the extent of calcification in the media of vitamin D-treated rats at 3 and 4 days. There was a close parallel between the effect of vitamin D dose on artery calcification and the effect of vitamin D dose on the elevation of serum calcium, which suggests that vitamin D may induce artery calcification through its effect on serum calcium. Because Warfarin treatment had no effect on the elevation in serum calcium produced by vitamin D, the synergy between Warfarin and vitamin D is probably best explained by the hypothesis that Warfarin inhibits the activity of matrix Gla protein as a calcification inhibitor. High levels of matrix Gla protein are found at sites of artery calcification in rats treated with vitamin D plus Warfarin, and chemical analysis showed that the protein that accumulated was indeed not gamma-carboxylated. These observations indicate that although the gamma-carboxyglutamate residues of matrix Gla protein are apparently required for its function as a calcification inhibitor, they are not required for its accumulation at calcification sites.", "entity": "1-Carboxyglutamic Acid", "aliases": "1 Carboxyglutamic Acid 1-Carboxyglutamic 3-Amino-1,1,3-propanetricarboxylic gamma Carboxyglutamate gamma-Carboxyglutamate gamma-Carboxyglutamic", "definition": "Found in various tissues, particularly in four blood-clotting proteins including prothrombin, in kidney protein, in bone protein, and in the protein present in various ectopic calcifications.\n    ", "id": "MESH:D015055"}
{"mention": "Antidepressant", "mention_text": "Antidepressant-induced mania in bipolar patients: identification of risk factors.", "entity": "Antidepressive Agents", "aliases": "Agents Antidepressive Antidepressant Drugs Antidepressants Thymoanaleptics Thymoleptics", "definition": "Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.\n    ", "id": "MESH:D000928"}
{"mention": "mania", "mention_text": "Antidepressant-induced mania in bipolar patients: identification of risk factors.", "entity": "Bipolar Disorder", "aliases": "Affective Psychosis Bipolar Depression Disorder Disorders Manic Mania Manias Depressive State States Manic-Depressive Psychoses", "definition": "A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.\n    ", "id": "MESH:D001714"}
{"mention": "bipolar", "mention_text": "Antidepressant-induced mania in bipolar patients: identification of risk factors.", "entity": "Bipolar Disorder", "aliases": "Affective Psychosis Bipolar Depression Disorder Disorders Manic Mania Manias Depressive State States Manic-Depressive Psychoses", "definition": "A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.\n    ", "id": "MESH:D001714"}
{"mention": "mania", "mention_text": "BACKGROUND: Concerns about possible risks of switching to mania associated with antidepressants continue to interfere with the establishment of an optimal treatment paradigm for bipolar depression. METHOD: The response of 44 patients meeting DSM-IV criteria for bipolar disorder to naturalistic treatment was assessed for at least 6 weeks using the Montgomery-Asberg Depression Rating Scale and the Bech-Rafaelson Mania Rating Scale. Patients who experienced a manic or hypomanic switch were compared with those who did not on several variables including age, sex, diagnosis (DSM-IV bipolar I vs. bipolar II), number of previous manic episodes, type of antidepressant therapy used (electroconvulsive therapy vs. antidepressant drugs and, more particularly, selective serotonin reuptake inhibitors [SSRIs]), use and type of mood stabilizers (lithium vs. anticonvulsants), and temperament of the patient, assessed during a normothymic period using the hyperthymia component of the Semi-structured Affective Temperament Interview. RESULTS: Switches to hypomania or mania occurred in 27% of all patients (N = 12) (and in 24% of the subgroup of patients treated with SSRIs [8/33]); 16% (N = 7) experienced manic episodes, and 11% (N = 5) experienced hypomanic episodes. Sex, age, diagnosis (bipolar I vs. bipolar II), and additional treatment did not affect the risk of switching. The incidence of mood switches seemed not to differ between patients receiving an anticonvulsant and those receiving no mood stabilizer. In contrast, mood switches were less frequent in patients receiving lithium (15%, 4/26) than in patients not treated with lithium (44%, 8/18; p = .04). The number of previous manic episodes did not affect the probability of switching, whereas a high score on the hyperthymia component of the Semistructured Affective Temperament Interview was associated with a greater risk of switching (p = .008). CONCLUSION: The frequency of mood switching associated with acute antidepressant therapy may be reduced by lithium treatment. Particular attention should be paid to patients with a hyperthymic temperament, who have a greater risk of mood switches.", "entity": "Bipolar Disorder", "aliases": "Affective Psychosis Bipolar Depression Disorder Disorders Manic Mania Manias Depressive State States Manic-Depressive Psychoses", "definition": "A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.\n    ", "id": "MESH:D001714"}
{"mention": "antidepressants", "mention_text": "BACKGROUND: Concerns about possible risks of switching to mania associated with antidepressants continue to interfere with the establishment of an optimal treatment paradigm for bipolar depression. METHOD: The response of 44 patients meeting DSM-IV criteria for bipolar disorder to naturalistic treatment was assessed for at least 6 weeks using the Montgomery-Asberg Depression Rating Scale and the Bech-Rafaelson Mania Rating Scale. Patients who experienced a manic or hypomanic switch were compared with those who did not on several variables including age, sex, diagnosis (DSM-IV bipolar I vs. bipolar II), number of previous manic episodes, type of antidepressant therapy used (electroconvulsive therapy vs. antidepressant drugs and, more particularly, selective serotonin reuptake inhibitors [SSRIs]), use and type of mood stabilizers (lithium vs. anticonvulsants), and temperament of the patient, assessed during a normothymic period using the hyperthymia component of the Semi-structured Affective Temperament Interview. RESULTS: Switches to hypomania or mania occurred in 27% of all patients (N = 12) (and in 24% of the subgroup of patients treated with SSRIs [8/33]); 16% (N = 7) experienced manic episodes, and 11% (N = 5) experienced hypomanic episodes. Sex, age, diagnosis (bipolar I vs. bipolar II), and additional treatment did not affect the risk of switching. The incidence of mood switches seemed not to differ between patients receiving an anticonvulsant and those receiving no mood stabilizer. In contrast, mood switches were less frequent in patients receiving lithium (15%, 4/26) than in patients not treated with lithium (44%, 8/18; p = .04). The number of previous manic episodes did not affect the probability of switching, whereas a high score on the hyperthymia component of the Semistructured Affective Temperament Interview was associated with a greater risk of switching (p = .008). CONCLUSION: The frequency of mood switching associated with acute antidepressant therapy may be reduced by lithium treatment. Particular attention should be paid to patients with a hyperthymic temperament, who have a greater risk of mood switches.", "entity": "Antidepressive Agents", "aliases": "Agents Antidepressive Antidepressant Drugs Antidepressants Thymoanaleptics Thymoleptics", "definition": "Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.\n    ", "id": "MESH:D000928"}
{"mention": "bipolar depression", "mention_text": "BACKGROUND: Concerns about possible risks of switching to mania associated with antidepressants continue to interfere with the establishment of an optimal treatment paradigm for bipolar depression. METHOD: The response of 44 patients meeting DSM-IV criteria for bipolar disorder to naturalistic treatment was assessed for at least 6 weeks using the Montgomery-Asberg Depression Rating Scale and the Bech-Rafaelson Mania Rating Scale. Patients who experienced a manic or hypomanic switch were compared with those who did not on several variables including age, sex, diagnosis (DSM-IV bipolar I vs. bipolar II), number of previous manic episodes, type of antidepressant therapy used (electroconvulsive therapy vs. antidepressant drugs and, more particularly, selective serotonin reuptake inhibitors [SSRIs]), use and type of mood stabilizers (lithium vs. anticonvulsants), and temperament of the patient, assessed during a normothymic period using the hyperthymia component of the Semi-structured Affective Temperament Interview. RESULTS: Switches to hypomania or mania occurred in 27% of all patients (N = 12) (and in 24% of the subgroup of patients treated with SSRIs [8/33]); 16% (N = 7) experienced manic episodes, and 11% (N = 5) experienced hypomanic episodes. Sex, age, diagnosis (bipolar I vs. bipolar II), and additional treatment did not affect the risk of switching. The incidence of mood switches seemed not to differ between patients receiving an anticonvulsant and those receiving no mood stabilizer. In contrast, mood switches were less frequent in patients receiving lithium (15%, 4/26) than in patients not treated with lithium (44%, 8/18; p = .04). The number of previous manic episodes did not affect the probability of switching, whereas a high score on the hyperthymia component of the Semistructured Affective Temperament Interview was associated with a greater risk of switching (p = .008). CONCLUSION: The frequency of mood switching associated with acute antidepressant therapy may be reduced by lithium treatment. Particular attention should be paid to patients with a hyperthymic temperament, who have a greater risk of mood switches.", "entity": "Bipolar Disorder", "aliases": "Affective Psychosis Bipolar Depression Disorder Disorders Manic Mania Manias Depressive State States Manic-Depressive Psychoses", "definition": "A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.\n    ", "id": "MESH:D001714"}
{"mention": "bipolar disorder", "mention_text": "BACKGROUND: Concerns about possible risks of switching to mania associated with antidepressants continue to interfere with the establishment of an optimal treatment paradigm for bipolar depression. METHOD: The response of 44 patients meeting DSM-IV criteria for bipolar disorder to naturalistic treatment was assessed for at least 6 weeks using the Montgomery-Asberg Depression Rating Scale and the Bech-Rafaelson Mania Rating Scale. Patients who experienced a manic or hypomanic switch were compared with those who did not on several variables including age, sex, diagnosis (DSM-IV bipolar I vs. bipolar II), number of previous manic episodes, type of antidepressant therapy used (electroconvulsive therapy vs. antidepressant drugs and, more particularly, selective serotonin reuptake inhibitors [SSRIs]), use and type of mood stabilizers (lithium vs. anticonvulsants), and temperament of the patient, assessed during a normothymic period using the hyperthymia component of the Semi-structured Affective Temperament Interview. RESULTS: Switches to hypomania or mania occurred in 27% of all patients (N = 12) (and in 24% of the subgroup of patients treated with SSRIs [8/33]); 16% (N = 7) experienced manic episodes, and 11% (N = 5) experienced hypomanic episodes. Sex, age, diagnosis (bipolar I vs. bipolar II), and additional treatment did not affect the risk of switching. The incidence of mood switches seemed not to differ between patients receiving an anticonvulsant and those receiving no mood stabilizer. In contrast, mood switches were less frequent in patients receiving lithium (15%, 4/26) than in patients not treated with lithium (44%, 8/18; p = .04). The number of previous manic episodes did not affect the probability of switching, whereas a high score on the hyperthymia component of the Semistructured Affective Temperament Interview was associated with a greater risk of switching (p = .008). CONCLUSION: The frequency of mood switching associated with acute antidepressant therapy may be reduced by lithium treatment. Particular attention should be paid to patients with a hyperthymic temperament, who have a greater risk of mood switches.", "entity": "Bipolar Disorder", "aliases": "Affective Psychosis Bipolar Depression Disorder Disorders Manic Mania Manias Depressive State States Manic-Depressive Psychoses", "definition": "A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.\n    ", "id": "MESH:D001714"}
{"mention": "manic", "mention_text": "BACKGROUND: Concerns about possible risks of switching to mania associated with antidepressants continue to interfere with the establishment of an optimal treatment paradigm for bipolar depression. METHOD: The response of 44 patients meeting DSM-IV criteria for bipolar disorder to naturalistic treatment was assessed for at least 6 weeks using the Montgomery-Asberg Depression Rating Scale and the Bech-Rafaelson Mania Rating Scale. Patients who experienced a manic or hypomanic switch were compared with those who did not on several variables including age, sex, diagnosis (DSM-IV bipolar I vs. bipolar II), number of previous manic episodes, type of antidepressant therapy used (electroconvulsive therapy vs. antidepressant drugs and, more particularly, selective serotonin reuptake inhibitors [SSRIs]), use and type of mood stabilizers (lithium vs. anticonvulsants), and temperament of the patient, assessed during a normothymic period using the hyperthymia component of the Semi-structured Affective Temperament Interview. RESULTS: Switches to hypomania or mania occurred in 27% of all patients (N = 12) (and in 24% of the subgroup of patients treated with SSRIs [8/33]); 16% (N = 7) experienced manic episodes, and 11% (N = 5) experienced hypomanic episodes. Sex, age, diagnosis (bipolar I vs. bipolar II), and additional treatment did not affect the risk of switching. The incidence of mood switches seemed not to differ between patients receiving an anticonvulsant and those receiving no mood stabilizer. In contrast, mood switches were less frequent in patients receiving lithium (15%, 4/26) than in patients not treated with lithium (44%, 8/18; p = .04). The number of previous manic episodes did not affect the probability of switching, whereas a high score on the hyperthymia component of the Semistructured Affective Temperament Interview was associated with a greater risk of switching (p = .008). CONCLUSION: The frequency of mood switching associated with acute antidepressant therapy may be reduced by lithium treatment. Particular attention should be paid to patients with a hyperthymic temperament, who have a greater risk of mood switches.", "entity": "Bipolar Disorder", "aliases": "Affective Psychosis Bipolar Depression Disorder Disorders Manic Mania Manias Depressive State States Manic-Depressive Psychoses", "definition": "A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.\n    ", "id": "MESH:D001714"}
{"mention": "hypomanic", "mention_text": "BACKGROUND: Concerns about possible risks of switching to mania associated with antidepressants continue to interfere with the establishment of an optimal treatment paradigm for bipolar depression. METHOD: The response of 44 patients meeting DSM-IV criteria for bipolar disorder to naturalistic treatment was assessed for at least 6 weeks using the Montgomery-Asberg Depression Rating Scale and the Bech-Rafaelson Mania Rating Scale. Patients who experienced a manic or hypomanic switch were compared with those who did not on several variables including age, sex, diagnosis (DSM-IV bipolar I vs. bipolar II), number of previous manic episodes, type of antidepressant therapy used (electroconvulsive therapy vs. antidepressant drugs and, more particularly, selective serotonin reuptake inhibitors [SSRIs]), use and type of mood stabilizers (lithium vs. anticonvulsants), and temperament of the patient, assessed during a normothymic period using the hyperthymia component of the Semi-structured Affective Temperament Interview. RESULTS: Switches to hypomania or mania occurred in 27% of all patients (N = 12) (and in 24% of the subgroup of patients treated with SSRIs [8/33]); 16% (N = 7) experienced manic episodes, and 11% (N = 5) experienced hypomanic episodes. Sex, age, diagnosis (bipolar I vs. bipolar II), and additional treatment did not affect the risk of switching. The incidence of mood switches seemed not to differ between patients receiving an anticonvulsant and those receiving no mood stabilizer. In contrast, mood switches were less frequent in patients receiving lithium (15%, 4/26) than in patients not treated with lithium (44%, 8/18; p = .04). The number of previous manic episodes did not affect the probability of switching, whereas a high score on the hyperthymia component of the Semistructured Affective Temperament Interview was associated with a greater risk of switching (p = .008). CONCLUSION: The frequency of mood switching associated with acute antidepressant therapy may be reduced by lithium treatment. Particular attention should be paid to patients with a hyperthymic temperament, who have a greater risk of mood switches.", "entity": "Bipolar Disorder", "aliases": "Affective Psychosis Bipolar Depression Disorder Disorders Manic Mania Manias Depressive State States Manic-Depressive Psychoses", "definition": "A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.\n    ", "id": "MESH:D001714"}
{"mention": "DSM-IV bipolar I", "mention_text": "BACKGROUND: Concerns about possible risks of switching to mania associated with antidepressants continue to interfere with the establishment of an optimal treatment paradigm for bipolar depression. METHOD: The response of 44 patients meeting DSM-IV criteria for bipolar disorder to naturalistic treatment was assessed for at least 6 weeks using the Montgomery-Asberg Depression Rating Scale and the Bech-Rafaelson Mania Rating Scale. Patients who experienced a manic or hypomanic switch were compared with those who did not on several variables including age, sex, diagnosis (DSM-IV bipolar I vs. bipolar II), number of previous manic episodes, type of antidepressant therapy used (electroconvulsive therapy vs. antidepressant drugs and, more particularly, selective serotonin reuptake inhibitors [SSRIs]), use and type of mood stabilizers (lithium vs. anticonvulsants), and temperament of the patient, assessed during a normothymic period using the hyperthymia component of the Semi-structured Affective Temperament Interview. RESULTS: Switches to hypomania or mania occurred in 27% of all patients (N = 12) (and in 24% of the subgroup of patients treated with SSRIs [8/33]); 16% (N = 7) experienced manic episodes, and 11% (N = 5) experienced hypomanic episodes. Sex, age, diagnosis (bipolar I vs. bipolar II), and additional treatment did not affect the risk of switching. The incidence of mood switches seemed not to differ between patients receiving an anticonvulsant and those receiving no mood stabilizer. In contrast, mood switches were less frequent in patients receiving lithium (15%, 4/26) than in patients not treated with lithium (44%, 8/18; p = .04). The number of previous manic episodes did not affect the probability of switching, whereas a high score on the hyperthymia component of the Semistructured Affective Temperament Interview was associated with a greater risk of switching (p = .008). CONCLUSION: The frequency of mood switching associated with acute antidepressant therapy may be reduced by lithium treatment. Particular attention should be paid to patients with a hyperthymic temperament, who have a greater risk of mood switches.", "entity": "Bipolar Disorder", "aliases": "Affective Psychosis Bipolar Depression Disorder Disorders Manic Mania Manias Depressive State States Manic-Depressive Psychoses", "definition": "A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.\n    ", "id": "MESH:D001714"}
{"mention": "bipolar II", "mention_text": "BACKGROUND: Concerns about possible risks of switching to mania associated with antidepressants continue to interfere with the establishment of an optimal treatment paradigm for bipolar depression. METHOD: The response of 44 patients meeting DSM-IV criteria for bipolar disorder to naturalistic treatment was assessed for at least 6 weeks using the Montgomery-Asberg Depression Rating Scale and the Bech-Rafaelson Mania Rating Scale. Patients who experienced a manic or hypomanic switch were compared with those who did not on several variables including age, sex, diagnosis (DSM-IV bipolar I vs. bipolar II), number of previous manic episodes, type of antidepressant therapy used (electroconvulsive therapy vs. antidepressant drugs and, more particularly, selective serotonin reuptake inhibitors [SSRIs]), use and type of mood stabilizers (lithium vs. anticonvulsants), and temperament of the patient, assessed during a normothymic period using the hyperthymia component of the Semi-structured Affective Temperament Interview. RESULTS: Switches to hypomania or mania occurred in 27% of all patients (N = 12) (and in 24% of the subgroup of patients treated with SSRIs [8/33]); 16% (N = 7) experienced manic episodes, and 11% (N = 5) experienced hypomanic episodes. Sex, age, diagnosis (bipolar I vs. bipolar II), and additional treatment did not affect the risk of switching. The incidence of mood switches seemed not to differ between patients receiving an anticonvulsant and those receiving no mood stabilizer. In contrast, mood switches were less frequent in patients receiving lithium (15%, 4/26) than in patients not treated with lithium (44%, 8/18; p = .04). The number of previous manic episodes did not affect the probability of switching, whereas a high score on the hyperthymia component of the Semistructured Affective Temperament Interview was associated with a greater risk of switching (p = .008). CONCLUSION: The frequency of mood switching associated with acute antidepressant therapy may be reduced by lithium treatment. Particular attention should be paid to patients with a hyperthymic temperament, who have a greater risk of mood switches.", "entity": "Bipolar Disorder", "aliases": "Affective Psychosis Bipolar Depression Disorder Disorders Manic Mania Manias Depressive State States Manic-Depressive Psychoses", "definition": "A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.\n    ", "id": "MESH:D001714"}
{"mention": "antidepressant", "mention_text": "BACKGROUND: Concerns about possible risks of switching to mania associated with antidepressants continue to interfere with the establishment of an optimal treatment paradigm for bipolar depression. METHOD: The response of 44 patients meeting DSM-IV criteria for bipolar disorder to naturalistic treatment was assessed for at least 6 weeks using the Montgomery-Asberg Depression Rating Scale and the Bech-Rafaelson Mania Rating Scale. Patients who experienced a manic or hypomanic switch were compared with those who did not on several variables including age, sex, diagnosis (DSM-IV bipolar I vs. bipolar II), number of previous manic episodes, type of antidepressant therapy used (electroconvulsive therapy vs. antidepressant drugs and, more particularly, selective serotonin reuptake inhibitors [SSRIs]), use and type of mood stabilizers (lithium vs. anticonvulsants), and temperament of the patient, assessed during a normothymic period using the hyperthymia component of the Semi-structured Affective Temperament Interview. RESULTS: Switches to hypomania or mania occurred in 27% of all patients (N = 12) (and in 24% of the subgroup of patients treated with SSRIs [8/33]); 16% (N = 7) experienced manic episodes, and 11% (N = 5) experienced hypomanic episodes. Sex, age, diagnosis (bipolar I vs. bipolar II), and additional treatment did not affect the risk of switching. The incidence of mood switches seemed not to differ between patients receiving an anticonvulsant and those receiving no mood stabilizer. In contrast, mood switches were less frequent in patients receiving lithium (15%, 4/26) than in patients not treated with lithium (44%, 8/18; p = .04). The number of previous manic episodes did not affect the probability of switching, whereas a high score on the hyperthymia component of the Semistructured Affective Temperament Interview was associated with a greater risk of switching (p = .008). CONCLUSION: The frequency of mood switching associated with acute antidepressant therapy may be reduced by lithium treatment. Particular attention should be paid to patients with a hyperthymic temperament, who have a greater risk of mood switches.", "entity": "Antidepressive Agents", "aliases": "Agents Antidepressive Antidepressant Drugs Antidepressants Thymoanaleptics Thymoleptics", "definition": "Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.\n    ", "id": "MESH:D000928"}
{"mention": "serotonin reuptake inhibitors", "mention_text": "BACKGROUND: Concerns about possible risks of switching to mania associated with antidepressants continue to interfere with the establishment of an optimal treatment paradigm for bipolar depression. METHOD: The response of 44 patients meeting DSM-IV criteria for bipolar disorder to naturalistic treatment was assessed for at least 6 weeks using the Montgomery-Asberg Depression Rating Scale and the Bech-Rafaelson Mania Rating Scale. Patients who experienced a manic or hypomanic switch were compared with those who did not on several variables including age, sex, diagnosis (DSM-IV bipolar I vs. bipolar II), number of previous manic episodes, type of antidepressant therapy used (electroconvulsive therapy vs. antidepressant drugs and, more particularly, selective serotonin reuptake inhibitors [SSRIs]), use and type of mood stabilizers (lithium vs. anticonvulsants), and temperament of the patient, assessed during a normothymic period using the hyperthymia component of the Semi-structured Affective Temperament Interview. RESULTS: Switches to hypomania or mania occurred in 27% of all patients (N = 12) (and in 24% of the subgroup of patients treated with SSRIs [8/33]); 16% (N = 7) experienced manic episodes, and 11% (N = 5) experienced hypomanic episodes. Sex, age, diagnosis (bipolar I vs. bipolar II), and additional treatment did not affect the risk of switching. The incidence of mood switches seemed not to differ between patients receiving an anticonvulsant and those receiving no mood stabilizer. In contrast, mood switches were less frequent in patients receiving lithium (15%, 4/26) than in patients not treated with lithium (44%, 8/18; p = .04). The number of previous manic episodes did not affect the probability of switching, whereas a high score on the hyperthymia component of the Semistructured Affective Temperament Interview was associated with a greater risk of switching (p = .008). CONCLUSION: The frequency of mood switching associated with acute antidepressant therapy may be reduced by lithium treatment. Particular attention should be paid to patients with a hyperthymic temperament, who have a greater risk of mood switches.", "entity": "Serotonin Uptake Inhibitors", "aliases": "5 HT Uptake Inhibitors Hydroxytryptamine 5-HT 5-Hydroxytryptamine Serotonin Reuptake Selective", "definition": "Compounds that specifically inhibit the reuptake of serotonin in the brain.\n    ", "id": "MESH:D017367"}
{"mention": "SSRIs", "mention_text": "BACKGROUND: Concerns about possible risks of switching to mania associated with antidepressants continue to interfere with the establishment of an optimal treatment paradigm for bipolar depression. METHOD: The response of 44 patients meeting DSM-IV criteria for bipolar disorder to naturalistic treatment was assessed for at least 6 weeks using the Montgomery-Asberg Depression Rating Scale and the Bech-Rafaelson Mania Rating Scale. Patients who experienced a manic or hypomanic switch were compared with those who did not on several variables including age, sex, diagnosis (DSM-IV bipolar I vs. bipolar II), number of previous manic episodes, type of antidepressant therapy used (electroconvulsive therapy vs. antidepressant drugs and, more particularly, selective serotonin reuptake inhibitors [SSRIs]), use and type of mood stabilizers (lithium vs. anticonvulsants), and temperament of the patient, assessed during a normothymic period using the hyperthymia component of the Semi-structured Affective Temperament Interview. RESULTS: Switches to hypomania or mania occurred in 27% of all patients (N = 12) (and in 24% of the subgroup of patients treated with SSRIs [8/33]); 16% (N = 7) experienced manic episodes, and 11% (N = 5) experienced hypomanic episodes. Sex, age, diagnosis (bipolar I vs. bipolar II), and additional treatment did not affect the risk of switching. The incidence of mood switches seemed not to differ between patients receiving an anticonvulsant and those receiving no mood stabilizer. In contrast, mood switches were less frequent in patients receiving lithium (15%, 4/26) than in patients not treated with lithium (44%, 8/18; p = .04). The number of previous manic episodes did not affect the probability of switching, whereas a high score on the hyperthymia component of the Semistructured Affective Temperament Interview was associated with a greater risk of switching (p = .008). CONCLUSION: The frequency of mood switching associated with acute antidepressant therapy may be reduced by lithium treatment. Particular attention should be paid to patients with a hyperthymic temperament, who have a greater risk of mood switches.", "entity": "Serotonin Uptake Inhibitors", "aliases": "5 HT Uptake Inhibitors Hydroxytryptamine 5-HT 5-Hydroxytryptamine Serotonin Reuptake Selective", "definition": "Compounds that specifically inhibit the reuptake of serotonin in the brain.\n    ", "id": "MESH:D017367"}
{"mention": "lithium", "mention_text": "BACKGROUND: Concerns about possible risks of switching to mania associated with antidepressants continue to interfere with the establishment of an optimal treatment paradigm for bipolar depression. METHOD: The response of 44 patients meeting DSM-IV criteria for bipolar disorder to naturalistic treatment was assessed for at least 6 weeks using the Montgomery-Asberg Depression Rating Scale and the Bech-Rafaelson Mania Rating Scale. Patients who experienced a manic or hypomanic switch were compared with those who did not on several variables including age, sex, diagnosis (DSM-IV bipolar I vs. bipolar II), number of previous manic episodes, type of antidepressant therapy used (electroconvulsive therapy vs. antidepressant drugs and, more particularly, selective serotonin reuptake inhibitors [SSRIs]), use and type of mood stabilizers (lithium vs. anticonvulsants), and temperament of the patient, assessed during a normothymic period using the hyperthymia component of the Semi-structured Affective Temperament Interview. RESULTS: Switches to hypomania or mania occurred in 27% of all patients (N = 12) (and in 24% of the subgroup of patients treated with SSRIs [8/33]); 16% (N = 7) experienced manic episodes, and 11% (N = 5) experienced hypomanic episodes. Sex, age, diagnosis (bipolar I vs. bipolar II), and additional treatment did not affect the risk of switching. The incidence of mood switches seemed not to differ between patients receiving an anticonvulsant and those receiving no mood stabilizer. In contrast, mood switches were less frequent in patients receiving lithium (15%, 4/26) than in patients not treated with lithium (44%, 8/18; p = .04). The number of previous manic episodes did not affect the probability of switching, whereas a high score on the hyperthymia component of the Semistructured Affective Temperament Interview was associated with a greater risk of switching (p = .008). CONCLUSION: The frequency of mood switching associated with acute antidepressant therapy may be reduced by lithium treatment. Particular attention should be paid to patients with a hyperthymic temperament, who have a greater risk of mood switches.", "entity": "Lithium", "aliases": "Lithium", "definition": "An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.\n    ", "id": "MESH:D008094"}
{"mention": "hypomania", "mention_text": "BACKGROUND: Concerns about possible risks of switching to mania associated with antidepressants continue to interfere with the establishment of an optimal treatment paradigm for bipolar depression. METHOD: The response of 44 patients meeting DSM-IV criteria for bipolar disorder to naturalistic treatment was assessed for at least 6 weeks using the Montgomery-Asberg Depression Rating Scale and the Bech-Rafaelson Mania Rating Scale. Patients who experienced a manic or hypomanic switch were compared with those who did not on several variables including age, sex, diagnosis (DSM-IV bipolar I vs. bipolar II), number of previous manic episodes, type of antidepressant therapy used (electroconvulsive therapy vs. antidepressant drugs and, more particularly, selective serotonin reuptake inhibitors [SSRIs]), use and type of mood stabilizers (lithium vs. anticonvulsants), and temperament of the patient, assessed during a normothymic period using the hyperthymia component of the Semi-structured Affective Temperament Interview. RESULTS: Switches to hypomania or mania occurred in 27% of all patients (N = 12) (and in 24% of the subgroup of patients treated with SSRIs [8/33]); 16% (N = 7) experienced manic episodes, and 11% (N = 5) experienced hypomanic episodes. Sex, age, diagnosis (bipolar I vs. bipolar II), and additional treatment did not affect the risk of switching. The incidence of mood switches seemed not to differ between patients receiving an anticonvulsant and those receiving no mood stabilizer. In contrast, mood switches were less frequent in patients receiving lithium (15%, 4/26) than in patients not treated with lithium (44%, 8/18; p = .04). The number of previous manic episodes did not affect the probability of switching, whereas a high score on the hyperthymia component of the Semistructured Affective Temperament Interview was associated with a greater risk of switching (p = .008). CONCLUSION: The frequency of mood switching associated with acute antidepressant therapy may be reduced by lithium treatment. Particular attention should be paid to patients with a hyperthymic temperament, who have a greater risk of mood switches.", "entity": "Bipolar Disorder", "aliases": "Affective Psychosis Bipolar Depression Disorder Disorders Manic Mania Manias Depressive State States Manic-Depressive Psychoses", "definition": "A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.\n    ", "id": "MESH:D001714"}
{"mention": "bipolar I", "mention_text": "BACKGROUND: Concerns about possible risks of switching to mania associated with antidepressants continue to interfere with the establishment of an optimal treatment paradigm for bipolar depression. METHOD: The response of 44 patients meeting DSM-IV criteria for bipolar disorder to naturalistic treatment was assessed for at least 6 weeks using the Montgomery-Asberg Depression Rating Scale and the Bech-Rafaelson Mania Rating Scale. Patients who experienced a manic or hypomanic switch were compared with those who did not on several variables including age, sex, diagnosis (DSM-IV bipolar I vs. bipolar II), number of previous manic episodes, type of antidepressant therapy used (electroconvulsive therapy vs. antidepressant drugs and, more particularly, selective serotonin reuptake inhibitors [SSRIs]), use and type of mood stabilizers (lithium vs. anticonvulsants), and temperament of the patient, assessed during a normothymic period using the hyperthymia component of the Semi-structured Affective Temperament Interview. RESULTS: Switches to hypomania or mania occurred in 27% of all patients (N = 12) (and in 24% of the subgroup of patients treated with SSRIs [8/33]); 16% (N = 7) experienced manic episodes, and 11% (N = 5) experienced hypomanic episodes. Sex, age, diagnosis (bipolar I vs. bipolar II), and additional treatment did not affect the risk of switching. The incidence of mood switches seemed not to differ between patients receiving an anticonvulsant and those receiving no mood stabilizer. In contrast, mood switches were less frequent in patients receiving lithium (15%, 4/26) than in patients not treated with lithium (44%, 8/18; p = .04). The number of previous manic episodes did not affect the probability of switching, whereas a high score on the hyperthymia component of the Semistructured Affective Temperament Interview was associated with a greater risk of switching (p = .008). CONCLUSION: The frequency of mood switching associated with acute antidepressant therapy may be reduced by lithium treatment. Particular attention should be paid to patients with a hyperthymic temperament, who have a greater risk of mood switches.", "entity": "Bipolar Disorder", "aliases": "Affective Psychosis Bipolar Depression Disorder Disorders Manic Mania Manias Depressive State States Manic-Depressive Psychoses", "definition": "A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.\n    ", "id": "MESH:D001714"}
{"mention": "Caffeine", "mention_text": "Caffeine-induced cardiac arrhythmia: an unrecognised danger of healthfood products.", "entity": "Caffeine", "aliases": "1,3,7-Trimethylxanthine Berlin-Chemie Brand of Caffeine Bristol-Myers Squibb Caffedrine Coffeinum N Purrum Dexitac Durvitan GlaxoSmithKline Merck dura No Doz Passauer Percoffedrinol Percutaféine Pierre Fabre Quick-Pep Republic Drug Seid Thompson 1 2 Vivarin", "definition": "A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling.\n    ", "id": "MESH:D002110"}
{"mention": "cardiac arrhythmia", "mention_text": "Caffeine-induced cardiac arrhythmia: an unrecognised danger of healthfood products.", "entity": "Arrhythmias, Cardiac", "aliases": "Arrhythmia Cardiac Arrhythmias Arrythmia Dysrhythmia", "definition": "Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.\n    ", "id": "MESH:D001145"}
{"mention": "mitral valve prolapse", "mention_text": "We describe a 25-year-old woman with pre-existing mitral valve prolapse who developed intractable ventricular fibrillation after consuming a \"natural energy\" guarana health drink containing a high concentration of caffeine. This case highlights the need for adequate labelling and regulation of such products.", "entity": "Mitral Valve Prolapse", "aliases": "Click Murmur Syndrome Click-Murmur Mitral Systolic Syndromes Floppy Valve Valves Prolapse Prolapses Prolapsed", "definition": "Abnormal protrusion or billowing of one or both of the leaflets of MITRAL VALVE into the LEFT ATRIUM during SYSTOLE. This allows the backflow of blood into left atrium leading to MITRAL VALVE INSUFFICIENCY; SYSTOLIC MURMURS; or CARDIAC ARRHYTHMIA.\n    ", "id": "MESH:D008945"}
{"mention": "ventricular fibrillation", "mention_text": "We describe a 25-year-old woman with pre-existing mitral valve prolapse who developed intractable ventricular fibrillation after consuming a \"natural energy\" guarana health drink containing a high concentration of caffeine. This case highlights the need for adequate labelling and regulation of such products.", "entity": "Ventricular Fibrillation", "aliases": "Fibrillation Ventricular Fibrillations", "definition": "A potentially lethal cardiac arrhythmia that is characterized by uncoordinated extremely rapid firing of electrical impulses (400-600/min) in HEART VENTRICLES. Such asynchronous ventricular quivering or fibrillation prevents any effective cardiac output and results in unconsciousness (SYNCOPE). It is one of the major electrocardiographic patterns seen with CARDIAC ARREST.\n    ", "id": "MESH:D014693"}
{"mention": "caffeine", "mention_text": "We describe a 25-year-old woman with pre-existing mitral valve prolapse who developed intractable ventricular fibrillation after consuming a \"natural energy\" guarana health drink containing a high concentration of caffeine. This case highlights the need for adequate labelling and regulation of such products.", "entity": "Caffeine", "aliases": "1,3,7-Trimethylxanthine Berlin-Chemie Brand of Caffeine Bristol-Myers Squibb Caffedrine Coffeinum N Purrum Dexitac Durvitan GlaxoSmithKline Merck dura No Doz Passauer Percoffedrinol Percutaféine Pierre Fabre Quick-Pep Republic Drug Seid Thompson 1 2 Vivarin", "definition": "A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling.\n    ", "id": "MESH:D002110"}
{"mention": "retention of urine", "mention_text": "Bladder retention of urine as a result of continuous intravenous infusion of fentanyl: 2 case reports.", "entity": "Urinary Retention", "aliases": "Retention Urinary", "definition": "Inability to empty the URINARY BLADDER with voiding (URINATION).\n    ", "id": "MESH:D016055"}
{"mention": "fentanyl", "mention_text": "Bladder retention of urine as a result of continuous intravenous infusion of fentanyl: 2 case reports.", "entity": "Fentanyl", "aliases": "Cephalon Brand of Fentanyl Buccal OraVescent Duragesic Durogesic Fentanest Citrate Fentora Janssen Pharmaceutica Phentanyl R 4263 R-4263 R4263 Sublimaze Transmucosal Oral", "definition": "A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1078)\n    ", "id": "MESH:D005283"}
{"mention": "pain", "mention_text": "Sedation has been commonly used in the neonate to decrease the stress and pain from the noxious stimuli and invasive procedures in the neonatal intensive care unit, as well as to facilitate synchrony between ventilator and spontaneous breaths. Fentanyl, an opioid analgesic, is frequently used in the neonatal intensive care unit setting for these very purposes. Various reported side effects of fentanyl administration include chest wall rigidity, hypotension, respiratory depression, and bradycardia. Here, 2 cases of urinary bladder retention leading to renal pelvocalyceal dilatation mimicking hydronephrosis as a result of continuous infusion of fentanyl are reported.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "Fentanyl", "mention_text": "Sedation has been commonly used in the neonate to decrease the stress and pain from the noxious stimuli and invasive procedures in the neonatal intensive care unit, as well as to facilitate synchrony between ventilator and spontaneous breaths. Fentanyl, an opioid analgesic, is frequently used in the neonatal intensive care unit setting for these very purposes. Various reported side effects of fentanyl administration include chest wall rigidity, hypotension, respiratory depression, and bradycardia. Here, 2 cases of urinary bladder retention leading to renal pelvocalyceal dilatation mimicking hydronephrosis as a result of continuous infusion of fentanyl are reported.", "entity": "Fentanyl", "aliases": "Cephalon Brand of Fentanyl Buccal OraVescent Duragesic Durogesic Fentanest Citrate Fentora Janssen Pharmaceutica Phentanyl R 4263 R-4263 R4263 Sublimaze Transmucosal Oral", "definition": "A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1078)\n    ", "id": "MESH:D005283"}
{"mention": "fentanyl", "mention_text": "Sedation has been commonly used in the neonate to decrease the stress and pain from the noxious stimuli and invasive procedures in the neonatal intensive care unit, as well as to facilitate synchrony between ventilator and spontaneous breaths. Fentanyl, an opioid analgesic, is frequently used in the neonatal intensive care unit setting for these very purposes. Various reported side effects of fentanyl administration include chest wall rigidity, hypotension, respiratory depression, and bradycardia. Here, 2 cases of urinary bladder retention leading to renal pelvocalyceal dilatation mimicking hydronephrosis as a result of continuous infusion of fentanyl are reported.", "entity": "Fentanyl", "aliases": "Cephalon Brand of Fentanyl Buccal OraVescent Duragesic Durogesic Fentanest Citrate Fentora Janssen Pharmaceutica Phentanyl R 4263 R-4263 R4263 Sublimaze Transmucosal Oral", "definition": "A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1078)\n    ", "id": "MESH:D005283"}
{"mention": "chest wall rigidity", "mention_text": "Sedation has been commonly used in the neonate to decrease the stress and pain from the noxious stimuli and invasive procedures in the neonatal intensive care unit, as well as to facilitate synchrony between ventilator and spontaneous breaths. Fentanyl, an opioid analgesic, is frequently used in the neonatal intensive care unit setting for these very purposes. Various reported side effects of fentanyl administration include chest wall rigidity, hypotension, respiratory depression, and bradycardia. Here, 2 cases of urinary bladder retention leading to renal pelvocalyceal dilatation mimicking hydronephrosis as a result of continuous infusion of fentanyl are reported.", "entity": "Muscle Rigidity", "aliases": "Catatonic Rigidity Cogwheel Rigidities Extensor Extrapyramidal Gegenhalten Gegenhaltens Muscle Muscular Nuchal", "definition": "Continuous involuntary sustained muscle contraction which is often a manifestation of BASAL GANGLIA DISEASES. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from MUSCLE SPASTICITY. (From Adams et al., Principles of Neurology, 6th ed, p73)\n    ", "id": "MESH:D009127"}
{"mention": "hypotension", "mention_text": "Sedation has been commonly used in the neonate to decrease the stress and pain from the noxious stimuli and invasive procedures in the neonatal intensive care unit, as well as to facilitate synchrony between ventilator and spontaneous breaths. Fentanyl, an opioid analgesic, is frequently used in the neonatal intensive care unit setting for these very purposes. Various reported side effects of fentanyl administration include chest wall rigidity, hypotension, respiratory depression, and bradycardia. Here, 2 cases of urinary bladder retention leading to renal pelvocalyceal dilatation mimicking hydronephrosis as a result of continuous infusion of fentanyl are reported.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "respiratory depression", "mention_text": "Sedation has been commonly used in the neonate to decrease the stress and pain from the noxious stimuli and invasive procedures in the neonatal intensive care unit, as well as to facilitate synchrony between ventilator and spontaneous breaths. Fentanyl, an opioid analgesic, is frequently used in the neonatal intensive care unit setting for these very purposes. Various reported side effects of fentanyl administration include chest wall rigidity, hypotension, respiratory depression, and bradycardia. Here, 2 cases of urinary bladder retention leading to renal pelvocalyceal dilatation mimicking hydronephrosis as a result of continuous infusion of fentanyl are reported.", "entity": "Respiratory Insufficiency", "aliases": "Depressions Ventilatory Respiratory Depression Failure Insufficiency", "definition": "Failure to adequately provide oxygen to cells of the body and to remove excess carbon dioxide from them. (Stedman, 25th ed)\n    ", "id": "MESH:D012131"}
{"mention": "bradycardia", "mention_text": "Sedation has been commonly used in the neonate to decrease the stress and pain from the noxious stimuli and invasive procedures in the neonatal intensive care unit, as well as to facilitate synchrony between ventilator and spontaneous breaths. Fentanyl, an opioid analgesic, is frequently used in the neonatal intensive care unit setting for these very purposes. Various reported side effects of fentanyl administration include chest wall rigidity, hypotension, respiratory depression, and bradycardia. Here, 2 cases of urinary bladder retention leading to renal pelvocalyceal dilatation mimicking hydronephrosis as a result of continuous infusion of fentanyl are reported.", "entity": "Bradycardia", "aliases": "Bradyarrhythmia Bradyarrhythmias Bradycardia Bradycardias", "definition": "Cardiac arrhythmias that are characterized by excessively slow HEART RATE, usually below 50 beats per minute in human adults. They can be classified broadly into SINOATRIAL NODE dysfunction and ATRIOVENTRICULAR BLOCK.\n    ", "id": "MESH:D001919"}
{"mention": "urinary bladder retention", "mention_text": "Sedation has been commonly used in the neonate to decrease the stress and pain from the noxious stimuli and invasive procedures in the neonatal intensive care unit, as well as to facilitate synchrony between ventilator and spontaneous breaths. Fentanyl, an opioid analgesic, is frequently used in the neonatal intensive care unit setting for these very purposes. Various reported side effects of fentanyl administration include chest wall rigidity, hypotension, respiratory depression, and bradycardia. Here, 2 cases of urinary bladder retention leading to renal pelvocalyceal dilatation mimicking hydronephrosis as a result of continuous infusion of fentanyl are reported.", "entity": "Urinary Bladder Diseases", "aliases": "Bladder Disease Diseases Urinary", "definition": "Pathological processes of the URINARY BLADDER.\n    ", "id": "MESH:D001745"}
{"mention": "hydronephrosis", "mention_text": "Sedation has been commonly used in the neonate to decrease the stress and pain from the noxious stimuli and invasive procedures in the neonatal intensive care unit, as well as to facilitate synchrony between ventilator and spontaneous breaths. Fentanyl, an opioid analgesic, is frequently used in the neonatal intensive care unit setting for these very purposes. Various reported side effects of fentanyl administration include chest wall rigidity, hypotension, respiratory depression, and bradycardia. Here, 2 cases of urinary bladder retention leading to renal pelvocalyceal dilatation mimicking hydronephrosis as a result of continuous infusion of fentanyl are reported.", "entity": "Hydronephrosis", "aliases": "Hydronephroses Hydronephrosis", "definition": "Abnormal enlargement or swelling of a KIDNEY due to dilation of the KIDNEY CALICES and the KIDNEY PELVIS. It is often associated with obstruction of the URETER or chronic kidney diseases that prevents normal drainage of urine into the URINARY BLADDER.\n    ", "id": "MESH:D006869"}
{"mention": "cardiomyopathy", "mention_text": "Combined antiretroviral therapy causes cardiomyopathy and elevates plasma lactate in transgenic AIDS mice.", "entity": "Cardiomyopathies", "aliases": "Cardiomyopathies Primary Secondary Cardiomyopathy Disease Myocardial Diseases Myocardiopathies Myocardiopathy", "definition": "A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).\n    ", "id": "MESH:D009202"}
{"mention": "lactate", "mention_text": "Combined antiretroviral therapy causes cardiomyopathy and elevates plasma lactate in transgenic AIDS mice.", "entity": "Lactic Acid", "aliases": "2 Hydroxypropanoic Acid Hydroxypropionic 2-Hydroxypropanoic 2-Hydroxypropionic Ammonium Lactate D Lactic D-Lactic L L-Lactic Propanoic 2-Hydroxy- (2R)- (2S)- Sarcolactic", "definition": "A normal intermediate in the fermentation (oxidation, metabolism) of sugar. The concentrated form is used internally to prevent gastrointestinal fermentation. (From Stedman, 26th ed)\n    ", "id": "MESH:D019344"}
{"mention": "AIDS", "mention_text": "Combined antiretroviral therapy causes cardiomyopathy and elevates plasma lactate in transgenic AIDS mice.", "entity": "Acquired Immunodeficiency Syndrome", "aliases": "AIDS Acquired Immune Deficiency Syndrome Immuno Immuno-Deficiency Syndromes Immunodeficiency Immunologic", "definition": "An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive T-lymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993.\n    ", "id": "MESH:D000163"}
{"mention": "cardiomyopathy", "mention_text": "Highly active antiretroviral therapy (HAART) is implicated in cardiomyopathy (CM) and in elevated plasma lactate (LA) in AIDS through mechanisms of mitochondrial dysfunction. To determine mitochondrial events from HAART in vivo, 8-week-old hemizygous transgenic AIDS mice (NL4-3Delta gag/pol; TG) and wild-type FVB/n littermates were treated with the HAART combination of zidovudine, lamivudine, and indinavir or vehicle control for 10 days or 35 days. At termination of the experiments, mice underwent echocardiography, quantitation of abundance of molecular markers of CM (ventricular mRNA encoding atrial natriuretic factor [ANF] and sarcoplasmic calcium ATPase [SERCA2]), and determination of plasma LA. Myocardial histologic features were analyzed semiquantitatively and results were confirmed by transmission electron microscopy. After 35 days in the TG + HAART cohort, left ventricular mass increased 160% by echocardiography. Molecularly, ANF mRNA increased 250% and SERCA2 mRNA decreased 57%. Biochemically, LA was elevated (8.5 +/- 2.0 mM). Pathologically, granular cytoplasmic changes were found in cardiac myocytes, indicating enlarged, damaged mitochondria. Findings were confirmed ultrastructurally. No changes were found in other cohorts. After 10 days, only ANF was elevated, and only in the TG + HAART cohort. Results show that cumulative HAART caused mitochondrial CM with elevated LA in AIDS transgenic mice.", "entity": "Cardiomyopathies", "aliases": "Cardiomyopathies Primary Secondary Cardiomyopathy Disease Myocardial Diseases Myocardiopathies Myocardiopathy", "definition": "A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).\n    ", "id": "MESH:D009202"}
{"mention": "CM", "mention_text": "Highly active antiretroviral therapy (HAART) is implicated in cardiomyopathy (CM) and in elevated plasma lactate (LA) in AIDS through mechanisms of mitochondrial dysfunction. To determine mitochondrial events from HAART in vivo, 8-week-old hemizygous transgenic AIDS mice (NL4-3Delta gag/pol; TG) and wild-type FVB/n littermates were treated with the HAART combination of zidovudine, lamivudine, and indinavir or vehicle control for 10 days or 35 days. At termination of the experiments, mice underwent echocardiography, quantitation of abundance of molecular markers of CM (ventricular mRNA encoding atrial natriuretic factor [ANF] and sarcoplasmic calcium ATPase [SERCA2]), and determination of plasma LA. Myocardial histologic features were analyzed semiquantitatively and results were confirmed by transmission electron microscopy. After 35 days in the TG + HAART cohort, left ventricular mass increased 160% by echocardiography. Molecularly, ANF mRNA increased 250% and SERCA2 mRNA decreased 57%. Biochemically, LA was elevated (8.5 +/- 2.0 mM). Pathologically, granular cytoplasmic changes were found in cardiac myocytes, indicating enlarged, damaged mitochondria. Findings were confirmed ultrastructurally. No changes were found in other cohorts. After 10 days, only ANF was elevated, and only in the TG + HAART cohort. Results show that cumulative HAART caused mitochondrial CM with elevated LA in AIDS transgenic mice.", "entity": "Cardiomyopathies", "aliases": "Cardiomyopathies Primary Secondary Cardiomyopathy Disease Myocardial Diseases Myocardiopathies Myocardiopathy", "definition": "A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).\n    ", "id": "MESH:D009202"}
{"mention": "lactate", "mention_text": "Highly active antiretroviral therapy (HAART) is implicated in cardiomyopathy (CM) and in elevated plasma lactate (LA) in AIDS through mechanisms of mitochondrial dysfunction. To determine mitochondrial events from HAART in vivo, 8-week-old hemizygous transgenic AIDS mice (NL4-3Delta gag/pol; TG) and wild-type FVB/n littermates were treated with the HAART combination of zidovudine, lamivudine, and indinavir or vehicle control for 10 days or 35 days. At termination of the experiments, mice underwent echocardiography, quantitation of abundance of molecular markers of CM (ventricular mRNA encoding atrial natriuretic factor [ANF] and sarcoplasmic calcium ATPase [SERCA2]), and determination of plasma LA. Myocardial histologic features were analyzed semiquantitatively and results were confirmed by transmission electron microscopy. After 35 days in the TG + HAART cohort, left ventricular mass increased 160% by echocardiography. Molecularly, ANF mRNA increased 250% and SERCA2 mRNA decreased 57%. Biochemically, LA was elevated (8.5 +/- 2.0 mM). Pathologically, granular cytoplasmic changes were found in cardiac myocytes, indicating enlarged, damaged mitochondria. Findings were confirmed ultrastructurally. No changes were found in other cohorts. After 10 days, only ANF was elevated, and only in the TG + HAART cohort. Results show that cumulative HAART caused mitochondrial CM with elevated LA in AIDS transgenic mice.", "entity": "Lactic Acid", "aliases": "2 Hydroxypropanoic Acid Hydroxypropionic 2-Hydroxypropanoic 2-Hydroxypropionic Ammonium Lactate D Lactic D-Lactic L L-Lactic Propanoic 2-Hydroxy- (2R)- (2S)- Sarcolactic", "definition": "A normal intermediate in the fermentation (oxidation, metabolism) of sugar. The concentrated form is used internally to prevent gastrointestinal fermentation. (From Stedman, 26th ed)\n    ", "id": "MESH:D019344"}
{"mention": "LA", "mention_text": "Highly active antiretroviral therapy (HAART) is implicated in cardiomyopathy (CM) and in elevated plasma lactate (LA) in AIDS through mechanisms of mitochondrial dysfunction. To determine mitochondrial events from HAART in vivo, 8-week-old hemizygous transgenic AIDS mice (NL4-3Delta gag/pol; TG) and wild-type FVB/n littermates were treated with the HAART combination of zidovudine, lamivudine, and indinavir or vehicle control for 10 days or 35 days. At termination of the experiments, mice underwent echocardiography, quantitation of abundance of molecular markers of CM (ventricular mRNA encoding atrial natriuretic factor [ANF] and sarcoplasmic calcium ATPase [SERCA2]), and determination of plasma LA. Myocardial histologic features were analyzed semiquantitatively and results were confirmed by transmission electron microscopy. After 35 days in the TG + HAART cohort, left ventricular mass increased 160% by echocardiography. Molecularly, ANF mRNA increased 250% and SERCA2 mRNA decreased 57%. Biochemically, LA was elevated (8.5 +/- 2.0 mM). Pathologically, granular cytoplasmic changes were found in cardiac myocytes, indicating enlarged, damaged mitochondria. Findings were confirmed ultrastructurally. No changes were found in other cohorts. After 10 days, only ANF was elevated, and only in the TG + HAART cohort. Results show that cumulative HAART caused mitochondrial CM with elevated LA in AIDS transgenic mice.", "entity": "Lactic Acid", "aliases": "2 Hydroxypropanoic Acid Hydroxypropionic 2-Hydroxypropanoic 2-Hydroxypropionic Ammonium Lactate D Lactic D-Lactic L L-Lactic Propanoic 2-Hydroxy- (2R)- (2S)- Sarcolactic", "definition": "A normal intermediate in the fermentation (oxidation, metabolism) of sugar. The concentrated form is used internally to prevent gastrointestinal fermentation. (From Stedman, 26th ed)\n    ", "id": "MESH:D019344"}
{"mention": "AIDS", "mention_text": "Highly active antiretroviral therapy (HAART) is implicated in cardiomyopathy (CM) and in elevated plasma lactate (LA) in AIDS through mechanisms of mitochondrial dysfunction. To determine mitochondrial events from HAART in vivo, 8-week-old hemizygous transgenic AIDS mice (NL4-3Delta gag/pol; TG) and wild-type FVB/n littermates were treated with the HAART combination of zidovudine, lamivudine, and indinavir or vehicle control for 10 days or 35 days. At termination of the experiments, mice underwent echocardiography, quantitation of abundance of molecular markers of CM (ventricular mRNA encoding atrial natriuretic factor [ANF] and sarcoplasmic calcium ATPase [SERCA2]), and determination of plasma LA. Myocardial histologic features were analyzed semiquantitatively and results were confirmed by transmission electron microscopy. After 35 days in the TG + HAART cohort, left ventricular mass increased 160% by echocardiography. Molecularly, ANF mRNA increased 250% and SERCA2 mRNA decreased 57%. Biochemically, LA was elevated (8.5 +/- 2.0 mM). Pathologically, granular cytoplasmic changes were found in cardiac myocytes, indicating enlarged, damaged mitochondria. Findings were confirmed ultrastructurally. No changes were found in other cohorts. After 10 days, only ANF was elevated, and only in the TG + HAART cohort. Results show that cumulative HAART caused mitochondrial CM with elevated LA in AIDS transgenic mice.", "entity": "Acquired Immunodeficiency Syndrome", "aliases": "AIDS Acquired Immune Deficiency Syndrome Immuno Immuno-Deficiency Syndromes Immunodeficiency Immunologic", "definition": "An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive T-lymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993.\n    ", "id": "MESH:D000163"}
{"mention": "mitochondrial dysfunction", "mention_text": "Highly active antiretroviral therapy (HAART) is implicated in cardiomyopathy (CM) and in elevated plasma lactate (LA) in AIDS through mechanisms of mitochondrial dysfunction. To determine mitochondrial events from HAART in vivo, 8-week-old hemizygous transgenic AIDS mice (NL4-3Delta gag/pol; TG) and wild-type FVB/n littermates were treated with the HAART combination of zidovudine, lamivudine, and indinavir or vehicle control for 10 days or 35 days. At termination of the experiments, mice underwent echocardiography, quantitation of abundance of molecular markers of CM (ventricular mRNA encoding atrial natriuretic factor [ANF] and sarcoplasmic calcium ATPase [SERCA2]), and determination of plasma LA. Myocardial histologic features were analyzed semiquantitatively and results were confirmed by transmission electron microscopy. After 35 days in the TG + HAART cohort, left ventricular mass increased 160% by echocardiography. Molecularly, ANF mRNA increased 250% and SERCA2 mRNA decreased 57%. Biochemically, LA was elevated (8.5 +/- 2.0 mM). Pathologically, granular cytoplasmic changes were found in cardiac myocytes, indicating enlarged, damaged mitochondria. Findings were confirmed ultrastructurally. No changes were found in other cohorts. After 10 days, only ANF was elevated, and only in the TG + HAART cohort. Results show that cumulative HAART caused mitochondrial CM with elevated LA in AIDS transgenic mice.", "entity": "Mitochondrial Diseases", "aliases": "Deficiencies Oxidative Phosphorylation Respiratory Chain Deficiency Disease Mitochondrial Disorder Disorders Electron Transport Diseases", "definition": "Diseases caused by abnormal function of the MITOCHONDRIA. They may be caused by mutations, acquired or inherited, in mitochondrial DNA or in nuclear genes that code for mitochondrial components. They may also be the result of acquired mitochondria dysfunction due to adverse effects of drugs, infections, or other environmental causes.\n    ", "id": "MESH:D028361"}
{"mention": "zidovudine", "mention_text": "Highly active antiretroviral therapy (HAART) is implicated in cardiomyopathy (CM) and in elevated plasma lactate (LA) in AIDS through mechanisms of mitochondrial dysfunction. To determine mitochondrial events from HAART in vivo, 8-week-old hemizygous transgenic AIDS mice (NL4-3Delta gag/pol; TG) and wild-type FVB/n littermates were treated with the HAART combination of zidovudine, lamivudine, and indinavir or vehicle control for 10 days or 35 days. At termination of the experiments, mice underwent echocardiography, quantitation of abundance of molecular markers of CM (ventricular mRNA encoding atrial natriuretic factor [ANF] and sarcoplasmic calcium ATPase [SERCA2]), and determination of plasma LA. Myocardial histologic features were analyzed semiquantitatively and results were confirmed by transmission electron microscopy. After 35 days in the TG + HAART cohort, left ventricular mass increased 160% by echocardiography. Molecularly, ANF mRNA increased 250% and SERCA2 mRNA decreased 57%. Biochemically, LA was elevated (8.5 +/- 2.0 mM). Pathologically, granular cytoplasmic changes were found in cardiac myocytes, indicating enlarged, damaged mitochondria. Findings were confirmed ultrastructurally. No changes were found in other cohorts. After 10 days, only ANF was elevated, and only in the TG + HAART cohort. Results show that cumulative HAART caused mitochondrial CM with elevated LA in AIDS transgenic mice.", "entity": "Zidovudine", "aliases": "3' Azido 2',3' Dideoxythymidine deoxythymidine 3'-Azido-2',3'-Dideoxythymidine 3'-Azido-3'-deoxythymidine AZT (Antiviral) Antiviral Azidothymidine BW A509U BWA 509U BWA-509U BWA509U Retrovir Zidovudine", "definition": "A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.\n    ", "id": "MESH:D015215"}
{"mention": "lamivudine", "mention_text": "Highly active antiretroviral therapy (HAART) is implicated in cardiomyopathy (CM) and in elevated plasma lactate (LA) in AIDS through mechanisms of mitochondrial dysfunction. To determine mitochondrial events from HAART in vivo, 8-week-old hemizygous transgenic AIDS mice (NL4-3Delta gag/pol; TG) and wild-type FVB/n littermates were treated with the HAART combination of zidovudine, lamivudine, and indinavir or vehicle control for 10 days or 35 days. At termination of the experiments, mice underwent echocardiography, quantitation of abundance of molecular markers of CM (ventricular mRNA encoding atrial natriuretic factor [ANF] and sarcoplasmic calcium ATPase [SERCA2]), and determination of plasma LA. Myocardial histologic features were analyzed semiquantitatively and results were confirmed by transmission electron microscopy. After 35 days in the TG + HAART cohort, left ventricular mass increased 160% by echocardiography. Molecularly, ANF mRNA increased 250% and SERCA2 mRNA decreased 57%. Biochemically, LA was elevated (8.5 +/- 2.0 mM). Pathologically, granular cytoplasmic changes were found in cardiac myocytes, indicating enlarged, damaged mitochondria. Findings were confirmed ultrastructurally. No changes were found in other cohorts. After 10 days, only ANF was elevated, and only in the TG + HAART cohort. Results show that cumulative HAART caused mitochondrial CM with elevated LA in AIDS transgenic mice.", "entity": "Lamivudine", "aliases": "2',3' Dideoxy 3' thiacytidine 2',3'-Dideoxy-3'-thiacytidine 3TC BCH 189 BCH-189 BCH189 Epivir GR-109714X GR109714X Lamivudine (2S-cis)-Isomer", "definition": "A reverse transcriptase inhibitor and ZALCITABINE analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease.\n    ", "id": "MESH:D019259"}
{"mention": "indinavir", "mention_text": "Highly active antiretroviral therapy (HAART) is implicated in cardiomyopathy (CM) and in elevated plasma lactate (LA) in AIDS through mechanisms of mitochondrial dysfunction. To determine mitochondrial events from HAART in vivo, 8-week-old hemizygous transgenic AIDS mice (NL4-3Delta gag/pol; TG) and wild-type FVB/n littermates were treated with the HAART combination of zidovudine, lamivudine, and indinavir or vehicle control for 10 days or 35 days. At termination of the experiments, mice underwent echocardiography, quantitation of abundance of molecular markers of CM (ventricular mRNA encoding atrial natriuretic factor [ANF] and sarcoplasmic calcium ATPase [SERCA2]), and determination of plasma LA. Myocardial histologic features were analyzed semiquantitatively and results were confirmed by transmission electron microscopy. After 35 days in the TG + HAART cohort, left ventricular mass increased 160% by echocardiography. Molecularly, ANF mRNA increased 250% and SERCA2 mRNA decreased 57%. Biochemically, LA was elevated (8.5 +/- 2.0 mM). Pathologically, granular cytoplasmic changes were found in cardiac myocytes, indicating enlarged, damaged mitochondria. Findings were confirmed ultrastructurally. No changes were found in other cohorts. After 10 days, only ANF was elevated, and only in the TG + HAART cohort. Results show that cumulative HAART caused mitochondrial CM with elevated LA in AIDS transgenic mice.", "entity": "Indinavir", "aliases": "Crixivan Indinavir Sulfate (1:1) L 735 524 735,524 L-735 L-735,524 L735 L735,524 MK 639 MK-639 MK639", "definition": "A potent and specific HIV protease inhibitor that appears to have good oral bioavailability.\n    ", "id": "MESH:D019469"}
{"mention": "calcium", "mention_text": "Highly active antiretroviral therapy (HAART) is implicated in cardiomyopathy (CM) and in elevated plasma lactate (LA) in AIDS through mechanisms of mitochondrial dysfunction. To determine mitochondrial events from HAART in vivo, 8-week-old hemizygous transgenic AIDS mice (NL4-3Delta gag/pol; TG) and wild-type FVB/n littermates were treated with the HAART combination of zidovudine, lamivudine, and indinavir or vehicle control for 10 days or 35 days. At termination of the experiments, mice underwent echocardiography, quantitation of abundance of molecular markers of CM (ventricular mRNA encoding atrial natriuretic factor [ANF] and sarcoplasmic calcium ATPase [SERCA2]), and determination of plasma LA. Myocardial histologic features were analyzed semiquantitatively and results were confirmed by transmission electron microscopy. After 35 days in the TG + HAART cohort, left ventricular mass increased 160% by echocardiography. Molecularly, ANF mRNA increased 250% and SERCA2 mRNA decreased 57%. Biochemically, LA was elevated (8.5 +/- 2.0 mM). Pathologically, granular cytoplasmic changes were found in cardiac myocytes, indicating enlarged, damaged mitochondria. Findings were confirmed ultrastructurally. No changes were found in other cohorts. After 10 days, only ANF was elevated, and only in the TG + HAART cohort. Results show that cumulative HAART caused mitochondrial CM with elevated LA in AIDS transgenic mice.", "entity": "Calcium", "aliases": "Blood Coagulation Factor IV Calcium", "definition": "A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.\n    ", "id": "MESH:D002118"}
{"mention": "Oral contraceptives", "mention_text": "Oral contraceptives and the risk of myocardial infarction.", "entity": "Contraceptives, Oral", "aliases": "Contraceptives Low-Dose Oral Phasic Low Dose", "definition": "Compounds, usually hormonal, taken orally in order to block ovulation and prevent the occurrence of pregnancy. The hormones are generally estrogen or progesterone or both.\n    ", "id": "MESH:D003276"}
{"mention": "myocardial infarction", "mention_text": "Oral contraceptives and the risk of myocardial infarction.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "oral contraceptives", "mention_text": "BACKGROUND: An association between the use of oral contraceptives and the risk of myocardial infarction has been found in some, but not all, studies. We investigated this association, according to the type of progestagen included in third-generation (i.e., desogestrel or gestodene) and second-generation (i.e., levonorgestrel) oral contraceptives, the dose of estrogen, and the presence or absence of prothrombotic mutations METHODS: In a nationwide, population-based, case-control study, we identified and enrolled 248 women 18 through 49 years of age who had had a first myocardial infarction between 1990 and 1995 and 925 control women who had not had a myocardial infarction and who were matched for age, calendar year of the index event, and area of residence. Subjects supplied information on oral-contraceptive use and major cardiovascular risk factors. An analysis for factor V Leiden and the G20210A mutation in the prothrombin gene was conducted in 217 patients and 763 controls RESULTS: The odds ratio for myocardial infarction among women who used any type of combined oral contraceptive, as compared with nonusers, was 2.0 (95 percent confidence interval, 1.5 to 2.8). The adjusted odds ratio was 2.5 (95 percent confidence interval, 1.5 to 4.1) among women who used second-generation oral contraceptives and 1.3 (95 percent confidence interval, 0.7 to 2.5) among those who used third-generation oral contraceptives. Among women who used oral contraceptives, the odds ratio was 2.1 (95 percent confidence interval, 1.5 to 3.0) for those without a prothrombotic mutation and 1.9 (95 percent confidence interval, 0.6 to 5.5) for those with a mutation CONCLUSIONS: The risk of myocardial infarction was increased among women who used second-generation oral contraceptives. The results with respect to the use of third-generation oral contraceptives were inconclusive but suggested that the risk was lower than the risk associated with second-generation oral contraceptives. The risk of myocardial infarction was similar among women who used oral contraceptives whether or not they had a prothrombotic mutation.", "entity": "Contraceptives, Oral", "aliases": "Contraceptives Low-Dose Oral Phasic Low Dose", "definition": "Compounds, usually hormonal, taken orally in order to block ovulation and prevent the occurrence of pregnancy. The hormones are generally estrogen or progesterone or both.\n    ", "id": "MESH:D003276"}
{"mention": "myocardial infarction", "mention_text": "BACKGROUND: An association between the use of oral contraceptives and the risk of myocardial infarction has been found in some, but not all, studies. We investigated this association, according to the type of progestagen included in third-generation (i.e., desogestrel or gestodene) and second-generation (i.e., levonorgestrel) oral contraceptives, the dose of estrogen, and the presence or absence of prothrombotic mutations METHODS: In a nationwide, population-based, case-control study, we identified and enrolled 248 women 18 through 49 years of age who had had a first myocardial infarction between 1990 and 1995 and 925 control women who had not had a myocardial infarction and who were matched for age, calendar year of the index event, and area of residence. Subjects supplied information on oral-contraceptive use and major cardiovascular risk factors. An analysis for factor V Leiden and the G20210A mutation in the prothrombin gene was conducted in 217 patients and 763 controls RESULTS: The odds ratio for myocardial infarction among women who used any type of combined oral contraceptive, as compared with nonusers, was 2.0 (95 percent confidence interval, 1.5 to 2.8). The adjusted odds ratio was 2.5 (95 percent confidence interval, 1.5 to 4.1) among women who used second-generation oral contraceptives and 1.3 (95 percent confidence interval, 0.7 to 2.5) among those who used third-generation oral contraceptives. Among women who used oral contraceptives, the odds ratio was 2.1 (95 percent confidence interval, 1.5 to 3.0) for those without a prothrombotic mutation and 1.9 (95 percent confidence interval, 0.6 to 5.5) for those with a mutation CONCLUSIONS: The risk of myocardial infarction was increased among women who used second-generation oral contraceptives. The results with respect to the use of third-generation oral contraceptives were inconclusive but suggested that the risk was lower than the risk associated with second-generation oral contraceptives. The risk of myocardial infarction was similar among women who used oral contraceptives whether or not they had a prothrombotic mutation.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "progestagen", "mention_text": "BACKGROUND: An association between the use of oral contraceptives and the risk of myocardial infarction has been found in some, but not all, studies. We investigated this association, according to the type of progestagen included in third-generation (i.e., desogestrel or gestodene) and second-generation (i.e., levonorgestrel) oral contraceptives, the dose of estrogen, and the presence or absence of prothrombotic mutations METHODS: In a nationwide, population-based, case-control study, we identified and enrolled 248 women 18 through 49 years of age who had had a first myocardial infarction between 1990 and 1995 and 925 control women who had not had a myocardial infarction and who were matched for age, calendar year of the index event, and area of residence. Subjects supplied information on oral-contraceptive use and major cardiovascular risk factors. An analysis for factor V Leiden and the G20210A mutation in the prothrombin gene was conducted in 217 patients and 763 controls RESULTS: The odds ratio for myocardial infarction among women who used any type of combined oral contraceptive, as compared with nonusers, was 2.0 (95 percent confidence interval, 1.5 to 2.8). The adjusted odds ratio was 2.5 (95 percent confidence interval, 1.5 to 4.1) among women who used second-generation oral contraceptives and 1.3 (95 percent confidence interval, 0.7 to 2.5) among those who used third-generation oral contraceptives. Among women who used oral contraceptives, the odds ratio was 2.1 (95 percent confidence interval, 1.5 to 3.0) for those without a prothrombotic mutation and 1.9 (95 percent confidence interval, 0.6 to 5.5) for those with a mutation CONCLUSIONS: The risk of myocardial infarction was increased among women who used second-generation oral contraceptives. The results with respect to the use of third-generation oral contraceptives were inconclusive but suggested that the risk was lower than the risk associated with second-generation oral contraceptives. The risk of myocardial infarction was similar among women who used oral contraceptives whether or not they had a prothrombotic mutation.", "entity": "Progestins", "aliases": "Effect Gestagen Gestagenic Progestin Progestogen Effects Agents Gestagens Progestagenic Progestagens Progestational Compounds Hormones Progestins Progestogens", "definition": "Compounds that interact with PROGESTERONE RECEPTORS in target tissues to bring about the effects similar to those of PROGESTERONE. Primary actions of progestins, including natural and synthetic steroids, are on the UTERUS and the MAMMARY GLAND in preparation for and in maintenance of PREGNANCY.\n    ", "id": "MESH:D011372"}
{"mention": "desogestrel", "mention_text": "BACKGROUND: An association between the use of oral contraceptives and the risk of myocardial infarction has been found in some, but not all, studies. We investigated this association, according to the type of progestagen included in third-generation (i.e., desogestrel or gestodene) and second-generation (i.e., levonorgestrel) oral contraceptives, the dose of estrogen, and the presence or absence of prothrombotic mutations METHODS: In a nationwide, population-based, case-control study, we identified and enrolled 248 women 18 through 49 years of age who had had a first myocardial infarction between 1990 and 1995 and 925 control women who had not had a myocardial infarction and who were matched for age, calendar year of the index event, and area of residence. Subjects supplied information on oral-contraceptive use and major cardiovascular risk factors. An analysis for factor V Leiden and the G20210A mutation in the prothrombin gene was conducted in 217 patients and 763 controls RESULTS: The odds ratio for myocardial infarction among women who used any type of combined oral contraceptive, as compared with nonusers, was 2.0 (95 percent confidence interval, 1.5 to 2.8). The adjusted odds ratio was 2.5 (95 percent confidence interval, 1.5 to 4.1) among women who used second-generation oral contraceptives and 1.3 (95 percent confidence interval, 0.7 to 2.5) among those who used third-generation oral contraceptives. Among women who used oral contraceptives, the odds ratio was 2.1 (95 percent confidence interval, 1.5 to 3.0) for those without a prothrombotic mutation and 1.9 (95 percent confidence interval, 0.6 to 5.5) for those with a mutation CONCLUSIONS: The risk of myocardial infarction was increased among women who used second-generation oral contraceptives. The results with respect to the use of third-generation oral contraceptives were inconclusive but suggested that the risk was lower than the risk associated with second-generation oral contraceptives. The risk of myocardial infarction was similar among women who used oral contraceptives whether or not they had a prothrombotic mutation.", "entity": "Desogestrel", "aliases": "13 Ethyl 11 methylene 18,19 dinor 17 alpha pregn 4 en 20 yn 17 ol 13-Ethyl-11-methylene-18,19-dinor-17 alpha-pregn-4-en-20-yn-17-ol Cerazette Desogestrel Marvelon Org 2969 Org-2969 Org2969 Organon Brand of", "definition": "A synthetic progestational hormone used often as the progestogenic component of combined oral contraceptive agents.\n    ", "id": "MESH:D017135"}
{"mention": "gestodene", "mention_text": "BACKGROUND: An association between the use of oral contraceptives and the risk of myocardial infarction has been found in some, but not all, studies. We investigated this association, according to the type of progestagen included in third-generation (i.e., desogestrel or gestodene) and second-generation (i.e., levonorgestrel) oral contraceptives, the dose of estrogen, and the presence or absence of prothrombotic mutations METHODS: In a nationwide, population-based, case-control study, we identified and enrolled 248 women 18 through 49 years of age who had had a first myocardial infarction between 1990 and 1995 and 925 control women who had not had a myocardial infarction and who were matched for age, calendar year of the index event, and area of residence. Subjects supplied information on oral-contraceptive use and major cardiovascular risk factors. An analysis for factor V Leiden and the G20210A mutation in the prothrombin gene was conducted in 217 patients and 763 controls RESULTS: The odds ratio for myocardial infarction among women who used any type of combined oral contraceptive, as compared with nonusers, was 2.0 (95 percent confidence interval, 1.5 to 2.8). The adjusted odds ratio was 2.5 (95 percent confidence interval, 1.5 to 4.1) among women who used second-generation oral contraceptives and 1.3 (95 percent confidence interval, 0.7 to 2.5) among those who used third-generation oral contraceptives. Among women who used oral contraceptives, the odds ratio was 2.1 (95 percent confidence interval, 1.5 to 3.0) for those without a prothrombotic mutation and 1.9 (95 percent confidence interval, 0.6 to 5.5) for those with a mutation CONCLUSIONS: The risk of myocardial infarction was increased among women who used second-generation oral contraceptives. The results with respect to the use of third-generation oral contraceptives were inconclusive but suggested that the risk was lower than the risk associated with second-generation oral contraceptives. The risk of myocardial infarction was similar among women who used oral contraceptives whether or not they had a prothrombotic mutation.", "entity": "Gestodene", "aliases": "13-ethyl-17-hydroxy-18,19-dinor-17 alpha-pregna-4,15-dien-20-yn-3-one 17-alpha-ethinyl-13-ethyl-17 beta-hydroxy-4,15-gonadien-3-one Gestoden Gestodene ((17alpha)-(+-))-isomer SH B 3331", "definition": "", "id": "MESH:C033273"}
{"mention": "levonorgestrel", "mention_text": "BACKGROUND: An association between the use of oral contraceptives and the risk of myocardial infarction has been found in some, but not all, studies. We investigated this association, according to the type of progestagen included in third-generation (i.e., desogestrel or gestodene) and second-generation (i.e., levonorgestrel) oral contraceptives, the dose of estrogen, and the presence or absence of prothrombotic mutations METHODS: In a nationwide, population-based, case-control study, we identified and enrolled 248 women 18 through 49 years of age who had had a first myocardial infarction between 1990 and 1995 and 925 control women who had not had a myocardial infarction and who were matched for age, calendar year of the index event, and area of residence. Subjects supplied information on oral-contraceptive use and major cardiovascular risk factors. An analysis for factor V Leiden and the G20210A mutation in the prothrombin gene was conducted in 217 patients and 763 controls RESULTS: The odds ratio for myocardial infarction among women who used any type of combined oral contraceptive, as compared with nonusers, was 2.0 (95 percent confidence interval, 1.5 to 2.8). The adjusted odds ratio was 2.5 (95 percent confidence interval, 1.5 to 4.1) among women who used second-generation oral contraceptives and 1.3 (95 percent confidence interval, 0.7 to 2.5) among those who used third-generation oral contraceptives. Among women who used oral contraceptives, the odds ratio was 2.1 (95 percent confidence interval, 1.5 to 3.0) for those without a prothrombotic mutation and 1.9 (95 percent confidence interval, 0.6 to 5.5) for those with a mutation CONCLUSIONS: The risk of myocardial infarction was increased among women who used second-generation oral contraceptives. The results with respect to the use of third-generation oral contraceptives were inconclusive but suggested that the risk was lower than the risk associated with second-generation oral contraceptives. The risk of myocardial infarction was similar among women who used oral contraceptives whether or not they had a prothrombotic mutation.", "entity": "Levonorgestrel", "aliases": "Alcala Brand of Levonorgestrel Aventis Pharma Berlex Capronor Cerazet D Norgestrel D-Norgestrel HRA 1 2 Hexal Paladin Wyeth Microlut Microval Mirena NorLevo Norgeston Norplant Norplant-2 Norplant2 Plan B Schering 3 Vikela Women's Capital duofem l l-Norgestrel", "definition": "A synthetic progestational hormone with actions similar to those of PROGESTERONE and about twice as potent as its racemic or (+-)-isomer (NORGESTREL). It is used for contraception, control of menstrual disorders, and treatment of endometriosis.\n    ", "id": "MESH:D016912"}
{"mention": "estrogen", "mention_text": "BACKGROUND: An association between the use of oral contraceptives and the risk of myocardial infarction has been found in some, but not all, studies. We investigated this association, according to the type of progestagen included in third-generation (i.e., desogestrel or gestodene) and second-generation (i.e., levonorgestrel) oral contraceptives, the dose of estrogen, and the presence or absence of prothrombotic mutations METHODS: In a nationwide, population-based, case-control study, we identified and enrolled 248 women 18 through 49 years of age who had had a first myocardial infarction between 1990 and 1995 and 925 control women who had not had a myocardial infarction and who were matched for age, calendar year of the index event, and area of residence. Subjects supplied information on oral-contraceptive use and major cardiovascular risk factors. An analysis for factor V Leiden and the G20210A mutation in the prothrombin gene was conducted in 217 patients and 763 controls RESULTS: The odds ratio for myocardial infarction among women who used any type of combined oral contraceptive, as compared with nonusers, was 2.0 (95 percent confidence interval, 1.5 to 2.8). The adjusted odds ratio was 2.5 (95 percent confidence interval, 1.5 to 4.1) among women who used second-generation oral contraceptives and 1.3 (95 percent confidence interval, 0.7 to 2.5) among those who used third-generation oral contraceptives. Among women who used oral contraceptives, the odds ratio was 2.1 (95 percent confidence interval, 1.5 to 3.0) for those without a prothrombotic mutation and 1.9 (95 percent confidence interval, 0.6 to 5.5) for those with a mutation CONCLUSIONS: The risk of myocardial infarction was increased among women who used second-generation oral contraceptives. The results with respect to the use of third-generation oral contraceptives were inconclusive but suggested that the risk was lower than the risk associated with second-generation oral contraceptives. The risk of myocardial infarction was similar among women who used oral contraceptives whether or not they had a prothrombotic mutation.", "entity": "Estrogens", "aliases": "Agents Estrogenic Agonists Estrogen Receptor Compounds Effects Effect Estrogens", "definition": "Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds.\n    ", "id": "MESH:D004967"}
{"mention": "oral-contraceptive", "mention_text": "BACKGROUND: An association between the use of oral contraceptives and the risk of myocardial infarction has been found in some, but not all, studies. We investigated this association, according to the type of progestagen included in third-generation (i.e., desogestrel or gestodene) and second-generation (i.e., levonorgestrel) oral contraceptives, the dose of estrogen, and the presence or absence of prothrombotic mutations METHODS: In a nationwide, population-based, case-control study, we identified and enrolled 248 women 18 through 49 years of age who had had a first myocardial infarction between 1990 and 1995 and 925 control women who had not had a myocardial infarction and who were matched for age, calendar year of the index event, and area of residence. Subjects supplied information on oral-contraceptive use and major cardiovascular risk factors. An analysis for factor V Leiden and the G20210A mutation in the prothrombin gene was conducted in 217 patients and 763 controls RESULTS: The odds ratio for myocardial infarction among women who used any type of combined oral contraceptive, as compared with nonusers, was 2.0 (95 percent confidence interval, 1.5 to 2.8). The adjusted odds ratio was 2.5 (95 percent confidence interval, 1.5 to 4.1) among women who used second-generation oral contraceptives and 1.3 (95 percent confidence interval, 0.7 to 2.5) among those who used third-generation oral contraceptives. Among women who used oral contraceptives, the odds ratio was 2.1 (95 percent confidence interval, 1.5 to 3.0) for those without a prothrombotic mutation and 1.9 (95 percent confidence interval, 0.6 to 5.5) for those with a mutation CONCLUSIONS: The risk of myocardial infarction was increased among women who used second-generation oral contraceptives. The results with respect to the use of third-generation oral contraceptives were inconclusive but suggested that the risk was lower than the risk associated with second-generation oral contraceptives. The risk of myocardial infarction was similar among women who used oral contraceptives whether or not they had a prothrombotic mutation.", "entity": "Contraceptives, Oral", "aliases": "Contraceptives Low-Dose Oral Phasic Low Dose", "definition": "Compounds, usually hormonal, taken orally in order to block ovulation and prevent the occurrence of pregnancy. The hormones are generally estrogen or progesterone or both.\n    ", "id": "MESH:D003276"}
{"mention": "oral contraceptive", "mention_text": "BACKGROUND: An association between the use of oral contraceptives and the risk of myocardial infarction has been found in some, but not all, studies. We investigated this association, according to the type of progestagen included in third-generation (i.e., desogestrel or gestodene) and second-generation (i.e., levonorgestrel) oral contraceptives, the dose of estrogen, and the presence or absence of prothrombotic mutations METHODS: In a nationwide, population-based, case-control study, we identified and enrolled 248 women 18 through 49 years of age who had had a first myocardial infarction between 1990 and 1995 and 925 control women who had not had a myocardial infarction and who were matched for age, calendar year of the index event, and area of residence. Subjects supplied information on oral-contraceptive use and major cardiovascular risk factors. An analysis for factor V Leiden and the G20210A mutation in the prothrombin gene was conducted in 217 patients and 763 controls RESULTS: The odds ratio for myocardial infarction among women who used any type of combined oral contraceptive, as compared with nonusers, was 2.0 (95 percent confidence interval, 1.5 to 2.8). The adjusted odds ratio was 2.5 (95 percent confidence interval, 1.5 to 4.1) among women who used second-generation oral contraceptives and 1.3 (95 percent confidence interval, 0.7 to 2.5) among those who used third-generation oral contraceptives. Among women who used oral contraceptives, the odds ratio was 2.1 (95 percent confidence interval, 1.5 to 3.0) for those without a prothrombotic mutation and 1.9 (95 percent confidence interval, 0.6 to 5.5) for those with a mutation CONCLUSIONS: The risk of myocardial infarction was increased among women who used second-generation oral contraceptives. The results with respect to the use of third-generation oral contraceptives were inconclusive but suggested that the risk was lower than the risk associated with second-generation oral contraceptives. The risk of myocardial infarction was similar among women who used oral contraceptives whether or not they had a prothrombotic mutation.", "entity": "Contraceptives, Oral", "aliases": "Contraceptives Low-Dose Oral Phasic Low Dose", "definition": "Compounds, usually hormonal, taken orally in order to block ovulation and prevent the occurrence of pregnancy. The hormones are generally estrogen or progesterone or both.\n    ", "id": "MESH:D003276"}
{"mention": "cocaine", "mention_text": "Effects of 5-HT1B receptor ligands microinjected into the accumbal shell or core on the cocaine-induced locomotor hyperactivity in rats.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "locomotor hyperactivity", "mention_text": "Effects of 5-HT1B receptor ligands microinjected into the accumbal shell or core on the cocaine-induced locomotor hyperactivity in rats.", "entity": "Movement Disorders", "aliases": "Dyskinesia Syndrome Syndromes Lingual-Facial-Buccal Linguofacial Oral Oral-facial Orofacial Tardive Dyskinesias Dystonia Dystonias Etat Marbre Lingual Facial Buccal Movement Disorder Disorders facial Status Marmoratus", "definition": "Syndromes which feature DYSKINESIAS as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions.\n    ", "id": "MESH:D009069"}
{"mention": "locomotor hyperactivity", "mention_text": "The present study was designed to examine the effect of 5-HT1B receptor ligands microinjected into the subregions of the nucleus accumbens (the shell and the core) on the locomotor hyperactivity induced by cocaine in rats. Male Wistar rats were implanted bilaterally with cannulae into the accumbens shell or core, and then were locally injected with GR 55562 (an antagonist of 5-HT1B receptors) or CP 93129 (an agonist of 5-HT1B receptors). Given alone to any accumbal subregion, GR 55562 (0.1-10 microg/side) or CP 93129 (0.1-10 microg/side) did not change basal locomotor activity. Systemic cocaine (10 mg/kg) significantly increased the locomotor activity of rats. GR 55562 (0.1-10 microg/side), administered intra-accumbens shell prior to cocaine, dose-dependently attenuated the psychostimulant-induced locomotor hyperactivity. Such attenuation was not found in animals which had been injected with GR 55562 into the accumbens core. When injected into the accumbens shell (but not the core) before cocaine, CP 93129 (0.1-10 microg/side) enhanced the locomotor response to cocaine; the maximum effect being observed after 10 microg/side of the agonist. The later enhancement was attenuated after intra-accumbens shell treatment with GR 55562 (1 microg/side). Our findings indicate that cocaine induced hyperlocomotion is modified by 5-HT1B receptor ligands microinjected into the accumbens shell, but not core, this modification consisting in inhibitory and facilitatory effects of the 5-HT1B receptor antagonist (GR 55562) and agonist (CP 93129), respectively. In other words, the present results suggest that the accumbal shell 5-HT1B receptors play a permissive role in the behavioural response to the psychostimulant.", "entity": "Movement Disorders", "aliases": "Dyskinesia Syndrome Syndromes Lingual-Facial-Buccal Linguofacial Oral Oral-facial Orofacial Tardive Dyskinesias Dystonia Dystonias Etat Marbre Lingual Facial Buccal Movement Disorder Disorders facial Status Marmoratus", "definition": "Syndromes which feature DYSKINESIAS as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions.\n    ", "id": "MESH:D009069"}
{"mention": "cocaine", "mention_text": "The present study was designed to examine the effect of 5-HT1B receptor ligands microinjected into the subregions of the nucleus accumbens (the shell and the core) on the locomotor hyperactivity induced by cocaine in rats. Male Wistar rats were implanted bilaterally with cannulae into the accumbens shell or core, and then were locally injected with GR 55562 (an antagonist of 5-HT1B receptors) or CP 93129 (an agonist of 5-HT1B receptors). Given alone to any accumbal subregion, GR 55562 (0.1-10 microg/side) or CP 93129 (0.1-10 microg/side) did not change basal locomotor activity. Systemic cocaine (10 mg/kg) significantly increased the locomotor activity of rats. GR 55562 (0.1-10 microg/side), administered intra-accumbens shell prior to cocaine, dose-dependently attenuated the psychostimulant-induced locomotor hyperactivity. Such attenuation was not found in animals which had been injected with GR 55562 into the accumbens core. When injected into the accumbens shell (but not the core) before cocaine, CP 93129 (0.1-10 microg/side) enhanced the locomotor response to cocaine; the maximum effect being observed after 10 microg/side of the agonist. The later enhancement was attenuated after intra-accumbens shell treatment with GR 55562 (1 microg/side). Our findings indicate that cocaine induced hyperlocomotion is modified by 5-HT1B receptor ligands microinjected into the accumbens shell, but not core, this modification consisting in inhibitory and facilitatory effects of the 5-HT1B receptor antagonist (GR 55562) and agonist (CP 93129), respectively. In other words, the present results suggest that the accumbal shell 5-HT1B receptors play a permissive role in the behavioural response to the psychostimulant.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "GR 55562", "mention_text": "The present study was designed to examine the effect of 5-HT1B receptor ligands microinjected into the subregions of the nucleus accumbens (the shell and the core) on the locomotor hyperactivity induced by cocaine in rats. Male Wistar rats were implanted bilaterally with cannulae into the accumbens shell or core, and then were locally injected with GR 55562 (an antagonist of 5-HT1B receptors) or CP 93129 (an agonist of 5-HT1B receptors). Given alone to any accumbal subregion, GR 55562 (0.1-10 microg/side) or CP 93129 (0.1-10 microg/side) did not change basal locomotor activity. Systemic cocaine (10 mg/kg) significantly increased the locomotor activity of rats. GR 55562 (0.1-10 microg/side), administered intra-accumbens shell prior to cocaine, dose-dependently attenuated the psychostimulant-induced locomotor hyperactivity. Such attenuation was not found in animals which had been injected with GR 55562 into the accumbens core. When injected into the accumbens shell (but not the core) before cocaine, CP 93129 (0.1-10 microg/side) enhanced the locomotor response to cocaine; the maximum effect being observed after 10 microg/side of the agonist. The later enhancement was attenuated after intra-accumbens shell treatment with GR 55562 (1 microg/side). Our findings indicate that cocaine induced hyperlocomotion is modified by 5-HT1B receptor ligands microinjected into the accumbens shell, but not core, this modification consisting in inhibitory and facilitatory effects of the 5-HT1B receptor antagonist (GR 55562) and agonist (CP 93129), respectively. In other words, the present results suggest that the accumbal shell 5-HT1B receptors play a permissive role in the behavioural response to the psychostimulant.", "entity": "3-(3-(dimethylamino)propyl)-4-hydroxy-N-(4-(4-pyridinyl)phenyl)benzamide", "aliases": "3-(3-(dimethylamino)propyl)-4-hydroxy-N-(4-(4-pyridinyl)phenyl)benzamide GR 55562 GR-55562 GR55562", "definition": "", "id": "MESH:C103477"}
{"mention": "CP 93129", "mention_text": "The present study was designed to examine the effect of 5-HT1B receptor ligands microinjected into the subregions of the nucleus accumbens (the shell and the core) on the locomotor hyperactivity induced by cocaine in rats. Male Wistar rats were implanted bilaterally with cannulae into the accumbens shell or core, and then were locally injected with GR 55562 (an antagonist of 5-HT1B receptors) or CP 93129 (an agonist of 5-HT1B receptors). Given alone to any accumbal subregion, GR 55562 (0.1-10 microg/side) or CP 93129 (0.1-10 microg/side) did not change basal locomotor activity. Systemic cocaine (10 mg/kg) significantly increased the locomotor activity of rats. GR 55562 (0.1-10 microg/side), administered intra-accumbens shell prior to cocaine, dose-dependently attenuated the psychostimulant-induced locomotor hyperactivity. Such attenuation was not found in animals which had been injected with GR 55562 into the accumbens core. When injected into the accumbens shell (but not the core) before cocaine, CP 93129 (0.1-10 microg/side) enhanced the locomotor response to cocaine; the maximum effect being observed after 10 microg/side of the agonist. The later enhancement was attenuated after intra-accumbens shell treatment with GR 55562 (1 microg/side). Our findings indicate that cocaine induced hyperlocomotion is modified by 5-HT1B receptor ligands microinjected into the accumbens shell, but not core, this modification consisting in inhibitory and facilitatory effects of the 5-HT1B receptor antagonist (GR 55562) and agonist (CP 93129), respectively. In other words, the present results suggest that the accumbal shell 5-HT1B receptors play a permissive role in the behavioural response to the psychostimulant.", "entity": "3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one", "aliases": "3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one CP 93129 CP-93,129", "definition": "", "id": "MESH:C065046"}
{"mention": "hyperlocomotion", "mention_text": "The present study was designed to examine the effect of 5-HT1B receptor ligands microinjected into the subregions of the nucleus accumbens (the shell and the core) on the locomotor hyperactivity induced by cocaine in rats. Male Wistar rats were implanted bilaterally with cannulae into the accumbens shell or core, and then were locally injected with GR 55562 (an antagonist of 5-HT1B receptors) or CP 93129 (an agonist of 5-HT1B receptors). Given alone to any accumbal subregion, GR 55562 (0.1-10 microg/side) or CP 93129 (0.1-10 microg/side) did not change basal locomotor activity. Systemic cocaine (10 mg/kg) significantly increased the locomotor activity of rats. GR 55562 (0.1-10 microg/side), administered intra-accumbens shell prior to cocaine, dose-dependently attenuated the psychostimulant-induced locomotor hyperactivity. Such attenuation was not found in animals which had been injected with GR 55562 into the accumbens core. When injected into the accumbens shell (but not the core) before cocaine, CP 93129 (0.1-10 microg/side) enhanced the locomotor response to cocaine; the maximum effect being observed after 10 microg/side of the agonist. The later enhancement was attenuated after intra-accumbens shell treatment with GR 55562 (1 microg/side). Our findings indicate that cocaine induced hyperlocomotion is modified by 5-HT1B receptor ligands microinjected into the accumbens shell, but not core, this modification consisting in inhibitory and facilitatory effects of the 5-HT1B receptor antagonist (GR 55562) and agonist (CP 93129), respectively. In other words, the present results suggest that the accumbal shell 5-HT1B receptors play a permissive role in the behavioural response to the psychostimulant.", "entity": "Movement Disorders", "aliases": "Dyskinesia Syndrome Syndromes Lingual-Facial-Buccal Linguofacial Oral Oral-facial Orofacial Tardive Dyskinesias Dystonia Dystonias Etat Marbre Lingual Facial Buccal Movement Disorder Disorders facial Status Marmoratus", "definition": "Syndromes which feature DYSKINESIAS as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions.\n    ", "id": "MESH:D009069"}
{"mention": "Ticlopidine", "mention_text": "Ticlopidine-induced cholestatic hepatitis.", "entity": "Ticlopidine", "aliases": "53 32C 53-32C 5332C Almirall Brand of Ticlopidine Hydrochloride Roche Ticlid Ticlodix Ticlodone Vitoria", "definition": "An effective inhibitor of platelet aggregation commonly used in the placement of STENTS in CORONARY ARTERIES.\n    ", "id": "MESH:D013988"}
{"mention": "cholestatic", "mention_text": "Ticlopidine-induced cholestatic hepatitis.", "entity": "Cholestasis", "aliases": "Bile Duct Obstruction Obstructions Biliary Stases Stasis Cholestases Cholestasis", "definition": "Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).\n    ", "id": "MESH:D002779"}
{"mention": "hepatitis", "mention_text": "Ticlopidine-induced cholestatic hepatitis.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "ticlopidine", "mention_text": "OBJECTIVE: To report 2 cases of ticlopidine-induced cholestatic hepatitis, investigate its mechanism, and compare the observed main characteristics with those of the published cases. CASE SUMMARIES: Two patients developed prolonged cholestatic hepatitis after receiving ticlopidine following percutaneous coronary angioplasty, with complete remission during the follow-up period. T-cell stimulation by therapeutic concentration of ticlopidine was demonstrated in vitro in the patients, but not in healthy controls. DISCUSSION: Cholestatic hepatitis is a rare complication of the antiplatelet agent ticlopidine; several cases have been reported but few in the English literature. Our patients developed jaundice following treatment with ticlopidine and showed the clinical and laboratory characteristics of cholestatic hepatitis, which resolved after discontinuation of the drug. Hepatitis may develop weeks after discontinuation of the drug and may run a prolonged course, but complete remission was observed in all reported cases. An objective causality assessment revealed that the adverse drug event was probably related to the use of ticlopidine. The mechanisms of this ticlopidine-induced cholestasis are unclear. Immune mechanisms may be involved in the drug's hepatotoxicity, as suggested by the T-cell stimulation study reported here. CONCLUSIONS: Cholestatic hepatitis is a rare adverse effect of ticlopidine that may be immune mediated. Patients receiving the drug should be monitored with liver function tests along with complete blood cell counts. This complication will be observed even less often in the future as ticlopidine is being replaced by the newer antiplatelet agent clopidogrel.", "entity": "Ticlopidine", "aliases": "53 32C 53-32C 5332C Almirall Brand of Ticlopidine Hydrochloride Roche Ticlid Ticlodix Ticlodone Vitoria", "definition": "An effective inhibitor of platelet aggregation commonly used in the placement of STENTS in CORONARY ARTERIES.\n    ", "id": "MESH:D013988"}
{"mention": "cholestatic", "mention_text": "OBJECTIVE: To report 2 cases of ticlopidine-induced cholestatic hepatitis, investigate its mechanism, and compare the observed main characteristics with those of the published cases. CASE SUMMARIES: Two patients developed prolonged cholestatic hepatitis after receiving ticlopidine following percutaneous coronary angioplasty, with complete remission during the follow-up period. T-cell stimulation by therapeutic concentration of ticlopidine was demonstrated in vitro in the patients, but not in healthy controls. DISCUSSION: Cholestatic hepatitis is a rare complication of the antiplatelet agent ticlopidine; several cases have been reported but few in the English literature. Our patients developed jaundice following treatment with ticlopidine and showed the clinical and laboratory characteristics of cholestatic hepatitis, which resolved after discontinuation of the drug. Hepatitis may develop weeks after discontinuation of the drug and may run a prolonged course, but complete remission was observed in all reported cases. An objective causality assessment revealed that the adverse drug event was probably related to the use of ticlopidine. The mechanisms of this ticlopidine-induced cholestasis are unclear. Immune mechanisms may be involved in the drug's hepatotoxicity, as suggested by the T-cell stimulation study reported here. CONCLUSIONS: Cholestatic hepatitis is a rare adverse effect of ticlopidine that may be immune mediated. Patients receiving the drug should be monitored with liver function tests along with complete blood cell counts. This complication will be observed even less often in the future as ticlopidine is being replaced by the newer antiplatelet agent clopidogrel.", "entity": "Cholestasis", "aliases": "Bile Duct Obstruction Obstructions Biliary Stases Stasis Cholestases Cholestasis", "definition": "Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).\n    ", "id": "MESH:D002779"}
{"mention": "hepatitis", "mention_text": "OBJECTIVE: To report 2 cases of ticlopidine-induced cholestatic hepatitis, investigate its mechanism, and compare the observed main characteristics with those of the published cases. CASE SUMMARIES: Two patients developed prolonged cholestatic hepatitis after receiving ticlopidine following percutaneous coronary angioplasty, with complete remission during the follow-up period. T-cell stimulation by therapeutic concentration of ticlopidine was demonstrated in vitro in the patients, but not in healthy controls. DISCUSSION: Cholestatic hepatitis is a rare complication of the antiplatelet agent ticlopidine; several cases have been reported but few in the English literature. Our patients developed jaundice following treatment with ticlopidine and showed the clinical and laboratory characteristics of cholestatic hepatitis, which resolved after discontinuation of the drug. Hepatitis may develop weeks after discontinuation of the drug and may run a prolonged course, but complete remission was observed in all reported cases. An objective causality assessment revealed that the adverse drug event was probably related to the use of ticlopidine. The mechanisms of this ticlopidine-induced cholestasis are unclear. Immune mechanisms may be involved in the drug's hepatotoxicity, as suggested by the T-cell stimulation study reported here. CONCLUSIONS: Cholestatic hepatitis is a rare adverse effect of ticlopidine that may be immune mediated. Patients receiving the drug should be monitored with liver function tests along with complete blood cell counts. This complication will be observed even less often in the future as ticlopidine is being replaced by the newer antiplatelet agent clopidogrel.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "Cholestatic", "mention_text": "OBJECTIVE: To report 2 cases of ticlopidine-induced cholestatic hepatitis, investigate its mechanism, and compare the observed main characteristics with those of the published cases. CASE SUMMARIES: Two patients developed prolonged cholestatic hepatitis after receiving ticlopidine following percutaneous coronary angioplasty, with complete remission during the follow-up period. T-cell stimulation by therapeutic concentration of ticlopidine was demonstrated in vitro in the patients, but not in healthy controls. DISCUSSION: Cholestatic hepatitis is a rare complication of the antiplatelet agent ticlopidine; several cases have been reported but few in the English literature. Our patients developed jaundice following treatment with ticlopidine and showed the clinical and laboratory characteristics of cholestatic hepatitis, which resolved after discontinuation of the drug. Hepatitis may develop weeks after discontinuation of the drug and may run a prolonged course, but complete remission was observed in all reported cases. An objective causality assessment revealed that the adverse drug event was probably related to the use of ticlopidine. The mechanisms of this ticlopidine-induced cholestasis are unclear. Immune mechanisms may be involved in the drug's hepatotoxicity, as suggested by the T-cell stimulation study reported here. CONCLUSIONS: Cholestatic hepatitis is a rare adverse effect of ticlopidine that may be immune mediated. Patients receiving the drug should be monitored with liver function tests along with complete blood cell counts. This complication will be observed even less often in the future as ticlopidine is being replaced by the newer antiplatelet agent clopidogrel.", "entity": "Cholestasis", "aliases": "Bile Duct Obstruction Obstructions Biliary Stases Stasis Cholestases Cholestasis", "definition": "Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).\n    ", "id": "MESH:D002779"}
{"mention": "jaundice", "mention_text": "OBJECTIVE: To report 2 cases of ticlopidine-induced cholestatic hepatitis, investigate its mechanism, and compare the observed main characteristics with those of the published cases. CASE SUMMARIES: Two patients developed prolonged cholestatic hepatitis after receiving ticlopidine following percutaneous coronary angioplasty, with complete remission during the follow-up period. T-cell stimulation by therapeutic concentration of ticlopidine was demonstrated in vitro in the patients, but not in healthy controls. DISCUSSION: Cholestatic hepatitis is a rare complication of the antiplatelet agent ticlopidine; several cases have been reported but few in the English literature. Our patients developed jaundice following treatment with ticlopidine and showed the clinical and laboratory characteristics of cholestatic hepatitis, which resolved after discontinuation of the drug. Hepatitis may develop weeks after discontinuation of the drug and may run a prolonged course, but complete remission was observed in all reported cases. An objective causality assessment revealed that the adverse drug event was probably related to the use of ticlopidine. The mechanisms of this ticlopidine-induced cholestasis are unclear. Immune mechanisms may be involved in the drug's hepatotoxicity, as suggested by the T-cell stimulation study reported here. CONCLUSIONS: Cholestatic hepatitis is a rare adverse effect of ticlopidine that may be immune mediated. Patients receiving the drug should be monitored with liver function tests along with complete blood cell counts. This complication will be observed even less often in the future as ticlopidine is being replaced by the newer antiplatelet agent clopidogrel.", "entity": "Jaundice", "aliases": "Hemolytic Jaundice Jaundices Icterus", "definition": "A clinical manifestation of HYPERBILIRUBINEMIA, characterized by the yellowish staining of the SKIN; MUCOUS MEMBRANE; and SCLERA. Clinical jaundice usually is a sign of LIVER dysfunction.\n    ", "id": "MESH:D007565"}
{"mention": "Hepatitis", "mention_text": "OBJECTIVE: To report 2 cases of ticlopidine-induced cholestatic hepatitis, investigate its mechanism, and compare the observed main characteristics with those of the published cases. CASE SUMMARIES: Two patients developed prolonged cholestatic hepatitis after receiving ticlopidine following percutaneous coronary angioplasty, with complete remission during the follow-up period. T-cell stimulation by therapeutic concentration of ticlopidine was demonstrated in vitro in the patients, but not in healthy controls. DISCUSSION: Cholestatic hepatitis is a rare complication of the antiplatelet agent ticlopidine; several cases have been reported but few in the English literature. Our patients developed jaundice following treatment with ticlopidine and showed the clinical and laboratory characteristics of cholestatic hepatitis, which resolved after discontinuation of the drug. Hepatitis may develop weeks after discontinuation of the drug and may run a prolonged course, but complete remission was observed in all reported cases. An objective causality assessment revealed that the adverse drug event was probably related to the use of ticlopidine. The mechanisms of this ticlopidine-induced cholestasis are unclear. Immune mechanisms may be involved in the drug's hepatotoxicity, as suggested by the T-cell stimulation study reported here. CONCLUSIONS: Cholestatic hepatitis is a rare adverse effect of ticlopidine that may be immune mediated. Patients receiving the drug should be monitored with liver function tests along with complete blood cell counts. This complication will be observed even less often in the future as ticlopidine is being replaced by the newer antiplatelet agent clopidogrel.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "cholestasis", "mention_text": "OBJECTIVE: To report 2 cases of ticlopidine-induced cholestatic hepatitis, investigate its mechanism, and compare the observed main characteristics with those of the published cases. CASE SUMMARIES: Two patients developed prolonged cholestatic hepatitis after receiving ticlopidine following percutaneous coronary angioplasty, with complete remission during the follow-up period. T-cell stimulation by therapeutic concentration of ticlopidine was demonstrated in vitro in the patients, but not in healthy controls. DISCUSSION: Cholestatic hepatitis is a rare complication of the antiplatelet agent ticlopidine; several cases have been reported but few in the English literature. Our patients developed jaundice following treatment with ticlopidine and showed the clinical and laboratory characteristics of cholestatic hepatitis, which resolved after discontinuation of the drug. Hepatitis may develop weeks after discontinuation of the drug and may run a prolonged course, but complete remission was observed in all reported cases. An objective causality assessment revealed that the adverse drug event was probably related to the use of ticlopidine. The mechanisms of this ticlopidine-induced cholestasis are unclear. Immune mechanisms may be involved in the drug's hepatotoxicity, as suggested by the T-cell stimulation study reported here. CONCLUSIONS: Cholestatic hepatitis is a rare adverse effect of ticlopidine that may be immune mediated. Patients receiving the drug should be monitored with liver function tests along with complete blood cell counts. This complication will be observed even less often in the future as ticlopidine is being replaced by the newer antiplatelet agent clopidogrel.", "entity": "Cholestasis", "aliases": "Bile Duct Obstruction Obstructions Biliary Stases Stasis Cholestases Cholestasis", "definition": "Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).\n    ", "id": "MESH:D002779"}
{"mention": "hepatotoxicity", "mention_text": "OBJECTIVE: To report 2 cases of ticlopidine-induced cholestatic hepatitis, investigate its mechanism, and compare the observed main characteristics with those of the published cases. CASE SUMMARIES: Two patients developed prolonged cholestatic hepatitis after receiving ticlopidine following percutaneous coronary angioplasty, with complete remission during the follow-up period. T-cell stimulation by therapeutic concentration of ticlopidine was demonstrated in vitro in the patients, but not in healthy controls. DISCUSSION: Cholestatic hepatitis is a rare complication of the antiplatelet agent ticlopidine; several cases have been reported but few in the English literature. Our patients developed jaundice following treatment with ticlopidine and showed the clinical and laboratory characteristics of cholestatic hepatitis, which resolved after discontinuation of the drug. Hepatitis may develop weeks after discontinuation of the drug and may run a prolonged course, but complete remission was observed in all reported cases. An objective causality assessment revealed that the adverse drug event was probably related to the use of ticlopidine. The mechanisms of this ticlopidine-induced cholestasis are unclear. Immune mechanisms may be involved in the drug's hepatotoxicity, as suggested by the T-cell stimulation study reported here. CONCLUSIONS: Cholestatic hepatitis is a rare adverse effect of ticlopidine that may be immune mediated. Patients receiving the drug should be monitored with liver function tests along with complete blood cell counts. This complication will be observed even less often in the future as ticlopidine is being replaced by the newer antiplatelet agent clopidogrel.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "clopidogrel", "mention_text": "OBJECTIVE: To report 2 cases of ticlopidine-induced cholestatic hepatitis, investigate its mechanism, and compare the observed main characteristics with those of the published cases. CASE SUMMARIES: Two patients developed prolonged cholestatic hepatitis after receiving ticlopidine following percutaneous coronary angioplasty, with complete remission during the follow-up period. T-cell stimulation by therapeutic concentration of ticlopidine was demonstrated in vitro in the patients, but not in healthy controls. DISCUSSION: Cholestatic hepatitis is a rare complication of the antiplatelet agent ticlopidine; several cases have been reported but few in the English literature. Our patients developed jaundice following treatment with ticlopidine and showed the clinical and laboratory characteristics of cholestatic hepatitis, which resolved after discontinuation of the drug. Hepatitis may develop weeks after discontinuation of the drug and may run a prolonged course, but complete remission was observed in all reported cases. An objective causality assessment revealed that the adverse drug event was probably related to the use of ticlopidine. The mechanisms of this ticlopidine-induced cholestasis are unclear. Immune mechanisms may be involved in the drug's hepatotoxicity, as suggested by the T-cell stimulation study reported here. CONCLUSIONS: Cholestatic hepatitis is a rare adverse effect of ticlopidine that may be immune mediated. Patients receiving the drug should be monitored with liver function tests along with complete blood cell counts. This complication will be observed even less often in the future as ticlopidine is being replaced by the newer antiplatelet agent clopidogrel.", "entity": "clopidogrel", "aliases": "BMS brand 1 of clopidogrel bisulfate 2 Iscover PCR 4099 PCR-4099 Plavix SC 25989C 25990C SR 25989 Sandoz besylate hydrochloride napadisilate (+)(S)-isomer clopidogrel-Mepha", "definition": "", "id": "MESH:C055162"}
{"mention": "sodium", "mention_text": "Epithelial sodium channel (ENaC) subunit mRNA and protein expression in rats with puromycin aminonucleoside-induced nephrotic syndrome.", "entity": "Sodium", "aliases": "Ion Level Sodium", "definition": "A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.\n    ", "id": "MESH:D012964"}
{"mention": "puromycin aminonucleoside", "mention_text": "Epithelial sodium channel (ENaC) subunit mRNA and protein expression in rats with puromycin aminonucleoside-induced nephrotic syndrome.", "entity": "Puromycin Aminonucleoside", "aliases": "3' Amino 3' deoxy N,N dimethyladenosine 3'-Amino-3'-deoxy-N,N-dimethyladenosine Aminonucleoside Puromycin", "definition": "PUROMYCIN derivative that lacks the methoxyphenylalanyl group on the amine of the sugar ring. It is an antibiotic with antineoplastic properties and can cause nephrosis.\n    ", "id": "MESH:D011692"}
{"mention": "nephrotic syndrome", "mention_text": "Epithelial sodium channel (ENaC) subunit mRNA and protein expression in rats with puromycin aminonucleoside-induced nephrotic syndrome.", "entity": "Nephrotic Syndrome", "aliases": "Nephrotic Syndrome Syndromes", "definition": "A condition characterized by severe PROTEINURIA, greater than 3.5 g/day in an average adult. The substantial loss of protein in the urine results in complications such as HYPOPROTEINEMIA; generalized EDEMA; HYPERTENSION; and HYPERLIPIDEMIAS. Diseases associated with nephrotic syndrome generally cause chronic kidney dysfunction.\n    ", "id": "MESH:D009404"}
{"mention": "nephrotic syndrome", "mention_text": "In experimental nephrotic syndrome, urinary sodium excretion is decreased during the early phase of the disease. The molecular mechanism(s) leading to salt retention has not been completely elucidated. The rate-limiting constituent of collecting duct sodium transport is the epithelial sodium channel (ENaC). We examined the abundance of ENaC subunit mRNAs and proteins in puromycin aminonucleoside (PAN)-induced nephrotic syndrome. The time courses of urinary sodium excretion, plasma aldosterone concentration and proteinuria were studied in male Sprague-Dawley rats treated with a single dose of either PAN or vehicle. The relative amounts of alphaENaC, betaENaC and gammaENaC mRNAs were determined in kidneys from these rats by real-time quantitative TaqMan PCR, and the amounts of proteins by Western blot. The kinetics of urinary sodium excretion and the appearance of proteinuria were comparable with those reported previously. Sodium retention occurred on days 2, 3 and 6 after PAN injection. A significant up-regulation of alphaENaC and betaENaC mRNA abundance on days 1 and 2 preceded sodium retention on days 2 and 3. Conversely, down-regulation of alphaENaC, betaENaC and gammaENaC mRNA expression on day 3 occurred in the presence of high aldosterone concentrations, and was followed by a return of sodium excretion to control values. The amounts of alphaENaC, betaENaC and gammaENaC proteins were not increased during PAN-induced sodium retention. In conclusion, ENaC mRNA expression, especially alphaENaC, is increased in the very early phase of the experimental model of PAN-induced nephrotic syndrome in rats, but appears to escape from the regulation by aldosterone after day 3.", "entity": "Nephrotic Syndrome", "aliases": "Nephrotic Syndrome Syndromes", "definition": "A condition characterized by severe PROTEINURIA, greater than 3.5 g/day in an average adult. The substantial loss of protein in the urine results in complications such as HYPOPROTEINEMIA; generalized EDEMA; HYPERTENSION; and HYPERLIPIDEMIAS. Diseases associated with nephrotic syndrome generally cause chronic kidney dysfunction.\n    ", "id": "MESH:D009404"}
{"mention": "sodium", "mention_text": "In experimental nephrotic syndrome, urinary sodium excretion is decreased during the early phase of the disease. The molecular mechanism(s) leading to salt retention has not been completely elucidated. The rate-limiting constituent of collecting duct sodium transport is the epithelial sodium channel (ENaC). We examined the abundance of ENaC subunit mRNAs and proteins in puromycin aminonucleoside (PAN)-induced nephrotic syndrome. The time courses of urinary sodium excretion, plasma aldosterone concentration and proteinuria were studied in male Sprague-Dawley rats treated with a single dose of either PAN or vehicle. The relative amounts of alphaENaC, betaENaC and gammaENaC mRNAs were determined in kidneys from these rats by real-time quantitative TaqMan PCR, and the amounts of proteins by Western blot. The kinetics of urinary sodium excretion and the appearance of proteinuria were comparable with those reported previously. Sodium retention occurred on days 2, 3 and 6 after PAN injection. A significant up-regulation of alphaENaC and betaENaC mRNA abundance on days 1 and 2 preceded sodium retention on days 2 and 3. Conversely, down-regulation of alphaENaC, betaENaC and gammaENaC mRNA expression on day 3 occurred in the presence of high aldosterone concentrations, and was followed by a return of sodium excretion to control values. The amounts of alphaENaC, betaENaC and gammaENaC proteins were not increased during PAN-induced sodium retention. In conclusion, ENaC mRNA expression, especially alphaENaC, is increased in the very early phase of the experimental model of PAN-induced nephrotic syndrome in rats, but appears to escape from the regulation by aldosterone after day 3.", "entity": "Sodium", "aliases": "Ion Level Sodium", "definition": "A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.\n    ", "id": "MESH:D012964"}
{"mention": "puromycin aminonucleoside", "mention_text": "In experimental nephrotic syndrome, urinary sodium excretion is decreased during the early phase of the disease. The molecular mechanism(s) leading to salt retention has not been completely elucidated. The rate-limiting constituent of collecting duct sodium transport is the epithelial sodium channel (ENaC). We examined the abundance of ENaC subunit mRNAs and proteins in puromycin aminonucleoside (PAN)-induced nephrotic syndrome. The time courses of urinary sodium excretion, plasma aldosterone concentration and proteinuria were studied in male Sprague-Dawley rats treated with a single dose of either PAN or vehicle. The relative amounts of alphaENaC, betaENaC and gammaENaC mRNAs were determined in kidneys from these rats by real-time quantitative TaqMan PCR, and the amounts of proteins by Western blot. The kinetics of urinary sodium excretion and the appearance of proteinuria were comparable with those reported previously. Sodium retention occurred on days 2, 3 and 6 after PAN injection. A significant up-regulation of alphaENaC and betaENaC mRNA abundance on days 1 and 2 preceded sodium retention on days 2 and 3. Conversely, down-regulation of alphaENaC, betaENaC and gammaENaC mRNA expression on day 3 occurred in the presence of high aldosterone concentrations, and was followed by a return of sodium excretion to control values. The amounts of alphaENaC, betaENaC and gammaENaC proteins were not increased during PAN-induced sodium retention. In conclusion, ENaC mRNA expression, especially alphaENaC, is increased in the very early phase of the experimental model of PAN-induced nephrotic syndrome in rats, but appears to escape from the regulation by aldosterone after day 3.", "entity": "Puromycin Aminonucleoside", "aliases": "3' Amino 3' deoxy N,N dimethyladenosine 3'-Amino-3'-deoxy-N,N-dimethyladenosine Aminonucleoside Puromycin", "definition": "PUROMYCIN derivative that lacks the methoxyphenylalanyl group on the amine of the sugar ring. It is an antibiotic with antineoplastic properties and can cause nephrosis.\n    ", "id": "MESH:D011692"}
{"mention": "PAN", "mention_text": "In experimental nephrotic syndrome, urinary sodium excretion is decreased during the early phase of the disease. The molecular mechanism(s) leading to salt retention has not been completely elucidated. The rate-limiting constituent of collecting duct sodium transport is the epithelial sodium channel (ENaC). We examined the abundance of ENaC subunit mRNAs and proteins in puromycin aminonucleoside (PAN)-induced nephrotic syndrome. The time courses of urinary sodium excretion, plasma aldosterone concentration and proteinuria were studied in male Sprague-Dawley rats treated with a single dose of either PAN or vehicle. The relative amounts of alphaENaC, betaENaC and gammaENaC mRNAs were determined in kidneys from these rats by real-time quantitative TaqMan PCR, and the amounts of proteins by Western blot. The kinetics of urinary sodium excretion and the appearance of proteinuria were comparable with those reported previously. Sodium retention occurred on days 2, 3 and 6 after PAN injection. A significant up-regulation of alphaENaC and betaENaC mRNA abundance on days 1 and 2 preceded sodium retention on days 2 and 3. Conversely, down-regulation of alphaENaC, betaENaC and gammaENaC mRNA expression on day 3 occurred in the presence of high aldosterone concentrations, and was followed by a return of sodium excretion to control values. The amounts of alphaENaC, betaENaC and gammaENaC proteins were not increased during PAN-induced sodium retention. In conclusion, ENaC mRNA expression, especially alphaENaC, is increased in the very early phase of the experimental model of PAN-induced nephrotic syndrome in rats, but appears to escape from the regulation by aldosterone after day 3.", "entity": "Puromycin Aminonucleoside", "aliases": "3' Amino 3' deoxy N,N dimethyladenosine 3'-Amino-3'-deoxy-N,N-dimethyladenosine Aminonucleoside Puromycin", "definition": "PUROMYCIN derivative that lacks the methoxyphenylalanyl group on the amine of the sugar ring. It is an antibiotic with antineoplastic properties and can cause nephrosis.\n    ", "id": "MESH:D011692"}
{"mention": "aldosterone", "mention_text": "In experimental nephrotic syndrome, urinary sodium excretion is decreased during the early phase of the disease. The molecular mechanism(s) leading to salt retention has not been completely elucidated. The rate-limiting constituent of collecting duct sodium transport is the epithelial sodium channel (ENaC). We examined the abundance of ENaC subunit mRNAs and proteins in puromycin aminonucleoside (PAN)-induced nephrotic syndrome. The time courses of urinary sodium excretion, plasma aldosterone concentration and proteinuria were studied in male Sprague-Dawley rats treated with a single dose of either PAN or vehicle. The relative amounts of alphaENaC, betaENaC and gammaENaC mRNAs were determined in kidneys from these rats by real-time quantitative TaqMan PCR, and the amounts of proteins by Western blot. The kinetics of urinary sodium excretion and the appearance of proteinuria were comparable with those reported previously. Sodium retention occurred on days 2, 3 and 6 after PAN injection. A significant up-regulation of alphaENaC and betaENaC mRNA abundance on days 1 and 2 preceded sodium retention on days 2 and 3. Conversely, down-regulation of alphaENaC, betaENaC and gammaENaC mRNA expression on day 3 occurred in the presence of high aldosterone concentrations, and was followed by a return of sodium excretion to control values. The amounts of alphaENaC, betaENaC and gammaENaC proteins were not increased during PAN-induced sodium retention. In conclusion, ENaC mRNA expression, especially alphaENaC, is increased in the very early phase of the experimental model of PAN-induced nephrotic syndrome in rats, but appears to escape from the regulation by aldosterone after day 3.", "entity": "Aldosterone", "aliases": "Aldosterone (+-)-Isomer (11 beta,17 alpha)-Isomer", "definition": "A hormone secreted by the ADRENAL CORTEX that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium.\n    ", "id": "MESH:D000450"}
{"mention": "proteinuria", "mention_text": "In experimental nephrotic syndrome, urinary sodium excretion is decreased during the early phase of the disease. The molecular mechanism(s) leading to salt retention has not been completely elucidated. The rate-limiting constituent of collecting duct sodium transport is the epithelial sodium channel (ENaC). We examined the abundance of ENaC subunit mRNAs and proteins in puromycin aminonucleoside (PAN)-induced nephrotic syndrome. The time courses of urinary sodium excretion, plasma aldosterone concentration and proteinuria were studied in male Sprague-Dawley rats treated with a single dose of either PAN or vehicle. The relative amounts of alphaENaC, betaENaC and gammaENaC mRNAs were determined in kidneys from these rats by real-time quantitative TaqMan PCR, and the amounts of proteins by Western blot. The kinetics of urinary sodium excretion and the appearance of proteinuria were comparable with those reported previously. Sodium retention occurred on days 2, 3 and 6 after PAN injection. A significant up-regulation of alphaENaC and betaENaC mRNA abundance on days 1 and 2 preceded sodium retention on days 2 and 3. Conversely, down-regulation of alphaENaC, betaENaC and gammaENaC mRNA expression on day 3 occurred in the presence of high aldosterone concentrations, and was followed by a return of sodium excretion to control values. The amounts of alphaENaC, betaENaC and gammaENaC proteins were not increased during PAN-induced sodium retention. In conclusion, ENaC mRNA expression, especially alphaENaC, is increased in the very early phase of the experimental model of PAN-induced nephrotic syndrome in rats, but appears to escape from the regulation by aldosterone after day 3.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "Sodium", "mention_text": "In experimental nephrotic syndrome, urinary sodium excretion is decreased during the early phase of the disease. The molecular mechanism(s) leading to salt retention has not been completely elucidated. The rate-limiting constituent of collecting duct sodium transport is the epithelial sodium channel (ENaC). We examined the abundance of ENaC subunit mRNAs and proteins in puromycin aminonucleoside (PAN)-induced nephrotic syndrome. The time courses of urinary sodium excretion, plasma aldosterone concentration and proteinuria were studied in male Sprague-Dawley rats treated with a single dose of either PAN or vehicle. The relative amounts of alphaENaC, betaENaC and gammaENaC mRNAs were determined in kidneys from these rats by real-time quantitative TaqMan PCR, and the amounts of proteins by Western blot. The kinetics of urinary sodium excretion and the appearance of proteinuria were comparable with those reported previously. Sodium retention occurred on days 2, 3 and 6 after PAN injection. A significant up-regulation of alphaENaC and betaENaC mRNA abundance on days 1 and 2 preceded sodium retention on days 2 and 3. Conversely, down-regulation of alphaENaC, betaENaC and gammaENaC mRNA expression on day 3 occurred in the presence of high aldosterone concentrations, and was followed by a return of sodium excretion to control values. The amounts of alphaENaC, betaENaC and gammaENaC proteins were not increased during PAN-induced sodium retention. In conclusion, ENaC mRNA expression, especially alphaENaC, is increased in the very early phase of the experimental model of PAN-induced nephrotic syndrome in rats, but appears to escape from the regulation by aldosterone after day 3.", "entity": "Sodium", "aliases": "Ion Level Sodium", "definition": "A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.\n    ", "id": "MESH:D012964"}
{"mention": "NO", "mention_text": "NO-induced migraine attack: strong increase in plasma calcitonin gene-related peptide (CGRP) concentration and negative correlation with platelet serotonin release.", "entity": "Nitric Oxide", "aliases": "Endogenous Nitrate Vasodilator Endothelium-Derived Nitric Oxide Mononitrogen Monoxide Nitrogen Endothelium Derived", "definition": "A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.\n    ", "id": "MESH:D009569"}
{"mention": "migraine", "mention_text": "NO-induced migraine attack: strong increase in plasma calcitonin gene-related peptide (CGRP) concentration and negative correlation with platelet serotonin release.", "entity": "Migraine Disorders", "aliases": "Abdominal Migraine Migraines Acute Confusional Cervical Syndrome Syndromes Disorder Disorders Headache Sick Headaches Hemicrania Variant Variants Status Migrainosus", "definition": "A class of disabling primary headache disorders, characterized by recurrent unilateral pulsatile headaches. The two major subtypes are common migraine (without aura) and classic migraine (with aura or neurological symptoms). (International Classification of Headache Disorders, 2nd ed. Cephalalgia 2004: suppl 1)\n    ", "id": "MESH:D008881"}
{"mention": "calcitonin gene-related peptide", "mention_text": "NO-induced migraine attack: strong increase in plasma calcitonin gene-related peptide (CGRP) concentration and negative correlation with platelet serotonin release.", "entity": "Calcitonin Gene-Related Peptide", "aliases": "Calcitonin Gene Related Peptide I II Gene-Related alpha CGRP alpha-CGRP beta beta-CGRP", "definition": "Calcitonin gene-related peptide. A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in neural tissue of the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator.\n    ", "id": "MESH:D015740"}
{"mention": "CGRP", "mention_text": "NO-induced migraine attack: strong increase in plasma calcitonin gene-related peptide (CGRP) concentration and negative correlation with platelet serotonin release.", "entity": "Calcitonin Gene-Related Peptide", "aliases": "Calcitonin Gene Related Peptide I II Gene-Related alpha CGRP alpha-CGRP beta beta-CGRP", "definition": "Calcitonin gene-related peptide. A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in neural tissue of the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator.\n    ", "id": "MESH:D015740"}
{"mention": "serotonin", "mention_text": "NO-induced migraine attack: strong increase in plasma calcitonin gene-related peptide (CGRP) concentration and negative correlation with platelet serotonin release.", "entity": "Serotonin", "aliases": "3-(2-Aminoethyl)-1H-indol-5-ol 5 Hydroxytryptamine 5-HT 5-Hydroxytryptamine Enteramine Hippophaine Serotonin", "definition": "A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.\n    ", "id": "MESH:D012701"}
{"mention": "calcitonin gene-related peptide", "mention_text": "The aim of the present study was to investigate changes in the plasma calcitonin gene-related peptide (CGRP) concentration and platelet serotonin (5-hydroxytriptamine, 5-HT) content during the immediate headache and the delayed genuine migraine attack provoked by nitroglycerin. Fifteen female migraineurs (without aura) and eight controls participated in the study. Sublingual nitroglycerin (0.5 mg) was administered. Blood was collected from the antecubital vein four times: 60 min before and after the nitroglycerin application, and 60 and 120 min after the beginning of the migraine attack (mean 344 and 404 min; 12 subjects). In those subjects who had no migraine attack (11 subjects) a similar time schedule was used. Plasma CGRP concentration increased significantly (P<0.01) during the migraine attack and returned to baseline after the cessation of the migraine. In addition, both change and peak, showed significant positive correlations with migraine headache intensity (P<0.001). However, plasma CGRP concentrations failed to change during immediate headache and in the subjects with no migraine attack. Basal CGRP concentration was significantly higher and platelet 5-HT content tended to be lower in subjects who experienced a migraine attack. Platelet serotonin content decreased significantly (P<0.01) after nitroglycerin in subjects with no migraine attack but no consistent change was observed in patients with migraine attack. In conclusion, the fact that plasma CGRP concentration correlates with the timing and severity of a migraine headache suggests a direct relationship between CGRP and migraine. In contrast, serotonin release from platelets does not provoke migraine, it may even counteract the headache and the concomitant CGRP release in this model.", "entity": "Calcitonin Gene-Related Peptide", "aliases": "Calcitonin Gene Related Peptide I II Gene-Related alpha CGRP alpha-CGRP beta beta-CGRP", "definition": "Calcitonin gene-related peptide. A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in neural tissue of the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator.\n    ", "id": "MESH:D015740"}
{"mention": "CGRP", "mention_text": "The aim of the present study was to investigate changes in the plasma calcitonin gene-related peptide (CGRP) concentration and platelet serotonin (5-hydroxytriptamine, 5-HT) content during the immediate headache and the delayed genuine migraine attack provoked by nitroglycerin. Fifteen female migraineurs (without aura) and eight controls participated in the study. Sublingual nitroglycerin (0.5 mg) was administered. Blood was collected from the antecubital vein four times: 60 min before and after the nitroglycerin application, and 60 and 120 min after the beginning of the migraine attack (mean 344 and 404 min; 12 subjects). In those subjects who had no migraine attack (11 subjects) a similar time schedule was used. Plasma CGRP concentration increased significantly (P<0.01) during the migraine attack and returned to baseline after the cessation of the migraine. In addition, both change and peak, showed significant positive correlations with migraine headache intensity (P<0.001). However, plasma CGRP concentrations failed to change during immediate headache and in the subjects with no migraine attack. Basal CGRP concentration was significantly higher and platelet 5-HT content tended to be lower in subjects who experienced a migraine attack. Platelet serotonin content decreased significantly (P<0.01) after nitroglycerin in subjects with no migraine attack but no consistent change was observed in patients with migraine attack. In conclusion, the fact that plasma CGRP concentration correlates with the timing and severity of a migraine headache suggests a direct relationship between CGRP and migraine. In contrast, serotonin release from platelets does not provoke migraine, it may even counteract the headache and the concomitant CGRP release in this model.", "entity": "Calcitonin Gene-Related Peptide", "aliases": "Calcitonin Gene Related Peptide I II Gene-Related alpha CGRP alpha-CGRP beta beta-CGRP", "definition": "Calcitonin gene-related peptide. A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in neural tissue of the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator.\n    ", "id": "MESH:D015740"}
{"mention": "serotonin", "mention_text": "The aim of the present study was to investigate changes in the plasma calcitonin gene-related peptide (CGRP) concentration and platelet serotonin (5-hydroxytriptamine, 5-HT) content during the immediate headache and the delayed genuine migraine attack provoked by nitroglycerin. Fifteen female migraineurs (without aura) and eight controls participated in the study. Sublingual nitroglycerin (0.5 mg) was administered. Blood was collected from the antecubital vein four times: 60 min before and after the nitroglycerin application, and 60 and 120 min after the beginning of the migraine attack (mean 344 and 404 min; 12 subjects). In those subjects who had no migraine attack (11 subjects) a similar time schedule was used. Plasma CGRP concentration increased significantly (P<0.01) during the migraine attack and returned to baseline after the cessation of the migraine. In addition, both change and peak, showed significant positive correlations with migraine headache intensity (P<0.001). However, plasma CGRP concentrations failed to change during immediate headache and in the subjects with no migraine attack. Basal CGRP concentration was significantly higher and platelet 5-HT content tended to be lower in subjects who experienced a migraine attack. Platelet serotonin content decreased significantly (P<0.01) after nitroglycerin in subjects with no migraine attack but no consistent change was observed in patients with migraine attack. In conclusion, the fact that plasma CGRP concentration correlates with the timing and severity of a migraine headache suggests a direct relationship between CGRP and migraine. In contrast, serotonin release from platelets does not provoke migraine, it may even counteract the headache and the concomitant CGRP release in this model.", "entity": "Serotonin", "aliases": "3-(2-Aminoethyl)-1H-indol-5-ol 5 Hydroxytryptamine 5-HT 5-Hydroxytryptamine Enteramine Hippophaine Serotonin", "definition": "A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.\n    ", "id": "MESH:D012701"}
{"mention": "5-hydroxytriptamine", "mention_text": "The aim of the present study was to investigate changes in the plasma calcitonin gene-related peptide (CGRP) concentration and platelet serotonin (5-hydroxytriptamine, 5-HT) content during the immediate headache and the delayed genuine migraine attack provoked by nitroglycerin. Fifteen female migraineurs (without aura) and eight controls participated in the study. Sublingual nitroglycerin (0.5 mg) was administered. Blood was collected from the antecubital vein four times: 60 min before and after the nitroglycerin application, and 60 and 120 min after the beginning of the migraine attack (mean 344 and 404 min; 12 subjects). In those subjects who had no migraine attack (11 subjects) a similar time schedule was used. Plasma CGRP concentration increased significantly (P<0.01) during the migraine attack and returned to baseline after the cessation of the migraine. In addition, both change and peak, showed significant positive correlations with migraine headache intensity (P<0.001). However, plasma CGRP concentrations failed to change during immediate headache and in the subjects with no migraine attack. Basal CGRP concentration was significantly higher and platelet 5-HT content tended to be lower in subjects who experienced a migraine attack. Platelet serotonin content decreased significantly (P<0.01) after nitroglycerin in subjects with no migraine attack but no consistent change was observed in patients with migraine attack. In conclusion, the fact that plasma CGRP concentration correlates with the timing and severity of a migraine headache suggests a direct relationship between CGRP and migraine. In contrast, serotonin release from platelets does not provoke migraine, it may even counteract the headache and the concomitant CGRP release in this model.", "entity": "Serotonin", "aliases": "3-(2-Aminoethyl)-1H-indol-5-ol 5 Hydroxytryptamine 5-HT 5-Hydroxytryptamine Enteramine Hippophaine Serotonin", "definition": "A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.\n    ", "id": "MESH:D012701"}
{"mention": "5-HT", "mention_text": "The aim of the present study was to investigate changes in the plasma calcitonin gene-related peptide (CGRP) concentration and platelet serotonin (5-hydroxytriptamine, 5-HT) content during the immediate headache and the delayed genuine migraine attack provoked by nitroglycerin. Fifteen female migraineurs (without aura) and eight controls participated in the study. Sublingual nitroglycerin (0.5 mg) was administered. Blood was collected from the antecubital vein four times: 60 min before and after the nitroglycerin application, and 60 and 120 min after the beginning of the migraine attack (mean 344 and 404 min; 12 subjects). In those subjects who had no migraine attack (11 subjects) a similar time schedule was used. Plasma CGRP concentration increased significantly (P<0.01) during the migraine attack and returned to baseline after the cessation of the migraine. In addition, both change and peak, showed significant positive correlations with migraine headache intensity (P<0.001). However, plasma CGRP concentrations failed to change during immediate headache and in the subjects with no migraine attack. Basal CGRP concentration was significantly higher and platelet 5-HT content tended to be lower in subjects who experienced a migraine attack. Platelet serotonin content decreased significantly (P<0.01) after nitroglycerin in subjects with no migraine attack but no consistent change was observed in patients with migraine attack. In conclusion, the fact that plasma CGRP concentration correlates with the timing and severity of a migraine headache suggests a direct relationship between CGRP and migraine. In contrast, serotonin release from platelets does not provoke migraine, it may even counteract the headache and the concomitant CGRP release in this model.", "entity": "Serotonin", "aliases": "3-(2-Aminoethyl)-1H-indol-5-ol 5 Hydroxytryptamine 5-HT 5-Hydroxytryptamine Enteramine Hippophaine Serotonin", "definition": "A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.\n    ", "id": "MESH:D012701"}
{"mention": "headache", "mention_text": "The aim of the present study was to investigate changes in the plasma calcitonin gene-related peptide (CGRP) concentration and platelet serotonin (5-hydroxytriptamine, 5-HT) content during the immediate headache and the delayed genuine migraine attack provoked by nitroglycerin. Fifteen female migraineurs (without aura) and eight controls participated in the study. Sublingual nitroglycerin (0.5 mg) was administered. Blood was collected from the antecubital vein four times: 60 min before and after the nitroglycerin application, and 60 and 120 min after the beginning of the migraine attack (mean 344 and 404 min; 12 subjects). In those subjects who had no migraine attack (11 subjects) a similar time schedule was used. Plasma CGRP concentration increased significantly (P<0.01) during the migraine attack and returned to baseline after the cessation of the migraine. In addition, both change and peak, showed significant positive correlations with migraine headache intensity (P<0.001). However, plasma CGRP concentrations failed to change during immediate headache and in the subjects with no migraine attack. Basal CGRP concentration was significantly higher and platelet 5-HT content tended to be lower in subjects who experienced a migraine attack. Platelet serotonin content decreased significantly (P<0.01) after nitroglycerin in subjects with no migraine attack but no consistent change was observed in patients with migraine attack. In conclusion, the fact that plasma CGRP concentration correlates with the timing and severity of a migraine headache suggests a direct relationship between CGRP and migraine. In contrast, serotonin release from platelets does not provoke migraine, it may even counteract the headache and the concomitant CGRP release in this model.", "entity": "Headache", "aliases": "Bilateral Headache Headaches Cephalalgia Cephalalgias Cephalgia Cephalgias Cephalodynia Cephalodynias Cranial Pain Pains Generalized Head Ocular Orthostatic Periorbital Retro-Ocular Sharp Throbbing Unilateral Vertex Hemicrania Retro", "definition": "The symptom of PAIN in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of HEADACHE DISORDERS.\n    ", "id": "MESH:D006261"}
{"mention": "migraine", "mention_text": "The aim of the present study was to investigate changes in the plasma calcitonin gene-related peptide (CGRP) concentration and platelet serotonin (5-hydroxytriptamine, 5-HT) content during the immediate headache and the delayed genuine migraine attack provoked by nitroglycerin. Fifteen female migraineurs (without aura) and eight controls participated in the study. Sublingual nitroglycerin (0.5 mg) was administered. Blood was collected from the antecubital vein four times: 60 min before and after the nitroglycerin application, and 60 and 120 min after the beginning of the migraine attack (mean 344 and 404 min; 12 subjects). In those subjects who had no migraine attack (11 subjects) a similar time schedule was used. Plasma CGRP concentration increased significantly (P<0.01) during the migraine attack and returned to baseline after the cessation of the migraine. In addition, both change and peak, showed significant positive correlations with migraine headache intensity (P<0.001). However, plasma CGRP concentrations failed to change during immediate headache and in the subjects with no migraine attack. Basal CGRP concentration was significantly higher and platelet 5-HT content tended to be lower in subjects who experienced a migraine attack. Platelet serotonin content decreased significantly (P<0.01) after nitroglycerin in subjects with no migraine attack but no consistent change was observed in patients with migraine attack. In conclusion, the fact that plasma CGRP concentration correlates with the timing and severity of a migraine headache suggests a direct relationship between CGRP and migraine. In contrast, serotonin release from platelets does not provoke migraine, it may even counteract the headache and the concomitant CGRP release in this model.", "entity": "Migraine Disorders", "aliases": "Abdominal Migraine Migraines Acute Confusional Cervical Syndrome Syndromes Disorder Disorders Headache Sick Headaches Hemicrania Variant Variants Status Migrainosus", "definition": "A class of disabling primary headache disorders, characterized by recurrent unilateral pulsatile headaches. The two major subtypes are common migraine (without aura) and classic migraine (with aura or neurological symptoms). (International Classification of Headache Disorders, 2nd ed. Cephalalgia 2004: suppl 1)\n    ", "id": "MESH:D008881"}
{"mention": "nitroglycerin", "mention_text": "The aim of the present study was to investigate changes in the plasma calcitonin gene-related peptide (CGRP) concentration and platelet serotonin (5-hydroxytriptamine, 5-HT) content during the immediate headache and the delayed genuine migraine attack provoked by nitroglycerin. Fifteen female migraineurs (without aura) and eight controls participated in the study. Sublingual nitroglycerin (0.5 mg) was administered. Blood was collected from the antecubital vein four times: 60 min before and after the nitroglycerin application, and 60 and 120 min after the beginning of the migraine attack (mean 344 and 404 min; 12 subjects). In those subjects who had no migraine attack (11 subjects) a similar time schedule was used. Plasma CGRP concentration increased significantly (P<0.01) during the migraine attack and returned to baseline after the cessation of the migraine. In addition, both change and peak, showed significant positive correlations with migraine headache intensity (P<0.001). However, plasma CGRP concentrations failed to change during immediate headache and in the subjects with no migraine attack. Basal CGRP concentration was significantly higher and platelet 5-HT content tended to be lower in subjects who experienced a migraine attack. Platelet serotonin content decreased significantly (P<0.01) after nitroglycerin in subjects with no migraine attack but no consistent change was observed in patients with migraine attack. In conclusion, the fact that plasma CGRP concentration correlates with the timing and severity of a migraine headache suggests a direct relationship between CGRP and migraine. In contrast, serotonin release from platelets does not provoke migraine, it may even counteract the headache and the concomitant CGRP release in this model.", "entity": "Nitroglycerin", "aliases": "Anginine Dynamite Gilustenon Glyceryl Trinitrate Nitrangin Nitro Bid Dur Nitro-Bid Nitro-Dur NitroBid NitroDur Nitrocard Nitroderm TTS Nitroglycerin Nitroglyn Nitrol Nitrolan Nitrong Nitrospan Nitrostat Perlinganit Susadrin Sustac Sustak Sustonit Transderm Tridil Trinitrin Trinitrolong", "definition": "A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives.\n    ", "id": "MESH:D005996"}
{"mention": "migraineurs (without aura)", "mention_text": "The aim of the present study was to investigate changes in the plasma calcitonin gene-related peptide (CGRP) concentration and platelet serotonin (5-hydroxytriptamine, 5-HT) content during the immediate headache and the delayed genuine migraine attack provoked by nitroglycerin. Fifteen female migraineurs (without aura) and eight controls participated in the study. Sublingual nitroglycerin (0.5 mg) was administered. Blood was collected from the antecubital vein four times: 60 min before and after the nitroglycerin application, and 60 and 120 min after the beginning of the migraine attack (mean 344 and 404 min; 12 subjects). In those subjects who had no migraine attack (11 subjects) a similar time schedule was used. Plasma CGRP concentration increased significantly (P<0.01) during the migraine attack and returned to baseline after the cessation of the migraine. In addition, both change and peak, showed significant positive correlations with migraine headache intensity (P<0.001). However, plasma CGRP concentrations failed to change during immediate headache and in the subjects with no migraine attack. Basal CGRP concentration was significantly higher and platelet 5-HT content tended to be lower in subjects who experienced a migraine attack. Platelet serotonin content decreased significantly (P<0.01) after nitroglycerin in subjects with no migraine attack but no consistent change was observed in patients with migraine attack. In conclusion, the fact that plasma CGRP concentration correlates with the timing and severity of a migraine headache suggests a direct relationship between CGRP and migraine. In contrast, serotonin release from platelets does not provoke migraine, it may even counteract the headache and the concomitant CGRP release in this model.", "entity": "Migraine without Aura", "aliases": "Common Migraine Migraines without Aura", "definition": "Recurrent unilateral pulsatile headaches, not preceded or accompanied by an aura, in attacks lasting 4-72 hours. It is characterized by PAIN of moderate to severe intensity; aggravated by physical activity; and associated with NAUSEA and / or PHOTOPHOBIA and PHONOPHOBIA. (International Classification of Headache Disorders, 2nd ed. Cephalalgia 2004: suppl 1)\n    ", "id": "MESH:D020326"}
{"mention": "Coronary aneurysm", "mention_text": "Coronary aneurysm after implantation of a paclitaxel-eluting stent.", "entity": "Coronary Aneurysm", "aliases": "Aneurysm Coronary Aneurysms", "definition": "Abnormal balloon- or sac-like dilatation in the wall of CORONARY VESSELS. Most coronary aneurysms are due to CORONARY ATHEROSCLEROSIS, and the rest are due to inflammatory diseases, such as KAWASAKI DISEASE.\n    ", "id": "MESH:D003323"}
{"mention": "paclitaxel", "mention_text": "Coronary aneurysm after implantation of a paclitaxel-eluting stent.", "entity": "Paclitaxel", "aliases": "7 epi Taxol 7-epi-Taxol Anzatax Bris Bristol-Myers Brand of Paclitaxel Squibb Bull Ivax Lemery NSC 125973 NSC-125973 NSC125973 Onxol (4 alpha)-Isomer Paxene Praxel A", "definition": "A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.\n    ", "id": "MESH:D017239"}
{"mention": "coronary aneurysm", "mention_text": "Formation of coronary aneurysm is a rare complication of stenting with bare metal stents, but based on experimental studies drug-eluting stents may induce toxic effects on the vessel wall with incomplete stent apposition, aneurysm formation and with the potential of stent thrombosis or vessel rupture. We present a 43-year-old man who developed a coronary aneurysm in the right coronary artery 6 months after receiving a paclitaxel-eluting stent. The patient was asymptomatic and the aneurysm was detected in a routine control. Angiography and intracoronary ultrasound demonstrated lack of contact between stent and vessel wall in a 15-mm long segment with maximal aneurysm diameter of 6.0 mm. The patient was successfully treated with a graft stent.", "entity": "Coronary Aneurysm", "aliases": "Aneurysm Coronary Aneurysms", "definition": "Abnormal balloon- or sac-like dilatation in the wall of CORONARY VESSELS. Most coronary aneurysms are due to CORONARY ATHEROSCLEROSIS, and the rest are due to inflammatory diseases, such as KAWASAKI DISEASE.\n    ", "id": "MESH:D003323"}
{"mention": "aneurysm", "mention_text": "Formation of coronary aneurysm is a rare complication of stenting with bare metal stents, but based on experimental studies drug-eluting stents may induce toxic effects on the vessel wall with incomplete stent apposition, aneurysm formation and with the potential of stent thrombosis or vessel rupture. We present a 43-year-old man who developed a coronary aneurysm in the right coronary artery 6 months after receiving a paclitaxel-eluting stent. The patient was asymptomatic and the aneurysm was detected in a routine control. Angiography and intracoronary ultrasound demonstrated lack of contact between stent and vessel wall in a 15-mm long segment with maximal aneurysm diameter of 6.0 mm. The patient was successfully treated with a graft stent.", "entity": "Aneurysm", "aliases": "Aneurysm Fusiform Aneurysms Saccular", "definition": "Pathological outpouching or sac-like dilatation in the wall of any blood vessel (ARTERIES or VEINS) or the heart (HEART ANEURYSM). It indicates a thin and weakened area in the wall which may later rupture. Aneurysms are classified by location, etiology, or other characteristics.\n    ", "id": "MESH:D000783"}
{"mention": "thrombosis", "mention_text": "Formation of coronary aneurysm is a rare complication of stenting with bare metal stents, but based on experimental studies drug-eluting stents may induce toxic effects on the vessel wall with incomplete stent apposition, aneurysm formation and with the potential of stent thrombosis or vessel rupture. We present a 43-year-old man who developed a coronary aneurysm in the right coronary artery 6 months after receiving a paclitaxel-eluting stent. The patient was asymptomatic and the aneurysm was detected in a routine control. Angiography and intracoronary ultrasound demonstrated lack of contact between stent and vessel wall in a 15-mm long segment with maximal aneurysm diameter of 6.0 mm. The patient was successfully treated with a graft stent.", "entity": "Thrombosis", "aliases": "Thromboses Thrombosis Thrombus", "definition": "Formation and development of a thrombus or blood clot in the blood vessel.\n    ", "id": "MESH:D013927"}
{"mention": "paclitaxel", "mention_text": "Formation of coronary aneurysm is a rare complication of stenting with bare metal stents, but based on experimental studies drug-eluting stents may induce toxic effects on the vessel wall with incomplete stent apposition, aneurysm formation and with the potential of stent thrombosis or vessel rupture. We present a 43-year-old man who developed a coronary aneurysm in the right coronary artery 6 months after receiving a paclitaxel-eluting stent. The patient was asymptomatic and the aneurysm was detected in a routine control. Angiography and intracoronary ultrasound demonstrated lack of contact between stent and vessel wall in a 15-mm long segment with maximal aneurysm diameter of 6.0 mm. The patient was successfully treated with a graft stent.", "entity": "Paclitaxel", "aliases": "7 epi Taxol 7-epi-Taxol Anzatax Bris Bristol-Myers Brand of Paclitaxel Squibb Bull Ivax Lemery NSC 125973 NSC-125973 NSC125973 Onxol (4 alpha)-Isomer Paxene Praxel A", "definition": "A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.\n    ", "id": "MESH:D017239"}
{"mention": "urotensin-II", "mention_text": "Behavioral effects of urotensin-II centrally administered in mice.", "entity": "Urotensins", "aliases": "Urotensins", "definition": "Teleost hormones. A family of small peptides isolated from urophyses of bony fishes. They have many different physiological effects, including long-lasting hypotensive activity and have been proposed as antihypertensives. There are at least four different compounds: urotensin I, urotensin II, urotensin III, and urotensin IV.\n    ", "id": "MESH:D014579"}
{"mention": "Urotensin-II", "mention_text": "Urotensin-II (U-II) receptors are widely distributed in the central nervous system. Intracerebroventricular (i.c.v.) injection of U-II causes hypertension and bradycardia and stimulates prolactin and thyrotropin secretion. However, the behavioral effects of centrally administered U-II have received little attention. In the present study, we tested the effects of i.c.v. injections of U-II on behavioral, metabolic, and endocrine responses in mice. Administration of graded doses of U-II (1-10,000 ng/mouse) provoked: (1) a dose-dependent reduction in the number of head dips in the hole-board test; (2) a dose-dependent reduction in the number of entries in the white chamber in the black-and-white compartment test, and in the number of entries in the central platform and open arms in the plus-maze test; and (3) a dose-dependent increase in the duration of immobility in the forced-swimming test and tail suspension test. Intracerebroventricular injection of U-II also caused an increase in: food intake at doses of 100 and 1,000 ng/mouse, water intake at doses of 100-10,000 ng/mouse, and horizontal locomotion activity at a dose of 10,000 ng/mouse. Whatever was the dose, the central administration of U-II had no effect on body temperature, nociception, apomorphine-induced penile erection and climbing behavior, and stress-induced plasma corticosterone level. Taken together, the present study demonstrates that the central injection of U-II at doses of 1-10,000 ng/mouse induces anxiogenic- and depressant-like effects in mouse. These data suggest that U-II may be involved in some aspects of psychiatric disorders.", "entity": "Urotensins", "aliases": "Urotensins", "definition": "Teleost hormones. A family of small peptides isolated from urophyses of bony fishes. They have many different physiological effects, including long-lasting hypotensive activity and have been proposed as antihypertensives. There are at least four different compounds: urotensin I, urotensin II, urotensin III, and urotensin IV.\n    ", "id": "MESH:D014579"}
{"mention": "U-II", "mention_text": "Urotensin-II (U-II) receptors are widely distributed in the central nervous system. Intracerebroventricular (i.c.v.) injection of U-II causes hypertension and bradycardia and stimulates prolactin and thyrotropin secretion. However, the behavioral effects of centrally administered U-II have received little attention. In the present study, we tested the effects of i.c.v. injections of U-II on behavioral, metabolic, and endocrine responses in mice. Administration of graded doses of U-II (1-10,000 ng/mouse) provoked: (1) a dose-dependent reduction in the number of head dips in the hole-board test; (2) a dose-dependent reduction in the number of entries in the white chamber in the black-and-white compartment test, and in the number of entries in the central platform and open arms in the plus-maze test; and (3) a dose-dependent increase in the duration of immobility in the forced-swimming test and tail suspension test. Intracerebroventricular injection of U-II also caused an increase in: food intake at doses of 100 and 1,000 ng/mouse, water intake at doses of 100-10,000 ng/mouse, and horizontal locomotion activity at a dose of 10,000 ng/mouse. Whatever was the dose, the central administration of U-II had no effect on body temperature, nociception, apomorphine-induced penile erection and climbing behavior, and stress-induced plasma corticosterone level. Taken together, the present study demonstrates that the central injection of U-II at doses of 1-10,000 ng/mouse induces anxiogenic- and depressant-like effects in mouse. These data suggest that U-II may be involved in some aspects of psychiatric disorders.", "entity": "Urotensins", "aliases": "Urotensins", "definition": "Teleost hormones. A family of small peptides isolated from urophyses of bony fishes. They have many different physiological effects, including long-lasting hypotensive activity and have been proposed as antihypertensives. There are at least four different compounds: urotensin I, urotensin II, urotensin III, and urotensin IV.\n    ", "id": "MESH:D014579"}
{"mention": "hypertension", "mention_text": "Urotensin-II (U-II) receptors are widely distributed in the central nervous system. Intracerebroventricular (i.c.v.) injection of U-II causes hypertension and bradycardia and stimulates prolactin and thyrotropin secretion. However, the behavioral effects of centrally administered U-II have received little attention. In the present study, we tested the effects of i.c.v. injections of U-II on behavioral, metabolic, and endocrine responses in mice. Administration of graded doses of U-II (1-10,000 ng/mouse) provoked: (1) a dose-dependent reduction in the number of head dips in the hole-board test; (2) a dose-dependent reduction in the number of entries in the white chamber in the black-and-white compartment test, and in the number of entries in the central platform and open arms in the plus-maze test; and (3) a dose-dependent increase in the duration of immobility in the forced-swimming test and tail suspension test. Intracerebroventricular injection of U-II also caused an increase in: food intake at doses of 100 and 1,000 ng/mouse, water intake at doses of 100-10,000 ng/mouse, and horizontal locomotion activity at a dose of 10,000 ng/mouse. Whatever was the dose, the central administration of U-II had no effect on body temperature, nociception, apomorphine-induced penile erection and climbing behavior, and stress-induced plasma corticosterone level. Taken together, the present study demonstrates that the central injection of U-II at doses of 1-10,000 ng/mouse induces anxiogenic- and depressant-like effects in mouse. These data suggest that U-II may be involved in some aspects of psychiatric disorders.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "bradycardia", "mention_text": "Urotensin-II (U-II) receptors are widely distributed in the central nervous system. Intracerebroventricular (i.c.v.) injection of U-II causes hypertension and bradycardia and stimulates prolactin and thyrotropin secretion. However, the behavioral effects of centrally administered U-II have received little attention. In the present study, we tested the effects of i.c.v. injections of U-II on behavioral, metabolic, and endocrine responses in mice. Administration of graded doses of U-II (1-10,000 ng/mouse) provoked: (1) a dose-dependent reduction in the number of head dips in the hole-board test; (2) a dose-dependent reduction in the number of entries in the white chamber in the black-and-white compartment test, and in the number of entries in the central platform and open arms in the plus-maze test; and (3) a dose-dependent increase in the duration of immobility in the forced-swimming test and tail suspension test. Intracerebroventricular injection of U-II also caused an increase in: food intake at doses of 100 and 1,000 ng/mouse, water intake at doses of 100-10,000 ng/mouse, and horizontal locomotion activity at a dose of 10,000 ng/mouse. Whatever was the dose, the central administration of U-II had no effect on body temperature, nociception, apomorphine-induced penile erection and climbing behavior, and stress-induced plasma corticosterone level. Taken together, the present study demonstrates that the central injection of U-II at doses of 1-10,000 ng/mouse induces anxiogenic- and depressant-like effects in mouse. These data suggest that U-II may be involved in some aspects of psychiatric disorders.", "entity": "Bradycardia", "aliases": "Bradyarrhythmia Bradyarrhythmias Bradycardia Bradycardias", "definition": "Cardiac arrhythmias that are characterized by excessively slow HEART RATE, usually below 50 beats per minute in human adults. They can be classified broadly into SINOATRIAL NODE dysfunction and ATRIOVENTRICULAR BLOCK.\n    ", "id": "MESH:D001919"}
{"mention": "apomorphine", "mention_text": "Urotensin-II (U-II) receptors are widely distributed in the central nervous system. Intracerebroventricular (i.c.v.) injection of U-II causes hypertension and bradycardia and stimulates prolactin and thyrotropin secretion. However, the behavioral effects of centrally administered U-II have received little attention. In the present study, we tested the effects of i.c.v. injections of U-II on behavioral, metabolic, and endocrine responses in mice. Administration of graded doses of U-II (1-10,000 ng/mouse) provoked: (1) a dose-dependent reduction in the number of head dips in the hole-board test; (2) a dose-dependent reduction in the number of entries in the white chamber in the black-and-white compartment test, and in the number of entries in the central platform and open arms in the plus-maze test; and (3) a dose-dependent increase in the duration of immobility in the forced-swimming test and tail suspension test. Intracerebroventricular injection of U-II also caused an increase in: food intake at doses of 100 and 1,000 ng/mouse, water intake at doses of 100-10,000 ng/mouse, and horizontal locomotion activity at a dose of 10,000 ng/mouse. Whatever was the dose, the central administration of U-II had no effect on body temperature, nociception, apomorphine-induced penile erection and climbing behavior, and stress-induced plasma corticosterone level. Taken together, the present study demonstrates that the central injection of U-II at doses of 1-10,000 ng/mouse induces anxiogenic- and depressant-like effects in mouse. These data suggest that U-II may be involved in some aspects of psychiatric disorders.", "entity": "Apomorphine", "aliases": "Aguettant Brand of Apomorphine Hydrochloride Anhydrous Apokinon Apomorphin Teclapharm Apomorphin-Teclapharm ApomorphinTeclapharm Chloride Hemihydrate Britaject Britannia", "definition": "A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use.\n    ", "id": "MESH:D001058"}
{"mention": "penile erection", "mention_text": "Urotensin-II (U-II) receptors are widely distributed in the central nervous system. Intracerebroventricular (i.c.v.) injection of U-II causes hypertension and bradycardia and stimulates prolactin and thyrotropin secretion. However, the behavioral effects of centrally administered U-II have received little attention. In the present study, we tested the effects of i.c.v. injections of U-II on behavioral, metabolic, and endocrine responses in mice. Administration of graded doses of U-II (1-10,000 ng/mouse) provoked: (1) a dose-dependent reduction in the number of head dips in the hole-board test; (2) a dose-dependent reduction in the number of entries in the white chamber in the black-and-white compartment test, and in the number of entries in the central platform and open arms in the plus-maze test; and (3) a dose-dependent increase in the duration of immobility in the forced-swimming test and tail suspension test. Intracerebroventricular injection of U-II also caused an increase in: food intake at doses of 100 and 1,000 ng/mouse, water intake at doses of 100-10,000 ng/mouse, and horizontal locomotion activity at a dose of 10,000 ng/mouse. Whatever was the dose, the central administration of U-II had no effect on body temperature, nociception, apomorphine-induced penile erection and climbing behavior, and stress-induced plasma corticosterone level. Taken together, the present study demonstrates that the central injection of U-II at doses of 1-10,000 ng/mouse induces anxiogenic- and depressant-like effects in mouse. These data suggest that U-II may be involved in some aspects of psychiatric disorders.", "entity": "Penile Diseases", "aliases": "Disease Penile Penis Diseases", "definition": "Pathological processes involving the PENIS or its component tissues.\n    ", "id": "MESH:D010409"}
{"mention": "corticosterone", "mention_text": "Urotensin-II (U-II) receptors are widely distributed in the central nervous system. Intracerebroventricular (i.c.v.) injection of U-II causes hypertension and bradycardia and stimulates prolactin and thyrotropin secretion. However, the behavioral effects of centrally administered U-II have received little attention. In the present study, we tested the effects of i.c.v. injections of U-II on behavioral, metabolic, and endocrine responses in mice. Administration of graded doses of U-II (1-10,000 ng/mouse) provoked: (1) a dose-dependent reduction in the number of head dips in the hole-board test; (2) a dose-dependent reduction in the number of entries in the white chamber in the black-and-white compartment test, and in the number of entries in the central platform and open arms in the plus-maze test; and (3) a dose-dependent increase in the duration of immobility in the forced-swimming test and tail suspension test. Intracerebroventricular injection of U-II also caused an increase in: food intake at doses of 100 and 1,000 ng/mouse, water intake at doses of 100-10,000 ng/mouse, and horizontal locomotion activity at a dose of 10,000 ng/mouse. Whatever was the dose, the central administration of U-II had no effect on body temperature, nociception, apomorphine-induced penile erection and climbing behavior, and stress-induced plasma corticosterone level. Taken together, the present study demonstrates that the central injection of U-II at doses of 1-10,000 ng/mouse induces anxiogenic- and depressant-like effects in mouse. These data suggest that U-II may be involved in some aspects of psychiatric disorders.", "entity": "Corticosterone", "aliases": "Corticosterone", "definition": "An adrenocortical steroid that has modest but significant activities as a mineralocorticoid and a glucocorticoid. (From Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1437)\n    ", "id": "MESH:D003345"}
{"mention": "psychiatric disorders", "mention_text": "Urotensin-II (U-II) receptors are widely distributed in the central nervous system. Intracerebroventricular (i.c.v.) injection of U-II causes hypertension and bradycardia and stimulates prolactin and thyrotropin secretion. However, the behavioral effects of centrally administered U-II have received little attention. In the present study, we tested the effects of i.c.v. injections of U-II on behavioral, metabolic, and endocrine responses in mice. Administration of graded doses of U-II (1-10,000 ng/mouse) provoked: (1) a dose-dependent reduction in the number of head dips in the hole-board test; (2) a dose-dependent reduction in the number of entries in the white chamber in the black-and-white compartment test, and in the number of entries in the central platform and open arms in the plus-maze test; and (3) a dose-dependent increase in the duration of immobility in the forced-swimming test and tail suspension test. Intracerebroventricular injection of U-II also caused an increase in: food intake at doses of 100 and 1,000 ng/mouse, water intake at doses of 100-10,000 ng/mouse, and horizontal locomotion activity at a dose of 10,000 ng/mouse. Whatever was the dose, the central administration of U-II had no effect on body temperature, nociception, apomorphine-induced penile erection and climbing behavior, and stress-induced plasma corticosterone level. Taken together, the present study demonstrates that the central injection of U-II at doses of 1-10,000 ng/mouse induces anxiogenic- and depressant-like effects in mouse. These data suggest that U-II may be involved in some aspects of psychiatric disorders.", "entity": "Mental Disorders", "aliases": "Behavior Disorders Diagnosis Psychiatric Disorder Mental", "definition": "Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.\n    ", "id": "MESH:D001523"}
{"mention": "dysphonia", "mention_text": "Recurrent dysphonia and acitretin.", "entity": "Dysphonia", "aliases": "Dysphonia Hyperkinetic Organic Tremor Spastic Neurologic Adducter Phonation Disorder Disorders", "definition": "Difficulty and/or pain in PHONATION or speaking.\n    ", "id": "MESH:D055154"}
{"mention": "acitretin", "mention_text": "Recurrent dysphonia and acitretin.", "entity": "Acitretin", "aliases": "13-cis-Acitretin Acitretin Andreu Brand Roche (Z,E,E,E)-Isomer of Etretin Hoffmann La Hoffmann-La Isoacitretin Isoetretin Neotigason Ro 10-1670 101670 13-7652 137652 Ro-10-1670 Ro-13-7652 Ro101670 Ro137652 Soriatane", "definition": "An oral retinoid effective in the treatment of psoriasis. It is the major metabolite of ETRETINATE with the advantage of a much shorter half-life when compared with etretinate.\n    ", "id": "MESH:D017255"}
{"mention": "dysphonia", "mention_text": "We report the case of a woman complaining of dysphonia while she was treated by acitretin. Her symptoms totally regressed after drug withdrawal and reappeared when acitretin was reintroduced. To our knowledge, this is the first case of acitretin-induced dysphonia. This effect may be related to the pharmacological effect of this drug on mucous membranes.", "entity": "Dysphonia", "aliases": "Dysphonia Hyperkinetic Organic Tremor Spastic Neurologic Adducter Phonation Disorder Disorders", "definition": "Difficulty and/or pain in PHONATION or speaking.\n    ", "id": "MESH:D055154"}
{"mention": "acitretin", "mention_text": "We report the case of a woman complaining of dysphonia while she was treated by acitretin. Her symptoms totally regressed after drug withdrawal and reappeared when acitretin was reintroduced. To our knowledge, this is the first case of acitretin-induced dysphonia. This effect may be related to the pharmacological effect of this drug on mucous membranes.", "entity": "Acitretin", "aliases": "13-cis-Acitretin Acitretin Andreu Brand Roche (Z,E,E,E)-Isomer of Etretin Hoffmann La Hoffmann-La Isoacitretin Isoetretin Neotigason Ro 10-1670 101670 13-7652 137652 Ro-10-1670 Ro-13-7652 Ro101670 Ro137652 Soriatane", "definition": "An oral retinoid effective in the treatment of psoriasis. It is the major metabolite of ETRETINATE with the advantage of a much shorter half-life when compared with etretinate.\n    ", "id": "MESH:D017255"}
{"mention": "pain", "mention_text": "Pharmacological modulation of pain-related brain activity during normal and central sensitization states in humans.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "pain", "mention_text": "Abnormal processing of somatosensory inputs in the central nervous system (central sensitization) is the mechanism accounting for the enhanced pain sensitivity in the skin surrounding tissue injury (secondary hyperalgesia). Secondary hyperalgesia shares clinical characteristics with neurogenic hyperalgesia in patients with neuropathic pain. Abnormal brain responses to somatosensory stimuli have been found in patients with hyperalgesia as well as in normal subjects during experimental central sensitization. The aim of this study was to assess the effects of gabapentin, a drug effective in neuropathic pain patients, on brain processing of nociceptive information in normal and central sensitization states. Using functional magnetic resonance imaging (fMRI) in normal volunteers, we studied the gabapentin-induced modulation of brain activity in response to nociceptive mechanical stimulation of normal skin and capsaicin-induced secondary hyperalgesia. The dose of gabapentin was 1,800 mg per os, in a single administration. We found that (i) gabapentin reduced the activations in the bilateral operculoinsular cortex, independently of the presence of central sensitization; (ii) gabapentin reduced the activation in the brainstem, only during central sensitization; (iii) gabapentin suppressed stimulus-induced deactivations, only during central sensitization; this effect was more robust than the effect on brain activation. The observed drug-induced effects were not due to changes in the baseline fMRI signal. These findings indicate that gabapentin has a measurable antinociceptive effect and a stronger antihyperalgesic effect most evident in the brain areas undergoing deactivation, thus supporting the concept that gabapentin is more effective in modulating nociceptive transmission when central sensitization is present.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "tissue injury", "mention_text": "Abnormal processing of somatosensory inputs in the central nervous system (central sensitization) is the mechanism accounting for the enhanced pain sensitivity in the skin surrounding tissue injury (secondary hyperalgesia). Secondary hyperalgesia shares clinical characteristics with neurogenic hyperalgesia in patients with neuropathic pain. Abnormal brain responses to somatosensory stimuli have been found in patients with hyperalgesia as well as in normal subjects during experimental central sensitization. The aim of this study was to assess the effects of gabapentin, a drug effective in neuropathic pain patients, on brain processing of nociceptive information in normal and central sensitization states. Using functional magnetic resonance imaging (fMRI) in normal volunteers, we studied the gabapentin-induced modulation of brain activity in response to nociceptive mechanical stimulation of normal skin and capsaicin-induced secondary hyperalgesia. The dose of gabapentin was 1,800 mg per os, in a single administration. We found that (i) gabapentin reduced the activations in the bilateral operculoinsular cortex, independently of the presence of central sensitization; (ii) gabapentin reduced the activation in the brainstem, only during central sensitization; (iii) gabapentin suppressed stimulus-induced deactivations, only during central sensitization; this effect was more robust than the effect on brain activation. The observed drug-induced effects were not due to changes in the baseline fMRI signal. These findings indicate that gabapentin has a measurable antinociceptive effect and a stronger antihyperalgesic effect most evident in the brain areas undergoing deactivation, thus supporting the concept that gabapentin is more effective in modulating nociceptive transmission when central sensitization is present.", "entity": "Soft Tissue Injuries", "aliases": "Injuries Soft Tissue Injury", "definition": "Injuries of tissue other than bone. The concept is usually general and does not customarily refer to internal organs or viscera. It is meaningful with reference to regions or organs where soft tissue (muscle, fat, skin) should be differentiated from bones or bone tissue, as \"soft tissue injuries of the hand\".\n    ", "id": "MESH:D017695"}
{"mention": "secondary hyperalgesia", "mention_text": "Abnormal processing of somatosensory inputs in the central nervous system (central sensitization) is the mechanism accounting for the enhanced pain sensitivity in the skin surrounding tissue injury (secondary hyperalgesia). Secondary hyperalgesia shares clinical characteristics with neurogenic hyperalgesia in patients with neuropathic pain. Abnormal brain responses to somatosensory stimuli have been found in patients with hyperalgesia as well as in normal subjects during experimental central sensitization. The aim of this study was to assess the effects of gabapentin, a drug effective in neuropathic pain patients, on brain processing of nociceptive information in normal and central sensitization states. Using functional magnetic resonance imaging (fMRI) in normal volunteers, we studied the gabapentin-induced modulation of brain activity in response to nociceptive mechanical stimulation of normal skin and capsaicin-induced secondary hyperalgesia. The dose of gabapentin was 1,800 mg per os, in a single administration. We found that (i) gabapentin reduced the activations in the bilateral operculoinsular cortex, independently of the presence of central sensitization; (ii) gabapentin reduced the activation in the brainstem, only during central sensitization; (iii) gabapentin suppressed stimulus-induced deactivations, only during central sensitization; this effect was more robust than the effect on brain activation. The observed drug-induced effects were not due to changes in the baseline fMRI signal. These findings indicate that gabapentin has a measurable antinociceptive effect and a stronger antihyperalgesic effect most evident in the brain areas undergoing deactivation, thus supporting the concept that gabapentin is more effective in modulating nociceptive transmission when central sensitization is present.", "entity": "Hyperalgesia", "aliases": "Allodynia Mechanical Tactile Thermal Allodynias Hyperalgesia Primary Secondary Hyperalgesias Hyperalgesic Sensations", "definition": "An increased sensation of pain or discomfort produced by mimimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve.\n    ", "id": "MESH:D006930"}
{"mention": "Secondary hyperalgesia", "mention_text": "Abnormal processing of somatosensory inputs in the central nervous system (central sensitization) is the mechanism accounting for the enhanced pain sensitivity in the skin surrounding tissue injury (secondary hyperalgesia). Secondary hyperalgesia shares clinical characteristics with neurogenic hyperalgesia in patients with neuropathic pain. Abnormal brain responses to somatosensory stimuli have been found in patients with hyperalgesia as well as in normal subjects during experimental central sensitization. The aim of this study was to assess the effects of gabapentin, a drug effective in neuropathic pain patients, on brain processing of nociceptive information in normal and central sensitization states. Using functional magnetic resonance imaging (fMRI) in normal volunteers, we studied the gabapentin-induced modulation of brain activity in response to nociceptive mechanical stimulation of normal skin and capsaicin-induced secondary hyperalgesia. The dose of gabapentin was 1,800 mg per os, in a single administration. We found that (i) gabapentin reduced the activations in the bilateral operculoinsular cortex, independently of the presence of central sensitization; (ii) gabapentin reduced the activation in the brainstem, only during central sensitization; (iii) gabapentin suppressed stimulus-induced deactivations, only during central sensitization; this effect was more robust than the effect on brain activation. The observed drug-induced effects were not due to changes in the baseline fMRI signal. These findings indicate that gabapentin has a measurable antinociceptive effect and a stronger antihyperalgesic effect most evident in the brain areas undergoing deactivation, thus supporting the concept that gabapentin is more effective in modulating nociceptive transmission when central sensitization is present.", "entity": "Hyperalgesia", "aliases": "Allodynia Mechanical Tactile Thermal Allodynias Hyperalgesia Primary Secondary Hyperalgesias Hyperalgesic Sensations", "definition": "An increased sensation of pain or discomfort produced by mimimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve.\n    ", "id": "MESH:D006930"}
{"mention": "neurogenic hyperalgesia", "mention_text": "Abnormal processing of somatosensory inputs in the central nervous system (central sensitization) is the mechanism accounting for the enhanced pain sensitivity in the skin surrounding tissue injury (secondary hyperalgesia). Secondary hyperalgesia shares clinical characteristics with neurogenic hyperalgesia in patients with neuropathic pain. Abnormal brain responses to somatosensory stimuli have been found in patients with hyperalgesia as well as in normal subjects during experimental central sensitization. The aim of this study was to assess the effects of gabapentin, a drug effective in neuropathic pain patients, on brain processing of nociceptive information in normal and central sensitization states. Using functional magnetic resonance imaging (fMRI) in normal volunteers, we studied the gabapentin-induced modulation of brain activity in response to nociceptive mechanical stimulation of normal skin and capsaicin-induced secondary hyperalgesia. The dose of gabapentin was 1,800 mg per os, in a single administration. We found that (i) gabapentin reduced the activations in the bilateral operculoinsular cortex, independently of the presence of central sensitization; (ii) gabapentin reduced the activation in the brainstem, only during central sensitization; (iii) gabapentin suppressed stimulus-induced deactivations, only during central sensitization; this effect was more robust than the effect on brain activation. The observed drug-induced effects were not due to changes in the baseline fMRI signal. These findings indicate that gabapentin has a measurable antinociceptive effect and a stronger antihyperalgesic effect most evident in the brain areas undergoing deactivation, thus supporting the concept that gabapentin is more effective in modulating nociceptive transmission when central sensitization is present.", "entity": "Hyperalgesia", "aliases": "Allodynia Mechanical Tactile Thermal Allodynias Hyperalgesia Primary Secondary Hyperalgesias Hyperalgesic Sensations", "definition": "An increased sensation of pain or discomfort produced by mimimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve.\n    ", "id": "MESH:D006930"}
{"mention": "neuropathic pain", "mention_text": "Abnormal processing of somatosensory inputs in the central nervous system (central sensitization) is the mechanism accounting for the enhanced pain sensitivity in the skin surrounding tissue injury (secondary hyperalgesia). Secondary hyperalgesia shares clinical characteristics with neurogenic hyperalgesia in patients with neuropathic pain. Abnormal brain responses to somatosensory stimuli have been found in patients with hyperalgesia as well as in normal subjects during experimental central sensitization. The aim of this study was to assess the effects of gabapentin, a drug effective in neuropathic pain patients, on brain processing of nociceptive information in normal and central sensitization states. Using functional magnetic resonance imaging (fMRI) in normal volunteers, we studied the gabapentin-induced modulation of brain activity in response to nociceptive mechanical stimulation of normal skin and capsaicin-induced secondary hyperalgesia. The dose of gabapentin was 1,800 mg per os, in a single administration. We found that (i) gabapentin reduced the activations in the bilateral operculoinsular cortex, independently of the presence of central sensitization; (ii) gabapentin reduced the activation in the brainstem, only during central sensitization; (iii) gabapentin suppressed stimulus-induced deactivations, only during central sensitization; this effect was more robust than the effect on brain activation. The observed drug-induced effects were not due to changes in the baseline fMRI signal. These findings indicate that gabapentin has a measurable antinociceptive effect and a stronger antihyperalgesic effect most evident in the brain areas undergoing deactivation, thus supporting the concept that gabapentin is more effective in modulating nociceptive transmission when central sensitization is present.", "entity": "Neuralgia", "aliases": "Atypical Neuralgia Neuralgias Iliohypogastric Nerve Ilioinguinal Pain Paroxysmal Pains Perineal Stump Supraorbital Vidian Neurodynia Neurodynias Neuropathic", "definition": "Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve.\n    ", "id": "MESH:D009437"}
{"mention": "hyperalgesia", "mention_text": "Abnormal processing of somatosensory inputs in the central nervous system (central sensitization) is the mechanism accounting for the enhanced pain sensitivity in the skin surrounding tissue injury (secondary hyperalgesia). Secondary hyperalgesia shares clinical characteristics with neurogenic hyperalgesia in patients with neuropathic pain. Abnormal brain responses to somatosensory stimuli have been found in patients with hyperalgesia as well as in normal subjects during experimental central sensitization. The aim of this study was to assess the effects of gabapentin, a drug effective in neuropathic pain patients, on brain processing of nociceptive information in normal and central sensitization states. Using functional magnetic resonance imaging (fMRI) in normal volunteers, we studied the gabapentin-induced modulation of brain activity in response to nociceptive mechanical stimulation of normal skin and capsaicin-induced secondary hyperalgesia. The dose of gabapentin was 1,800 mg per os, in a single administration. We found that (i) gabapentin reduced the activations in the bilateral operculoinsular cortex, independently of the presence of central sensitization; (ii) gabapentin reduced the activation in the brainstem, only during central sensitization; (iii) gabapentin suppressed stimulus-induced deactivations, only during central sensitization; this effect was more robust than the effect on brain activation. The observed drug-induced effects were not due to changes in the baseline fMRI signal. These findings indicate that gabapentin has a measurable antinociceptive effect and a stronger antihyperalgesic effect most evident in the brain areas undergoing deactivation, thus supporting the concept that gabapentin is more effective in modulating nociceptive transmission when central sensitization is present.", "entity": "Hyperalgesia", "aliases": "Allodynia Mechanical Tactile Thermal Allodynias Hyperalgesia Primary Secondary Hyperalgesias Hyperalgesic Sensations", "definition": "An increased sensation of pain or discomfort produced by mimimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve.\n    ", "id": "MESH:D006930"}
{"mention": "gabapentin", "mention_text": "Abnormal processing of somatosensory inputs in the central nervous system (central sensitization) is the mechanism accounting for the enhanced pain sensitivity in the skin surrounding tissue injury (secondary hyperalgesia). Secondary hyperalgesia shares clinical characteristics with neurogenic hyperalgesia in patients with neuropathic pain. Abnormal brain responses to somatosensory stimuli have been found in patients with hyperalgesia as well as in normal subjects during experimental central sensitization. The aim of this study was to assess the effects of gabapentin, a drug effective in neuropathic pain patients, on brain processing of nociceptive information in normal and central sensitization states. Using functional magnetic resonance imaging (fMRI) in normal volunteers, we studied the gabapentin-induced modulation of brain activity in response to nociceptive mechanical stimulation of normal skin and capsaicin-induced secondary hyperalgesia. The dose of gabapentin was 1,800 mg per os, in a single administration. We found that (i) gabapentin reduced the activations in the bilateral operculoinsular cortex, independently of the presence of central sensitization; (ii) gabapentin reduced the activation in the brainstem, only during central sensitization; (iii) gabapentin suppressed stimulus-induced deactivations, only during central sensitization; this effect was more robust than the effect on brain activation. The observed drug-induced effects were not due to changes in the baseline fMRI signal. These findings indicate that gabapentin has a measurable antinociceptive effect and a stronger antihyperalgesic effect most evident in the brain areas undergoing deactivation, thus supporting the concept that gabapentin is more effective in modulating nociceptive transmission when central sensitization is present.", "entity": "gabapentin", "aliases": "1-(aminomethyl)cyclohexaneacetic acid Apo-Gabapentin Convalis Gabapentin Hexal Stada Gabapentin-ratiopharm Neurontin Novo-Gabapentin PMS-Gabapentin gabapentin", "definition": "", "id": "MESH:C040029"}
{"mention": "capsaicin", "mention_text": "Abnormal processing of somatosensory inputs in the central nervous system (central sensitization) is the mechanism accounting for the enhanced pain sensitivity in the skin surrounding tissue injury (secondary hyperalgesia). Secondary hyperalgesia shares clinical characteristics with neurogenic hyperalgesia in patients with neuropathic pain. Abnormal brain responses to somatosensory stimuli have been found in patients with hyperalgesia as well as in normal subjects during experimental central sensitization. The aim of this study was to assess the effects of gabapentin, a drug effective in neuropathic pain patients, on brain processing of nociceptive information in normal and central sensitization states. Using functional magnetic resonance imaging (fMRI) in normal volunteers, we studied the gabapentin-induced modulation of brain activity in response to nociceptive mechanical stimulation of normal skin and capsaicin-induced secondary hyperalgesia. The dose of gabapentin was 1,800 mg per os, in a single administration. We found that (i) gabapentin reduced the activations in the bilateral operculoinsular cortex, independently of the presence of central sensitization; (ii) gabapentin reduced the activation in the brainstem, only during central sensitization; (iii) gabapentin suppressed stimulus-induced deactivations, only during central sensitization; this effect was more robust than the effect on brain activation. The observed drug-induced effects were not due to changes in the baseline fMRI signal. These findings indicate that gabapentin has a measurable antinociceptive effect and a stronger antihyperalgesic effect most evident in the brain areas undergoing deactivation, thus supporting the concept that gabapentin is more effective in modulating nociceptive transmission when central sensitization is present.", "entity": "Capsaicin", "aliases": "8 Methyl N Vanillyl 6 Nonenamide 8-Methyl-N-Vanillyl-6-Nonenamide Alacan Brand of Capsaicin Antiphlogistine Rub A-535 Axsain Capsaicine Capsicum Farmaya Capsidol Capsin Capzasin Carter Horner Centrum Elan Flemming Gelcen Katrum Link Medicis NGX 4010 NGX-4010 NGX4010 Smaller Thompson Vinas Zacin Zostrix", "definition": "An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.\n    ", "id": "MESH:D002211"}
{"mention": "MDMA", "mention_text": "MDMA polydrug users show process-specific central executive impairments coupled with impaired social and emotional judgement processes.", "entity": "N-Methyl-3,4-methylenedioxyamphetamine", "aliases": "Ecstasy (Drug) Hydrochloride N-Methyl-3,4-methylenedioxyamphetamine MDMA Methylenedioxymethamphetamine N Methyl 3,4 methylenedioxyamphetamine", "definition": "An N-substituted amphetamine analog. It is a widely abused drug classified as a hallucinogen and causes marked, long-lasting changes in brain serotonergic systems. It is commonly referred to as MDMA or ecstasy.\n    ", "id": "MESH:D018817"}
{"mention": "impaired social and emotional judgement processes", "mention_text": "MDMA polydrug users show process-specific central executive impairments coupled with impaired social and emotional judgement processes.", "entity": "Cognition Disorders", "aliases": "Cognition Disorders Disorder Overinclusion", "definition": "Disturbances in the mental process related to thinking, reasoning, and judgment.\n    ", "id": "MESH:D003072"}
{"mention": "memory deficits", "mention_text": "In recent years working memory deficits have been reported in users of MDMA (3,4-methylenedioxymethamphetamine, ecstasy). The current study aimed to assess the impact of MDMA use on three separate central executive processes (set shifting, inhibition and memory updating) and also on \"prefrontal\" mediated social and emotional judgement processes. Fifteen polydrug ecstasy users and 15 polydrug non-ecstasy user controls completed a general drug use questionnaire, the Brixton Spatial Anticipation task (set shifting), Backward Digit Span procedure (memory updating), Inhibition of Return (inhibition), an emotional intelligence scale, the Tromso Social Intelligence Scale and the Dysexecutive Questionnaire (DEX). Compared with MDMA-free polydrug controls, MDMA polydrug users showed impairments in set shifting and memory updating, and also in social and emotional judgement processes. The latter two deficits remained significant after controlling for other drug use. These data lend further support to the proposal that cognitive processes mediated by the prefrontal cortex may be impaired by recreational ecstasy use.", "entity": "Memory Disorders", "aliases": "Age Related Memory Disorders Age-Related Disorder Cognitive Retention Deficit Deficits Semantic Spatial Loss Losses", "definition": "Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions.\n    ", "id": "MESH:D008569"}
{"mention": "MDMA", "mention_text": "In recent years working memory deficits have been reported in users of MDMA (3,4-methylenedioxymethamphetamine, ecstasy). The current study aimed to assess the impact of MDMA use on three separate central executive processes (set shifting, inhibition and memory updating) and also on \"prefrontal\" mediated social and emotional judgement processes. Fifteen polydrug ecstasy users and 15 polydrug non-ecstasy user controls completed a general drug use questionnaire, the Brixton Spatial Anticipation task (set shifting), Backward Digit Span procedure (memory updating), Inhibition of Return (inhibition), an emotional intelligence scale, the Tromso Social Intelligence Scale and the Dysexecutive Questionnaire (DEX). Compared with MDMA-free polydrug controls, MDMA polydrug users showed impairments in set shifting and memory updating, and also in social and emotional judgement processes. The latter two deficits remained significant after controlling for other drug use. These data lend further support to the proposal that cognitive processes mediated by the prefrontal cortex may be impaired by recreational ecstasy use.", "entity": "N-Methyl-3,4-methylenedioxyamphetamine", "aliases": "Ecstasy (Drug) Hydrochloride N-Methyl-3,4-methylenedioxyamphetamine MDMA Methylenedioxymethamphetamine N Methyl 3,4 methylenedioxyamphetamine", "definition": "An N-substituted amphetamine analog. It is a widely abused drug classified as a hallucinogen and causes marked, long-lasting changes in brain serotonergic systems. It is commonly referred to as MDMA or ecstasy.\n    ", "id": "MESH:D018817"}
{"mention": "3,4-methylenedioxymethamphetamine", "mention_text": "In recent years working memory deficits have been reported in users of MDMA (3,4-methylenedioxymethamphetamine, ecstasy). The current study aimed to assess the impact of MDMA use on three separate central executive processes (set shifting, inhibition and memory updating) and also on \"prefrontal\" mediated social and emotional judgement processes. Fifteen polydrug ecstasy users and 15 polydrug non-ecstasy user controls completed a general drug use questionnaire, the Brixton Spatial Anticipation task (set shifting), Backward Digit Span procedure (memory updating), Inhibition of Return (inhibition), an emotional intelligence scale, the Tromso Social Intelligence Scale and the Dysexecutive Questionnaire (DEX). Compared with MDMA-free polydrug controls, MDMA polydrug users showed impairments in set shifting and memory updating, and also in social and emotional judgement processes. The latter two deficits remained significant after controlling for other drug use. These data lend further support to the proposal that cognitive processes mediated by the prefrontal cortex may be impaired by recreational ecstasy use.", "entity": "N-Methyl-3,4-methylenedioxyamphetamine", "aliases": "Ecstasy (Drug) Hydrochloride N-Methyl-3,4-methylenedioxyamphetamine MDMA Methylenedioxymethamphetamine N Methyl 3,4 methylenedioxyamphetamine", "definition": "An N-substituted amphetamine analog. It is a widely abused drug classified as a hallucinogen and causes marked, long-lasting changes in brain serotonergic systems. It is commonly referred to as MDMA or ecstasy.\n    ", "id": "MESH:D018817"}
{"mention": "ecstasy", "mention_text": "In recent years working memory deficits have been reported in users of MDMA (3,4-methylenedioxymethamphetamine, ecstasy). The current study aimed to assess the impact of MDMA use on three separate central executive processes (set shifting, inhibition and memory updating) and also on \"prefrontal\" mediated social and emotional judgement processes. Fifteen polydrug ecstasy users and 15 polydrug non-ecstasy user controls completed a general drug use questionnaire, the Brixton Spatial Anticipation task (set shifting), Backward Digit Span procedure (memory updating), Inhibition of Return (inhibition), an emotional intelligence scale, the Tromso Social Intelligence Scale and the Dysexecutive Questionnaire (DEX). Compared with MDMA-free polydrug controls, MDMA polydrug users showed impairments in set shifting and memory updating, and also in social and emotional judgement processes. The latter two deficits remained significant after controlling for other drug use. These data lend further support to the proposal that cognitive processes mediated by the prefrontal cortex may be impaired by recreational ecstasy use.", "entity": "N-Methyl-3,4-methylenedioxyamphetamine", "aliases": "Ecstasy (Drug) Hydrochloride N-Methyl-3,4-methylenedioxyamphetamine MDMA Methylenedioxymethamphetamine N Methyl 3,4 methylenedioxyamphetamine", "definition": "An N-substituted amphetamine analog. It is a widely abused drug classified as a hallucinogen and causes marked, long-lasting changes in brain serotonergic systems. It is commonly referred to as MDMA or ecstasy.\n    ", "id": "MESH:D018817"}
{"mention": "citrate", "mention_text": "Severe citrate toxicity complicating volunteer apheresis platelet donation.", "entity": "sodium citrate", "aliases": "Citra ph anhydrous sodium citrate dihydrate trisodium", "definition": "", "id": "MESH:C102006"}
{"mention": "toxicity", "mention_text": "Severe citrate toxicity complicating volunteer apheresis platelet donation.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "citrate", "mention_text": "We report a case of severe citrate toxicity during volunteer donor apheresis platelet collection. The donor was a 40-year-old female, first-time apheresis platelet donor. Past medical history was remarkable for hypertension, hyperlipidemia, and depression. Reported medications included bumetanide, pravastatin, and paroxetine. Thirty minutes from the start of the procedure, the donor noted tingling around the mouth, hands, and feet. She then very rapidly developed acute onset of severe facial and extremity tetany. Empirical treatment with intravenous calcium gluconate was initiated, and muscle contractions slowly subsided over approximately 10 to 15 minutes. The events are consistent with a severe reaction to calcium chelation by sodium citrate anticoagulant resulting in symptomatic systemic hypocalcemia. Upon additional retrospective analysis, it was noted that bumetanide is a loop diuretic that may cause significant hypocalcemia. We conclude that careful screening for medications and underlying conditions predisposing to hypocalcemia is recommended to help prevent severe reactions due to citrate toxicity. Laboratory measurement of pre-procedure serum calcium levels in selected donors may identify cases requiring heightened vigilance. The case also illustrates the importance of maintaining preparedness for managing rare but serious reactions in volunteer apheresis blood donors.", "entity": "sodium citrate", "aliases": "Citra ph anhydrous sodium citrate dihydrate trisodium", "definition": "", "id": "MESH:C102006"}
{"mention": "toxicity", "mention_text": "We report a case of severe citrate toxicity during volunteer donor apheresis platelet collection. The donor was a 40-year-old female, first-time apheresis platelet donor. Past medical history was remarkable for hypertension, hyperlipidemia, and depression. Reported medications included bumetanide, pravastatin, and paroxetine. Thirty minutes from the start of the procedure, the donor noted tingling around the mouth, hands, and feet. She then very rapidly developed acute onset of severe facial and extremity tetany. Empirical treatment with intravenous calcium gluconate was initiated, and muscle contractions slowly subsided over approximately 10 to 15 minutes. The events are consistent with a severe reaction to calcium chelation by sodium citrate anticoagulant resulting in symptomatic systemic hypocalcemia. Upon additional retrospective analysis, it was noted that bumetanide is a loop diuretic that may cause significant hypocalcemia. We conclude that careful screening for medications and underlying conditions predisposing to hypocalcemia is recommended to help prevent severe reactions due to citrate toxicity. Laboratory measurement of pre-procedure serum calcium levels in selected donors may identify cases requiring heightened vigilance. The case also illustrates the importance of maintaining preparedness for managing rare but serious reactions in volunteer apheresis blood donors.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "hypertension", "mention_text": "We report a case of severe citrate toxicity during volunteer donor apheresis platelet collection. The donor was a 40-year-old female, first-time apheresis platelet donor. Past medical history was remarkable for hypertension, hyperlipidemia, and depression. Reported medications included bumetanide, pravastatin, and paroxetine. Thirty minutes from the start of the procedure, the donor noted tingling around the mouth, hands, and feet. She then very rapidly developed acute onset of severe facial and extremity tetany. Empirical treatment with intravenous calcium gluconate was initiated, and muscle contractions slowly subsided over approximately 10 to 15 minutes. The events are consistent with a severe reaction to calcium chelation by sodium citrate anticoagulant resulting in symptomatic systemic hypocalcemia. Upon additional retrospective analysis, it was noted that bumetanide is a loop diuretic that may cause significant hypocalcemia. We conclude that careful screening for medications and underlying conditions predisposing to hypocalcemia is recommended to help prevent severe reactions due to citrate toxicity. Laboratory measurement of pre-procedure serum calcium levels in selected donors may identify cases requiring heightened vigilance. The case also illustrates the importance of maintaining preparedness for managing rare but serious reactions in volunteer apheresis blood donors.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "hyperlipidemia", "mention_text": "We report a case of severe citrate toxicity during volunteer donor apheresis platelet collection. The donor was a 40-year-old female, first-time apheresis platelet donor. Past medical history was remarkable for hypertension, hyperlipidemia, and depression. Reported medications included bumetanide, pravastatin, and paroxetine. Thirty minutes from the start of the procedure, the donor noted tingling around the mouth, hands, and feet. She then very rapidly developed acute onset of severe facial and extremity tetany. Empirical treatment with intravenous calcium gluconate was initiated, and muscle contractions slowly subsided over approximately 10 to 15 minutes. The events are consistent with a severe reaction to calcium chelation by sodium citrate anticoagulant resulting in symptomatic systemic hypocalcemia. Upon additional retrospective analysis, it was noted that bumetanide is a loop diuretic that may cause significant hypocalcemia. We conclude that careful screening for medications and underlying conditions predisposing to hypocalcemia is recommended to help prevent severe reactions due to citrate toxicity. Laboratory measurement of pre-procedure serum calcium levels in selected donors may identify cases requiring heightened vigilance. The case also illustrates the importance of maintaining preparedness for managing rare but serious reactions in volunteer apheresis blood donors.", "entity": "Hyperlipidemias", "aliases": "Hyperlipemia Hyperlipemias Hyperlipidemia Hyperlipidemias Lipemia Lipemias Lipidemia Lipidemias", "definition": "Conditions with excess LIPIDS in the blood.\n    ", "id": "MESH:D006949"}
{"mention": "depression", "mention_text": "We report a case of severe citrate toxicity during volunteer donor apheresis platelet collection. The donor was a 40-year-old female, first-time apheresis platelet donor. Past medical history was remarkable for hypertension, hyperlipidemia, and depression. Reported medications included bumetanide, pravastatin, and paroxetine. Thirty minutes from the start of the procedure, the donor noted tingling around the mouth, hands, and feet. She then very rapidly developed acute onset of severe facial and extremity tetany. Empirical treatment with intravenous calcium gluconate was initiated, and muscle contractions slowly subsided over approximately 10 to 15 minutes. The events are consistent with a severe reaction to calcium chelation by sodium citrate anticoagulant resulting in symptomatic systemic hypocalcemia. Upon additional retrospective analysis, it was noted that bumetanide is a loop diuretic that may cause significant hypocalcemia. We conclude that careful screening for medications and underlying conditions predisposing to hypocalcemia is recommended to help prevent severe reactions due to citrate toxicity. Laboratory measurement of pre-procedure serum calcium levels in selected donors may identify cases requiring heightened vigilance. The case also illustrates the importance of maintaining preparedness for managing rare but serious reactions in volunteer apheresis blood donors.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "bumetanide", "mention_text": "We report a case of severe citrate toxicity during volunteer donor apheresis platelet collection. The donor was a 40-year-old female, first-time apheresis platelet donor. Past medical history was remarkable for hypertension, hyperlipidemia, and depression. Reported medications included bumetanide, pravastatin, and paroxetine. Thirty minutes from the start of the procedure, the donor noted tingling around the mouth, hands, and feet. She then very rapidly developed acute onset of severe facial and extremity tetany. Empirical treatment with intravenous calcium gluconate was initiated, and muscle contractions slowly subsided over approximately 10 to 15 minutes. The events are consistent with a severe reaction to calcium chelation by sodium citrate anticoagulant resulting in symptomatic systemic hypocalcemia. Upon additional retrospective analysis, it was noted that bumetanide is a loop diuretic that may cause significant hypocalcemia. We conclude that careful screening for medications and underlying conditions predisposing to hypocalcemia is recommended to help prevent severe reactions due to citrate toxicity. Laboratory measurement of pre-procedure serum calcium levels in selected donors may identify cases requiring heightened vigilance. The case also illustrates the importance of maintaining preparedness for managing rare but serious reactions in volunteer apheresis blood donors.", "entity": "Bumetanide", "aliases": "AstraZeneca Brand of Bumetanide Atlantis Bumedyl Farmacusi Grossmann Leo Roche Senosiain Bumethanide Bumex Burinex Drenural Fordiuran Miccil PF 1593 PF-1593 PF1593", "definition": "A sulfamyl diuretic.\n    ", "id": "MESH:D002034"}
{"mention": "pravastatin", "mention_text": "We report a case of severe citrate toxicity during volunteer donor apheresis platelet collection. The donor was a 40-year-old female, first-time apheresis platelet donor. Past medical history was remarkable for hypertension, hyperlipidemia, and depression. Reported medications included bumetanide, pravastatin, and paroxetine. Thirty minutes from the start of the procedure, the donor noted tingling around the mouth, hands, and feet. She then very rapidly developed acute onset of severe facial and extremity tetany. Empirical treatment with intravenous calcium gluconate was initiated, and muscle contractions slowly subsided over approximately 10 to 15 minutes. The events are consistent with a severe reaction to calcium chelation by sodium citrate anticoagulant resulting in symptomatic systemic hypocalcemia. Upon additional retrospective analysis, it was noted that bumetanide is a loop diuretic that may cause significant hypocalcemia. We conclude that careful screening for medications and underlying conditions predisposing to hypocalcemia is recommended to help prevent severe reactions due to citrate toxicity. Laboratory measurement of pre-procedure serum calcium levels in selected donors may identify cases requiring heightened vigilance. The case also illustrates the importance of maintaining preparedness for managing rare but serious reactions in volunteer apheresis blood donors.", "entity": "Pravastatin", "aliases": "Apo Pravastatin Apo-Pravastatin Apotex Brand of Sodium Aventis Bristacol Bristol-Myers Squibb CS 514 CS-514 CS514 Elisor Eptastatin Esteve Juste Lin Lin-Pravastatin Linson Pharma Lipemol Liplat Lipostat Mevalotin Nu Nu-Pharma Nu-Pravastatin Prareduct Pravachol Pravacol Pravasin Monosodium Salt (6 beta)-Isomer tert Octylamine tert-Octylamine RMS 431 RMS-431 RMS431 SQ 31,000 31000 SQ-31,000 SQ-31000 SQ31,000 SQ31000 Sankyo Selektine Vasten", "definition": "An antilipemic fungal metabolite isolated from cultures of Nocardia autotrophica. It acts as a competitive inhibitor of HMG CoA reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES).\n    ", "id": "MESH:D017035"}
{"mention": "paroxetine", "mention_text": "We report a case of severe citrate toxicity during volunteer donor apheresis platelet collection. The donor was a 40-year-old female, first-time apheresis platelet donor. Past medical history was remarkable for hypertension, hyperlipidemia, and depression. Reported medications included bumetanide, pravastatin, and paroxetine. Thirty minutes from the start of the procedure, the donor noted tingling around the mouth, hands, and feet. She then very rapidly developed acute onset of severe facial and extremity tetany. Empirical treatment with intravenous calcium gluconate was initiated, and muscle contractions slowly subsided over approximately 10 to 15 minutes. The events are consistent with a severe reaction to calcium chelation by sodium citrate anticoagulant resulting in symptomatic systemic hypocalcemia. Upon additional retrospective analysis, it was noted that bumetanide is a loop diuretic that may cause significant hypocalcemia. We conclude that careful screening for medications and underlying conditions predisposing to hypocalcemia is recommended to help prevent severe reactions due to citrate toxicity. Laboratory measurement of pre-procedure serum calcium levels in selected donors may identify cases requiring heightened vigilance. The case also illustrates the importance of maintaining preparedness for managing rare but serious reactions in volunteer apheresis blood donors.", "entity": "Paroxetine", "aliases": "Acetate Paroxetine Anhydrous Hydrochloride Aropax BRL 29060 BRL-29060 BRL29060 FG 7051 FG-7051 FG7051 Hemihydrate Maleate cis-(+)-Isomer cis-(-)-Isomer trans-(+)-Isomer Paxil Seroxat", "definition": "A serotonin uptake inhibitor that is effective in the treatment of depression.\n    ", "id": "MESH:D017374"}
{"mention": "tetany", "mention_text": "We report a case of severe citrate toxicity during volunteer donor apheresis platelet collection. The donor was a 40-year-old female, first-time apheresis platelet donor. Past medical history was remarkable for hypertension, hyperlipidemia, and depression. Reported medications included bumetanide, pravastatin, and paroxetine. Thirty minutes from the start of the procedure, the donor noted tingling around the mouth, hands, and feet. She then very rapidly developed acute onset of severe facial and extremity tetany. Empirical treatment with intravenous calcium gluconate was initiated, and muscle contractions slowly subsided over approximately 10 to 15 minutes. The events are consistent with a severe reaction to calcium chelation by sodium citrate anticoagulant resulting in symptomatic systemic hypocalcemia. Upon additional retrospective analysis, it was noted that bumetanide is a loop diuretic that may cause significant hypocalcemia. We conclude that careful screening for medications and underlying conditions predisposing to hypocalcemia is recommended to help prevent severe reactions due to citrate toxicity. Laboratory measurement of pre-procedure serum calcium levels in selected donors may identify cases requiring heightened vigilance. The case also illustrates the importance of maintaining preparedness for managing rare but serious reactions in volunteer apheresis blood donors.", "entity": "Tetany", "aliases": "Neonatal Tetanies Tetany Spasmophilia Spasmophilias Tetanilla Tetanillas", "definition": "A disorder characterized by muscle twitches, cramps, and carpopedal spasm, and when severe, laryngospasm and seizures. This condition is associated with unstable depolarization of axonal membranes, primarily in the peripheral nervous system. Tetany usually results from HYPOCALCEMIA or reduced serum levels of MAGNESIUM that may be associated with HYPERVENTILATION; HYPOPARATHYROIDISM; RICKETS; UREMIA; or other conditions. (From Adams et al., Principles of Neurology, 6th ed, p1490)\n    ", "id": "MESH:D013746"}
{"mention": "calcium gluconate", "mention_text": "We report a case of severe citrate toxicity during volunteer donor apheresis platelet collection. The donor was a 40-year-old female, first-time apheresis platelet donor. Past medical history was remarkable for hypertension, hyperlipidemia, and depression. Reported medications included bumetanide, pravastatin, and paroxetine. Thirty minutes from the start of the procedure, the donor noted tingling around the mouth, hands, and feet. She then very rapidly developed acute onset of severe facial and extremity tetany. Empirical treatment with intravenous calcium gluconate was initiated, and muscle contractions slowly subsided over approximately 10 to 15 minutes. The events are consistent with a severe reaction to calcium chelation by sodium citrate anticoagulant resulting in symptomatic systemic hypocalcemia. Upon additional retrospective analysis, it was noted that bumetanide is a loop diuretic that may cause significant hypocalcemia. We conclude that careful screening for medications and underlying conditions predisposing to hypocalcemia is recommended to help prevent severe reactions due to citrate toxicity. Laboratory measurement of pre-procedure serum calcium levels in selected donors may identify cases requiring heightened vigilance. The case also illustrates the importance of maintaining preparedness for managing rare but serious reactions in volunteer apheresis blood donors.", "entity": "Calcium Gluconate", "aliases": "3M Brand of Calcium Gluconate Monohydrate Braun CBG Calciofon Calcipot Calcivitol Calglucon Chaix et du Marais Coophavet Ebucin Flopak Plain Fresenius Kabi Glucal Glucobiogen de Lavoisier Gluconato Calc Merial Pharmtech", "definition": "The calcium salt of gluconic acid. The compound has a variety of uses, including its use as a calcium replenisher in hypocalcemic states.\n    ", "id": "MESH:D002125"}
{"mention": "muscle contractions", "mention_text": "We report a case of severe citrate toxicity during volunteer donor apheresis platelet collection. The donor was a 40-year-old female, first-time apheresis platelet donor. Past medical history was remarkable for hypertension, hyperlipidemia, and depression. Reported medications included bumetanide, pravastatin, and paroxetine. Thirty minutes from the start of the procedure, the donor noted tingling around the mouth, hands, and feet. She then very rapidly developed acute onset of severe facial and extremity tetany. Empirical treatment with intravenous calcium gluconate was initiated, and muscle contractions slowly subsided over approximately 10 to 15 minutes. The events are consistent with a severe reaction to calcium chelation by sodium citrate anticoagulant resulting in symptomatic systemic hypocalcemia. Upon additional retrospective analysis, it was noted that bumetanide is a loop diuretic that may cause significant hypocalcemia. We conclude that careful screening for medications and underlying conditions predisposing to hypocalcemia is recommended to help prevent severe reactions due to citrate toxicity. Laboratory measurement of pre-procedure serum calcium levels in selected donors may identify cases requiring heightened vigilance. The case also illustrates the importance of maintaining preparedness for managing rare but serious reactions in volunteer apheresis blood donors.", "entity": "Crisponi syndrome", "aliases": "CNTF Receptor-Related Disorders Cold-Induced Sweating Syndrome Crisponi syndrome Sohar-Crisponi", "definition": "", "id": "MESH:C536214"}
{"mention": "calcium", "mention_text": "We report a case of severe citrate toxicity during volunteer donor apheresis platelet collection. The donor was a 40-year-old female, first-time apheresis platelet donor. Past medical history was remarkable for hypertension, hyperlipidemia, and depression. Reported medications included bumetanide, pravastatin, and paroxetine. Thirty minutes from the start of the procedure, the donor noted tingling around the mouth, hands, and feet. She then very rapidly developed acute onset of severe facial and extremity tetany. Empirical treatment with intravenous calcium gluconate was initiated, and muscle contractions slowly subsided over approximately 10 to 15 minutes. The events are consistent with a severe reaction to calcium chelation by sodium citrate anticoagulant resulting in symptomatic systemic hypocalcemia. Upon additional retrospective analysis, it was noted that bumetanide is a loop diuretic that may cause significant hypocalcemia. We conclude that careful screening for medications and underlying conditions predisposing to hypocalcemia is recommended to help prevent severe reactions due to citrate toxicity. Laboratory measurement of pre-procedure serum calcium levels in selected donors may identify cases requiring heightened vigilance. The case also illustrates the importance of maintaining preparedness for managing rare but serious reactions in volunteer apheresis blood donors.", "entity": "Calcium", "aliases": "Blood Coagulation Factor IV Calcium", "definition": "A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.\n    ", "id": "MESH:D002118"}
{"mention": "sodium citrate", "mention_text": "We report a case of severe citrate toxicity during volunteer donor apheresis platelet collection. The donor was a 40-year-old female, first-time apheresis platelet donor. Past medical history was remarkable for hypertension, hyperlipidemia, and depression. Reported medications included bumetanide, pravastatin, and paroxetine. Thirty minutes from the start of the procedure, the donor noted tingling around the mouth, hands, and feet. She then very rapidly developed acute onset of severe facial and extremity tetany. Empirical treatment with intravenous calcium gluconate was initiated, and muscle contractions slowly subsided over approximately 10 to 15 minutes. The events are consistent with a severe reaction to calcium chelation by sodium citrate anticoagulant resulting in symptomatic systemic hypocalcemia. Upon additional retrospective analysis, it was noted that bumetanide is a loop diuretic that may cause significant hypocalcemia. We conclude that careful screening for medications and underlying conditions predisposing to hypocalcemia is recommended to help prevent severe reactions due to citrate toxicity. Laboratory measurement of pre-procedure serum calcium levels in selected donors may identify cases requiring heightened vigilance. The case also illustrates the importance of maintaining preparedness for managing rare but serious reactions in volunteer apheresis blood donors.", "entity": "sodium citrate", "aliases": "Citra ph anhydrous sodium citrate dihydrate trisodium", "definition": "", "id": "MESH:C102006"}
{"mention": "hypocalcemia", "mention_text": "We report a case of severe citrate toxicity during volunteer donor apheresis platelet collection. The donor was a 40-year-old female, first-time apheresis platelet donor. Past medical history was remarkable for hypertension, hyperlipidemia, and depression. Reported medications included bumetanide, pravastatin, and paroxetine. Thirty minutes from the start of the procedure, the donor noted tingling around the mouth, hands, and feet. She then very rapidly developed acute onset of severe facial and extremity tetany. Empirical treatment with intravenous calcium gluconate was initiated, and muscle contractions slowly subsided over approximately 10 to 15 minutes. The events are consistent with a severe reaction to calcium chelation by sodium citrate anticoagulant resulting in symptomatic systemic hypocalcemia. Upon additional retrospective analysis, it was noted that bumetanide is a loop diuretic that may cause significant hypocalcemia. We conclude that careful screening for medications and underlying conditions predisposing to hypocalcemia is recommended to help prevent severe reactions due to citrate toxicity. Laboratory measurement of pre-procedure serum calcium levels in selected donors may identify cases requiring heightened vigilance. The case also illustrates the importance of maintaining preparedness for managing rare but serious reactions in volunteer apheresis blood donors.", "entity": "Hypocalcemia", "aliases": "Hypocalcemia Hypocalcemias", "definition": "Reduction of the blood calcium below normal. Manifestations include hyperactive deep tendon reflexes, Chvostek's sign, muscle and abdominal cramps, and carpopedal spasm. (Dorland, 27th ed)\n    ", "id": "MESH:D006996"}
{"mention": "loop diuretic", "mention_text": "We report a case of severe citrate toxicity during volunteer donor apheresis platelet collection. The donor was a 40-year-old female, first-time apheresis platelet donor. Past medical history was remarkable for hypertension, hyperlipidemia, and depression. Reported medications included bumetanide, pravastatin, and paroxetine. Thirty minutes from the start of the procedure, the donor noted tingling around the mouth, hands, and feet. She then very rapidly developed acute onset of severe facial and extremity tetany. Empirical treatment with intravenous calcium gluconate was initiated, and muscle contractions slowly subsided over approximately 10 to 15 minutes. The events are consistent with a severe reaction to calcium chelation by sodium citrate anticoagulant resulting in symptomatic systemic hypocalcemia. Upon additional retrospective analysis, it was noted that bumetanide is a loop diuretic that may cause significant hypocalcemia. We conclude that careful screening for medications and underlying conditions predisposing to hypocalcemia is recommended to help prevent severe reactions due to citrate toxicity. Laboratory measurement of pre-procedure serum calcium levels in selected donors may identify cases requiring heightened vigilance. The case also illustrates the importance of maintaining preparedness for managing rare but serious reactions in volunteer apheresis blood donors.", "entity": "Sodium Potassium Chloride Symporter Inhibitors", "aliases": "Bumetanide Sensitive Na K Cl Transporter Inhibitors Na-K-Cl-Transporter Ceiling Diuretics High Loop Na-K-CL Symporter CL Sodium Potassium Chloride Cotransporter", "definition": "Agents that inhibit SODIUM-POTASSIUM-CHLORIDE SYMPORTERS which are concentrated in the thick ascending limb at the junction of the LOOP OF HENLE and KIDNEY TUBULES, DISTAL. They act as DIURETICS. Excess use is associated with HYPOKALEMIA and HYPERGLYCEMIA.\n    ", "id": "MESH:D049994"}
{"mention": "Proteinuria", "mention_text": "Proteinuria after conversion to sirolimus in renal transplant recipients.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "sirolimus", "mention_text": "Proteinuria after conversion to sirolimus in renal transplant recipients.", "entity": "Sirolimus", "aliases": "AY 22 989 22-989 22989 I 2190A I-2190A I2190A Rapamune Rapamycin Sirolimus Wyeth Brand of", "definition": "A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.\n    ", "id": "MESH:D020123"}
{"mention": "Sirolimus", "mention_text": "Sirolimus (SRL) is a new, potent immunosuppressive agent. More recently, proteinuria has been reported as a consequence of sirolimus therapy, although the mechanism has remained unclear. We retrospectively examined the records of 25 renal transplant patients, who developed or displayed increased proteinuria after SRL conversion. The patient cohort (14 men, 11 women) was treated with SRL as conversion therapy, due to chronic allograft nephropathy (CAN) (n = 15) neoplasia (n = 8); Kaposi's sarcoma, Four skin cancers, One intestinal tumors, One renal cell carsinom) or BK virus nephropathy (n = 2). SRL was started at a mean of 78 +/- 42 (15 to 163) months after transplantation. Mean follow-up on SRL therapy was 20 +/- 12 (6 to 43) months. Proteinuria increased from 0.445 (0 to 1.5) g/d before conversion to 3.2 g/dL (0.2 to 12) after conversion (P = 0.001). Before conversion 8 (32%) patients had no proteinuria, whereas afterwards all patients had proteinuria. In 28% of patients proteinuria remained unchanged, whereas it increased in 68% of patients. In 40% it increased by more than 100%. Twenty-eight percent of patients showed increased proteinuria to the nephrotic range. Biopsies performed in five patients revealed new pathological changes: One membranoproliferative glomerulopathy and interstitial nephritis. These patients showed persistently good graft function. Serum creatinine values did not change significantly: 1.98 +/- 0.8 mg/dL before SRL therapy and 2.53 +/- 1.9 mg/dL at last follow-up (P = .14). Five grafts were lost and the patients returned to dialysis. Five patients displayed CAN and Kaposi's sarcoma. Mean urinary protein of patients who returned to dialysis was 1.26 (0.5 to 3.5) g/d before and 4.7 (3 to 12) g/d after conversion (P = .01). Mean serum creatinine level before conversion was 2.21 mg/dL and thereafter, 4.93 mg/dL (P = .02). Heavy proteinuria was common after the use of SRL as rescue therapy for renal transplantation. Therefore, conversion should be considered for patients who have not developed advanced CAN and proteinuria. The possibility of de novo glomerular pathology under SRL treatment requires further investigation by renal biopsy.", "entity": "Sirolimus", "aliases": "AY 22 989 22-989 22989 I 2190A I-2190A I2190A Rapamune Rapamycin Sirolimus Wyeth Brand of", "definition": "A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.\n    ", "id": "MESH:D020123"}
{"mention": "SRL", "mention_text": "Sirolimus (SRL) is a new, potent immunosuppressive agent. More recently, proteinuria has been reported as a consequence of sirolimus therapy, although the mechanism has remained unclear. We retrospectively examined the records of 25 renal transplant patients, who developed or displayed increased proteinuria after SRL conversion. The patient cohort (14 men, 11 women) was treated with SRL as conversion therapy, due to chronic allograft nephropathy (CAN) (n = 15) neoplasia (n = 8); Kaposi's sarcoma, Four skin cancers, One intestinal tumors, One renal cell carsinom) or BK virus nephropathy (n = 2). SRL was started at a mean of 78 +/- 42 (15 to 163) months after transplantation. Mean follow-up on SRL therapy was 20 +/- 12 (6 to 43) months. Proteinuria increased from 0.445 (0 to 1.5) g/d before conversion to 3.2 g/dL (0.2 to 12) after conversion (P = 0.001). Before conversion 8 (32%) patients had no proteinuria, whereas afterwards all patients had proteinuria. In 28% of patients proteinuria remained unchanged, whereas it increased in 68% of patients. In 40% it increased by more than 100%. Twenty-eight percent of patients showed increased proteinuria to the nephrotic range. Biopsies performed in five patients revealed new pathological changes: One membranoproliferative glomerulopathy and interstitial nephritis. These patients showed persistently good graft function. Serum creatinine values did not change significantly: 1.98 +/- 0.8 mg/dL before SRL therapy and 2.53 +/- 1.9 mg/dL at last follow-up (P = .14). Five grafts were lost and the patients returned to dialysis. Five patients displayed CAN and Kaposi's sarcoma. Mean urinary protein of patients who returned to dialysis was 1.26 (0.5 to 3.5) g/d before and 4.7 (3 to 12) g/d after conversion (P = .01). Mean serum creatinine level before conversion was 2.21 mg/dL and thereafter, 4.93 mg/dL (P = .02). Heavy proteinuria was common after the use of SRL as rescue therapy for renal transplantation. Therefore, conversion should be considered for patients who have not developed advanced CAN and proteinuria. The possibility of de novo glomerular pathology under SRL treatment requires further investigation by renal biopsy.", "entity": "Sirolimus", "aliases": "AY 22 989 22-989 22989 I 2190A I-2190A I2190A Rapamune Rapamycin Sirolimus Wyeth Brand of", "definition": "A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.\n    ", "id": "MESH:D020123"}
{"mention": "proteinuria", "mention_text": "Sirolimus (SRL) is a new, potent immunosuppressive agent. More recently, proteinuria has been reported as a consequence of sirolimus therapy, although the mechanism has remained unclear. We retrospectively examined the records of 25 renal transplant patients, who developed or displayed increased proteinuria after SRL conversion. The patient cohort (14 men, 11 women) was treated with SRL as conversion therapy, due to chronic allograft nephropathy (CAN) (n = 15) neoplasia (n = 8); Kaposi's sarcoma, Four skin cancers, One intestinal tumors, One renal cell carsinom) or BK virus nephropathy (n = 2). SRL was started at a mean of 78 +/- 42 (15 to 163) months after transplantation. Mean follow-up on SRL therapy was 20 +/- 12 (6 to 43) months. Proteinuria increased from 0.445 (0 to 1.5) g/d before conversion to 3.2 g/dL (0.2 to 12) after conversion (P = 0.001). Before conversion 8 (32%) patients had no proteinuria, whereas afterwards all patients had proteinuria. In 28% of patients proteinuria remained unchanged, whereas it increased in 68% of patients. In 40% it increased by more than 100%. Twenty-eight percent of patients showed increased proteinuria to the nephrotic range. Biopsies performed in five patients revealed new pathological changes: One membranoproliferative glomerulopathy and interstitial nephritis. These patients showed persistently good graft function. Serum creatinine values did not change significantly: 1.98 +/- 0.8 mg/dL before SRL therapy and 2.53 +/- 1.9 mg/dL at last follow-up (P = .14). Five grafts were lost and the patients returned to dialysis. Five patients displayed CAN and Kaposi's sarcoma. Mean urinary protein of patients who returned to dialysis was 1.26 (0.5 to 3.5) g/d before and 4.7 (3 to 12) g/d after conversion (P = .01). Mean serum creatinine level before conversion was 2.21 mg/dL and thereafter, 4.93 mg/dL (P = .02). Heavy proteinuria was common after the use of SRL as rescue therapy for renal transplantation. Therefore, conversion should be considered for patients who have not developed advanced CAN and proteinuria. The possibility of de novo glomerular pathology under SRL treatment requires further investigation by renal biopsy.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "sirolimus", "mention_text": "Sirolimus (SRL) is a new, potent immunosuppressive agent. More recently, proteinuria has been reported as a consequence of sirolimus therapy, although the mechanism has remained unclear. We retrospectively examined the records of 25 renal transplant patients, who developed or displayed increased proteinuria after SRL conversion. The patient cohort (14 men, 11 women) was treated with SRL as conversion therapy, due to chronic allograft nephropathy (CAN) (n = 15) neoplasia (n = 8); Kaposi's sarcoma, Four skin cancers, One intestinal tumors, One renal cell carsinom) or BK virus nephropathy (n = 2). SRL was started at a mean of 78 +/- 42 (15 to 163) months after transplantation. Mean follow-up on SRL therapy was 20 +/- 12 (6 to 43) months. Proteinuria increased from 0.445 (0 to 1.5) g/d before conversion to 3.2 g/dL (0.2 to 12) after conversion (P = 0.001). Before conversion 8 (32%) patients had no proteinuria, whereas afterwards all patients had proteinuria. In 28% of patients proteinuria remained unchanged, whereas it increased in 68% of patients. In 40% it increased by more than 100%. Twenty-eight percent of patients showed increased proteinuria to the nephrotic range. Biopsies performed in five patients revealed new pathological changes: One membranoproliferative glomerulopathy and interstitial nephritis. These patients showed persistently good graft function. Serum creatinine values did not change significantly: 1.98 +/- 0.8 mg/dL before SRL therapy and 2.53 +/- 1.9 mg/dL at last follow-up (P = .14). Five grafts were lost and the patients returned to dialysis. Five patients displayed CAN and Kaposi's sarcoma. Mean urinary protein of patients who returned to dialysis was 1.26 (0.5 to 3.5) g/d before and 4.7 (3 to 12) g/d after conversion (P = .01). Mean serum creatinine level before conversion was 2.21 mg/dL and thereafter, 4.93 mg/dL (P = .02). Heavy proteinuria was common after the use of SRL as rescue therapy for renal transplantation. Therefore, conversion should be considered for patients who have not developed advanced CAN and proteinuria. The possibility of de novo glomerular pathology under SRL treatment requires further investigation by renal biopsy.", "entity": "Sirolimus", "aliases": "AY 22 989 22-989 22989 I 2190A I-2190A I2190A Rapamune Rapamycin Sirolimus Wyeth Brand of", "definition": "A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.\n    ", "id": "MESH:D020123"}
{"mention": "chronic allograft nephropathy", "mention_text": "Sirolimus (SRL) is a new, potent immunosuppressive agent. More recently, proteinuria has been reported as a consequence of sirolimus therapy, although the mechanism has remained unclear. We retrospectively examined the records of 25 renal transplant patients, who developed or displayed increased proteinuria after SRL conversion. The patient cohort (14 men, 11 women) was treated with SRL as conversion therapy, due to chronic allograft nephropathy (CAN) (n = 15) neoplasia (n = 8); Kaposi's sarcoma, Four skin cancers, One intestinal tumors, One renal cell carsinom) or BK virus nephropathy (n = 2). SRL was started at a mean of 78 +/- 42 (15 to 163) months after transplantation. Mean follow-up on SRL therapy was 20 +/- 12 (6 to 43) months. Proteinuria increased from 0.445 (0 to 1.5) g/d before conversion to 3.2 g/dL (0.2 to 12) after conversion (P = 0.001). Before conversion 8 (32%) patients had no proteinuria, whereas afterwards all patients had proteinuria. In 28% of patients proteinuria remained unchanged, whereas it increased in 68% of patients. In 40% it increased by more than 100%. Twenty-eight percent of patients showed increased proteinuria to the nephrotic range. Biopsies performed in five patients revealed new pathological changes: One membranoproliferative glomerulopathy and interstitial nephritis. These patients showed persistently good graft function. Serum creatinine values did not change significantly: 1.98 +/- 0.8 mg/dL before SRL therapy and 2.53 +/- 1.9 mg/dL at last follow-up (P = .14). Five grafts were lost and the patients returned to dialysis. Five patients displayed CAN and Kaposi's sarcoma. Mean urinary protein of patients who returned to dialysis was 1.26 (0.5 to 3.5) g/d before and 4.7 (3 to 12) g/d after conversion (P = .01). Mean serum creatinine level before conversion was 2.21 mg/dL and thereafter, 4.93 mg/dL (P = .02). Heavy proteinuria was common after the use of SRL as rescue therapy for renal transplantation. Therefore, conversion should be considered for patients who have not developed advanced CAN and proteinuria. The possibility of de novo glomerular pathology under SRL treatment requires further investigation by renal biopsy.", "entity": "Renal Insufficiency, Chronic", "aliases": "Chronic Kidney Disease Diseases Insufficiencies Insufficiency Renal", "definition": "Conditions in which the KIDNEYS perform below the normal level for more than three months. Chronic kidney insufficiency is classified by five stages according to the decline in GLOMERULAR FILTRATION RATE and the degree of kidney damage (as measured by the level of PROTEINURIA). The most severe form is the end-stage renal disease (CHRONIC KIDNEY FAILURE). (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002)\n    ", "id": "MESH:D051436"}
{"mention": "CAN", "mention_text": "Sirolimus (SRL) is a new, potent immunosuppressive agent. More recently, proteinuria has been reported as a consequence of sirolimus therapy, although the mechanism has remained unclear. We retrospectively examined the records of 25 renal transplant patients, who developed or displayed increased proteinuria after SRL conversion. The patient cohort (14 men, 11 women) was treated with SRL as conversion therapy, due to chronic allograft nephropathy (CAN) (n = 15) neoplasia (n = 8); Kaposi's sarcoma, Four skin cancers, One intestinal tumors, One renal cell carsinom) or BK virus nephropathy (n = 2). SRL was started at a mean of 78 +/- 42 (15 to 163) months after transplantation. Mean follow-up on SRL therapy was 20 +/- 12 (6 to 43) months. Proteinuria increased from 0.445 (0 to 1.5) g/d before conversion to 3.2 g/dL (0.2 to 12) after conversion (P = 0.001). Before conversion 8 (32%) patients had no proteinuria, whereas afterwards all patients had proteinuria. In 28% of patients proteinuria remained unchanged, whereas it increased in 68% of patients. In 40% it increased by more than 100%. Twenty-eight percent of patients showed increased proteinuria to the nephrotic range. Biopsies performed in five patients revealed new pathological changes: One membranoproliferative glomerulopathy and interstitial nephritis. These patients showed persistently good graft function. Serum creatinine values did not change significantly: 1.98 +/- 0.8 mg/dL before SRL therapy and 2.53 +/- 1.9 mg/dL at last follow-up (P = .14). Five grafts were lost and the patients returned to dialysis. Five patients displayed CAN and Kaposi's sarcoma. Mean urinary protein of patients who returned to dialysis was 1.26 (0.5 to 3.5) g/d before and 4.7 (3 to 12) g/d after conversion (P = .01). Mean serum creatinine level before conversion was 2.21 mg/dL and thereafter, 4.93 mg/dL (P = .02). Heavy proteinuria was common after the use of SRL as rescue therapy for renal transplantation. Therefore, conversion should be considered for patients who have not developed advanced CAN and proteinuria. The possibility of de novo glomerular pathology under SRL treatment requires further investigation by renal biopsy.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "neoplasia", "mention_text": "Sirolimus (SRL) is a new, potent immunosuppressive agent. More recently, proteinuria has been reported as a consequence of sirolimus therapy, although the mechanism has remained unclear. We retrospectively examined the records of 25 renal transplant patients, who developed or displayed increased proteinuria after SRL conversion. The patient cohort (14 men, 11 women) was treated with SRL as conversion therapy, due to chronic allograft nephropathy (CAN) (n = 15) neoplasia (n = 8); Kaposi's sarcoma, Four skin cancers, One intestinal tumors, One renal cell carsinom) or BK virus nephropathy (n = 2). SRL was started at a mean of 78 +/- 42 (15 to 163) months after transplantation. Mean follow-up on SRL therapy was 20 +/- 12 (6 to 43) months. Proteinuria increased from 0.445 (0 to 1.5) g/d before conversion to 3.2 g/dL (0.2 to 12) after conversion (P = 0.001). Before conversion 8 (32%) patients had no proteinuria, whereas afterwards all patients had proteinuria. In 28% of patients proteinuria remained unchanged, whereas it increased in 68% of patients. In 40% it increased by more than 100%. Twenty-eight percent of patients showed increased proteinuria to the nephrotic range. Biopsies performed in five patients revealed new pathological changes: One membranoproliferative glomerulopathy and interstitial nephritis. These patients showed persistently good graft function. Serum creatinine values did not change significantly: 1.98 +/- 0.8 mg/dL before SRL therapy and 2.53 +/- 1.9 mg/dL at last follow-up (P = .14). Five grafts were lost and the patients returned to dialysis. Five patients displayed CAN and Kaposi's sarcoma. Mean urinary protein of patients who returned to dialysis was 1.26 (0.5 to 3.5) g/d before and 4.7 (3 to 12) g/d after conversion (P = .01). Mean serum creatinine level before conversion was 2.21 mg/dL and thereafter, 4.93 mg/dL (P = .02). Heavy proteinuria was common after the use of SRL as rescue therapy for renal transplantation. Therefore, conversion should be considered for patients who have not developed advanced CAN and proteinuria. The possibility of de novo glomerular pathology under SRL treatment requires further investigation by renal biopsy.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "Kaposi's sarcoma", "mention_text": "Sirolimus (SRL) is a new, potent immunosuppressive agent. More recently, proteinuria has been reported as a consequence of sirolimus therapy, although the mechanism has remained unclear. We retrospectively examined the records of 25 renal transplant patients, who developed or displayed increased proteinuria after SRL conversion. The patient cohort (14 men, 11 women) was treated with SRL as conversion therapy, due to chronic allograft nephropathy (CAN) (n = 15) neoplasia (n = 8); Kaposi's sarcoma, Four skin cancers, One intestinal tumors, One renal cell carsinom) or BK virus nephropathy (n = 2). SRL was started at a mean of 78 +/- 42 (15 to 163) months after transplantation. Mean follow-up on SRL therapy was 20 +/- 12 (6 to 43) months. Proteinuria increased from 0.445 (0 to 1.5) g/d before conversion to 3.2 g/dL (0.2 to 12) after conversion (P = 0.001). Before conversion 8 (32%) patients had no proteinuria, whereas afterwards all patients had proteinuria. In 28% of patients proteinuria remained unchanged, whereas it increased in 68% of patients. In 40% it increased by more than 100%. Twenty-eight percent of patients showed increased proteinuria to the nephrotic range. Biopsies performed in five patients revealed new pathological changes: One membranoproliferative glomerulopathy and interstitial nephritis. These patients showed persistently good graft function. Serum creatinine values did not change significantly: 1.98 +/- 0.8 mg/dL before SRL therapy and 2.53 +/- 1.9 mg/dL at last follow-up (P = .14). Five grafts were lost and the patients returned to dialysis. Five patients displayed CAN and Kaposi's sarcoma. Mean urinary protein of patients who returned to dialysis was 1.26 (0.5 to 3.5) g/d before and 4.7 (3 to 12) g/d after conversion (P = .01). Mean serum creatinine level before conversion was 2.21 mg/dL and thereafter, 4.93 mg/dL (P = .02). Heavy proteinuria was common after the use of SRL as rescue therapy for renal transplantation. Therefore, conversion should be considered for patients who have not developed advanced CAN and proteinuria. The possibility of de novo glomerular pathology under SRL treatment requires further investigation by renal biopsy.", "entity": "Sarcoma, Kaposi", "aliases": "Kaposi Sarcoma Kaposi's Kaposis Multiple Idiopathic Pigmented Hemangiosarcoma", "definition": "A multicentric, malignant neoplastic vascular proliferation characterized by the development of bluish-red cutaneous nodules, usually on the lower extremities, most often on the toes or feet, and slowly increasing in size and number and spreading to more proximal areas. The tumors have endothelium-lined channels and vascular spaces admixed with variably sized aggregates of spindle-shaped cells, and often remain confined to the skin and subcutaneous tissue, but widespread visceral involvement may occur. Kaposi's sarcoma occurs spontaneously in Jewish and Italian males in Europe and the United States. An aggressive variant in young children is endemic in some areas of Africa. A third form occurs in about 0.04% of kidney transplant patients. There is also a high incidence in AIDS patients. (From Dorland, 27th ed & Holland et al., Cancer Medicine, 3d ed, pp2105-7) HHV-8 is the suspected cause.\n    ", "id": "MESH:D012514"}
{"mention": "skin cancers", "mention_text": "Sirolimus (SRL) is a new, potent immunosuppressive agent. More recently, proteinuria has been reported as a consequence of sirolimus therapy, although the mechanism has remained unclear. We retrospectively examined the records of 25 renal transplant patients, who developed or displayed increased proteinuria after SRL conversion. The patient cohort (14 men, 11 women) was treated with SRL as conversion therapy, due to chronic allograft nephropathy (CAN) (n = 15) neoplasia (n = 8); Kaposi's sarcoma, Four skin cancers, One intestinal tumors, One renal cell carsinom) or BK virus nephropathy (n = 2). SRL was started at a mean of 78 +/- 42 (15 to 163) months after transplantation. Mean follow-up on SRL therapy was 20 +/- 12 (6 to 43) months. Proteinuria increased from 0.445 (0 to 1.5) g/d before conversion to 3.2 g/dL (0.2 to 12) after conversion (P = 0.001). Before conversion 8 (32%) patients had no proteinuria, whereas afterwards all patients had proteinuria. In 28% of patients proteinuria remained unchanged, whereas it increased in 68% of patients. In 40% it increased by more than 100%. Twenty-eight percent of patients showed increased proteinuria to the nephrotic range. Biopsies performed in five patients revealed new pathological changes: One membranoproliferative glomerulopathy and interstitial nephritis. These patients showed persistently good graft function. Serum creatinine values did not change significantly: 1.98 +/- 0.8 mg/dL before SRL therapy and 2.53 +/- 1.9 mg/dL at last follow-up (P = .14). Five grafts were lost and the patients returned to dialysis. Five patients displayed CAN and Kaposi's sarcoma. Mean urinary protein of patients who returned to dialysis was 1.26 (0.5 to 3.5) g/d before and 4.7 (3 to 12) g/d after conversion (P = .01). Mean serum creatinine level before conversion was 2.21 mg/dL and thereafter, 4.93 mg/dL (P = .02). Heavy proteinuria was common after the use of SRL as rescue therapy for renal transplantation. Therefore, conversion should be considered for patients who have not developed advanced CAN and proteinuria. The possibility of de novo glomerular pathology under SRL treatment requires further investigation by renal biopsy.", "entity": "Skin Neoplasms", "aliases": "Cancer of Skin the Cancers Neoplasm Neoplasms", "definition": "Tumors or cancer of the SKIN.\n    ", "id": "MESH:D012878"}
{"mention": "intestinal tumors", "mention_text": "Sirolimus (SRL) is a new, potent immunosuppressive agent. More recently, proteinuria has been reported as a consequence of sirolimus therapy, although the mechanism has remained unclear. We retrospectively examined the records of 25 renal transplant patients, who developed or displayed increased proteinuria after SRL conversion. The patient cohort (14 men, 11 women) was treated with SRL as conversion therapy, due to chronic allograft nephropathy (CAN) (n = 15) neoplasia (n = 8); Kaposi's sarcoma, Four skin cancers, One intestinal tumors, One renal cell carsinom) or BK virus nephropathy (n = 2). SRL was started at a mean of 78 +/- 42 (15 to 163) months after transplantation. Mean follow-up on SRL therapy was 20 +/- 12 (6 to 43) months. Proteinuria increased from 0.445 (0 to 1.5) g/d before conversion to 3.2 g/dL (0.2 to 12) after conversion (P = 0.001). Before conversion 8 (32%) patients had no proteinuria, whereas afterwards all patients had proteinuria. In 28% of patients proteinuria remained unchanged, whereas it increased in 68% of patients. In 40% it increased by more than 100%. Twenty-eight percent of patients showed increased proteinuria to the nephrotic range. Biopsies performed in five patients revealed new pathological changes: One membranoproliferative glomerulopathy and interstitial nephritis. These patients showed persistently good graft function. Serum creatinine values did not change significantly: 1.98 +/- 0.8 mg/dL before SRL therapy and 2.53 +/- 1.9 mg/dL at last follow-up (P = .14). Five grafts were lost and the patients returned to dialysis. Five patients displayed CAN and Kaposi's sarcoma. Mean urinary protein of patients who returned to dialysis was 1.26 (0.5 to 3.5) g/d before and 4.7 (3 to 12) g/d after conversion (P = .01). Mean serum creatinine level before conversion was 2.21 mg/dL and thereafter, 4.93 mg/dL (P = .02). Heavy proteinuria was common after the use of SRL as rescue therapy for renal transplantation. Therefore, conversion should be considered for patients who have not developed advanced CAN and proteinuria. The possibility of de novo glomerular pathology under SRL treatment requires further investigation by renal biopsy.", "entity": "Intestinal Neoplasms", "aliases": "Cancer of Intestines the Intestinal Cancers Neoplasm Neoplasms", "definition": "Tumors or cancer of the INTESTINES.\n    ", "id": "MESH:D007414"}
{"mention": "renal cell carsinom", "mention_text": "Sirolimus (SRL) is a new, potent immunosuppressive agent. More recently, proteinuria has been reported as a consequence of sirolimus therapy, although the mechanism has remained unclear. We retrospectively examined the records of 25 renal transplant patients, who developed or displayed increased proteinuria after SRL conversion. The patient cohort (14 men, 11 women) was treated with SRL as conversion therapy, due to chronic allograft nephropathy (CAN) (n = 15) neoplasia (n = 8); Kaposi's sarcoma, Four skin cancers, One intestinal tumors, One renal cell carsinom) or BK virus nephropathy (n = 2). SRL was started at a mean of 78 +/- 42 (15 to 163) months after transplantation. Mean follow-up on SRL therapy was 20 +/- 12 (6 to 43) months. Proteinuria increased from 0.445 (0 to 1.5) g/d before conversion to 3.2 g/dL (0.2 to 12) after conversion (P = 0.001). Before conversion 8 (32%) patients had no proteinuria, whereas afterwards all patients had proteinuria. In 28% of patients proteinuria remained unchanged, whereas it increased in 68% of patients. In 40% it increased by more than 100%. Twenty-eight percent of patients showed increased proteinuria to the nephrotic range. Biopsies performed in five patients revealed new pathological changes: One membranoproliferative glomerulopathy and interstitial nephritis. These patients showed persistently good graft function. Serum creatinine values did not change significantly: 1.98 +/- 0.8 mg/dL before SRL therapy and 2.53 +/- 1.9 mg/dL at last follow-up (P = .14). Five grafts were lost and the patients returned to dialysis. Five patients displayed CAN and Kaposi's sarcoma. Mean urinary protein of patients who returned to dialysis was 1.26 (0.5 to 3.5) g/d before and 4.7 (3 to 12) g/d after conversion (P = .01). Mean serum creatinine level before conversion was 2.21 mg/dL and thereafter, 4.93 mg/dL (P = .02). Heavy proteinuria was common after the use of SRL as rescue therapy for renal transplantation. Therefore, conversion should be considered for patients who have not developed advanced CAN and proteinuria. The possibility of de novo glomerular pathology under SRL treatment requires further investigation by renal biopsy.", "entity": "Carcinoma, Renal Cell", "aliases": "Adenocarcinoma Of Kidney Renal Cell Adenocarcinomas Cancer Cancers Carcinoma Collecting Duct (Kidney) Hypernephroid Nephroid Carcinomas Chromophil Chromophobe Clear of the Grawitz Tumor Hypernephroma Hypernephromas Papillary Sarcomatoid", "definition": "A heterogeneous group of sporadic or hereditary carcinoma derived from cells of the KIDNEYS. There are several subtypes including the clear cells, the papillary, the chromophobe, the collecting duct, the spindle cells (sarcomatoid), or mixed cell-type carcinoma.\n    ", "id": "MESH:D002292"}
{"mention": "nephropathy", "mention_text": "Sirolimus (SRL) is a new, potent immunosuppressive agent. More recently, proteinuria has been reported as a consequence of sirolimus therapy, although the mechanism has remained unclear. We retrospectively examined the records of 25 renal transplant patients, who developed or displayed increased proteinuria after SRL conversion. The patient cohort (14 men, 11 women) was treated with SRL as conversion therapy, due to chronic allograft nephropathy (CAN) (n = 15) neoplasia (n = 8); Kaposi's sarcoma, Four skin cancers, One intestinal tumors, One renal cell carsinom) or BK virus nephropathy (n = 2). SRL was started at a mean of 78 +/- 42 (15 to 163) months after transplantation. Mean follow-up on SRL therapy was 20 +/- 12 (6 to 43) months. Proteinuria increased from 0.445 (0 to 1.5) g/d before conversion to 3.2 g/dL (0.2 to 12) after conversion (P = 0.001). Before conversion 8 (32%) patients had no proteinuria, whereas afterwards all patients had proteinuria. In 28% of patients proteinuria remained unchanged, whereas it increased in 68% of patients. In 40% it increased by more than 100%. Twenty-eight percent of patients showed increased proteinuria to the nephrotic range. Biopsies performed in five patients revealed new pathological changes: One membranoproliferative glomerulopathy and interstitial nephritis. These patients showed persistently good graft function. Serum creatinine values did not change significantly: 1.98 +/- 0.8 mg/dL before SRL therapy and 2.53 +/- 1.9 mg/dL at last follow-up (P = .14). Five grafts were lost and the patients returned to dialysis. Five patients displayed CAN and Kaposi's sarcoma. Mean urinary protein of patients who returned to dialysis was 1.26 (0.5 to 3.5) g/d before and 4.7 (3 to 12) g/d after conversion (P = .01). Mean serum creatinine level before conversion was 2.21 mg/dL and thereafter, 4.93 mg/dL (P = .02). Heavy proteinuria was common after the use of SRL as rescue therapy for renal transplantation. Therefore, conversion should be considered for patients who have not developed advanced CAN and proteinuria. The possibility of de novo glomerular pathology under SRL treatment requires further investigation by renal biopsy.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "Proteinuria", "mention_text": "Sirolimus (SRL) is a new, potent immunosuppressive agent. More recently, proteinuria has been reported as a consequence of sirolimus therapy, although the mechanism has remained unclear. We retrospectively examined the records of 25 renal transplant patients, who developed or displayed increased proteinuria after SRL conversion. The patient cohort (14 men, 11 women) was treated with SRL as conversion therapy, due to chronic allograft nephropathy (CAN) (n = 15) neoplasia (n = 8); Kaposi's sarcoma, Four skin cancers, One intestinal tumors, One renal cell carsinom) or BK virus nephropathy (n = 2). SRL was started at a mean of 78 +/- 42 (15 to 163) months after transplantation. Mean follow-up on SRL therapy was 20 +/- 12 (6 to 43) months. Proteinuria increased from 0.445 (0 to 1.5) g/d before conversion to 3.2 g/dL (0.2 to 12) after conversion (P = 0.001). Before conversion 8 (32%) patients had no proteinuria, whereas afterwards all patients had proteinuria. In 28% of patients proteinuria remained unchanged, whereas it increased in 68% of patients. In 40% it increased by more than 100%. Twenty-eight percent of patients showed increased proteinuria to the nephrotic range. Biopsies performed in five patients revealed new pathological changes: One membranoproliferative glomerulopathy and interstitial nephritis. These patients showed persistently good graft function. Serum creatinine values did not change significantly: 1.98 +/- 0.8 mg/dL before SRL therapy and 2.53 +/- 1.9 mg/dL at last follow-up (P = .14). Five grafts were lost and the patients returned to dialysis. Five patients displayed CAN and Kaposi's sarcoma. Mean urinary protein of patients who returned to dialysis was 1.26 (0.5 to 3.5) g/d before and 4.7 (3 to 12) g/d after conversion (P = .01). Mean serum creatinine level before conversion was 2.21 mg/dL and thereafter, 4.93 mg/dL (P = .02). Heavy proteinuria was common after the use of SRL as rescue therapy for renal transplantation. Therefore, conversion should be considered for patients who have not developed advanced CAN and proteinuria. The possibility of de novo glomerular pathology under SRL treatment requires further investigation by renal biopsy.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "nephrotic", "mention_text": "Sirolimus (SRL) is a new, potent immunosuppressive agent. More recently, proteinuria has been reported as a consequence of sirolimus therapy, although the mechanism has remained unclear. We retrospectively examined the records of 25 renal transplant patients, who developed or displayed increased proteinuria after SRL conversion. The patient cohort (14 men, 11 women) was treated with SRL as conversion therapy, due to chronic allograft nephropathy (CAN) (n = 15) neoplasia (n = 8); Kaposi's sarcoma, Four skin cancers, One intestinal tumors, One renal cell carsinom) or BK virus nephropathy (n = 2). SRL was started at a mean of 78 +/- 42 (15 to 163) months after transplantation. Mean follow-up on SRL therapy was 20 +/- 12 (6 to 43) months. Proteinuria increased from 0.445 (0 to 1.5) g/d before conversion to 3.2 g/dL (0.2 to 12) after conversion (P = 0.001). Before conversion 8 (32%) patients had no proteinuria, whereas afterwards all patients had proteinuria. In 28% of patients proteinuria remained unchanged, whereas it increased in 68% of patients. In 40% it increased by more than 100%. Twenty-eight percent of patients showed increased proteinuria to the nephrotic range. Biopsies performed in five patients revealed new pathological changes: One membranoproliferative glomerulopathy and interstitial nephritis. These patients showed persistently good graft function. Serum creatinine values did not change significantly: 1.98 +/- 0.8 mg/dL before SRL therapy and 2.53 +/- 1.9 mg/dL at last follow-up (P = .14). Five grafts were lost and the patients returned to dialysis. Five patients displayed CAN and Kaposi's sarcoma. Mean urinary protein of patients who returned to dialysis was 1.26 (0.5 to 3.5) g/d before and 4.7 (3 to 12) g/d after conversion (P = .01). Mean serum creatinine level before conversion was 2.21 mg/dL and thereafter, 4.93 mg/dL (P = .02). Heavy proteinuria was common after the use of SRL as rescue therapy for renal transplantation. Therefore, conversion should be considered for patients who have not developed advanced CAN and proteinuria. The possibility of de novo glomerular pathology under SRL treatment requires further investigation by renal biopsy.", "entity": "Nephrotic Syndrome", "aliases": "Nephrotic Syndrome Syndromes", "definition": "A condition characterized by severe PROTEINURIA, greater than 3.5 g/day in an average adult. The substantial loss of protein in the urine results in complications such as HYPOPROTEINEMIA; generalized EDEMA; HYPERTENSION; and HYPERLIPIDEMIAS. Diseases associated with nephrotic syndrome generally cause chronic kidney dysfunction.\n    ", "id": "MESH:D009404"}
{"mention": "membranoproliferative glomerulopathy", "mention_text": "Sirolimus (SRL) is a new, potent immunosuppressive agent. More recently, proteinuria has been reported as a consequence of sirolimus therapy, although the mechanism has remained unclear. We retrospectively examined the records of 25 renal transplant patients, who developed or displayed increased proteinuria after SRL conversion. The patient cohort (14 men, 11 women) was treated with SRL as conversion therapy, due to chronic allograft nephropathy (CAN) (n = 15) neoplasia (n = 8); Kaposi's sarcoma, Four skin cancers, One intestinal tumors, One renal cell carsinom) or BK virus nephropathy (n = 2). SRL was started at a mean of 78 +/- 42 (15 to 163) months after transplantation. Mean follow-up on SRL therapy was 20 +/- 12 (6 to 43) months. Proteinuria increased from 0.445 (0 to 1.5) g/d before conversion to 3.2 g/dL (0.2 to 12) after conversion (P = 0.001). Before conversion 8 (32%) patients had no proteinuria, whereas afterwards all patients had proteinuria. In 28% of patients proteinuria remained unchanged, whereas it increased in 68% of patients. In 40% it increased by more than 100%. Twenty-eight percent of patients showed increased proteinuria to the nephrotic range. Biopsies performed in five patients revealed new pathological changes: One membranoproliferative glomerulopathy and interstitial nephritis. These patients showed persistently good graft function. Serum creatinine values did not change significantly: 1.98 +/- 0.8 mg/dL before SRL therapy and 2.53 +/- 1.9 mg/dL at last follow-up (P = .14). Five grafts were lost and the patients returned to dialysis. Five patients displayed CAN and Kaposi's sarcoma. Mean urinary protein of patients who returned to dialysis was 1.26 (0.5 to 3.5) g/d before and 4.7 (3 to 12) g/d after conversion (P = .01). Mean serum creatinine level before conversion was 2.21 mg/dL and thereafter, 4.93 mg/dL (P = .02). Heavy proteinuria was common after the use of SRL as rescue therapy for renal transplantation. Therefore, conversion should be considered for patients who have not developed advanced CAN and proteinuria. The possibility of de novo glomerular pathology under SRL treatment requires further investigation by renal biopsy.", "entity": "Glomerulonephritis, Membranous", "aliases": "Extramembranous Glomerulopathy Glomerulonephritides Idiopathic Membranous Glomerulonephritis Glomerulonephropathy Heymann Nephritis Nephropathy", "definition": "A type of glomerulonephritis that is characterized by the accumulation of immune deposits (COMPLEMENT MEMBRANE ATTACK COMPLEX) on the outer aspect of the GLOMERULAR BASEMENT MEMBRANE. It progresses from subepithelial dense deposits, to basement membrane reaction and eventual thickening of the basement membrane.\n    ", "id": "MESH:D015433"}
{"mention": "interstitial nephritis", "mention_text": "Sirolimus (SRL) is a new, potent immunosuppressive agent. More recently, proteinuria has been reported as a consequence of sirolimus therapy, although the mechanism has remained unclear. We retrospectively examined the records of 25 renal transplant patients, who developed or displayed increased proteinuria after SRL conversion. The patient cohort (14 men, 11 women) was treated with SRL as conversion therapy, due to chronic allograft nephropathy (CAN) (n = 15) neoplasia (n = 8); Kaposi's sarcoma, Four skin cancers, One intestinal tumors, One renal cell carsinom) or BK virus nephropathy (n = 2). SRL was started at a mean of 78 +/- 42 (15 to 163) months after transplantation. Mean follow-up on SRL therapy was 20 +/- 12 (6 to 43) months. Proteinuria increased from 0.445 (0 to 1.5) g/d before conversion to 3.2 g/dL (0.2 to 12) after conversion (P = 0.001). Before conversion 8 (32%) patients had no proteinuria, whereas afterwards all patients had proteinuria. In 28% of patients proteinuria remained unchanged, whereas it increased in 68% of patients. In 40% it increased by more than 100%. Twenty-eight percent of patients showed increased proteinuria to the nephrotic range. Biopsies performed in five patients revealed new pathological changes: One membranoproliferative glomerulopathy and interstitial nephritis. These patients showed persistently good graft function. Serum creatinine values did not change significantly: 1.98 +/- 0.8 mg/dL before SRL therapy and 2.53 +/- 1.9 mg/dL at last follow-up (P = .14). Five grafts were lost and the patients returned to dialysis. Five patients displayed CAN and Kaposi's sarcoma. Mean urinary protein of patients who returned to dialysis was 1.26 (0.5 to 3.5) g/d before and 4.7 (3 to 12) g/d after conversion (P = .01). Mean serum creatinine level before conversion was 2.21 mg/dL and thereafter, 4.93 mg/dL (P = .02). Heavy proteinuria was common after the use of SRL as rescue therapy for renal transplantation. Therefore, conversion should be considered for patients who have not developed advanced CAN and proteinuria. The possibility of de novo glomerular pathology under SRL treatment requires further investigation by renal biopsy.", "entity": "Nephritis, Interstitial", "aliases": "Interstitial Nephritides Nephritis Tubulointerstitial", "definition": "Inflammation of the interstitial tissue of the kidney. This term is generally used for primary inflammation of KIDNEY TUBULES and/or surrounding interstitium. For primary inflammation of glomerular interstitium, see GLOMERULONEPHRITIS. Infiltration of the inflammatory cells into the interstitial compartment results in EDEMA, increased spaces between the tubules, and tubular renal dysfunction.\n    ", "id": "MESH:D009395"}
{"mention": "creatinine", "mention_text": "Sirolimus (SRL) is a new, potent immunosuppressive agent. More recently, proteinuria has been reported as a consequence of sirolimus therapy, although the mechanism has remained unclear. We retrospectively examined the records of 25 renal transplant patients, who developed or displayed increased proteinuria after SRL conversion. The patient cohort (14 men, 11 women) was treated with SRL as conversion therapy, due to chronic allograft nephropathy (CAN) (n = 15) neoplasia (n = 8); Kaposi's sarcoma, Four skin cancers, One intestinal tumors, One renal cell carsinom) or BK virus nephropathy (n = 2). SRL was started at a mean of 78 +/- 42 (15 to 163) months after transplantation. Mean follow-up on SRL therapy was 20 +/- 12 (6 to 43) months. Proteinuria increased from 0.445 (0 to 1.5) g/d before conversion to 3.2 g/dL (0.2 to 12) after conversion (P = 0.001). Before conversion 8 (32%) patients had no proteinuria, whereas afterwards all patients had proteinuria. In 28% of patients proteinuria remained unchanged, whereas it increased in 68% of patients. In 40% it increased by more than 100%. Twenty-eight percent of patients showed increased proteinuria to the nephrotic range. Biopsies performed in five patients revealed new pathological changes: One membranoproliferative glomerulopathy and interstitial nephritis. These patients showed persistently good graft function. Serum creatinine values did not change significantly: 1.98 +/- 0.8 mg/dL before SRL therapy and 2.53 +/- 1.9 mg/dL at last follow-up (P = .14). Five grafts were lost and the patients returned to dialysis. Five patients displayed CAN and Kaposi's sarcoma. Mean urinary protein of patients who returned to dialysis was 1.26 (0.5 to 3.5) g/d before and 4.7 (3 to 12) g/d after conversion (P = .01). Mean serum creatinine level before conversion was 2.21 mg/dL and thereafter, 4.93 mg/dL (P = .02). Heavy proteinuria was common after the use of SRL as rescue therapy for renal transplantation. Therefore, conversion should be considered for patients who have not developed advanced CAN and proteinuria. The possibility of de novo glomerular pathology under SRL treatment requires further investigation by renal biopsy.", "entity": "Creatinine", "aliases": "Creatinine Sulfate Salt Krebiozen", "definition": "", "id": "MESH:D003404"}
{"mention": "cyclophosphamide", "mention_text": "In vitro characterization of parasympathetic and sympathetic responses in cyclophosphamide-induced cystitis in the rat.", "entity": "Cyclophosphamide", "aliases": "Anhydrous Cyclophosphamide B 518 B-518 B518 Monohydrate (R)-Isomer (S)-Isomer Cyclophosphane Cytophosphan Cytophosphane Cytoxan Endoxan NSC 26271 NSC-26271 NSC26271 Neosar Procytox Sendoxan", "definition": "Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.\n    ", "id": "MESH:D003520"}
{"mention": "cystitis", "mention_text": "In vitro characterization of parasympathetic and sympathetic responses in cyclophosphamide-induced cystitis in the rat.", "entity": "Cystitis", "aliases": "Cystitides Cystitis", "definition": "Inflammation of the URINARY BLADDER, either from bacterial or non-bacterial causes. Cystitis is usually associated with painful urination (dysuria), increased frequency, urgency, and suprapubic pain.\n    ", "id": "MESH:D003556"}
{"mention": "cyclophosphamide", "mention_text": "In cyclophosphamide-induced cystitis in the rat, detrusor function is impaired and the expression and effects of muscarinic receptors altered. Whether or not the neuronal transmission may be affected by cystitis was presently investigated. Responses of urinary strip preparations from control and cyclophosphamide-pretreated rats to electrical field stimulation and to agonists were assessed in the absence and presence of muscarinic, adrenergic and purinergic receptor antagonists. Generally, atropine reduced contractions, but in contrast to controls, it also reduced responses to low electrical field stimulation intensity (1-5 Hz) in inflamed preparations. In both types, purinoceptor desensitization with alpha,beta-methylene adenosine-5'-triphosphate (alpha,beta-meATP) caused further reductions at low frequencies (<10 Hz). The muscarinic receptor antagonists atropine, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) ('M(1)/M(3)/M(5)-selective'), methoctramine ('M(2)-selective') and pirenzepine ('M(1)-selective') antagonized the tonic component of the electrical field stimulation-evoked contractile response more potently than the phasic component. 4-DAMP inhibited the tonic contractions in controls more potently than methoctramine and pirenzepine. In inflamed preparations, the muscarinic receptor antagonism on the phasic component of the electrical field stimulation-evoked contraction was decreased and the pirenzepine and 4-DAMP antagonism on the tonic component was much less efficient than in controls. In contrast to controls, methoctramine increased -- instead of decreased -- the tonic responses at high frequencies. While contractions to carbachol and ATP were the same in inflamed and in control strips when related to a reference potassium response, isoprenaline-induced relaxations were smaller in inflamed strips. Thus, in cystitis substantial changes of the efferent functional responses occur. While postjunctional beta-adrenoceptor-mediated relaxations are reduced, effects by prejunctional inhibitory muscarinic receptors may be increased.", "entity": "Cyclophosphamide", "aliases": "Anhydrous Cyclophosphamide B 518 B-518 B518 Monohydrate (R)-Isomer (S)-Isomer Cyclophosphane Cytophosphan Cytophosphane Cytoxan Endoxan NSC 26271 NSC-26271 NSC26271 Neosar Procytox Sendoxan", "definition": "Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.\n    ", "id": "MESH:D003520"}
{"mention": "cystitis", "mention_text": "In cyclophosphamide-induced cystitis in the rat, detrusor function is impaired and the expression and effects of muscarinic receptors altered. Whether or not the neuronal transmission may be affected by cystitis was presently investigated. Responses of urinary strip preparations from control and cyclophosphamide-pretreated rats to electrical field stimulation and to agonists were assessed in the absence and presence of muscarinic, adrenergic and purinergic receptor antagonists. Generally, atropine reduced contractions, but in contrast to controls, it also reduced responses to low electrical field stimulation intensity (1-5 Hz) in inflamed preparations. In both types, purinoceptor desensitization with alpha,beta-methylene adenosine-5'-triphosphate (alpha,beta-meATP) caused further reductions at low frequencies (<10 Hz). The muscarinic receptor antagonists atropine, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) ('M(1)/M(3)/M(5)-selective'), methoctramine ('M(2)-selective') and pirenzepine ('M(1)-selective') antagonized the tonic component of the electrical field stimulation-evoked contractile response more potently than the phasic component. 4-DAMP inhibited the tonic contractions in controls more potently than methoctramine and pirenzepine. In inflamed preparations, the muscarinic receptor antagonism on the phasic component of the electrical field stimulation-evoked contraction was decreased and the pirenzepine and 4-DAMP antagonism on the tonic component was much less efficient than in controls. In contrast to controls, methoctramine increased -- instead of decreased -- the tonic responses at high frequencies. While contractions to carbachol and ATP were the same in inflamed and in control strips when related to a reference potassium response, isoprenaline-induced relaxations were smaller in inflamed strips. Thus, in cystitis substantial changes of the efferent functional responses occur. While postjunctional beta-adrenoceptor-mediated relaxations are reduced, effects by prejunctional inhibitory muscarinic receptors may be increased.", "entity": "Cystitis", "aliases": "Cystitides Cystitis", "definition": "Inflammation of the URINARY BLADDER, either from bacterial or non-bacterial causes. Cystitis is usually associated with painful urination (dysuria), increased frequency, urgency, and suprapubic pain.\n    ", "id": "MESH:D003556"}
{"mention": "atropine", "mention_text": "In cyclophosphamide-induced cystitis in the rat, detrusor function is impaired and the expression and effects of muscarinic receptors altered. Whether or not the neuronal transmission may be affected by cystitis was presently investigated. Responses of urinary strip preparations from control and cyclophosphamide-pretreated rats to electrical field stimulation and to agonists were assessed in the absence and presence of muscarinic, adrenergic and purinergic receptor antagonists. Generally, atropine reduced contractions, but in contrast to controls, it also reduced responses to low electrical field stimulation intensity (1-5 Hz) in inflamed preparations. In both types, purinoceptor desensitization with alpha,beta-methylene adenosine-5'-triphosphate (alpha,beta-meATP) caused further reductions at low frequencies (<10 Hz). The muscarinic receptor antagonists atropine, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) ('M(1)/M(3)/M(5)-selective'), methoctramine ('M(2)-selective') and pirenzepine ('M(1)-selective') antagonized the tonic component of the electrical field stimulation-evoked contractile response more potently than the phasic component. 4-DAMP inhibited the tonic contractions in controls more potently than methoctramine and pirenzepine. In inflamed preparations, the muscarinic receptor antagonism on the phasic component of the electrical field stimulation-evoked contraction was decreased and the pirenzepine and 4-DAMP antagonism on the tonic component was much less efficient than in controls. In contrast to controls, methoctramine increased -- instead of decreased -- the tonic responses at high frequencies. While contractions to carbachol and ATP were the same in inflamed and in control strips when related to a reference potassium response, isoprenaline-induced relaxations were smaller in inflamed strips. Thus, in cystitis substantial changes of the efferent functional responses occur. While postjunctional beta-adrenoceptor-mediated relaxations are reduced, effects by prejunctional inhibitory muscarinic receptors may be increased.", "entity": "Atropine", "aliases": "Anhydrous Atropine Sulfate AtroPen Atropin Augenöl Chauvin Brand Winzer Atropinol of Survival Technology", "definition": "An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.\n    ", "id": "MESH:D001285"}
{"mention": "alpha,beta-methylene adenosine-5'-triphosphate", "mention_text": "In cyclophosphamide-induced cystitis in the rat, detrusor function is impaired and the expression and effects of muscarinic receptors altered. Whether or not the neuronal transmission may be affected by cystitis was presently investigated. Responses of urinary strip preparations from control and cyclophosphamide-pretreated rats to electrical field stimulation and to agonists were assessed in the absence and presence of muscarinic, adrenergic and purinergic receptor antagonists. Generally, atropine reduced contractions, but in contrast to controls, it also reduced responses to low electrical field stimulation intensity (1-5 Hz) in inflamed preparations. In both types, purinoceptor desensitization with alpha,beta-methylene adenosine-5'-triphosphate (alpha,beta-meATP) caused further reductions at low frequencies (<10 Hz). The muscarinic receptor antagonists atropine, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) ('M(1)/M(3)/M(5)-selective'), methoctramine ('M(2)-selective') and pirenzepine ('M(1)-selective') antagonized the tonic component of the electrical field stimulation-evoked contractile response more potently than the phasic component. 4-DAMP inhibited the tonic contractions in controls more potently than methoctramine and pirenzepine. In inflamed preparations, the muscarinic receptor antagonism on the phasic component of the electrical field stimulation-evoked contraction was decreased and the pirenzepine and 4-DAMP antagonism on the tonic component was much less efficient than in controls. In contrast to controls, methoctramine increased -- instead of decreased -- the tonic responses at high frequencies. While contractions to carbachol and ATP were the same in inflamed and in control strips when related to a reference potassium response, isoprenaline-induced relaxations were smaller in inflamed strips. Thus, in cystitis substantial changes of the efferent functional responses occur. While postjunctional beta-adrenoceptor-mediated relaxations are reduced, effects by prejunctional inhibitory muscarinic receptors may be increased.", "entity": "alpha,beta-methyleneadenosine 5'-triphosphate", "aliases": "AMPCPP APCPP APPCP App(Ch)2P HPCPP adenosine 5'-(alpha,beta-methylene)triphosphate alpha beta-methylene ATP alpha,beta-MeATP alpha,beta-methylATP alpha,beta-methylene alpha,beta-methyleneadenosine 5'-triphosphate lithium salt magnesium-(alpha,beta-methylene)ATP", "definition": "", "id": "MESH:C002630"}
{"mention": "alpha,beta-meATP", "mention_text": "In cyclophosphamide-induced cystitis in the rat, detrusor function is impaired and the expression and effects of muscarinic receptors altered. Whether or not the neuronal transmission may be affected by cystitis was presently investigated. Responses of urinary strip preparations from control and cyclophosphamide-pretreated rats to electrical field stimulation and to agonists were assessed in the absence and presence of muscarinic, adrenergic and purinergic receptor antagonists. Generally, atropine reduced contractions, but in contrast to controls, it also reduced responses to low electrical field stimulation intensity (1-5 Hz) in inflamed preparations. In both types, purinoceptor desensitization with alpha,beta-methylene adenosine-5'-triphosphate (alpha,beta-meATP) caused further reductions at low frequencies (<10 Hz). The muscarinic receptor antagonists atropine, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) ('M(1)/M(3)/M(5)-selective'), methoctramine ('M(2)-selective') and pirenzepine ('M(1)-selective') antagonized the tonic component of the electrical field stimulation-evoked contractile response more potently than the phasic component. 4-DAMP inhibited the tonic contractions in controls more potently than methoctramine and pirenzepine. In inflamed preparations, the muscarinic receptor antagonism on the phasic component of the electrical field stimulation-evoked contraction was decreased and the pirenzepine and 4-DAMP antagonism on the tonic component was much less efficient than in controls. In contrast to controls, methoctramine increased -- instead of decreased -- the tonic responses at high frequencies. While contractions to carbachol and ATP were the same in inflamed and in control strips when related to a reference potassium response, isoprenaline-induced relaxations were smaller in inflamed strips. Thus, in cystitis substantial changes of the efferent functional responses occur. While postjunctional beta-adrenoceptor-mediated relaxations are reduced, effects by prejunctional inhibitory muscarinic receptors may be increased.", "entity": "alpha,beta-methyleneadenosine 5'-triphosphate", "aliases": "AMPCPP APCPP APPCP App(Ch)2P HPCPP adenosine 5'-(alpha,beta-methylene)triphosphate alpha beta-methylene ATP alpha,beta-MeATP alpha,beta-methylATP alpha,beta-methylene alpha,beta-methyleneadenosine 5'-triphosphate lithium salt magnesium-(alpha,beta-methylene)ATP", "definition": "", "id": "MESH:C002630"}
{"mention": "4-diphenylacetoxy-N-methylpiperidine", "mention_text": "In cyclophosphamide-induced cystitis in the rat, detrusor function is impaired and the expression and effects of muscarinic receptors altered. Whether or not the neuronal transmission may be affected by cystitis was presently investigated. Responses of urinary strip preparations from control and cyclophosphamide-pretreated rats to electrical field stimulation and to agonists were assessed in the absence and presence of muscarinic, adrenergic and purinergic receptor antagonists. Generally, atropine reduced contractions, but in contrast to controls, it also reduced responses to low electrical field stimulation intensity (1-5 Hz) in inflamed preparations. In both types, purinoceptor desensitization with alpha,beta-methylene adenosine-5'-triphosphate (alpha,beta-meATP) caused further reductions at low frequencies (<10 Hz). The muscarinic receptor antagonists atropine, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) ('M(1)/M(3)/M(5)-selective'), methoctramine ('M(2)-selective') and pirenzepine ('M(1)-selective') antagonized the tonic component of the electrical field stimulation-evoked contractile response more potently than the phasic component. 4-DAMP inhibited the tonic contractions in controls more potently than methoctramine and pirenzepine. In inflamed preparations, the muscarinic receptor antagonism on the phasic component of the electrical field stimulation-evoked contraction was decreased and the pirenzepine and 4-DAMP antagonism on the tonic component was much less efficient than in controls. In contrast to controls, methoctramine increased -- instead of decreased -- the tonic responses at high frequencies. While contractions to carbachol and ATP were the same in inflamed and in control strips when related to a reference potassium response, isoprenaline-induced relaxations were smaller in inflamed strips. Thus, in cystitis substantial changes of the efferent functional responses occur. While postjunctional beta-adrenoceptor-mediated relaxations are reduced, effects by prejunctional inhibitory muscarinic receptors may be increased.", "entity": "4-diphenylacetoxy-1,1-dimethylpiperidinium", "aliases": "1-dimethyl-4-diphenylacetoxypiperidinium 4-DAMP methiodide methobromide 4-diphenylacetoxy-1,1-dimethylpiperidinium iodide 4-diphenylacetoxy-N-methylpiperidine", "definition": "", "id": "MESH:C042375"}
{"mention": "4-DAMP", "mention_text": "In cyclophosphamide-induced cystitis in the rat, detrusor function is impaired and the expression and effects of muscarinic receptors altered. Whether or not the neuronal transmission may be affected by cystitis was presently investigated. Responses of urinary strip preparations from control and cyclophosphamide-pretreated rats to electrical field stimulation and to agonists were assessed in the absence and presence of muscarinic, adrenergic and purinergic receptor antagonists. Generally, atropine reduced contractions, but in contrast to controls, it also reduced responses to low electrical field stimulation intensity (1-5 Hz) in inflamed preparations. In both types, purinoceptor desensitization with alpha,beta-methylene adenosine-5'-triphosphate (alpha,beta-meATP) caused further reductions at low frequencies (<10 Hz). The muscarinic receptor antagonists atropine, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) ('M(1)/M(3)/M(5)-selective'), methoctramine ('M(2)-selective') and pirenzepine ('M(1)-selective') antagonized the tonic component of the electrical field stimulation-evoked contractile response more potently than the phasic component. 4-DAMP inhibited the tonic contractions in controls more potently than methoctramine and pirenzepine. In inflamed preparations, the muscarinic receptor antagonism on the phasic component of the electrical field stimulation-evoked contraction was decreased and the pirenzepine and 4-DAMP antagonism on the tonic component was much less efficient than in controls. In contrast to controls, methoctramine increased -- instead of decreased -- the tonic responses at high frequencies. While contractions to carbachol and ATP were the same in inflamed and in control strips when related to a reference potassium response, isoprenaline-induced relaxations were smaller in inflamed strips. Thus, in cystitis substantial changes of the efferent functional responses occur. While postjunctional beta-adrenoceptor-mediated relaxations are reduced, effects by prejunctional inhibitory muscarinic receptors may be increased.", "entity": "4-diphenylacetoxy-1,1-dimethylpiperidinium", "aliases": "1-dimethyl-4-diphenylacetoxypiperidinium 4-DAMP methiodide methobromide 4-diphenylacetoxy-1,1-dimethylpiperidinium iodide 4-diphenylacetoxy-N-methylpiperidine", "definition": "", "id": "MESH:C042375"}
{"mention": "methoctramine", "mention_text": "In cyclophosphamide-induced cystitis in the rat, detrusor function is impaired and the expression and effects of muscarinic receptors altered. Whether or not the neuronal transmission may be affected by cystitis was presently investigated. Responses of urinary strip preparations from control and cyclophosphamide-pretreated rats to electrical field stimulation and to agonists were assessed in the absence and presence of muscarinic, adrenergic and purinergic receptor antagonists. Generally, atropine reduced contractions, but in contrast to controls, it also reduced responses to low electrical field stimulation intensity (1-5 Hz) in inflamed preparations. In both types, purinoceptor desensitization with alpha,beta-methylene adenosine-5'-triphosphate (alpha,beta-meATP) caused further reductions at low frequencies (<10 Hz). The muscarinic receptor antagonists atropine, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) ('M(1)/M(3)/M(5)-selective'), methoctramine ('M(2)-selective') and pirenzepine ('M(1)-selective') antagonized the tonic component of the electrical field stimulation-evoked contractile response more potently than the phasic component. 4-DAMP inhibited the tonic contractions in controls more potently than methoctramine and pirenzepine. In inflamed preparations, the muscarinic receptor antagonism on the phasic component of the electrical field stimulation-evoked contraction was decreased and the pirenzepine and 4-DAMP antagonism on the tonic component was much less efficient than in controls. In contrast to controls, methoctramine increased -- instead of decreased -- the tonic responses at high frequencies. While contractions to carbachol and ATP were the same in inflamed and in control strips when related to a reference potassium response, isoprenaline-induced relaxations were smaller in inflamed strips. Thus, in cystitis substantial changes of the efferent functional responses occur. While postjunctional beta-adrenoceptor-mediated relaxations are reduced, effects by prejunctional inhibitory muscarinic receptors may be increased.", "entity": "methoctramine", "aliases": "N,N'-bis(6-((2-methoxybenzyl)amino)hexyl)-1,8-octanediamine tetrahydrochloride methoctramine", "definition": "", "id": "MESH:C054938"}
{"mention": "pirenzepine", "mention_text": "In cyclophosphamide-induced cystitis in the rat, detrusor function is impaired and the expression and effects of muscarinic receptors altered. Whether or not the neuronal transmission may be affected by cystitis was presently investigated. Responses of urinary strip preparations from control and cyclophosphamide-pretreated rats to electrical field stimulation and to agonists were assessed in the absence and presence of muscarinic, adrenergic and purinergic receptor antagonists. Generally, atropine reduced contractions, but in contrast to controls, it also reduced responses to low electrical field stimulation intensity (1-5 Hz) in inflamed preparations. In both types, purinoceptor desensitization with alpha,beta-methylene adenosine-5'-triphosphate (alpha,beta-meATP) caused further reductions at low frequencies (<10 Hz). The muscarinic receptor antagonists atropine, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) ('M(1)/M(3)/M(5)-selective'), methoctramine ('M(2)-selective') and pirenzepine ('M(1)-selective') antagonized the tonic component of the electrical field stimulation-evoked contractile response more potently than the phasic component. 4-DAMP inhibited the tonic contractions in controls more potently than methoctramine and pirenzepine. In inflamed preparations, the muscarinic receptor antagonism on the phasic component of the electrical field stimulation-evoked contraction was decreased and the pirenzepine and 4-DAMP antagonism on the tonic component was much less efficient than in controls. In contrast to controls, methoctramine increased -- instead of decreased -- the tonic responses at high frequencies. While contractions to carbachol and ATP were the same in inflamed and in control strips when related to a reference potassium response, isoprenaline-induced relaxations were smaller in inflamed strips. Thus, in cystitis substantial changes of the efferent functional responses occur. While postjunctional beta-adrenoceptor-mediated relaxations are reduced, effects by prejunctional inhibitory muscarinic receptors may be increased.", "entity": "Pirenzepine", "aliases": "Azupharma Brand of Pirenzepine Dihydrochloride Boehringer Ingelheim Dolorgiet Gastrotsepin Gastrozepin L-S 519 LS LS-519 LS519 Piren basan Piren-basan Pirenzepin ratiopharm Pirenzepin-ratiopharm Pyrenzepine Sagitta Ulcoprotect Ulgescum ct-Arzneimittel pirenzepin von ct", "definition": "An antimuscarinic agent that inhibits gastric secretion at lower doses than are required to affect gastrointestinal motility, salivary, central nervous system, cardiovascular, ocular, and urinary function. It promotes the healing of duodenal ulcers and due to its cytoprotective action is beneficial in the prevention of duodenal ulcer recurrence. It also potentiates the effect of other antiulcer agents such as CIMETIDINE and RANITIDINE. It is generally well tolerated by patients.\n    ", "id": "MESH:D010890"}
{"mention": "carbachol", "mention_text": "In cyclophosphamide-induced cystitis in the rat, detrusor function is impaired and the expression and effects of muscarinic receptors altered. Whether or not the neuronal transmission may be affected by cystitis was presently investigated. Responses of urinary strip preparations from control and cyclophosphamide-pretreated rats to electrical field stimulation and to agonists were assessed in the absence and presence of muscarinic, adrenergic and purinergic receptor antagonists. Generally, atropine reduced contractions, but in contrast to controls, it also reduced responses to low electrical field stimulation intensity (1-5 Hz) in inflamed preparations. In both types, purinoceptor desensitization with alpha,beta-methylene adenosine-5'-triphosphate (alpha,beta-meATP) caused further reductions at low frequencies (<10 Hz). The muscarinic receptor antagonists atropine, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) ('M(1)/M(3)/M(5)-selective'), methoctramine ('M(2)-selective') and pirenzepine ('M(1)-selective') antagonized the tonic component of the electrical field stimulation-evoked contractile response more potently than the phasic component. 4-DAMP inhibited the tonic contractions in controls more potently than methoctramine and pirenzepine. In inflamed preparations, the muscarinic receptor antagonism on the phasic component of the electrical field stimulation-evoked contraction was decreased and the pirenzepine and 4-DAMP antagonism on the tonic component was much less efficient than in controls. In contrast to controls, methoctramine increased -- instead of decreased -- the tonic responses at high frequencies. While contractions to carbachol and ATP were the same in inflamed and in control strips when related to a reference potassium response, isoprenaline-induced relaxations were smaller in inflamed strips. Thus, in cystitis substantial changes of the efferent functional responses occur. While postjunctional beta-adrenoceptor-mediated relaxations are reduced, effects by prejunctional inhibitory muscarinic receptors may be increased.", "entity": "Carbachol", "aliases": "Alcon Brand 1 of Carbachol 2 Allphar Bioniche Bipharma Isopto Carbacholine Carbamann Carbamoylcholine Carbamylcholine Carbastat Carbocholine Carboptic Chauvin Doryl Jestryl Mann Merck Miostat Novartis NutraMax Optopics", "definition": "A slowly hydrolyzed cholinergic agonist that acts at both muscarinic and nicotinic receptors.\n    ", "id": "MESH:D002217"}
{"mention": "ATP", "mention_text": "In cyclophosphamide-induced cystitis in the rat, detrusor function is impaired and the expression and effects of muscarinic receptors altered. Whether or not the neuronal transmission may be affected by cystitis was presently investigated. Responses of urinary strip preparations from control and cyclophosphamide-pretreated rats to electrical field stimulation and to agonists were assessed in the absence and presence of muscarinic, adrenergic and purinergic receptor antagonists. Generally, atropine reduced contractions, but in contrast to controls, it also reduced responses to low electrical field stimulation intensity (1-5 Hz) in inflamed preparations. In both types, purinoceptor desensitization with alpha,beta-methylene adenosine-5'-triphosphate (alpha,beta-meATP) caused further reductions at low frequencies (<10 Hz). The muscarinic receptor antagonists atropine, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) ('M(1)/M(3)/M(5)-selective'), methoctramine ('M(2)-selective') and pirenzepine ('M(1)-selective') antagonized the tonic component of the electrical field stimulation-evoked contractile response more potently than the phasic component. 4-DAMP inhibited the tonic contractions in controls more potently than methoctramine and pirenzepine. In inflamed preparations, the muscarinic receptor antagonism on the phasic component of the electrical field stimulation-evoked contraction was decreased and the pirenzepine and 4-DAMP antagonism on the tonic component was much less efficient than in controls. In contrast to controls, methoctramine increased -- instead of decreased -- the tonic responses at high frequencies. While contractions to carbachol and ATP were the same in inflamed and in control strips when related to a reference potassium response, isoprenaline-induced relaxations were smaller in inflamed strips. Thus, in cystitis substantial changes of the efferent functional responses occur. While postjunctional beta-adrenoceptor-mediated relaxations are reduced, effects by prejunctional inhibitory muscarinic receptors may be increased.", "entity": "Adenosine Triphosphate", "aliases": "ATP MgCl2 ATP-MgCl2 Adenosine Triphosphate Calcium Salt Chromium Ammonium Magnesium Chloride Manganese Adenylpyrophosphate Atriphos CaATP Cr(H2O)4 CrATP MgATP MnATP Striadyne", "definition": "An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.\n    ", "id": "MESH:D000255"}
{"mention": "potassium", "mention_text": "In cyclophosphamide-induced cystitis in the rat, detrusor function is impaired and the expression and effects of muscarinic receptors altered. Whether or not the neuronal transmission may be affected by cystitis was presently investigated. Responses of urinary strip preparations from control and cyclophosphamide-pretreated rats to electrical field stimulation and to agonists were assessed in the absence and presence of muscarinic, adrenergic and purinergic receptor antagonists. Generally, atropine reduced contractions, but in contrast to controls, it also reduced responses to low electrical field stimulation intensity (1-5 Hz) in inflamed preparations. In both types, purinoceptor desensitization with alpha,beta-methylene adenosine-5'-triphosphate (alpha,beta-meATP) caused further reductions at low frequencies (<10 Hz). The muscarinic receptor antagonists atropine, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) ('M(1)/M(3)/M(5)-selective'), methoctramine ('M(2)-selective') and pirenzepine ('M(1)-selective') antagonized the tonic component of the electrical field stimulation-evoked contractile response more potently than the phasic component. 4-DAMP inhibited the tonic contractions in controls more potently than methoctramine and pirenzepine. In inflamed preparations, the muscarinic receptor antagonism on the phasic component of the electrical field stimulation-evoked contraction was decreased and the pirenzepine and 4-DAMP antagonism on the tonic component was much less efficient than in controls. In contrast to controls, methoctramine increased -- instead of decreased -- the tonic responses at high frequencies. While contractions to carbachol and ATP were the same in inflamed and in control strips when related to a reference potassium response, isoprenaline-induced relaxations were smaller in inflamed strips. Thus, in cystitis substantial changes of the efferent functional responses occur. While postjunctional beta-adrenoceptor-mediated relaxations are reduced, effects by prejunctional inhibitory muscarinic receptors may be increased.", "entity": "Potassium", "aliases": "Potassium", "definition": "An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.\n    ", "id": "MESH:D011188"}
{"mention": "isoprenaline", "mention_text": "In cyclophosphamide-induced cystitis in the rat, detrusor function is impaired and the expression and effects of muscarinic receptors altered. Whether or not the neuronal transmission may be affected by cystitis was presently investigated. Responses of urinary strip preparations from control and cyclophosphamide-pretreated rats to electrical field stimulation and to agonists were assessed in the absence and presence of muscarinic, adrenergic and purinergic receptor antagonists. Generally, atropine reduced contractions, but in contrast to controls, it also reduced responses to low electrical field stimulation intensity (1-5 Hz) in inflamed preparations. In both types, purinoceptor desensitization with alpha,beta-methylene adenosine-5'-triphosphate (alpha,beta-meATP) caused further reductions at low frequencies (<10 Hz). The muscarinic receptor antagonists atropine, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) ('M(1)/M(3)/M(5)-selective'), methoctramine ('M(2)-selective') and pirenzepine ('M(1)-selective') antagonized the tonic component of the electrical field stimulation-evoked contractile response more potently than the phasic component. 4-DAMP inhibited the tonic contractions in controls more potently than methoctramine and pirenzepine. In inflamed preparations, the muscarinic receptor antagonism on the phasic component of the electrical field stimulation-evoked contraction was decreased and the pirenzepine and 4-DAMP antagonism on the tonic component was much less efficient than in controls. In contrast to controls, methoctramine increased -- instead of decreased -- the tonic responses at high frequencies. While contractions to carbachol and ATP were the same in inflamed and in control strips when related to a reference potassium response, isoprenaline-induced relaxations were smaller in inflamed strips. Thus, in cystitis substantial changes of the efferent functional responses occur. While postjunctional beta-adrenoceptor-mediated relaxations are reduced, effects by prejunctional inhibitory muscarinic receptors may be increased.", "entity": "Isoproterenol", "aliases": "4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol Euspiran Hydrochloride Isoproterenol Isadrin Isadrine Isoprenaline Isopropyl Noradrenaline Isopropylarterenol Isopropylnoradrenaline Isopropylnorepinephrine Sulfate Isuprel Izadrin Norisodrine Novodrin", "definition": "Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.\n    ", "id": "MESH:D007545"}
{"mention": "benzodiazepines", "mention_text": "Associations between use of benzodiazepines or related drugs and health, physical abilities and cognitive function: a non-randomised clinical study in the elderly.", "entity": "Benzodiazepines", "aliases": "Benzodiazepine Compounds Benzodiazepines", "definition": "A group of two-ring heterocyclic compounds consisting of a benzene ring fused to a diazepine ring.\n    ", "id": "MESH:D001569"}
{"mention": "benzodiazepines", "mention_text": "OBJECTIVE: To describe associations between the use of benzodiazepines or related drugs (BZDs/RDs) and health, functional abilities and cognitive function in the elderly. METHODS: A non-randomised clinical study of patients aged > or =65 years admitted to acute hospital wards during 1 month. 164 patients (mean age +/- standard deviation [SD] 81.6 +/- 6.8 years) were admitted. Of these, nearly half (n = 78) had used BZDs/RDs before admission, and the remainder (n = 86) were non-users. Cognitive ability was assessed by the Mini-Mental State Examination (MMSE). Patients scoring > or =20 MMSE sum points were interviewed (n = 79) and questioned regarding symptoms and functional abilities during the week prior to admission. Data on use of BZDs/RDs before admission, current medications and discharge diagnoses were collected from medical records. Health, physical abilities and cognitive function were compared between BZD/RD users and non-users, and adjustments were made for confounding variables. The residual serum concentrations of oxazepam, temazepam and zopiclone were analysed. RESULTS: The mean +/- SD duration of BZD/RD use was 7 +/- 7 years (range 1-31). Two or three BZDs/RDs were concomitantly taken by 26% of users (n = 20). Long-term use of these drugs was associated with female sex and use of a higher number of drugs with effects on the CNS, which tended to be related to diagnosed dementia. After adjustment for these variables as confounders, use of BZDs/RDs was not associated with cognitive function as measured by the MMSE. However, use of BZDs/RDs was associated with dizziness, inability to sleep after awaking at night and tiredness in the mornings during the week prior to admission and with stronger depressive symptoms measured at the beginning of the hospital stay. Use of BZDs/RDs tended to be associated with a reduced ability to walk and shorter night-time sleep during the week prior to admission. A higher residual serum concentration of temazepam correlated with a lower MMSE sum score after adjustment for confounding variables. CONCLUSIONS: Long-term use and concomitant use of more than one BZD/RD were common in elderly patients hospitalised because of acute illnesses. Long-term use was associated with daytime and night-time symptoms indicative of poorer health and potentially caused by the adverse effects of these drugs.", "entity": "Benzodiazepines", "aliases": "Benzodiazepine Compounds Benzodiazepines", "definition": "A group of two-ring heterocyclic compounds consisting of a benzene ring fused to a diazepine ring.\n    ", "id": "MESH:D001569"}
{"mention": "BZDs", "mention_text": "OBJECTIVE: To describe associations between the use of benzodiazepines or related drugs (BZDs/RDs) and health, functional abilities and cognitive function in the elderly. METHODS: A non-randomised clinical study of patients aged > or =65 years admitted to acute hospital wards during 1 month. 164 patients (mean age +/- standard deviation [SD] 81.6 +/- 6.8 years) were admitted. Of these, nearly half (n = 78) had used BZDs/RDs before admission, and the remainder (n = 86) were non-users. Cognitive ability was assessed by the Mini-Mental State Examination (MMSE). Patients scoring > or =20 MMSE sum points were interviewed (n = 79) and questioned regarding symptoms and functional abilities during the week prior to admission. Data on use of BZDs/RDs before admission, current medications and discharge diagnoses were collected from medical records. Health, physical abilities and cognitive function were compared between BZD/RD users and non-users, and adjustments were made for confounding variables. The residual serum concentrations of oxazepam, temazepam and zopiclone were analysed. RESULTS: The mean +/- SD duration of BZD/RD use was 7 +/- 7 years (range 1-31). Two or three BZDs/RDs were concomitantly taken by 26% of users (n = 20). Long-term use of these drugs was associated with female sex and use of a higher number of drugs with effects on the CNS, which tended to be related to diagnosed dementia. After adjustment for these variables as confounders, use of BZDs/RDs was not associated with cognitive function as measured by the MMSE. However, use of BZDs/RDs was associated with dizziness, inability to sleep after awaking at night and tiredness in the mornings during the week prior to admission and with stronger depressive symptoms measured at the beginning of the hospital stay. Use of BZDs/RDs tended to be associated with a reduced ability to walk and shorter night-time sleep during the week prior to admission. A higher residual serum concentration of temazepam correlated with a lower MMSE sum score after adjustment for confounding variables. CONCLUSIONS: Long-term use and concomitant use of more than one BZD/RD were common in elderly patients hospitalised because of acute illnesses. Long-term use was associated with daytime and night-time symptoms indicative of poorer health and potentially caused by the adverse effects of these drugs.", "entity": "Benzodiazepines", "aliases": "Benzodiazepine Compounds Benzodiazepines", "definition": "A group of two-ring heterocyclic compounds consisting of a benzene ring fused to a diazepine ring.\n    ", "id": "MESH:D001569"}
{"mention": "oxazepam", "mention_text": "OBJECTIVE: To describe associations between the use of benzodiazepines or related drugs (BZDs/RDs) and health, functional abilities and cognitive function in the elderly. METHODS: A non-randomised clinical study of patients aged > or =65 years admitted to acute hospital wards during 1 month. 164 patients (mean age +/- standard deviation [SD] 81.6 +/- 6.8 years) were admitted. Of these, nearly half (n = 78) had used BZDs/RDs before admission, and the remainder (n = 86) were non-users. Cognitive ability was assessed by the Mini-Mental State Examination (MMSE). Patients scoring > or =20 MMSE sum points were interviewed (n = 79) and questioned regarding symptoms and functional abilities during the week prior to admission. Data on use of BZDs/RDs before admission, current medications and discharge diagnoses were collected from medical records. Health, physical abilities and cognitive function were compared between BZD/RD users and non-users, and adjustments were made for confounding variables. The residual serum concentrations of oxazepam, temazepam and zopiclone were analysed. RESULTS: The mean +/- SD duration of BZD/RD use was 7 +/- 7 years (range 1-31). Two or three BZDs/RDs were concomitantly taken by 26% of users (n = 20). Long-term use of these drugs was associated with female sex and use of a higher number of drugs with effects on the CNS, which tended to be related to diagnosed dementia. After adjustment for these variables as confounders, use of BZDs/RDs was not associated with cognitive function as measured by the MMSE. However, use of BZDs/RDs was associated with dizziness, inability to sleep after awaking at night and tiredness in the mornings during the week prior to admission and with stronger depressive symptoms measured at the beginning of the hospital stay. Use of BZDs/RDs tended to be associated with a reduced ability to walk and shorter night-time sleep during the week prior to admission. A higher residual serum concentration of temazepam correlated with a lower MMSE sum score after adjustment for confounding variables. CONCLUSIONS: Long-term use and concomitant use of more than one BZD/RD were common in elderly patients hospitalised because of acute illnesses. Long-term use was associated with daytime and night-time symptoms indicative of poorer health and potentially caused by the adverse effects of these drugs.", "entity": "Oxazepam", "aliases": "Adumbran Oxazepam Serax Tazepam", "definition": "A benzodiazepine used in the treatment of anxiety, alcohol withdrawal, and insomnia.\n    ", "id": "MESH:D010076"}
{"mention": "temazepam", "mention_text": "OBJECTIVE: To describe associations between the use of benzodiazepines or related drugs (BZDs/RDs) and health, functional abilities and cognitive function in the elderly. METHODS: A non-randomised clinical study of patients aged > or =65 years admitted to acute hospital wards during 1 month. 164 patients (mean age +/- standard deviation [SD] 81.6 +/- 6.8 years) were admitted. Of these, nearly half (n = 78) had used BZDs/RDs before admission, and the remainder (n = 86) were non-users. Cognitive ability was assessed by the Mini-Mental State Examination (MMSE). Patients scoring > or =20 MMSE sum points were interviewed (n = 79) and questioned regarding symptoms and functional abilities during the week prior to admission. Data on use of BZDs/RDs before admission, current medications and discharge diagnoses were collected from medical records. Health, physical abilities and cognitive function were compared between BZD/RD users and non-users, and adjustments were made for confounding variables. The residual serum concentrations of oxazepam, temazepam and zopiclone were analysed. RESULTS: The mean +/- SD duration of BZD/RD use was 7 +/- 7 years (range 1-31). Two or three BZDs/RDs were concomitantly taken by 26% of users (n = 20). Long-term use of these drugs was associated with female sex and use of a higher number of drugs with effects on the CNS, which tended to be related to diagnosed dementia. After adjustment for these variables as confounders, use of BZDs/RDs was not associated with cognitive function as measured by the MMSE. However, use of BZDs/RDs was associated with dizziness, inability to sleep after awaking at night and tiredness in the mornings during the week prior to admission and with stronger depressive symptoms measured at the beginning of the hospital stay. Use of BZDs/RDs tended to be associated with a reduced ability to walk and shorter night-time sleep during the week prior to admission. A higher residual serum concentration of temazepam correlated with a lower MMSE sum score after adjustment for confounding variables. CONCLUSIONS: Long-term use and concomitant use of more than one BZD/RD were common in elderly patients hospitalised because of acute illnesses. Long-term use was associated with daytime and night-time symptoms indicative of poorer health and potentially caused by the adverse effects of these drugs.", "entity": "Temazepam", "aliases": "3 Hydroxydiazepam 3-Hydroxydiazepam AHP Brand of Temazepam Alphapharm Apo Apo-Temazepam Apotex Dasuen Desitin Euhypnos Gen Gen-Temazepam Genopharm Genpharm ICN Katwijk Knoll Levanxol Mallinckrodt Methyloxazepam Nocturne Norkotral Tema Normison Normitab Nortem Norton Novartis Novo Novo-Temazepam Novopharm Nu Pharm Nu-Pharm Nu-Temazepam Orion Oxydiazepam PMS PMS-Temazepam Pfizer 1 2 Pharmascience Planum Pronervon T Remestan Restoril Ro 5 5345 Ro-5-5345 Ro55345 SaH 47 603 47-603 47603 Scheffler Sig", "definition": "A benzodiazepine that acts as a GAMMA-AMINOBUTYRIC ACID modulator and anti-anxiety agent.\n    ", "id": "MESH:D013693"}
{"mention": "zopiclone", "mention_text": "OBJECTIVE: To describe associations between the use of benzodiazepines or related drugs (BZDs/RDs) and health, functional abilities and cognitive function in the elderly. METHODS: A non-randomised clinical study of patients aged > or =65 years admitted to acute hospital wards during 1 month. 164 patients (mean age +/- standard deviation [SD] 81.6 +/- 6.8 years) were admitted. Of these, nearly half (n = 78) had used BZDs/RDs before admission, and the remainder (n = 86) were non-users. Cognitive ability was assessed by the Mini-Mental State Examination (MMSE). Patients scoring > or =20 MMSE sum points were interviewed (n = 79) and questioned regarding symptoms and functional abilities during the week prior to admission. Data on use of BZDs/RDs before admission, current medications and discharge diagnoses were collected from medical records. Health, physical abilities and cognitive function were compared between BZD/RD users and non-users, and adjustments were made for confounding variables. The residual serum concentrations of oxazepam, temazepam and zopiclone were analysed. RESULTS: The mean +/- SD duration of BZD/RD use was 7 +/- 7 years (range 1-31). Two or three BZDs/RDs were concomitantly taken by 26% of users (n = 20). Long-term use of these drugs was associated with female sex and use of a higher number of drugs with effects on the CNS, which tended to be related to diagnosed dementia. After adjustment for these variables as confounders, use of BZDs/RDs was not associated with cognitive function as measured by the MMSE. However, use of BZDs/RDs was associated with dizziness, inability to sleep after awaking at night and tiredness in the mornings during the week prior to admission and with stronger depressive symptoms measured at the beginning of the hospital stay. Use of BZDs/RDs tended to be associated with a reduced ability to walk and shorter night-time sleep during the week prior to admission. A higher residual serum concentration of temazepam correlated with a lower MMSE sum score after adjustment for confounding variables. CONCLUSIONS: Long-term use and concomitant use of more than one BZD/RD were common in elderly patients hospitalised because of acute illnesses. Long-term use was associated with daytime and night-time symptoms indicative of poorer health and potentially caused by the adverse effects of these drugs.", "entity": "zopiclone", "aliases": "6-(5-chloro-2-pyridyl)-6,7-dihydro- 7-oxo-5H-pyrrolo(3,4-b)pyrazin-5-yl 4-methyl-1- piperazinecarboxylate Imovane Limovan Nu-Zopiclone Optidorm RP 27 267 Rhovane Siaten Somnosan Ximovan Zileze Zimoclone Zimovane Zop Zopi-Puren Zopicalm Zopicalma Zopiclon AL AZU AbZ Stada TAD beta Zopiclon-TEVA Zopiclon-neuraxpharm Zopiclon-ratiopharm Zopitan Zorclone ratio-Zopiclone zopiclodura zopiclon von ct zopiclone", "definition": "", "id": "MESH:C515050"}
{"mention": "dementia", "mention_text": "OBJECTIVE: To describe associations between the use of benzodiazepines or related drugs (BZDs/RDs) and health, functional abilities and cognitive function in the elderly. METHODS: A non-randomised clinical study of patients aged > or =65 years admitted to acute hospital wards during 1 month. 164 patients (mean age +/- standard deviation [SD] 81.6 +/- 6.8 years) were admitted. Of these, nearly half (n = 78) had used BZDs/RDs before admission, and the remainder (n = 86) were non-users. Cognitive ability was assessed by the Mini-Mental State Examination (MMSE). Patients scoring > or =20 MMSE sum points were interviewed (n = 79) and questioned regarding symptoms and functional abilities during the week prior to admission. Data on use of BZDs/RDs before admission, current medications and discharge diagnoses were collected from medical records. Health, physical abilities and cognitive function were compared between BZD/RD users and non-users, and adjustments were made for confounding variables. The residual serum concentrations of oxazepam, temazepam and zopiclone were analysed. RESULTS: The mean +/- SD duration of BZD/RD use was 7 +/- 7 years (range 1-31). Two or three BZDs/RDs were concomitantly taken by 26% of users (n = 20). Long-term use of these drugs was associated with female sex and use of a higher number of drugs with effects on the CNS, which tended to be related to diagnosed dementia. After adjustment for these variables as confounders, use of BZDs/RDs was not associated with cognitive function as measured by the MMSE. However, use of BZDs/RDs was associated with dizziness, inability to sleep after awaking at night and tiredness in the mornings during the week prior to admission and with stronger depressive symptoms measured at the beginning of the hospital stay. Use of BZDs/RDs tended to be associated with a reduced ability to walk and shorter night-time sleep during the week prior to admission. A higher residual serum concentration of temazepam correlated with a lower MMSE sum score after adjustment for confounding variables. CONCLUSIONS: Long-term use and concomitant use of more than one BZD/RD were common in elderly patients hospitalised because of acute illnesses. Long-term use was associated with daytime and night-time symptoms indicative of poorer health and potentially caused by the adverse effects of these drugs.", "entity": "Dementia", "aliases": "Amentia Amentias Dementia Familial Dementias Senile Paranoid", "definition": "An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness.\n    ", "id": "MESH:D003704"}
{"mention": "dizziness", "mention_text": "OBJECTIVE: To describe associations between the use of benzodiazepines or related drugs (BZDs/RDs) and health, functional abilities and cognitive function in the elderly. METHODS: A non-randomised clinical study of patients aged > or =65 years admitted to acute hospital wards during 1 month. 164 patients (mean age +/- standard deviation [SD] 81.6 +/- 6.8 years) were admitted. Of these, nearly half (n = 78) had used BZDs/RDs before admission, and the remainder (n = 86) were non-users. Cognitive ability was assessed by the Mini-Mental State Examination (MMSE). Patients scoring > or =20 MMSE sum points were interviewed (n = 79) and questioned regarding symptoms and functional abilities during the week prior to admission. Data on use of BZDs/RDs before admission, current medications and discharge diagnoses were collected from medical records. Health, physical abilities and cognitive function were compared between BZD/RD users and non-users, and adjustments were made for confounding variables. The residual serum concentrations of oxazepam, temazepam and zopiclone were analysed. RESULTS: The mean +/- SD duration of BZD/RD use was 7 +/- 7 years (range 1-31). Two or three BZDs/RDs were concomitantly taken by 26% of users (n = 20). Long-term use of these drugs was associated with female sex and use of a higher number of drugs with effects on the CNS, which tended to be related to diagnosed dementia. After adjustment for these variables as confounders, use of BZDs/RDs was not associated with cognitive function as measured by the MMSE. However, use of BZDs/RDs was associated with dizziness, inability to sleep after awaking at night and tiredness in the mornings during the week prior to admission and with stronger depressive symptoms measured at the beginning of the hospital stay. Use of BZDs/RDs tended to be associated with a reduced ability to walk and shorter night-time sleep during the week prior to admission. A higher residual serum concentration of temazepam correlated with a lower MMSE sum score after adjustment for confounding variables. CONCLUSIONS: Long-term use and concomitant use of more than one BZD/RD were common in elderly patients hospitalised because of acute illnesses. Long-term use was associated with daytime and night-time symptoms indicative of poorer health and potentially caused by the adverse effects of these drugs.", "entity": "Dizziness", "aliases": "Dizziness Dizzyness Light Headedness Light-Headedness Lightheadedness Orthostasis", "definition": "An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness.\n    ", "id": "MESH:D004244"}
{"mention": "inability to sleep", "mention_text": "OBJECTIVE: To describe associations between the use of benzodiazepines or related drugs (BZDs/RDs) and health, functional abilities and cognitive function in the elderly. METHODS: A non-randomised clinical study of patients aged > or =65 years admitted to acute hospital wards during 1 month. 164 patients (mean age +/- standard deviation [SD] 81.6 +/- 6.8 years) were admitted. Of these, nearly half (n = 78) had used BZDs/RDs before admission, and the remainder (n = 86) were non-users. Cognitive ability was assessed by the Mini-Mental State Examination (MMSE). Patients scoring > or =20 MMSE sum points were interviewed (n = 79) and questioned regarding symptoms and functional abilities during the week prior to admission. Data on use of BZDs/RDs before admission, current medications and discharge diagnoses were collected from medical records. Health, physical abilities and cognitive function were compared between BZD/RD users and non-users, and adjustments were made for confounding variables. The residual serum concentrations of oxazepam, temazepam and zopiclone were analysed. RESULTS: The mean +/- SD duration of BZD/RD use was 7 +/- 7 years (range 1-31). Two or three BZDs/RDs were concomitantly taken by 26% of users (n = 20). Long-term use of these drugs was associated with female sex and use of a higher number of drugs with effects on the CNS, which tended to be related to diagnosed dementia. After adjustment for these variables as confounders, use of BZDs/RDs was not associated with cognitive function as measured by the MMSE. However, use of BZDs/RDs was associated with dizziness, inability to sleep after awaking at night and tiredness in the mornings during the week prior to admission and with stronger depressive symptoms measured at the beginning of the hospital stay. Use of BZDs/RDs tended to be associated with a reduced ability to walk and shorter night-time sleep during the week prior to admission. A higher residual serum concentration of temazepam correlated with a lower MMSE sum score after adjustment for confounding variables. CONCLUSIONS: Long-term use and concomitant use of more than one BZD/RD were common in elderly patients hospitalised because of acute illnesses. Long-term use was associated with daytime and night-time symptoms indicative of poorer health and potentially caused by the adverse effects of these drugs.", "entity": "Sleep Initiation and Maintenance Disorders", "aliases": "Awakening Early Chronic Insomnia DIMS (Disorders of Initiating and Maintaining Sleep) Disorders Sleep Dysfunction Initiation Dysfunctions Disorder Nonorganic Primary Psychophysiological Rebound Secondary Transient Insomnias Maintenance Sleeplessness", "definition": "Disorders characterized by impairment of the ability to initiate or maintain sleep. This may occur as a primary disorder or in association with another medical or psychiatric condition.\n    ", "id": "MESH:D007319"}
{"mention": "tiredness", "mention_text": "OBJECTIVE: To describe associations between the use of benzodiazepines or related drugs (BZDs/RDs) and health, functional abilities and cognitive function in the elderly. METHODS: A non-randomised clinical study of patients aged > or =65 years admitted to acute hospital wards during 1 month. 164 patients (mean age +/- standard deviation [SD] 81.6 +/- 6.8 years) were admitted. Of these, nearly half (n = 78) had used BZDs/RDs before admission, and the remainder (n = 86) were non-users. Cognitive ability was assessed by the Mini-Mental State Examination (MMSE). Patients scoring > or =20 MMSE sum points were interviewed (n = 79) and questioned regarding symptoms and functional abilities during the week prior to admission. Data on use of BZDs/RDs before admission, current medications and discharge diagnoses were collected from medical records. Health, physical abilities and cognitive function were compared between BZD/RD users and non-users, and adjustments were made for confounding variables. The residual serum concentrations of oxazepam, temazepam and zopiclone were analysed. RESULTS: The mean +/- SD duration of BZD/RD use was 7 +/- 7 years (range 1-31). Two or three BZDs/RDs were concomitantly taken by 26% of users (n = 20). Long-term use of these drugs was associated with female sex and use of a higher number of drugs with effects on the CNS, which tended to be related to diagnosed dementia. After adjustment for these variables as confounders, use of BZDs/RDs was not associated with cognitive function as measured by the MMSE. However, use of BZDs/RDs was associated with dizziness, inability to sleep after awaking at night and tiredness in the mornings during the week prior to admission and with stronger depressive symptoms measured at the beginning of the hospital stay. Use of BZDs/RDs tended to be associated with a reduced ability to walk and shorter night-time sleep during the week prior to admission. A higher residual serum concentration of temazepam correlated with a lower MMSE sum score after adjustment for confounding variables. CONCLUSIONS: Long-term use and concomitant use of more than one BZD/RD were common in elderly patients hospitalised because of acute illnesses. Long-term use was associated with daytime and night-time symptoms indicative of poorer health and potentially caused by the adverse effects of these drugs.", "entity": "Fatigue", "aliases": "Fatigue Lassitude", "definition": "The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.\n    ", "id": "MESH:D005221"}
{"mention": "depressive symptoms", "mention_text": "OBJECTIVE: To describe associations between the use of benzodiazepines or related drugs (BZDs/RDs) and health, functional abilities and cognitive function in the elderly. METHODS: A non-randomised clinical study of patients aged > or =65 years admitted to acute hospital wards during 1 month. 164 patients (mean age +/- standard deviation [SD] 81.6 +/- 6.8 years) were admitted. Of these, nearly half (n = 78) had used BZDs/RDs before admission, and the remainder (n = 86) were non-users. Cognitive ability was assessed by the Mini-Mental State Examination (MMSE). Patients scoring > or =20 MMSE sum points were interviewed (n = 79) and questioned regarding symptoms and functional abilities during the week prior to admission. Data on use of BZDs/RDs before admission, current medications and discharge diagnoses were collected from medical records. Health, physical abilities and cognitive function were compared between BZD/RD users and non-users, and adjustments were made for confounding variables. The residual serum concentrations of oxazepam, temazepam and zopiclone were analysed. RESULTS: The mean +/- SD duration of BZD/RD use was 7 +/- 7 years (range 1-31). Two or three BZDs/RDs were concomitantly taken by 26% of users (n = 20). Long-term use of these drugs was associated with female sex and use of a higher number of drugs with effects on the CNS, which tended to be related to diagnosed dementia. After adjustment for these variables as confounders, use of BZDs/RDs was not associated with cognitive function as measured by the MMSE. However, use of BZDs/RDs was associated with dizziness, inability to sleep after awaking at night and tiredness in the mornings during the week prior to admission and with stronger depressive symptoms measured at the beginning of the hospital stay. Use of BZDs/RDs tended to be associated with a reduced ability to walk and shorter night-time sleep during the week prior to admission. A higher residual serum concentration of temazepam correlated with a lower MMSE sum score after adjustment for confounding variables. CONCLUSIONS: Long-term use and concomitant use of more than one BZD/RD were common in elderly patients hospitalised because of acute illnesses. Long-term use was associated with daytime and night-time symptoms indicative of poorer health and potentially caused by the adverse effects of these drugs.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "vocal fold palsy", "mention_text": "Acute vocal fold palsy after acute disulfiram intoxication.", "entity": "Vocal Cord Paralysis", "aliases": "Acquired Vocal Cord Palsy Bilateral Paresis Congenital Laryngeal Nerve Recurrent Paralyses Paralysis Palsies Fold Unilateral Pareses Partial (Paresis) Cords Total", "definition": "Congenital or acquired paralysis of one or both VOCAL CORDS. This condition is caused by defects in the CENTRAL NERVOUS SYSTEM, the VAGUS NERVE and branches of LARYNGEAL NERVES. Common symptoms are VOICE DISORDERS including HOARSENESS or APHONIA.\n    ", "id": "MESH:D014826"}
{"mention": "disulfiram", "mention_text": "Acute vocal fold palsy after acute disulfiram intoxication.", "entity": "Disulfiram", "aliases": "Alcophobin Allphar Brand of Disulfiram Altana Pharma Antabus Antabuse Anticol Bis(diethylthiocarbamoyl) Disulfide Bohm Dicupral Tetraethylthiuram Dumex Esperal Odyssey Orphan Sanofi Synthelabo Tetraethylthioperoxydicarbonic Diamide ((H2N)C(S))2S2 Teturam", "definition": "A carbamate derivative used as an alcohol deterrent. It is a relatively nontoxic substance when administered alone, but markedly alters the intermediary metabolism of alcohol. When alcohol is ingested after administration of disulfiram, blood acetaldehyde concentrations are increased, followed by flushing, systemic vasodilation, respiratory difficulties, nausea, hypotension, and other symptoms (acetaldehyde syndrome). It acts by inhibiting aldehyde dehydrogenase.\n    ", "id": "MESH:D004221"}
{"mention": "peripheral neuropathy", "mention_text": "Acute peripheral neuropathy caused by a disulfiram overdose is very rare and there is no report of it leading to vocal fold palsy. A 49-year-old woman was transferred to our department because of quadriparesis, lancinating pain, sensory loss, and paresthesia of the distal limbs. One month previously, she had taken a single high dose of disulfiram (130 tablets of ALCOHOL STOP TAB, Shin-Poong Pharm. Co., Ansan, Korea) in a suicide attempt. She was not an alcoholic. For the first few days after ingestion, she was in a confused state and had mild to moderate ataxia and giddiness. She noticed hoarseness and distally accentuated motor and sensory dysfunction after she had recovered from this state. A nerve conduction study was consistent with severe sensorimotor axonal polyneuropathy. Laryngeal electromyography (thyroarytenoid muscle) showed ample denervation potentials. Laryngoscopy revealed asymmetric vocal fold movements during phonation. Her vocal change and weakness began to improve spontaneously about 3 weeks after transfer. This was a case of acute palsy of the recurrent laryngeal nerve and superimposed severe acute sensorimotor axonal polyneuropathy caused by high-dose disulfiram intoxication.", "entity": "Peripheral Nervous System Diseases", "aliases": "Nerve Disease Peripheral Diseases Neuropathy PNS (Peripheral Nervous System) System Disorders Neuropathies", "definition": "Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.\n    ", "id": "MESH:D010523"}
{"mention": "disulfiram", "mention_text": "Acute peripheral neuropathy caused by a disulfiram overdose is very rare and there is no report of it leading to vocal fold palsy. A 49-year-old woman was transferred to our department because of quadriparesis, lancinating pain, sensory loss, and paresthesia of the distal limbs. One month previously, she had taken a single high dose of disulfiram (130 tablets of ALCOHOL STOP TAB, Shin-Poong Pharm. Co., Ansan, Korea) in a suicide attempt. She was not an alcoholic. For the first few days after ingestion, she was in a confused state and had mild to moderate ataxia and giddiness. She noticed hoarseness and distally accentuated motor and sensory dysfunction after she had recovered from this state. A nerve conduction study was consistent with severe sensorimotor axonal polyneuropathy. Laryngeal electromyography (thyroarytenoid muscle) showed ample denervation potentials. Laryngoscopy revealed asymmetric vocal fold movements during phonation. Her vocal change and weakness began to improve spontaneously about 3 weeks after transfer. This was a case of acute palsy of the recurrent laryngeal nerve and superimposed severe acute sensorimotor axonal polyneuropathy caused by high-dose disulfiram intoxication.", "entity": "Disulfiram", "aliases": "Alcophobin Allphar Brand of Disulfiram Altana Pharma Antabus Antabuse Anticol Bis(diethylthiocarbamoyl) Disulfide Bohm Dicupral Tetraethylthiuram Dumex Esperal Odyssey Orphan Sanofi Synthelabo Tetraethylthioperoxydicarbonic Diamide ((H2N)C(S))2S2 Teturam", "definition": "A carbamate derivative used as an alcohol deterrent. It is a relatively nontoxic substance when administered alone, but markedly alters the intermediary metabolism of alcohol. When alcohol is ingested after administration of disulfiram, blood acetaldehyde concentrations are increased, followed by flushing, systemic vasodilation, respiratory difficulties, nausea, hypotension, and other symptoms (acetaldehyde syndrome). It acts by inhibiting aldehyde dehydrogenase.\n    ", "id": "MESH:D004221"}
{"mention": "overdose", "mention_text": "Acute peripheral neuropathy caused by a disulfiram overdose is very rare and there is no report of it leading to vocal fold palsy. A 49-year-old woman was transferred to our department because of quadriparesis, lancinating pain, sensory loss, and paresthesia of the distal limbs. One month previously, she had taken a single high dose of disulfiram (130 tablets of ALCOHOL STOP TAB, Shin-Poong Pharm. Co., Ansan, Korea) in a suicide attempt. She was not an alcoholic. For the first few days after ingestion, she was in a confused state and had mild to moderate ataxia and giddiness. She noticed hoarseness and distally accentuated motor and sensory dysfunction after she had recovered from this state. A nerve conduction study was consistent with severe sensorimotor axonal polyneuropathy. Laryngeal electromyography (thyroarytenoid muscle) showed ample denervation potentials. Laryngoscopy revealed asymmetric vocal fold movements during phonation. Her vocal change and weakness began to improve spontaneously about 3 weeks after transfer. This was a case of acute palsy of the recurrent laryngeal nerve and superimposed severe acute sensorimotor axonal polyneuropathy caused by high-dose disulfiram intoxication.", "entity": "Drug Overdose", "aliases": "Drug Overdose Overdoses", "definition": "Accidental or deliberate use of a medication or street drug in excess of normal dosage.\n    ", "id": "MESH:D062787"}
{"mention": "vocal fold palsy", "mention_text": "Acute peripheral neuropathy caused by a disulfiram overdose is very rare and there is no report of it leading to vocal fold palsy. A 49-year-old woman was transferred to our department because of quadriparesis, lancinating pain, sensory loss, and paresthesia of the distal limbs. One month previously, she had taken a single high dose of disulfiram (130 tablets of ALCOHOL STOP TAB, Shin-Poong Pharm. Co., Ansan, Korea) in a suicide attempt. She was not an alcoholic. For the first few days after ingestion, she was in a confused state and had mild to moderate ataxia and giddiness. She noticed hoarseness and distally accentuated motor and sensory dysfunction after she had recovered from this state. A nerve conduction study was consistent with severe sensorimotor axonal polyneuropathy. Laryngeal electromyography (thyroarytenoid muscle) showed ample denervation potentials. Laryngoscopy revealed asymmetric vocal fold movements during phonation. Her vocal change and weakness began to improve spontaneously about 3 weeks after transfer. This was a case of acute palsy of the recurrent laryngeal nerve and superimposed severe acute sensorimotor axonal polyneuropathy caused by high-dose disulfiram intoxication.", "entity": "Vocal Cord Paralysis", "aliases": "Acquired Vocal Cord Palsy Bilateral Paresis Congenital Laryngeal Nerve Recurrent Paralyses Paralysis Palsies Fold Unilateral Pareses Partial (Paresis) Cords Total", "definition": "Congenital or acquired paralysis of one or both VOCAL CORDS. This condition is caused by defects in the CENTRAL NERVOUS SYSTEM, the VAGUS NERVE and branches of LARYNGEAL NERVES. Common symptoms are VOICE DISORDERS including HOARSENESS or APHONIA.\n    ", "id": "MESH:D014826"}
{"mention": "quadriparesis", "mention_text": "Acute peripheral neuropathy caused by a disulfiram overdose is very rare and there is no report of it leading to vocal fold palsy. A 49-year-old woman was transferred to our department because of quadriparesis, lancinating pain, sensory loss, and paresthesia of the distal limbs. One month previously, she had taken a single high dose of disulfiram (130 tablets of ALCOHOL STOP TAB, Shin-Poong Pharm. Co., Ansan, Korea) in a suicide attempt. She was not an alcoholic. For the first few days after ingestion, she was in a confused state and had mild to moderate ataxia and giddiness. She noticed hoarseness and distally accentuated motor and sensory dysfunction after she had recovered from this state. A nerve conduction study was consistent with severe sensorimotor axonal polyneuropathy. Laryngeal electromyography (thyroarytenoid muscle) showed ample denervation potentials. Laryngoscopy revealed asymmetric vocal fold movements during phonation. Her vocal change and weakness began to improve spontaneously about 3 weeks after transfer. This was a case of acute palsy of the recurrent laryngeal nerve and superimposed severe acute sensorimotor axonal polyneuropathy caused by high-dose disulfiram intoxication.", "entity": "Quadriplegia", "aliases": "Flaccid Quadriplegia Quadriplegias Tetraplegia Tetraplegias Locked In Syndrome Locked-In Syndromes Paralysis Spinal Quadriplegic Quadripareses Quadriparesis Spastic", "definition": "Severe or complete loss of motor function in all four limbs which may result from BRAIN DISEASES; SPINAL CORD DISEASES; PERIPHERAL NERVOUS SYSTEM DISEASES; NEUROMUSCULAR DISEASES; or rarely MUSCULAR DISEASES. The locked-in syndrome is characterized by quadriplegia in combination with cranial muscle paralysis. Consciousness is spared and the only retained voluntary motor activity may be limited eye movements. This condition is usually caused by a lesion in the upper BRAIN STEM which injures the descending cortico-spinal and cortico-bulbar tracts.\n    ", "id": "MESH:D011782"}
{"mention": "pain", "mention_text": "Acute peripheral neuropathy caused by a disulfiram overdose is very rare and there is no report of it leading to vocal fold palsy. A 49-year-old woman was transferred to our department because of quadriparesis, lancinating pain, sensory loss, and paresthesia of the distal limbs. One month previously, she had taken a single high dose of disulfiram (130 tablets of ALCOHOL STOP TAB, Shin-Poong Pharm. Co., Ansan, Korea) in a suicide attempt. She was not an alcoholic. For the first few days after ingestion, she was in a confused state and had mild to moderate ataxia and giddiness. She noticed hoarseness and distally accentuated motor and sensory dysfunction after she had recovered from this state. A nerve conduction study was consistent with severe sensorimotor axonal polyneuropathy. Laryngeal electromyography (thyroarytenoid muscle) showed ample denervation potentials. Laryngoscopy revealed asymmetric vocal fold movements during phonation. Her vocal change and weakness began to improve spontaneously about 3 weeks after transfer. This was a case of acute palsy of the recurrent laryngeal nerve and superimposed severe acute sensorimotor axonal polyneuropathy caused by high-dose disulfiram intoxication.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "sensory loss", "mention_text": "Acute peripheral neuropathy caused by a disulfiram overdose is very rare and there is no report of it leading to vocal fold palsy. A 49-year-old woman was transferred to our department because of quadriparesis, lancinating pain, sensory loss, and paresthesia of the distal limbs. One month previously, she had taken a single high dose of disulfiram (130 tablets of ALCOHOL STOP TAB, Shin-Poong Pharm. Co., Ansan, Korea) in a suicide attempt. She was not an alcoholic. For the first few days after ingestion, she was in a confused state and had mild to moderate ataxia and giddiness. She noticed hoarseness and distally accentuated motor and sensory dysfunction after she had recovered from this state. A nerve conduction study was consistent with severe sensorimotor axonal polyneuropathy. Laryngeal electromyography (thyroarytenoid muscle) showed ample denervation potentials. Laryngoscopy revealed asymmetric vocal fold movements during phonation. Her vocal change and weakness began to improve spontaneously about 3 weeks after transfer. This was a case of acute palsy of the recurrent laryngeal nerve and superimposed severe acute sensorimotor axonal polyneuropathy caused by high-dose disulfiram intoxication.", "entity": "Hereditary Sensory and Autonomic Neuropathy Type Ie", "aliases": "Dnmt1-Related Dementia Deafness and Sensory Neuropathy Hereditary Type Ie Autonomic 1 with Hearing Loss Hsn Hsnie", "definition": "", "id": "MESH:C580162"}
{"mention": "paresthesia", "mention_text": "Acute peripheral neuropathy caused by a disulfiram overdose is very rare and there is no report of it leading to vocal fold palsy. A 49-year-old woman was transferred to our department because of quadriparesis, lancinating pain, sensory loss, and paresthesia of the distal limbs. One month previously, she had taken a single high dose of disulfiram (130 tablets of ALCOHOL STOP TAB, Shin-Poong Pharm. Co., Ansan, Korea) in a suicide attempt. She was not an alcoholic. For the first few days after ingestion, she was in a confused state and had mild to moderate ataxia and giddiness. She noticed hoarseness and distally accentuated motor and sensory dysfunction after she had recovered from this state. A nerve conduction study was consistent with severe sensorimotor axonal polyneuropathy. Laryngeal electromyography (thyroarytenoid muscle) showed ample denervation potentials. Laryngoscopy revealed asymmetric vocal fold movements during phonation. Her vocal change and weakness began to improve spontaneously about 3 weeks after transfer. This was a case of acute palsy of the recurrent laryngeal nerve and superimposed severe acute sensorimotor axonal polyneuropathy caused by high-dose disulfiram intoxication.", "entity": "Paresthesia", "aliases": "Distal Paresthesia Paresthesias Dysesthesia Dysesthesias Formication Formications Painful", "definition": "Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation.\n    ", "id": "MESH:D010292"}
{"mention": "ALCOHOL", "mention_text": "Acute peripheral neuropathy caused by a disulfiram overdose is very rare and there is no report of it leading to vocal fold palsy. A 49-year-old woman was transferred to our department because of quadriparesis, lancinating pain, sensory loss, and paresthesia of the distal limbs. One month previously, she had taken a single high dose of disulfiram (130 tablets of ALCOHOL STOP TAB, Shin-Poong Pharm. Co., Ansan, Korea) in a suicide attempt. She was not an alcoholic. For the first few days after ingestion, she was in a confused state and had mild to moderate ataxia and giddiness. She noticed hoarseness and distally accentuated motor and sensory dysfunction after she had recovered from this state. A nerve conduction study was consistent with severe sensorimotor axonal polyneuropathy. Laryngeal electromyography (thyroarytenoid muscle) showed ample denervation potentials. Laryngoscopy revealed asymmetric vocal fold movements during phonation. Her vocal change and weakness began to improve spontaneously about 3 weeks after transfer. This was a case of acute palsy of the recurrent laryngeal nerve and superimposed severe acute sensorimotor axonal polyneuropathy caused by high-dose disulfiram intoxication.", "entity": "Ethanol", "aliases": "Absolute Alcohol Ethyl Grain Ethanol", "definition": "A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.\n    ", "id": "MESH:D000431"}
{"mention": "ataxia", "mention_text": "Acute peripheral neuropathy caused by a disulfiram overdose is very rare and there is no report of it leading to vocal fold palsy. A 49-year-old woman was transferred to our department because of quadriparesis, lancinating pain, sensory loss, and paresthesia of the distal limbs. One month previously, she had taken a single high dose of disulfiram (130 tablets of ALCOHOL STOP TAB, Shin-Poong Pharm. Co., Ansan, Korea) in a suicide attempt. She was not an alcoholic. For the first few days after ingestion, she was in a confused state and had mild to moderate ataxia and giddiness. She noticed hoarseness and distally accentuated motor and sensory dysfunction after she had recovered from this state. A nerve conduction study was consistent with severe sensorimotor axonal polyneuropathy. Laryngeal electromyography (thyroarytenoid muscle) showed ample denervation potentials. Laryngoscopy revealed asymmetric vocal fold movements during phonation. Her vocal change and weakness began to improve spontaneously about 3 weeks after transfer. This was a case of acute palsy of the recurrent laryngeal nerve and superimposed severe acute sensorimotor axonal polyneuropathy caused by high-dose disulfiram intoxication.", "entity": "Ataxia", "aliases": "Appendicular Ataxia Ataxias Limb Motor Sensory Truncal Ataxy Coordination Impairment Impairments Lack Dyscoordination Dyssynergia Incoordination Incoordinations of Rubral Tremor Tremors", "definition": "Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or PERIPHERAL NERVE DISEASES. Motor ataxia may be associated with CEREBELLAR DISEASES; CEREBRAL CORTEX diseases; THALAMIC DISEASES; BASAL GANGLIA DISEASES; injury to the RED NUCLEUS; and other conditions.\n    ", "id": "MESH:D001259"}
{"mention": "giddiness", "mention_text": "Acute peripheral neuropathy caused by a disulfiram overdose is very rare and there is no report of it leading to vocal fold palsy. A 49-year-old woman was transferred to our department because of quadriparesis, lancinating pain, sensory loss, and paresthesia of the distal limbs. One month previously, she had taken a single high dose of disulfiram (130 tablets of ALCOHOL STOP TAB, Shin-Poong Pharm. Co., Ansan, Korea) in a suicide attempt. She was not an alcoholic. For the first few days after ingestion, she was in a confused state and had mild to moderate ataxia and giddiness. She noticed hoarseness and distally accentuated motor and sensory dysfunction after she had recovered from this state. A nerve conduction study was consistent with severe sensorimotor axonal polyneuropathy. Laryngeal electromyography (thyroarytenoid muscle) showed ample denervation potentials. Laryngoscopy revealed asymmetric vocal fold movements during phonation. Her vocal change and weakness began to improve spontaneously about 3 weeks after transfer. This was a case of acute palsy of the recurrent laryngeal nerve and superimposed severe acute sensorimotor axonal polyneuropathy caused by high-dose disulfiram intoxication.", "entity": "Dizziness", "aliases": "Dizziness Dizzyness Light Headedness Light-Headedness Lightheadedness Orthostasis", "definition": "An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness.\n    ", "id": "MESH:D004244"}
{"mention": "hoarseness", "mention_text": "Acute peripheral neuropathy caused by a disulfiram overdose is very rare and there is no report of it leading to vocal fold palsy. A 49-year-old woman was transferred to our department because of quadriparesis, lancinating pain, sensory loss, and paresthesia of the distal limbs. One month previously, she had taken a single high dose of disulfiram (130 tablets of ALCOHOL STOP TAB, Shin-Poong Pharm. Co., Ansan, Korea) in a suicide attempt. She was not an alcoholic. For the first few days after ingestion, she was in a confused state and had mild to moderate ataxia and giddiness. She noticed hoarseness and distally accentuated motor and sensory dysfunction after she had recovered from this state. A nerve conduction study was consistent with severe sensorimotor axonal polyneuropathy. Laryngeal electromyography (thyroarytenoid muscle) showed ample denervation potentials. Laryngoscopy revealed asymmetric vocal fold movements during phonation. Her vocal change and weakness began to improve spontaneously about 3 weeks after transfer. This was a case of acute palsy of the recurrent laryngeal nerve and superimposed severe acute sensorimotor axonal polyneuropathy caused by high-dose disulfiram intoxication.", "entity": "Hoarseness", "aliases": "Hoarseness of Voice Neurogenic Hoarsenesses", "definition": "An unnaturally deep or rough quality of voice.\n    ", "id": "MESH:D006685"}
{"mention": "polyneuropathy", "mention_text": "Acute peripheral neuropathy caused by a disulfiram overdose is very rare and there is no report of it leading to vocal fold palsy. A 49-year-old woman was transferred to our department because of quadriparesis, lancinating pain, sensory loss, and paresthesia of the distal limbs. One month previously, she had taken a single high dose of disulfiram (130 tablets of ALCOHOL STOP TAB, Shin-Poong Pharm. Co., Ansan, Korea) in a suicide attempt. She was not an alcoholic. For the first few days after ingestion, she was in a confused state and had mild to moderate ataxia and giddiness. She noticed hoarseness and distally accentuated motor and sensory dysfunction after she had recovered from this state. A nerve conduction study was consistent with severe sensorimotor axonal polyneuropathy. Laryngeal electromyography (thyroarytenoid muscle) showed ample denervation potentials. Laryngoscopy revealed asymmetric vocal fold movements during phonation. Her vocal change and weakness began to improve spontaneously about 3 weeks after transfer. This was a case of acute palsy of the recurrent laryngeal nerve and superimposed severe acute sensorimotor axonal polyneuropathy caused by high-dose disulfiram intoxication.", "entity": "Polyneuropathies", "aliases": "Acquired Polyneuropathies Polyneuropathy Critical Illness Familial Inherited Motor", "definition": "Diseases of multiple peripheral nerves simultaneously. Polyneuropathies usually are characterized by symmetrical, bilateral distal motor and sensory impairment with a graded increase in severity distally. The pathological processes affecting peripheral nerves include degeneration of the axon, myelin or both. The various forms of polyneuropathy are categorized by the type of nerve affected (e.g., sensory, motor, or autonomic), by the distribution of nerve injury (e.g., distal vs. proximal), by nerve component primarily affected (e.g., demyelinating vs. axonal), by etiology, or by pattern of inheritance.\n    ", "id": "MESH:D011115"}
{"mention": "palsy", "mention_text": "Acute peripheral neuropathy caused by a disulfiram overdose is very rare and there is no report of it leading to vocal fold palsy. A 49-year-old woman was transferred to our department because of quadriparesis, lancinating pain, sensory loss, and paresthesia of the distal limbs. One month previously, she had taken a single high dose of disulfiram (130 tablets of ALCOHOL STOP TAB, Shin-Poong Pharm. Co., Ansan, Korea) in a suicide attempt. She was not an alcoholic. For the first few days after ingestion, she was in a confused state and had mild to moderate ataxia and giddiness. She noticed hoarseness and distally accentuated motor and sensory dysfunction after she had recovered from this state. A nerve conduction study was consistent with severe sensorimotor axonal polyneuropathy. Laryngeal electromyography (thyroarytenoid muscle) showed ample denervation potentials. Laryngoscopy revealed asymmetric vocal fold movements during phonation. Her vocal change and weakness began to improve spontaneously about 3 weeks after transfer. This was a case of acute palsy of the recurrent laryngeal nerve and superimposed severe acute sensorimotor axonal polyneuropathy caused by high-dose disulfiram intoxication.", "entity": "Paralysis", "aliases": "Palsies Palsy Paralyses Paralysis Todd Todd's Plegia Plegias Todds", "definition": "A general term most often used to describe severe or complete loss of muscle strength due to motor system disease from the level of the cerebral cortex to the muscle fiber. This term may also occasionally refer to a loss of sensory function. (From Adams et al., Principles of Neurology, 6th ed, p45)\n    ", "id": "MESH:D010243"}
{"mention": "thrombosis", "mention_text": "Higher optical density of an antigen assay predicts thrombosis in patients with heparin-induced thrombocytopenia.", "entity": "Thrombosis", "aliases": "Thromboses Thrombosis Thrombus", "definition": "Formation and development of a thrombus or blood clot in the blood vessel.\n    ", "id": "MESH:D013927"}
{"mention": "heparin", "mention_text": "Higher optical density of an antigen assay predicts thrombosis in patients with heparin-induced thrombocytopenia.", "entity": "Heparin", "aliases": "Heparin Sodium Unfractionated Heparinic Acid Liquaemin alpha alpha-Heparin", "definition": "A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.\n    ", "id": "MESH:D006493"}
{"mention": "thrombocytopenia", "mention_text": "Higher optical density of an antigen assay predicts thrombosis in patients with heparin-induced thrombocytopenia.", "entity": "Thrombocytopenia", "aliases": "Thrombocytopenia Thrombocytopenias Thrombopenia Thrombopenias", "definition": "A subnormal level of BLOOD PLATELETS.\n    ", "id": "MESH:D013921"}
{"mention": "heparin", "mention_text": "OBJECTIVES: To correlate optical density and percent inhibition of a two-step heparin-induced thrombocytopenia (HIT) antigen assay with thrombosis; the assay utilizes reaction inhibition characteristics of a high heparin concentration. PATIENTS AND METHODS: Patients with more than 50% decrease in platelet count or thrombocytopenia (<150 x 10(9)/L) after exposure to heparin, who had a positive two-step antigen assay [optical density (OD) >0.4 and >50 inhibition with high concentration of heparin] were included in the study. RESULTS: Forty of 94 HIT patients had thrombosis at diagnosis; 54/94 had isolated-HIT without thrombosis. Eight of the isolated-HIT patients developed thrombosis within the next 30 d; thus, a total of 48 patients had thrombosis at day 30. At diagnosis there was no significant difference in OD between HIT patients with thrombosis and those with isolated-HIT. However, OD was significantly higher in all patients with thrombosis (n = 48, 1.34 +/- 0.89), including isolated-HIT patients who later developed thrombosis within 30 d (n = 8, 1.84 +/- 0.64) as compared to isolated-HIT patients who did not develop thrombosis (0.96 +/- 0.75; P = 0.011 and P = 0.008). The Receiver Operative Characteristic Curve showed that OD >1.27 in the isolated-HIT group had a significantly higher chance of developing thrombosis by day 30. None of these groups showed significant difference in percent inhibition. Multivariate analysis showed a 2.8-fold increased risk of thrombosis in females. Similarly, thrombotic risk increased with age and OD values. CONCLUSION: Higher OD is associated with significant risk of subsequent thrombosis in patients with isolated-HIT; percent inhibition, however, was not predictive.", "entity": "Heparin", "aliases": "Heparin Sodium Unfractionated Heparinic Acid Liquaemin alpha alpha-Heparin", "definition": "A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.\n    ", "id": "MESH:D006493"}
{"mention": "thrombocytopenia", "mention_text": "OBJECTIVES: To correlate optical density and percent inhibition of a two-step heparin-induced thrombocytopenia (HIT) antigen assay with thrombosis; the assay utilizes reaction inhibition characteristics of a high heparin concentration. PATIENTS AND METHODS: Patients with more than 50% decrease in platelet count or thrombocytopenia (<150 x 10(9)/L) after exposure to heparin, who had a positive two-step antigen assay [optical density (OD) >0.4 and >50 inhibition with high concentration of heparin] were included in the study. RESULTS: Forty of 94 HIT patients had thrombosis at diagnosis; 54/94 had isolated-HIT without thrombosis. Eight of the isolated-HIT patients developed thrombosis within the next 30 d; thus, a total of 48 patients had thrombosis at day 30. At diagnosis there was no significant difference in OD between HIT patients with thrombosis and those with isolated-HIT. However, OD was significantly higher in all patients with thrombosis (n = 48, 1.34 +/- 0.89), including isolated-HIT patients who later developed thrombosis within 30 d (n = 8, 1.84 +/- 0.64) as compared to isolated-HIT patients who did not develop thrombosis (0.96 +/- 0.75; P = 0.011 and P = 0.008). The Receiver Operative Characteristic Curve showed that OD >1.27 in the isolated-HIT group had a significantly higher chance of developing thrombosis by day 30. None of these groups showed significant difference in percent inhibition. Multivariate analysis showed a 2.8-fold increased risk of thrombosis in females. Similarly, thrombotic risk increased with age and OD values. CONCLUSION: Higher OD is associated with significant risk of subsequent thrombosis in patients with isolated-HIT; percent inhibition, however, was not predictive.", "entity": "Thrombocytopenia", "aliases": "Thrombocytopenia Thrombocytopenias Thrombopenia Thrombopenias", "definition": "A subnormal level of BLOOD PLATELETS.\n    ", "id": "MESH:D013921"}
{"mention": "HIT", "mention_text": "OBJECTIVES: To correlate optical density and percent inhibition of a two-step heparin-induced thrombocytopenia (HIT) antigen assay with thrombosis; the assay utilizes reaction inhibition characteristics of a high heparin concentration. PATIENTS AND METHODS: Patients with more than 50% decrease in platelet count or thrombocytopenia (<150 x 10(9)/L) after exposure to heparin, who had a positive two-step antigen assay [optical density (OD) >0.4 and >50 inhibition with high concentration of heparin] were included in the study. RESULTS: Forty of 94 HIT patients had thrombosis at diagnosis; 54/94 had isolated-HIT without thrombosis. Eight of the isolated-HIT patients developed thrombosis within the next 30 d; thus, a total of 48 patients had thrombosis at day 30. At diagnosis there was no significant difference in OD between HIT patients with thrombosis and those with isolated-HIT. However, OD was significantly higher in all patients with thrombosis (n = 48, 1.34 +/- 0.89), including isolated-HIT patients who later developed thrombosis within 30 d (n = 8, 1.84 +/- 0.64) as compared to isolated-HIT patients who did not develop thrombosis (0.96 +/- 0.75; P = 0.011 and P = 0.008). The Receiver Operative Characteristic Curve showed that OD >1.27 in the isolated-HIT group had a significantly higher chance of developing thrombosis by day 30. None of these groups showed significant difference in percent inhibition. Multivariate analysis showed a 2.8-fold increased risk of thrombosis in females. Similarly, thrombotic risk increased with age and OD values. CONCLUSION: Higher OD is associated with significant risk of subsequent thrombosis in patients with isolated-HIT; percent inhibition, however, was not predictive.", "entity": "Thrombocytopenia", "aliases": "Thrombocytopenia Thrombocytopenias Thrombopenia Thrombopenias", "definition": "A subnormal level of BLOOD PLATELETS.\n    ", "id": "MESH:D013921"}
{"mention": "thrombosis", "mention_text": "OBJECTIVES: To correlate optical density and percent inhibition of a two-step heparin-induced thrombocytopenia (HIT) antigen assay with thrombosis; the assay utilizes reaction inhibition characteristics of a high heparin concentration. PATIENTS AND METHODS: Patients with more than 50% decrease in platelet count or thrombocytopenia (<150 x 10(9)/L) after exposure to heparin, who had a positive two-step antigen assay [optical density (OD) >0.4 and >50 inhibition with high concentration of heparin] were included in the study. RESULTS: Forty of 94 HIT patients had thrombosis at diagnosis; 54/94 had isolated-HIT without thrombosis. Eight of the isolated-HIT patients developed thrombosis within the next 30 d; thus, a total of 48 patients had thrombosis at day 30. At diagnosis there was no significant difference in OD between HIT patients with thrombosis and those with isolated-HIT. However, OD was significantly higher in all patients with thrombosis (n = 48, 1.34 +/- 0.89), including isolated-HIT patients who later developed thrombosis within 30 d (n = 8, 1.84 +/- 0.64) as compared to isolated-HIT patients who did not develop thrombosis (0.96 +/- 0.75; P = 0.011 and P = 0.008). The Receiver Operative Characteristic Curve showed that OD >1.27 in the isolated-HIT group had a significantly higher chance of developing thrombosis by day 30. None of these groups showed significant difference in percent inhibition. Multivariate analysis showed a 2.8-fold increased risk of thrombosis in females. Similarly, thrombotic risk increased with age and OD values. CONCLUSION: Higher OD is associated with significant risk of subsequent thrombosis in patients with isolated-HIT; percent inhibition, however, was not predictive.", "entity": "Thrombosis", "aliases": "Thromboses Thrombosis Thrombus", "definition": "Formation and development of a thrombus or blood clot in the blood vessel.\n    ", "id": "MESH:D013927"}
{"mention": "thrombotic", "mention_text": "OBJECTIVES: To correlate optical density and percent inhibition of a two-step heparin-induced thrombocytopenia (HIT) antigen assay with thrombosis; the assay utilizes reaction inhibition characteristics of a high heparin concentration. PATIENTS AND METHODS: Patients with more than 50% decrease in platelet count or thrombocytopenia (<150 x 10(9)/L) after exposure to heparin, who had a positive two-step antigen assay [optical density (OD) >0.4 and >50 inhibition with high concentration of heparin] were included in the study. RESULTS: Forty of 94 HIT patients had thrombosis at diagnosis; 54/94 had isolated-HIT without thrombosis. Eight of the isolated-HIT patients developed thrombosis within the next 30 d; thus, a total of 48 patients had thrombosis at day 30. At diagnosis there was no significant difference in OD between HIT patients with thrombosis and those with isolated-HIT. However, OD was significantly higher in all patients with thrombosis (n = 48, 1.34 +/- 0.89), including isolated-HIT patients who later developed thrombosis within 30 d (n = 8, 1.84 +/- 0.64) as compared to isolated-HIT patients who did not develop thrombosis (0.96 +/- 0.75; P = 0.011 and P = 0.008). The Receiver Operative Characteristic Curve showed that OD >1.27 in the isolated-HIT group had a significantly higher chance of developing thrombosis by day 30. None of these groups showed significant difference in percent inhibition. Multivariate analysis showed a 2.8-fold increased risk of thrombosis in females. Similarly, thrombotic risk increased with age and OD values. CONCLUSION: Higher OD is associated with significant risk of subsequent thrombosis in patients with isolated-HIT; percent inhibition, however, was not predictive.", "entity": "Thrombosis", "aliases": "Thromboses Thrombosis Thrombus", "definition": "Formation and development of a thrombus or blood clot in the blood vessel.\n    ", "id": "MESH:D013927"}
{"mention": "retinal vein occlusion", "mention_text": "Central retinal vein occlusion associated with clomiphene-induced ovulation.", "entity": "Retinal Vein Occlusion", "aliases": "Occlusion Retinal Vein Occlusions Thromboses Thrombosis", "definition": "Blockage of the RETINAL VEIN. Those at high risk for this condition include patients with HYPERTENSION; DIABETES MELLITUS; ATHEROSCLEROSIS; and other CARDIOVASCULAR DISEASES.\n    ", "id": "MESH:D012170"}
{"mention": "clomiphene", "mention_text": "Central retinal vein occlusion associated with clomiphene-induced ovulation.", "entity": "Clomiphene", "aliases": "Chloramiphene Citrate Clomiphene Clomid Clomide Clomifen Clomifene Hydrochloride Clostilbegit Dyneric Gravosan Klostilbegit Serophene", "definition": "A triphenyl ethylene stilbene derivative which is an estrogen agonist or antagonist depending on the target tissue. Note that ENCLOMIPHENE and ZUCLOMIPHENE are the (E) and (Z) isomers of Clomiphene respectively.\n    ", "id": "MESH:D002996"}
{"mention": "retinal vein occlusion", "mention_text": "OBJECTIVE: To report a case of central retinal vein occlusion associated with clomiphene citrate (CC). DESIGN: Case study. SETTING: Ophthalmology clinic of an academic hospital. PATIENT(S): A 36-year-old woman referred from the infertility clinic for blurred vision. INTERVENTION(S): Ophthalmic examination after CC therapy. MAIN OUTCOME MEASURE(S): Central retinal vein occlusion after ovulation induction with CC. RESULT(S): A 36-year-old Chinese woman developed central retinal vein occlusion after eight courses of CC. A search of the literature on the thromboembolic complications of CC does not include this severe ophthalmic complication, although mild visual disturbance after CC intake is not uncommon. CONCLUSION(S): This is the first reported case of central retinal vein occlusion after treatment with CC. Extra caution is warranted in treating infertility patients with CC, and patients should be well informed of this side effect before commencement of therapy.", "entity": "Retinal Vein Occlusion", "aliases": "Occlusion Retinal Vein Occlusions Thromboses Thrombosis", "definition": "Blockage of the RETINAL VEIN. Those at high risk for this condition include patients with HYPERTENSION; DIABETES MELLITUS; ATHEROSCLEROSIS; and other CARDIOVASCULAR DISEASES.\n    ", "id": "MESH:D012170"}
{"mention": "clomiphene citrate", "mention_text": "OBJECTIVE: To report a case of central retinal vein occlusion associated with clomiphene citrate (CC). DESIGN: Case study. SETTING: Ophthalmology clinic of an academic hospital. PATIENT(S): A 36-year-old woman referred from the infertility clinic for blurred vision. INTERVENTION(S): Ophthalmic examination after CC therapy. MAIN OUTCOME MEASURE(S): Central retinal vein occlusion after ovulation induction with CC. RESULT(S): A 36-year-old Chinese woman developed central retinal vein occlusion after eight courses of CC. A search of the literature on the thromboembolic complications of CC does not include this severe ophthalmic complication, although mild visual disturbance after CC intake is not uncommon. CONCLUSION(S): This is the first reported case of central retinal vein occlusion after treatment with CC. Extra caution is warranted in treating infertility patients with CC, and patients should be well informed of this side effect before commencement of therapy.", "entity": "Clomiphene", "aliases": "Chloramiphene Citrate Clomiphene Clomid Clomide Clomifen Clomifene Hydrochloride Clostilbegit Dyneric Gravosan Klostilbegit Serophene", "definition": "A triphenyl ethylene stilbene derivative which is an estrogen agonist or antagonist depending on the target tissue. Note that ENCLOMIPHENE and ZUCLOMIPHENE are the (E) and (Z) isomers of Clomiphene respectively.\n    ", "id": "MESH:D002996"}
{"mention": "CC", "mention_text": "OBJECTIVE: To report a case of central retinal vein occlusion associated with clomiphene citrate (CC). DESIGN: Case study. SETTING: Ophthalmology clinic of an academic hospital. PATIENT(S): A 36-year-old woman referred from the infertility clinic for blurred vision. INTERVENTION(S): Ophthalmic examination after CC therapy. MAIN OUTCOME MEASURE(S): Central retinal vein occlusion after ovulation induction with CC. RESULT(S): A 36-year-old Chinese woman developed central retinal vein occlusion after eight courses of CC. A search of the literature on the thromboembolic complications of CC does not include this severe ophthalmic complication, although mild visual disturbance after CC intake is not uncommon. CONCLUSION(S): This is the first reported case of central retinal vein occlusion after treatment with CC. Extra caution is warranted in treating infertility patients with CC, and patients should be well informed of this side effect before commencement of therapy.", "entity": "Clomiphene", "aliases": "Chloramiphene Citrate Clomiphene Clomid Clomide Clomifen Clomifene Hydrochloride Clostilbegit Dyneric Gravosan Klostilbegit Serophene", "definition": "A triphenyl ethylene stilbene derivative which is an estrogen agonist or antagonist depending on the target tissue. Note that ENCLOMIPHENE and ZUCLOMIPHENE are the (E) and (Z) isomers of Clomiphene respectively.\n    ", "id": "MESH:D002996"}
{"mention": "infertility", "mention_text": "OBJECTIVE: To report a case of central retinal vein occlusion associated with clomiphene citrate (CC). DESIGN: Case study. SETTING: Ophthalmology clinic of an academic hospital. PATIENT(S): A 36-year-old woman referred from the infertility clinic for blurred vision. INTERVENTION(S): Ophthalmic examination after CC therapy. MAIN OUTCOME MEASURE(S): Central retinal vein occlusion after ovulation induction with CC. RESULT(S): A 36-year-old Chinese woman developed central retinal vein occlusion after eight courses of CC. A search of the literature on the thromboembolic complications of CC does not include this severe ophthalmic complication, although mild visual disturbance after CC intake is not uncommon. CONCLUSION(S): This is the first reported case of central retinal vein occlusion after treatment with CC. Extra caution is warranted in treating infertility patients with CC, and patients should be well informed of this side effect before commencement of therapy.", "entity": "Infertility, Female", "aliases": "Female Infertility Sterility Sub-Fertility Subfertility Postpartum Sub Fertility", "definition": "Diminished or absent ability of a female to achieve conception.\n    ", "id": "MESH:D007247"}
{"mention": "blurred vision", "mention_text": "OBJECTIVE: To report a case of central retinal vein occlusion associated with clomiphene citrate (CC). DESIGN: Case study. SETTING: Ophthalmology clinic of an academic hospital. PATIENT(S): A 36-year-old woman referred from the infertility clinic for blurred vision. INTERVENTION(S): Ophthalmic examination after CC therapy. MAIN OUTCOME MEASURE(S): Central retinal vein occlusion after ovulation induction with CC. RESULT(S): A 36-year-old Chinese woman developed central retinal vein occlusion after eight courses of CC. A search of the literature on the thromboembolic complications of CC does not include this severe ophthalmic complication, although mild visual disturbance after CC intake is not uncommon. CONCLUSION(S): This is the first reported case of central retinal vein occlusion after treatment with CC. Extra caution is warranted in treating infertility patients with CC, and patients should be well informed of this side effect before commencement of therapy.", "entity": "Vision Disorders", "aliases": "Blindness Day Disabilities Vision Disability Disorder Visual Disorders Hemeralopia Hemeralopias Impairment Impairments Macropsia Macropsias Metamorphopsia Metamorphopsias Micropsia Micropsias", "definition": "Visual impairments limiting one or more of the basic functions of the eye: visual acuity, dark adaptation, color vision, or peripheral vision. These may result from EYE DISEASES; OPTIC NERVE DISEASES; VISUAL PATHWAY diseases; OCCIPITAL LOBE diseases; OCULAR MOTILITY DISORDERS; and other conditions (From Newell, Ophthalmology: Principles and Concepts, 7th ed, p132).\n    ", "id": "MESH:D014786"}
{"mention": "thromboembolic", "mention_text": "OBJECTIVE: To report a case of central retinal vein occlusion associated with clomiphene citrate (CC). DESIGN: Case study. SETTING: Ophthalmology clinic of an academic hospital. PATIENT(S): A 36-year-old woman referred from the infertility clinic for blurred vision. INTERVENTION(S): Ophthalmic examination after CC therapy. MAIN OUTCOME MEASURE(S): Central retinal vein occlusion after ovulation induction with CC. RESULT(S): A 36-year-old Chinese woman developed central retinal vein occlusion after eight courses of CC. A search of the literature on the thromboembolic complications of CC does not include this severe ophthalmic complication, although mild visual disturbance after CC intake is not uncommon. CONCLUSION(S): This is the first reported case of central retinal vein occlusion after treatment with CC. Extra caution is warranted in treating infertility patients with CC, and patients should be well informed of this side effect before commencement of therapy.", "entity": "Thromboembolism", "aliases": "Thromboembolism Thromboembolisms", "definition": "Obstruction of a blood vessel (embolism) by a blood clot (THROMBUS) in the blood stream.\n    ", "id": "MESH:D013923"}
{"mention": "visual disturbance", "mention_text": "OBJECTIVE: To report a case of central retinal vein occlusion associated with clomiphene citrate (CC). DESIGN: Case study. SETTING: Ophthalmology clinic of an academic hospital. PATIENT(S): A 36-year-old woman referred from the infertility clinic for blurred vision. INTERVENTION(S): Ophthalmic examination after CC therapy. MAIN OUTCOME MEASURE(S): Central retinal vein occlusion after ovulation induction with CC. RESULT(S): A 36-year-old Chinese woman developed central retinal vein occlusion after eight courses of CC. A search of the literature on the thromboembolic complications of CC does not include this severe ophthalmic complication, although mild visual disturbance after CC intake is not uncommon. CONCLUSION(S): This is the first reported case of central retinal vein occlusion after treatment with CC. Extra caution is warranted in treating infertility patients with CC, and patients should be well informed of this side effect before commencement of therapy.", "entity": "Vision Disorders", "aliases": "Blindness Day Disabilities Vision Disability Disorder Visual Disorders Hemeralopia Hemeralopias Impairment Impairments Macropsia Macropsias Metamorphopsia Metamorphopsias Micropsia Micropsias", "definition": "Visual impairments limiting one or more of the basic functions of the eye: visual acuity, dark adaptation, color vision, or peripheral vision. These may result from EYE DISEASES; OPTIC NERVE DISEASES; VISUAL PATHWAY diseases; OCCIPITAL LOBE diseases; OCULAR MOTILITY DISORDERS; and other conditions (From Newell, Ophthalmology: Principles and Concepts, 7th ed, p132).\n    ", "id": "MESH:D014786"}
{"mention": "Nicotine", "mention_text": "Nicotine-induced nystagmus correlates with midpontine activation.", "entity": "Nicotine", "aliases": "Bitartrate Nicotine Tartrate", "definition": "Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.\n    ", "id": "MESH:D009538"}
{"mention": "nystagmus", "mention_text": "Nicotine-induced nystagmus correlates with midpontine activation.", "entity": "Nystagmus, Pathologic", "aliases": "Alternating Nystagmus Periodic Conjugate Convergence Dissociated Fatigable Positional Horizontal Jerk Multidirectional Non Non-Fatigable Pathologic Pendular Permanent Rebound Retraction Rotary Rotational See-Saw Spontaneous Ocular Symptomatic Temporary Unidirectional Vertical See Saw", "definition": "Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. (Adams et al., Principles of Neurology, 6th ed, p272)\n    ", "id": "MESH:D009759"}
{"mention": "nicotine", "mention_text": "The pathomechanism of nicotine-induced nystagmus (NIN) is unknown. The aim of this study was to delineate brain structures that are involved in NIN generation. Eight healthy volunteers inhaled nicotine in darkness during a functional magnetic resonance imaging (fMRI) experiment; eye movements were registered using video-oculography. NIN correlated with blood oxygen level-dependent (BOLD) activity levels in a midpontine site in the posterior basis pontis. NIN-induced midpontine activation may correspond to activation of the dorsomedial pontine nuclei and the nucleus reticularis tegmenti pontis, structures known to participate in the generation of multidirectional saccades and smooth pursuit eye movements.", "entity": "Nicotine", "aliases": "Bitartrate Nicotine Tartrate", "definition": "Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.\n    ", "id": "MESH:D009538"}
{"mention": "nystagmus", "mention_text": "The pathomechanism of nicotine-induced nystagmus (NIN) is unknown. The aim of this study was to delineate brain structures that are involved in NIN generation. Eight healthy volunteers inhaled nicotine in darkness during a functional magnetic resonance imaging (fMRI) experiment; eye movements were registered using video-oculography. NIN correlated with blood oxygen level-dependent (BOLD) activity levels in a midpontine site in the posterior basis pontis. NIN-induced midpontine activation may correspond to activation of the dorsomedial pontine nuclei and the nucleus reticularis tegmenti pontis, structures known to participate in the generation of multidirectional saccades and smooth pursuit eye movements.", "entity": "Nystagmus, Pathologic", "aliases": "Alternating Nystagmus Periodic Conjugate Convergence Dissociated Fatigable Positional Horizontal Jerk Multidirectional Non Non-Fatigable Pathologic Pendular Permanent Rebound Retraction Rotary Rotational See-Saw Spontaneous Ocular Symptomatic Temporary Unidirectional Vertical See Saw", "definition": "Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. (Adams et al., Principles of Neurology, 6th ed, p272)\n    ", "id": "MESH:D009759"}
{"mention": "NIN", "mention_text": "The pathomechanism of nicotine-induced nystagmus (NIN) is unknown. The aim of this study was to delineate brain structures that are involved in NIN generation. Eight healthy volunteers inhaled nicotine in darkness during a functional magnetic resonance imaging (fMRI) experiment; eye movements were registered using video-oculography. NIN correlated with blood oxygen level-dependent (BOLD) activity levels in a midpontine site in the posterior basis pontis. NIN-induced midpontine activation may correspond to activation of the dorsomedial pontine nuclei and the nucleus reticularis tegmenti pontis, structures known to participate in the generation of multidirectional saccades and smooth pursuit eye movements.", "entity": "Nystagmus, Pathologic", "aliases": "Alternating Nystagmus Periodic Conjugate Convergence Dissociated Fatigable Positional Horizontal Jerk Multidirectional Non Non-Fatigable Pathologic Pendular Permanent Rebound Retraction Rotary Rotational See-Saw Spontaneous Ocular Symptomatic Temporary Unidirectional Vertical See Saw", "definition": "Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. (Adams et al., Principles of Neurology, 6th ed, p272)\n    ", "id": "MESH:D009759"}
{"mention": "oxygen", "mention_text": "The pathomechanism of nicotine-induced nystagmus (NIN) is unknown. The aim of this study was to delineate brain structures that are involved in NIN generation. Eight healthy volunteers inhaled nicotine in darkness during a functional magnetic resonance imaging (fMRI) experiment; eye movements were registered using video-oculography. NIN correlated with blood oxygen level-dependent (BOLD) activity levels in a midpontine site in the posterior basis pontis. NIN-induced midpontine activation may correspond to activation of the dorsomedial pontine nuclei and the nucleus reticularis tegmenti pontis, structures known to participate in the generation of multidirectional saccades and smooth pursuit eye movements.", "entity": "Oxygen", "aliases": "Dioxygen Oxygen", "definition": "An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.\n    ", "id": "MESH:D010100"}
{"mention": "verapamil", "mention_text": "Protective effect of verapamil on gastric hemorrhagic ulcers in severe atherosclerotic rats.", "entity": "Verapamil", "aliases": "Calan Cordilox Dexverapamil Falicard Finoptin Hydrochloride Verapamil Iproveratril Isoptin Isoptine Izoptin Lekoptin Sandoz Brand of", "definition": "A calcium channel blocker that is a class IV anti-arrhythmia agent.\n    ", "id": "MESH:D014700"}
{"mention": "gastric hemorrhagic", "mention_text": "Protective effect of verapamil on gastric hemorrhagic ulcers in severe atherosclerotic rats.", "entity": "Gastrointestinal Hemorrhage", "aliases": "Gastrointestinal Hemorrhage Hemorrhages Hematochezia Hematochezias", "definition": "Bleeding in any segment of the GASTROINTESTINAL TRACT from ESOPHAGUS to RECTUM.\n    ", "id": "MESH:D006471"}
{"mention": "ulcers", "mention_text": "Protective effect of verapamil on gastric hemorrhagic ulcers in severe atherosclerotic rats.", "entity": "Ulcer", "aliases": "Ulcer Ulcers", "definition": "A lesion on the surface of the skin or a mucous surface, produced by the sloughing of inflammatory necrotic tissue.\n    ", "id": "MESH:D014456"}
{"mention": "atherosclerotic", "mention_text": "Protective effect of verapamil on gastric hemorrhagic ulcers in severe atherosclerotic rats.", "entity": "Atherosclerosis", "aliases": "Atherogenesis Atheroscleroses Atherosclerosis", "definition": "A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA.\n    ", "id": "MESH:D050197"}
{"mention": "gastric hemorrhage", "mention_text": "Studies concerning with pathogenesis of gastric hemorrhage and mucosal ulceration produced in atherosclerotic rats are lacking. The aim of this study is to examine the role of gastric acid back-diffusion, mast cell histamine release, lipid peroxide (LPO) generation and mucosal microvascular permeability in modulating gastric hemorrhage and ulcer in rats with atherosclerosis induced by coadministration of vitamin D2 and cholesterol. Additionally, the protective effect of verapamil on this ulcer model was evaluated. Male Wistar rats were challenged intragastrically once daily for 9 days with 1.0 ml/kg of corn oil containing vitamin D2 and cholesterol to induce atherosclerosis. Control rats received corn oil only. After gastric surgery, rat stomachs were irrigated for 3 h with either simulated gastric juice or normal saline. Gastric acid back-diffusion, mucosal LPO generation, histamine concentration, microvascular permeability, luminal hemoglobin content and ulcer areas were determined. Elevated atherosclerotic parameters, such as serum calcium, total cholesterol and low-density lipoprotein concentration were obtained in atherosclerotic rats. Severe gastric ulcers accompanied with increased ulcerogenic factors, including gastric acid back-diffusion, histamine release, LPO generation and luminal hemoglobin content were also observed in these rats. Moreover, a positive correlation of histamine to gastric hemorrhage and to ulcer was found in those atherosclerotic rats. This hemorrhagic ulcer and various ulcerogenic parameters were dose-dependently ameliorated by daily intragastric verapamil. Atherosclerosis could produce gastric hemorrhagic ulcer via aggravation of gastric acid back-diffusion, LPO generation, histamine release and microvascular permeability that could be ameliorated by verapamil in rats.", "entity": "Gastrointestinal Hemorrhage", "aliases": "Gastrointestinal Hemorrhage Hemorrhages Hematochezia Hematochezias", "definition": "Bleeding in any segment of the GASTROINTESTINAL TRACT from ESOPHAGUS to RECTUM.\n    ", "id": "MESH:D006471"}
{"mention": "atherosclerotic", "mention_text": "Studies concerning with pathogenesis of gastric hemorrhage and mucosal ulceration produced in atherosclerotic rats are lacking. The aim of this study is to examine the role of gastric acid back-diffusion, mast cell histamine release, lipid peroxide (LPO) generation and mucosal microvascular permeability in modulating gastric hemorrhage and ulcer in rats with atherosclerosis induced by coadministration of vitamin D2 and cholesterol. Additionally, the protective effect of verapamil on this ulcer model was evaluated. Male Wistar rats were challenged intragastrically once daily for 9 days with 1.0 ml/kg of corn oil containing vitamin D2 and cholesterol to induce atherosclerosis. Control rats received corn oil only. After gastric surgery, rat stomachs were irrigated for 3 h with either simulated gastric juice or normal saline. Gastric acid back-diffusion, mucosal LPO generation, histamine concentration, microvascular permeability, luminal hemoglobin content and ulcer areas were determined. Elevated atherosclerotic parameters, such as serum calcium, total cholesterol and low-density lipoprotein concentration were obtained in atherosclerotic rats. Severe gastric ulcers accompanied with increased ulcerogenic factors, including gastric acid back-diffusion, histamine release, LPO generation and luminal hemoglobin content were also observed in these rats. Moreover, a positive correlation of histamine to gastric hemorrhage and to ulcer was found in those atherosclerotic rats. This hemorrhagic ulcer and various ulcerogenic parameters were dose-dependently ameliorated by daily intragastric verapamil. Atherosclerosis could produce gastric hemorrhagic ulcer via aggravation of gastric acid back-diffusion, LPO generation, histamine release and microvascular permeability that could be ameliorated by verapamil in rats.", "entity": "Atherosclerosis", "aliases": "Atherogenesis Atheroscleroses Atherosclerosis", "definition": "A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA.\n    ", "id": "MESH:D050197"}
{"mention": "histamine", "mention_text": "Studies concerning with pathogenesis of gastric hemorrhage and mucosal ulceration produced in atherosclerotic rats are lacking. The aim of this study is to examine the role of gastric acid back-diffusion, mast cell histamine release, lipid peroxide (LPO) generation and mucosal microvascular permeability in modulating gastric hemorrhage and ulcer in rats with atherosclerosis induced by coadministration of vitamin D2 and cholesterol. Additionally, the protective effect of verapamil on this ulcer model was evaluated. Male Wistar rats were challenged intragastrically once daily for 9 days with 1.0 ml/kg of corn oil containing vitamin D2 and cholesterol to induce atherosclerosis. Control rats received corn oil only. After gastric surgery, rat stomachs were irrigated for 3 h with either simulated gastric juice or normal saline. Gastric acid back-diffusion, mucosal LPO generation, histamine concentration, microvascular permeability, luminal hemoglobin content and ulcer areas were determined. Elevated atherosclerotic parameters, such as serum calcium, total cholesterol and low-density lipoprotein concentration were obtained in atherosclerotic rats. Severe gastric ulcers accompanied with increased ulcerogenic factors, including gastric acid back-diffusion, histamine release, LPO generation and luminal hemoglobin content were also observed in these rats. Moreover, a positive correlation of histamine to gastric hemorrhage and to ulcer was found in those atherosclerotic rats. This hemorrhagic ulcer and various ulcerogenic parameters were dose-dependently ameliorated by daily intragastric verapamil. Atherosclerosis could produce gastric hemorrhagic ulcer via aggravation of gastric acid back-diffusion, LPO generation, histamine release and microvascular permeability that could be ameliorated by verapamil in rats.", "entity": "Histamine", "aliases": "Ceplene Dihydrochloride Histamine Hydrochloride Peremin", "definition": "An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.\n    ", "id": "MESH:D006632"}
{"mention": "ulcer", "mention_text": "Studies concerning with pathogenesis of gastric hemorrhage and mucosal ulceration produced in atherosclerotic rats are lacking. The aim of this study is to examine the role of gastric acid back-diffusion, mast cell histamine release, lipid peroxide (LPO) generation and mucosal microvascular permeability in modulating gastric hemorrhage and ulcer in rats with atherosclerosis induced by coadministration of vitamin D2 and cholesterol. Additionally, the protective effect of verapamil on this ulcer model was evaluated. Male Wistar rats were challenged intragastrically once daily for 9 days with 1.0 ml/kg of corn oil containing vitamin D2 and cholesterol to induce atherosclerosis. Control rats received corn oil only. After gastric surgery, rat stomachs were irrigated for 3 h with either simulated gastric juice or normal saline. Gastric acid back-diffusion, mucosal LPO generation, histamine concentration, microvascular permeability, luminal hemoglobin content and ulcer areas were determined. Elevated atherosclerotic parameters, such as serum calcium, total cholesterol and low-density lipoprotein concentration were obtained in atherosclerotic rats. Severe gastric ulcers accompanied with increased ulcerogenic factors, including gastric acid back-diffusion, histamine release, LPO generation and luminal hemoglobin content were also observed in these rats. Moreover, a positive correlation of histamine to gastric hemorrhage and to ulcer was found in those atherosclerotic rats. This hemorrhagic ulcer and various ulcerogenic parameters were dose-dependently ameliorated by daily intragastric verapamil. Atherosclerosis could produce gastric hemorrhagic ulcer via aggravation of gastric acid back-diffusion, LPO generation, histamine release and microvascular permeability that could be ameliorated by verapamil in rats.", "entity": "Ulcer", "aliases": "Ulcer Ulcers", "definition": "A lesion on the surface of the skin or a mucous surface, produced by the sloughing of inflammatory necrotic tissue.\n    ", "id": "MESH:D014456"}
{"mention": "atherosclerosis", "mention_text": "Studies concerning with pathogenesis of gastric hemorrhage and mucosal ulceration produced in atherosclerotic rats are lacking. The aim of this study is to examine the role of gastric acid back-diffusion, mast cell histamine release, lipid peroxide (LPO) generation and mucosal microvascular permeability in modulating gastric hemorrhage and ulcer in rats with atherosclerosis induced by coadministration of vitamin D2 and cholesterol. Additionally, the protective effect of verapamil on this ulcer model was evaluated. Male Wistar rats were challenged intragastrically once daily for 9 days with 1.0 ml/kg of corn oil containing vitamin D2 and cholesterol to induce atherosclerosis. Control rats received corn oil only. After gastric surgery, rat stomachs were irrigated for 3 h with either simulated gastric juice or normal saline. Gastric acid back-diffusion, mucosal LPO generation, histamine concentration, microvascular permeability, luminal hemoglobin content and ulcer areas were determined. Elevated atherosclerotic parameters, such as serum calcium, total cholesterol and low-density lipoprotein concentration were obtained in atherosclerotic rats. Severe gastric ulcers accompanied with increased ulcerogenic factors, including gastric acid back-diffusion, histamine release, LPO generation and luminal hemoglobin content were also observed in these rats. Moreover, a positive correlation of histamine to gastric hemorrhage and to ulcer was found in those atherosclerotic rats. This hemorrhagic ulcer and various ulcerogenic parameters were dose-dependently ameliorated by daily intragastric verapamil. Atherosclerosis could produce gastric hemorrhagic ulcer via aggravation of gastric acid back-diffusion, LPO generation, histamine release and microvascular permeability that could be ameliorated by verapamil in rats.", "entity": "Atherosclerosis", "aliases": "Atherogenesis Atheroscleroses Atherosclerosis", "definition": "A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA.\n    ", "id": "MESH:D050197"}
{"mention": "vitamin D2", "mention_text": "Studies concerning with pathogenesis of gastric hemorrhage and mucosal ulceration produced in atherosclerotic rats are lacking. The aim of this study is to examine the role of gastric acid back-diffusion, mast cell histamine release, lipid peroxide (LPO) generation and mucosal microvascular permeability in modulating gastric hemorrhage and ulcer in rats with atherosclerosis induced by coadministration of vitamin D2 and cholesterol. Additionally, the protective effect of verapamil on this ulcer model was evaluated. Male Wistar rats were challenged intragastrically once daily for 9 days with 1.0 ml/kg of corn oil containing vitamin D2 and cholesterol to induce atherosclerosis. Control rats received corn oil only. After gastric surgery, rat stomachs were irrigated for 3 h with either simulated gastric juice or normal saline. Gastric acid back-diffusion, mucosal LPO generation, histamine concentration, microvascular permeability, luminal hemoglobin content and ulcer areas were determined. Elevated atherosclerotic parameters, such as serum calcium, total cholesterol and low-density lipoprotein concentration were obtained in atherosclerotic rats. Severe gastric ulcers accompanied with increased ulcerogenic factors, including gastric acid back-diffusion, histamine release, LPO generation and luminal hemoglobin content were also observed in these rats. Moreover, a positive correlation of histamine to gastric hemorrhage and to ulcer was found in those atherosclerotic rats. This hemorrhagic ulcer and various ulcerogenic parameters were dose-dependently ameliorated by daily intragastric verapamil. Atherosclerosis could produce gastric hemorrhagic ulcer via aggravation of gastric acid back-diffusion, LPO generation, histamine release and microvascular permeability that could be ameliorated by verapamil in rats.", "entity": "Ergocalciferols", "aliases": "Calciferols D2 Vitamin Ergocalciferol Ergocalciferols D 2", "definition": "Derivatives of ERGOSTEROL formed by ULTRAVIOLET RAYS breaking of the C9-C10 bond. They differ from CHOLECALCIFEROL in having a double bond between C22 and C23 and a methyl group at C24.\n    ", "id": "MESH:D004872"}
{"mention": "cholesterol", "mention_text": "Studies concerning with pathogenesis of gastric hemorrhage and mucosal ulceration produced in atherosclerotic rats are lacking. The aim of this study is to examine the role of gastric acid back-diffusion, mast cell histamine release, lipid peroxide (LPO) generation and mucosal microvascular permeability in modulating gastric hemorrhage and ulcer in rats with atherosclerosis induced by coadministration of vitamin D2 and cholesterol. Additionally, the protective effect of verapamil on this ulcer model was evaluated. Male Wistar rats were challenged intragastrically once daily for 9 days with 1.0 ml/kg of corn oil containing vitamin D2 and cholesterol to induce atherosclerosis. Control rats received corn oil only. After gastric surgery, rat stomachs were irrigated for 3 h with either simulated gastric juice or normal saline. Gastric acid back-diffusion, mucosal LPO generation, histamine concentration, microvascular permeability, luminal hemoglobin content and ulcer areas were determined. Elevated atherosclerotic parameters, such as serum calcium, total cholesterol and low-density lipoprotein concentration were obtained in atherosclerotic rats. Severe gastric ulcers accompanied with increased ulcerogenic factors, including gastric acid back-diffusion, histamine release, LPO generation and luminal hemoglobin content were also observed in these rats. Moreover, a positive correlation of histamine to gastric hemorrhage and to ulcer was found in those atherosclerotic rats. This hemorrhagic ulcer and various ulcerogenic parameters were dose-dependently ameliorated by daily intragastric verapamil. Atherosclerosis could produce gastric hemorrhagic ulcer via aggravation of gastric acid back-diffusion, LPO generation, histamine release and microvascular permeability that could be ameliorated by verapamil in rats.", "entity": "Cholesterol", "aliases": "Cholesterol Epicholesterol", "definition": "The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.\n    ", "id": "MESH:D002784"}
{"mention": "verapamil", "mention_text": "Studies concerning with pathogenesis of gastric hemorrhage and mucosal ulceration produced in atherosclerotic rats are lacking. The aim of this study is to examine the role of gastric acid back-diffusion, mast cell histamine release, lipid peroxide (LPO) generation and mucosal microvascular permeability in modulating gastric hemorrhage and ulcer in rats with atherosclerosis induced by coadministration of vitamin D2 and cholesterol. Additionally, the protective effect of verapamil on this ulcer model was evaluated. Male Wistar rats were challenged intragastrically once daily for 9 days with 1.0 ml/kg of corn oil containing vitamin D2 and cholesterol to induce atherosclerosis. Control rats received corn oil only. After gastric surgery, rat stomachs were irrigated for 3 h with either simulated gastric juice or normal saline. Gastric acid back-diffusion, mucosal LPO generation, histamine concentration, microvascular permeability, luminal hemoglobin content and ulcer areas were determined. Elevated atherosclerotic parameters, such as serum calcium, total cholesterol and low-density lipoprotein concentration were obtained in atherosclerotic rats. Severe gastric ulcers accompanied with increased ulcerogenic factors, including gastric acid back-diffusion, histamine release, LPO generation and luminal hemoglobin content were also observed in these rats. Moreover, a positive correlation of histamine to gastric hemorrhage and to ulcer was found in those atherosclerotic rats. This hemorrhagic ulcer and various ulcerogenic parameters were dose-dependently ameliorated by daily intragastric verapamil. Atherosclerosis could produce gastric hemorrhagic ulcer via aggravation of gastric acid back-diffusion, LPO generation, histamine release and microvascular permeability that could be ameliorated by verapamil in rats.", "entity": "Verapamil", "aliases": "Calan Cordilox Dexverapamil Falicard Finoptin Hydrochloride Verapamil Iproveratril Isoptin Isoptine Izoptin Lekoptin Sandoz Brand of", "definition": "A calcium channel blocker that is a class IV anti-arrhythmia agent.\n    ", "id": "MESH:D014700"}
{"mention": "luminal", "mention_text": "Studies concerning with pathogenesis of gastric hemorrhage and mucosal ulceration produced in atherosclerotic rats are lacking. The aim of this study is to examine the role of gastric acid back-diffusion, mast cell histamine release, lipid peroxide (LPO) generation and mucosal microvascular permeability in modulating gastric hemorrhage and ulcer in rats with atherosclerosis induced by coadministration of vitamin D2 and cholesterol. Additionally, the protective effect of verapamil on this ulcer model was evaluated. Male Wistar rats were challenged intragastrically once daily for 9 days with 1.0 ml/kg of corn oil containing vitamin D2 and cholesterol to induce atherosclerosis. Control rats received corn oil only. After gastric surgery, rat stomachs were irrigated for 3 h with either simulated gastric juice or normal saline. Gastric acid back-diffusion, mucosal LPO generation, histamine concentration, microvascular permeability, luminal hemoglobin content and ulcer areas were determined. Elevated atherosclerotic parameters, such as serum calcium, total cholesterol and low-density lipoprotein concentration were obtained in atherosclerotic rats. Severe gastric ulcers accompanied with increased ulcerogenic factors, including gastric acid back-diffusion, histamine release, LPO generation and luminal hemoglobin content were also observed in these rats. Moreover, a positive correlation of histamine to gastric hemorrhage and to ulcer was found in those atherosclerotic rats. This hemorrhagic ulcer and various ulcerogenic parameters were dose-dependently ameliorated by daily intragastric verapamil. Atherosclerosis could produce gastric hemorrhagic ulcer via aggravation of gastric acid back-diffusion, LPO generation, histamine release and microvascular permeability that could be ameliorated by verapamil in rats.", "entity": "Phenobarbital", "aliases": "Acid Phenylethylbarbituric Gardenal Hysteps Luminal Monosodium Salt Phenobarbital Phenemal Sodium Phenobarbitone Phenylbarbital", "definition": "A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.\n    ", "id": "MESH:D010634"}
{"mention": "calcium", "mention_text": "Studies concerning with pathogenesis of gastric hemorrhage and mucosal ulceration produced in atherosclerotic rats are lacking. The aim of this study is to examine the role of gastric acid back-diffusion, mast cell histamine release, lipid peroxide (LPO) generation and mucosal microvascular permeability in modulating gastric hemorrhage and ulcer in rats with atherosclerosis induced by coadministration of vitamin D2 and cholesterol. Additionally, the protective effect of verapamil on this ulcer model was evaluated. Male Wistar rats were challenged intragastrically once daily for 9 days with 1.0 ml/kg of corn oil containing vitamin D2 and cholesterol to induce atherosclerosis. Control rats received corn oil only. After gastric surgery, rat stomachs were irrigated for 3 h with either simulated gastric juice or normal saline. Gastric acid back-diffusion, mucosal LPO generation, histamine concentration, microvascular permeability, luminal hemoglobin content and ulcer areas were determined. Elevated atherosclerotic parameters, such as serum calcium, total cholesterol and low-density lipoprotein concentration were obtained in atherosclerotic rats. Severe gastric ulcers accompanied with increased ulcerogenic factors, including gastric acid back-diffusion, histamine release, LPO generation and luminal hemoglobin content were also observed in these rats. Moreover, a positive correlation of histamine to gastric hemorrhage and to ulcer was found in those atherosclerotic rats. This hemorrhagic ulcer and various ulcerogenic parameters were dose-dependently ameliorated by daily intragastric verapamil. Atherosclerosis could produce gastric hemorrhagic ulcer via aggravation of gastric acid back-diffusion, LPO generation, histamine release and microvascular permeability that could be ameliorated by verapamil in rats.", "entity": "Calcium", "aliases": "Blood Coagulation Factor IV Calcium", "definition": "A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.\n    ", "id": "MESH:D002118"}
{"mention": "ulcers", "mention_text": "Studies concerning with pathogenesis of gastric hemorrhage and mucosal ulceration produced in atherosclerotic rats are lacking. The aim of this study is to examine the role of gastric acid back-diffusion, mast cell histamine release, lipid peroxide (LPO) generation and mucosal microvascular permeability in modulating gastric hemorrhage and ulcer in rats with atherosclerosis induced by coadministration of vitamin D2 and cholesterol. Additionally, the protective effect of verapamil on this ulcer model was evaluated. Male Wistar rats were challenged intragastrically once daily for 9 days with 1.0 ml/kg of corn oil containing vitamin D2 and cholesterol to induce atherosclerosis. Control rats received corn oil only. After gastric surgery, rat stomachs were irrigated for 3 h with either simulated gastric juice or normal saline. Gastric acid back-diffusion, mucosal LPO generation, histamine concentration, microvascular permeability, luminal hemoglobin content and ulcer areas were determined. Elevated atherosclerotic parameters, such as serum calcium, total cholesterol and low-density lipoprotein concentration were obtained in atherosclerotic rats. Severe gastric ulcers accompanied with increased ulcerogenic factors, including gastric acid back-diffusion, histamine release, LPO generation and luminal hemoglobin content were also observed in these rats. Moreover, a positive correlation of histamine to gastric hemorrhage and to ulcer was found in those atherosclerotic rats. This hemorrhagic ulcer and various ulcerogenic parameters were dose-dependently ameliorated by daily intragastric verapamil. Atherosclerosis could produce gastric hemorrhagic ulcer via aggravation of gastric acid back-diffusion, LPO generation, histamine release and microvascular permeability that could be ameliorated by verapamil in rats.", "entity": "Ulcer", "aliases": "Ulcer Ulcers", "definition": "A lesion on the surface of the skin or a mucous surface, produced by the sloughing of inflammatory necrotic tissue.\n    ", "id": "MESH:D014456"}
{"mention": "hemorrhagic", "mention_text": "Studies concerning with pathogenesis of gastric hemorrhage and mucosal ulceration produced in atherosclerotic rats are lacking. The aim of this study is to examine the role of gastric acid back-diffusion, mast cell histamine release, lipid peroxide (LPO) generation and mucosal microvascular permeability in modulating gastric hemorrhage and ulcer in rats with atherosclerosis induced by coadministration of vitamin D2 and cholesterol. Additionally, the protective effect of verapamil on this ulcer model was evaluated. Male Wistar rats were challenged intragastrically once daily for 9 days with 1.0 ml/kg of corn oil containing vitamin D2 and cholesterol to induce atherosclerosis. Control rats received corn oil only. After gastric surgery, rat stomachs were irrigated for 3 h with either simulated gastric juice or normal saline. Gastric acid back-diffusion, mucosal LPO generation, histamine concentration, microvascular permeability, luminal hemoglobin content and ulcer areas were determined. Elevated atherosclerotic parameters, such as serum calcium, total cholesterol and low-density lipoprotein concentration were obtained in atherosclerotic rats. Severe gastric ulcers accompanied with increased ulcerogenic factors, including gastric acid back-diffusion, histamine release, LPO generation and luminal hemoglobin content were also observed in these rats. Moreover, a positive correlation of histamine to gastric hemorrhage and to ulcer was found in those atherosclerotic rats. This hemorrhagic ulcer and various ulcerogenic parameters were dose-dependently ameliorated by daily intragastric verapamil. Atherosclerosis could produce gastric hemorrhagic ulcer via aggravation of gastric acid back-diffusion, LPO generation, histamine release and microvascular permeability that could be ameliorated by verapamil in rats.", "entity": "Gastrointestinal Hemorrhage", "aliases": "Gastrointestinal Hemorrhage Hemorrhages Hematochezia Hematochezias", "definition": "Bleeding in any segment of the GASTROINTESTINAL TRACT from ESOPHAGUS to RECTUM.\n    ", "id": "MESH:D006471"}
{"mention": "Atherosclerosis", "mention_text": "Studies concerning with pathogenesis of gastric hemorrhage and mucosal ulceration produced in atherosclerotic rats are lacking. The aim of this study is to examine the role of gastric acid back-diffusion, mast cell histamine release, lipid peroxide (LPO) generation and mucosal microvascular permeability in modulating gastric hemorrhage and ulcer in rats with atherosclerosis induced by coadministration of vitamin D2 and cholesterol. Additionally, the protective effect of verapamil on this ulcer model was evaluated. Male Wistar rats were challenged intragastrically once daily for 9 days with 1.0 ml/kg of corn oil containing vitamin D2 and cholesterol to induce atherosclerosis. Control rats received corn oil only. After gastric surgery, rat stomachs were irrigated for 3 h with either simulated gastric juice or normal saline. Gastric acid back-diffusion, mucosal LPO generation, histamine concentration, microvascular permeability, luminal hemoglobin content and ulcer areas were determined. Elevated atherosclerotic parameters, such as serum calcium, total cholesterol and low-density lipoprotein concentration were obtained in atherosclerotic rats. Severe gastric ulcers accompanied with increased ulcerogenic factors, including gastric acid back-diffusion, histamine release, LPO generation and luminal hemoglobin content were also observed in these rats. Moreover, a positive correlation of histamine to gastric hemorrhage and to ulcer was found in those atherosclerotic rats. This hemorrhagic ulcer and various ulcerogenic parameters were dose-dependently ameliorated by daily intragastric verapamil. Atherosclerosis could produce gastric hemorrhagic ulcer via aggravation of gastric acid back-diffusion, LPO generation, histamine release and microvascular permeability that could be ameliorated by verapamil in rats.", "entity": "Atherosclerosis", "aliases": "Atherogenesis Atheroscleroses Atherosclerosis", "definition": "A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA.\n    ", "id": "MESH:D050197"}
{"mention": "gastric hemorrhagic", "mention_text": "Studies concerning with pathogenesis of gastric hemorrhage and mucosal ulceration produced in atherosclerotic rats are lacking. The aim of this study is to examine the role of gastric acid back-diffusion, mast cell histamine release, lipid peroxide (LPO) generation and mucosal microvascular permeability in modulating gastric hemorrhage and ulcer in rats with atherosclerosis induced by coadministration of vitamin D2 and cholesterol. Additionally, the protective effect of verapamil on this ulcer model was evaluated. Male Wistar rats were challenged intragastrically once daily for 9 days with 1.0 ml/kg of corn oil containing vitamin D2 and cholesterol to induce atherosclerosis. Control rats received corn oil only. After gastric surgery, rat stomachs were irrigated for 3 h with either simulated gastric juice or normal saline. Gastric acid back-diffusion, mucosal LPO generation, histamine concentration, microvascular permeability, luminal hemoglobin content and ulcer areas were determined. Elevated atherosclerotic parameters, such as serum calcium, total cholesterol and low-density lipoprotein concentration were obtained in atherosclerotic rats. Severe gastric ulcers accompanied with increased ulcerogenic factors, including gastric acid back-diffusion, histamine release, LPO generation and luminal hemoglobin content were also observed in these rats. Moreover, a positive correlation of histamine to gastric hemorrhage and to ulcer was found in those atherosclerotic rats. This hemorrhagic ulcer and various ulcerogenic parameters were dose-dependently ameliorated by daily intragastric verapamil. Atherosclerosis could produce gastric hemorrhagic ulcer via aggravation of gastric acid back-diffusion, LPO generation, histamine release and microvascular permeability that could be ameliorated by verapamil in rats.", "entity": "Gastrointestinal Hemorrhage", "aliases": "Gastrointestinal Hemorrhage Hemorrhages Hematochezia Hematochezias", "definition": "Bleeding in any segment of the GASTROINTESTINAL TRACT from ESOPHAGUS to RECTUM.\n    ", "id": "MESH:D006471"}
{"mention": "Adriamycin", "mention_text": "Adriamycin-induced autophagic cardiomyocyte death plays a pathogenic role in a rat model of heart failure.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "death", "mention_text": "Adriamycin-induced autophagic cardiomyocyte death plays a pathogenic role in a rat model of heart failure.", "entity": "Death", "aliases": "Cardiac Death Determination of Near-Death Experience", "definition": "Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.\n    ", "id": "MESH:D003643"}
{"mention": "heart failure", "mention_text": "Adriamycin-induced autophagic cardiomyocyte death plays a pathogenic role in a rat model of heart failure.", "entity": "Heart Failure", "aliases": "Cardiac Failure Congestive Heart Decompensation Left Sided Left-Sided Right Right-Sided Myocardial", "definition": "A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.\n    ", "id": "MESH:D006333"}
{"mention": "heart failure", "mention_text": "BACKGROUND: The mechanisms underlying heart failure induced by adriamycin are very complicated and still unclear. The aim of this study was to investigate whether autophagy was involved in the progression of heart failure induced by adriamycin, so that we can develop a novel treatment strategy for heart failure. METHODS: 3-methyladenine (3MA), a specific inhibitor on autophagy was used in a heart failure model of rats induced by adriamycin. Neonatal cardiomyocytes were isolated from Sprague-Dawley rat hearts and randomly divided into controls, an adriamycin-treated group, and a 3MA plus adriamycin-treated group. We then examined the morphology, expression of beclin 1 gene, mitochondrial permeability transition (MPT), and Na+-K+ ATPase activity in vivo. We also assessed cell viability, mitochondrial membrane potential changes and counted autophagic vacuoles in cultured cardiomyocytes. In addition, we analyzed the expression of autophagy associated gene, beclin 1 using RT-PCR and Western blotting in an animal model. RESULTS: 3MA significantly improved cardiac function and reduced mitochondrial injury. Furthermore, adriamycin induced the formation of autophagic vacuoles, and 3MA strongly downregulated the expression of beclin 1 in adriamycin-induced failing heart and inhibited the formation of autophagic vacuoles. CONCLUSION: Autophagic cardiomyocyte death plays an important role in the pathogenesis of heart failure in rats induced by adriamycin. Mitochondrial injury may be involved in the progression of heart failure caused by adriamycin via the autophagy pathway.", "entity": "Heart Failure", "aliases": "Cardiac Failure Congestive Heart Decompensation Left Sided Left-Sided Right Right-Sided Myocardial", "definition": "A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.\n    ", "id": "MESH:D006333"}
{"mention": "adriamycin", "mention_text": "BACKGROUND: The mechanisms underlying heart failure induced by adriamycin are very complicated and still unclear. The aim of this study was to investigate whether autophagy was involved in the progression of heart failure induced by adriamycin, so that we can develop a novel treatment strategy for heart failure. METHODS: 3-methyladenine (3MA), a specific inhibitor on autophagy was used in a heart failure model of rats induced by adriamycin. Neonatal cardiomyocytes were isolated from Sprague-Dawley rat hearts and randomly divided into controls, an adriamycin-treated group, and a 3MA plus adriamycin-treated group. We then examined the morphology, expression of beclin 1 gene, mitochondrial permeability transition (MPT), and Na+-K+ ATPase activity in vivo. We also assessed cell viability, mitochondrial membrane potential changes and counted autophagic vacuoles in cultured cardiomyocytes. In addition, we analyzed the expression of autophagy associated gene, beclin 1 using RT-PCR and Western blotting in an animal model. RESULTS: 3MA significantly improved cardiac function and reduced mitochondrial injury. Furthermore, adriamycin induced the formation of autophagic vacuoles, and 3MA strongly downregulated the expression of beclin 1 in adriamycin-induced failing heart and inhibited the formation of autophagic vacuoles. CONCLUSION: Autophagic cardiomyocyte death plays an important role in the pathogenesis of heart failure in rats induced by adriamycin. Mitochondrial injury may be involved in the progression of heart failure caused by adriamycin via the autophagy pathway.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "3-methyladenine", "mention_text": "BACKGROUND: The mechanisms underlying heart failure induced by adriamycin are very complicated and still unclear. The aim of this study was to investigate whether autophagy was involved in the progression of heart failure induced by adriamycin, so that we can develop a novel treatment strategy for heart failure. METHODS: 3-methyladenine (3MA), a specific inhibitor on autophagy was used in a heart failure model of rats induced by adriamycin. Neonatal cardiomyocytes were isolated from Sprague-Dawley rat hearts and randomly divided into controls, an adriamycin-treated group, and a 3MA plus adriamycin-treated group. We then examined the morphology, expression of beclin 1 gene, mitochondrial permeability transition (MPT), and Na+-K+ ATPase activity in vivo. We also assessed cell viability, mitochondrial membrane potential changes and counted autophagic vacuoles in cultured cardiomyocytes. In addition, we analyzed the expression of autophagy associated gene, beclin 1 using RT-PCR and Western blotting in an animal model. RESULTS: 3MA significantly improved cardiac function and reduced mitochondrial injury. Furthermore, adriamycin induced the formation of autophagic vacuoles, and 3MA strongly downregulated the expression of beclin 1 in adriamycin-induced failing heart and inhibited the formation of autophagic vacuoles. CONCLUSION: Autophagic cardiomyocyte death plays an important role in the pathogenesis of heart failure in rats induced by adriamycin. Mitochondrial injury may be involved in the progression of heart failure caused by adriamycin via the autophagy pathway.", "entity": "3-methyladenine", "aliases": "3-methyladenine N(3)-methyladenine", "definition": "", "id": "MESH:C025946"}
{"mention": "3MA", "mention_text": "BACKGROUND: The mechanisms underlying heart failure induced by adriamycin are very complicated and still unclear. The aim of this study was to investigate whether autophagy was involved in the progression of heart failure induced by adriamycin, so that we can develop a novel treatment strategy for heart failure. METHODS: 3-methyladenine (3MA), a specific inhibitor on autophagy was used in a heart failure model of rats induced by adriamycin. Neonatal cardiomyocytes were isolated from Sprague-Dawley rat hearts and randomly divided into controls, an adriamycin-treated group, and a 3MA plus adriamycin-treated group. We then examined the morphology, expression of beclin 1 gene, mitochondrial permeability transition (MPT), and Na+-K+ ATPase activity in vivo. We also assessed cell viability, mitochondrial membrane potential changes and counted autophagic vacuoles in cultured cardiomyocytes. In addition, we analyzed the expression of autophagy associated gene, beclin 1 using RT-PCR and Western blotting in an animal model. RESULTS: 3MA significantly improved cardiac function and reduced mitochondrial injury. Furthermore, adriamycin induced the formation of autophagic vacuoles, and 3MA strongly downregulated the expression of beclin 1 in adriamycin-induced failing heart and inhibited the formation of autophagic vacuoles. CONCLUSION: Autophagic cardiomyocyte death plays an important role in the pathogenesis of heart failure in rats induced by adriamycin. Mitochondrial injury may be involved in the progression of heart failure caused by adriamycin via the autophagy pathway.", "entity": "3-methyladenine", "aliases": "3-methyladenine N(3)-methyladenine", "definition": "", "id": "MESH:C025946"}
{"mention": "K", "mention_text": "BACKGROUND: The mechanisms underlying heart failure induced by adriamycin are very complicated and still unclear. The aim of this study was to investigate whether autophagy was involved in the progression of heart failure induced by adriamycin, so that we can develop a novel treatment strategy for heart failure. METHODS: 3-methyladenine (3MA), a specific inhibitor on autophagy was used in a heart failure model of rats induced by adriamycin. Neonatal cardiomyocytes were isolated from Sprague-Dawley rat hearts and randomly divided into controls, an adriamycin-treated group, and a 3MA plus adriamycin-treated group. We then examined the morphology, expression of beclin 1 gene, mitochondrial permeability transition (MPT), and Na+-K+ ATPase activity in vivo. We also assessed cell viability, mitochondrial membrane potential changes and counted autophagic vacuoles in cultured cardiomyocytes. In addition, we analyzed the expression of autophagy associated gene, beclin 1 using RT-PCR and Western blotting in an animal model. RESULTS: 3MA significantly improved cardiac function and reduced mitochondrial injury. Furthermore, adriamycin induced the formation of autophagic vacuoles, and 3MA strongly downregulated the expression of beclin 1 in adriamycin-induced failing heart and inhibited the formation of autophagic vacuoles. CONCLUSION: Autophagic cardiomyocyte death plays an important role in the pathogenesis of heart failure in rats induced by adriamycin. Mitochondrial injury may be involved in the progression of heart failure caused by adriamycin via the autophagy pathway.", "entity": "Potassium", "aliases": "Potassium", "definition": "An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.\n    ", "id": "MESH:D011188"}
{"mention": "death", "mention_text": "BACKGROUND: The mechanisms underlying heart failure induced by adriamycin are very complicated and still unclear. The aim of this study was to investigate whether autophagy was involved in the progression of heart failure induced by adriamycin, so that we can develop a novel treatment strategy for heart failure. METHODS: 3-methyladenine (3MA), a specific inhibitor on autophagy was used in a heart failure model of rats induced by adriamycin. Neonatal cardiomyocytes were isolated from Sprague-Dawley rat hearts and randomly divided into controls, an adriamycin-treated group, and a 3MA plus adriamycin-treated group. We then examined the morphology, expression of beclin 1 gene, mitochondrial permeability transition (MPT), and Na+-K+ ATPase activity in vivo. We also assessed cell viability, mitochondrial membrane potential changes and counted autophagic vacuoles in cultured cardiomyocytes. In addition, we analyzed the expression of autophagy associated gene, beclin 1 using RT-PCR and Western blotting in an animal model. RESULTS: 3MA significantly improved cardiac function and reduced mitochondrial injury. Furthermore, adriamycin induced the formation of autophagic vacuoles, and 3MA strongly downregulated the expression of beclin 1 in adriamycin-induced failing heart and inhibited the formation of autophagic vacuoles. CONCLUSION: Autophagic cardiomyocyte death plays an important role in the pathogenesis of heart failure in rats induced by adriamycin. Mitochondrial injury may be involved in the progression of heart failure caused by adriamycin via the autophagy pathway.", "entity": "Death", "aliases": "Cardiac Death Determination of Near-Death Experience", "definition": "Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.\n    ", "id": "MESH:D003643"}
{"mention": "Confusion", "mention_text": "Confusion, a rather serious adverse drug reaction with valproic acid: a review of the French Pharmacovigilance database.", "entity": "Confusion", "aliases": "Bewilderment Confusion Post Ictal Post-Ictal Reactive Confusional State States Disorientation", "definition": "A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation.\n    ", "id": "MESH:D003221"}
{"mention": "valproic acid", "mention_text": "Confusion, a rather serious adverse drug reaction with valproic acid: a review of the French Pharmacovigilance database.", "entity": "Valproic Acid", "aliases": "2 Propylpentanoic Acid 2-Propylpentanoic Acetate Dipropyl Propylisopropylacetic Valproic Calcium Valproate Convulsofin Depakene Depakine Depakote Divalproex Sodium Ergenyl Magnesium Semisodium Salt (2:1) Vupral", "definition": "A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.\n    ", "id": "MESH:D014635"}
{"mention": "Confusion", "mention_text": "INTRODUCTION: Confusion is an adverse drug reaction frequently observed with valproic acid. Some case reports are published in the literature but no systematic study from a sample of patients has been published. We performed this study in order to describe the main characteristics of this adverse drug reaction. METHODS: Using the French Pharmacovigilance database, we selected the cases of confusion reported since 1985 with valproic acid. RESULTS: 272 cases of confusion were reported with valproic acid: 153 women and 119 men. Confusion mostly occurred during the two first weeks following valproic acid exposure (39.7%). It was \"serious\" for almost 2/3 of the patients (62.5%) and its outcome favourable in most of the cases (82%). The occurrence of this ADR was more frequent in patients aged between 61 and 80 years. CONCLUSION: This work shows that confusion with valproic acid is a serious, rather frequent but reversible adverse drug reaction. It occurs especially in older patients and during the first two weeks of treatment.", "entity": "Confusion", "aliases": "Bewilderment Confusion Post Ictal Post-Ictal Reactive Confusional State States Disorientation", "definition": "A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation.\n    ", "id": "MESH:D003221"}
{"mention": "valproic acid", "mention_text": "INTRODUCTION: Confusion is an adverse drug reaction frequently observed with valproic acid. Some case reports are published in the literature but no systematic study from a sample of patients has been published. We performed this study in order to describe the main characteristics of this adverse drug reaction. METHODS: Using the French Pharmacovigilance database, we selected the cases of confusion reported since 1985 with valproic acid. RESULTS: 272 cases of confusion were reported with valproic acid: 153 women and 119 men. Confusion mostly occurred during the two first weeks following valproic acid exposure (39.7%). It was \"serious\" for almost 2/3 of the patients (62.5%) and its outcome favourable in most of the cases (82%). The occurrence of this ADR was more frequent in patients aged between 61 and 80 years. CONCLUSION: This work shows that confusion with valproic acid is a serious, rather frequent but reversible adverse drug reaction. It occurs especially in older patients and during the first two weeks of treatment.", "entity": "Valproic Acid", "aliases": "2 Propylpentanoic Acid 2-Propylpentanoic Acetate Dipropyl Propylisopropylacetic Valproic Calcium Valproate Convulsofin Depakene Depakine Depakote Divalproex Sodium Ergenyl Magnesium Semisodium Salt (2:1) Vupral", "definition": "A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.\n    ", "id": "MESH:D014635"}
{"mention": "confusion", "mention_text": "INTRODUCTION: Confusion is an adverse drug reaction frequently observed with valproic acid. Some case reports are published in the literature but no systematic study from a sample of patients has been published. We performed this study in order to describe the main characteristics of this adverse drug reaction. METHODS: Using the French Pharmacovigilance database, we selected the cases of confusion reported since 1985 with valproic acid. RESULTS: 272 cases of confusion were reported with valproic acid: 153 women and 119 men. Confusion mostly occurred during the two first weeks following valproic acid exposure (39.7%). It was \"serious\" for almost 2/3 of the patients (62.5%) and its outcome favourable in most of the cases (82%). The occurrence of this ADR was more frequent in patients aged between 61 and 80 years. CONCLUSION: This work shows that confusion with valproic acid is a serious, rather frequent but reversible adverse drug reaction. It occurs especially in older patients and during the first two weeks of treatment.", "entity": "Confusion", "aliases": "Bewilderment Confusion Post Ictal Post-Ictal Reactive Confusional State States Disorientation", "definition": "A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation.\n    ", "id": "MESH:D003221"}
{"mention": "memory deficits", "mention_text": "Learning and memory deficits in ecstasy users and their neural correlates during a face-learning task.", "entity": "Memory Disorders", "aliases": "Age Related Memory Disorders Age-Related Disorder Cognitive Retention Deficit Deficits Semantic Spatial Loss Losses", "definition": "Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions.\n    ", "id": "MESH:D008569"}
{"mention": "ecstasy", "mention_text": "Learning and memory deficits in ecstasy users and their neural correlates during a face-learning task.", "entity": "N-Methyl-3,4-methylenedioxyamphetamine", "aliases": "Ecstasy (Drug) Hydrochloride N-Methyl-3,4-methylenedioxyamphetamine MDMA Methylenedioxymethamphetamine N Methyl 3,4 methylenedioxyamphetamine", "definition": "An N-substituted amphetamine analog. It is a widely abused drug classified as a hallucinogen and causes marked, long-lasting changes in brain serotonergic systems. It is commonly referred to as MDMA or ecstasy.\n    ", "id": "MESH:D018817"}
{"mention": "ecstasy", "mention_text": "It has been consistently shown that ecstasy users display impairments in learning and memory performance. In addition, working memory processing in ecstasy users has been shown to be associated with neural alterations in hippocampal and/or cortical regions as measured by functional magnetic resonance imaging (fMRI). Using functional imaging and a face-learning task, we investigated neural correlates of encoding and recalling face-name associations in 20 recreational drug users whose predominant drug use was ecstasy and 20 controls. To address the potential confounding effects of the cannabis use of the ecstasy using group, a second analysis included 14 previously tested cannabis users (Nestor, L., Roberts, G., Garavan, H., Hester, R., 2008. Deficits in learning and memory: parahippocampal hyperactivity and frontocortical hypoactivity in cannabis users. Neuroimage 40, 1328-1339). Ecstasy users performed significantly worse in learning and memory compared to controls and cannabis users. A conjunction analysis of the encode and recall phases of the task revealed ecstasy-specific hyperactivity in bilateral frontal regions, left temporal, right parietal, bilateral temporal, and bilateral occipital brain regions. Ecstasy-specific hypoactivity was evident in the right dorsal anterior cingulated cortex (ACC) and left posterior cingulated cortex. In both ecstasy and cannabis groups brain activation was decreased in the right medial frontal gyrus, left parahippocampal gyrus, left dorsal cingulate gyrus, and left caudate. These results elucidated ecstasy-related deficits, only some of which might be attributed to cannabis use. These ecstasy-specific effects may be related to the vulnerability of isocortical and allocortical regions to the neurotoxic effects of ecstasy.", "entity": "N-Methyl-3,4-methylenedioxyamphetamine", "aliases": "Ecstasy (Drug) Hydrochloride N-Methyl-3,4-methylenedioxyamphetamine MDMA Methylenedioxymethamphetamine N Methyl 3,4 methylenedioxyamphetamine", "definition": "An N-substituted amphetamine analog. It is a widely abused drug classified as a hallucinogen and causes marked, long-lasting changes in brain serotonergic systems. It is commonly referred to as MDMA or ecstasy.\n    ", "id": "MESH:D018817"}
{"mention": "impairments in learning", "mention_text": "It has been consistently shown that ecstasy users display impairments in learning and memory performance. In addition, working memory processing in ecstasy users has been shown to be associated with neural alterations in hippocampal and/or cortical regions as measured by functional magnetic resonance imaging (fMRI). Using functional imaging and a face-learning task, we investigated neural correlates of encoding and recalling face-name associations in 20 recreational drug users whose predominant drug use was ecstasy and 20 controls. To address the potential confounding effects of the cannabis use of the ecstasy using group, a second analysis included 14 previously tested cannabis users (Nestor, L., Roberts, G., Garavan, H., Hester, R., 2008. Deficits in learning and memory: parahippocampal hyperactivity and frontocortical hypoactivity in cannabis users. Neuroimage 40, 1328-1339). Ecstasy users performed significantly worse in learning and memory compared to controls and cannabis users. A conjunction analysis of the encode and recall phases of the task revealed ecstasy-specific hyperactivity in bilateral frontal regions, left temporal, right parietal, bilateral temporal, and bilateral occipital brain regions. Ecstasy-specific hypoactivity was evident in the right dorsal anterior cingulated cortex (ACC) and left posterior cingulated cortex. In both ecstasy and cannabis groups brain activation was decreased in the right medial frontal gyrus, left parahippocampal gyrus, left dorsal cingulate gyrus, and left caudate. These results elucidated ecstasy-related deficits, only some of which might be attributed to cannabis use. These ecstasy-specific effects may be related to the vulnerability of isocortical and allocortical regions to the neurotoxic effects of ecstasy.", "entity": "Learning Disorders", "aliases": "Academic Disorder Developmental Disorders Adult Learning of Scholastic Skills Disabilities Disability Disturbance Disturbances Development", "definition": "Conditions characterized by a significant discrepancy between an individual's perceived level of intellect and their ability to acquire new language and other cognitive skills. These disorders may result from organic or psychological conditions. Relatively common subtypes include DYSLEXIA, dyscalculia, and dysgraphia.\n    ", "id": "MESH:D007859"}
{"mention": "cannabis", "mention_text": "It has been consistently shown that ecstasy users display impairments in learning and memory performance. In addition, working memory processing in ecstasy users has been shown to be associated with neural alterations in hippocampal and/or cortical regions as measured by functional magnetic resonance imaging (fMRI). Using functional imaging and a face-learning task, we investigated neural correlates of encoding and recalling face-name associations in 20 recreational drug users whose predominant drug use was ecstasy and 20 controls. To address the potential confounding effects of the cannabis use of the ecstasy using group, a second analysis included 14 previously tested cannabis users (Nestor, L., Roberts, G., Garavan, H., Hester, R., 2008. Deficits in learning and memory: parahippocampal hyperactivity and frontocortical hypoactivity in cannabis users. Neuroimage 40, 1328-1339). Ecstasy users performed significantly worse in learning and memory compared to controls and cannabis users. A conjunction analysis of the encode and recall phases of the task revealed ecstasy-specific hyperactivity in bilateral frontal regions, left temporal, right parietal, bilateral temporal, and bilateral occipital brain regions. Ecstasy-specific hypoactivity was evident in the right dorsal anterior cingulated cortex (ACC) and left posterior cingulated cortex. In both ecstasy and cannabis groups brain activation was decreased in the right medial frontal gyrus, left parahippocampal gyrus, left dorsal cingulate gyrus, and left caudate. These results elucidated ecstasy-related deficits, only some of which might be attributed to cannabis use. These ecstasy-specific effects may be related to the vulnerability of isocortical and allocortical regions to the neurotoxic effects of ecstasy.", "entity": "Cannabis", "aliases": "Bhang Bhangs Cannabi Cannabis indica indicas sativa sativas Ganja Ganjas Hashish Hashishs Hemp Plant Plants Hemps Marihuana Marihuanas Marijuana Marijuanas", "definition": "The plant genus in the Cannabaceae plant family, Urticales order, Hamamelidae subclass. The flowering tops are called many slang terms including pot, marijuana, hashish, bhang, and ganja. The stem is an important source of hemp fiber.\n    ", "id": "MESH:D002188"}
{"mention": "Deficits in learning", "mention_text": "It has been consistently shown that ecstasy users display impairments in learning and memory performance. In addition, working memory processing in ecstasy users has been shown to be associated with neural alterations in hippocampal and/or cortical regions as measured by functional magnetic resonance imaging (fMRI). Using functional imaging and a face-learning task, we investigated neural correlates of encoding and recalling face-name associations in 20 recreational drug users whose predominant drug use was ecstasy and 20 controls. To address the potential confounding effects of the cannabis use of the ecstasy using group, a second analysis included 14 previously tested cannabis users (Nestor, L., Roberts, G., Garavan, H., Hester, R., 2008. Deficits in learning and memory: parahippocampal hyperactivity and frontocortical hypoactivity in cannabis users. Neuroimage 40, 1328-1339). Ecstasy users performed significantly worse in learning and memory compared to controls and cannabis users. A conjunction analysis of the encode and recall phases of the task revealed ecstasy-specific hyperactivity in bilateral frontal regions, left temporal, right parietal, bilateral temporal, and bilateral occipital brain regions. Ecstasy-specific hypoactivity was evident in the right dorsal anterior cingulated cortex (ACC) and left posterior cingulated cortex. In both ecstasy and cannabis groups brain activation was decreased in the right medial frontal gyrus, left parahippocampal gyrus, left dorsal cingulate gyrus, and left caudate. These results elucidated ecstasy-related deficits, only some of which might be attributed to cannabis use. These ecstasy-specific effects may be related to the vulnerability of isocortical and allocortical regions to the neurotoxic effects of ecstasy.", "entity": "Learning Disorders", "aliases": "Academic Disorder Developmental Disorders Adult Learning of Scholastic Skills Disabilities Disability Disturbance Disturbances Development", "definition": "Conditions characterized by a significant discrepancy between an individual's perceived level of intellect and their ability to acquire new language and other cognitive skills. These disorders may result from organic or psychological conditions. Relatively common subtypes include DYSLEXIA, dyscalculia, and dysgraphia.\n    ", "id": "MESH:D007859"}
{"mention": "hyperactivity", "mention_text": "It has been consistently shown that ecstasy users display impairments in learning and memory performance. In addition, working memory processing in ecstasy users has been shown to be associated with neural alterations in hippocampal and/or cortical regions as measured by functional magnetic resonance imaging (fMRI). Using functional imaging and a face-learning task, we investigated neural correlates of encoding and recalling face-name associations in 20 recreational drug users whose predominant drug use was ecstasy and 20 controls. To address the potential confounding effects of the cannabis use of the ecstasy using group, a second analysis included 14 previously tested cannabis users (Nestor, L., Roberts, G., Garavan, H., Hester, R., 2008. Deficits in learning and memory: parahippocampal hyperactivity and frontocortical hypoactivity in cannabis users. Neuroimage 40, 1328-1339). Ecstasy users performed significantly worse in learning and memory compared to controls and cannabis users. A conjunction analysis of the encode and recall phases of the task revealed ecstasy-specific hyperactivity in bilateral frontal regions, left temporal, right parietal, bilateral temporal, and bilateral occipital brain regions. Ecstasy-specific hypoactivity was evident in the right dorsal anterior cingulated cortex (ACC) and left posterior cingulated cortex. In both ecstasy and cannabis groups brain activation was decreased in the right medial frontal gyrus, left parahippocampal gyrus, left dorsal cingulate gyrus, and left caudate. These results elucidated ecstasy-related deficits, only some of which might be attributed to cannabis use. These ecstasy-specific effects may be related to the vulnerability of isocortical and allocortical regions to the neurotoxic effects of ecstasy.", "entity": "Hyperkinesis", "aliases": "Generalized Hyperkinesia Hyperkinesias Hyperactivity Motor Hyperkinesis Hyperkinetic Movement Movements", "definition": "Excessive movement of muscles of the body as a whole, which may be associated with organic or psychological disorders.\n    ", "id": "MESH:D006948"}
{"mention": "Ecstasy", "mention_text": "It has been consistently shown that ecstasy users display impairments in learning and memory performance. In addition, working memory processing in ecstasy users has been shown to be associated with neural alterations in hippocampal and/or cortical regions as measured by functional magnetic resonance imaging (fMRI). Using functional imaging and a face-learning task, we investigated neural correlates of encoding and recalling face-name associations in 20 recreational drug users whose predominant drug use was ecstasy and 20 controls. To address the potential confounding effects of the cannabis use of the ecstasy using group, a second analysis included 14 previously tested cannabis users (Nestor, L., Roberts, G., Garavan, H., Hester, R., 2008. Deficits in learning and memory: parahippocampal hyperactivity and frontocortical hypoactivity in cannabis users. Neuroimage 40, 1328-1339). Ecstasy users performed significantly worse in learning and memory compared to controls and cannabis users. A conjunction analysis of the encode and recall phases of the task revealed ecstasy-specific hyperactivity in bilateral frontal regions, left temporal, right parietal, bilateral temporal, and bilateral occipital brain regions. Ecstasy-specific hypoactivity was evident in the right dorsal anterior cingulated cortex (ACC) and left posterior cingulated cortex. In both ecstasy and cannabis groups brain activation was decreased in the right medial frontal gyrus, left parahippocampal gyrus, left dorsal cingulate gyrus, and left caudate. These results elucidated ecstasy-related deficits, only some of which might be attributed to cannabis use. These ecstasy-specific effects may be related to the vulnerability of isocortical and allocortical regions to the neurotoxic effects of ecstasy.", "entity": "N-Methyl-3,4-methylenedioxyamphetamine", "aliases": "Ecstasy (Drug) Hydrochloride N-Methyl-3,4-methylenedioxyamphetamine MDMA Methylenedioxymethamphetamine N Methyl 3,4 methylenedioxyamphetamine", "definition": "An N-substituted amphetamine analog. It is a widely abused drug classified as a hallucinogen and causes marked, long-lasting changes in brain serotonergic systems. It is commonly referred to as MDMA or ecstasy.\n    ", "id": "MESH:D018817"}
{"mention": "neurotoxic", "mention_text": "It has been consistently shown that ecstasy users display impairments in learning and memory performance. In addition, working memory processing in ecstasy users has been shown to be associated with neural alterations in hippocampal and/or cortical regions as measured by functional magnetic resonance imaging (fMRI). Using functional imaging and a face-learning task, we investigated neural correlates of encoding and recalling face-name associations in 20 recreational drug users whose predominant drug use was ecstasy and 20 controls. To address the potential confounding effects of the cannabis use of the ecstasy using group, a second analysis included 14 previously tested cannabis users (Nestor, L., Roberts, G., Garavan, H., Hester, R., 2008. Deficits in learning and memory: parahippocampal hyperactivity and frontocortical hypoactivity in cannabis users. Neuroimage 40, 1328-1339). Ecstasy users performed significantly worse in learning and memory compared to controls and cannabis users. A conjunction analysis of the encode and recall phases of the task revealed ecstasy-specific hyperactivity in bilateral frontal regions, left temporal, right parietal, bilateral temporal, and bilateral occipital brain regions. Ecstasy-specific hypoactivity was evident in the right dorsal anterior cingulated cortex (ACC) and left posterior cingulated cortex. In both ecstasy and cannabis groups brain activation was decreased in the right medial frontal gyrus, left parahippocampal gyrus, left dorsal cingulate gyrus, and left caudate. These results elucidated ecstasy-related deficits, only some of which might be attributed to cannabis use. These ecstasy-specific effects may be related to the vulnerability of isocortical and allocortical regions to the neurotoxic effects of ecstasy.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "argatroban", "mention_text": "Prolonged elevation of plasma argatroban in a cardiac transplant patient with a suspected history of heparin-induced thrombocytopenia with thrombosis.", "entity": "argatroban", "aliases": "4-methyl-1-(N(2)-(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl)-L-arginyl)-2-piperidinecarboxylic acid Acova MCI 9038 MCI-9038 MD 805 MD-805 MD805 MMTQAP MPQA Novastan argatroban", "definition": "", "id": "MESH:C031942"}
{"mention": "heparin", "mention_text": "Prolonged elevation of plasma argatroban in a cardiac transplant patient with a suspected history of heparin-induced thrombocytopenia with thrombosis.", "entity": "Heparin", "aliases": "Heparin Sodium Unfractionated Heparinic Acid Liquaemin alpha alpha-Heparin", "definition": "A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.\n    ", "id": "MESH:D006493"}
{"mention": "thrombocytopenia", "mention_text": "Prolonged elevation of plasma argatroban in a cardiac transplant patient with a suspected history of heparin-induced thrombocytopenia with thrombosis.", "entity": "Thrombocytopenia", "aliases": "Thrombocytopenia Thrombocytopenias Thrombopenia Thrombopenias", "definition": "A subnormal level of BLOOD PLATELETS.\n    ", "id": "MESH:D013921"}
{"mention": "thrombosis", "mention_text": "Prolonged elevation of plasma argatroban in a cardiac transplant patient with a suspected history of heparin-induced thrombocytopenia with thrombosis.", "entity": "Thrombosis", "aliases": "Thromboses Thrombosis Thrombus", "definition": "Formation and development of a thrombus or blood clot in the blood vessel.\n    ", "id": "MESH:D013927"}
{"mention": "heparin", "mention_text": "BACKGROUND: Direct thrombin inhibitors (DTIs) provide an alternative method of anticoagulation for patients with a history of heparin-induced thrombocytopenia (HIT) or HIT with thrombosis (HITT) undergoing cardiopulmonary bypass (CPB). In the following report, a 65-year-old critically ill patient with a suspected history of HITT was administered argatroban for anticoagulation on bypass during heart transplantation. The patient required massive transfusion support (55 units of red blood cells, 42 units of fresh-frozen plasma, 40 units of cryoprecipitate, 40 units of platelets, and three doses of recombinant Factor VIIa) for severe intraoperative and postoperative bleeding. STUDY DESIGN AND METHODS: Plasma samples from before and after CPB were analyzed postoperatively for argatroban concentration using a modified ecarin clotting time (ECT) assay. RESULTS: Unexpectedly high concentrations of argatroban were measured in these samples (range, 0-32 microg/mL), and a prolonged plasma argatroban half life (t(1/2)) of 514 minutes was observed (published elimination t(1/2) is 39-51 minutes [< or = 181 minutes with hepatic impairment]). CONCLUSIONS: Correlation of plasma argatroban concentration versus the patient's coagulation variables and clinical course suggest that prolonged elevated levels of plasma argatroban may have contributed to the patient's extended coagulopathy. Because DTIs do not have reversal agents, surgical teams and transfusion services should remain aware of the possibility of massive transfusion events during anticoagulation with these agents. This is the first report to measure plasma argatroban concentration in the context of CPB and extended coagulopathy.", "entity": "Heparin", "aliases": "Heparin Sodium Unfractionated Heparinic Acid Liquaemin alpha alpha-Heparin", "definition": "A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.\n    ", "id": "MESH:D006493"}
{"mention": "thrombocytopenia", "mention_text": "BACKGROUND: Direct thrombin inhibitors (DTIs) provide an alternative method of anticoagulation for patients with a history of heparin-induced thrombocytopenia (HIT) or HIT with thrombosis (HITT) undergoing cardiopulmonary bypass (CPB). In the following report, a 65-year-old critically ill patient with a suspected history of HITT was administered argatroban for anticoagulation on bypass during heart transplantation. The patient required massive transfusion support (55 units of red blood cells, 42 units of fresh-frozen plasma, 40 units of cryoprecipitate, 40 units of platelets, and three doses of recombinant Factor VIIa) for severe intraoperative and postoperative bleeding. STUDY DESIGN AND METHODS: Plasma samples from before and after CPB were analyzed postoperatively for argatroban concentration using a modified ecarin clotting time (ECT) assay. RESULTS: Unexpectedly high concentrations of argatroban were measured in these samples (range, 0-32 microg/mL), and a prolonged plasma argatroban half life (t(1/2)) of 514 minutes was observed (published elimination t(1/2) is 39-51 minutes [< or = 181 minutes with hepatic impairment]). CONCLUSIONS: Correlation of plasma argatroban concentration versus the patient's coagulation variables and clinical course suggest that prolonged elevated levels of plasma argatroban may have contributed to the patient's extended coagulopathy. Because DTIs do not have reversal agents, surgical teams and transfusion services should remain aware of the possibility of massive transfusion events during anticoagulation with these agents. This is the first report to measure plasma argatroban concentration in the context of CPB and extended coagulopathy.", "entity": "Thrombocytopenia", "aliases": "Thrombocytopenia Thrombocytopenias Thrombopenia Thrombopenias", "definition": "A subnormal level of BLOOD PLATELETS.\n    ", "id": "MESH:D013921"}
{"mention": "HIT", "mention_text": "BACKGROUND: Direct thrombin inhibitors (DTIs) provide an alternative method of anticoagulation for patients with a history of heparin-induced thrombocytopenia (HIT) or HIT with thrombosis (HITT) undergoing cardiopulmonary bypass (CPB). In the following report, a 65-year-old critically ill patient with a suspected history of HITT was administered argatroban for anticoagulation on bypass during heart transplantation. The patient required massive transfusion support (55 units of red blood cells, 42 units of fresh-frozen plasma, 40 units of cryoprecipitate, 40 units of platelets, and three doses of recombinant Factor VIIa) for severe intraoperative and postoperative bleeding. STUDY DESIGN AND METHODS: Plasma samples from before and after CPB were analyzed postoperatively for argatroban concentration using a modified ecarin clotting time (ECT) assay. RESULTS: Unexpectedly high concentrations of argatroban were measured in these samples (range, 0-32 microg/mL), and a prolonged plasma argatroban half life (t(1/2)) of 514 minutes was observed (published elimination t(1/2) is 39-51 minutes [< or = 181 minutes with hepatic impairment]). CONCLUSIONS: Correlation of plasma argatroban concentration versus the patient's coagulation variables and clinical course suggest that prolonged elevated levels of plasma argatroban may have contributed to the patient's extended coagulopathy. Because DTIs do not have reversal agents, surgical teams and transfusion services should remain aware of the possibility of massive transfusion events during anticoagulation with these agents. This is the first report to measure plasma argatroban concentration in the context of CPB and extended coagulopathy.", "entity": "Thrombocytopenia", "aliases": "Thrombocytopenia Thrombocytopenias Thrombopenia Thrombopenias", "definition": "A subnormal level of BLOOD PLATELETS.\n    ", "id": "MESH:D013921"}
{"mention": "thrombosis", "mention_text": "BACKGROUND: Direct thrombin inhibitors (DTIs) provide an alternative method of anticoagulation for patients with a history of heparin-induced thrombocytopenia (HIT) or HIT with thrombosis (HITT) undergoing cardiopulmonary bypass (CPB). In the following report, a 65-year-old critically ill patient with a suspected history of HITT was administered argatroban for anticoagulation on bypass during heart transplantation. The patient required massive transfusion support (55 units of red blood cells, 42 units of fresh-frozen plasma, 40 units of cryoprecipitate, 40 units of platelets, and three doses of recombinant Factor VIIa) for severe intraoperative and postoperative bleeding. STUDY DESIGN AND METHODS: Plasma samples from before and after CPB were analyzed postoperatively for argatroban concentration using a modified ecarin clotting time (ECT) assay. RESULTS: Unexpectedly high concentrations of argatroban were measured in these samples (range, 0-32 microg/mL), and a prolonged plasma argatroban half life (t(1/2)) of 514 minutes was observed (published elimination t(1/2) is 39-51 minutes [< or = 181 minutes with hepatic impairment]). CONCLUSIONS: Correlation of plasma argatroban concentration versus the patient's coagulation variables and clinical course suggest that prolonged elevated levels of plasma argatroban may have contributed to the patient's extended coagulopathy. Because DTIs do not have reversal agents, surgical teams and transfusion services should remain aware of the possibility of massive transfusion events during anticoagulation with these agents. This is the first report to measure plasma argatroban concentration in the context of CPB and extended coagulopathy.", "entity": "Thrombosis", "aliases": "Thromboses Thrombosis Thrombus", "definition": "Formation and development of a thrombus or blood clot in the blood vessel.\n    ", "id": "MESH:D013927"}
{"mention": "critically ill", "mention_text": "BACKGROUND: Direct thrombin inhibitors (DTIs) provide an alternative method of anticoagulation for patients with a history of heparin-induced thrombocytopenia (HIT) or HIT with thrombosis (HITT) undergoing cardiopulmonary bypass (CPB). In the following report, a 65-year-old critically ill patient with a suspected history of HITT was administered argatroban for anticoagulation on bypass during heart transplantation. The patient required massive transfusion support (55 units of red blood cells, 42 units of fresh-frozen plasma, 40 units of cryoprecipitate, 40 units of platelets, and three doses of recombinant Factor VIIa) for severe intraoperative and postoperative bleeding. STUDY DESIGN AND METHODS: Plasma samples from before and after CPB were analyzed postoperatively for argatroban concentration using a modified ecarin clotting time (ECT) assay. RESULTS: Unexpectedly high concentrations of argatroban were measured in these samples (range, 0-32 microg/mL), and a prolonged plasma argatroban half life (t(1/2)) of 514 minutes was observed (published elimination t(1/2) is 39-51 minutes [< or = 181 minutes with hepatic impairment]). CONCLUSIONS: Correlation of plasma argatroban concentration versus the patient's coagulation variables and clinical course suggest that prolonged elevated levels of plasma argatroban may have contributed to the patient's extended coagulopathy. Because DTIs do not have reversal agents, surgical teams and transfusion services should remain aware of the possibility of massive transfusion events during anticoagulation with these agents. This is the first report to measure plasma argatroban concentration in the context of CPB and extended coagulopathy.", "entity": "Critical Illness", "aliases": "Critical Illness Illnesses Critically Ill", "definition": "A disease or state in which death is possible or imminent.\n    ", "id": "MESH:D016638"}
{"mention": "argatroban", "mention_text": "BACKGROUND: Direct thrombin inhibitors (DTIs) provide an alternative method of anticoagulation for patients with a history of heparin-induced thrombocytopenia (HIT) or HIT with thrombosis (HITT) undergoing cardiopulmonary bypass (CPB). In the following report, a 65-year-old critically ill patient with a suspected history of HITT was administered argatroban for anticoagulation on bypass during heart transplantation. The patient required massive transfusion support (55 units of red blood cells, 42 units of fresh-frozen plasma, 40 units of cryoprecipitate, 40 units of platelets, and three doses of recombinant Factor VIIa) for severe intraoperative and postoperative bleeding. STUDY DESIGN AND METHODS: Plasma samples from before and after CPB were analyzed postoperatively for argatroban concentration using a modified ecarin clotting time (ECT) assay. RESULTS: Unexpectedly high concentrations of argatroban were measured in these samples (range, 0-32 microg/mL), and a prolonged plasma argatroban half life (t(1/2)) of 514 minutes was observed (published elimination t(1/2) is 39-51 minutes [< or = 181 minutes with hepatic impairment]). CONCLUSIONS: Correlation of plasma argatroban concentration versus the patient's coagulation variables and clinical course suggest that prolonged elevated levels of plasma argatroban may have contributed to the patient's extended coagulopathy. Because DTIs do not have reversal agents, surgical teams and transfusion services should remain aware of the possibility of massive transfusion events during anticoagulation with these agents. This is the first report to measure plasma argatroban concentration in the context of CPB and extended coagulopathy.", "entity": "argatroban", "aliases": "4-methyl-1-(N(2)-(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl)-L-arginyl)-2-piperidinecarboxylic acid Acova MCI 9038 MCI-9038 MD 805 MD-805 MD805 MMTQAP MPQA Novastan argatroban", "definition": "", "id": "MESH:C031942"}
{"mention": "postoperative bleeding", "mention_text": "BACKGROUND: Direct thrombin inhibitors (DTIs) provide an alternative method of anticoagulation for patients with a history of heparin-induced thrombocytopenia (HIT) or HIT with thrombosis (HITT) undergoing cardiopulmonary bypass (CPB). In the following report, a 65-year-old critically ill patient with a suspected history of HITT was administered argatroban for anticoagulation on bypass during heart transplantation. The patient required massive transfusion support (55 units of red blood cells, 42 units of fresh-frozen plasma, 40 units of cryoprecipitate, 40 units of platelets, and three doses of recombinant Factor VIIa) for severe intraoperative and postoperative bleeding. STUDY DESIGN AND METHODS: Plasma samples from before and after CPB were analyzed postoperatively for argatroban concentration using a modified ecarin clotting time (ECT) assay. RESULTS: Unexpectedly high concentrations of argatroban were measured in these samples (range, 0-32 microg/mL), and a prolonged plasma argatroban half life (t(1/2)) of 514 minutes was observed (published elimination t(1/2) is 39-51 minutes [< or = 181 minutes with hepatic impairment]). CONCLUSIONS: Correlation of plasma argatroban concentration versus the patient's coagulation variables and clinical course suggest that prolonged elevated levels of plasma argatroban may have contributed to the patient's extended coagulopathy. Because DTIs do not have reversal agents, surgical teams and transfusion services should remain aware of the possibility of massive transfusion events during anticoagulation with these agents. This is the first report to measure plasma argatroban concentration in the context of CPB and extended coagulopathy.", "entity": "Postoperative Hemorrhage", "aliases": "Blood Loss Postoperative Hemorrhage Hemorrhages", "definition": "Hemorrhage following any surgical procedure. It may be immediate or delayed and is not restricted to the surgical wound.\n    ", "id": "MESH:D019106"}
{"mention": "hepatic impairment", "mention_text": "BACKGROUND: Direct thrombin inhibitors (DTIs) provide an alternative method of anticoagulation for patients with a history of heparin-induced thrombocytopenia (HIT) or HIT with thrombosis (HITT) undergoing cardiopulmonary bypass (CPB). In the following report, a 65-year-old critically ill patient with a suspected history of HITT was administered argatroban for anticoagulation on bypass during heart transplantation. The patient required massive transfusion support (55 units of red blood cells, 42 units of fresh-frozen plasma, 40 units of cryoprecipitate, 40 units of platelets, and three doses of recombinant Factor VIIa) for severe intraoperative and postoperative bleeding. STUDY DESIGN AND METHODS: Plasma samples from before and after CPB were analyzed postoperatively for argatroban concentration using a modified ecarin clotting time (ECT) assay. RESULTS: Unexpectedly high concentrations of argatroban were measured in these samples (range, 0-32 microg/mL), and a prolonged plasma argatroban half life (t(1/2)) of 514 minutes was observed (published elimination t(1/2) is 39-51 minutes [< or = 181 minutes with hepatic impairment]). CONCLUSIONS: Correlation of plasma argatroban concentration versus the patient's coagulation variables and clinical course suggest that prolonged elevated levels of plasma argatroban may have contributed to the patient's extended coagulopathy. Because DTIs do not have reversal agents, surgical teams and transfusion services should remain aware of the possibility of massive transfusion events during anticoagulation with these agents. This is the first report to measure plasma argatroban concentration in the context of CPB and extended coagulopathy.", "entity": "Liver Diseases", "aliases": "Disease Liver Diseases Dysfunction Dysfunctions", "definition": "Pathological processes of the LIVER.\n    ", "id": "MESH:D008107"}
{"mention": "coagulopathy", "mention_text": "BACKGROUND: Direct thrombin inhibitors (DTIs) provide an alternative method of anticoagulation for patients with a history of heparin-induced thrombocytopenia (HIT) or HIT with thrombosis (HITT) undergoing cardiopulmonary bypass (CPB). In the following report, a 65-year-old critically ill patient with a suspected history of HITT was administered argatroban for anticoagulation on bypass during heart transplantation. The patient required massive transfusion support (55 units of red blood cells, 42 units of fresh-frozen plasma, 40 units of cryoprecipitate, 40 units of platelets, and three doses of recombinant Factor VIIa) for severe intraoperative and postoperative bleeding. STUDY DESIGN AND METHODS: Plasma samples from before and after CPB were analyzed postoperatively for argatroban concentration using a modified ecarin clotting time (ECT) assay. RESULTS: Unexpectedly high concentrations of argatroban were measured in these samples (range, 0-32 microg/mL), and a prolonged plasma argatroban half life (t(1/2)) of 514 minutes was observed (published elimination t(1/2) is 39-51 minutes [< or = 181 minutes with hepatic impairment]). CONCLUSIONS: Correlation of plasma argatroban concentration versus the patient's coagulation variables and clinical course suggest that prolonged elevated levels of plasma argatroban may have contributed to the patient's extended coagulopathy. Because DTIs do not have reversal agents, surgical teams and transfusion services should remain aware of the possibility of massive transfusion events during anticoagulation with these agents. This is the first report to measure plasma argatroban concentration in the context of CPB and extended coagulopathy.", "entity": "Blood Coagulation Disorders", "aliases": "Blood Coagulation Disorder Disorders", "definition": "Hemorrhagic and thrombotic disorders that occur as a consequence of abnormalities in blood coagulation due to a variety of factors such as COAGULATION PROTEIN DISORDERS; BLOOD PLATELET DISORDERS; BLOOD PROTEIN DISORDERS or nutritional conditions.\n    ", "id": "MESH:D001778"}
{"mention": "Antituberculosis", "mention_text": "Antituberculosis therapy-induced acute liver failure: magnitude, profile, prognosis, and predictors of outcome.", "entity": "Antitubercular Agents", "aliases": "Agents Antitubercular Tuberculostatic Drugs", "definition": "Drugs used in the treatment of tuberculosis. They are divided into two main classes: \"first-line\" agents, those with the greatest efficacy and acceptable degrees of toxicity used successfully in the great majority of cases; and \"second-line\" drugs used in drug-resistant cases or those in which some other patient-related condition has compromised the effectiveness of primary therapy.\n    ", "id": "MESH:D000995"}
{"mention": "acute liver failure", "mention_text": "Antituberculosis therapy-induced acute liver failure: magnitude, profile, prognosis, and predictors of outcome.", "entity": "Liver Failure, Acute", "aliases": "Acute Hepatic Failure Liver Fulminant Failures Fulminating", "definition": "A form of rapid-onset LIVER FAILURE, also known as fulminant hepatic failure, caused by severe liver injury or massive loss of HEPATOCYTES. It is characterized by sudden development of liver dysfunction and JAUNDICE. Acute liver failure may progress to exhibit cerebral dysfunction even HEPATIC COMA depending on the etiology that includes hepatic ISCHEMIA, drug toxicity, malignant infiltration, and viral hepatitis such as post-transfusion HEPATITIS B and HEPATITIS C.\n    ", "id": "MESH:D017114"}
{"mention": "Antituberculosis", "mention_text": "Antituberculosis therapy (ATT)-associated acute liver failure (ATT-ALF) is the commonest drug-induced ALF in South Asia. Prospective studies on ATT-ALF are lacking. The current study prospectively evaluated the magnitude, clinical course, outcome, and prognostic factors in ATT-ALF. From January 1986 to January 2009, 1223 consecutive ALF patients were evaluated: ATT alone was the cause in 70 (5.7%) patients. Another 15 (1.2%) had ATT and simultaneous hepatitis virus infection. In 44 (62.8%) patients, ATT was prescribed empirically without definitive evidence of tuberculosis. ATT-ALF patients were younger (32.87 [+/-15.8] years), and 49 (70%) of them were women. Most had hyperacute presentation; the median icterus encephalopathy interval was 4.5 (0-30) days. The median duration of ATT before ALF was 30 (7-350) days. At presentation, advanced encephalopathy and cerebral edema were present in 51 (76%) and 29 (41.4%) patients, respectively. Gastrointestinal bleed, seizures, infection, and acute renal failure were documented in seven (10%), five (7.1%), 26 (37.1%), and seven (10%) patients, respectively. Compared with hepatitis E virus (HEV) and non-A non-E-induced ALF, ATT-ALF patients had nearly similar presentations except for older age and less elevation of liver enzymes. The mortality rate among patients with ATT-ALF was high (67.1%, n = 47), and only 23 (32.9%) patients recovered with medical treatment. In multivariate analysis, three factors independently predicted mortality: serum bilirubin (>or=10.8 mg/dL), prothrombin time (PT) prolongation (>or=26 seconds), and grade III/IV encephalopathy at presentation. CONCLUSION: ATT-ALF constituted 5.7% of ALF at our center and had a high mortality rate. Because the mortality rate is so high, determining which factors are predictors is less important. A high proportion of patients had consumed ATT empirically, which could have been prevented.", "entity": "Antitubercular Agents", "aliases": "Agents Antitubercular Tuberculostatic Drugs", "definition": "Drugs used in the treatment of tuberculosis. They are divided into two main classes: \"first-line\" agents, those with the greatest efficacy and acceptable degrees of toxicity used successfully in the great majority of cases; and \"second-line\" drugs used in drug-resistant cases or those in which some other patient-related condition has compromised the effectiveness of primary therapy.\n    ", "id": "MESH:D000995"}
{"mention": "acute liver failure", "mention_text": "Antituberculosis therapy (ATT)-associated acute liver failure (ATT-ALF) is the commonest drug-induced ALF in South Asia. Prospective studies on ATT-ALF are lacking. The current study prospectively evaluated the magnitude, clinical course, outcome, and prognostic factors in ATT-ALF. From January 1986 to January 2009, 1223 consecutive ALF patients were evaluated: ATT alone was the cause in 70 (5.7%) patients. Another 15 (1.2%) had ATT and simultaneous hepatitis virus infection. In 44 (62.8%) patients, ATT was prescribed empirically without definitive evidence of tuberculosis. ATT-ALF patients were younger (32.87 [+/-15.8] years), and 49 (70%) of them were women. Most had hyperacute presentation; the median icterus encephalopathy interval was 4.5 (0-30) days. The median duration of ATT before ALF was 30 (7-350) days. At presentation, advanced encephalopathy and cerebral edema were present in 51 (76%) and 29 (41.4%) patients, respectively. Gastrointestinal bleed, seizures, infection, and acute renal failure were documented in seven (10%), five (7.1%), 26 (37.1%), and seven (10%) patients, respectively. Compared with hepatitis E virus (HEV) and non-A non-E-induced ALF, ATT-ALF patients had nearly similar presentations except for older age and less elevation of liver enzymes. The mortality rate among patients with ATT-ALF was high (67.1%, n = 47), and only 23 (32.9%) patients recovered with medical treatment. In multivariate analysis, three factors independently predicted mortality: serum bilirubin (>or=10.8 mg/dL), prothrombin time (PT) prolongation (>or=26 seconds), and grade III/IV encephalopathy at presentation. CONCLUSION: ATT-ALF constituted 5.7% of ALF at our center and had a high mortality rate. Because the mortality rate is so high, determining which factors are predictors is less important. A high proportion of patients had consumed ATT empirically, which could have been prevented.", "entity": "Liver Failure, Acute", "aliases": "Acute Hepatic Failure Liver Fulminant Failures Fulminating", "definition": "A form of rapid-onset LIVER FAILURE, also known as fulminant hepatic failure, caused by severe liver injury or massive loss of HEPATOCYTES. It is characterized by sudden development of liver dysfunction and JAUNDICE. Acute liver failure may progress to exhibit cerebral dysfunction even HEPATIC COMA depending on the etiology that includes hepatic ISCHEMIA, drug toxicity, malignant infiltration, and viral hepatitis such as post-transfusion HEPATITIS B and HEPATITIS C.\n    ", "id": "MESH:D017114"}
{"mention": "ALF", "mention_text": "Antituberculosis therapy (ATT)-associated acute liver failure (ATT-ALF) is the commonest drug-induced ALF in South Asia. Prospective studies on ATT-ALF are lacking. The current study prospectively evaluated the magnitude, clinical course, outcome, and prognostic factors in ATT-ALF. From January 1986 to January 2009, 1223 consecutive ALF patients were evaluated: ATT alone was the cause in 70 (5.7%) patients. Another 15 (1.2%) had ATT and simultaneous hepatitis virus infection. In 44 (62.8%) patients, ATT was prescribed empirically without definitive evidence of tuberculosis. ATT-ALF patients were younger (32.87 [+/-15.8] years), and 49 (70%) of them were women. Most had hyperacute presentation; the median icterus encephalopathy interval was 4.5 (0-30) days. The median duration of ATT before ALF was 30 (7-350) days. At presentation, advanced encephalopathy and cerebral edema were present in 51 (76%) and 29 (41.4%) patients, respectively. Gastrointestinal bleed, seizures, infection, and acute renal failure were documented in seven (10%), five (7.1%), 26 (37.1%), and seven (10%) patients, respectively. Compared with hepatitis E virus (HEV) and non-A non-E-induced ALF, ATT-ALF patients had nearly similar presentations except for older age and less elevation of liver enzymes. The mortality rate among patients with ATT-ALF was high (67.1%, n = 47), and only 23 (32.9%) patients recovered with medical treatment. In multivariate analysis, three factors independently predicted mortality: serum bilirubin (>or=10.8 mg/dL), prothrombin time (PT) prolongation (>or=26 seconds), and grade III/IV encephalopathy at presentation. CONCLUSION: ATT-ALF constituted 5.7% of ALF at our center and had a high mortality rate. Because the mortality rate is so high, determining which factors are predictors is less important. A high proportion of patients had consumed ATT empirically, which could have been prevented.", "entity": "Liver Failure, Acute", "aliases": "Acute Hepatic Failure Liver Fulminant Failures Fulminating", "definition": "A form of rapid-onset LIVER FAILURE, also known as fulminant hepatic failure, caused by severe liver injury or massive loss of HEPATOCYTES. It is characterized by sudden development of liver dysfunction and JAUNDICE. Acute liver failure may progress to exhibit cerebral dysfunction even HEPATIC COMA depending on the etiology that includes hepatic ISCHEMIA, drug toxicity, malignant infiltration, and viral hepatitis such as post-transfusion HEPATITIS B and HEPATITIS C.\n    ", "id": "MESH:D017114"}
{"mention": "hepatitis virus infection", "mention_text": "Antituberculosis therapy (ATT)-associated acute liver failure (ATT-ALF) is the commonest drug-induced ALF in South Asia. Prospective studies on ATT-ALF are lacking. The current study prospectively evaluated the magnitude, clinical course, outcome, and prognostic factors in ATT-ALF. From January 1986 to January 2009, 1223 consecutive ALF patients were evaluated: ATT alone was the cause in 70 (5.7%) patients. Another 15 (1.2%) had ATT and simultaneous hepatitis virus infection. In 44 (62.8%) patients, ATT was prescribed empirically without definitive evidence of tuberculosis. ATT-ALF patients were younger (32.87 [+/-15.8] years), and 49 (70%) of them were women. Most had hyperacute presentation; the median icterus encephalopathy interval was 4.5 (0-30) days. The median duration of ATT before ALF was 30 (7-350) days. At presentation, advanced encephalopathy and cerebral edema were present in 51 (76%) and 29 (41.4%) patients, respectively. Gastrointestinal bleed, seizures, infection, and acute renal failure were documented in seven (10%), five (7.1%), 26 (37.1%), and seven (10%) patients, respectively. Compared with hepatitis E virus (HEV) and non-A non-E-induced ALF, ATT-ALF patients had nearly similar presentations except for older age and less elevation of liver enzymes. The mortality rate among patients with ATT-ALF was high (67.1%, n = 47), and only 23 (32.9%) patients recovered with medical treatment. In multivariate analysis, three factors independently predicted mortality: serum bilirubin (>or=10.8 mg/dL), prothrombin time (PT) prolongation (>or=26 seconds), and grade III/IV encephalopathy at presentation. CONCLUSION: ATT-ALF constituted 5.7% of ALF at our center and had a high mortality rate. Because the mortality rate is so high, determining which factors are predictors is less important. A high proportion of patients had consumed ATT empirically, which could have been prevented.", "entity": "Hepatitis, Viral, Human", "aliases": "Hepatitis Viral Human", "definition": "INFLAMMATION of the LIVER in humans due to infection by VIRUSES. There are several significant types of human viral hepatitis with infection caused by enteric-transmission (HEPATITIS A; HEPATITIS E) or blood transfusion (HEPATITIS B; HEPATITIS C; and HEPATITIS D).\n    ", "id": "MESH:D006525"}
{"mention": "tuberculosis", "mention_text": "Antituberculosis therapy (ATT)-associated acute liver failure (ATT-ALF) is the commonest drug-induced ALF in South Asia. Prospective studies on ATT-ALF are lacking. The current study prospectively evaluated the magnitude, clinical course, outcome, and prognostic factors in ATT-ALF. From January 1986 to January 2009, 1223 consecutive ALF patients were evaluated: ATT alone was the cause in 70 (5.7%) patients. Another 15 (1.2%) had ATT and simultaneous hepatitis virus infection. In 44 (62.8%) patients, ATT was prescribed empirically without definitive evidence of tuberculosis. ATT-ALF patients were younger (32.87 [+/-15.8] years), and 49 (70%) of them were women. Most had hyperacute presentation; the median icterus encephalopathy interval was 4.5 (0-30) days. The median duration of ATT before ALF was 30 (7-350) days. At presentation, advanced encephalopathy and cerebral edema were present in 51 (76%) and 29 (41.4%) patients, respectively. Gastrointestinal bleed, seizures, infection, and acute renal failure were documented in seven (10%), five (7.1%), 26 (37.1%), and seven (10%) patients, respectively. Compared with hepatitis E virus (HEV) and non-A non-E-induced ALF, ATT-ALF patients had nearly similar presentations except for older age and less elevation of liver enzymes. The mortality rate among patients with ATT-ALF was high (67.1%, n = 47), and only 23 (32.9%) patients recovered with medical treatment. In multivariate analysis, three factors independently predicted mortality: serum bilirubin (>or=10.8 mg/dL), prothrombin time (PT) prolongation (>or=26 seconds), and grade III/IV encephalopathy at presentation. CONCLUSION: ATT-ALF constituted 5.7% of ALF at our center and had a high mortality rate. Because the mortality rate is so high, determining which factors are predictors is less important. A high proportion of patients had consumed ATT empirically, which could have been prevented.", "entity": "Tuberculosis", "aliases": "Disease Koch's Kochs Koch Tuberculoses Tuberculosis", "definition": "Any of the infectious diseases of man and other animals caused by species of MYCOBACTERIUM.\n    ", "id": "MESH:D014376"}
{"mention": "icterus", "mention_text": "Antituberculosis therapy (ATT)-associated acute liver failure (ATT-ALF) is the commonest drug-induced ALF in South Asia. Prospective studies on ATT-ALF are lacking. The current study prospectively evaluated the magnitude, clinical course, outcome, and prognostic factors in ATT-ALF. From January 1986 to January 2009, 1223 consecutive ALF patients were evaluated: ATT alone was the cause in 70 (5.7%) patients. Another 15 (1.2%) had ATT and simultaneous hepatitis virus infection. In 44 (62.8%) patients, ATT was prescribed empirically without definitive evidence of tuberculosis. ATT-ALF patients were younger (32.87 [+/-15.8] years), and 49 (70%) of them were women. Most had hyperacute presentation; the median icterus encephalopathy interval was 4.5 (0-30) days. The median duration of ATT before ALF was 30 (7-350) days. At presentation, advanced encephalopathy and cerebral edema were present in 51 (76%) and 29 (41.4%) patients, respectively. Gastrointestinal bleed, seizures, infection, and acute renal failure were documented in seven (10%), five (7.1%), 26 (37.1%), and seven (10%) patients, respectively. Compared with hepatitis E virus (HEV) and non-A non-E-induced ALF, ATT-ALF patients had nearly similar presentations except for older age and less elevation of liver enzymes. The mortality rate among patients with ATT-ALF was high (67.1%, n = 47), and only 23 (32.9%) patients recovered with medical treatment. In multivariate analysis, three factors independently predicted mortality: serum bilirubin (>or=10.8 mg/dL), prothrombin time (PT) prolongation (>or=26 seconds), and grade III/IV encephalopathy at presentation. CONCLUSION: ATT-ALF constituted 5.7% of ALF at our center and had a high mortality rate. Because the mortality rate is so high, determining which factors are predictors is less important. A high proportion of patients had consumed ATT empirically, which could have been prevented.", "entity": "Jaundice", "aliases": "Hemolytic Jaundice Jaundices Icterus", "definition": "A clinical manifestation of HYPERBILIRUBINEMIA, characterized by the yellowish staining of the SKIN; MUCOUS MEMBRANE; and SCLERA. Clinical jaundice usually is a sign of LIVER dysfunction.\n    ", "id": "MESH:D007565"}
{"mention": "encephalopathy", "mention_text": "Antituberculosis therapy (ATT)-associated acute liver failure (ATT-ALF) is the commonest drug-induced ALF in South Asia. Prospective studies on ATT-ALF are lacking. The current study prospectively evaluated the magnitude, clinical course, outcome, and prognostic factors in ATT-ALF. From January 1986 to January 2009, 1223 consecutive ALF patients were evaluated: ATT alone was the cause in 70 (5.7%) patients. Another 15 (1.2%) had ATT and simultaneous hepatitis virus infection. In 44 (62.8%) patients, ATT was prescribed empirically without definitive evidence of tuberculosis. ATT-ALF patients were younger (32.87 [+/-15.8] years), and 49 (70%) of them were women. Most had hyperacute presentation; the median icterus encephalopathy interval was 4.5 (0-30) days. The median duration of ATT before ALF was 30 (7-350) days. At presentation, advanced encephalopathy and cerebral edema were present in 51 (76%) and 29 (41.4%) patients, respectively. Gastrointestinal bleed, seizures, infection, and acute renal failure were documented in seven (10%), five (7.1%), 26 (37.1%), and seven (10%) patients, respectively. Compared with hepatitis E virus (HEV) and non-A non-E-induced ALF, ATT-ALF patients had nearly similar presentations except for older age and less elevation of liver enzymes. The mortality rate among patients with ATT-ALF was high (67.1%, n = 47), and only 23 (32.9%) patients recovered with medical treatment. In multivariate analysis, three factors independently predicted mortality: serum bilirubin (>or=10.8 mg/dL), prothrombin time (PT) prolongation (>or=26 seconds), and grade III/IV encephalopathy at presentation. CONCLUSION: ATT-ALF constituted 5.7% of ALF at our center and had a high mortality rate. Because the mortality rate is so high, determining which factors are predictors is less important. A high proportion of patients had consumed ATT empirically, which could have been prevented.", "entity": "Brain Diseases", "aliases": "Brain Disease Diseases Disorder Disorders CNS Intracranial Central Nervous System Encephalon", "definition": "Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.\n    ", "id": "MESH:D001927"}
{"mention": "cerebral edema", "mention_text": "Antituberculosis therapy (ATT)-associated acute liver failure (ATT-ALF) is the commonest drug-induced ALF in South Asia. Prospective studies on ATT-ALF are lacking. The current study prospectively evaluated the magnitude, clinical course, outcome, and prognostic factors in ATT-ALF. From January 1986 to January 2009, 1223 consecutive ALF patients were evaluated: ATT alone was the cause in 70 (5.7%) patients. Another 15 (1.2%) had ATT and simultaneous hepatitis virus infection. In 44 (62.8%) patients, ATT was prescribed empirically without definitive evidence of tuberculosis. ATT-ALF patients were younger (32.87 [+/-15.8] years), and 49 (70%) of them were women. Most had hyperacute presentation; the median icterus encephalopathy interval was 4.5 (0-30) days. The median duration of ATT before ALF was 30 (7-350) days. At presentation, advanced encephalopathy and cerebral edema were present in 51 (76%) and 29 (41.4%) patients, respectively. Gastrointestinal bleed, seizures, infection, and acute renal failure were documented in seven (10%), five (7.1%), 26 (37.1%), and seven (10%) patients, respectively. Compared with hepatitis E virus (HEV) and non-A non-E-induced ALF, ATT-ALF patients had nearly similar presentations except for older age and less elevation of liver enzymes. The mortality rate among patients with ATT-ALF was high (67.1%, n = 47), and only 23 (32.9%) patients recovered with medical treatment. In multivariate analysis, three factors independently predicted mortality: serum bilirubin (>or=10.8 mg/dL), prothrombin time (PT) prolongation (>or=26 seconds), and grade III/IV encephalopathy at presentation. CONCLUSION: ATT-ALF constituted 5.7% of ALF at our center and had a high mortality rate. Because the mortality rate is so high, determining which factors are predictors is less important. A high proportion of patients had consumed ATT empirically, which could have been prevented.", "entity": "Brain Edema", "aliases": "Brain Edema Cytotoxic Vasogenic Swelling Swellings Cerebral Edemas Intracranial", "definition": "Increased intracellular or extracellular fluid in brain tissue. Cytotoxic brain edema (swelling due to increased intracellular fluid) is indicative of a disturbance in cell metabolism, and is commonly associated with hypoxic or ischemic injuries (see HYPOXIA, BRAIN). An increase in extracellular fluid may be caused by increased brain capillary permeability (vasogenic edema), an osmotic gradient, local blockages in interstitial fluid pathways, or by obstruction of CSF flow (e.g., obstructive HYDROCEPHALUS). (From Childs Nerv Syst 1992 Sep; 8(6):301-6)\n    ", "id": "MESH:D001929"}
{"mention": "Gastrointestinal bleed", "mention_text": "Antituberculosis therapy (ATT)-associated acute liver failure (ATT-ALF) is the commonest drug-induced ALF in South Asia. Prospective studies on ATT-ALF are lacking. The current study prospectively evaluated the magnitude, clinical course, outcome, and prognostic factors in ATT-ALF. From January 1986 to January 2009, 1223 consecutive ALF patients were evaluated: ATT alone was the cause in 70 (5.7%) patients. Another 15 (1.2%) had ATT and simultaneous hepatitis virus infection. In 44 (62.8%) patients, ATT was prescribed empirically without definitive evidence of tuberculosis. ATT-ALF patients were younger (32.87 [+/-15.8] years), and 49 (70%) of them were women. Most had hyperacute presentation; the median icterus encephalopathy interval was 4.5 (0-30) days. The median duration of ATT before ALF was 30 (7-350) days. At presentation, advanced encephalopathy and cerebral edema were present in 51 (76%) and 29 (41.4%) patients, respectively. Gastrointestinal bleed, seizures, infection, and acute renal failure were documented in seven (10%), five (7.1%), 26 (37.1%), and seven (10%) patients, respectively. Compared with hepatitis E virus (HEV) and non-A non-E-induced ALF, ATT-ALF patients had nearly similar presentations except for older age and less elevation of liver enzymes. The mortality rate among patients with ATT-ALF was high (67.1%, n = 47), and only 23 (32.9%) patients recovered with medical treatment. In multivariate analysis, three factors independently predicted mortality: serum bilirubin (>or=10.8 mg/dL), prothrombin time (PT) prolongation (>or=26 seconds), and grade III/IV encephalopathy at presentation. CONCLUSION: ATT-ALF constituted 5.7% of ALF at our center and had a high mortality rate. Because the mortality rate is so high, determining which factors are predictors is less important. A high proportion of patients had consumed ATT empirically, which could have been prevented.", "entity": "Gastrointestinal Hemorrhage", "aliases": "Gastrointestinal Hemorrhage Hemorrhages Hematochezia Hematochezias", "definition": "Bleeding in any segment of the GASTROINTESTINAL TRACT from ESOPHAGUS to RECTUM.\n    ", "id": "MESH:D006471"}
{"mention": "seizures", "mention_text": "Antituberculosis therapy (ATT)-associated acute liver failure (ATT-ALF) is the commonest drug-induced ALF in South Asia. Prospective studies on ATT-ALF are lacking. The current study prospectively evaluated the magnitude, clinical course, outcome, and prognostic factors in ATT-ALF. From January 1986 to January 2009, 1223 consecutive ALF patients were evaluated: ATT alone was the cause in 70 (5.7%) patients. Another 15 (1.2%) had ATT and simultaneous hepatitis virus infection. In 44 (62.8%) patients, ATT was prescribed empirically without definitive evidence of tuberculosis. ATT-ALF patients were younger (32.87 [+/-15.8] years), and 49 (70%) of them were women. Most had hyperacute presentation; the median icterus encephalopathy interval was 4.5 (0-30) days. The median duration of ATT before ALF was 30 (7-350) days. At presentation, advanced encephalopathy and cerebral edema were present in 51 (76%) and 29 (41.4%) patients, respectively. Gastrointestinal bleed, seizures, infection, and acute renal failure were documented in seven (10%), five (7.1%), 26 (37.1%), and seven (10%) patients, respectively. Compared with hepatitis E virus (HEV) and non-A non-E-induced ALF, ATT-ALF patients had nearly similar presentations except for older age and less elevation of liver enzymes. The mortality rate among patients with ATT-ALF was high (67.1%, n = 47), and only 23 (32.9%) patients recovered with medical treatment. In multivariate analysis, three factors independently predicted mortality: serum bilirubin (>or=10.8 mg/dL), prothrombin time (PT) prolongation (>or=26 seconds), and grade III/IV encephalopathy at presentation. CONCLUSION: ATT-ALF constituted 5.7% of ALF at our center and had a high mortality rate. Because the mortality rate is so high, determining which factors are predictors is less important. A high proportion of patients had consumed ATT empirically, which could have been prevented.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "infection", "mention_text": "Antituberculosis therapy (ATT)-associated acute liver failure (ATT-ALF) is the commonest drug-induced ALF in South Asia. Prospective studies on ATT-ALF are lacking. The current study prospectively evaluated the magnitude, clinical course, outcome, and prognostic factors in ATT-ALF. From January 1986 to January 2009, 1223 consecutive ALF patients were evaluated: ATT alone was the cause in 70 (5.7%) patients. Another 15 (1.2%) had ATT and simultaneous hepatitis virus infection. In 44 (62.8%) patients, ATT was prescribed empirically without definitive evidence of tuberculosis. ATT-ALF patients were younger (32.87 [+/-15.8] years), and 49 (70%) of them were women. Most had hyperacute presentation; the median icterus encephalopathy interval was 4.5 (0-30) days. The median duration of ATT before ALF was 30 (7-350) days. At presentation, advanced encephalopathy and cerebral edema were present in 51 (76%) and 29 (41.4%) patients, respectively. Gastrointestinal bleed, seizures, infection, and acute renal failure were documented in seven (10%), five (7.1%), 26 (37.1%), and seven (10%) patients, respectively. Compared with hepatitis E virus (HEV) and non-A non-E-induced ALF, ATT-ALF patients had nearly similar presentations except for older age and less elevation of liver enzymes. The mortality rate among patients with ATT-ALF was high (67.1%, n = 47), and only 23 (32.9%) patients recovered with medical treatment. In multivariate analysis, three factors independently predicted mortality: serum bilirubin (>or=10.8 mg/dL), prothrombin time (PT) prolongation (>or=26 seconds), and grade III/IV encephalopathy at presentation. CONCLUSION: ATT-ALF constituted 5.7% of ALF at our center and had a high mortality rate. Because the mortality rate is so high, determining which factors are predictors is less important. A high proportion of patients had consumed ATT empirically, which could have been prevented.", "entity": "Infection", "aliases": "Infection Infections", "definition": "Invasion of the host organism by microorganisms that can cause pathological conditions or diseases.\n    ", "id": "MESH:D007239"}
{"mention": "acute renal failure", "mention_text": "Antituberculosis therapy (ATT)-associated acute liver failure (ATT-ALF) is the commonest drug-induced ALF in South Asia. Prospective studies on ATT-ALF are lacking. The current study prospectively evaluated the magnitude, clinical course, outcome, and prognostic factors in ATT-ALF. From January 1986 to January 2009, 1223 consecutive ALF patients were evaluated: ATT alone was the cause in 70 (5.7%) patients. Another 15 (1.2%) had ATT and simultaneous hepatitis virus infection. In 44 (62.8%) patients, ATT was prescribed empirically without definitive evidence of tuberculosis. ATT-ALF patients were younger (32.87 [+/-15.8] years), and 49 (70%) of them were women. Most had hyperacute presentation; the median icterus encephalopathy interval was 4.5 (0-30) days. The median duration of ATT before ALF was 30 (7-350) days. At presentation, advanced encephalopathy and cerebral edema were present in 51 (76%) and 29 (41.4%) patients, respectively. Gastrointestinal bleed, seizures, infection, and acute renal failure were documented in seven (10%), five (7.1%), 26 (37.1%), and seven (10%) patients, respectively. Compared with hepatitis E virus (HEV) and non-A non-E-induced ALF, ATT-ALF patients had nearly similar presentations except for older age and less elevation of liver enzymes. The mortality rate among patients with ATT-ALF was high (67.1%, n = 47), and only 23 (32.9%) patients recovered with medical treatment. In multivariate analysis, three factors independently predicted mortality: serum bilirubin (>or=10.8 mg/dL), prothrombin time (PT) prolongation (>or=26 seconds), and grade III/IV encephalopathy at presentation. CONCLUSION: ATT-ALF constituted 5.7% of ALF at our center and had a high mortality rate. Because the mortality rate is so high, determining which factors are predictors is less important. A high proportion of patients had consumed ATT empirically, which could have been prevented.", "entity": "Acute Kidney Injury", "aliases": "Acute Kidney Failure Failures Injuries Injury Insufficiencies Insufficiency Renal", "definition": "Abrupt reduction in kidney function. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions.\n    ", "id": "MESH:D058186"}
{"mention": "hepatitis E", "mention_text": "Antituberculosis therapy (ATT)-associated acute liver failure (ATT-ALF) is the commonest drug-induced ALF in South Asia. Prospective studies on ATT-ALF are lacking. The current study prospectively evaluated the magnitude, clinical course, outcome, and prognostic factors in ATT-ALF. From January 1986 to January 2009, 1223 consecutive ALF patients were evaluated: ATT alone was the cause in 70 (5.7%) patients. Another 15 (1.2%) had ATT and simultaneous hepatitis virus infection. In 44 (62.8%) patients, ATT was prescribed empirically without definitive evidence of tuberculosis. ATT-ALF patients were younger (32.87 [+/-15.8] years), and 49 (70%) of them were women. Most had hyperacute presentation; the median icterus encephalopathy interval was 4.5 (0-30) days. The median duration of ATT before ALF was 30 (7-350) days. At presentation, advanced encephalopathy and cerebral edema were present in 51 (76%) and 29 (41.4%) patients, respectively. Gastrointestinal bleed, seizures, infection, and acute renal failure were documented in seven (10%), five (7.1%), 26 (37.1%), and seven (10%) patients, respectively. Compared with hepatitis E virus (HEV) and non-A non-E-induced ALF, ATT-ALF patients had nearly similar presentations except for older age and less elevation of liver enzymes. The mortality rate among patients with ATT-ALF was high (67.1%, n = 47), and only 23 (32.9%) patients recovered with medical treatment. In multivariate analysis, three factors independently predicted mortality: serum bilirubin (>or=10.8 mg/dL), prothrombin time (PT) prolongation (>or=26 seconds), and grade III/IV encephalopathy at presentation. CONCLUSION: ATT-ALF constituted 5.7% of ALF at our center and had a high mortality rate. Because the mortality rate is so high, determining which factors are predictors is less important. A high proportion of patients had consumed ATT empirically, which could have been prevented.", "entity": "Hepatitis E", "aliases": "ET-NANBH Enterically Transmitted Non A Non B Hepatitis Enterically-Transmitted Non-A Non-B Epidemic Hepatitides Water-Borne E Viral Water Borne", "definition": "Acute INFLAMMATION of the LIVER in humans; caused by HEPATITIS E VIRUS, a non-enveloped single-stranded RNA virus. Similar to HEPATITIS A, its incubation period is 15-60 days and is enterically transmitted, usually by fecal-oral transmission.\n    ", "id": "MESH:D016751"}
{"mention": "bilirubin", "mention_text": "Antituberculosis therapy (ATT)-associated acute liver failure (ATT-ALF) is the commonest drug-induced ALF in South Asia. Prospective studies on ATT-ALF are lacking. The current study prospectively evaluated the magnitude, clinical course, outcome, and prognostic factors in ATT-ALF. From January 1986 to January 2009, 1223 consecutive ALF patients were evaluated: ATT alone was the cause in 70 (5.7%) patients. Another 15 (1.2%) had ATT and simultaneous hepatitis virus infection. In 44 (62.8%) patients, ATT was prescribed empirically without definitive evidence of tuberculosis. ATT-ALF patients were younger (32.87 [+/-15.8] years), and 49 (70%) of them were women. Most had hyperacute presentation; the median icterus encephalopathy interval was 4.5 (0-30) days. The median duration of ATT before ALF was 30 (7-350) days. At presentation, advanced encephalopathy and cerebral edema were present in 51 (76%) and 29 (41.4%) patients, respectively. Gastrointestinal bleed, seizures, infection, and acute renal failure were documented in seven (10%), five (7.1%), 26 (37.1%), and seven (10%) patients, respectively. Compared with hepatitis E virus (HEV) and non-A non-E-induced ALF, ATT-ALF patients had nearly similar presentations except for older age and less elevation of liver enzymes. The mortality rate among patients with ATT-ALF was high (67.1%, n = 47), and only 23 (32.9%) patients recovered with medical treatment. In multivariate analysis, three factors independently predicted mortality: serum bilirubin (>or=10.8 mg/dL), prothrombin time (PT) prolongation (>or=26 seconds), and grade III/IV encephalopathy at presentation. CONCLUSION: ATT-ALF constituted 5.7% of ALF at our center and had a high mortality rate. Because the mortality rate is so high, determining which factors are predictors is less important. A high proportion of patients had consumed ATT empirically, which could have been prevented.", "entity": "Bilirubin", "aliases": "Bilirubin IX alpha (15E)-Isomer (4E)-Isomer (4E,15E)-Isomer Calcium Salt Disodium Monosodium Bilirubinate Hematoidin delta delta-Bilirubin", "definition": "A bile pigment that is a degradation product of HEME.\n    ", "id": "MESH:D001663"}
{"mention": "Central nervous system complications", "mention_text": "Central nervous system complications during treatment of acute lymphoblastic leukemia in a single pediatric institution.", "entity": "Central Nervous System Diseases", "aliases": "CNS Disease Diseases Central Nervous System Disorders", "definition": "Diseases of any component of the brain (including the cerebral hemispheres, diencephalon, brain stem, and cerebellum) or the spinal cord.\n    ", "id": "MESH:D002493"}
{"mention": "acute lymphoblastic leukemia", "mention_text": "Central nervous system complications during treatment of acute lymphoblastic leukemia in a single pediatric institution.", "entity": "Precursor Cell Lymphoblastic Leukemia-Lymphoma", "aliases": "ALL Childhood Acute Lymphoblastic Leukemia Lymphocytic Lymphoid L1 L2 Philadelphia-Positive Adult Lymphoma Precursor Cell Leukemia-Lymphoma", "definition": "A neoplasm characterized by abnormalities of the lymphoid cell precursors leading to excessive lymphoblasts in the marrow and other organs. It is the most common cancer in children and accounts for the vast majority of all childhood leukemias.\n    ", "id": "MESH:D054198"}
{"mention": "Central nervous system (CNS) complications", "mention_text": "Central nervous system (CNS) complications during treatment of childhood acute lymphoblastic leukemia (ALL) remain a challenging clinical problem. Outcome improvement with more intensive chemotherapy has significantly increased the incidence and severity of adverse events. This study analyzed the incidence of neurological complications during ALL treatment in a single pediatric institution, focusing on clinical, radiological, and electrophysiological findings. Exclusion criteria included CNS leukemic infiltration at diagnosis, therapy-related peripheral neuropathy, late-onset encephalopathy, or long-term neurocognitive defects. During a 9-year period, we retrospectively collected 27 neurological events (11%) in as many patients, from 253 children enrolled in the ALL front-line protocol. CNS complications included posterior reversible leukoencephalopathy syndrome (n = 10), stroke (n = 5), temporal lobe epilepsy (n = 2), high-dose methotrexate toxicity (n = 2), syndrome of inappropriate antidiuretic hormone secretion (n = 1), and other unclassified events (n = 7). In conclusion, CNS complications are frequent events during ALL therapy, and require rapid detection and prompt treatment to limit permanent damage.", "entity": "Central Nervous System Diseases", "aliases": "CNS Disease Diseases Central Nervous System Disorders", "definition": "Diseases of any component of the brain (including the cerebral hemispheres, diencephalon, brain stem, and cerebellum) or the spinal cord.\n    ", "id": "MESH:D002493"}
{"mention": "acute lymphoblastic leukemia", "mention_text": "Central nervous system (CNS) complications during treatment of childhood acute lymphoblastic leukemia (ALL) remain a challenging clinical problem. Outcome improvement with more intensive chemotherapy has significantly increased the incidence and severity of adverse events. This study analyzed the incidence of neurological complications during ALL treatment in a single pediatric institution, focusing on clinical, radiological, and electrophysiological findings. Exclusion criteria included CNS leukemic infiltration at diagnosis, therapy-related peripheral neuropathy, late-onset encephalopathy, or long-term neurocognitive defects. During a 9-year period, we retrospectively collected 27 neurological events (11%) in as many patients, from 253 children enrolled in the ALL front-line protocol. CNS complications included posterior reversible leukoencephalopathy syndrome (n = 10), stroke (n = 5), temporal lobe epilepsy (n = 2), high-dose methotrexate toxicity (n = 2), syndrome of inappropriate antidiuretic hormone secretion (n = 1), and other unclassified events (n = 7). In conclusion, CNS complications are frequent events during ALL therapy, and require rapid detection and prompt treatment to limit permanent damage.", "entity": "Precursor Cell Lymphoblastic Leukemia-Lymphoma", "aliases": "ALL Childhood Acute Lymphoblastic Leukemia Lymphocytic Lymphoid L1 L2 Philadelphia-Positive Adult Lymphoma Precursor Cell Leukemia-Lymphoma", "definition": "A neoplasm characterized by abnormalities of the lymphoid cell precursors leading to excessive lymphoblasts in the marrow and other organs. It is the most common cancer in children and accounts for the vast majority of all childhood leukemias.\n    ", "id": "MESH:D054198"}
{"mention": "ALL", "mention_text": "Central nervous system (CNS) complications during treatment of childhood acute lymphoblastic leukemia (ALL) remain a challenging clinical problem. Outcome improvement with more intensive chemotherapy has significantly increased the incidence and severity of adverse events. This study analyzed the incidence of neurological complications during ALL treatment in a single pediatric institution, focusing on clinical, radiological, and electrophysiological findings. Exclusion criteria included CNS leukemic infiltration at diagnosis, therapy-related peripheral neuropathy, late-onset encephalopathy, or long-term neurocognitive defects. During a 9-year period, we retrospectively collected 27 neurological events (11%) in as many patients, from 253 children enrolled in the ALL front-line protocol. CNS complications included posterior reversible leukoencephalopathy syndrome (n = 10), stroke (n = 5), temporal lobe epilepsy (n = 2), high-dose methotrexate toxicity (n = 2), syndrome of inappropriate antidiuretic hormone secretion (n = 1), and other unclassified events (n = 7). In conclusion, CNS complications are frequent events during ALL therapy, and require rapid detection and prompt treatment to limit permanent damage.", "entity": "Precursor Cell Lymphoblastic Leukemia-Lymphoma", "aliases": "ALL Childhood Acute Lymphoblastic Leukemia Lymphocytic Lymphoid L1 L2 Philadelphia-Positive Adult Lymphoma Precursor Cell Leukemia-Lymphoma", "definition": "A neoplasm characterized by abnormalities of the lymphoid cell precursors leading to excessive lymphoblasts in the marrow and other organs. It is the most common cancer in children and accounts for the vast majority of all childhood leukemias.\n    ", "id": "MESH:D054198"}
{"mention": "neurological complications", "mention_text": "Central nervous system (CNS) complications during treatment of childhood acute lymphoblastic leukemia (ALL) remain a challenging clinical problem. Outcome improvement with more intensive chemotherapy has significantly increased the incidence and severity of adverse events. This study analyzed the incidence of neurological complications during ALL treatment in a single pediatric institution, focusing on clinical, radiological, and electrophysiological findings. Exclusion criteria included CNS leukemic infiltration at diagnosis, therapy-related peripheral neuropathy, late-onset encephalopathy, or long-term neurocognitive defects. During a 9-year period, we retrospectively collected 27 neurological events (11%) in as many patients, from 253 children enrolled in the ALL front-line protocol. CNS complications included posterior reversible leukoencephalopathy syndrome (n = 10), stroke (n = 5), temporal lobe epilepsy (n = 2), high-dose methotrexate toxicity (n = 2), syndrome of inappropriate antidiuretic hormone secretion (n = 1), and other unclassified events (n = 7). In conclusion, CNS complications are frequent events during ALL therapy, and require rapid detection and prompt treatment to limit permanent damage.", "entity": "Central Nervous System Diseases", "aliases": "CNS Disease Diseases Central Nervous System Disorders", "definition": "Diseases of any component of the brain (including the cerebral hemispheres, diencephalon, brain stem, and cerebellum) or the spinal cord.\n    ", "id": "MESH:D002493"}
{"mention": "leukemic infiltration", "mention_text": "Central nervous system (CNS) complications during treatment of childhood acute lymphoblastic leukemia (ALL) remain a challenging clinical problem. Outcome improvement with more intensive chemotherapy has significantly increased the incidence and severity of adverse events. This study analyzed the incidence of neurological complications during ALL treatment in a single pediatric institution, focusing on clinical, radiological, and electrophysiological findings. Exclusion criteria included CNS leukemic infiltration at diagnosis, therapy-related peripheral neuropathy, late-onset encephalopathy, or long-term neurocognitive defects. During a 9-year period, we retrospectively collected 27 neurological events (11%) in as many patients, from 253 children enrolled in the ALL front-line protocol. CNS complications included posterior reversible leukoencephalopathy syndrome (n = 10), stroke (n = 5), temporal lobe epilepsy (n = 2), high-dose methotrexate toxicity (n = 2), syndrome of inappropriate antidiuretic hormone secretion (n = 1), and other unclassified events (n = 7). In conclusion, CNS complications are frequent events during ALL therapy, and require rapid detection and prompt treatment to limit permanent damage.", "entity": "Leukemic Infiltration", "aliases": "Infiltration Leukemic Infiltrations", "definition": "A pathologic change in leukemia in which leukemic cells permeate various organs at any stage of the disease. All types of leukemia show various degrees of infiltration, depending upon the type of leukemia. The degree of infiltration may vary from site to site. The liver and spleen are common sites of infiltration, the greatest appearing in myelocytic leukemia, but infiltration is seen also in the granulocytic and lymphocytic types. The kidney is also a common site and of the gastrointestinal system, the stomach and ileum are commonly involved. In lymphocytic leukemia the skin is often infiltrated. The central nervous system too is a common site.\n    ", "id": "MESH:D017254"}
{"mention": "peripheral neuropathy", "mention_text": "Central nervous system (CNS) complications during treatment of childhood acute lymphoblastic leukemia (ALL) remain a challenging clinical problem. Outcome improvement with more intensive chemotherapy has significantly increased the incidence and severity of adverse events. This study analyzed the incidence of neurological complications during ALL treatment in a single pediatric institution, focusing on clinical, radiological, and electrophysiological findings. Exclusion criteria included CNS leukemic infiltration at diagnosis, therapy-related peripheral neuropathy, late-onset encephalopathy, or long-term neurocognitive defects. During a 9-year period, we retrospectively collected 27 neurological events (11%) in as many patients, from 253 children enrolled in the ALL front-line protocol. CNS complications included posterior reversible leukoencephalopathy syndrome (n = 10), stroke (n = 5), temporal lobe epilepsy (n = 2), high-dose methotrexate toxicity (n = 2), syndrome of inappropriate antidiuretic hormone secretion (n = 1), and other unclassified events (n = 7). In conclusion, CNS complications are frequent events during ALL therapy, and require rapid detection and prompt treatment to limit permanent damage.", "entity": "Peripheral Nervous System Diseases", "aliases": "Nerve Disease Peripheral Diseases Neuropathy PNS (Peripheral Nervous System) System Disorders Neuropathies", "definition": "Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.\n    ", "id": "MESH:D010523"}
{"mention": "encephalopathy", "mention_text": "Central nervous system (CNS) complications during treatment of childhood acute lymphoblastic leukemia (ALL) remain a challenging clinical problem. Outcome improvement with more intensive chemotherapy has significantly increased the incidence and severity of adverse events. This study analyzed the incidence of neurological complications during ALL treatment in a single pediatric institution, focusing on clinical, radiological, and electrophysiological findings. Exclusion criteria included CNS leukemic infiltration at diagnosis, therapy-related peripheral neuropathy, late-onset encephalopathy, or long-term neurocognitive defects. During a 9-year period, we retrospectively collected 27 neurological events (11%) in as many patients, from 253 children enrolled in the ALL front-line protocol. CNS complications included posterior reversible leukoencephalopathy syndrome (n = 10), stroke (n = 5), temporal lobe epilepsy (n = 2), high-dose methotrexate toxicity (n = 2), syndrome of inappropriate antidiuretic hormone secretion (n = 1), and other unclassified events (n = 7). In conclusion, CNS complications are frequent events during ALL therapy, and require rapid detection and prompt treatment to limit permanent damage.", "entity": "Brain Diseases", "aliases": "Brain Disease Diseases Disorder Disorders CNS Intracranial Central Nervous System Encephalon", "definition": "Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.\n    ", "id": "MESH:D001927"}
{"mention": "neurocognitive defects", "mention_text": "Central nervous system (CNS) complications during treatment of childhood acute lymphoblastic leukemia (ALL) remain a challenging clinical problem. Outcome improvement with more intensive chemotherapy has significantly increased the incidence and severity of adverse events. This study analyzed the incidence of neurological complications during ALL treatment in a single pediatric institution, focusing on clinical, radiological, and electrophysiological findings. Exclusion criteria included CNS leukemic infiltration at diagnosis, therapy-related peripheral neuropathy, late-onset encephalopathy, or long-term neurocognitive defects. During a 9-year period, we retrospectively collected 27 neurological events (11%) in as many patients, from 253 children enrolled in the ALL front-line protocol. CNS complications included posterior reversible leukoencephalopathy syndrome (n = 10), stroke (n = 5), temporal lobe epilepsy (n = 2), high-dose methotrexate toxicity (n = 2), syndrome of inappropriate antidiuretic hormone secretion (n = 1), and other unclassified events (n = 7). In conclusion, CNS complications are frequent events during ALL therapy, and require rapid detection and prompt treatment to limit permanent damage.", "entity": "Central Nervous System Diseases", "aliases": "CNS Disease Diseases Central Nervous System Disorders", "definition": "Diseases of any component of the brain (including the cerebral hemispheres, diencephalon, brain stem, and cerebellum) or the spinal cord.\n    ", "id": "MESH:D002493"}
{"mention": "leukoencephalopathy", "mention_text": "Central nervous system (CNS) complications during treatment of childhood acute lymphoblastic leukemia (ALL) remain a challenging clinical problem. Outcome improvement with more intensive chemotherapy has significantly increased the incidence and severity of adverse events. This study analyzed the incidence of neurological complications during ALL treatment in a single pediatric institution, focusing on clinical, radiological, and electrophysiological findings. Exclusion criteria included CNS leukemic infiltration at diagnosis, therapy-related peripheral neuropathy, late-onset encephalopathy, or long-term neurocognitive defects. During a 9-year period, we retrospectively collected 27 neurological events (11%) in as many patients, from 253 children enrolled in the ALL front-line protocol. CNS complications included posterior reversible leukoencephalopathy syndrome (n = 10), stroke (n = 5), temporal lobe epilepsy (n = 2), high-dose methotrexate toxicity (n = 2), syndrome of inappropriate antidiuretic hormone secretion (n = 1), and other unclassified events (n = 7). In conclusion, CNS complications are frequent events during ALL therapy, and require rapid detection and prompt treatment to limit permanent damage.", "entity": "Leukoencephalopathies", "aliases": "CACH Syndrome Syndromes CACH/VWM Centralis Diffusa Myelinosis Diffusas Childhood Ataxia with Central Nervous System Hypomyelination Hypomyelinization Diffuse Cree Leukoencephalopathies Leukoencephalopathy Disease White Matter Diseases Vanishing Leukodystrophy", "definition": "Any of various diseases affecting the white matter of the central nervous system.\n    ", "id": "MESH:D056784"}
{"mention": "stroke", "mention_text": "Central nervous system (CNS) complications during treatment of childhood acute lymphoblastic leukemia (ALL) remain a challenging clinical problem. Outcome improvement with more intensive chemotherapy has significantly increased the incidence and severity of adverse events. This study analyzed the incidence of neurological complications during ALL treatment in a single pediatric institution, focusing on clinical, radiological, and electrophysiological findings. Exclusion criteria included CNS leukemic infiltration at diagnosis, therapy-related peripheral neuropathy, late-onset encephalopathy, or long-term neurocognitive defects. During a 9-year period, we retrospectively collected 27 neurological events (11%) in as many patients, from 253 children enrolled in the ALL front-line protocol. CNS complications included posterior reversible leukoencephalopathy syndrome (n = 10), stroke (n = 5), temporal lobe epilepsy (n = 2), high-dose methotrexate toxicity (n = 2), syndrome of inappropriate antidiuretic hormone secretion (n = 1), and other unclassified events (n = 7). In conclusion, CNS complications are frequent events during ALL therapy, and require rapid detection and prompt treatment to limit permanent damage.", "entity": "Stroke", "aliases": "Acute Cerebrovascular Accident Accidents Stroke Strokes Apoplexy Brain Vascular CVA (Cerebrovascular Accident) CVAs Cerebral", "definition": "A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)\n    ", "id": "MESH:D020521"}
{"mention": "temporal lobe epilepsy", "mention_text": "Central nervous system (CNS) complications during treatment of childhood acute lymphoblastic leukemia (ALL) remain a challenging clinical problem. Outcome improvement with more intensive chemotherapy has significantly increased the incidence and severity of adverse events. This study analyzed the incidence of neurological complications during ALL treatment in a single pediatric institution, focusing on clinical, radiological, and electrophysiological findings. Exclusion criteria included CNS leukemic infiltration at diagnosis, therapy-related peripheral neuropathy, late-onset encephalopathy, or long-term neurocognitive defects. During a 9-year period, we retrospectively collected 27 neurological events (11%) in as many patients, from 253 children enrolled in the ALL front-line protocol. CNS complications included posterior reversible leukoencephalopathy syndrome (n = 10), stroke (n = 5), temporal lobe epilepsy (n = 2), high-dose methotrexate toxicity (n = 2), syndrome of inappropriate antidiuretic hormone secretion (n = 1), and other unclassified events (n = 7). In conclusion, CNS complications are frequent events during ALL therapy, and require rapid detection and prompt treatment to limit permanent damage.", "entity": "Epilepsy, Temporal Lobe", "aliases": "Benign Psychomotor Epilepsy Childhood Epilepsies Lateral Temporal Lobe Uncinate", "definition": "A localization-related (focal) form of epilepsy characterized by recurrent seizures that arise from foci within the temporal lobe, most commonly from its mesial aspect. A wide variety of psychic phenomena may be associated, including illusions, hallucinations, dyscognitive states, and affective experiences. The majority of complex partial seizures (see EPILEPSY, COMPLEX PARTIAL) originate from the temporal lobes. Temporal lobe seizures may be classified by etiology as cryptogenic, familial, or symptomatic (i.e., related to an identified disease process or lesion). (From Adams et al., Principles of Neurology, 6th ed, p321)\n    ", "id": "MESH:D004833"}
{"mention": "methotrexate", "mention_text": "Central nervous system (CNS) complications during treatment of childhood acute lymphoblastic leukemia (ALL) remain a challenging clinical problem. Outcome improvement with more intensive chemotherapy has significantly increased the incidence and severity of adverse events. This study analyzed the incidence of neurological complications during ALL treatment in a single pediatric institution, focusing on clinical, radiological, and electrophysiological findings. Exclusion criteria included CNS leukemic infiltration at diagnosis, therapy-related peripheral neuropathy, late-onset encephalopathy, or long-term neurocognitive defects. During a 9-year period, we retrospectively collected 27 neurological events (11%) in as many patients, from 253 children enrolled in the ALL front-line protocol. CNS complications included posterior reversible leukoencephalopathy syndrome (n = 10), stroke (n = 5), temporal lobe epilepsy (n = 2), high-dose methotrexate toxicity (n = 2), syndrome of inappropriate antidiuretic hormone secretion (n = 1), and other unclassified events (n = 7). In conclusion, CNS complications are frequent events during ALL therapy, and require rapid detection and prompt treatment to limit permanent damage.", "entity": "Methotrexate", "aliases": "Amethopterin Dicesium Salt Methotrexate Hydrate Sodium (D)-Isomer (DL)-Isomer Disodium Mexate", "definition": "An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.\n    ", "id": "MESH:D008727"}
{"mention": "toxicity", "mention_text": "Central nervous system (CNS) complications during treatment of childhood acute lymphoblastic leukemia (ALL) remain a challenging clinical problem. Outcome improvement with more intensive chemotherapy has significantly increased the incidence and severity of adverse events. This study analyzed the incidence of neurological complications during ALL treatment in a single pediatric institution, focusing on clinical, radiological, and electrophysiological findings. Exclusion criteria included CNS leukemic infiltration at diagnosis, therapy-related peripheral neuropathy, late-onset encephalopathy, or long-term neurocognitive defects. During a 9-year period, we retrospectively collected 27 neurological events (11%) in as many patients, from 253 children enrolled in the ALL front-line protocol. CNS complications included posterior reversible leukoencephalopathy syndrome (n = 10), stroke (n = 5), temporal lobe epilepsy (n = 2), high-dose methotrexate toxicity (n = 2), syndrome of inappropriate antidiuretic hormone secretion (n = 1), and other unclassified events (n = 7). In conclusion, CNS complications are frequent events during ALL therapy, and require rapid detection and prompt treatment to limit permanent damage.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "inappropriate antidiuretic hormone secretion", "mention_text": "Central nervous system (CNS) complications during treatment of childhood acute lymphoblastic leukemia (ALL) remain a challenging clinical problem. Outcome improvement with more intensive chemotherapy has significantly increased the incidence and severity of adverse events. This study analyzed the incidence of neurological complications during ALL treatment in a single pediatric institution, focusing on clinical, radiological, and electrophysiological findings. Exclusion criteria included CNS leukemic infiltration at diagnosis, therapy-related peripheral neuropathy, late-onset encephalopathy, or long-term neurocognitive defects. During a 9-year period, we retrospectively collected 27 neurological events (11%) in as many patients, from 253 children enrolled in the ALL front-line protocol. CNS complications included posterior reversible leukoencephalopathy syndrome (n = 10), stroke (n = 5), temporal lobe epilepsy (n = 2), high-dose methotrexate toxicity (n = 2), syndrome of inappropriate antidiuretic hormone secretion (n = 1), and other unclassified events (n = 7). In conclusion, CNS complications are frequent events during ALL therapy, and require rapid detection and prompt treatment to limit permanent damage.", "entity": "Inappropriate ADH Syndrome", "aliases": "ADH Syndrome Inappropriate Antidiuretic Hormone Secretion Vasopressin SIADH Schwartz Bartter Schwartz-Bartter of (SIADH)", "definition": "A condition of HYPONATREMIA and renal salt loss attributed to overexpansion of BODY FLUIDS resulting from sustained release of ANTIDIURETIC HORMONES which stimulates renal resorption of water. It is characterized by normal KIDNEY function, high urine OSMOLALITY, low serum osmolality, and neurological dysfunction. Etiologies include ADH-producing neoplasms, injuries or diseases involving the HYPOTHALAMUS, the PITUITARY GLAND, and the LUNG. This syndrome can also be drug-induced.\n    ", "id": "MESH:D007177"}
{"mention": "capecitabine", "mention_text": "Safety of capecitabine: a review.", "entity": "capecitabine", "aliases": "N(4)-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine Xeloda capecitabine", "definition": "", "id": "MESH:C110904"}
{"mention": "5-fluorouracil", "mention_text": "IMPORTANCE OF THE FIELD: Fluoropyrimidines, in particular 5-fluorouracil (5-FU), have been the mainstay of treatment for several solid tumors, including colorectal, breast and head and neck cancers, for > 40 years. AREAS COVERED IN THIS REVIEW: This article reviews the pharmacology and efficacy of capecitabine with a special emphasis on its safety. WHAT THE READER WILL GAIN: The reader will gain better insight into the safety of capecitabine in special populations such as patients with advanced age, renal and kidney disease. We also explore different dosing and schedules of capecitabine administration. TAKE HOME MESSAGE: Capecitabine is an oral prodrug of 5-FU and was developed to fulfill the need for a more convenient therapy and provide an improved safety/efficacy profile. It has shown promising results alone or in combination with other chemotherapeutic agents in colorectal, breast, pancreaticobiliary, gastric, renal cell and head and neck cancers. The most commonly reported toxic effects of capecitabine are diarrhea, nausea, vomiting, stomatitis and hand-foot syndrome. Capecitabine has a well-established safety profile and can be given safely to patients with advanced age, hepatic and renal dysfunctions.", "entity": "Fluorouracil", "aliases": "5 FU Lederle medac Fluorouracil biosyn HU Hexal 5-FU 5-Fluorouracil 5-Fluorouracil-biosyn 5-HU 5FU Adrucil Allergan Brand of CSP Carac Dakota Fluorouracile Dermatech Dermik Efudex Efudix Ferrer Fluoro Uracile ICN Fluoro-Uracile Fluoroplex GRY Mononitrate Monopotassium Salt Monosodium Potassium Teva Fluorouracil-GRY Fluorouracilo Far Fluoruracil Fluracedyl Flurodex Gry Haemato fu Haemato-fu Neocorp Neofluor Onkofluor Onkoworks Pharmachemie Ribofluor Riemser Roche ribosepharm", "definition": "A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.\n    ", "id": "MESH:D005472"}
{"mention": "5-FU", "mention_text": "IMPORTANCE OF THE FIELD: Fluoropyrimidines, in particular 5-fluorouracil (5-FU), have been the mainstay of treatment for several solid tumors, including colorectal, breast and head and neck cancers, for > 40 years. AREAS COVERED IN THIS REVIEW: This article reviews the pharmacology and efficacy of capecitabine with a special emphasis on its safety. WHAT THE READER WILL GAIN: The reader will gain better insight into the safety of capecitabine in special populations such as patients with advanced age, renal and kidney disease. We also explore different dosing and schedules of capecitabine administration. TAKE HOME MESSAGE: Capecitabine is an oral prodrug of 5-FU and was developed to fulfill the need for a more convenient therapy and provide an improved safety/efficacy profile. It has shown promising results alone or in combination with other chemotherapeutic agents in colorectal, breast, pancreaticobiliary, gastric, renal cell and head and neck cancers. The most commonly reported toxic effects of capecitabine are diarrhea, nausea, vomiting, stomatitis and hand-foot syndrome. Capecitabine has a well-established safety profile and can be given safely to patients with advanced age, hepatic and renal dysfunctions.", "entity": "Fluorouracil", "aliases": "5 FU Lederle medac Fluorouracil biosyn HU Hexal 5-FU 5-Fluorouracil 5-Fluorouracil-biosyn 5-HU 5FU Adrucil Allergan Brand of CSP Carac Dakota Fluorouracile Dermatech Dermik Efudex Efudix Ferrer Fluoro Uracile ICN Fluoro-Uracile Fluoroplex GRY Mononitrate Monopotassium Salt Monosodium Potassium Teva Fluorouracil-GRY Fluorouracilo Far Fluoruracil Fluracedyl Flurodex Gry Haemato fu Haemato-fu Neocorp Neofluor Onkofluor Onkoworks Pharmachemie Ribofluor Riemser Roche ribosepharm", "definition": "A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.\n    ", "id": "MESH:D005472"}
{"mention": "tumors", "mention_text": "IMPORTANCE OF THE FIELD: Fluoropyrimidines, in particular 5-fluorouracil (5-FU), have been the mainstay of treatment for several solid tumors, including colorectal, breast and head and neck cancers, for > 40 years. AREAS COVERED IN THIS REVIEW: This article reviews the pharmacology and efficacy of capecitabine with a special emphasis on its safety. WHAT THE READER WILL GAIN: The reader will gain better insight into the safety of capecitabine in special populations such as patients with advanced age, renal and kidney disease. We also explore different dosing and schedules of capecitabine administration. TAKE HOME MESSAGE: Capecitabine is an oral prodrug of 5-FU and was developed to fulfill the need for a more convenient therapy and provide an improved safety/efficacy profile. It has shown promising results alone or in combination with other chemotherapeutic agents in colorectal, breast, pancreaticobiliary, gastric, renal cell and head and neck cancers. The most commonly reported toxic effects of capecitabine are diarrhea, nausea, vomiting, stomatitis and hand-foot syndrome. Capecitabine has a well-established safety profile and can be given safely to patients with advanced age, hepatic and renal dysfunctions.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "head and neck cancers", "mention_text": "IMPORTANCE OF THE FIELD: Fluoropyrimidines, in particular 5-fluorouracil (5-FU), have been the mainstay of treatment for several solid tumors, including colorectal, breast and head and neck cancers, for > 40 years. AREAS COVERED IN THIS REVIEW: This article reviews the pharmacology and efficacy of capecitabine with a special emphasis on its safety. WHAT THE READER WILL GAIN: The reader will gain better insight into the safety of capecitabine in special populations such as patients with advanced age, renal and kidney disease. We also explore different dosing and schedules of capecitabine administration. TAKE HOME MESSAGE: Capecitabine is an oral prodrug of 5-FU and was developed to fulfill the need for a more convenient therapy and provide an improved safety/efficacy profile. It has shown promising results alone or in combination with other chemotherapeutic agents in colorectal, breast, pancreaticobiliary, gastric, renal cell and head and neck cancers. The most commonly reported toxic effects of capecitabine are diarrhea, nausea, vomiting, stomatitis and hand-foot syndrome. Capecitabine has a well-established safety profile and can be given safely to patients with advanced age, hepatic and renal dysfunctions.", "entity": "Head and Neck Neoplasms", "aliases": "Cancer of Head and Neck the Neoplasms Neoplasm UADT Upper Aerodigestive Tract", "definition": "Soft tissue tumors or cancer arising from the mucosal surfaces of the LIP; oral cavity; PHARYNX; LARYNX; and cervical esophagus. Other sites included are the NOSE and PARANASAL SINUSES; SALIVARY GLANDS; THYROID GLAND and PARATHYROID GLANDS; and MELANOMA and non-melanoma skin cancers of the head and neck. (from Holland et al., Cancer Medicine, 4th ed, p1651)\n    ", "id": "MESH:D006258"}
{"mention": "capecitabine", "mention_text": "IMPORTANCE OF THE FIELD: Fluoropyrimidines, in particular 5-fluorouracil (5-FU), have been the mainstay of treatment for several solid tumors, including colorectal, breast and head and neck cancers, for > 40 years. AREAS COVERED IN THIS REVIEW: This article reviews the pharmacology and efficacy of capecitabine with a special emphasis on its safety. WHAT THE READER WILL GAIN: The reader will gain better insight into the safety of capecitabine in special populations such as patients with advanced age, renal and kidney disease. We also explore different dosing and schedules of capecitabine administration. TAKE HOME MESSAGE: Capecitabine is an oral prodrug of 5-FU and was developed to fulfill the need for a more convenient therapy and provide an improved safety/efficacy profile. It has shown promising results alone or in combination with other chemotherapeutic agents in colorectal, breast, pancreaticobiliary, gastric, renal cell and head and neck cancers. The most commonly reported toxic effects of capecitabine are diarrhea, nausea, vomiting, stomatitis and hand-foot syndrome. Capecitabine has a well-established safety profile and can be given safely to patients with advanced age, hepatic and renal dysfunctions.", "entity": "capecitabine", "aliases": "N(4)-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine Xeloda capecitabine", "definition": "", "id": "MESH:C110904"}
{"mention": "renal and kidney disease", "mention_text": "IMPORTANCE OF THE FIELD: Fluoropyrimidines, in particular 5-fluorouracil (5-FU), have been the mainstay of treatment for several solid tumors, including colorectal, breast and head and neck cancers, for > 40 years. AREAS COVERED IN THIS REVIEW: This article reviews the pharmacology and efficacy of capecitabine with a special emphasis on its safety. WHAT THE READER WILL GAIN: The reader will gain better insight into the safety of capecitabine in special populations such as patients with advanced age, renal and kidney disease. We also explore different dosing and schedules of capecitabine administration. TAKE HOME MESSAGE: Capecitabine is an oral prodrug of 5-FU and was developed to fulfill the need for a more convenient therapy and provide an improved safety/efficacy profile. It has shown promising results alone or in combination with other chemotherapeutic agents in colorectal, breast, pancreaticobiliary, gastric, renal cell and head and neck cancers. The most commonly reported toxic effects of capecitabine are diarrhea, nausea, vomiting, stomatitis and hand-foot syndrome. Capecitabine has a well-established safety profile and can be given safely to patients with advanced age, hepatic and renal dysfunctions.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "Capecitabine", "mention_text": "IMPORTANCE OF THE FIELD: Fluoropyrimidines, in particular 5-fluorouracil (5-FU), have been the mainstay of treatment for several solid tumors, including colorectal, breast and head and neck cancers, for > 40 years. AREAS COVERED IN THIS REVIEW: This article reviews the pharmacology and efficacy of capecitabine with a special emphasis on its safety. WHAT THE READER WILL GAIN: The reader will gain better insight into the safety of capecitabine in special populations such as patients with advanced age, renal and kidney disease. We also explore different dosing and schedules of capecitabine administration. TAKE HOME MESSAGE: Capecitabine is an oral prodrug of 5-FU and was developed to fulfill the need for a more convenient therapy and provide an improved safety/efficacy profile. It has shown promising results alone or in combination with other chemotherapeutic agents in colorectal, breast, pancreaticobiliary, gastric, renal cell and head and neck cancers. The most commonly reported toxic effects of capecitabine are diarrhea, nausea, vomiting, stomatitis and hand-foot syndrome. Capecitabine has a well-established safety profile and can be given safely to patients with advanced age, hepatic and renal dysfunctions.", "entity": "capecitabine", "aliases": "N(4)-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine Xeloda capecitabine", "definition": "", "id": "MESH:C110904"}
{"mention": "diarrhea", "mention_text": "IMPORTANCE OF THE FIELD: Fluoropyrimidines, in particular 5-fluorouracil (5-FU), have been the mainstay of treatment for several solid tumors, including colorectal, breast and head and neck cancers, for > 40 years. AREAS COVERED IN THIS REVIEW: This article reviews the pharmacology and efficacy of capecitabine with a special emphasis on its safety. WHAT THE READER WILL GAIN: The reader will gain better insight into the safety of capecitabine in special populations such as patients with advanced age, renal and kidney disease. We also explore different dosing and schedules of capecitabine administration. TAKE HOME MESSAGE: Capecitabine is an oral prodrug of 5-FU and was developed to fulfill the need for a more convenient therapy and provide an improved safety/efficacy profile. It has shown promising results alone or in combination with other chemotherapeutic agents in colorectal, breast, pancreaticobiliary, gastric, renal cell and head and neck cancers. The most commonly reported toxic effects of capecitabine are diarrhea, nausea, vomiting, stomatitis and hand-foot syndrome. Capecitabine has a well-established safety profile and can be given safely to patients with advanced age, hepatic and renal dysfunctions.", "entity": "Diarrhea", "aliases": "Diarrhea Diarrheas", "definition": "An increased liquidity or decreased consistency of FECES, such as running stool. Fecal consistency is related to the ratio of water-holding capacity of insoluble solids to total water, rather than the amount of water present. Diarrhea is not hyperdefecation or increased fecal weight.\n    ", "id": "MESH:D003967"}
{"mention": "nausea", "mention_text": "IMPORTANCE OF THE FIELD: Fluoropyrimidines, in particular 5-fluorouracil (5-FU), have been the mainstay of treatment for several solid tumors, including colorectal, breast and head and neck cancers, for > 40 years. AREAS COVERED IN THIS REVIEW: This article reviews the pharmacology and efficacy of capecitabine with a special emphasis on its safety. WHAT THE READER WILL GAIN: The reader will gain better insight into the safety of capecitabine in special populations such as patients with advanced age, renal and kidney disease. We also explore different dosing and schedules of capecitabine administration. TAKE HOME MESSAGE: Capecitabine is an oral prodrug of 5-FU and was developed to fulfill the need for a more convenient therapy and provide an improved safety/efficacy profile. It has shown promising results alone or in combination with other chemotherapeutic agents in colorectal, breast, pancreaticobiliary, gastric, renal cell and head and neck cancers. The most commonly reported toxic effects of capecitabine are diarrhea, nausea, vomiting, stomatitis and hand-foot syndrome. Capecitabine has a well-established safety profile and can be given safely to patients with advanced age, hepatic and renal dysfunctions.", "entity": "Nausea", "aliases": "Nausea", "definition": "An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.\n    ", "id": "MESH:D009325"}
{"mention": "vomiting", "mention_text": "IMPORTANCE OF THE FIELD: Fluoropyrimidines, in particular 5-fluorouracil (5-FU), have been the mainstay of treatment for several solid tumors, including colorectal, breast and head and neck cancers, for > 40 years. AREAS COVERED IN THIS REVIEW: This article reviews the pharmacology and efficacy of capecitabine with a special emphasis on its safety. WHAT THE READER WILL GAIN: The reader will gain better insight into the safety of capecitabine in special populations such as patients with advanced age, renal and kidney disease. We also explore different dosing and schedules of capecitabine administration. TAKE HOME MESSAGE: Capecitabine is an oral prodrug of 5-FU and was developed to fulfill the need for a more convenient therapy and provide an improved safety/efficacy profile. It has shown promising results alone or in combination with other chemotherapeutic agents in colorectal, breast, pancreaticobiliary, gastric, renal cell and head and neck cancers. The most commonly reported toxic effects of capecitabine are diarrhea, nausea, vomiting, stomatitis and hand-foot syndrome. Capecitabine has a well-established safety profile and can be given safely to patients with advanced age, hepatic and renal dysfunctions.", "entity": "Vomiting", "aliases": "Emesis Vomiting", "definition": "The forcible expulsion of the contents of the STOMACH through the MOUTH.\n    ", "id": "MESH:D014839"}
{"mention": "stomatitis", "mention_text": "IMPORTANCE OF THE FIELD: Fluoropyrimidines, in particular 5-fluorouracil (5-FU), have been the mainstay of treatment for several solid tumors, including colorectal, breast and head and neck cancers, for > 40 years. AREAS COVERED IN THIS REVIEW: This article reviews the pharmacology and efficacy of capecitabine with a special emphasis on its safety. WHAT THE READER WILL GAIN: The reader will gain better insight into the safety of capecitabine in special populations such as patients with advanced age, renal and kidney disease. We also explore different dosing and schedules of capecitabine administration. TAKE HOME MESSAGE: Capecitabine is an oral prodrug of 5-FU and was developed to fulfill the need for a more convenient therapy and provide an improved safety/efficacy profile. It has shown promising results alone or in combination with other chemotherapeutic agents in colorectal, breast, pancreaticobiliary, gastric, renal cell and head and neck cancers. The most commonly reported toxic effects of capecitabine are diarrhea, nausea, vomiting, stomatitis and hand-foot syndrome. Capecitabine has a well-established safety profile and can be given safely to patients with advanced age, hepatic and renal dysfunctions.", "entity": "Stomatitis", "aliases": "Mucositides Oral Mucositis Oromucositides Oromucositis Stomatitides Stomatitis", "definition": "INFLAMMATION of the soft tissues of the MOUTH, such as MUCOSA; PALATE; GINGIVA; and LIP.\n    ", "id": "MESH:D013280"}
{"mention": "hand-foot syndrome", "mention_text": "IMPORTANCE OF THE FIELD: Fluoropyrimidines, in particular 5-fluorouracil (5-FU), have been the mainstay of treatment for several solid tumors, including colorectal, breast and head and neck cancers, for > 40 years. AREAS COVERED IN THIS REVIEW: This article reviews the pharmacology and efficacy of capecitabine with a special emphasis on its safety. WHAT THE READER WILL GAIN: The reader will gain better insight into the safety of capecitabine in special populations such as patients with advanced age, renal and kidney disease. We also explore different dosing and schedules of capecitabine administration. TAKE HOME MESSAGE: Capecitabine is an oral prodrug of 5-FU and was developed to fulfill the need for a more convenient therapy and provide an improved safety/efficacy profile. It has shown promising results alone or in combination with other chemotherapeutic agents in colorectal, breast, pancreaticobiliary, gastric, renal cell and head and neck cancers. The most commonly reported toxic effects of capecitabine are diarrhea, nausea, vomiting, stomatitis and hand-foot syndrome. Capecitabine has a well-established safety profile and can be given safely to patients with advanced age, hepatic and renal dysfunctions.", "entity": "Hand-Foot Syndrome", "aliases": "Acral Erythema Chemotherapy-Induced Erythemas Chemotherapy Induced Palmoplantar Erythrodysesthesia Erythrodysesthesias Hand Foot Syndrome Hand-Foot Syndromes", "definition": "Chemotherapy-induced dermal side effects that are associated with the use of various CYTOSTATIC AGENTS. Symptoms range from mild ERYTHEMA and/or PARESTHESIA to severe ulcerative dermatitis with debilitating pain involving typically palmoplantar and intertriginous areas. These cutaneous manifestations are sometimes accompanied by nail anomalies.\n    ", "id": "MESH:D060831"}
{"mention": "renal dysfunctions", "mention_text": "IMPORTANCE OF THE FIELD: Fluoropyrimidines, in particular 5-fluorouracil (5-FU), have been the mainstay of treatment for several solid tumors, including colorectal, breast and head and neck cancers, for > 40 years. AREAS COVERED IN THIS REVIEW: This article reviews the pharmacology and efficacy of capecitabine with a special emphasis on its safety. WHAT THE READER WILL GAIN: The reader will gain better insight into the safety of capecitabine in special populations such as patients with advanced age, renal and kidney disease. We also explore different dosing and schedules of capecitabine administration. TAKE HOME MESSAGE: Capecitabine is an oral prodrug of 5-FU and was developed to fulfill the need for a more convenient therapy and provide an improved safety/efficacy profile. It has shown promising results alone or in combination with other chemotherapeutic agents in colorectal, breast, pancreaticobiliary, gastric, renal cell and head and neck cancers. The most commonly reported toxic effects of capecitabine are diarrhea, nausea, vomiting, stomatitis and hand-foot syndrome. Capecitabine has a well-established safety profile and can be given safely to patients with advanced age, hepatic and renal dysfunctions.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "neurotensin", "mention_text": "Effects of pallidal neurotensin on haloperidol-induced parkinsonian catalepsy: behavioral and electrophysiological studies.", "entity": "Neurotensin", "aliases": "Neurotensin", "definition": "A biologically active tridecapeptide isolated from the hypothalamus. It has been shown to induce hypotension in the rat, to stimulate contraction of guinea pig ileum and rat uterus, and to cause relaxation of rat duodenum. There is also evidence that it acts as both a peripheral and a central nervous system neurotransmitter.\n    ", "id": "MESH:D009496"}
{"mention": "haloperidol", "mention_text": "Effects of pallidal neurotensin on haloperidol-induced parkinsonian catalepsy: behavioral and electrophysiological studies.", "entity": "Haloperidol", "aliases": "Haldol Haloperidol", "definition": "A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)\n    ", "id": "MESH:D006220"}
{"mention": "parkinsonian catalepsy", "mention_text": "Effects of pallidal neurotensin on haloperidol-induced parkinsonian catalepsy: behavioral and electrophysiological studies.", "entity": "Catalepsy", "aliases": "Anochlesia Anochlesias Catalepsies Catalepsy Cerea Flexibilitas Flexibilities Waxy Flexibility", "definition": "A condition characterized by inactivity, decreased responsiveness to stimuli, and a tendency to maintain an immobile posture. The limbs tend to remain in whatever position they are placed (waxy flexibility). Catalepsy may be associated with PSYCHOTIC DISORDERS (e.g., SCHIZOPHRENIA, CATATONIC), nervous system drug toxicity, and other conditions.\n    ", "id": "MESH:D002375"}
{"mention": "neurotensin", "mention_text": "OBJECTIVE: The globus pallidus plays a critical role in movement regulation. Previous studies have indicated that the globus pallidus receives neurotensinergic innervation from the striatum, and systemic administration of a neurotensin analog could produce antiparkinsonian effects. The present study aimed to investigate the effects of pallidal neurotensin on haloperidol-induced parkinsonian symptoms. METHODS: Behavioral experiments and electrophysiological recordings were performed in the present study. RESULTS: Bilateral infusions of neurotensin into the globus pallidus reversed haloperidol-induced parkinsonian catalepsy in rats. Electrophysiological recordings showed that microinjection of neurotensin induced excitation of pallidal neurons in the presence of systemic haloperidol administration. The neurotensin type-1 receptor antagonist SR48692 blocked both the behavioral and the electrophysiological effects induced by neurotensin. CONCLUSION: Activation of pallidal neurotensin receptors may be involved in neurotensin-induced antiparkinsonian effects.", "entity": "Neurotensin", "aliases": "Neurotensin", "definition": "A biologically active tridecapeptide isolated from the hypothalamus. It has been shown to induce hypotension in the rat, to stimulate contraction of guinea pig ileum and rat uterus, and to cause relaxation of rat duodenum. There is also evidence that it acts as both a peripheral and a central nervous system neurotransmitter.\n    ", "id": "MESH:D009496"}
{"mention": "haloperidol", "mention_text": "OBJECTIVE: The globus pallidus plays a critical role in movement regulation. Previous studies have indicated that the globus pallidus receives neurotensinergic innervation from the striatum, and systemic administration of a neurotensin analog could produce antiparkinsonian effects. The present study aimed to investigate the effects of pallidal neurotensin on haloperidol-induced parkinsonian symptoms. METHODS: Behavioral experiments and electrophysiological recordings were performed in the present study. RESULTS: Bilateral infusions of neurotensin into the globus pallidus reversed haloperidol-induced parkinsonian catalepsy in rats. Electrophysiological recordings showed that microinjection of neurotensin induced excitation of pallidal neurons in the presence of systemic haloperidol administration. The neurotensin type-1 receptor antagonist SR48692 blocked both the behavioral and the electrophysiological effects induced by neurotensin. CONCLUSION: Activation of pallidal neurotensin receptors may be involved in neurotensin-induced antiparkinsonian effects.", "entity": "Haloperidol", "aliases": "Haldol Haloperidol", "definition": "A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)\n    ", "id": "MESH:D006220"}
{"mention": "parkinsonian symptoms", "mention_text": "OBJECTIVE: The globus pallidus plays a critical role in movement regulation. Previous studies have indicated that the globus pallidus receives neurotensinergic innervation from the striatum, and systemic administration of a neurotensin analog could produce antiparkinsonian effects. The present study aimed to investigate the effects of pallidal neurotensin on haloperidol-induced parkinsonian symptoms. METHODS: Behavioral experiments and electrophysiological recordings were performed in the present study. RESULTS: Bilateral infusions of neurotensin into the globus pallidus reversed haloperidol-induced parkinsonian catalepsy in rats. Electrophysiological recordings showed that microinjection of neurotensin induced excitation of pallidal neurons in the presence of systemic haloperidol administration. The neurotensin type-1 receptor antagonist SR48692 blocked both the behavioral and the electrophysiological effects induced by neurotensin. CONCLUSION: Activation of pallidal neurotensin receptors may be involved in neurotensin-induced antiparkinsonian effects.", "entity": "Parkinson Disease, Secondary", "aliases": "Atherosclerotic Parkinsonism Parkinson Disease Secondary Vascular Symptomatic", "definition": "Conditions which feature clinical manifestations resembling primary Parkinson disease that are caused by a known or suspected condition. Examples include parkinsonism caused by vascular injury, drugs, trauma, toxin exposure, neoplasms, infections and degenerative or hereditary conditions. Clinical features may include bradykinesia, rigidity, parkinsonian gait, and masked facies. In general, tremor is less prominent in secondary parkinsonism than in the primary form. (From Joynt, Clinical Neurology, 1998, Ch38, pp39-42)\n    ", "id": "MESH:D010302"}
{"mention": "parkinsonian catalepsy", "mention_text": "OBJECTIVE: The globus pallidus plays a critical role in movement regulation. Previous studies have indicated that the globus pallidus receives neurotensinergic innervation from the striatum, and systemic administration of a neurotensin analog could produce antiparkinsonian effects. The present study aimed to investigate the effects of pallidal neurotensin on haloperidol-induced parkinsonian symptoms. METHODS: Behavioral experiments and electrophysiological recordings were performed in the present study. RESULTS: Bilateral infusions of neurotensin into the globus pallidus reversed haloperidol-induced parkinsonian catalepsy in rats. Electrophysiological recordings showed that microinjection of neurotensin induced excitation of pallidal neurons in the presence of systemic haloperidol administration. The neurotensin type-1 receptor antagonist SR48692 blocked both the behavioral and the electrophysiological effects induced by neurotensin. CONCLUSION: Activation of pallidal neurotensin receptors may be involved in neurotensin-induced antiparkinsonian effects.", "entity": "Catalepsy", "aliases": "Anochlesia Anochlesias Catalepsies Catalepsy Cerea Flexibilitas Flexibilities Waxy Flexibility", "definition": "A condition characterized by inactivity, decreased responsiveness to stimuli, and a tendency to maintain an immobile posture. The limbs tend to remain in whatever position they are placed (waxy flexibility). Catalepsy may be associated with PSYCHOTIC DISORDERS (e.g., SCHIZOPHRENIA, CATATONIC), nervous system drug toxicity, and other conditions.\n    ", "id": "MESH:D002375"}
{"mention": "neurotensin type-1 receptor antagonist", "mention_text": "OBJECTIVE: The globus pallidus plays a critical role in movement regulation. Previous studies have indicated that the globus pallidus receives neurotensinergic innervation from the striatum, and systemic administration of a neurotensin analog could produce antiparkinsonian effects. The present study aimed to investigate the effects of pallidal neurotensin on haloperidol-induced parkinsonian symptoms. METHODS: Behavioral experiments and electrophysiological recordings were performed in the present study. RESULTS: Bilateral infusions of neurotensin into the globus pallidus reversed haloperidol-induced parkinsonian catalepsy in rats. Electrophysiological recordings showed that microinjection of neurotensin induced excitation of pallidal neurons in the presence of systemic haloperidol administration. The neurotensin type-1 receptor antagonist SR48692 blocked both the behavioral and the electrophysiological effects induced by neurotensin. CONCLUSION: Activation of pallidal neurotensin receptors may be involved in neurotensin-induced antiparkinsonian effects.", "entity": "SR 48692", "aliases": "2-((1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl)pyrazol-3-yl)carbonylamino)tricyclo(3.3.1.1.(3.7))decan-2-carboxylic acid Meclinertant SR 48692 SR-48692 SR48692", "definition": "", "id": "MESH:C079087"}
{"mention": "SR48692", "mention_text": "OBJECTIVE: The globus pallidus plays a critical role in movement regulation. Previous studies have indicated that the globus pallidus receives neurotensinergic innervation from the striatum, and systemic administration of a neurotensin analog could produce antiparkinsonian effects. The present study aimed to investigate the effects of pallidal neurotensin on haloperidol-induced parkinsonian symptoms. METHODS: Behavioral experiments and electrophysiological recordings were performed in the present study. RESULTS: Bilateral infusions of neurotensin into the globus pallidus reversed haloperidol-induced parkinsonian catalepsy in rats. Electrophysiological recordings showed that microinjection of neurotensin induced excitation of pallidal neurons in the presence of systemic haloperidol administration. The neurotensin type-1 receptor antagonist SR48692 blocked both the behavioral and the electrophysiological effects induced by neurotensin. CONCLUSION: Activation of pallidal neurotensin receptors may be involved in neurotensin-induced antiparkinsonian effects.", "entity": "SR 48692", "aliases": "2-((1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl)pyrazol-3-yl)carbonylamino)tricyclo(3.3.1.1.(3.7))decan-2-carboxylic acid Meclinertant SR 48692 SR-48692 SR48692", "definition": "", "id": "MESH:C079087"}
{"mention": "depression", "mention_text": "Antihypertensive drugs and depression: a reappraisal.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "hypertensive", "mention_text": "Eighty-nine new referral hypertensive out-patients and 46 new referral non-hypertensive chronically physically ill out-patients completed a mood rating scale at regular intervals for one year. The results showed a high prevalence of depression in both groups of patients, with no preponderance in the hypertensive group. Hypertensive patients with psychiatric histories had a higher prevalence of depression than the comparison patients. This was accounted for by a significant number of depressions occurring in methyl dopa treated patients with psychiatric histories.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "depression", "mention_text": "Eighty-nine new referral hypertensive out-patients and 46 new referral non-hypertensive chronically physically ill out-patients completed a mood rating scale at regular intervals for one year. The results showed a high prevalence of depression in both groups of patients, with no preponderance in the hypertensive group. Hypertensive patients with psychiatric histories had a higher prevalence of depression than the comparison patients. This was accounted for by a significant number of depressions occurring in methyl dopa treated patients with psychiatric histories.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "Hypertensive", "mention_text": "Eighty-nine new referral hypertensive out-patients and 46 new referral non-hypertensive chronically physically ill out-patients completed a mood rating scale at regular intervals for one year. The results showed a high prevalence of depression in both groups of patients, with no preponderance in the hypertensive group. Hypertensive patients with psychiatric histories had a higher prevalence of depression than the comparison patients. This was accounted for by a significant number of depressions occurring in methyl dopa treated patients with psychiatric histories.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "psychiatric", "mention_text": "Eighty-nine new referral hypertensive out-patients and 46 new referral non-hypertensive chronically physically ill out-patients completed a mood rating scale at regular intervals for one year. The results showed a high prevalence of depression in both groups of patients, with no preponderance in the hypertensive group. Hypertensive patients with psychiatric histories had a higher prevalence of depression than the comparison patients. This was accounted for by a significant number of depressions occurring in methyl dopa treated patients with psychiatric histories.", "entity": "Mental Disorders", "aliases": "Behavior Disorders Diagnosis Psychiatric Disorder Mental", "definition": "Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.\n    ", "id": "MESH:D001523"}
{"mention": "depressions", "mention_text": "Eighty-nine new referral hypertensive out-patients and 46 new referral non-hypertensive chronically physically ill out-patients completed a mood rating scale at regular intervals for one year. The results showed a high prevalence of depression in both groups of patients, with no preponderance in the hypertensive group. Hypertensive patients with psychiatric histories had a higher prevalence of depression than the comparison patients. This was accounted for by a significant number of depressions occurring in methyl dopa treated patients with psychiatric histories.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "methyl dopa", "mention_text": "Eighty-nine new referral hypertensive out-patients and 46 new referral non-hypertensive chronically physically ill out-patients completed a mood rating scale at regular intervals for one year. The results showed a high prevalence of depression in both groups of patients, with no preponderance in the hypertensive group. Hypertensive patients with psychiatric histories had a higher prevalence of depression than the comparison patients. This was accounted for by a significant number of depressions occurring in methyl dopa treated patients with psychiatric histories.", "entity": "Methyldopa", "aliases": "Aldomet Alphamethyldopa Alphapharm Brand of Methyldopa Apo Apo-Methyldopa Apotex Biopat Cahill May Roberts Clonmel Dopamet Dopegit Dopegyt Dopergit Hydopa Meldopa Merck Sharp & Dohme Nu-Pharm Orion Methyldopate Nu Medopa Pharm Nu-Medopa Rhône Poulenc Rorer Rhône-Poulenc Sembrina alpha Methyl L Dopa alpha-Methyl-L-Dopa alpha-Methyldopa", "definition": "An alpha-2 adrenergic agonist that has both central and peripheral nervous system effects. Its primary clinical use is as an antihypertensive agent.\n    ", "id": "MESH:D008750"}
{"mention": "nitroprusside", "mention_text": "Pulmonary shunt and cardiovascular responses to CPAP during nitroprusside-induced hypotension.", "entity": "Nitroprusside", "aliases": "Abbott Brand of Sodium Nitroprusside Bayer Cyanonitrosylferrate Disodium Salt Faulding Fides Ecopharma Ketostix Naniprus Nipride Nipruton Nitriate Nitroferricyanide Nitropress Nitroprussiat Dihydrate Roche SERB", "definition": "A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.\n    ", "id": "MESH:D009599"}
{"mention": "hypotension", "mention_text": "Pulmonary shunt and cardiovascular responses to CPAP during nitroprusside-induced hypotension.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "sodium nitroprusside", "mention_text": "The effects of continuous positive airway pressure (CPAP) on cardiovascular dynamics and pulmonary shunt (QS/QT) were investigated in 12 dogs before and during sodium nitroprusside infusion that decreased mean arterial blood pressure 40-50 per cent. Before nitroprusside infusion, 5 cm H2O CPAP significantly, P less than .05, decreased arterial blood pressure, but did not significantly alter heart rate, cardiac output, systemic vascular resistance, or QS/QT. Ten cm H2O CPAP before nitroprusside infusion produced a further decrease in arterial blood pressure and significantly increased heart rate and decreased cardiac output and QS/QT. Nitroprusside caused significant decreases in arterial blood pressure and systemic vascular resistance and increases in heart rate, but did not change cardiac output or QS/QT. Five cm H2O CPAP during nitroprusside did not further alter any of the above-mentioned variables. However, 10 cm H2O CPAP decreased arterial blood pressure, cardiac output, and QS/QT. These data indicate that nitroprusside infusion rates that decrease mean arterial blood pressure by 40-50 per cent do not change cardiac output or QS/QT. During nitroprusside infusion low levels of CPAP do not markedly alter cardiovascular dynamics, but high levels of CPAP (10 cm H2O), while decreasing QS/QT, produce marked decreases in arterial blood pressure and cardiac output.", "entity": "Nitroprusside", "aliases": "Abbott Brand of Sodium Nitroprusside Bayer Cyanonitrosylferrate Disodium Salt Faulding Fides Ecopharma Ketostix Naniprus Nipride Nipruton Nitriate Nitroferricyanide Nitropress Nitroprussiat Dihydrate Roche SERB", "definition": "A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.\n    ", "id": "MESH:D009599"}
{"mention": "nitroprusside", "mention_text": "The effects of continuous positive airway pressure (CPAP) on cardiovascular dynamics and pulmonary shunt (QS/QT) were investigated in 12 dogs before and during sodium nitroprusside infusion that decreased mean arterial blood pressure 40-50 per cent. Before nitroprusside infusion, 5 cm H2O CPAP significantly, P less than .05, decreased arterial blood pressure, but did not significantly alter heart rate, cardiac output, systemic vascular resistance, or QS/QT. Ten cm H2O CPAP before nitroprusside infusion produced a further decrease in arterial blood pressure and significantly increased heart rate and decreased cardiac output and QS/QT. Nitroprusside caused significant decreases in arterial blood pressure and systemic vascular resistance and increases in heart rate, but did not change cardiac output or QS/QT. Five cm H2O CPAP during nitroprusside did not further alter any of the above-mentioned variables. However, 10 cm H2O CPAP decreased arterial blood pressure, cardiac output, and QS/QT. These data indicate that nitroprusside infusion rates that decrease mean arterial blood pressure by 40-50 per cent do not change cardiac output or QS/QT. During nitroprusside infusion low levels of CPAP do not markedly alter cardiovascular dynamics, but high levels of CPAP (10 cm H2O), while decreasing QS/QT, produce marked decreases in arterial blood pressure and cardiac output.", "entity": "Nitroprusside", "aliases": "Abbott Brand of Sodium Nitroprusside Bayer Cyanonitrosylferrate Disodium Salt Faulding Fides Ecopharma Ketostix Naniprus Nipride Nipruton Nitriate Nitroferricyanide Nitropress Nitroprussiat Dihydrate Roche SERB", "definition": "A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.\n    ", "id": "MESH:D009599"}
{"mention": "H2O", "mention_text": "The effects of continuous positive airway pressure (CPAP) on cardiovascular dynamics and pulmonary shunt (QS/QT) were investigated in 12 dogs before and during sodium nitroprusside infusion that decreased mean arterial blood pressure 40-50 per cent. Before nitroprusside infusion, 5 cm H2O CPAP significantly, P less than .05, decreased arterial blood pressure, but did not significantly alter heart rate, cardiac output, systemic vascular resistance, or QS/QT. Ten cm H2O CPAP before nitroprusside infusion produced a further decrease in arterial blood pressure and significantly increased heart rate and decreased cardiac output and QS/QT. Nitroprusside caused significant decreases in arterial blood pressure and systemic vascular resistance and increases in heart rate, but did not change cardiac output or QS/QT. Five cm H2O CPAP during nitroprusside did not further alter any of the above-mentioned variables. However, 10 cm H2O CPAP decreased arterial blood pressure, cardiac output, and QS/QT. These data indicate that nitroprusside infusion rates that decrease mean arterial blood pressure by 40-50 per cent do not change cardiac output or QS/QT. During nitroprusside infusion low levels of CPAP do not markedly alter cardiovascular dynamics, but high levels of CPAP (10 cm H2O), while decreasing QS/QT, produce marked decreases in arterial blood pressure and cardiac output.", "entity": "Water", "aliases": "Hydrogen Oxide Water", "definition": "A clear, odorless, tasteless liquid that is essential for most animal and plant life and is an excellent solvent for many substances. The chemical formula is hydrogen oxide (H2O). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)\n    ", "id": "MESH:D014867"}
{"mention": "decrease in arterial blood pressure", "mention_text": "The effects of continuous positive airway pressure (CPAP) on cardiovascular dynamics and pulmonary shunt (QS/QT) were investigated in 12 dogs before and during sodium nitroprusside infusion that decreased mean arterial blood pressure 40-50 per cent. Before nitroprusside infusion, 5 cm H2O CPAP significantly, P less than .05, decreased arterial blood pressure, but did not significantly alter heart rate, cardiac output, systemic vascular resistance, or QS/QT. Ten cm H2O CPAP before nitroprusside infusion produced a further decrease in arterial blood pressure and significantly increased heart rate and decreased cardiac output and QS/QT. Nitroprusside caused significant decreases in arterial blood pressure and systemic vascular resistance and increases in heart rate, but did not change cardiac output or QS/QT. Five cm H2O CPAP during nitroprusside did not further alter any of the above-mentioned variables. However, 10 cm H2O CPAP decreased arterial blood pressure, cardiac output, and QS/QT. These data indicate that nitroprusside infusion rates that decrease mean arterial blood pressure by 40-50 per cent do not change cardiac output or QS/QT. During nitroprusside infusion low levels of CPAP do not markedly alter cardiovascular dynamics, but high levels of CPAP (10 cm H2O), while decreasing QS/QT, produce marked decreases in arterial blood pressure and cardiac output.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "decreased cardiac output", "mention_text": "The effects of continuous positive airway pressure (CPAP) on cardiovascular dynamics and pulmonary shunt (QS/QT) were investigated in 12 dogs before and during sodium nitroprusside infusion that decreased mean arterial blood pressure 40-50 per cent. Before nitroprusside infusion, 5 cm H2O CPAP significantly, P less than .05, decreased arterial blood pressure, but did not significantly alter heart rate, cardiac output, systemic vascular resistance, or QS/QT. Ten cm H2O CPAP before nitroprusside infusion produced a further decrease in arterial blood pressure and significantly increased heart rate and decreased cardiac output and QS/QT. Nitroprusside caused significant decreases in arterial blood pressure and systemic vascular resistance and increases in heart rate, but did not change cardiac output or QS/QT. Five cm H2O CPAP during nitroprusside did not further alter any of the above-mentioned variables. However, 10 cm H2O CPAP decreased arterial blood pressure, cardiac output, and QS/QT. These data indicate that nitroprusside infusion rates that decrease mean arterial blood pressure by 40-50 per cent do not change cardiac output or QS/QT. During nitroprusside infusion low levels of CPAP do not markedly alter cardiovascular dynamics, but high levels of CPAP (10 cm H2O), while decreasing QS/QT, produce marked decreases in arterial blood pressure and cardiac output.", "entity": "Cardiac Output, Low", "aliases": "Cardiac Output Low Syndrome", "definition": "A state of subnormal or depressed cardiac output at rest or during stress. It is a characteristic of CARDIOVASCULAR DISEASES, including congenital, valvular, rheumatic, hypertensive, coronary, and cardiomyopathic. The serious form of low cardiac output is characterized by marked reduction in STROKE VOLUME, and systemic vasoconstriction resulting in cold, pale, and sometimes cyanotic extremities.\n    ", "id": "MESH:D002303"}
{"mention": "Nitroprusside", "mention_text": "The effects of continuous positive airway pressure (CPAP) on cardiovascular dynamics and pulmonary shunt (QS/QT) were investigated in 12 dogs before and during sodium nitroprusside infusion that decreased mean arterial blood pressure 40-50 per cent. Before nitroprusside infusion, 5 cm H2O CPAP significantly, P less than .05, decreased arterial blood pressure, but did not significantly alter heart rate, cardiac output, systemic vascular resistance, or QS/QT. Ten cm H2O CPAP before nitroprusside infusion produced a further decrease in arterial blood pressure and significantly increased heart rate and decreased cardiac output and QS/QT. Nitroprusside caused significant decreases in arterial blood pressure and systemic vascular resistance and increases in heart rate, but did not change cardiac output or QS/QT. Five cm H2O CPAP during nitroprusside did not further alter any of the above-mentioned variables. However, 10 cm H2O CPAP decreased arterial blood pressure, cardiac output, and QS/QT. These data indicate that nitroprusside infusion rates that decrease mean arterial blood pressure by 40-50 per cent do not change cardiac output or QS/QT. During nitroprusside infusion low levels of CPAP do not markedly alter cardiovascular dynamics, but high levels of CPAP (10 cm H2O), while decreasing QS/QT, produce marked decreases in arterial blood pressure and cardiac output.", "entity": "Nitroprusside", "aliases": "Abbott Brand of Sodium Nitroprusside Bayer Cyanonitrosylferrate Disodium Salt Faulding Fides Ecopharma Ketostix Naniprus Nipride Nipruton Nitriate Nitroferricyanide Nitropress Nitroprussiat Dihydrate Roche SERB", "definition": "A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.\n    ", "id": "MESH:D009599"}
{"mention": "decreases in arterial blood pressure", "mention_text": "The effects of continuous positive airway pressure (CPAP) on cardiovascular dynamics and pulmonary shunt (QS/QT) were investigated in 12 dogs before and during sodium nitroprusside infusion that decreased mean arterial blood pressure 40-50 per cent. Before nitroprusside infusion, 5 cm H2O CPAP significantly, P less than .05, decreased arterial blood pressure, but did not significantly alter heart rate, cardiac output, systemic vascular resistance, or QS/QT. Ten cm H2O CPAP before nitroprusside infusion produced a further decrease in arterial blood pressure and significantly increased heart rate and decreased cardiac output and QS/QT. Nitroprusside caused significant decreases in arterial blood pressure and systemic vascular resistance and increases in heart rate, but did not change cardiac output or QS/QT. Five cm H2O CPAP during nitroprusside did not further alter any of the above-mentioned variables. However, 10 cm H2O CPAP decreased arterial blood pressure, cardiac output, and QS/QT. These data indicate that nitroprusside infusion rates that decrease mean arterial blood pressure by 40-50 per cent do not change cardiac output or QS/QT. During nitroprusside infusion low levels of CPAP do not markedly alter cardiovascular dynamics, but high levels of CPAP (10 cm H2O), while decreasing QS/QT, produce marked decreases in arterial blood pressure and cardiac output.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "bradycardia", "mention_text": "Mediation of enhanced reflex vagal bradycardia by L-dopa via central dopamine formation in dogs.", "entity": "Bradycardia", "aliases": "Bradyarrhythmia Bradyarrhythmias Bradycardia Bradycardias", "definition": "Cardiac arrhythmias that are characterized by excessively slow HEART RATE, usually below 50 beats per minute in human adults. They can be classified broadly into SINOATRIAL NODE dysfunction and ATRIOVENTRICULAR BLOCK.\n    ", "id": "MESH:D001919"}
{"mention": "L-dopa", "mention_text": "Mediation of enhanced reflex vagal bradycardia by L-dopa via central dopamine formation in dogs.", "entity": "Levodopa", "aliases": "3 Hydroxy L tyrosine 3-Hydroxy-L-tyrosine Dopaflex Dopar 3,4 Dihydroxyphenylalanine Dopa L-3,4-Dihydroxyphenylalanine L-Dopa Larodopa Levodopa Levopa Medphano Brand of Roberts Roche", "definition": "The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.\n    ", "id": "MESH:D007980"}
{"mention": "dopamine", "mention_text": "Mediation of enhanced reflex vagal bradycardia by L-dopa via central dopamine formation in dogs.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "L-Dopa", "mention_text": "L-Dopa (5 mg/kg i.v.) decreased blood pressure and heart rate after extracerebral decarboxylase inhibition with MK-486 (25 mg/kg i.v.) in anesthetize MAO-inhibited dogs. In addition, reflex bradycardia caused by injected norepinephrine was significantly enhanced by L-dopa, DL-Threo-dihydroxyphenylserine had no effect on blood pressure, heart rate or reflex responses to norepinephrine. FLA-63, a dopamine-beta-oxidase inhibitor, did not have any effect on the hypotension, bradycardia or reflex-enhancing effect of L-dopa. Pimozide did not affect the actions of L-dopa on blood pressure and heart rate but completely blocked the enhancement of reflexes. Removal of the carotid sinuses caused an elevation blood pressure and heart rate and abolished the negative chronotropic effect of norepinephrine. However, L-dopa restored the bradycardia caused by norepinephrine in addition to decreasing blood pressure and heart rate. 5-HTP (5 mg/kg i.v.) decreased blood pressure and heart rate and decreased the reflex bradycardia to norepinephrine. It is concluded that L-dopa enhances reflex bradycardia through central alpha-receptor stimulation. Furthermore, the effects are mediated through dopamine rather than norepinephrine and do not require the carotid sinus baroreceptors.", "entity": "Levodopa", "aliases": "3 Hydroxy L tyrosine 3-Hydroxy-L-tyrosine Dopaflex Dopar 3,4 Dihydroxyphenylalanine Dopa L-3,4-Dihydroxyphenylalanine L-Dopa Larodopa Levodopa Levopa Medphano Brand of Roberts Roche", "definition": "The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.\n    ", "id": "MESH:D007980"}
{"mention": "MK-486", "mention_text": "L-Dopa (5 mg/kg i.v.) decreased blood pressure and heart rate after extracerebral decarboxylase inhibition with MK-486 (25 mg/kg i.v.) in anesthetize MAO-inhibited dogs. In addition, reflex bradycardia caused by injected norepinephrine was significantly enhanced by L-dopa, DL-Threo-dihydroxyphenylserine had no effect on blood pressure, heart rate or reflex responses to norepinephrine. FLA-63, a dopamine-beta-oxidase inhibitor, did not have any effect on the hypotension, bradycardia or reflex-enhancing effect of L-dopa. Pimozide did not affect the actions of L-dopa on blood pressure and heart rate but completely blocked the enhancement of reflexes. Removal of the carotid sinuses caused an elevation blood pressure and heart rate and abolished the negative chronotropic effect of norepinephrine. However, L-dopa restored the bradycardia caused by norepinephrine in addition to decreasing blood pressure and heart rate. 5-HTP (5 mg/kg i.v.) decreased blood pressure and heart rate and decreased the reflex bradycardia to norepinephrine. It is concluded that L-dopa enhances reflex bradycardia through central alpha-receptor stimulation. Furthermore, the effects are mediated through dopamine rather than norepinephrine and do not require the carotid sinus baroreceptors.", "entity": "Carbidopa", "aliases": "Carbidopa (R)-Isomer (S)-Isomer Lodosin Lodosyn MK 485 486 MK-485 MK-486 MK485 MK486 Methyldopahydrazine", "definition": "An inhibitor of DOPA DECARBOXYLASE, preventing conversion of LEVODOPA to dopamine. It is used in PARKINSON DISEASE to reduce peripheral adverse effects of LEVODOPA. It has no antiparkinson actions by itself.\n    ", "id": "MESH:D002230"}
{"mention": "MAO", "mention_text": "L-Dopa (5 mg/kg i.v.) decreased blood pressure and heart rate after extracerebral decarboxylase inhibition with MK-486 (25 mg/kg i.v.) in anesthetize MAO-inhibited dogs. In addition, reflex bradycardia caused by injected norepinephrine was significantly enhanced by L-dopa, DL-Threo-dihydroxyphenylserine had no effect on blood pressure, heart rate or reflex responses to norepinephrine. FLA-63, a dopamine-beta-oxidase inhibitor, did not have any effect on the hypotension, bradycardia or reflex-enhancing effect of L-dopa. Pimozide did not affect the actions of L-dopa on blood pressure and heart rate but completely blocked the enhancement of reflexes. Removal of the carotid sinuses caused an elevation blood pressure and heart rate and abolished the negative chronotropic effect of norepinephrine. However, L-dopa restored the bradycardia caused by norepinephrine in addition to decreasing blood pressure and heart rate. 5-HTP (5 mg/kg i.v.) decreased blood pressure and heart rate and decreased the reflex bradycardia to norepinephrine. It is concluded that L-dopa enhances reflex bradycardia through central alpha-receptor stimulation. Furthermore, the effects are mediated through dopamine rather than norepinephrine and do not require the carotid sinus baroreceptors.", "entity": "Monoamine Oxidase", "aliases": "Amine Oxidase (Flavin-Containing) MAO A B MAO-A MAO-B Monoamine Tyramine Type", "definition": "An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4.\n    ", "id": "MESH:D008995"}
{"mention": "bradycardia", "mention_text": "L-Dopa (5 mg/kg i.v.) decreased blood pressure and heart rate after extracerebral decarboxylase inhibition with MK-486 (25 mg/kg i.v.) in anesthetize MAO-inhibited dogs. In addition, reflex bradycardia caused by injected norepinephrine was significantly enhanced by L-dopa, DL-Threo-dihydroxyphenylserine had no effect on blood pressure, heart rate or reflex responses to norepinephrine. FLA-63, a dopamine-beta-oxidase inhibitor, did not have any effect on the hypotension, bradycardia or reflex-enhancing effect of L-dopa. Pimozide did not affect the actions of L-dopa on blood pressure and heart rate but completely blocked the enhancement of reflexes. Removal of the carotid sinuses caused an elevation blood pressure and heart rate and abolished the negative chronotropic effect of norepinephrine. However, L-dopa restored the bradycardia caused by norepinephrine in addition to decreasing blood pressure and heart rate. 5-HTP (5 mg/kg i.v.) decreased blood pressure and heart rate and decreased the reflex bradycardia to norepinephrine. It is concluded that L-dopa enhances reflex bradycardia through central alpha-receptor stimulation. Furthermore, the effects are mediated through dopamine rather than norepinephrine and do not require the carotid sinus baroreceptors.", "entity": "Bradycardia", "aliases": "Bradyarrhythmia Bradyarrhythmias Bradycardia Bradycardias", "definition": "Cardiac arrhythmias that are characterized by excessively slow HEART RATE, usually below 50 beats per minute in human adults. They can be classified broadly into SINOATRIAL NODE dysfunction and ATRIOVENTRICULAR BLOCK.\n    ", "id": "MESH:D001919"}
{"mention": "norepinephrine", "mention_text": "L-Dopa (5 mg/kg i.v.) decreased blood pressure and heart rate after extracerebral decarboxylase inhibition with MK-486 (25 mg/kg i.v.) in anesthetize MAO-inhibited dogs. In addition, reflex bradycardia caused by injected norepinephrine was significantly enhanced by L-dopa, DL-Threo-dihydroxyphenylserine had no effect on blood pressure, heart rate or reflex responses to norepinephrine. FLA-63, a dopamine-beta-oxidase inhibitor, did not have any effect on the hypotension, bradycardia or reflex-enhancing effect of L-dopa. Pimozide did not affect the actions of L-dopa on blood pressure and heart rate but completely blocked the enhancement of reflexes. Removal of the carotid sinuses caused an elevation blood pressure and heart rate and abolished the negative chronotropic effect of norepinephrine. However, L-dopa restored the bradycardia caused by norepinephrine in addition to decreasing blood pressure and heart rate. 5-HTP (5 mg/kg i.v.) decreased blood pressure and heart rate and decreased the reflex bradycardia to norepinephrine. It is concluded that L-dopa enhances reflex bradycardia through central alpha-receptor stimulation. Furthermore, the effects are mediated through dopamine rather than norepinephrine and do not require the carotid sinus baroreceptors.", "entity": "Norepinephrine", "aliases": "Abbott Brand of Levophed Bitartrate Arterenol Aventis Norepinephrine Hydrochloride Noradrenaline Levarterenol Levonor Levonorepinephrine Noradrénaline tartrate renaudin Norepinephrin d-Tartrate (1:1) (+)-Isomer (+,-)-Isomer l-Tartrate Monohydrate (1:2) Renaudin", "definition": "Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.\n    ", "id": "MESH:D009638"}
{"mention": "L-dopa", "mention_text": "L-Dopa (5 mg/kg i.v.) decreased blood pressure and heart rate after extracerebral decarboxylase inhibition with MK-486 (25 mg/kg i.v.) in anesthetize MAO-inhibited dogs. In addition, reflex bradycardia caused by injected norepinephrine was significantly enhanced by L-dopa, DL-Threo-dihydroxyphenylserine had no effect on blood pressure, heart rate or reflex responses to norepinephrine. FLA-63, a dopamine-beta-oxidase inhibitor, did not have any effect on the hypotension, bradycardia or reflex-enhancing effect of L-dopa. Pimozide did not affect the actions of L-dopa on blood pressure and heart rate but completely blocked the enhancement of reflexes. Removal of the carotid sinuses caused an elevation blood pressure and heart rate and abolished the negative chronotropic effect of norepinephrine. However, L-dopa restored the bradycardia caused by norepinephrine in addition to decreasing blood pressure and heart rate. 5-HTP (5 mg/kg i.v.) decreased blood pressure and heart rate and decreased the reflex bradycardia to norepinephrine. It is concluded that L-dopa enhances reflex bradycardia through central alpha-receptor stimulation. Furthermore, the effects are mediated through dopamine rather than norepinephrine and do not require the carotid sinus baroreceptors.", "entity": "Levodopa", "aliases": "3 Hydroxy L tyrosine 3-Hydroxy-L-tyrosine Dopaflex Dopar 3,4 Dihydroxyphenylalanine Dopa L-3,4-Dihydroxyphenylalanine L-Dopa Larodopa Levodopa Levopa Medphano Brand of Roberts Roche", "definition": "The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.\n    ", "id": "MESH:D007980"}
{"mention": "DL-Threo-dihydroxyphenylserine", "mention_text": "L-Dopa (5 mg/kg i.v.) decreased blood pressure and heart rate after extracerebral decarboxylase inhibition with MK-486 (25 mg/kg i.v.) in anesthetize MAO-inhibited dogs. In addition, reflex bradycardia caused by injected norepinephrine was significantly enhanced by L-dopa, DL-Threo-dihydroxyphenylserine had no effect on blood pressure, heart rate or reflex responses to norepinephrine. FLA-63, a dopamine-beta-oxidase inhibitor, did not have any effect on the hypotension, bradycardia or reflex-enhancing effect of L-dopa. Pimozide did not affect the actions of L-dopa on blood pressure and heart rate but completely blocked the enhancement of reflexes. Removal of the carotid sinuses caused an elevation blood pressure and heart rate and abolished the negative chronotropic effect of norepinephrine. However, L-dopa restored the bradycardia caused by norepinephrine in addition to decreasing blood pressure and heart rate. 5-HTP (5 mg/kg i.v.) decreased blood pressure and heart rate and decreased the reflex bradycardia to norepinephrine. It is concluded that L-dopa enhances reflex bradycardia through central alpha-receptor stimulation. Furthermore, the effects are mediated through dopamine rather than norepinephrine and do not require the carotid sinus baroreceptors.", "entity": "Droxidopa", "aliases": "3,4 Dihydroxyphenylserine threo DOPS 3,4-Dihydroxyphenylserine 3,4-threo-DOPS DL DL-threo-3,4-Dihydroxyphenylserine Droxidopa (DL-Tyr)-Isomer erythro erythro-3,4-Dihydroxyphenylserine threo-DOPS", "definition": "A precursor of noradrenaline that is used in the treatment of parkinsonism. The racemic form (DL-threo-3,4-dihydroxyphenylserine) has also been used, and has been investigated in the treatment of orthostatic hypotension. There is a deficit of noradrenaline as well as of dopamine in Parkinson's disease and it has been proposed that this underlies the sudden transient freezing seen usually in advanced disease. Administration of DL-threo-3,4-dihydroxyphenylserine has been claimed to result in an improvement in this phenomenon but controlled studies have failed to demonstrate improvement. (Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1995)\n    ", "id": "MESH:D015103"}
{"mention": "FLA-63", "mention_text": "L-Dopa (5 mg/kg i.v.) decreased blood pressure and heart rate after extracerebral decarboxylase inhibition with MK-486 (25 mg/kg i.v.) in anesthetize MAO-inhibited dogs. In addition, reflex bradycardia caused by injected norepinephrine was significantly enhanced by L-dopa, DL-Threo-dihydroxyphenylserine had no effect on blood pressure, heart rate or reflex responses to norepinephrine. FLA-63, a dopamine-beta-oxidase inhibitor, did not have any effect on the hypotension, bradycardia or reflex-enhancing effect of L-dopa. Pimozide did not affect the actions of L-dopa on blood pressure and heart rate but completely blocked the enhancement of reflexes. Removal of the carotid sinuses caused an elevation blood pressure and heart rate and abolished the negative chronotropic effect of norepinephrine. However, L-dopa restored the bradycardia caused by norepinephrine in addition to decreasing blood pressure and heart rate. 5-HTP (5 mg/kg i.v.) decreased blood pressure and heart rate and decreased the reflex bradycardia to norepinephrine. It is concluded that L-dopa enhances reflex bradycardia through central alpha-receptor stimulation. Furthermore, the effects are mediated through dopamine rather than norepinephrine and do not require the carotid sinus baroreceptors.", "entity": "Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide", "aliases": "Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide FLA 63", "definition": "An inhibitor of the last step of noradrenaline biosynthesis.\n    ", "id": "MESH:D005406"}
{"mention": "dopamine", "mention_text": "L-Dopa (5 mg/kg i.v.) decreased blood pressure and heart rate after extracerebral decarboxylase inhibition with MK-486 (25 mg/kg i.v.) in anesthetize MAO-inhibited dogs. In addition, reflex bradycardia caused by injected norepinephrine was significantly enhanced by L-dopa, DL-Threo-dihydroxyphenylserine had no effect on blood pressure, heart rate or reflex responses to norepinephrine. FLA-63, a dopamine-beta-oxidase inhibitor, did not have any effect on the hypotension, bradycardia or reflex-enhancing effect of L-dopa. Pimozide did not affect the actions of L-dopa on blood pressure and heart rate but completely blocked the enhancement of reflexes. Removal of the carotid sinuses caused an elevation blood pressure and heart rate and abolished the negative chronotropic effect of norepinephrine. However, L-dopa restored the bradycardia caused by norepinephrine in addition to decreasing blood pressure and heart rate. 5-HTP (5 mg/kg i.v.) decreased blood pressure and heart rate and decreased the reflex bradycardia to norepinephrine. It is concluded that L-dopa enhances reflex bradycardia through central alpha-receptor stimulation. Furthermore, the effects are mediated through dopamine rather than norepinephrine and do not require the carotid sinus baroreceptors.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "hypotension", "mention_text": "L-Dopa (5 mg/kg i.v.) decreased blood pressure and heart rate after extracerebral decarboxylase inhibition with MK-486 (25 mg/kg i.v.) in anesthetize MAO-inhibited dogs. In addition, reflex bradycardia caused by injected norepinephrine was significantly enhanced by L-dopa, DL-Threo-dihydroxyphenylserine had no effect on blood pressure, heart rate or reflex responses to norepinephrine. FLA-63, a dopamine-beta-oxidase inhibitor, did not have any effect on the hypotension, bradycardia or reflex-enhancing effect of L-dopa. Pimozide did not affect the actions of L-dopa on blood pressure and heart rate but completely blocked the enhancement of reflexes. Removal of the carotid sinuses caused an elevation blood pressure and heart rate and abolished the negative chronotropic effect of norepinephrine. However, L-dopa restored the bradycardia caused by norepinephrine in addition to decreasing blood pressure and heart rate. 5-HTP (5 mg/kg i.v.) decreased blood pressure and heart rate and decreased the reflex bradycardia to norepinephrine. It is concluded that L-dopa enhances reflex bradycardia through central alpha-receptor stimulation. Furthermore, the effects are mediated through dopamine rather than norepinephrine and do not require the carotid sinus baroreceptors.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "Pimozide", "mention_text": "L-Dopa (5 mg/kg i.v.) decreased blood pressure and heart rate after extracerebral decarboxylase inhibition with MK-486 (25 mg/kg i.v.) in anesthetize MAO-inhibited dogs. In addition, reflex bradycardia caused by injected norepinephrine was significantly enhanced by L-dopa, DL-Threo-dihydroxyphenylserine had no effect on blood pressure, heart rate or reflex responses to norepinephrine. FLA-63, a dopamine-beta-oxidase inhibitor, did not have any effect on the hypotension, bradycardia or reflex-enhancing effect of L-dopa. Pimozide did not affect the actions of L-dopa on blood pressure and heart rate but completely blocked the enhancement of reflexes. Removal of the carotid sinuses caused an elevation blood pressure and heart rate and abolished the negative chronotropic effect of norepinephrine. However, L-dopa restored the bradycardia caused by norepinephrine in addition to decreasing blood pressure and heart rate. 5-HTP (5 mg/kg i.v.) decreased blood pressure and heart rate and decreased the reflex bradycardia to norepinephrine. It is concluded that L-dopa enhances reflex bradycardia through central alpha-receptor stimulation. Furthermore, the effects are mediated through dopamine rather than norepinephrine and do not require the carotid sinus baroreceptors.", "entity": "Pimozide", "aliases": "ASTA Medica Brand of Pimozide Antalon Janssen Orap forte Pharmascience R-6238 R6238", "definition": "A diphenylbutylpiperidine that is effective as an antipsychotic agent and as an alternative to HALOPERIDOL for the suppression of vocal and motor tics in patients with Tourette syndrome. Although the precise mechanism of action is unknown, blockade of postsynaptic dopamine receptors has been postulated. (From AMA Drug Evaluations Annual, 1994, p403)\n    ", "id": "MESH:D010868"}
{"mention": "5-HTP", "mention_text": "L-Dopa (5 mg/kg i.v.) decreased blood pressure and heart rate after extracerebral decarboxylase inhibition with MK-486 (25 mg/kg i.v.) in anesthetize MAO-inhibited dogs. In addition, reflex bradycardia caused by injected norepinephrine was significantly enhanced by L-dopa, DL-Threo-dihydroxyphenylserine had no effect on blood pressure, heart rate or reflex responses to norepinephrine. FLA-63, a dopamine-beta-oxidase inhibitor, did not have any effect on the hypotension, bradycardia or reflex-enhancing effect of L-dopa. Pimozide did not affect the actions of L-dopa on blood pressure and heart rate but completely blocked the enhancement of reflexes. Removal of the carotid sinuses caused an elevation blood pressure and heart rate and abolished the negative chronotropic effect of norepinephrine. However, L-dopa restored the bradycardia caused by norepinephrine in addition to decreasing blood pressure and heart rate. 5-HTP (5 mg/kg i.v.) decreased blood pressure and heart rate and decreased the reflex bradycardia to norepinephrine. It is concluded that L-dopa enhances reflex bradycardia through central alpha-receptor stimulation. Furthermore, the effects are mediated through dopamine rather than norepinephrine and do not require the carotid sinus baroreceptors.", "entity": "5-Hydroxytryptophan", "aliases": "5 Hydroxytryptophan 5-HTP 5-Hydroxy- Tryptophan 5-Hydroxytryptophan Oxitriptan Oxytryptophan Hydroxy", "definition": "The immediate precursor in the biosynthesis of SEROTONIN from tryptophan. It is used as an antiepileptic and antidepressant.\n    ", "id": "MESH:D006916"}
{"mention": "Cocaine", "mention_text": "Cocaine-induced myocardial infarction: clinical observations and pathogenetic considerations.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "myocardial infarction", "mention_text": "Cocaine-induced myocardial infarction: clinical observations and pathogenetic considerations.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "cocaine", "mention_text": "Clinical and experimental data published to date suggest several possible mechanisms by which cocaine may result in acute myocardial infarction. In individuals with preexisting, high-grade coronary arterial narrowing, acute myocardial infarction may result from an increase in myocardial oxygen demand associated with cocaine-induced increase in rate-pressure product. In other individuals with no underlying atherosclerotic obstruction, coronary occlusion may be due to spasm, thrombus, or both. With regard to spasm, the clinical findings are largely circumstantial, and the locus of cocaine-induced vasoconstriction remains speculative. Although certain clinical and experimental findings support the hypothesis that spasm involves the epicardial, medium-size vessels, other data suggest intramural vasoconstriction. Diffuse intramural vasoconstriction is not consistent with reports of segmental, discrete infarction. Whereas certain in vivo data suggest that these effects are alpha-mediated, other in vitro data suggest the opposite. The finding of cocaine-induced vasoconstriction in segments of (noninnervated) human umbilical artery suggests that the presence or absence of intact innervation is not sufficient to explain the discrepant data involving the possibility of alpha-mediated effects. Finally, the contribution of a primary, thrombotic effect of cocaine has not been excluded.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "acute myocardial infarction", "mention_text": "Clinical and experimental data published to date suggest several possible mechanisms by which cocaine may result in acute myocardial infarction. In individuals with preexisting, high-grade coronary arterial narrowing, acute myocardial infarction may result from an increase in myocardial oxygen demand associated with cocaine-induced increase in rate-pressure product. In other individuals with no underlying atherosclerotic obstruction, coronary occlusion may be due to spasm, thrombus, or both. With regard to spasm, the clinical findings are largely circumstantial, and the locus of cocaine-induced vasoconstriction remains speculative. Although certain clinical and experimental findings support the hypothesis that spasm involves the epicardial, medium-size vessels, other data suggest intramural vasoconstriction. Diffuse intramural vasoconstriction is not consistent with reports of segmental, discrete infarction. Whereas certain in vivo data suggest that these effects are alpha-mediated, other in vitro data suggest the opposite. The finding of cocaine-induced vasoconstriction in segments of (noninnervated) human umbilical artery suggests that the presence or absence of intact innervation is not sufficient to explain the discrepant data involving the possibility of alpha-mediated effects. Finally, the contribution of a primary, thrombotic effect of cocaine has not been excluded.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "oxygen", "mention_text": "Clinical and experimental data published to date suggest several possible mechanisms by which cocaine may result in acute myocardial infarction. In individuals with preexisting, high-grade coronary arterial narrowing, acute myocardial infarction may result from an increase in myocardial oxygen demand associated with cocaine-induced increase in rate-pressure product. In other individuals with no underlying atherosclerotic obstruction, coronary occlusion may be due to spasm, thrombus, or both. With regard to spasm, the clinical findings are largely circumstantial, and the locus of cocaine-induced vasoconstriction remains speculative. Although certain clinical and experimental findings support the hypothesis that spasm involves the epicardial, medium-size vessels, other data suggest intramural vasoconstriction. Diffuse intramural vasoconstriction is not consistent with reports of segmental, discrete infarction. Whereas certain in vivo data suggest that these effects are alpha-mediated, other in vitro data suggest the opposite. The finding of cocaine-induced vasoconstriction in segments of (noninnervated) human umbilical artery suggests that the presence or absence of intact innervation is not sufficient to explain the discrepant data involving the possibility of alpha-mediated effects. Finally, the contribution of a primary, thrombotic effect of cocaine has not been excluded.", "entity": "Oxygen", "aliases": "Dioxygen Oxygen", "definition": "An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.\n    ", "id": "MESH:D010100"}
{"mention": "atherosclerotic obstruction", "mention_text": "Clinical and experimental data published to date suggest several possible mechanisms by which cocaine may result in acute myocardial infarction. In individuals with preexisting, high-grade coronary arterial narrowing, acute myocardial infarction may result from an increase in myocardial oxygen demand associated with cocaine-induced increase in rate-pressure product. In other individuals with no underlying atherosclerotic obstruction, coronary occlusion may be due to spasm, thrombus, or both. With regard to spasm, the clinical findings are largely circumstantial, and the locus of cocaine-induced vasoconstriction remains speculative. Although certain clinical and experimental findings support the hypothesis that spasm involves the epicardial, medium-size vessels, other data suggest intramural vasoconstriction. Diffuse intramural vasoconstriction is not consistent with reports of segmental, discrete infarction. Whereas certain in vivo data suggest that these effects are alpha-mediated, other in vitro data suggest the opposite. The finding of cocaine-induced vasoconstriction in segments of (noninnervated) human umbilical artery suggests that the presence or absence of intact innervation is not sufficient to explain the discrepant data involving the possibility of alpha-mediated effects. Finally, the contribution of a primary, thrombotic effect of cocaine has not been excluded.", "entity": "Atherosclerosis", "aliases": "Atherogenesis Atheroscleroses Atherosclerosis", "definition": "A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA.\n    ", "id": "MESH:D050197"}
{"mention": "coronary occlusion", "mention_text": "Clinical and experimental data published to date suggest several possible mechanisms by which cocaine may result in acute myocardial infarction. In individuals with preexisting, high-grade coronary arterial narrowing, acute myocardial infarction may result from an increase in myocardial oxygen demand associated with cocaine-induced increase in rate-pressure product. In other individuals with no underlying atherosclerotic obstruction, coronary occlusion may be due to spasm, thrombus, or both. With regard to spasm, the clinical findings are largely circumstantial, and the locus of cocaine-induced vasoconstriction remains speculative. Although certain clinical and experimental findings support the hypothesis that spasm involves the epicardial, medium-size vessels, other data suggest intramural vasoconstriction. Diffuse intramural vasoconstriction is not consistent with reports of segmental, discrete infarction. Whereas certain in vivo data suggest that these effects are alpha-mediated, other in vitro data suggest the opposite. The finding of cocaine-induced vasoconstriction in segments of (noninnervated) human umbilical artery suggests that the presence or absence of intact innervation is not sufficient to explain the discrepant data involving the possibility of alpha-mediated effects. Finally, the contribution of a primary, thrombotic effect of cocaine has not been excluded.", "entity": "Coronary Occlusion", "aliases": "Coronary Occlusion Occlusions", "definition": "Complete blockage of blood flow through one of the CORONARY ARTERIES, usually from CORONARY ATHEROSCLEROSIS.\n    ", "id": "MESH:D054059"}
{"mention": "spasm", "mention_text": "Clinical and experimental data published to date suggest several possible mechanisms by which cocaine may result in acute myocardial infarction. In individuals with preexisting, high-grade coronary arterial narrowing, acute myocardial infarction may result from an increase in myocardial oxygen demand associated with cocaine-induced increase in rate-pressure product. In other individuals with no underlying atherosclerotic obstruction, coronary occlusion may be due to spasm, thrombus, or both. With regard to spasm, the clinical findings are largely circumstantial, and the locus of cocaine-induced vasoconstriction remains speculative. Although certain clinical and experimental findings support the hypothesis that spasm involves the epicardial, medium-size vessels, other data suggest intramural vasoconstriction. Diffuse intramural vasoconstriction is not consistent with reports of segmental, discrete infarction. Whereas certain in vivo data suggest that these effects are alpha-mediated, other in vitro data suggest the opposite. The finding of cocaine-induced vasoconstriction in segments of (noninnervated) human umbilical artery suggests that the presence or absence of intact innervation is not sufficient to explain the discrepant data involving the possibility of alpha-mediated effects. Finally, the contribution of a primary, thrombotic effect of cocaine has not been excluded.", "entity": "Spasm", "aliases": "Ciliary Body Spasm Spasms Generalized Muscle Muscular", "definition": "An involuntary contraction of a muscle or group of muscles. Spasms may involve SKELETAL MUSCLE or SMOOTH MUSCLE.\n    ", "id": "MESH:D013035"}
{"mention": "thrombus", "mention_text": "Clinical and experimental data published to date suggest several possible mechanisms by which cocaine may result in acute myocardial infarction. In individuals with preexisting, high-grade coronary arterial narrowing, acute myocardial infarction may result from an increase in myocardial oxygen demand associated with cocaine-induced increase in rate-pressure product. In other individuals with no underlying atherosclerotic obstruction, coronary occlusion may be due to spasm, thrombus, or both. With regard to spasm, the clinical findings are largely circumstantial, and the locus of cocaine-induced vasoconstriction remains speculative. Although certain clinical and experimental findings support the hypothesis that spasm involves the epicardial, medium-size vessels, other data suggest intramural vasoconstriction. Diffuse intramural vasoconstriction is not consistent with reports of segmental, discrete infarction. Whereas certain in vivo data suggest that these effects are alpha-mediated, other in vitro data suggest the opposite. The finding of cocaine-induced vasoconstriction in segments of (noninnervated) human umbilical artery suggests that the presence or absence of intact innervation is not sufficient to explain the discrepant data involving the possibility of alpha-mediated effects. Finally, the contribution of a primary, thrombotic effect of cocaine has not been excluded.", "entity": "Thrombosis", "aliases": "Thromboses Thrombosis Thrombus", "definition": "Formation and development of a thrombus or blood clot in the blood vessel.\n    ", "id": "MESH:D013927"}
{"mention": "infarction", "mention_text": "Clinical and experimental data published to date suggest several possible mechanisms by which cocaine may result in acute myocardial infarction. In individuals with preexisting, high-grade coronary arterial narrowing, acute myocardial infarction may result from an increase in myocardial oxygen demand associated with cocaine-induced increase in rate-pressure product. In other individuals with no underlying atherosclerotic obstruction, coronary occlusion may be due to spasm, thrombus, or both. With regard to spasm, the clinical findings are largely circumstantial, and the locus of cocaine-induced vasoconstriction remains speculative. Although certain clinical and experimental findings support the hypothesis that spasm involves the epicardial, medium-size vessels, other data suggest intramural vasoconstriction. Diffuse intramural vasoconstriction is not consistent with reports of segmental, discrete infarction. Whereas certain in vivo data suggest that these effects are alpha-mediated, other in vitro data suggest the opposite. The finding of cocaine-induced vasoconstriction in segments of (noninnervated) human umbilical artery suggests that the presence or absence of intact innervation is not sufficient to explain the discrepant data involving the possibility of alpha-mediated effects. Finally, the contribution of a primary, thrombotic effect of cocaine has not been excluded.", "entity": "Infarction", "aliases": "Infarction Infarctions", "definition": "Formation of an infarct, which is NECROSIS in tissue due to local ISCHEMIA resulting from obstruction of BLOOD CIRCULATION, most commonly by a THROMBUS or EMBOLUS.\n    ", "id": "MESH:D007238"}
{"mention": "thrombotic", "mention_text": "Clinical and experimental data published to date suggest several possible mechanisms by which cocaine may result in acute myocardial infarction. In individuals with preexisting, high-grade coronary arterial narrowing, acute myocardial infarction may result from an increase in myocardial oxygen demand associated with cocaine-induced increase in rate-pressure product. In other individuals with no underlying atherosclerotic obstruction, coronary occlusion may be due to spasm, thrombus, or both. With regard to spasm, the clinical findings are largely circumstantial, and the locus of cocaine-induced vasoconstriction remains speculative. Although certain clinical and experimental findings support the hypothesis that spasm involves the epicardial, medium-size vessels, other data suggest intramural vasoconstriction. Diffuse intramural vasoconstriction is not consistent with reports of segmental, discrete infarction. Whereas certain in vivo data suggest that these effects are alpha-mediated, other in vitro data suggest the opposite. The finding of cocaine-induced vasoconstriction in segments of (noninnervated) human umbilical artery suggests that the presence or absence of intact innervation is not sufficient to explain the discrepant data involving the possibility of alpha-mediated effects. Finally, the contribution of a primary, thrombotic effect of cocaine has not been excluded.", "entity": "Thrombosis", "aliases": "Thromboses Thrombosis Thrombus", "definition": "Formation and development of a thrombus or blood clot in the blood vessel.\n    ", "id": "MESH:D013927"}
{"mention": "Rabbit syndrome", "mention_text": "Rabbit syndrome, antidepressant use, and cerebral perfusion SPECT scan findings.", "entity": "Basal Ganglia Diseases", "aliases": "Basal Ganglia Disease Diseases Disorder Disorders Extrapyramidal Lenticulostriate", "definition": "Diseases of the BASAL GANGLIA including the PUTAMEN; GLOBUS PALLIDUS; claustrum; AMYGDALA; and CAUDATE NUCLEUS. DYSKINESIAS (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include CEREBROVASCULAR DISORDERS; NEURODEGENERATIVE DISEASES; and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D001480"}
{"mention": "antidepressant", "mention_text": "Rabbit syndrome, antidepressant use, and cerebral perfusion SPECT scan findings.", "entity": "Antidepressive Agents", "aliases": "Agents Antidepressive Antidepressant Drugs Antidepressants Thymoanaleptics Thymoleptics", "definition": "Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.\n    ", "id": "MESH:D000928"}
{"mention": "rabbit syndrome", "mention_text": "The rabbit syndrome is an extrapyramidal side effect associated with chronic neuroleptic therapy. Its occurrence in a patient being treated with imipramine is described, representing the first reported case of this syndrome in conjunction with antidepressants. Repeated cerebral perfusion SPECT scans revealed decreased basal ganglia perfusion while the movement disorder was present, and a return to normal perfusion when the rabbit syndrome resolved.", "entity": "Basal Ganglia Diseases", "aliases": "Basal Ganglia Disease Diseases Disorder Disorders Extrapyramidal Lenticulostriate", "definition": "Diseases of the BASAL GANGLIA including the PUTAMEN; GLOBUS PALLIDUS; claustrum; AMYGDALA; and CAUDATE NUCLEUS. DYSKINESIAS (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include CEREBROVASCULAR DISORDERS; NEURODEGENERATIVE DISEASES; and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D001480"}
{"mention": "imipramine", "mention_text": "The rabbit syndrome is an extrapyramidal side effect associated with chronic neuroleptic therapy. Its occurrence in a patient being treated with imipramine is described, representing the first reported case of this syndrome in conjunction with antidepressants. Repeated cerebral perfusion SPECT scans revealed decreased basal ganglia perfusion while the movement disorder was present, and a return to normal perfusion when the rabbit syndrome resolved.", "entity": "Imipramine", "aliases": "Imidobenzyle Imipramine Hydrochloride Monohydrochloride Imizin Janimine Melipramine Norchlorimipramine Pryleugan Tofranil", "definition": "The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group.\n    ", "id": "MESH:D007099"}
{"mention": "antidepressants", "mention_text": "The rabbit syndrome is an extrapyramidal side effect associated with chronic neuroleptic therapy. Its occurrence in a patient being treated with imipramine is described, representing the first reported case of this syndrome in conjunction with antidepressants. Repeated cerebral perfusion SPECT scans revealed decreased basal ganglia perfusion while the movement disorder was present, and a return to normal perfusion when the rabbit syndrome resolved.", "entity": "Antidepressive Agents", "aliases": "Agents Antidepressive Antidepressant Drugs Antidepressants Thymoanaleptics Thymoleptics", "definition": "Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.\n    ", "id": "MESH:D000928"}
{"mention": "decreased basal ganglia perfusion", "mention_text": "The rabbit syndrome is an extrapyramidal side effect associated with chronic neuroleptic therapy. Its occurrence in a patient being treated with imipramine is described, representing the first reported case of this syndrome in conjunction with antidepressants. Repeated cerebral perfusion SPECT scans revealed decreased basal ganglia perfusion while the movement disorder was present, and a return to normal perfusion when the rabbit syndrome resolved.", "entity": "Basal Ganglia Diseases", "aliases": "Basal Ganglia Disease Diseases Disorder Disorders Extrapyramidal Lenticulostriate", "definition": "Diseases of the BASAL GANGLIA including the PUTAMEN; GLOBUS PALLIDUS; claustrum; AMYGDALA; and CAUDATE NUCLEUS. DYSKINESIAS (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include CEREBROVASCULAR DISORDERS; NEURODEGENERATIVE DISEASES; and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D001480"}
{"mention": "movement disorder", "mention_text": "The rabbit syndrome is an extrapyramidal side effect associated with chronic neuroleptic therapy. Its occurrence in a patient being treated with imipramine is described, representing the first reported case of this syndrome in conjunction with antidepressants. Repeated cerebral perfusion SPECT scans revealed decreased basal ganglia perfusion while the movement disorder was present, and a return to normal perfusion when the rabbit syndrome resolved.", "entity": "Movement Disorders", "aliases": "Dyskinesia Syndrome Syndromes Lingual-Facial-Buccal Linguofacial Oral Oral-facial Orofacial Tardive Dyskinesias Dystonia Dystonias Etat Marbre Lingual Facial Buccal Movement Disorder Disorders facial Status Marmoratus", "definition": "Syndromes which feature DYSKINESIAS as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions.\n    ", "id": "MESH:D009069"}
{"mention": "ipratropium bromide", "mention_text": "Acute bronchodilating effects of ipratropium bromide and theophylline in chronic obstructive pulmonary disease.", "entity": "Ipratropium", "aliases": "(endo,syn)-(+-)-3-(3-Hydroxy-1-oxo-2-phenylpropoxy)-8-methyl-8-(1-methylethyl)-8-azoniabicyclo(3.2.1)octane Anhydrous Ipratropium Bromide Atrovent Monohydrate (endo,anti)-Isomer (exo,syn)-Isomer endo-Isomer Itrop N Isopropylatropine N-Isopropylatropine Sch 1000 1178 Sch-1000 Sch-1178 Sch1000 Sch1178", "definition": "A muscarinic antagonist structurally related to ATROPINE but often considered safer and more effective for inhalation use. It is used for various bronchial disorders, in rhinitis, and as an antiarrhythmic.\n    ", "id": "MESH:D009241"}
{"mention": "theophylline", "mention_text": "Acute bronchodilating effects of ipratropium bromide and theophylline in chronic obstructive pulmonary disease.", "entity": "Theophylline", "aliases": "1,3 Dimethylxanthine 1,3-Dimethylxanthine 3,7-Dihydro-1,3-dimethyl-1H-purine-2,6-dione Accurbron Aerobin Aerolate Afonilum Retard Anhydrous Theophylline Aquaphyllin Armophylline Bronchoparat Bronkodyl Constant T Constant-T ConstantT Elixophyllin Euphylong Fameasan Brand of Sodium Glycinate Fujisawa Glycine Theophyllinate Lodrane Monospan Mundipharma Nuelin S.A. Quibron SR T-SR TSR Slo Phyllin Slo-Phyllin SloPhyllin Somophyllin Somophyllin-T SomophyllinT Sustaire Synophylate Theo 24 Dur Theo-24 T", "definition": "A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLATE CYCLASE and cyclic AMP.\n    ", "id": "MESH:D013806"}
{"mention": "chronic obstructive pulmonary disease", "mention_text": "Acute bronchodilating effects of ipratropium bromide and theophylline in chronic obstructive pulmonary disease.", "entity": "Pulmonary Disease, Chronic Obstructive", "aliases": "Airflow Obstruction Chronic Obstructions COAD COPD Obstructive Airway Disease Lung Pulmonary", "definition": "A disease of chronic diffuse irreversible airflow obstruction. Subcategories of COPD include CHRONIC BRONCHITIS and PULMONARY EMPHYSEMA.\n    ", "id": "MESH:D029424"}
{"mention": "ipratropium bromide", "mention_text": "The bronchodilator effects of a single dose of ipratropium bromide aerosol (36 micrograms) and short-acting theophylline tablets (dose titrated to produce serum levels of 10-20 micrograms/mL) were compared in a double-blind, placebo-controlled crossover study in 21 patients with stable, chronic obstructive pulmonary disease. Mean peak forced expiratory volume in 1 second (FEV1) increases over baseline and the proportion of patients attaining at least a 15% increase in the FEV1 (responders) were 31% and 90%, respectively, for ipratropium and 17% and 50%, respectively, for theophylline. The average FEV1 increases during the 6-hour observation period were 18% for ipratropium and 8% for theophylline. The mean duration of action was 3.8 hours with ipratropium and 2.4 hours with theophylline. While side effects were rare, those experienced after theophylline use did involve the cardiovascular and gastrointestinal systems. These results show that ipratropium is a more potent bronchodilator than oral theophylline in patients with chronic airflow obstruction.", "entity": "Ipratropium", "aliases": "(endo,syn)-(+-)-3-(3-Hydroxy-1-oxo-2-phenylpropoxy)-8-methyl-8-(1-methylethyl)-8-azoniabicyclo(3.2.1)octane Anhydrous Ipratropium Bromide Atrovent Monohydrate (endo,anti)-Isomer (exo,syn)-Isomer endo-Isomer Itrop N Isopropylatropine N-Isopropylatropine Sch 1000 1178 Sch-1000 Sch-1178 Sch1000 Sch1178", "definition": "A muscarinic antagonist structurally related to ATROPINE but often considered safer and more effective for inhalation use. It is used for various bronchial disorders, in rhinitis, and as an antiarrhythmic.\n    ", "id": "MESH:D009241"}
{"mention": "theophylline", "mention_text": "The bronchodilator effects of a single dose of ipratropium bromide aerosol (36 micrograms) and short-acting theophylline tablets (dose titrated to produce serum levels of 10-20 micrograms/mL) were compared in a double-blind, placebo-controlled crossover study in 21 patients with stable, chronic obstructive pulmonary disease. Mean peak forced expiratory volume in 1 second (FEV1) increases over baseline and the proportion of patients attaining at least a 15% increase in the FEV1 (responders) were 31% and 90%, respectively, for ipratropium and 17% and 50%, respectively, for theophylline. The average FEV1 increases during the 6-hour observation period were 18% for ipratropium and 8% for theophylline. The mean duration of action was 3.8 hours with ipratropium and 2.4 hours with theophylline. While side effects were rare, those experienced after theophylline use did involve the cardiovascular and gastrointestinal systems. These results show that ipratropium is a more potent bronchodilator than oral theophylline in patients with chronic airflow obstruction.", "entity": "Theophylline", "aliases": "1,3 Dimethylxanthine 1,3-Dimethylxanthine 3,7-Dihydro-1,3-dimethyl-1H-purine-2,6-dione Accurbron Aerobin Aerolate Afonilum Retard Anhydrous Theophylline Aquaphyllin Armophylline Bronchoparat Bronkodyl Constant T Constant-T ConstantT Elixophyllin Euphylong Fameasan Brand of Sodium Glycinate Fujisawa Glycine Theophyllinate Lodrane Monospan Mundipharma Nuelin S.A. Quibron SR T-SR TSR Slo Phyllin Slo-Phyllin SloPhyllin Somophyllin Somophyllin-T SomophyllinT Sustaire Synophylate Theo 24 Dur Theo-24 T", "definition": "A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLATE CYCLASE and cyclic AMP.\n    ", "id": "MESH:D013806"}
{"mention": "chronic obstructive pulmonary disease", "mention_text": "The bronchodilator effects of a single dose of ipratropium bromide aerosol (36 micrograms) and short-acting theophylline tablets (dose titrated to produce serum levels of 10-20 micrograms/mL) were compared in a double-blind, placebo-controlled crossover study in 21 patients with stable, chronic obstructive pulmonary disease. Mean peak forced expiratory volume in 1 second (FEV1) increases over baseline and the proportion of patients attaining at least a 15% increase in the FEV1 (responders) were 31% and 90%, respectively, for ipratropium and 17% and 50%, respectively, for theophylline. The average FEV1 increases during the 6-hour observation period were 18% for ipratropium and 8% for theophylline. The mean duration of action was 3.8 hours with ipratropium and 2.4 hours with theophylline. While side effects were rare, those experienced after theophylline use did involve the cardiovascular and gastrointestinal systems. These results show that ipratropium is a more potent bronchodilator than oral theophylline in patients with chronic airflow obstruction.", "entity": "Pulmonary Disease, Chronic Obstructive", "aliases": "Airflow Obstruction Chronic Obstructions COAD COPD Obstructive Airway Disease Lung Pulmonary", "definition": "A disease of chronic diffuse irreversible airflow obstruction. Subcategories of COPD include CHRONIC BRONCHITIS and PULMONARY EMPHYSEMA.\n    ", "id": "MESH:D029424"}
{"mention": "ipratropium", "mention_text": "The bronchodilator effects of a single dose of ipratropium bromide aerosol (36 micrograms) and short-acting theophylline tablets (dose titrated to produce serum levels of 10-20 micrograms/mL) were compared in a double-blind, placebo-controlled crossover study in 21 patients with stable, chronic obstructive pulmonary disease. Mean peak forced expiratory volume in 1 second (FEV1) increases over baseline and the proportion of patients attaining at least a 15% increase in the FEV1 (responders) were 31% and 90%, respectively, for ipratropium and 17% and 50%, respectively, for theophylline. The average FEV1 increases during the 6-hour observation period were 18% for ipratropium and 8% for theophylline. The mean duration of action was 3.8 hours with ipratropium and 2.4 hours with theophylline. While side effects were rare, those experienced after theophylline use did involve the cardiovascular and gastrointestinal systems. These results show that ipratropium is a more potent bronchodilator than oral theophylline in patients with chronic airflow obstruction.", "entity": "Ipratropium", "aliases": "(endo,syn)-(+-)-3-(3-Hydroxy-1-oxo-2-phenylpropoxy)-8-methyl-8-(1-methylethyl)-8-azoniabicyclo(3.2.1)octane Anhydrous Ipratropium Bromide Atrovent Monohydrate (endo,anti)-Isomer (exo,syn)-Isomer endo-Isomer Itrop N Isopropylatropine N-Isopropylatropine Sch 1000 1178 Sch-1000 Sch-1178 Sch1000 Sch1178", "definition": "A muscarinic antagonist structurally related to ATROPINE but often considered safer and more effective for inhalation use. It is used for various bronchial disorders, in rhinitis, and as an antiarrhythmic.\n    ", "id": "MESH:D009241"}
{"mention": "gastrointestinal systems", "mention_text": "The bronchodilator effects of a single dose of ipratropium bromide aerosol (36 micrograms) and short-acting theophylline tablets (dose titrated to produce serum levels of 10-20 micrograms/mL) were compared in a double-blind, placebo-controlled crossover study in 21 patients with stable, chronic obstructive pulmonary disease. Mean peak forced expiratory volume in 1 second (FEV1) increases over baseline and the proportion of patients attaining at least a 15% increase in the FEV1 (responders) were 31% and 90%, respectively, for ipratropium and 17% and 50%, respectively, for theophylline. The average FEV1 increases during the 6-hour observation period were 18% for ipratropium and 8% for theophylline. The mean duration of action was 3.8 hours with ipratropium and 2.4 hours with theophylline. While side effects were rare, those experienced after theophylline use did involve the cardiovascular and gastrointestinal systems. These results show that ipratropium is a more potent bronchodilator than oral theophylline in patients with chronic airflow obstruction.", "entity": "Gastrointestinal Diseases", "aliases": "Cholera Infantum Disease Gastrointestinal Diseases Disorder Functional Disorders", "definition": "Diseases in any segment of the GASTROINTESTINAL TRACT from ESOPHAGUS to RECTUM.\n    ", "id": "MESH:D005767"}
{"mention": "chronic airflow obstruction", "mention_text": "The bronchodilator effects of a single dose of ipratropium bromide aerosol (36 micrograms) and short-acting theophylline tablets (dose titrated to produce serum levels of 10-20 micrograms/mL) were compared in a double-blind, placebo-controlled crossover study in 21 patients with stable, chronic obstructive pulmonary disease. Mean peak forced expiratory volume in 1 second (FEV1) increases over baseline and the proportion of patients attaining at least a 15% increase in the FEV1 (responders) were 31% and 90%, respectively, for ipratropium and 17% and 50%, respectively, for theophylline. The average FEV1 increases during the 6-hour observation period were 18% for ipratropium and 8% for theophylline. The mean duration of action was 3.8 hours with ipratropium and 2.4 hours with theophylline. While side effects were rare, those experienced after theophylline use did involve the cardiovascular and gastrointestinal systems. These results show that ipratropium is a more potent bronchodilator than oral theophylline in patients with chronic airflow obstruction.", "entity": "Pulmonary Disease, Chronic Obstructive", "aliases": "Airflow Obstruction Chronic Obstructions COAD COPD Obstructive Airway Disease Lung Pulmonary", "definition": "A disease of chronic diffuse irreversible airflow obstruction. Subcategories of COPD include CHRONIC BRONCHITIS and PULMONARY EMPHYSEMA.\n    ", "id": "MESH:D029424"}
{"mention": "nephropathy", "mention_text": "Irreversible damage to the medullary interstitium in experimental analgesic nephropathy in F344 rats.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "Renal papillary necrosis", "mention_text": "Renal papillary necrosis (RPN) and a decreased urinary concentrating ability developed during continuous long-term treatment with aspirin and paracetamol in female Fischer 344 rats. Renal structure and concentrating ability were examined after a recovery period of up to 18 weeks, when no analgesics were given, to investigate whether the analgesic-induced changes were reversible. There was no evidence of repair to the damaged medullary interstitial matrix, or proliferation of remaining undamaged type 1 medullary interstitial cells after the recovery period following analgesic treatment. The recovery of urinary concentrating ability was related to the length of analgesic treatment and the extent of the resulting inner medullary structural damage. During the early stages of analgesic treatment, the changes in urinary concentrating ability were reversible, but after prolonged analgesic treatment, maximum urinary concentrating ability failed to recover. This study shows that prolonged analgesic treatment in Fischer 344 rats causes progressive and irreversible damage to the interstitial matrix and type 1 interstitial cells leading to RPN. The associated urinary concentrating defect is reversible only during the early stages of structural damage to the inner medulla.", "entity": "Kidney Papillary Necrosis", "aliases": "Kidney Papillary Necrosis Renal Medullary Necrotizing Papillitides Papillitis", "definition": "A complication of kidney diseases characterized by cell death involving KIDNEY PAPILLA in the KIDNEY MEDULLA. Damages to this area may hinder the kidney to concentrate urine resulting in POLYURIA. Sloughed off necrotic tissue may block KIDNEY PELVIS or URETER. Necrosis of multiple renal papillae can lead to KIDNEY FAILURE.\n    ", "id": "MESH:D007681"}
{"mention": "RPN", "mention_text": "Renal papillary necrosis (RPN) and a decreased urinary concentrating ability developed during continuous long-term treatment with aspirin and paracetamol in female Fischer 344 rats. Renal structure and concentrating ability were examined after a recovery period of up to 18 weeks, when no analgesics were given, to investigate whether the analgesic-induced changes were reversible. There was no evidence of repair to the damaged medullary interstitial matrix, or proliferation of remaining undamaged type 1 medullary interstitial cells after the recovery period following analgesic treatment. The recovery of urinary concentrating ability was related to the length of analgesic treatment and the extent of the resulting inner medullary structural damage. During the early stages of analgesic treatment, the changes in urinary concentrating ability were reversible, but after prolonged analgesic treatment, maximum urinary concentrating ability failed to recover. This study shows that prolonged analgesic treatment in Fischer 344 rats causes progressive and irreversible damage to the interstitial matrix and type 1 interstitial cells leading to RPN. The associated urinary concentrating defect is reversible only during the early stages of structural damage to the inner medulla.", "entity": "Kidney Papillary Necrosis", "aliases": "Kidney Papillary Necrosis Renal Medullary Necrotizing Papillitides Papillitis", "definition": "A complication of kidney diseases characterized by cell death involving KIDNEY PAPILLA in the KIDNEY MEDULLA. Damages to this area may hinder the kidney to concentrate urine resulting in POLYURIA. Sloughed off necrotic tissue may block KIDNEY PELVIS or URETER. Necrosis of multiple renal papillae can lead to KIDNEY FAILURE.\n    ", "id": "MESH:D007681"}
{"mention": "aspirin", "mention_text": "Renal papillary necrosis (RPN) and a decreased urinary concentrating ability developed during continuous long-term treatment with aspirin and paracetamol in female Fischer 344 rats. Renal structure and concentrating ability were examined after a recovery period of up to 18 weeks, when no analgesics were given, to investigate whether the analgesic-induced changes were reversible. There was no evidence of repair to the damaged medullary interstitial matrix, or proliferation of remaining undamaged type 1 medullary interstitial cells after the recovery period following analgesic treatment. The recovery of urinary concentrating ability was related to the length of analgesic treatment and the extent of the resulting inner medullary structural damage. During the early stages of analgesic treatment, the changes in urinary concentrating ability were reversible, but after prolonged analgesic treatment, maximum urinary concentrating ability failed to recover. This study shows that prolonged analgesic treatment in Fischer 344 rats causes progressive and irreversible damage to the interstitial matrix and type 1 interstitial cells leading to RPN. The associated urinary concentrating defect is reversible only during the early stages of structural damage to the inner medulla.", "entity": "Aspirin", "aliases": "2-(Acetyloxy)benzoic Acid Acetylsalicylic Acetysal Acylpyrin Aloxiprimum Aspirin Colfarit Dispril Easprin Ecotrin Endosprin Magnecyl Micristin Polopirin Polopiryna Solprin Solupsan Zorprin", "definition": "The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)\n    ", "id": "MESH:D001241"}
{"mention": "paracetamol", "mention_text": "Renal papillary necrosis (RPN) and a decreased urinary concentrating ability developed during continuous long-term treatment with aspirin and paracetamol in female Fischer 344 rats. Renal structure and concentrating ability were examined after a recovery period of up to 18 weeks, when no analgesics were given, to investigate whether the analgesic-induced changes were reversible. There was no evidence of repair to the damaged medullary interstitial matrix, or proliferation of remaining undamaged type 1 medullary interstitial cells after the recovery period following analgesic treatment. The recovery of urinary concentrating ability was related to the length of analgesic treatment and the extent of the resulting inner medullary structural damage. During the early stages of analgesic treatment, the changes in urinary concentrating ability were reversible, but after prolonged analgesic treatment, maximum urinary concentrating ability failed to recover. This study shows that prolonged analgesic treatment in Fischer 344 rats causes progressive and irreversible damage to the interstitial matrix and type 1 interstitial cells leading to RPN. The associated urinary concentrating defect is reversible only during the early stages of structural damage to the inner medulla.", "entity": "Acetaminophen", "aliases": "APAP Acamol Acephen Acetaco Acetamidophenol Acetaminophen Acetominophen Algotropyl Anacin 3 Anacin-3 Anacin3 Datril Hydroxyacetanilide N-(4-Hydroxyphenyl)acetanilide N-Acetyl-p-aminophenol Panadol Paracetamol Tylenol p-Acetamidophenol p-Hydroxyacetanilide", "definition": "Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.\n    ", "id": "MESH:D000082"}
{"mention": "lithium", "mention_text": "Less frequent lithium administration and lower urine volume.", "entity": "Lithium", "aliases": "Lithium", "definition": "An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.\n    ", "id": "MESH:D008094"}
{"mention": "lithium", "mention_text": "OBJECTIVE: This study was designed to determine whether patients maintained on a regimen of lithium on a once-per-day schedule have lower urine volumes than do patients receiving multiple doses per day. METHOD: This was a cross-sectional study of 85 patients from a lithium clinic who received different dose schedules. Patients were admitted to the hospital for measurement of lithium level, creatinine clearance, urine volume, and maximum osmolality. RESULTS: Multiple daily doses of lithium were associated with higher urine volumes. The dosing schedule, duration of lithium treatment, and daily dose of lithium did not affect maximum osmolality or creatinine clearance. CONCLUSIONS: Urine volume can be reduced by giving lithium once daily and/or by lowering the total daily dose. Lithium-induced polyuria seems to be related to extrarenal as well as to renal effects.", "entity": "Lithium", "aliases": "Lithium", "definition": "An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.\n    ", "id": "MESH:D008094"}
{"mention": "creatinine", "mention_text": "OBJECTIVE: This study was designed to determine whether patients maintained on a regimen of lithium on a once-per-day schedule have lower urine volumes than do patients receiving multiple doses per day. METHOD: This was a cross-sectional study of 85 patients from a lithium clinic who received different dose schedules. Patients were admitted to the hospital for measurement of lithium level, creatinine clearance, urine volume, and maximum osmolality. RESULTS: Multiple daily doses of lithium were associated with higher urine volumes. The dosing schedule, duration of lithium treatment, and daily dose of lithium did not affect maximum osmolality or creatinine clearance. CONCLUSIONS: Urine volume can be reduced by giving lithium once daily and/or by lowering the total daily dose. Lithium-induced polyuria seems to be related to extrarenal as well as to renal effects.", "entity": "Creatinine", "aliases": "Creatinine Sulfate Salt Krebiozen", "definition": "", "id": "MESH:D003404"}
{"mention": "Lithium", "mention_text": "OBJECTIVE: This study was designed to determine whether patients maintained on a regimen of lithium on a once-per-day schedule have lower urine volumes than do patients receiving multiple doses per day. METHOD: This was a cross-sectional study of 85 patients from a lithium clinic who received different dose schedules. Patients were admitted to the hospital for measurement of lithium level, creatinine clearance, urine volume, and maximum osmolality. RESULTS: Multiple daily doses of lithium were associated with higher urine volumes. The dosing schedule, duration of lithium treatment, and daily dose of lithium did not affect maximum osmolality or creatinine clearance. CONCLUSIONS: Urine volume can be reduced by giving lithium once daily and/or by lowering the total daily dose. Lithium-induced polyuria seems to be related to extrarenal as well as to renal effects.", "entity": "Lithium", "aliases": "Lithium", "definition": "An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.\n    ", "id": "MESH:D008094"}
{"mention": "polyuria", "mention_text": "OBJECTIVE: This study was designed to determine whether patients maintained on a regimen of lithium on a once-per-day schedule have lower urine volumes than do patients receiving multiple doses per day. METHOD: This was a cross-sectional study of 85 patients from a lithium clinic who received different dose schedules. Patients were admitted to the hospital for measurement of lithium level, creatinine clearance, urine volume, and maximum osmolality. RESULTS: Multiple daily doses of lithium were associated with higher urine volumes. The dosing schedule, duration of lithium treatment, and daily dose of lithium did not affect maximum osmolality or creatinine clearance. CONCLUSIONS: Urine volume can be reduced by giving lithium once daily and/or by lowering the total daily dose. Lithium-induced polyuria seems to be related to extrarenal as well as to renal effects.", "entity": "Polyuria", "aliases": "Polyuria Polyurias", "definition": "Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes (DIABETES MELLITUS; DIABETES INSIPIDUS).\n    ", "id": "MESH:D011141"}
{"mention": "adriamycin", "mention_text": "Effect of adriamycin combined with whole body hyperthermia on tumor and normal tissues.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "hyperthermia", "mention_text": "Effect of adriamycin combined with whole body hyperthermia on tumor and normal tissues.", "entity": "Fever", "aliases": "Fever Fevers Hyperthermia Hyperthermias Pyrexia Pyrexias", "definition": "An abnormal elevation of body temperature, usually as a result of a pathologic process.\n    ", "id": "MESH:D005334"}
{"mention": "tumor", "mention_text": "Effect of adriamycin combined with whole body hyperthermia on tumor and normal tissues.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "Adriamycin", "mention_text": "Thermal enhancement of Adriamycin-mediated antitumor activity and normal tissue toxicities by whole body hyperthermia were compared using a F344 rat model. Antitumor activity was studied using a tumor growth delay assay. Acute normal tissue toxicities (i.e., leukopenia and thrombocytopenia) and late normal tissue toxicities (i.e., myocardial and kidney injury) were evaluated by functional/physiological assays and by morphological techniques. Whole body hyperthermia (120 min at 41.5 degrees C) enhanced both Adriamycin-mediated antitumor activity and toxic side effects. The thermal enhancement ratio calculated for antitumor activity was 1.6. Thermal enhancement ratios estimated for \"acute\" hematological changes were 1.3, whereas those estimated for \"late\" damage (based on morphological cardiac and renal lesions) varied between 2.4 and 4.3. Thus, while whole body hyperthermia enhances Adriamycin-mediated antitumor effect, normal tissue toxicity is also increased, and the potential therapeutic gain of the combined modality treatment is eroded.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "toxicities", "mention_text": "Thermal enhancement of Adriamycin-mediated antitumor activity and normal tissue toxicities by whole body hyperthermia were compared using a F344 rat model. Antitumor activity was studied using a tumor growth delay assay. Acute normal tissue toxicities (i.e., leukopenia and thrombocytopenia) and late normal tissue toxicities (i.e., myocardial and kidney injury) were evaluated by functional/physiological assays and by morphological techniques. Whole body hyperthermia (120 min at 41.5 degrees C) enhanced both Adriamycin-mediated antitumor activity and toxic side effects. The thermal enhancement ratio calculated for antitumor activity was 1.6. Thermal enhancement ratios estimated for \"acute\" hematological changes were 1.3, whereas those estimated for \"late\" damage (based on morphological cardiac and renal lesions) varied between 2.4 and 4.3. Thus, while whole body hyperthermia enhances Adriamycin-mediated antitumor effect, normal tissue toxicity is also increased, and the potential therapeutic gain of the combined modality treatment is eroded.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "hyperthermia", "mention_text": "Thermal enhancement of Adriamycin-mediated antitumor activity and normal tissue toxicities by whole body hyperthermia were compared using a F344 rat model. Antitumor activity was studied using a tumor growth delay assay. Acute normal tissue toxicities (i.e., leukopenia and thrombocytopenia) and late normal tissue toxicities (i.e., myocardial and kidney injury) were evaluated by functional/physiological assays and by morphological techniques. Whole body hyperthermia (120 min at 41.5 degrees C) enhanced both Adriamycin-mediated antitumor activity and toxic side effects. The thermal enhancement ratio calculated for antitumor activity was 1.6. Thermal enhancement ratios estimated for \"acute\" hematological changes were 1.3, whereas those estimated for \"late\" damage (based on morphological cardiac and renal lesions) varied between 2.4 and 4.3. Thus, while whole body hyperthermia enhances Adriamycin-mediated antitumor effect, normal tissue toxicity is also increased, and the potential therapeutic gain of the combined modality treatment is eroded.", "entity": "Fever", "aliases": "Fever Fevers Hyperthermia Hyperthermias Pyrexia Pyrexias", "definition": "An abnormal elevation of body temperature, usually as a result of a pathologic process.\n    ", "id": "MESH:D005334"}
{"mention": "tumor", "mention_text": "Thermal enhancement of Adriamycin-mediated antitumor activity and normal tissue toxicities by whole body hyperthermia were compared using a F344 rat model. Antitumor activity was studied using a tumor growth delay assay. Acute normal tissue toxicities (i.e., leukopenia and thrombocytopenia) and late normal tissue toxicities (i.e., myocardial and kidney injury) were evaluated by functional/physiological assays and by morphological techniques. Whole body hyperthermia (120 min at 41.5 degrees C) enhanced both Adriamycin-mediated antitumor activity and toxic side effects. The thermal enhancement ratio calculated for antitumor activity was 1.6. Thermal enhancement ratios estimated for \"acute\" hematological changes were 1.3, whereas those estimated for \"late\" damage (based on morphological cardiac and renal lesions) varied between 2.4 and 4.3. Thus, while whole body hyperthermia enhances Adriamycin-mediated antitumor effect, normal tissue toxicity is also increased, and the potential therapeutic gain of the combined modality treatment is eroded.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "leukopenia", "mention_text": "Thermal enhancement of Adriamycin-mediated antitumor activity and normal tissue toxicities by whole body hyperthermia were compared using a F344 rat model. Antitumor activity was studied using a tumor growth delay assay. Acute normal tissue toxicities (i.e., leukopenia and thrombocytopenia) and late normal tissue toxicities (i.e., myocardial and kidney injury) were evaluated by functional/physiological assays and by morphological techniques. Whole body hyperthermia (120 min at 41.5 degrees C) enhanced both Adriamycin-mediated antitumor activity and toxic side effects. The thermal enhancement ratio calculated for antitumor activity was 1.6. Thermal enhancement ratios estimated for \"acute\" hematological changes were 1.3, whereas those estimated for \"late\" damage (based on morphological cardiac and renal lesions) varied between 2.4 and 4.3. Thus, while whole body hyperthermia enhances Adriamycin-mediated antitumor effect, normal tissue toxicity is also increased, and the potential therapeutic gain of the combined modality treatment is eroded.", "entity": "Leukopenia", "aliases": "Leukocytopenia Leukocytopenias Leukopenia Leukopenias", "definition": "", "id": "MESH:D007970"}
{"mention": "thrombocytopenia", "mention_text": "Thermal enhancement of Adriamycin-mediated antitumor activity and normal tissue toxicities by whole body hyperthermia were compared using a F344 rat model. Antitumor activity was studied using a tumor growth delay assay. Acute normal tissue toxicities (i.e., leukopenia and thrombocytopenia) and late normal tissue toxicities (i.e., myocardial and kidney injury) were evaluated by functional/physiological assays and by morphological techniques. Whole body hyperthermia (120 min at 41.5 degrees C) enhanced both Adriamycin-mediated antitumor activity and toxic side effects. The thermal enhancement ratio calculated for antitumor activity was 1.6. Thermal enhancement ratios estimated for \"acute\" hematological changes were 1.3, whereas those estimated for \"late\" damage (based on morphological cardiac and renal lesions) varied between 2.4 and 4.3. Thus, while whole body hyperthermia enhances Adriamycin-mediated antitumor effect, normal tissue toxicity is also increased, and the potential therapeutic gain of the combined modality treatment is eroded.", "entity": "Thrombocytopenia", "aliases": "Thrombocytopenia Thrombocytopenias Thrombopenia Thrombopenias", "definition": "A subnormal level of BLOOD PLATELETS.\n    ", "id": "MESH:D013921"}
{"mention": "kidney injury", "mention_text": "Thermal enhancement of Adriamycin-mediated antitumor activity and normal tissue toxicities by whole body hyperthermia were compared using a F344 rat model. Antitumor activity was studied using a tumor growth delay assay. Acute normal tissue toxicities (i.e., leukopenia and thrombocytopenia) and late normal tissue toxicities (i.e., myocardial and kidney injury) were evaluated by functional/physiological assays and by morphological techniques. Whole body hyperthermia (120 min at 41.5 degrees C) enhanced both Adriamycin-mediated antitumor activity and toxic side effects. The thermal enhancement ratio calculated for antitumor activity was 1.6. Thermal enhancement ratios estimated for \"acute\" hematological changes were 1.3, whereas those estimated for \"late\" damage (based on morphological cardiac and renal lesions) varied between 2.4 and 4.3. Thus, while whole body hyperthermia enhances Adriamycin-mediated antitumor effect, normal tissue toxicity is also increased, and the potential therapeutic gain of the combined modality treatment is eroded.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "renal lesions", "mention_text": "Thermal enhancement of Adriamycin-mediated antitumor activity and normal tissue toxicities by whole body hyperthermia were compared using a F344 rat model. Antitumor activity was studied using a tumor growth delay assay. Acute normal tissue toxicities (i.e., leukopenia and thrombocytopenia) and late normal tissue toxicities (i.e., myocardial and kidney injury) were evaluated by functional/physiological assays and by morphological techniques. Whole body hyperthermia (120 min at 41.5 degrees C) enhanced both Adriamycin-mediated antitumor activity and toxic side effects. The thermal enhancement ratio calculated for antitumor activity was 1.6. Thermal enhancement ratios estimated for \"acute\" hematological changes were 1.3, whereas those estimated for \"late\" damage (based on morphological cardiac and renal lesions) varied between 2.4 and 4.3. Thus, while whole body hyperthermia enhances Adriamycin-mediated antitumor effect, normal tissue toxicity is also increased, and the potential therapeutic gain of the combined modality treatment is eroded.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "toxicity", "mention_text": "Thermal enhancement of Adriamycin-mediated antitumor activity and normal tissue toxicities by whole body hyperthermia were compared using a F344 rat model. Antitumor activity was studied using a tumor growth delay assay. Acute normal tissue toxicities (i.e., leukopenia and thrombocytopenia) and late normal tissue toxicities (i.e., myocardial and kidney injury) were evaluated by functional/physiological assays and by morphological techniques. Whole body hyperthermia (120 min at 41.5 degrees C) enhanced both Adriamycin-mediated antitumor activity and toxic side effects. The thermal enhancement ratio calculated for antitumor activity was 1.6. Thermal enhancement ratios estimated for \"acute\" hematological changes were 1.3, whereas those estimated for \"late\" damage (based on morphological cardiac and renal lesions) varied between 2.4 and 4.3. Thus, while whole body hyperthermia enhances Adriamycin-mediated antitumor effect, normal tissue toxicity is also increased, and the potential therapeutic gain of the combined modality treatment is eroded.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "Prazosin", "mention_text": "Prazosin-induced stress incontinence.", "entity": "Prazosin", "aliases": "Douglas Brand of Prazosin Hydrochloride Furazosin HCL Minipress Pfizer Pratsiol", "definition": "A selective adrenergic alpha-1 antagonist used in the treatment of HEART FAILURE; HYPERTENSION; PHEOCHROMOCYTOMA; RAYNAUD DISEASE; PROSTATIC HYPERTROPHY; and URINARY RETENTION.\n    ", "id": "MESH:D011224"}
{"mention": "stress incontinence", "mention_text": "Prazosin-induced stress incontinence.", "entity": "Urinary Incontinence, Stress", "aliases": "Incontinence Urinary Stress", "definition": "Involuntary discharge of URINE as a result of physical activities that increase abdominal pressure on the URINARY BLADDER without detrusor contraction or overdistended bladder. The subtypes are classified by the degree of leakage, descent and opening of the bladder neck and URETHRA without bladder contraction, and sphincter deficiency.\n    ", "id": "MESH:D014550"}
{"mention": "stress incontinence", "mention_text": "A case of genuine stress incontinence due to prazosin, a common antihypertensive drug, is presented. Prazosin exerts its antihypertensive effects through vasodilatation caused by selective blockade of postsynaptic alpha-1 adrenergic receptors. As an alpha-blocker, it also exerts a significant relaxant effect on the bladder neck and urethra. The patient's clinical course is described and correlated with initial urodynamic studies while on prazosin and subsequent studies while taking verapamil. Her incontinence resolved with the change of medication. The restoration of continence was accompanied by a substantial rise in maximum urethral pressure, maximum urethral closure pressure, and functional urethral length. Patients who present with stress incontinence while taking prazosin should change their antihypertensive medication before considering surgery, because their incontinence may resolve spontaneously with a change in drug therapy.", "entity": "Urinary Incontinence, Stress", "aliases": "Incontinence Urinary Stress", "definition": "Involuntary discharge of URINE as a result of physical activities that increase abdominal pressure on the URINARY BLADDER without detrusor contraction or overdistended bladder. The subtypes are classified by the degree of leakage, descent and opening of the bladder neck and URETHRA without bladder contraction, and sphincter deficiency.\n    ", "id": "MESH:D014550"}
{"mention": "prazosin", "mention_text": "A case of genuine stress incontinence due to prazosin, a common antihypertensive drug, is presented. Prazosin exerts its antihypertensive effects through vasodilatation caused by selective blockade of postsynaptic alpha-1 adrenergic receptors. As an alpha-blocker, it also exerts a significant relaxant effect on the bladder neck and urethra. The patient's clinical course is described and correlated with initial urodynamic studies while on prazosin and subsequent studies while taking verapamil. Her incontinence resolved with the change of medication. The restoration of continence was accompanied by a substantial rise in maximum urethral pressure, maximum urethral closure pressure, and functional urethral length. Patients who present with stress incontinence while taking prazosin should change their antihypertensive medication before considering surgery, because their incontinence may resolve spontaneously with a change in drug therapy.", "entity": "Prazosin", "aliases": "Douglas Brand of Prazosin Hydrochloride Furazosin HCL Minipress Pfizer Pratsiol", "definition": "A selective adrenergic alpha-1 antagonist used in the treatment of HEART FAILURE; HYPERTENSION; PHEOCHROMOCYTOMA; RAYNAUD DISEASE; PROSTATIC HYPERTROPHY; and URINARY RETENTION.\n    ", "id": "MESH:D011224"}
{"mention": "Prazosin", "mention_text": "A case of genuine stress incontinence due to prazosin, a common antihypertensive drug, is presented. Prazosin exerts its antihypertensive effects through vasodilatation caused by selective blockade of postsynaptic alpha-1 adrenergic receptors. As an alpha-blocker, it also exerts a significant relaxant effect on the bladder neck and urethra. The patient's clinical course is described and correlated with initial urodynamic studies while on prazosin and subsequent studies while taking verapamil. Her incontinence resolved with the change of medication. The restoration of continence was accompanied by a substantial rise in maximum urethral pressure, maximum urethral closure pressure, and functional urethral length. Patients who present with stress incontinence while taking prazosin should change their antihypertensive medication before considering surgery, because their incontinence may resolve spontaneously with a change in drug therapy.", "entity": "Prazosin", "aliases": "Douglas Brand of Prazosin Hydrochloride Furazosin HCL Minipress Pfizer Pratsiol", "definition": "A selective adrenergic alpha-1 antagonist used in the treatment of HEART FAILURE; HYPERTENSION; PHEOCHROMOCYTOMA; RAYNAUD DISEASE; PROSTATIC HYPERTROPHY; and URINARY RETENTION.\n    ", "id": "MESH:D011224"}
{"mention": "verapamil", "mention_text": "A case of genuine stress incontinence due to prazosin, a common antihypertensive drug, is presented. Prazosin exerts its antihypertensive effects through vasodilatation caused by selective blockade of postsynaptic alpha-1 adrenergic receptors. As an alpha-blocker, it also exerts a significant relaxant effect on the bladder neck and urethra. The patient's clinical course is described and correlated with initial urodynamic studies while on prazosin and subsequent studies while taking verapamil. Her incontinence resolved with the change of medication. The restoration of continence was accompanied by a substantial rise in maximum urethral pressure, maximum urethral closure pressure, and functional urethral length. Patients who present with stress incontinence while taking prazosin should change their antihypertensive medication before considering surgery, because their incontinence may resolve spontaneously with a change in drug therapy.", "entity": "Verapamil", "aliases": "Calan Cordilox Dexverapamil Falicard Finoptin Hydrochloride Verapamil Iproveratril Isoptin Isoptine Izoptin Lekoptin Sandoz Brand of", "definition": "A calcium channel blocker that is a class IV anti-arrhythmia agent.\n    ", "id": "MESH:D014700"}
{"mention": "incontinence", "mention_text": "A case of genuine stress incontinence due to prazosin, a common antihypertensive drug, is presented. Prazosin exerts its antihypertensive effects through vasodilatation caused by selective blockade of postsynaptic alpha-1 adrenergic receptors. As an alpha-blocker, it also exerts a significant relaxant effect on the bladder neck and urethra. The patient's clinical course is described and correlated with initial urodynamic studies while on prazosin and subsequent studies while taking verapamil. Her incontinence resolved with the change of medication. The restoration of continence was accompanied by a substantial rise in maximum urethral pressure, maximum urethral closure pressure, and functional urethral length. Patients who present with stress incontinence while taking prazosin should change their antihypertensive medication before considering surgery, because their incontinence may resolve spontaneously with a change in drug therapy.", "entity": "Urinary Incontinence", "aliases": "Incontinence Urinary", "definition": "Involuntary loss of URINE, such as leaking of urine. It is a symptom of various underlying pathological processes. Major types of incontinence include URINARY URGE INCONTINENCE and URINARY STRESS INCONTINENCE.\n    ", "id": "MESH:D014549"}
{"mention": "Myocardial infarction", "mention_text": "Myocardial infarction following sublingual administration of isosorbide dinitrate.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "isosorbide dinitrate", "mention_text": "Myocardial infarction following sublingual administration of isosorbide dinitrate.", "entity": "Isosorbide Dinitrate", "aliases": "Cardonit 40 Dilatrate Dinitrate Isosorbide Iso Bid Iso-Bid IsoBid Isodinit Isoket Retard 120 Retard-120 Retard120 Isomak R Isordil Isotrate Nitrosorbide Sorbitrate Sorbonit", "definition": "A vasodilator used in the treatment of ANGINA PECTORIS. Its actions are similar to NITROGLYCERIN but with a slower onset of action.\n    ", "id": "MESH:D007548"}
{"mention": "necrosis", "mention_text": "A 78-year-old with healed septal necrosis suffered a recurrent myocardial infarction of the anterior wall following the administration of isosorbide dinitrate 5 mg sublingually. After detailing the course of events, we discuss the role of paradoxical coronary spasm and hypotension-mediated myocardial ischemia occurring downstream to significant coronary arterial stenosis in the pathophysiology of acute coronary insufficiency.", "entity": "Necrosis", "aliases": "Necroses Necrosis", "definition": "The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. Distinguish it from APOPTOSIS which is a normal, regulated cellular process.\n    ", "id": "MESH:D009336"}
{"mention": "myocardial infarction", "mention_text": "A 78-year-old with healed septal necrosis suffered a recurrent myocardial infarction of the anterior wall following the administration of isosorbide dinitrate 5 mg sublingually. After detailing the course of events, we discuss the role of paradoxical coronary spasm and hypotension-mediated myocardial ischemia occurring downstream to significant coronary arterial stenosis in the pathophysiology of acute coronary insufficiency.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "isosorbide dinitrate", "mention_text": "A 78-year-old with healed septal necrosis suffered a recurrent myocardial infarction of the anterior wall following the administration of isosorbide dinitrate 5 mg sublingually. After detailing the course of events, we discuss the role of paradoxical coronary spasm and hypotension-mediated myocardial ischemia occurring downstream to significant coronary arterial stenosis in the pathophysiology of acute coronary insufficiency.", "entity": "Isosorbide Dinitrate", "aliases": "Cardonit 40 Dilatrate Dinitrate Isosorbide Iso Bid Iso-Bid IsoBid Isodinit Isoket Retard 120 Retard-120 Retard120 Isomak R Isordil Isotrate Nitrosorbide Sorbitrate Sorbonit", "definition": "A vasodilator used in the treatment of ANGINA PECTORIS. Its actions are similar to NITROGLYCERIN but with a slower onset of action.\n    ", "id": "MESH:D007548"}
{"mention": "spasm", "mention_text": "A 78-year-old with healed septal necrosis suffered a recurrent myocardial infarction of the anterior wall following the administration of isosorbide dinitrate 5 mg sublingually. After detailing the course of events, we discuss the role of paradoxical coronary spasm and hypotension-mediated myocardial ischemia occurring downstream to significant coronary arterial stenosis in the pathophysiology of acute coronary insufficiency.", "entity": "Spasm", "aliases": "Ciliary Body Spasm Spasms Generalized Muscle Muscular", "definition": "An involuntary contraction of a muscle or group of muscles. Spasms may involve SKELETAL MUSCLE or SMOOTH MUSCLE.\n    ", "id": "MESH:D013035"}
{"mention": "hypotension", "mention_text": "A 78-year-old with healed septal necrosis suffered a recurrent myocardial infarction of the anterior wall following the administration of isosorbide dinitrate 5 mg sublingually. After detailing the course of events, we discuss the role of paradoxical coronary spasm and hypotension-mediated myocardial ischemia occurring downstream to significant coronary arterial stenosis in the pathophysiology of acute coronary insufficiency.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "myocardial ischemia", "mention_text": "A 78-year-old with healed septal necrosis suffered a recurrent myocardial infarction of the anterior wall following the administration of isosorbide dinitrate 5 mg sublingually. After detailing the course of events, we discuss the role of paradoxical coronary spasm and hypotension-mediated myocardial ischemia occurring downstream to significant coronary arterial stenosis in the pathophysiology of acute coronary insufficiency.", "entity": "Myocardial Ischemia", "aliases": "Disease Ischemic Heart Diseases Ischemia Myocardial Ischemias", "definition": "A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).\n    ", "id": "MESH:D017202"}
{"mention": "coronary arterial stenosis", "mention_text": "A 78-year-old with healed septal necrosis suffered a recurrent myocardial infarction of the anterior wall following the administration of isosorbide dinitrate 5 mg sublingually. After detailing the course of events, we discuss the role of paradoxical coronary spasm and hypotension-mediated myocardial ischemia occurring downstream to significant coronary arterial stenosis in the pathophysiology of acute coronary insufficiency.", "entity": "Coronary Stenosis", "aliases": "Artery Stenoses Coronary Stenosis", "definition": "Narrowing or constriction of a coronary artery.\n    ", "id": "MESH:D023921"}
{"mention": "acute coronary insufficiency", "mention_text": "A 78-year-old with healed septal necrosis suffered a recurrent myocardial infarction of the anterior wall following the administration of isosorbide dinitrate 5 mg sublingually. After detailing the course of events, we discuss the role of paradoxical coronary spasm and hypotension-mediated myocardial ischemia occurring downstream to significant coronary arterial stenosis in the pathophysiology of acute coronary insufficiency.", "entity": "Acute Coronary Syndrome", "aliases": "Acute Coronary Syndrome Syndromes", "definition": "An episode of MYOCARDIAL ISCHEMIA that generally lasts longer than a transient anginal episode that ultimately may lead to MYOCARDIAL INFARCTION.\n    ", "id": "MESH:D054058"}
{"mention": "Fluoxetine", "mention_text": "Fluoxetine-induced akathisia: clinical and theoretical implications.", "entity": "Fluoxetine", "aliases": "Fluoxetin Fluoxetine Hydrochloride Lilly 110140 Lilly-110140 Lilly110140 N-Methyl-gamma-(4-(trifluoromethyl)phenoxy)benzenepropanamine Prozac Sarafem", "definition": "The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants.\n    ", "id": "MESH:D005473"}
{"mention": "akathisia", "mention_text": "Fluoxetine-induced akathisia: clinical and theoretical implications.", "entity": "Akathisia, Drug-Induced", "aliases": "Acathisia Drug Induced Drug-Induced Akathisia Tardive Pseudoakathisia", "definition": "A condition associated with the use of certain medications and characterized by an internal sense of motor restlessness often described as an inability to resist the urge to move.\n    ", "id": "MESH:D017109"}
{"mention": "fluoxetine", "mention_text": "Five patients receiving fluoxetine for the treatment of obsessive compulsive disorder or major depression developed akathisia. The typical fluoxetine-induced symptoms of restlessness, constant pacing, purposeless movements of the feet and legs, and marked anxiety were indistinguishable from those of neuroleptic-induced akathisia. Three patients who had experienced neuroleptic-induced akathisia in the past reported that the symptoms of fluoxetine-induced akathisia were identical, although somewhat milder. Akathisia appeared to be a common side effect of fluoxetine and generally responded well to treatment with the beta-adrenergic antagonist propranolol, dose reduction, or both. The authors suggest that fluoxetine-induced akathisia may be caused by serotonergically mediated inhibition of dopaminergic neurotransmission and that the pathophysiology of fluoxetine-induced akathisia and tricyclic antidepressant-induced \"jitteriness\" may be identical.", "entity": "Fluoxetine", "aliases": "Fluoxetin Fluoxetine Hydrochloride Lilly 110140 Lilly-110140 Lilly110140 N-Methyl-gamma-(4-(trifluoromethyl)phenoxy)benzenepropanamine Prozac Sarafem", "definition": "The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants.\n    ", "id": "MESH:D005473"}
{"mention": "obsessive compulsive disorder", "mention_text": "Five patients receiving fluoxetine for the treatment of obsessive compulsive disorder or major depression developed akathisia. The typical fluoxetine-induced symptoms of restlessness, constant pacing, purposeless movements of the feet and legs, and marked anxiety were indistinguishable from those of neuroleptic-induced akathisia. Three patients who had experienced neuroleptic-induced akathisia in the past reported that the symptoms of fluoxetine-induced akathisia were identical, although somewhat milder. Akathisia appeared to be a common side effect of fluoxetine and generally responded well to treatment with the beta-adrenergic antagonist propranolol, dose reduction, or both. The authors suggest that fluoxetine-induced akathisia may be caused by serotonergically mediated inhibition of dopaminergic neurotransmission and that the pathophysiology of fluoxetine-induced akathisia and tricyclic antidepressant-induced \"jitteriness\" may be identical.", "entity": "Obsessive-Compulsive Disorder", "aliases": "Anankastic Personalities Personality Disorder Obsessive-Compulsive Disorders Neuroses Neurosis Obsessive Compulsive", "definition": "An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which the individual does not derive pleasure although it may provide a release from tension.\n    ", "id": "MESH:D009771"}
{"mention": "major depression", "mention_text": "Five patients receiving fluoxetine for the treatment of obsessive compulsive disorder or major depression developed akathisia. The typical fluoxetine-induced symptoms of restlessness, constant pacing, purposeless movements of the feet and legs, and marked anxiety were indistinguishable from those of neuroleptic-induced akathisia. Three patients who had experienced neuroleptic-induced akathisia in the past reported that the symptoms of fluoxetine-induced akathisia were identical, although somewhat milder. Akathisia appeared to be a common side effect of fluoxetine and generally responded well to treatment with the beta-adrenergic antagonist propranolol, dose reduction, or both. The authors suggest that fluoxetine-induced akathisia may be caused by serotonergically mediated inhibition of dopaminergic neurotransmission and that the pathophysiology of fluoxetine-induced akathisia and tricyclic antidepressant-induced \"jitteriness\" may be identical.", "entity": "Depressive Disorder, Major", "aliases": "Depression Involutional Depressive Disorder Major Disorders Melancholia Psychoses Psychosis Paraphrenia", "definition": "Marked depression appearing in the involution period and characterized by hallucinations, delusions, paranoia, and agitation.\n    ", "id": "MESH:D003865"}
{"mention": "akathisia", "mention_text": "Five patients receiving fluoxetine for the treatment of obsessive compulsive disorder or major depression developed akathisia. The typical fluoxetine-induced symptoms of restlessness, constant pacing, purposeless movements of the feet and legs, and marked anxiety were indistinguishable from those of neuroleptic-induced akathisia. Three patients who had experienced neuroleptic-induced akathisia in the past reported that the symptoms of fluoxetine-induced akathisia were identical, although somewhat milder. Akathisia appeared to be a common side effect of fluoxetine and generally responded well to treatment with the beta-adrenergic antagonist propranolol, dose reduction, or both. The authors suggest that fluoxetine-induced akathisia may be caused by serotonergically mediated inhibition of dopaminergic neurotransmission and that the pathophysiology of fluoxetine-induced akathisia and tricyclic antidepressant-induced \"jitteriness\" may be identical.", "entity": "Akathisia, Drug-Induced", "aliases": "Acathisia Drug Induced Drug-Induced Akathisia Tardive Pseudoakathisia", "definition": "A condition associated with the use of certain medications and characterized by an internal sense of motor restlessness often described as an inability to resist the urge to move.\n    ", "id": "MESH:D017109"}
{"mention": "anxiety", "mention_text": "Five patients receiving fluoxetine for the treatment of obsessive compulsive disorder or major depression developed akathisia. The typical fluoxetine-induced symptoms of restlessness, constant pacing, purposeless movements of the feet and legs, and marked anxiety were indistinguishable from those of neuroleptic-induced akathisia. Three patients who had experienced neuroleptic-induced akathisia in the past reported that the symptoms of fluoxetine-induced akathisia were identical, although somewhat milder. Akathisia appeared to be a common side effect of fluoxetine and generally responded well to treatment with the beta-adrenergic antagonist propranolol, dose reduction, or both. The authors suggest that fluoxetine-induced akathisia may be caused by serotonergically mediated inhibition of dopaminergic neurotransmission and that the pathophysiology of fluoxetine-induced akathisia and tricyclic antidepressant-induced \"jitteriness\" may be identical.", "entity": "Anxiety Disorders", "aliases": "Anxiety Disorder Disorders Neuroses State Neurotic States", "definition": "Persistent and disabling ANXIETY.\n    ", "id": "MESH:D001008"}
{"mention": "Akathisia", "mention_text": "Five patients receiving fluoxetine for the treatment of obsessive compulsive disorder or major depression developed akathisia. The typical fluoxetine-induced symptoms of restlessness, constant pacing, purposeless movements of the feet and legs, and marked anxiety were indistinguishable from those of neuroleptic-induced akathisia. Three patients who had experienced neuroleptic-induced akathisia in the past reported that the symptoms of fluoxetine-induced akathisia were identical, although somewhat milder. Akathisia appeared to be a common side effect of fluoxetine and generally responded well to treatment with the beta-adrenergic antagonist propranolol, dose reduction, or both. The authors suggest that fluoxetine-induced akathisia may be caused by serotonergically mediated inhibition of dopaminergic neurotransmission and that the pathophysiology of fluoxetine-induced akathisia and tricyclic antidepressant-induced \"jitteriness\" may be identical.", "entity": "Akathisia, Drug-Induced", "aliases": "Acathisia Drug Induced Drug-Induced Akathisia Tardive Pseudoakathisia", "definition": "A condition associated with the use of certain medications and characterized by an internal sense of motor restlessness often described as an inability to resist the urge to move.\n    ", "id": "MESH:D017109"}
{"mention": "propranolol", "mention_text": "Five patients receiving fluoxetine for the treatment of obsessive compulsive disorder or major depression developed akathisia. The typical fluoxetine-induced symptoms of restlessness, constant pacing, purposeless movements of the feet and legs, and marked anxiety were indistinguishable from those of neuroleptic-induced akathisia. Three patients who had experienced neuroleptic-induced akathisia in the past reported that the symptoms of fluoxetine-induced akathisia were identical, although somewhat milder. Akathisia appeared to be a common side effect of fluoxetine and generally responded well to treatment with the beta-adrenergic antagonist propranolol, dose reduction, or both. The authors suggest that fluoxetine-induced akathisia may be caused by serotonergically mediated inhibition of dopaminergic neurotransmission and that the pathophysiology of fluoxetine-induced akathisia and tricyclic antidepressant-induced \"jitteriness\" may be identical.", "entity": "Propranolol", "aliases": "AY 20694 AY-20694 AY20694 Anaprilin Anapriline Avlocardyl Betadren Dexpropranolol Dociton Hydrochloride Propranolol Inderal Obsidan Obzidan Propanolol Rexigen", "definition": "A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.\n    ", "id": "MESH:D011433"}
{"mention": "antidepressant", "mention_text": "Five patients receiving fluoxetine for the treatment of obsessive compulsive disorder or major depression developed akathisia. The typical fluoxetine-induced symptoms of restlessness, constant pacing, purposeless movements of the feet and legs, and marked anxiety were indistinguishable from those of neuroleptic-induced akathisia. Three patients who had experienced neuroleptic-induced akathisia in the past reported that the symptoms of fluoxetine-induced akathisia were identical, although somewhat milder. Akathisia appeared to be a common side effect of fluoxetine and generally responded well to treatment with the beta-adrenergic antagonist propranolol, dose reduction, or both. The authors suggest that fluoxetine-induced akathisia may be caused by serotonergically mediated inhibition of dopaminergic neurotransmission and that the pathophysiology of fluoxetine-induced akathisia and tricyclic antidepressant-induced \"jitteriness\" may be identical.", "entity": "Antidepressive Agents", "aliases": "Agents Antidepressive Antidepressant Drugs Antidepressants Thymoanaleptics Thymoleptics", "definition": "Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.\n    ", "id": "MESH:D000928"}
{"mention": "Chronic active hepatitis", "mention_text": "Chronic active hepatitis associated with diclofenac sodium therapy.", "entity": "Hepatitis, Chronic", "aliases": "Chronic Active Hepatitis Cryptogenic Persistent Hepatitides", "definition": "INFLAMMATION of the LIVER with ongoing hepatocellular injury for 6 months or more, characterized by NECROSIS of HEPATOCYTES and inflammatory cell (LEUKOCYTES) infiltration. Chronic hepatitis can be caused by viruses, medications, autoimmune diseases, and other unknown factors.\n    ", "id": "MESH:D006521"}
{"mention": "diclofenac sodium", "mention_text": "Chronic active hepatitis associated with diclofenac sodium therapy.", "entity": "Diclofenac", "aliases": "Dichlofenal Diclofenac Potassium Sodium Diclonate P Diclophenac Dicrofenac Feloran GP 45,840 GP-45,840 GP45,840 Novapirina Orthofen Orthophen Ortofen SR 38 SR-38 SR38 Voltaren Voltarol", "definition": "A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt.\n    ", "id": "MESH:D004008"}
{"mention": "Diclofenac sodium", "mention_text": "Diclofenac sodium (Voltarol, Geigy Pharmaceuticals) is a non-steroidal anti-inflammatory derivative of phenylacetic acid. Although generally well-tolerated, asymptomatic abnormalities of liver function have been recorded and, less commonly, severe hepatitis induced by diclofenac. The patient described developed chronic active hepatitis after six months therapy with diclofenac sodium which progressed despite the withdrawal of the drug, a finding not previously reported.", "entity": "Diclofenac", "aliases": "Dichlofenal Diclofenac Potassium Sodium Diclonate P Diclophenac Dicrofenac Feloran GP 45,840 GP-45,840 GP45,840 Novapirina Orthofen Orthophen Ortofen SR 38 SR-38 SR38 Voltaren Voltarol", "definition": "A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt.\n    ", "id": "MESH:D004008"}
{"mention": "Voltarol", "mention_text": "Diclofenac sodium (Voltarol, Geigy Pharmaceuticals) is a non-steroidal anti-inflammatory derivative of phenylacetic acid. Although generally well-tolerated, asymptomatic abnormalities of liver function have been recorded and, less commonly, severe hepatitis induced by diclofenac. The patient described developed chronic active hepatitis after six months therapy with diclofenac sodium which progressed despite the withdrawal of the drug, a finding not previously reported.", "entity": "Diclofenac", "aliases": "Dichlofenal Diclofenac Potassium Sodium Diclonate P Diclophenac Dicrofenac Feloran GP 45,840 GP-45,840 GP45,840 Novapirina Orthofen Orthophen Ortofen SR 38 SR-38 SR38 Voltaren Voltarol", "definition": "A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt.\n    ", "id": "MESH:D004008"}
{"mention": "phenylacetic acid", "mention_text": "Diclofenac sodium (Voltarol, Geigy Pharmaceuticals) is a non-steroidal anti-inflammatory derivative of phenylacetic acid. Although generally well-tolerated, asymptomatic abnormalities of liver function have been recorded and, less commonly, severe hepatitis induced by diclofenac. The patient described developed chronic active hepatitis after six months therapy with diclofenac sodium which progressed despite the withdrawal of the drug, a finding not previously reported.", "entity": "phenylacetic acid", "aliases": "phenylacetate phenylacetic acid ammonium salt calcium cesium lithium mercury potassium rubidium sodium carboxy-(11)C-labeled cpd", "definition": "", "id": "MESH:C025136"}
{"mention": "abnormalities of liver function", "mention_text": "Diclofenac sodium (Voltarol, Geigy Pharmaceuticals) is a non-steroidal anti-inflammatory derivative of phenylacetic acid. Although generally well-tolerated, asymptomatic abnormalities of liver function have been recorded and, less commonly, severe hepatitis induced by diclofenac. The patient described developed chronic active hepatitis after six months therapy with diclofenac sodium which progressed despite the withdrawal of the drug, a finding not previously reported.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "hepatitis", "mention_text": "Diclofenac sodium (Voltarol, Geigy Pharmaceuticals) is a non-steroidal anti-inflammatory derivative of phenylacetic acid. Although generally well-tolerated, asymptomatic abnormalities of liver function have been recorded and, less commonly, severe hepatitis induced by diclofenac. The patient described developed chronic active hepatitis after six months therapy with diclofenac sodium which progressed despite the withdrawal of the drug, a finding not previously reported.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "diclofenac", "mention_text": "Diclofenac sodium (Voltarol, Geigy Pharmaceuticals) is a non-steroidal anti-inflammatory derivative of phenylacetic acid. Although generally well-tolerated, asymptomatic abnormalities of liver function have been recorded and, less commonly, severe hepatitis induced by diclofenac. The patient described developed chronic active hepatitis after six months therapy with diclofenac sodium which progressed despite the withdrawal of the drug, a finding not previously reported.", "entity": "Diclofenac", "aliases": "Dichlofenal Diclofenac Potassium Sodium Diclonate P Diclophenac Dicrofenac Feloran GP 45,840 GP-45,840 GP45,840 Novapirina Orthofen Orthophen Ortofen SR 38 SR-38 SR38 Voltaren Voltarol", "definition": "A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt.\n    ", "id": "MESH:D004008"}
{"mention": "chronic active hepatitis", "mention_text": "Diclofenac sodium (Voltarol, Geigy Pharmaceuticals) is a non-steroidal anti-inflammatory derivative of phenylacetic acid. Although generally well-tolerated, asymptomatic abnormalities of liver function have been recorded and, less commonly, severe hepatitis induced by diclofenac. The patient described developed chronic active hepatitis after six months therapy with diclofenac sodium which progressed despite the withdrawal of the drug, a finding not previously reported.", "entity": "Hepatitis, Chronic", "aliases": "Chronic Active Hepatitis Cryptogenic Persistent Hepatitides", "definition": "INFLAMMATION of the LIVER with ongoing hepatocellular injury for 6 months or more, characterized by NECROSIS of HEPATOCYTES and inflammatory cell (LEUKOCYTES) infiltration. Chronic hepatitis can be caused by viruses, medications, autoimmune diseases, and other unknown factors.\n    ", "id": "MESH:D006521"}
{"mention": "diclofenac sodium", "mention_text": "Diclofenac sodium (Voltarol, Geigy Pharmaceuticals) is a non-steroidal anti-inflammatory derivative of phenylacetic acid. Although generally well-tolerated, asymptomatic abnormalities of liver function have been recorded and, less commonly, severe hepatitis induced by diclofenac. The patient described developed chronic active hepatitis after six months therapy with diclofenac sodium which progressed despite the withdrawal of the drug, a finding not previously reported.", "entity": "Diclofenac", "aliases": "Dichlofenal Diclofenac Potassium Sodium Diclonate P Diclophenac Dicrofenac Feloran GP 45,840 GP-45,840 GP45,840 Novapirina Orthofen Orthophen Ortofen SR 38 SR-38 SR38 Voltaren Voltarol", "definition": "A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt.\n    ", "id": "MESH:D004008"}
{"mention": "Stroke", "mention_text": "Stroke associated with cocaine use.", "entity": "Stroke", "aliases": "Acute Cerebrovascular Accident Accidents Stroke Strokes Apoplexy Brain Vascular CVA (Cerebrovascular Accident) CVAs Cerebral", "definition": "A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)\n    ", "id": "MESH:D020521"}
{"mention": "cocaine", "mention_text": "Stroke associated with cocaine use.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "cocaine", "mention_text": "We describe eight patients in whom cocaine use was related to stroke and review 39 cases from the literature. Among these 47 patients the mean (+/- SD) age was 32.5 +/- 12.1 years; 76% (34/45) were men. Stroke followed cocaine use by inhalation, intranasal, intravenous, and intramuscular routes. Intracranial aneurysms or arteriovenous malformations were present in 17 of 32 patients studied angiographically or at autopsy; cerebral vasculitis was present in two patients. Cerebral infarction occurred in 10 patients (22%), intracerebral hemorrhage in 22 (49%), and subarachnoid hemorrhage in 13 (29%). These data indicate that (1) the apparent incidence of stroke related to cocaine use is increasing; (2) cocaine-associated stroke occurs primarily in young adults; (3) stroke may follow any route of cocaine administration; (4) stroke after cocaine use is frequently associated with intracranial aneurysms and arteriovenous malformations; and (5) in cocaine-associated stroke, the frequency of intracranial hemorrhage exceeds that of cerebral infarction.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "stroke", "mention_text": "We describe eight patients in whom cocaine use was related to stroke and review 39 cases from the literature. Among these 47 patients the mean (+/- SD) age was 32.5 +/- 12.1 years; 76% (34/45) were men. Stroke followed cocaine use by inhalation, intranasal, intravenous, and intramuscular routes. Intracranial aneurysms or arteriovenous malformations were present in 17 of 32 patients studied angiographically or at autopsy; cerebral vasculitis was present in two patients. Cerebral infarction occurred in 10 patients (22%), intracerebral hemorrhage in 22 (49%), and subarachnoid hemorrhage in 13 (29%). These data indicate that (1) the apparent incidence of stroke related to cocaine use is increasing; (2) cocaine-associated stroke occurs primarily in young adults; (3) stroke may follow any route of cocaine administration; (4) stroke after cocaine use is frequently associated with intracranial aneurysms and arteriovenous malformations; and (5) in cocaine-associated stroke, the frequency of intracranial hemorrhage exceeds that of cerebral infarction.", "entity": "Stroke", "aliases": "Acute Cerebrovascular Accident Accidents Stroke Strokes Apoplexy Brain Vascular CVA (Cerebrovascular Accident) CVAs Cerebral", "definition": "A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)\n    ", "id": "MESH:D020521"}
{"mention": "Stroke", "mention_text": "We describe eight patients in whom cocaine use was related to stroke and review 39 cases from the literature. Among these 47 patients the mean (+/- SD) age was 32.5 +/- 12.1 years; 76% (34/45) were men. Stroke followed cocaine use by inhalation, intranasal, intravenous, and intramuscular routes. Intracranial aneurysms or arteriovenous malformations were present in 17 of 32 patients studied angiographically or at autopsy; cerebral vasculitis was present in two patients. Cerebral infarction occurred in 10 patients (22%), intracerebral hemorrhage in 22 (49%), and subarachnoid hemorrhage in 13 (29%). These data indicate that (1) the apparent incidence of stroke related to cocaine use is increasing; (2) cocaine-associated stroke occurs primarily in young adults; (3) stroke may follow any route of cocaine administration; (4) stroke after cocaine use is frequently associated with intracranial aneurysms and arteriovenous malformations; and (5) in cocaine-associated stroke, the frequency of intracranial hemorrhage exceeds that of cerebral infarction.", "entity": "Stroke", "aliases": "Acute Cerebrovascular Accident Accidents Stroke Strokes Apoplexy Brain Vascular CVA (Cerebrovascular Accident) CVAs Cerebral", "definition": "A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)\n    ", "id": "MESH:D020521"}
{"mention": "Intracranial aneurysms", "mention_text": "We describe eight patients in whom cocaine use was related to stroke and review 39 cases from the literature. Among these 47 patients the mean (+/- SD) age was 32.5 +/- 12.1 years; 76% (34/45) were men. Stroke followed cocaine use by inhalation, intranasal, intravenous, and intramuscular routes. Intracranial aneurysms or arteriovenous malformations were present in 17 of 32 patients studied angiographically or at autopsy; cerebral vasculitis was present in two patients. Cerebral infarction occurred in 10 patients (22%), intracerebral hemorrhage in 22 (49%), and subarachnoid hemorrhage in 13 (29%). These data indicate that (1) the apparent incidence of stroke related to cocaine use is increasing; (2) cocaine-associated stroke occurs primarily in young adults; (3) stroke may follow any route of cocaine administration; (4) stroke after cocaine use is frequently associated with intracranial aneurysms and arteriovenous malformations; and (5) in cocaine-associated stroke, the frequency of intracranial hemorrhage exceeds that of cerebral infarction.", "entity": "Intracranial Aneurysm", "aliases": "Aneurysm Anterior Cerebral Artery Communicating Basilar Berry Brain Giant Intracranial Mycotic Middle Posterior Aneurysms", "definition": "Abnormal outpouching in the wall of intracranial blood vessels. Most common are the saccular (berry) aneurysms located at branch points in CIRCLE OF WILLIS at the base of the brain. Vessel rupture results in SUBARACHNOID HEMORRHAGE or INTRACRANIAL HEMORRHAGES. Giant aneurysms (>2.5 cm in diameter) may compress adjacent structures, including the OCULOMOTOR NERVE. (From Adams et al., Principles of Neurology, 6th ed, p841)\n    ", "id": "MESH:D002532"}
{"mention": "arteriovenous malformations", "mention_text": "We describe eight patients in whom cocaine use was related to stroke and review 39 cases from the literature. Among these 47 patients the mean (+/- SD) age was 32.5 +/- 12.1 years; 76% (34/45) were men. Stroke followed cocaine use by inhalation, intranasal, intravenous, and intramuscular routes. Intracranial aneurysms or arteriovenous malformations were present in 17 of 32 patients studied angiographically or at autopsy; cerebral vasculitis was present in two patients. Cerebral infarction occurred in 10 patients (22%), intracerebral hemorrhage in 22 (49%), and subarachnoid hemorrhage in 13 (29%). These data indicate that (1) the apparent incidence of stroke related to cocaine use is increasing; (2) cocaine-associated stroke occurs primarily in young adults; (3) stroke may follow any route of cocaine administration; (4) stroke after cocaine use is frequently associated with intracranial aneurysms and arteriovenous malformations; and (5) in cocaine-associated stroke, the frequency of intracranial hemorrhage exceeds that of cerebral infarction.", "entity": "Arteriovenous Malformations", "aliases": "Arteriovenous Malformation Malformations", "definition": "Abnormal formation of blood vessels that shunt arterial blood directly into veins without passing through the CAPILLARIES. They usually are crooked, dilated, and with thick vessel walls. A common type is the congenital arteriovenous fistula. The lack of blood flow and oxygen in the capillaries can lead to tissue damage in the affected areas.\n    ", "id": "MESH:D001165"}
{"mention": "cerebral vasculitis", "mention_text": "We describe eight patients in whom cocaine use was related to stroke and review 39 cases from the literature. Among these 47 patients the mean (+/- SD) age was 32.5 +/- 12.1 years; 76% (34/45) were men. Stroke followed cocaine use by inhalation, intranasal, intravenous, and intramuscular routes. Intracranial aneurysms or arteriovenous malformations were present in 17 of 32 patients studied angiographically or at autopsy; cerebral vasculitis was present in two patients. Cerebral infarction occurred in 10 patients (22%), intracerebral hemorrhage in 22 (49%), and subarachnoid hemorrhage in 13 (29%). These data indicate that (1) the apparent incidence of stroke related to cocaine use is increasing; (2) cocaine-associated stroke occurs primarily in young adults; (3) stroke may follow any route of cocaine administration; (4) stroke after cocaine use is frequently associated with intracranial aneurysms and arteriovenous malformations; and (5) in cocaine-associated stroke, the frequency of intracranial hemorrhage exceeds that of cerebral infarction.", "entity": "Vasculitis, Central Nervous System", "aliases": "Angiitis Central Nervous System Cerebral Granulomatous Arteritis Postzoster CNS Vasculitis Primary Secondary", "definition": "Inflammation of blood vessels within the central nervous system. Primary vasculitis is usually caused by autoimmune or idiopathic factors, while secondary vasculitis is caused by existing disease process. Clinical manifestations are highly variable but include HEADACHE; SEIZURES; behavioral alterations; INTRACRANIAL HEMORRHAGES; TRANSIENT ISCHEMIC ATTACK; and BRAIN INFARCTION. (From Adams et al., Principles of Neurology, 6th ed, pp856-61)\n    ", "id": "MESH:D020293"}
{"mention": "Cerebral infarction", "mention_text": "We describe eight patients in whom cocaine use was related to stroke and review 39 cases from the literature. Among these 47 patients the mean (+/- SD) age was 32.5 +/- 12.1 years; 76% (34/45) were men. Stroke followed cocaine use by inhalation, intranasal, intravenous, and intramuscular routes. Intracranial aneurysms or arteriovenous malformations were present in 17 of 32 patients studied angiographically or at autopsy; cerebral vasculitis was present in two patients. Cerebral infarction occurred in 10 patients (22%), intracerebral hemorrhage in 22 (49%), and subarachnoid hemorrhage in 13 (29%). These data indicate that (1) the apparent incidence of stroke related to cocaine use is increasing; (2) cocaine-associated stroke occurs primarily in young adults; (3) stroke may follow any route of cocaine administration; (4) stroke after cocaine use is frequently associated with intracranial aneurysms and arteriovenous malformations; and (5) in cocaine-associated stroke, the frequency of intracranial hemorrhage exceeds that of cerebral infarction.", "entity": "Cerebral Infarction", "aliases": "Anterior Choroidal Artery Infarction Cerebral Left Hemisphere Right Infarctions Subcortical Posterior", "definition": "The formation of an area of NECROSIS in the CEREBRUM caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., INFARCTION, ANTERIOR CEREBRAL ARTERY), and etiology (e.g., embolic infarction).\n    ", "id": "MESH:D002544"}
{"mention": "intracerebral hemorrhage", "mention_text": "We describe eight patients in whom cocaine use was related to stroke and review 39 cases from the literature. Among these 47 patients the mean (+/- SD) age was 32.5 +/- 12.1 years; 76% (34/45) were men. Stroke followed cocaine use by inhalation, intranasal, intravenous, and intramuscular routes. Intracranial aneurysms or arteriovenous malformations were present in 17 of 32 patients studied angiographically or at autopsy; cerebral vasculitis was present in two patients. Cerebral infarction occurred in 10 patients (22%), intracerebral hemorrhage in 22 (49%), and subarachnoid hemorrhage in 13 (29%). These data indicate that (1) the apparent incidence of stroke related to cocaine use is increasing; (2) cocaine-associated stroke occurs primarily in young adults; (3) stroke may follow any route of cocaine administration; (4) stroke after cocaine use is frequently associated with intracranial aneurysms and arteriovenous malformations; and (5) in cocaine-associated stroke, the frequency of intracranial hemorrhage exceeds that of cerebral infarction.", "entity": "Cerebral Hemorrhage", "aliases": "Brain Hemorrhage Cerebral Hemorrhages Parenchymal Cerebrum Intracerebral", "definition": "Bleeding into one or both CEREBRAL HEMISPHERES including the BASAL GANGLIA and the CEREBRAL CORTEX. It is often associated with HYPERTENSION and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D002543"}
{"mention": "subarachnoid hemorrhage", "mention_text": "We describe eight patients in whom cocaine use was related to stroke and review 39 cases from the literature. Among these 47 patients the mean (+/- SD) age was 32.5 +/- 12.1 years; 76% (34/45) were men. Stroke followed cocaine use by inhalation, intranasal, intravenous, and intramuscular routes. Intracranial aneurysms or arteriovenous malformations were present in 17 of 32 patients studied angiographically or at autopsy; cerebral vasculitis was present in two patients. Cerebral infarction occurred in 10 patients (22%), intracerebral hemorrhage in 22 (49%), and subarachnoid hemorrhage in 13 (29%). These data indicate that (1) the apparent incidence of stroke related to cocaine use is increasing; (2) cocaine-associated stroke occurs primarily in young adults; (3) stroke may follow any route of cocaine administration; (4) stroke after cocaine use is frequently associated with intracranial aneurysms and arteriovenous malformations; and (5) in cocaine-associated stroke, the frequency of intracranial hemorrhage exceeds that of cerebral infarction.", "entity": "Subarachnoid Hemorrhage", "aliases": "Aneurysmal Subarachnoid Hemorrhage Hemorrhages Intracranial Perinatal Spontaneous SAH (Subarachnoid Hemorrhage) SAHs", "definition": "Bleeding into the intracranial or spinal SUBARACHNOID SPACE, most resulting from INTRACRANIAL ANEURYSM rupture. It can occur after traumatic injuries (SUBARACHNOID HEMORRHAGE, TRAUMATIC). Clinical features include HEADACHE; NAUSEA; VOMITING, nuchal rigidity, variable neurological deficits and reduced mental status.\n    ", "id": "MESH:D013345"}
{"mention": "intracranial aneurysms", "mention_text": "We describe eight patients in whom cocaine use was related to stroke and review 39 cases from the literature. Among these 47 patients the mean (+/- SD) age was 32.5 +/- 12.1 years; 76% (34/45) were men. Stroke followed cocaine use by inhalation, intranasal, intravenous, and intramuscular routes. Intracranial aneurysms or arteriovenous malformations were present in 17 of 32 patients studied angiographically or at autopsy; cerebral vasculitis was present in two patients. Cerebral infarction occurred in 10 patients (22%), intracerebral hemorrhage in 22 (49%), and subarachnoid hemorrhage in 13 (29%). These data indicate that (1) the apparent incidence of stroke related to cocaine use is increasing; (2) cocaine-associated stroke occurs primarily in young adults; (3) stroke may follow any route of cocaine administration; (4) stroke after cocaine use is frequently associated with intracranial aneurysms and arteriovenous malformations; and (5) in cocaine-associated stroke, the frequency of intracranial hemorrhage exceeds that of cerebral infarction.", "entity": "Intracranial Aneurysm", "aliases": "Aneurysm Anterior Cerebral Artery Communicating Basilar Berry Brain Giant Intracranial Mycotic Middle Posterior Aneurysms", "definition": "Abnormal outpouching in the wall of intracranial blood vessels. Most common are the saccular (berry) aneurysms located at branch points in CIRCLE OF WILLIS at the base of the brain. Vessel rupture results in SUBARACHNOID HEMORRHAGE or INTRACRANIAL HEMORRHAGES. Giant aneurysms (>2.5 cm in diameter) may compress adjacent structures, including the OCULOMOTOR NERVE. (From Adams et al., Principles of Neurology, 6th ed, p841)\n    ", "id": "MESH:D002532"}
{"mention": "intracranial hemorrhage", "mention_text": "We describe eight patients in whom cocaine use was related to stroke and review 39 cases from the literature. Among these 47 patients the mean (+/- SD) age was 32.5 +/- 12.1 years; 76% (34/45) were men. Stroke followed cocaine use by inhalation, intranasal, intravenous, and intramuscular routes. Intracranial aneurysms or arteriovenous malformations were present in 17 of 32 patients studied angiographically or at autopsy; cerebral vasculitis was present in two patients. Cerebral infarction occurred in 10 patients (22%), intracerebral hemorrhage in 22 (49%), and subarachnoid hemorrhage in 13 (29%). These data indicate that (1) the apparent incidence of stroke related to cocaine use is increasing; (2) cocaine-associated stroke occurs primarily in young adults; (3) stroke may follow any route of cocaine administration; (4) stroke after cocaine use is frequently associated with intracranial aneurysms and arteriovenous malformations; and (5) in cocaine-associated stroke, the frequency of intracranial hemorrhage exceeds that of cerebral infarction.", "entity": "Intracranial Hemorrhages", "aliases": "Brain Hemorrhage Hemorrhages Intracranial Posterior Fossa", "definition": "Bleeding within the SKULL, including hemorrhages in the brain and the three membranes of MENINGES. The escape of blood often leads to the formation of HEMATOMA in the cranial epidural, subdural, and subarachnoid spaces.\n    ", "id": "MESH:D020300"}
{"mention": "cerebral infarction", "mention_text": "We describe eight patients in whom cocaine use was related to stroke and review 39 cases from the literature. Among these 47 patients the mean (+/- SD) age was 32.5 +/- 12.1 years; 76% (34/45) were men. Stroke followed cocaine use by inhalation, intranasal, intravenous, and intramuscular routes. Intracranial aneurysms or arteriovenous malformations were present in 17 of 32 patients studied angiographically or at autopsy; cerebral vasculitis was present in two patients. Cerebral infarction occurred in 10 patients (22%), intracerebral hemorrhage in 22 (49%), and subarachnoid hemorrhage in 13 (29%). These data indicate that (1) the apparent incidence of stroke related to cocaine use is increasing; (2) cocaine-associated stroke occurs primarily in young adults; (3) stroke may follow any route of cocaine administration; (4) stroke after cocaine use is frequently associated with intracranial aneurysms and arteriovenous malformations; and (5) in cocaine-associated stroke, the frequency of intracranial hemorrhage exceeds that of cerebral infarction.", "entity": "Cerebral Infarction", "aliases": "Anterior Choroidal Artery Infarction Cerebral Left Hemisphere Right Infarctions Subcortical Posterior", "definition": "The formation of an area of NECROSIS in the CEREBRUM caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., INFARCTION, ANTERIOR CEREBRAL ARTERY), and etiology (e.g., embolic infarction).\n    ", "id": "MESH:D002544"}
{"mention": "Glyburide", "mention_text": "Glyburide-induced hepatitis.", "entity": "Glyburide", "aliases": "Daonil Diabeta Euglucon 5 N Glibenclamide Glybenclamide Glyburide HB 419 420 HB-419 HB-420 HB419 HB420 Maninil Micronase Neogluconin", "definition": "An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.\n    ", "id": "MESH:D005905"}
{"mention": "hepatitis", "mention_text": "Glyburide-induced hepatitis.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "hepatotoxicity", "mention_text": "Drug-induced hepatotoxicity, although common, has been reported only infrequently with sulfonylureas. For glyburide, a second-generation sulfonylurea, only two brief reports of hepatotoxicity exist. Two patients with type II diabetes mellitus developed an acute hepatitis-like syndrome soon after initiation of glyburide therapy. There was no serologic evidence of viral infection, and a liver biopsy sample showed a histologic pattern consistent with drug-induced hepatitis. Both patients recovered quickly after stopping glyburide therapy and have remained well for a follow-up period of 1 year. Glyburide can produce an acute hepatitis-like illness in some persons.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "sulfonylureas", "mention_text": "Drug-induced hepatotoxicity, although common, has been reported only infrequently with sulfonylureas. For glyburide, a second-generation sulfonylurea, only two brief reports of hepatotoxicity exist. Two patients with type II diabetes mellitus developed an acute hepatitis-like syndrome soon after initiation of glyburide therapy. There was no serologic evidence of viral infection, and a liver biopsy sample showed a histologic pattern consistent with drug-induced hepatitis. Both patients recovered quickly after stopping glyburide therapy and have remained well for a follow-up period of 1 year. Glyburide can produce an acute hepatitis-like illness in some persons.", "entity": "Sulfonylurea Compounds", "aliases": "Compounds Sulfonylurea", "definition": "", "id": "MESH:D013453"}
{"mention": "glyburide", "mention_text": "Drug-induced hepatotoxicity, although common, has been reported only infrequently with sulfonylureas. For glyburide, a second-generation sulfonylurea, only two brief reports of hepatotoxicity exist. Two patients with type II diabetes mellitus developed an acute hepatitis-like syndrome soon after initiation of glyburide therapy. There was no serologic evidence of viral infection, and a liver biopsy sample showed a histologic pattern consistent with drug-induced hepatitis. Both patients recovered quickly after stopping glyburide therapy and have remained well for a follow-up period of 1 year. Glyburide can produce an acute hepatitis-like illness in some persons.", "entity": "Glyburide", "aliases": "Daonil Diabeta Euglucon 5 N Glibenclamide Glybenclamide Glyburide HB 419 420 HB-419 HB-420 HB419 HB420 Maninil Micronase Neogluconin", "definition": "An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.\n    ", "id": "MESH:D005905"}
{"mention": "sulfonylurea", "mention_text": "Drug-induced hepatotoxicity, although common, has been reported only infrequently with sulfonylureas. For glyburide, a second-generation sulfonylurea, only two brief reports of hepatotoxicity exist. Two patients with type II diabetes mellitus developed an acute hepatitis-like syndrome soon after initiation of glyburide therapy. There was no serologic evidence of viral infection, and a liver biopsy sample showed a histologic pattern consistent with drug-induced hepatitis. Both patients recovered quickly after stopping glyburide therapy and have remained well for a follow-up period of 1 year. Glyburide can produce an acute hepatitis-like illness in some persons.", "entity": "Sulfonylurea Compounds", "aliases": "Compounds Sulfonylurea", "definition": "", "id": "MESH:D013453"}
{"mention": "type II diabetes mellitus", "mention_text": "Drug-induced hepatotoxicity, although common, has been reported only infrequently with sulfonylureas. For glyburide, a second-generation sulfonylurea, only two brief reports of hepatotoxicity exist. Two patients with type II diabetes mellitus developed an acute hepatitis-like syndrome soon after initiation of glyburide therapy. There was no serologic evidence of viral infection, and a liver biopsy sample showed a histologic pattern consistent with drug-induced hepatitis. Both patients recovered quickly after stopping glyburide therapy and have remained well for a follow-up period of 1 year. Glyburide can produce an acute hepatitis-like illness in some persons.", "entity": "Diabetes Mellitus, Type 2", "aliases": "Adult-Onset Diabetes Mellitus Adult Onset Ketosis Resistant Ketosis-Resistant Maturity Maturity-Onset Non Insulin Dependent Non-Insulin-Dependent Noninsulin Noninsulin-Dependent Slow Slow-Onset Stable Type 2 II MODY NIDDM", "definition": "A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.\n    ", "id": "MESH:D003924"}
{"mention": "acute hepatitis-like syndrome", "mention_text": "Drug-induced hepatotoxicity, although common, has been reported only infrequently with sulfonylureas. For glyburide, a second-generation sulfonylurea, only two brief reports of hepatotoxicity exist. Two patients with type II diabetes mellitus developed an acute hepatitis-like syndrome soon after initiation of glyburide therapy. There was no serologic evidence of viral infection, and a liver biopsy sample showed a histologic pattern consistent with drug-induced hepatitis. Both patients recovered quickly after stopping glyburide therapy and have remained well for a follow-up period of 1 year. Glyburide can produce an acute hepatitis-like illness in some persons.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "viral infection", "mention_text": "Drug-induced hepatotoxicity, although common, has been reported only infrequently with sulfonylureas. For glyburide, a second-generation sulfonylurea, only two brief reports of hepatotoxicity exist. Two patients with type II diabetes mellitus developed an acute hepatitis-like syndrome soon after initiation of glyburide therapy. There was no serologic evidence of viral infection, and a liver biopsy sample showed a histologic pattern consistent with drug-induced hepatitis. Both patients recovered quickly after stopping glyburide therapy and have remained well for a follow-up period of 1 year. Glyburide can produce an acute hepatitis-like illness in some persons.", "entity": "Virus Diseases", "aliases": "Disease Viral Virus Diseases", "definition": "A general term for diseases produced by viruses.\n    ", "id": "MESH:D014777"}
{"mention": "drug-induced hepatitis", "mention_text": "Drug-induced hepatotoxicity, although common, has been reported only infrequently with sulfonylureas. For glyburide, a second-generation sulfonylurea, only two brief reports of hepatotoxicity exist. Two patients with type II diabetes mellitus developed an acute hepatitis-like syndrome soon after initiation of glyburide therapy. There was no serologic evidence of viral infection, and a liver biopsy sample showed a histologic pattern consistent with drug-induced hepatitis. Both patients recovered quickly after stopping glyburide therapy and have remained well for a follow-up period of 1 year. Glyburide can produce an acute hepatitis-like illness in some persons.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "Glyburide", "mention_text": "Drug-induced hepatotoxicity, although common, has been reported only infrequently with sulfonylureas. For glyburide, a second-generation sulfonylurea, only two brief reports of hepatotoxicity exist. Two patients with type II diabetes mellitus developed an acute hepatitis-like syndrome soon after initiation of glyburide therapy. There was no serologic evidence of viral infection, and a liver biopsy sample showed a histologic pattern consistent with drug-induced hepatitis. Both patients recovered quickly after stopping glyburide therapy and have remained well for a follow-up period of 1 year. Glyburide can produce an acute hepatitis-like illness in some persons.", "entity": "Glyburide", "aliases": "Daonil Diabeta Euglucon 5 N Glibenclamide Glybenclamide Glyburide HB 419 420 HB-419 HB-420 HB419 HB420 Maninil Micronase Neogluconin", "definition": "An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.\n    ", "id": "MESH:D005905"}
{"mention": "acute hepatitis-like illness", "mention_text": "Drug-induced hepatotoxicity, although common, has been reported only infrequently with sulfonylureas. For glyburide, a second-generation sulfonylurea, only two brief reports of hepatotoxicity exist. Two patients with type II diabetes mellitus developed an acute hepatitis-like syndrome soon after initiation of glyburide therapy. There was no serologic evidence of viral infection, and a liver biopsy sample showed a histologic pattern consistent with drug-induced hepatitis. Both patients recovered quickly after stopping glyburide therapy and have remained well for a follow-up period of 1 year. Glyburide can produce an acute hepatitis-like illness in some persons.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "hemorrhage", "mention_text": "Systolic pressure variation is greater during hemorrhage than during sodium nitroprusside-induced hypotension in ventilated dogs.", "entity": "Hemorrhage", "aliases": "Bleeding Hemorrhage Hemorrhages", "definition": "Bleeding or escape of blood from a vessel.\n    ", "id": "MESH:D006470"}
{"mention": "sodium nitroprusside", "mention_text": "Systolic pressure variation is greater during hemorrhage than during sodium nitroprusside-induced hypotension in ventilated dogs.", "entity": "Nitroprusside", "aliases": "Abbott Brand of Sodium Nitroprusside Bayer Cyanonitrosylferrate Disodium Salt Faulding Fides Ecopharma Ketostix Naniprus Nipride Nipruton Nitriate Nitroferricyanide Nitropress Nitroprussiat Dihydrate Roche SERB", "definition": "A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.\n    ", "id": "MESH:D009599"}
{"mention": "hypotension", "mention_text": "Systolic pressure variation is greater during hemorrhage than during sodium nitroprusside-induced hypotension in ventilated dogs.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "hypotension", "mention_text": "The systolic pressure variation (SPV), which is the difference between the maximal and minimal values of the systolic blood pressure (SBP) after one positive-pressure breath, was studied in ventilated dogs subjected to hypotension. Mean arterial pressure was decreased to 50 mm Hg for 30 minutes either by hemorrhage (HEM, n = 7) or by continuous infusion of sodium nitroprusside (SNP, n = 7). During HEM-induced hypotension the cardiac output was significantly lower and systemic vascular resistance higher compared with that in the SNP group. The systemic, central venous, pulmonary capillary wedge pressures, and heart rates, were similar in the two groups. Analysis of the respiratory changes in the arterial pressure waveform enabled differentiation between the two groups. The SPV during hypotension was 15.7 +/- 6.7 mm Hg in the HEM group, compared with 9.1 +/- 2.0 mm Hg in the SNP group (P less than 0.02). The delta down, which is the measure of decrease of SBP after a mechanical breath, was 20.3 +/- 8.4 and 10.1 +/- 3.8 mm Hg in the HEM and SNP groups, respectively, during hypotension (P less than 0.02). It is concluded that increases in the SPV and the delta down are characteristic of a hypotensive state due to a predominant decrease in preload. They are thus more important during absolute hypovolemia than during deliberate hypotension.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "hemorrhage", "mention_text": "The systolic pressure variation (SPV), which is the difference between the maximal and minimal values of the systolic blood pressure (SBP) after one positive-pressure breath, was studied in ventilated dogs subjected to hypotension. Mean arterial pressure was decreased to 50 mm Hg for 30 minutes either by hemorrhage (HEM, n = 7) or by continuous infusion of sodium nitroprusside (SNP, n = 7). During HEM-induced hypotension the cardiac output was significantly lower and systemic vascular resistance higher compared with that in the SNP group. The systemic, central venous, pulmonary capillary wedge pressures, and heart rates, were similar in the two groups. Analysis of the respiratory changes in the arterial pressure waveform enabled differentiation between the two groups. The SPV during hypotension was 15.7 +/- 6.7 mm Hg in the HEM group, compared with 9.1 +/- 2.0 mm Hg in the SNP group (P less than 0.02). The delta down, which is the measure of decrease of SBP after a mechanical breath, was 20.3 +/- 8.4 and 10.1 +/- 3.8 mm Hg in the HEM and SNP groups, respectively, during hypotension (P less than 0.02). It is concluded that increases in the SPV and the delta down are characteristic of a hypotensive state due to a predominant decrease in preload. They are thus more important during absolute hypovolemia than during deliberate hypotension.", "entity": "Hemorrhage", "aliases": "Bleeding Hemorrhage Hemorrhages", "definition": "Bleeding or escape of blood from a vessel.\n    ", "id": "MESH:D006470"}
{"mention": "HEM", "mention_text": "The systolic pressure variation (SPV), which is the difference between the maximal and minimal values of the systolic blood pressure (SBP) after one positive-pressure breath, was studied in ventilated dogs subjected to hypotension. Mean arterial pressure was decreased to 50 mm Hg for 30 minutes either by hemorrhage (HEM, n = 7) or by continuous infusion of sodium nitroprusside (SNP, n = 7). During HEM-induced hypotension the cardiac output was significantly lower and systemic vascular resistance higher compared with that in the SNP group. The systemic, central venous, pulmonary capillary wedge pressures, and heart rates, were similar in the two groups. Analysis of the respiratory changes in the arterial pressure waveform enabled differentiation between the two groups. The SPV during hypotension was 15.7 +/- 6.7 mm Hg in the HEM group, compared with 9.1 +/- 2.0 mm Hg in the SNP group (P less than 0.02). The delta down, which is the measure of decrease of SBP after a mechanical breath, was 20.3 +/- 8.4 and 10.1 +/- 3.8 mm Hg in the HEM and SNP groups, respectively, during hypotension (P less than 0.02). It is concluded that increases in the SPV and the delta down are characteristic of a hypotensive state due to a predominant decrease in preload. They are thus more important during absolute hypovolemia than during deliberate hypotension.", "entity": "Hemorrhage", "aliases": "Bleeding Hemorrhage Hemorrhages", "definition": "Bleeding or escape of blood from a vessel.\n    ", "id": "MESH:D006470"}
{"mention": "sodium nitroprusside", "mention_text": "The systolic pressure variation (SPV), which is the difference between the maximal and minimal values of the systolic blood pressure (SBP) after one positive-pressure breath, was studied in ventilated dogs subjected to hypotension. Mean arterial pressure was decreased to 50 mm Hg for 30 minutes either by hemorrhage (HEM, n = 7) or by continuous infusion of sodium nitroprusside (SNP, n = 7). During HEM-induced hypotension the cardiac output was significantly lower and systemic vascular resistance higher compared with that in the SNP group. The systemic, central venous, pulmonary capillary wedge pressures, and heart rates, were similar in the two groups. Analysis of the respiratory changes in the arterial pressure waveform enabled differentiation between the two groups. The SPV during hypotension was 15.7 +/- 6.7 mm Hg in the HEM group, compared with 9.1 +/- 2.0 mm Hg in the SNP group (P less than 0.02). The delta down, which is the measure of decrease of SBP after a mechanical breath, was 20.3 +/- 8.4 and 10.1 +/- 3.8 mm Hg in the HEM and SNP groups, respectively, during hypotension (P less than 0.02). It is concluded that increases in the SPV and the delta down are characteristic of a hypotensive state due to a predominant decrease in preload. They are thus more important during absolute hypovolemia than during deliberate hypotension.", "entity": "Nitroprusside", "aliases": "Abbott Brand of Sodium Nitroprusside Bayer Cyanonitrosylferrate Disodium Salt Faulding Fides Ecopharma Ketostix Naniprus Nipride Nipruton Nitriate Nitroferricyanide Nitropress Nitroprussiat Dihydrate Roche SERB", "definition": "A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.\n    ", "id": "MESH:D009599"}
{"mention": "SNP", "mention_text": "The systolic pressure variation (SPV), which is the difference between the maximal and minimal values of the systolic blood pressure (SBP) after one positive-pressure breath, was studied in ventilated dogs subjected to hypotension. Mean arterial pressure was decreased to 50 mm Hg for 30 minutes either by hemorrhage (HEM, n = 7) or by continuous infusion of sodium nitroprusside (SNP, n = 7). During HEM-induced hypotension the cardiac output was significantly lower and systemic vascular resistance higher compared with that in the SNP group. The systemic, central venous, pulmonary capillary wedge pressures, and heart rates, were similar in the two groups. Analysis of the respiratory changes in the arterial pressure waveform enabled differentiation between the two groups. The SPV during hypotension was 15.7 +/- 6.7 mm Hg in the HEM group, compared with 9.1 +/- 2.0 mm Hg in the SNP group (P less than 0.02). The delta down, which is the measure of decrease of SBP after a mechanical breath, was 20.3 +/- 8.4 and 10.1 +/- 3.8 mm Hg in the HEM and SNP groups, respectively, during hypotension (P less than 0.02). It is concluded that increases in the SPV and the delta down are characteristic of a hypotensive state due to a predominant decrease in preload. They are thus more important during absolute hypovolemia than during deliberate hypotension.", "entity": "Nitroprusside", "aliases": "Abbott Brand of Sodium Nitroprusside Bayer Cyanonitrosylferrate Disodium Salt Faulding Fides Ecopharma Ketostix Naniprus Nipride Nipruton Nitriate Nitroferricyanide Nitropress Nitroprussiat Dihydrate Roche SERB", "definition": "A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.\n    ", "id": "MESH:D009599"}
{"mention": "hypotensive", "mention_text": "The systolic pressure variation (SPV), which is the difference between the maximal and minimal values of the systolic blood pressure (SBP) after one positive-pressure breath, was studied in ventilated dogs subjected to hypotension. Mean arterial pressure was decreased to 50 mm Hg for 30 minutes either by hemorrhage (HEM, n = 7) or by continuous infusion of sodium nitroprusside (SNP, n = 7). During HEM-induced hypotension the cardiac output was significantly lower and systemic vascular resistance higher compared with that in the SNP group. The systemic, central venous, pulmonary capillary wedge pressures, and heart rates, were similar in the two groups. Analysis of the respiratory changes in the arterial pressure waveform enabled differentiation between the two groups. The SPV during hypotension was 15.7 +/- 6.7 mm Hg in the HEM group, compared with 9.1 +/- 2.0 mm Hg in the SNP group (P less than 0.02). The delta down, which is the measure of decrease of SBP after a mechanical breath, was 20.3 +/- 8.4 and 10.1 +/- 3.8 mm Hg in the HEM and SNP groups, respectively, during hypotension (P less than 0.02). It is concluded that increases in the SPV and the delta down are characteristic of a hypotensive state due to a predominant decrease in preload. They are thus more important during absolute hypovolemia than during deliberate hypotension.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "hypovolemia", "mention_text": "The systolic pressure variation (SPV), which is the difference between the maximal and minimal values of the systolic blood pressure (SBP) after one positive-pressure breath, was studied in ventilated dogs subjected to hypotension. Mean arterial pressure was decreased to 50 mm Hg for 30 minutes either by hemorrhage (HEM, n = 7) or by continuous infusion of sodium nitroprusside (SNP, n = 7). During HEM-induced hypotension the cardiac output was significantly lower and systemic vascular resistance higher compared with that in the SNP group. The systemic, central venous, pulmonary capillary wedge pressures, and heart rates, were similar in the two groups. Analysis of the respiratory changes in the arterial pressure waveform enabled differentiation between the two groups. The SPV during hypotension was 15.7 +/- 6.7 mm Hg in the HEM group, compared with 9.1 +/- 2.0 mm Hg in the SNP group (P less than 0.02). The delta down, which is the measure of decrease of SBP after a mechanical breath, was 20.3 +/- 8.4 and 10.1 +/- 3.8 mm Hg in the HEM and SNP groups, respectively, during hypotension (P less than 0.02). It is concluded that increases in the SPV and the delta down are characteristic of a hypotensive state due to a predominant decrease in preload. They are thus more important during absolute hypovolemia than during deliberate hypotension.", "entity": "Hypovolemia", "aliases": "Hypovolemia Hypovolemias Hypovolemic Hypovolemics", "definition": "An abnormally low volume of blood circulating through the body. It may result in hypovolemic shock (see SHOCK).\n    ", "id": "MESH:D020896"}
{"mention": "spasm", "mention_text": "Drug-induced arterial spasm relieved by lidocaine. Case report.", "entity": "Spasm", "aliases": "Ciliary Body Spasm Spasms Generalized Muscle Muscular", "definition": "An involuntary contraction of a muscle or group of muscles. Spasms may involve SKELETAL MUSCLE or SMOOTH MUSCLE.\n    ", "id": "MESH:D013035"}
{"mention": "lidocaine", "mention_text": "Drug-induced arterial spasm relieved by lidocaine. Case report.", "entity": "Lidocaine", "aliases": "2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide 2-2EtN-2MePhAcN Astrazeneca Brand of Lidocaine Dalcaine Jenapharm Lidocanine Hydrochloride Carbonate (2:1) Hydrocarbonate Monoacetate Monohydrochloride Monohydrate Sulfate (1:1) Lignocaine Novocol Octocaine Strathmann Xylesthesin Xylocaine Xylocitin Xyloneural", "definition": "A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.\n    ", "id": "MESH:D008012"}
{"mention": "sodium pentothal", "mention_text": "Following major intracranial surgery in a 35-year-old man, sodium pentothal was intravenously infused to minimize cerebral ischaemia. Intense vasospasm with threatened gangrene arose in the arm used for the infusion. Since the cranial condition precluded use of more usual methods, lidocaine was given intra-arterially, with careful cardiovascular monitoring, to counteract the vasospasm. The treatment was rapidly successful.", "entity": "Thiopental", "aliases": "Abbott Brand of Thiopental Sodium Altana Pharma Bomathal Braun Merial Nesdonal Nycomed Penthiobarbital Pentothal Sodico Pharmtech Pisa Rhone Merieux Sodipental Thiomebumal Thionembutal Thiopentobarbital Thiopentone Tiobarbital Trapanal", "definition": "A barbiturate that is administered intravenously for the induction of general anesthesia or for the production of complete anesthesia of short duration.\n    ", "id": "MESH:D013874"}
{"mention": "cerebral ischaemia", "mention_text": "Following major intracranial surgery in a 35-year-old man, sodium pentothal was intravenously infused to minimize cerebral ischaemia. Intense vasospasm with threatened gangrene arose in the arm used for the infusion. Since the cranial condition precluded use of more usual methods, lidocaine was given intra-arterially, with careful cardiovascular monitoring, to counteract the vasospasm. The treatment was rapidly successful.", "entity": "Brain Ischemia", "aliases": "Brain Ischemia Ischemias Cerebral Encephalopathy Ischemic Encephalopathies", "definition": "Localized reduction of blood flow to brain tissue due to arterial obstruction or systemic hypoperfusion. This frequently occurs in conjunction with brain hypoxia (HYPOXIA, BRAIN). Prolonged ischemia is associated with BRAIN INFARCTION.\n    ", "id": "MESH:D002545"}
{"mention": "vasospasm", "mention_text": "Following major intracranial surgery in a 35-year-old man, sodium pentothal was intravenously infused to minimize cerebral ischaemia. Intense vasospasm with threatened gangrene arose in the arm used for the infusion. Since the cranial condition precluded use of more usual methods, lidocaine was given intra-arterially, with careful cardiovascular monitoring, to counteract the vasospasm. The treatment was rapidly successful.", "entity": "Vasospasm, Intracranial", "aliases": "Angiospasm Cerebral Intracranial Angiospasms Artery Spasm Spasms Vasospasm Vasospasms Cerebrovascular Vascular", "definition": "Constriction of arteries in the SKULL due to sudden, sharp, and often persistent smooth muscle contraction in blood vessels. Intracranial vasospasm results in reduced vessel lumen caliber, restricted blood flow to the brain, and BRAIN ISCHEMIA that may lead to hypoxic-ischemic brain injury (HYPOXIA-ISCHEMIA, BRAIN).\n    ", "id": "MESH:D020301"}
{"mention": "gangrene", "mention_text": "Following major intracranial surgery in a 35-year-old man, sodium pentothal was intravenously infused to minimize cerebral ischaemia. Intense vasospasm with threatened gangrene arose in the arm used for the infusion. Since the cranial condition precluded use of more usual methods, lidocaine was given intra-arterially, with careful cardiovascular monitoring, to counteract the vasospasm. The treatment was rapidly successful.", "entity": "Gangrene", "aliases": "Gangrene Gangrenes", "definition": "Death and putrefaction of tissue usually due to a loss of blood supply.\n    ", "id": "MESH:D005734"}
{"mention": "lidocaine", "mention_text": "Following major intracranial surgery in a 35-year-old man, sodium pentothal was intravenously infused to minimize cerebral ischaemia. Intense vasospasm with threatened gangrene arose in the arm used for the infusion. Since the cranial condition precluded use of more usual methods, lidocaine was given intra-arterially, with careful cardiovascular monitoring, to counteract the vasospasm. The treatment was rapidly successful.", "entity": "Lidocaine", "aliases": "2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide 2-2EtN-2MePhAcN Astrazeneca Brand of Lidocaine Dalcaine Jenapharm Lidocanine Hydrochloride Carbonate (2:1) Hydrocarbonate Monoacetate Monohydrochloride Monohydrate Sulfate (1:1) Lignocaine Novocol Octocaine Strathmann Xylesthesin Xylocaine Xylocitin Xyloneural", "definition": "A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.\n    ", "id": "MESH:D008012"}
{"mention": "isoflurane", "mention_text": "Cerebral blood flow and metabolism during isoflurane-induced hypotension in patients subjected to surgery for cerebral aneurysms.", "entity": "Isoflurane", "aliases": "Isoflurane", "definition": "A stable, non-explosive inhalation anesthetic, relatively free from significant side effects.\n    ", "id": "MESH:D007530"}
{"mention": "hypotension", "mention_text": "Cerebral blood flow and metabolism during isoflurane-induced hypotension in patients subjected to surgery for cerebral aneurysms.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "cerebral aneurysms", "mention_text": "Cerebral blood flow and metabolism during isoflurane-induced hypotension in patients subjected to surgery for cerebral aneurysms.", "entity": "Intracranial Aneurysm", "aliases": "Aneurysm Anterior Cerebral Artery Communicating Basilar Berry Brain Giant Intracranial Mycotic Middle Posterior Aneurysms", "definition": "Abnormal outpouching in the wall of intracranial blood vessels. Most common are the saccular (berry) aneurysms located at branch points in CIRCLE OF WILLIS at the base of the brain. Vessel rupture results in SUBARACHNOID HEMORRHAGE or INTRACRANIAL HEMORRHAGES. Giant aneurysms (>2.5 cm in diameter) may compress adjacent structures, including the OCULOMOTOR NERVE. (From Adams et al., Principles of Neurology, 6th ed, p841)\n    ", "id": "MESH:D002532"}
{"mention": "oxygen", "mention_text": "Cerebral blood flow and cerebral metabolic rate for oxygen were measured during isoflurane-induced hypotension in 10 patients subjected to craniotomy for clipping of a cerebral aneurysm. Flow and metabolism were measured 5-13 days after the subarachnoid haemorrhage by a modification of the classical Kety-Schmidt technique using xenon-133 i.v. Anaesthesia was maintained with an inspired isoflurane concentration of 0.75% (plus 67% nitrous oxide in oxygen), during which CBF and CMRO2 were 34.3 +/- 2.1 ml/100 g min-1 and 2.32 +/- 0.16 ml/100 g min-1 at PaCO2 4.1 +/- 0.1 kPa (mean +/- SEM). Controlled hypotension to an average MAP of 50-55 mm Hg was induced by increasing the dose of isoflurane, and maintained at an inspired concentration of 2.2 +/- 0.2%. This resulted in a significant decrease in CMRO2 (to 1.73 +/- 0.16 ml/100 g min-1), while CBF was unchanged. After the clipping of the aneurysm the isoflurane concentration was reduced to 0.75%. There was a significant increase in CBF, although CMRO2 was unchanged, compared with pre-hypotensive values. These changes might offer protection to brain tissue during periods of induced hypotension.", "entity": "Oxygen", "aliases": "Dioxygen Oxygen", "definition": "An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.\n    ", "id": "MESH:D010100"}
{"mention": "isoflurane", "mention_text": "Cerebral blood flow and cerebral metabolic rate for oxygen were measured during isoflurane-induced hypotension in 10 patients subjected to craniotomy for clipping of a cerebral aneurysm. Flow and metabolism were measured 5-13 days after the subarachnoid haemorrhage by a modification of the classical Kety-Schmidt technique using xenon-133 i.v. Anaesthesia was maintained with an inspired isoflurane concentration of 0.75% (plus 67% nitrous oxide in oxygen), during which CBF and CMRO2 were 34.3 +/- 2.1 ml/100 g min-1 and 2.32 +/- 0.16 ml/100 g min-1 at PaCO2 4.1 +/- 0.1 kPa (mean +/- SEM). Controlled hypotension to an average MAP of 50-55 mm Hg was induced by increasing the dose of isoflurane, and maintained at an inspired concentration of 2.2 +/- 0.2%. This resulted in a significant decrease in CMRO2 (to 1.73 +/- 0.16 ml/100 g min-1), while CBF was unchanged. After the clipping of the aneurysm the isoflurane concentration was reduced to 0.75%. There was a significant increase in CBF, although CMRO2 was unchanged, compared with pre-hypotensive values. These changes might offer protection to brain tissue during periods of induced hypotension.", "entity": "Isoflurane", "aliases": "Isoflurane", "definition": "A stable, non-explosive inhalation anesthetic, relatively free from significant side effects.\n    ", "id": "MESH:D007530"}
{"mention": "hypotension", "mention_text": "Cerebral blood flow and cerebral metabolic rate for oxygen were measured during isoflurane-induced hypotension in 10 patients subjected to craniotomy for clipping of a cerebral aneurysm. Flow and metabolism were measured 5-13 days after the subarachnoid haemorrhage by a modification of the classical Kety-Schmidt technique using xenon-133 i.v. Anaesthesia was maintained with an inspired isoflurane concentration of 0.75% (plus 67% nitrous oxide in oxygen), during which CBF and CMRO2 were 34.3 +/- 2.1 ml/100 g min-1 and 2.32 +/- 0.16 ml/100 g min-1 at PaCO2 4.1 +/- 0.1 kPa (mean +/- SEM). Controlled hypotension to an average MAP of 50-55 mm Hg was induced by increasing the dose of isoflurane, and maintained at an inspired concentration of 2.2 +/- 0.2%. This resulted in a significant decrease in CMRO2 (to 1.73 +/- 0.16 ml/100 g min-1), while CBF was unchanged. After the clipping of the aneurysm the isoflurane concentration was reduced to 0.75%. There was a significant increase in CBF, although CMRO2 was unchanged, compared with pre-hypotensive values. These changes might offer protection to brain tissue during periods of induced hypotension.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "cerebral aneurysm", "mention_text": "Cerebral blood flow and cerebral metabolic rate for oxygen were measured during isoflurane-induced hypotension in 10 patients subjected to craniotomy for clipping of a cerebral aneurysm. Flow and metabolism were measured 5-13 days after the subarachnoid haemorrhage by a modification of the classical Kety-Schmidt technique using xenon-133 i.v. Anaesthesia was maintained with an inspired isoflurane concentration of 0.75% (plus 67% nitrous oxide in oxygen), during which CBF and CMRO2 were 34.3 +/- 2.1 ml/100 g min-1 and 2.32 +/- 0.16 ml/100 g min-1 at PaCO2 4.1 +/- 0.1 kPa (mean +/- SEM). Controlled hypotension to an average MAP of 50-55 mm Hg was induced by increasing the dose of isoflurane, and maintained at an inspired concentration of 2.2 +/- 0.2%. This resulted in a significant decrease in CMRO2 (to 1.73 +/- 0.16 ml/100 g min-1), while CBF was unchanged. After the clipping of the aneurysm the isoflurane concentration was reduced to 0.75%. There was a significant increase in CBF, although CMRO2 was unchanged, compared with pre-hypotensive values. These changes might offer protection to brain tissue during periods of induced hypotension.", "entity": "Intracranial Aneurysm", "aliases": "Aneurysm Anterior Cerebral Artery Communicating Basilar Berry Brain Giant Intracranial Mycotic Middle Posterior Aneurysms", "definition": "Abnormal outpouching in the wall of intracranial blood vessels. Most common are the saccular (berry) aneurysms located at branch points in CIRCLE OF WILLIS at the base of the brain. Vessel rupture results in SUBARACHNOID HEMORRHAGE or INTRACRANIAL HEMORRHAGES. Giant aneurysms (>2.5 cm in diameter) may compress adjacent structures, including the OCULOMOTOR NERVE. (From Adams et al., Principles of Neurology, 6th ed, p841)\n    ", "id": "MESH:D002532"}
{"mention": "subarachnoid haemorrhage", "mention_text": "Cerebral blood flow and cerebral metabolic rate for oxygen were measured during isoflurane-induced hypotension in 10 patients subjected to craniotomy for clipping of a cerebral aneurysm. Flow and metabolism were measured 5-13 days after the subarachnoid haemorrhage by a modification of the classical Kety-Schmidt technique using xenon-133 i.v. Anaesthesia was maintained with an inspired isoflurane concentration of 0.75% (plus 67% nitrous oxide in oxygen), during which CBF and CMRO2 were 34.3 +/- 2.1 ml/100 g min-1 and 2.32 +/- 0.16 ml/100 g min-1 at PaCO2 4.1 +/- 0.1 kPa (mean +/- SEM). Controlled hypotension to an average MAP of 50-55 mm Hg was induced by increasing the dose of isoflurane, and maintained at an inspired concentration of 2.2 +/- 0.2%. This resulted in a significant decrease in CMRO2 (to 1.73 +/- 0.16 ml/100 g min-1), while CBF was unchanged. After the clipping of the aneurysm the isoflurane concentration was reduced to 0.75%. There was a significant increase in CBF, although CMRO2 was unchanged, compared with pre-hypotensive values. These changes might offer protection to brain tissue during periods of induced hypotension.", "entity": "Subarachnoid Hemorrhage", "aliases": "Aneurysmal Subarachnoid Hemorrhage Hemorrhages Intracranial Perinatal Spontaneous SAH (Subarachnoid Hemorrhage) SAHs", "definition": "Bleeding into the intracranial or spinal SUBARACHNOID SPACE, most resulting from INTRACRANIAL ANEURYSM rupture. It can occur after traumatic injuries (SUBARACHNOID HEMORRHAGE, TRAUMATIC). Clinical features include HEADACHE; NAUSEA; VOMITING, nuchal rigidity, variable neurological deficits and reduced mental status.\n    ", "id": "MESH:D013345"}
{"mention": "xenon", "mention_text": "Cerebral blood flow and cerebral metabolic rate for oxygen were measured during isoflurane-induced hypotension in 10 patients subjected to craniotomy for clipping of a cerebral aneurysm. Flow and metabolism were measured 5-13 days after the subarachnoid haemorrhage by a modification of the classical Kety-Schmidt technique using xenon-133 i.v. Anaesthesia was maintained with an inspired isoflurane concentration of 0.75% (plus 67% nitrous oxide in oxygen), during which CBF and CMRO2 were 34.3 +/- 2.1 ml/100 g min-1 and 2.32 +/- 0.16 ml/100 g min-1 at PaCO2 4.1 +/- 0.1 kPa (mean +/- SEM). Controlled hypotension to an average MAP of 50-55 mm Hg was induced by increasing the dose of isoflurane, and maintained at an inspired concentration of 2.2 +/- 0.2%. This resulted in a significant decrease in CMRO2 (to 1.73 +/- 0.16 ml/100 g min-1), while CBF was unchanged. After the clipping of the aneurysm the isoflurane concentration was reduced to 0.75%. There was a significant increase in CBF, although CMRO2 was unchanged, compared with pre-hypotensive values. These changes might offer protection to brain tissue during periods of induced hypotension.", "entity": "Xenon", "aliases": "Xenon", "definition": "A noble gas with the atomic symbol Xe, atomic number 54, and atomic weight 131.30. It is found in the earth's atmosphere and has been used as an anesthetic.\n    ", "id": "MESH:D014978"}
{"mention": "nitrous oxide", "mention_text": "Cerebral blood flow and cerebral metabolic rate for oxygen were measured during isoflurane-induced hypotension in 10 patients subjected to craniotomy for clipping of a cerebral aneurysm. Flow and metabolism were measured 5-13 days after the subarachnoid haemorrhage by a modification of the classical Kety-Schmidt technique using xenon-133 i.v. Anaesthesia was maintained with an inspired isoflurane concentration of 0.75% (plus 67% nitrous oxide in oxygen), during which CBF and CMRO2 were 34.3 +/- 2.1 ml/100 g min-1 and 2.32 +/- 0.16 ml/100 g min-1 at PaCO2 4.1 +/- 0.1 kPa (mean +/- SEM). Controlled hypotension to an average MAP of 50-55 mm Hg was induced by increasing the dose of isoflurane, and maintained at an inspired concentration of 2.2 +/- 0.2%. This resulted in a significant decrease in CMRO2 (to 1.73 +/- 0.16 ml/100 g min-1), while CBF was unchanged. After the clipping of the aneurysm the isoflurane concentration was reduced to 0.75%. There was a significant increase in CBF, although CMRO2 was unchanged, compared with pre-hypotensive values. These changes might offer protection to brain tissue during periods of induced hypotension.", "entity": "Nitrous Oxide", "aliases": "Gas Laughing Nitrogen Protoxide Nitrous Oxide", "definition": "Nitrogen oxide (N2O). A colorless, odorless gas that is used as an anesthetic and analgesic. High concentrations cause a narcotic effect and may replace oxygen, causing death by asphyxia. It is also used as a food aerosol in the preparation of whipping cream.\n    ", "id": "MESH:D009609"}
{"mention": "Hg", "mention_text": "Cerebral blood flow and cerebral metabolic rate for oxygen were measured during isoflurane-induced hypotension in 10 patients subjected to craniotomy for clipping of a cerebral aneurysm. Flow and metabolism were measured 5-13 days after the subarachnoid haemorrhage by a modification of the classical Kety-Schmidt technique using xenon-133 i.v. Anaesthesia was maintained with an inspired isoflurane concentration of 0.75% (plus 67% nitrous oxide in oxygen), during which CBF and CMRO2 were 34.3 +/- 2.1 ml/100 g min-1 and 2.32 +/- 0.16 ml/100 g min-1 at PaCO2 4.1 +/- 0.1 kPa (mean +/- SEM). Controlled hypotension to an average MAP of 50-55 mm Hg was induced by increasing the dose of isoflurane, and maintained at an inspired concentration of 2.2 +/- 0.2%. This resulted in a significant decrease in CMRO2 (to 1.73 +/- 0.16 ml/100 g min-1), while CBF was unchanged. After the clipping of the aneurysm the isoflurane concentration was reduced to 0.75%. There was a significant increase in CBF, although CMRO2 was unchanged, compared with pre-hypotensive values. These changes might offer protection to brain tissue during periods of induced hypotension.", "entity": "Mercury", "aliases": "Mercury", "definition": "A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to MERCURY POISONING. Because of its toxicity, the clinical use of mercury and mercurials is diminishing.\n    ", "id": "MESH:D008628"}
{"mention": "aneurysm", "mention_text": "Cerebral blood flow and cerebral metabolic rate for oxygen were measured during isoflurane-induced hypotension in 10 patients subjected to craniotomy for clipping of a cerebral aneurysm. Flow and metabolism were measured 5-13 days after the subarachnoid haemorrhage by a modification of the classical Kety-Schmidt technique using xenon-133 i.v. Anaesthesia was maintained with an inspired isoflurane concentration of 0.75% (plus 67% nitrous oxide in oxygen), during which CBF and CMRO2 were 34.3 +/- 2.1 ml/100 g min-1 and 2.32 +/- 0.16 ml/100 g min-1 at PaCO2 4.1 +/- 0.1 kPa (mean +/- SEM). Controlled hypotension to an average MAP of 50-55 mm Hg was induced by increasing the dose of isoflurane, and maintained at an inspired concentration of 2.2 +/- 0.2%. This resulted in a significant decrease in CMRO2 (to 1.73 +/- 0.16 ml/100 g min-1), while CBF was unchanged. After the clipping of the aneurysm the isoflurane concentration was reduced to 0.75%. There was a significant increase in CBF, although CMRO2 was unchanged, compared with pre-hypotensive values. These changes might offer protection to brain tissue during periods of induced hypotension.", "entity": "Aneurysm", "aliases": "Aneurysm Fusiform Aneurysms Saccular", "definition": "Pathological outpouching or sac-like dilatation in the wall of any blood vessel (ARTERIES or VEINS) or the heart (HEART ANEURYSM). It indicates a thin and weakened area in the wall which may later rupture. Aneurysms are classified by location, etiology, or other characteristics.\n    ", "id": "MESH:D000783"}
{"mention": "hypotensive", "mention_text": "Cerebral blood flow and cerebral metabolic rate for oxygen were measured during isoflurane-induced hypotension in 10 patients subjected to craniotomy for clipping of a cerebral aneurysm. Flow and metabolism were measured 5-13 days after the subarachnoid haemorrhage by a modification of the classical Kety-Schmidt technique using xenon-133 i.v. Anaesthesia was maintained with an inspired isoflurane concentration of 0.75% (plus 67% nitrous oxide in oxygen), during which CBF and CMRO2 were 34.3 +/- 2.1 ml/100 g min-1 and 2.32 +/- 0.16 ml/100 g min-1 at PaCO2 4.1 +/- 0.1 kPa (mean +/- SEM). Controlled hypotension to an average MAP of 50-55 mm Hg was induced by increasing the dose of isoflurane, and maintained at an inspired concentration of 2.2 +/- 0.2%. This resulted in a significant decrease in CMRO2 (to 1.73 +/- 0.16 ml/100 g min-1), while CBF was unchanged. After the clipping of the aneurysm the isoflurane concentration was reduced to 0.75%. There was a significant increase in CBF, although CMRO2 was unchanged, compared with pre-hypotensive values. These changes might offer protection to brain tissue during periods of induced hypotension.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "Allergic reaction", "mention_text": "Allergic reaction to 5-fluorouracil infusion.", "entity": "Drug Hypersensitivity", "aliases": "Allergies Drug Allergy Hypersensitivities Hypersensitivity", "definition": "Immunologically mediated adverse reactions to medicinal substances used legally or illegally.\n    ", "id": "MESH:D004342"}
{"mention": "5-fluorouracil", "mention_text": "Allergic reaction to 5-fluorouracil infusion.", "entity": "Fluorouracil", "aliases": "5 FU Lederle medac Fluorouracil biosyn HU Hexal 5-FU 5-Fluorouracil 5-Fluorouracil-biosyn 5-HU 5FU Adrucil Allergan Brand of CSP Carac Dakota Fluorouracile Dermatech Dermik Efudex Efudix Ferrer Fluoro Uracile ICN Fluoro-Uracile Fluoroplex GRY Mononitrate Monopotassium Salt Monosodium Potassium Teva Fluorouracil-GRY Fluorouracilo Far Fluoruracil Fluracedyl Flurodex Gry Haemato fu Haemato-fu Neocorp Neofluor Onkofluor Onkoworks Pharmachemie Ribofluor Riemser Roche ribosepharm", "definition": "A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.\n    ", "id": "MESH:D005472"}
{"mention": "allergic reaction", "mention_text": "An allergic reaction consisting of angioneurotic edema secondary to continuous infusion 5-fluorouracil occurred in a patient with recurrent carcinoma of the oral cavity, cirrhosis, and cisplatin-induced impaired renal function. This reaction occurred during the sixth and seventh courses of infusional chemotherapy. Oral diphenhydramine and prednisone were ineffective in preventing the recurrence of the allergic reaction. Discontinuance of effective chemotherapy in this patient during partial remission resulted in fatal disease progression.", "entity": "Drug Hypersensitivity", "aliases": "Allergies Drug Allergy Hypersensitivities Hypersensitivity", "definition": "Immunologically mediated adverse reactions to medicinal substances used legally or illegally.\n    ", "id": "MESH:D004342"}
{"mention": "angioneurotic edema", "mention_text": "An allergic reaction consisting of angioneurotic edema secondary to continuous infusion 5-fluorouracil occurred in a patient with recurrent carcinoma of the oral cavity, cirrhosis, and cisplatin-induced impaired renal function. This reaction occurred during the sixth and seventh courses of infusional chemotherapy. Oral diphenhydramine and prednisone were ineffective in preventing the recurrence of the allergic reaction. Discontinuance of effective chemotherapy in this patient during partial remission resulted in fatal disease progression.", "entity": "Angioedema", "aliases": "Angioedema Angioedemas Angioneurotic Edema Edemas Quincke's Giant Urticaria Urticarias Quincke Quinckes", "definition": "Swelling involving the deep DERMIS, subcutaneous, or submucosal tissues, representing localized EDEMA. Angioedema often occurs in the face, lips, tongue, and larynx.\n    ", "id": "MESH:D000799"}
{"mention": "5-fluorouracil", "mention_text": "An allergic reaction consisting of angioneurotic edema secondary to continuous infusion 5-fluorouracil occurred in a patient with recurrent carcinoma of the oral cavity, cirrhosis, and cisplatin-induced impaired renal function. This reaction occurred during the sixth and seventh courses of infusional chemotherapy. Oral diphenhydramine and prednisone were ineffective in preventing the recurrence of the allergic reaction. Discontinuance of effective chemotherapy in this patient during partial remission resulted in fatal disease progression.", "entity": "Fluorouracil", "aliases": "5 FU Lederle medac Fluorouracil biosyn HU Hexal 5-FU 5-Fluorouracil 5-Fluorouracil-biosyn 5-HU 5FU Adrucil Allergan Brand of CSP Carac Dakota Fluorouracile Dermatech Dermik Efudex Efudix Ferrer Fluoro Uracile ICN Fluoro-Uracile Fluoroplex GRY Mononitrate Monopotassium Salt Monosodium Potassium Teva Fluorouracil-GRY Fluorouracilo Far Fluoruracil Fluracedyl Flurodex Gry Haemato fu Haemato-fu Neocorp Neofluor Onkofluor Onkoworks Pharmachemie Ribofluor Riemser Roche ribosepharm", "definition": "A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.\n    ", "id": "MESH:D005472"}
{"mention": "carcinoma of the oral cavity", "mention_text": "An allergic reaction consisting of angioneurotic edema secondary to continuous infusion 5-fluorouracil occurred in a patient with recurrent carcinoma of the oral cavity, cirrhosis, and cisplatin-induced impaired renal function. This reaction occurred during the sixth and seventh courses of infusional chemotherapy. Oral diphenhydramine and prednisone were ineffective in preventing the recurrence of the allergic reaction. Discontinuance of effective chemotherapy in this patient during partial remission resulted in fatal disease progression.", "entity": "Mouth Neoplasms", "aliases": "Cancer of Mouth the Oral Cancers Neoplasm Neoplasms", "definition": "Tumors or cancer of the MOUTH.\n    ", "id": "MESH:D009062"}
{"mention": "cirrhosis", "mention_text": "An allergic reaction consisting of angioneurotic edema secondary to continuous infusion 5-fluorouracil occurred in a patient with recurrent carcinoma of the oral cavity, cirrhosis, and cisplatin-induced impaired renal function. This reaction occurred during the sixth and seventh courses of infusional chemotherapy. Oral diphenhydramine and prednisone were ineffective in preventing the recurrence of the allergic reaction. Discontinuance of effective chemotherapy in this patient during partial remission resulted in fatal disease progression.", "entity": "Fibrosis", "aliases": "Cirrhosis Fibroses Fibrosis", "definition": "Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.\n    ", "id": "MESH:D005355"}
{"mention": "cisplatin", "mention_text": "An allergic reaction consisting of angioneurotic edema secondary to continuous infusion 5-fluorouracil occurred in a patient with recurrent carcinoma of the oral cavity, cirrhosis, and cisplatin-induced impaired renal function. This reaction occurred during the sixth and seventh courses of infusional chemotherapy. Oral diphenhydramine and prednisone were ineffective in preventing the recurrence of the allergic reaction. Discontinuance of effective chemotherapy in this patient during partial remission resulted in fatal disease progression.", "entity": "Cisplatin", "aliases": "Biocisplatinum Cisplatin Diamminodichloride Platinum Dichlorodiammineplatinum NSC-119875 Platidiam Platino Platinol cis Diamminedichloroplatinum cis-Diamminedichloroplatinum cis-Diamminedichloroplatinum(II) cis-Dichlorodiammineplatinum(II) cis-Platinum", "definition": "An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.\n    ", "id": "MESH:D002945"}
{"mention": "impaired renal function", "mention_text": "An allergic reaction consisting of angioneurotic edema secondary to continuous infusion 5-fluorouracil occurred in a patient with recurrent carcinoma of the oral cavity, cirrhosis, and cisplatin-induced impaired renal function. This reaction occurred during the sixth and seventh courses of infusional chemotherapy. Oral diphenhydramine and prednisone were ineffective in preventing the recurrence of the allergic reaction. Discontinuance of effective chemotherapy in this patient during partial remission resulted in fatal disease progression.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "diphenhydramine", "mention_text": "An allergic reaction consisting of angioneurotic edema secondary to continuous infusion 5-fluorouracil occurred in a patient with recurrent carcinoma of the oral cavity, cirrhosis, and cisplatin-induced impaired renal function. This reaction occurred during the sixth and seventh courses of infusional chemotherapy. Oral diphenhydramine and prednisone were ineffective in preventing the recurrence of the allergic reaction. Discontinuance of effective chemotherapy in this patient during partial remission resulted in fatal disease progression.", "entity": "Diphenhydramine", "aliases": "2-Diphenylmethoxy-N,N-dimethylethylamine Allerdryl Benadryl Benhydramin Benylin Benzhydramine Citrate Diphenhydramine Dimedrol (1:1) Hydrochloride Diphenylhydramin Diphenylhydramine Dormin", "definition": "A histamine H1 antagonist used as an antiemetic, antitussive, for dermatoses and pruritus, for hypersensitivity reactions, as a hypnotic, an antiparkinson, and as an ingredient in common cold preparations. It has some undesired antimuscarinic and sedative effects.\n    ", "id": "MESH:D004155"}
{"mention": "prednisone", "mention_text": "An allergic reaction consisting of angioneurotic edema secondary to continuous infusion 5-fluorouracil occurred in a patient with recurrent carcinoma of the oral cavity, cirrhosis, and cisplatin-induced impaired renal function. This reaction occurred during the sixth and seventh courses of infusional chemotherapy. Oral diphenhydramine and prednisone were ineffective in preventing the recurrence of the allergic reaction. Discontinuance of effective chemotherapy in this patient during partial remission resulted in fatal disease progression.", "entity": "Prednisone", "aliases": "Apo-Prednisone Apotex Brand of Prednisone Aventis Cortan Cortancyl Cutason Dacortin Decortin Decortisyl Dehydrocortisone Deltasone Diba Encorton Encortone Enkortolon Fawns & McAllan Ferring GALENpharma Halsey Drug Hexal Hoechst ICN Kortancyl Lichtenstein Liquid Pred Merck Merz Meticorten Orasone Panafcort Panasol Pharmacia Predni Tablinen Prednidib Predniment Prednison Galen acsis Pronisone Rectodelt Schering-Plough Seatrace Solvay Sone Sterapred Trommsdorff Ultracorten Winpred acis delta-Cortis", "definition": "A synthetic anti-inflammatory glucocorticoid derived from CORTISONE. It is biologically inert and converted to PREDNISOLONE in the liver.\n    ", "id": "MESH:D011241"}
{"mention": "Amiodarone", "mention_text": "Amiodarone-induced sinoatrial block.", "entity": "Amiodarone", "aliases": "ASTA Medica Brand of Amiodarone Hydrochloride Alphapharm Amiobeta Amiodarex Amiodarona Amiohexal Aratac Armstrong Berenguer Infale Betapharm Braxan Corbionax Cordarex Cordarone G Gam Hexal Kordaron L 3428 L-3428 L3428 Leurquin Ortacrone Pharma Investi Rytmarone SKF 33134 A 33134-A 33134A Sanofi Winthrop Tachydaron Trangorex Wyeth", "definition": "An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.\n    ", "id": "MESH:D000638"}
{"mention": "sinoatrial block", "mention_text": "Amiodarone-induced sinoatrial block.", "entity": "Sinoatrial Block", "aliases": "Block Sinoatrial Exit Blocks", "definition": "Disturbance in the atrial activation that is caused by transient failure of impulse conduction from the SINOATRIAL NODE to the HEART ATRIA. It is characterized by a delayed in heartbeat and pauses between P waves in an ELECTROCARDIOGRAM.\n    ", "id": "MESH:D012848"}
{"mention": "sinoatrial block", "mention_text": "We observed sinoatrial block due to chronic amiodarone administration in a 5-year-old boy with primary cardiomyopathy, Wolff-Parkinson-White syndrome and supraventricular tachycardia. Reduction in the dosage of amiodarone resulted in the disappearance of the sinoatrial block and the persistence of asymptomatic sinus bradycardia.", "entity": "Sinoatrial Block", "aliases": "Block Sinoatrial Exit Blocks", "definition": "Disturbance in the atrial activation that is caused by transient failure of impulse conduction from the SINOATRIAL NODE to the HEART ATRIA. It is characterized by a delayed in heartbeat and pauses between P waves in an ELECTROCARDIOGRAM.\n    ", "id": "MESH:D012848"}
{"mention": "amiodarone", "mention_text": "We observed sinoatrial block due to chronic amiodarone administration in a 5-year-old boy with primary cardiomyopathy, Wolff-Parkinson-White syndrome and supraventricular tachycardia. Reduction in the dosage of amiodarone resulted in the disappearance of the sinoatrial block and the persistence of asymptomatic sinus bradycardia.", "entity": "Amiodarone", "aliases": "ASTA Medica Brand of Amiodarone Hydrochloride Alphapharm Amiobeta Amiodarex Amiodarona Amiohexal Aratac Armstrong Berenguer Infale Betapharm Braxan Corbionax Cordarex Cordarone G Gam Hexal Kordaron L 3428 L-3428 L3428 Leurquin Ortacrone Pharma Investi Rytmarone SKF 33134 A 33134-A 33134A Sanofi Winthrop Tachydaron Trangorex Wyeth", "definition": "An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.\n    ", "id": "MESH:D000638"}
{"mention": "primary cardiomyopathy", "mention_text": "We observed sinoatrial block due to chronic amiodarone administration in a 5-year-old boy with primary cardiomyopathy, Wolff-Parkinson-White syndrome and supraventricular tachycardia. Reduction in the dosage of amiodarone resulted in the disappearance of the sinoatrial block and the persistence of asymptomatic sinus bradycardia.", "entity": "Cardiomyopathies", "aliases": "Cardiomyopathies Primary Secondary Cardiomyopathy Disease Myocardial Diseases Myocardiopathies Myocardiopathy", "definition": "A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).\n    ", "id": "MESH:D009202"}
{"mention": "Wolff-Parkinson-White syndrome", "mention_text": "We observed sinoatrial block due to chronic amiodarone administration in a 5-year-old boy with primary cardiomyopathy, Wolff-Parkinson-White syndrome and supraventricular tachycardia. Reduction in the dosage of amiodarone resulted in the disappearance of the sinoatrial block and the persistence of asymptomatic sinus bradycardia.", "entity": "Wolff-Parkinson-White Syndrome", "aliases": "Anomalous Ventricular Excitation Syndrome Auriculoventricular Accessory Pathway False Bundle-Branch Block WPW Wolf-Parkinson-White Wolff-Parkinson-White Pre-Excitation with Arrhythmia Wolf Parkinson White Wolff", "definition": "A form of ventricular pre-excitation characterized by a short PR interval and a long QRS interval with a delta wave. In this syndrome, atrial impulses are abnormally conducted to the HEART VENTRICLES via an ACCESSORY CONDUCTING PATHWAY that is located between the wall of the right or left atria and the ventricles, also known as a BUNDLE OF KENT. The inherited form can be caused by mutation of PRKAG2 gene encoding a gamma-2 regulatory subunit of AMP-activated protein kinase.\n    ", "id": "MESH:D014927"}
{"mention": "supraventricular tachycardia", "mention_text": "We observed sinoatrial block due to chronic amiodarone administration in a 5-year-old boy with primary cardiomyopathy, Wolff-Parkinson-White syndrome and supraventricular tachycardia. Reduction in the dosage of amiodarone resulted in the disappearance of the sinoatrial block and the persistence of asymptomatic sinus bradycardia.", "entity": "Tachycardia, Supraventricular", "aliases": "Supraventricular Tachycardia Tachycardias", "definition": "A generic expression for any tachycardia that originates above the BUNDLE OF HIS.\n    ", "id": "MESH:D013617"}
{"mention": "sinus bradycardia", "mention_text": "We observed sinoatrial block due to chronic amiodarone administration in a 5-year-old boy with primary cardiomyopathy, Wolff-Parkinson-White syndrome and supraventricular tachycardia. Reduction in the dosage of amiodarone resulted in the disappearance of the sinoatrial block and the persistence of asymptomatic sinus bradycardia.", "entity": "Sick Sinus Syndrome", "aliases": "Dysfunction Sinus Node Dysfunctions Sick Syndrome Disease Diseases", "definition": "A condition caused by dysfunctions related to the SINOATRIAL NODE including impulse generation (CARDIAC SINUS ARREST) and impulse conduction (SINOATRIAL EXIT BLOCK). It is characterized by persistent BRADYCARDIA, chronic ATRIAL FIBRILLATION, and failure to resume sinus rhythm following CARDIOVERSION. This syndrome can be congenital or acquired, particularly after surgical correction for heart defects.\n    ", "id": "MESH:D012804"}
{"mention": "sulphasalazine", "mention_text": "Possible teratogenicity of sulphasalazine.", "entity": "Sulfasalazine", "aliases": "Alphapharm Brand of Sulfasalazine Ashbourne Asulfidine Azulfadine Azulfidine EN Colo Pleon Colo-Pleon FNA Henning Berlin Heyl Pfizer Pyralin Ratiopharm Salazopyrin Salazosulfapyridine Salicylazosulfapyridine Sanofi Synthelabo Sulfasalazin medac Sulfasalazin-Heyl Sulphasalazine Ucine Ulcol ratio ratio-Sulfasalazine", "definition": "A drug that is used in the management of inflammatory bowel diseases. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid (see MESALAMINE) released in the colon. (From Martindale, The Extra Pharmacopoeia, 30th ed, p907)\n    ", "id": "MESH:D012460"}
{"mention": "inflammatory bowel disease", "mention_text": "Three infants, born of two mothers with inflammatory bowel disease who received treatment with sulphasalazine throughout pregnancy, were found to have major congenital anomalies. In the singleton pregnancy, the mother had ulcerative colitis, and the infant, a male, had coarctation of the aorta and a ventricular septal defect. In the twin pregnancy, the mother had Crohn's disease. The first twin, a female, had a left Potter-type IIa polycystic kidney and a rudimentary left uterine cornu. The second twin, a male, had some features of Potter's facies, hypoplastic lungs, absent kidneys and ureters, and talipes equinovarus. Despite reports to the contrary, it is suggested that sulphasalazine may be teratogenic.", "entity": "Inflammatory Bowel Diseases", "aliases": "Bowel Diseases Inflammatory Disease", "definition": "Chronic, non-specific inflammation of the GASTROINTESTINAL TRACT. Etiology may be genetic or environmental. This term includes CROHN DISEASE and ULCERATIVE COLITIS.\n    ", "id": "MESH:D015212"}
{"mention": "sulphasalazine", "mention_text": "Three infants, born of two mothers with inflammatory bowel disease who received treatment with sulphasalazine throughout pregnancy, were found to have major congenital anomalies. In the singleton pregnancy, the mother had ulcerative colitis, and the infant, a male, had coarctation of the aorta and a ventricular septal defect. In the twin pregnancy, the mother had Crohn's disease. The first twin, a female, had a left Potter-type IIa polycystic kidney and a rudimentary left uterine cornu. The second twin, a male, had some features of Potter's facies, hypoplastic lungs, absent kidneys and ureters, and talipes equinovarus. Despite reports to the contrary, it is suggested that sulphasalazine may be teratogenic.", "entity": "Sulfasalazine", "aliases": "Alphapharm Brand of Sulfasalazine Ashbourne Asulfidine Azulfadine Azulfidine EN Colo Pleon Colo-Pleon FNA Henning Berlin Heyl Pfizer Pyralin Ratiopharm Salazopyrin Salazosulfapyridine Salicylazosulfapyridine Sanofi Synthelabo Sulfasalazin medac Sulfasalazin-Heyl Sulphasalazine Ucine Ulcol ratio ratio-Sulfasalazine", "definition": "A drug that is used in the management of inflammatory bowel diseases. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid (see MESALAMINE) released in the colon. (From Martindale, The Extra Pharmacopoeia, 30th ed, p907)\n    ", "id": "MESH:D012460"}
{"mention": "congenital anomalies", "mention_text": "Three infants, born of two mothers with inflammatory bowel disease who received treatment with sulphasalazine throughout pregnancy, were found to have major congenital anomalies. In the singleton pregnancy, the mother had ulcerative colitis, and the infant, a male, had coarctation of the aorta and a ventricular septal defect. In the twin pregnancy, the mother had Crohn's disease. The first twin, a female, had a left Potter-type IIa polycystic kidney and a rudimentary left uterine cornu. The second twin, a male, had some features of Potter's facies, hypoplastic lungs, absent kidneys and ureters, and talipes equinovarus. Despite reports to the contrary, it is suggested that sulphasalazine may be teratogenic.", "entity": "Congenital Abnormalities", "aliases": "Abnormalities Congenital Abnormality Birth Defect Defects Deformities Deformity", "definition": "Malformations of organs or body parts during development in utero.\n    ", "id": "MESH:D000013"}
{"mention": "ulcerative colitis", "mention_text": "Three infants, born of two mothers with inflammatory bowel disease who received treatment with sulphasalazine throughout pregnancy, were found to have major congenital anomalies. In the singleton pregnancy, the mother had ulcerative colitis, and the infant, a male, had coarctation of the aorta and a ventricular septal defect. In the twin pregnancy, the mother had Crohn's disease. The first twin, a female, had a left Potter-type IIa polycystic kidney and a rudimentary left uterine cornu. The second twin, a male, had some features of Potter's facies, hypoplastic lungs, absent kidneys and ureters, and talipes equinovarus. Despite reports to the contrary, it is suggested that sulphasalazine may be teratogenic.", "entity": "Colitis, Ulcerative", "aliases": "Colitis Gravis Ulcerative Idiopathic Proctocolitis Inflammatory Bowel Disease Type", "definition": "Inflammation of the COLON that is predominantly confined to the MUCOSA. Its major symptoms include DIARRHEA, rectal BLEEDING, the passage of MUCUS, and ABDOMINAL PAIN.\n    ", "id": "MESH:D003093"}
{"mention": "coarctation of the aorta", "mention_text": "Three infants, born of two mothers with inflammatory bowel disease who received treatment with sulphasalazine throughout pregnancy, were found to have major congenital anomalies. In the singleton pregnancy, the mother had ulcerative colitis, and the infant, a male, had coarctation of the aorta and a ventricular septal defect. In the twin pregnancy, the mother had Crohn's disease. The first twin, a female, had a left Potter-type IIa polycystic kidney and a rudimentary left uterine cornu. The second twin, a male, had some features of Potter's facies, hypoplastic lungs, absent kidneys and ureters, and talipes equinovarus. Despite reports to the contrary, it is suggested that sulphasalazine may be teratogenic.", "entity": "Aortic Coarctation", "aliases": "Aorta Coarctation Coarctations Dominant Aortic of the", "definition": "A birth defect characterized by the narrowing of the AORTA that can be of varying degree and at any point from the transverse arch to the iliac bifurcation. Aortic coarctation causes arterial HYPERTENSION before the point of narrowing and arterial HYPOTENSION beyond the narrowed portion.\n    ", "id": "MESH:D001017"}
{"mention": "ventricular septal defect", "mention_text": "Three infants, born of two mothers with inflammatory bowel disease who received treatment with sulphasalazine throughout pregnancy, were found to have major congenital anomalies. In the singleton pregnancy, the mother had ulcerative colitis, and the infant, a male, had coarctation of the aorta and a ventricular septal defect. In the twin pregnancy, the mother had Crohn's disease. The first twin, a female, had a left Potter-type IIa polycystic kidney and a rudimentary left uterine cornu. The second twin, a male, had some features of Potter's facies, hypoplastic lungs, absent kidneys and ureters, and talipes equinovarus. Despite reports to the contrary, it is suggested that sulphasalazine may be teratogenic.", "entity": "Heart Septal Defects, Ventricular", "aliases": "Defect Intraventricular Septal Ventricular Defects Heart", "definition": "Developmental abnormalities in any portion of the VENTRICULAR SEPTUM resulting in abnormal communications between the two lower chambers of the heart. Classification of ventricular septal defects is based on location of the communication, such as perimembranous, inlet, outlet (infundibular), central muscular, marginal muscular, or apical muscular defect.\n    ", "id": "MESH:D006345"}
{"mention": "Crohn's disease", "mention_text": "Three infants, born of two mothers with inflammatory bowel disease who received treatment with sulphasalazine throughout pregnancy, were found to have major congenital anomalies. In the singleton pregnancy, the mother had ulcerative colitis, and the infant, a male, had coarctation of the aorta and a ventricular septal defect. In the twin pregnancy, the mother had Crohn's disease. The first twin, a female, had a left Potter-type IIa polycystic kidney and a rudimentary left uterine cornu. The second twin, a male, had some features of Potter's facies, hypoplastic lungs, absent kidneys and ureters, and talipes equinovarus. Despite reports to the contrary, it is suggested that sulphasalazine may be teratogenic.", "entity": "Crohn Disease", "aliases": "Colitis Granulomatous Crohn Disease Crohn's Enteritis Crohns Regional Ileitis Terminal Ileocolitis Inflammatory Bowel 1 Ileitides", "definition": "A chronic transmural inflammation that may involve any part of the DIGESTIVE TRACT from MOUTH to ANUS, mostly found in the ILEUM, the CECUM, and the COLON. In Crohn disease, the inflammation, extending through the intestinal wall from the MUCOSA to the serosa, is characteristically asymmetric and segmental. Epithelioid GRANULOMAS may be seen in some patients.\n    ", "id": "MESH:D003424"}
{"mention": "Potter-type IIa polycystic kidney", "mention_text": "Three infants, born of two mothers with inflammatory bowel disease who received treatment with sulphasalazine throughout pregnancy, were found to have major congenital anomalies. In the singleton pregnancy, the mother had ulcerative colitis, and the infant, a male, had coarctation of the aorta and a ventricular septal defect. In the twin pregnancy, the mother had Crohn's disease. The first twin, a female, had a left Potter-type IIa polycystic kidney and a rudimentary left uterine cornu. The second twin, a male, had some features of Potter's facies, hypoplastic lungs, absent kidneys and ureters, and talipes equinovarus. Despite reports to the contrary, it is suggested that sulphasalazine may be teratogenic.", "entity": "Polycystic Kidney Diseases", "aliases": "Disease Polycystic Kidney Renal Diseases Kidneys", "definition": "Hereditary diseases that are characterized by the progressive expansion of a large number of tightly packed CYSTS within the KIDNEYS. They include diseases with autosomal dominant and autosomal recessive inheritance.\n    ", "id": "MESH:D007690"}
{"mention": "talipes equinovarus", "mention_text": "Three infants, born of two mothers with inflammatory bowel disease who received treatment with sulphasalazine throughout pregnancy, were found to have major congenital anomalies. In the singleton pregnancy, the mother had ulcerative colitis, and the infant, a male, had coarctation of the aorta and a ventricular septal defect. In the twin pregnancy, the mother had Crohn's disease. The first twin, a female, had a left Potter-type IIa polycystic kidney and a rudimentary left uterine cornu. The second twin, a male, had some features of Potter's facies, hypoplastic lungs, absent kidneys and ureters, and talipes equinovarus. Despite reports to the contrary, it is suggested that sulphasalazine may be teratogenic.", "entity": "Clubfoot", "aliases": "Clubfoot Congenital Talipes Equinovarus Pie Torcido Torcidos Talipe", "definition": "A deformed foot in which the foot is plantarflexed, inverted and adducted.\n    ", "id": "MESH:D003025"}
{"mention": "Veno-occlusive liver disease", "mention_text": "Veno-occlusive liver disease after dacarbazine therapy (DTIC) for melanoma.", "entity": "Hepatic Veno-Occlusive Disease", "aliases": "Disease Hepatic Veno-Occlusive Veno Occlusive Diseases Sinusoidal Obstruction Syndrome", "definition": "Liver disease that is caused by injuries to the ENDOTHELIAL CELLS of the vessels and subendothelial EDEMA, but not by THROMBOSIS. Extracellular matrix, rich in FIBRONECTINS, is usually deposited around the HEPATIC VEINS leading to venous outflow occlusion and sinusoidal obstruction.\n    ", "id": "MESH:D006504"}
{"mention": "dacarbazine", "mention_text": "Veno-occlusive liver disease after dacarbazine therapy (DTIC) for melanoma.", "entity": "Dacarbazine", "aliases": "5-(3,3-Dimethyl-1-triazeno)imidazole-4-carboxamide Biocarbazine Carboxamide Dimethyl Imidazole DIC DTIC Dome DTIC-Dome DTICDome Dacarbazine Decarbazine Deticene Triazeno ICDT NSC 45388 NSC-45388 NSC45388", "definition": "An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564)\n    ", "id": "MESH:D003606"}
{"mention": "DTIC", "mention_text": "Veno-occlusive liver disease after dacarbazine therapy (DTIC) for melanoma.", "entity": "Dacarbazine", "aliases": "5-(3,3-Dimethyl-1-triazeno)imidazole-4-carboxamide Biocarbazine Carboxamide Dimethyl Imidazole DIC DTIC Dome DTIC-Dome DTICDome Dacarbazine Decarbazine Deticene Triazeno ICDT NSC 45388 NSC-45388 NSC45388", "definition": "An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564)\n    ", "id": "MESH:D003606"}
{"mention": "melanoma", "mention_text": "Veno-occlusive liver disease after dacarbazine therapy (DTIC) for melanoma.", "entity": "Melanoma", "aliases": "Malignant Melanoma Melanomas", "definition": "A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)\n    ", "id": "MESH:D008545"}
{"mention": "veno-occlusive disease of the liver", "mention_text": "A case of veno-occlusive disease of the liver with fatal outcome after dacarbazine (DTIC) therapy for melanoma is reported. There was a fulminant clinical course from start of symptoms until death. At autopsy the liver was enlarged and firm with signs of venous congestion. Small- and medium-sized hepatic veins were blocked by thrombosis. Eosinophilic infiltrations were found around the vessels. Published cases from the literature are reviewed and pertinent features discussed.", "entity": "Hepatic Veno-Occlusive Disease", "aliases": "Disease Hepatic Veno-Occlusive Veno Occlusive Diseases Sinusoidal Obstruction Syndrome", "definition": "Liver disease that is caused by injuries to the ENDOTHELIAL CELLS of the vessels and subendothelial EDEMA, but not by THROMBOSIS. Extracellular matrix, rich in FIBRONECTINS, is usually deposited around the HEPATIC VEINS leading to venous outflow occlusion and sinusoidal obstruction.\n    ", "id": "MESH:D006504"}
{"mention": "dacarbazine", "mention_text": "A case of veno-occlusive disease of the liver with fatal outcome after dacarbazine (DTIC) therapy for melanoma is reported. There was a fulminant clinical course from start of symptoms until death. At autopsy the liver was enlarged and firm with signs of venous congestion. Small- and medium-sized hepatic veins were blocked by thrombosis. Eosinophilic infiltrations were found around the vessels. Published cases from the literature are reviewed and pertinent features discussed.", "entity": "Dacarbazine", "aliases": "5-(3,3-Dimethyl-1-triazeno)imidazole-4-carboxamide Biocarbazine Carboxamide Dimethyl Imidazole DIC DTIC Dome DTIC-Dome DTICDome Dacarbazine Decarbazine Deticene Triazeno ICDT NSC 45388 NSC-45388 NSC45388", "definition": "An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564)\n    ", "id": "MESH:D003606"}
{"mention": "DTIC", "mention_text": "A case of veno-occlusive disease of the liver with fatal outcome after dacarbazine (DTIC) therapy for melanoma is reported. There was a fulminant clinical course from start of symptoms until death. At autopsy the liver was enlarged and firm with signs of venous congestion. Small- and medium-sized hepatic veins were blocked by thrombosis. Eosinophilic infiltrations were found around the vessels. Published cases from the literature are reviewed and pertinent features discussed.", "entity": "Dacarbazine", "aliases": "5-(3,3-Dimethyl-1-triazeno)imidazole-4-carboxamide Biocarbazine Carboxamide Dimethyl Imidazole DIC DTIC Dome DTIC-Dome DTICDome Dacarbazine Decarbazine Deticene Triazeno ICDT NSC 45388 NSC-45388 NSC45388", "definition": "An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564)\n    ", "id": "MESH:D003606"}
{"mention": "melanoma", "mention_text": "A case of veno-occlusive disease of the liver with fatal outcome after dacarbazine (DTIC) therapy for melanoma is reported. There was a fulminant clinical course from start of symptoms until death. At autopsy the liver was enlarged and firm with signs of venous congestion. Small- and medium-sized hepatic veins were blocked by thrombosis. Eosinophilic infiltrations were found around the vessels. Published cases from the literature are reviewed and pertinent features discussed.", "entity": "Melanoma", "aliases": "Malignant Melanoma Melanomas", "definition": "A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)\n    ", "id": "MESH:D008545"}
{"mention": "death", "mention_text": "A case of veno-occlusive disease of the liver with fatal outcome after dacarbazine (DTIC) therapy for melanoma is reported. There was a fulminant clinical course from start of symptoms until death. At autopsy the liver was enlarged and firm with signs of venous congestion. Small- and medium-sized hepatic veins were blocked by thrombosis. Eosinophilic infiltrations were found around the vessels. Published cases from the literature are reviewed and pertinent features discussed.", "entity": "Death", "aliases": "Cardiac Death Determination of Near-Death Experience", "definition": "Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.\n    ", "id": "MESH:D003643"}
{"mention": "venous congestion", "mention_text": "A case of veno-occlusive disease of the liver with fatal outcome after dacarbazine (DTIC) therapy for melanoma is reported. There was a fulminant clinical course from start of symptoms until death. At autopsy the liver was enlarged and firm with signs of venous congestion. Small- and medium-sized hepatic veins were blocked by thrombosis. Eosinophilic infiltrations were found around the vessels. Published cases from the literature are reviewed and pertinent features discussed.", "entity": "Hyperemia", "aliases": "Active Hyperemia Arterial Congestion Venous Engorgement Passive Reactive Hyperemias", "definition": "The presence of an increased amount of blood in a body part or an organ leading to congestion or engorgement of blood vessels. Hyperemia can be due to increase of blood flow into the area (active or arterial), or due to obstruction of outflow of blood from the area (passive or venous).\n    ", "id": "MESH:D006940"}
{"mention": "thrombosis", "mention_text": "A case of veno-occlusive disease of the liver with fatal outcome after dacarbazine (DTIC) therapy for melanoma is reported. There was a fulminant clinical course from start of symptoms until death. At autopsy the liver was enlarged and firm with signs of venous congestion. Small- and medium-sized hepatic veins were blocked by thrombosis. Eosinophilic infiltrations were found around the vessels. Published cases from the literature are reviewed and pertinent features discussed.", "entity": "Thrombosis", "aliases": "Thromboses Thrombosis Thrombus", "definition": "Formation and development of a thrombus or blood clot in the blood vessel.\n    ", "id": "MESH:D013927"}
{"mention": "tardive dyskinesia", "mention_text": "A case of tardive dyskinesia caused by metoclopramide.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "metoclopramide", "mention_text": "A case of tardive dyskinesia caused by metoclopramide.", "entity": "Metoclopramide", "aliases": "4-Amino-5-chloro-N-(2-(diethylamino)ethyl)-2-methoxybenzamide Berk Brand of Metoclopramide Hydrochloride Cerucal Dihydrochloride Maxolon Metaclopramide Monohydrochloride Monohydrate Primperan Reglan Rimetin Temmler", "definition": "A dopamine D2 antagonist that is used as an antiemetic.\n    ", "id": "MESH:D008787"}
{"mention": "Abnormal involuntary movements", "mention_text": "Abnormal involuntary movements appeared in the mouth, tongue, neck and abdomen of a 64-year-old male patient after he took metoclopramide for gastrointestinal disorder in a regimen of 30 mg per day for a total of about 260 days. The symptoms exacerbated to a maximum in a month. When the metoclopramide administration was discontinued, the abnormal movements gradually improved to a considerable extent. Attention to the possible induction of specific tardive dyskinesia is called for in the use of this drug.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "metoclopramide", "mention_text": "Abnormal involuntary movements appeared in the mouth, tongue, neck and abdomen of a 64-year-old male patient after he took metoclopramide for gastrointestinal disorder in a regimen of 30 mg per day for a total of about 260 days. The symptoms exacerbated to a maximum in a month. When the metoclopramide administration was discontinued, the abnormal movements gradually improved to a considerable extent. Attention to the possible induction of specific tardive dyskinesia is called for in the use of this drug.", "entity": "Metoclopramide", "aliases": "4-Amino-5-chloro-N-(2-(diethylamino)ethyl)-2-methoxybenzamide Berk Brand of Metoclopramide Hydrochloride Cerucal Dihydrochloride Maxolon Metaclopramide Monohydrochloride Monohydrate Primperan Reglan Rimetin Temmler", "definition": "A dopamine D2 antagonist that is used as an antiemetic.\n    ", "id": "MESH:D008787"}
{"mention": "gastrointestinal disorder", "mention_text": "Abnormal involuntary movements appeared in the mouth, tongue, neck and abdomen of a 64-year-old male patient after he took metoclopramide for gastrointestinal disorder in a regimen of 30 mg per day for a total of about 260 days. The symptoms exacerbated to a maximum in a month. When the metoclopramide administration was discontinued, the abnormal movements gradually improved to a considerable extent. Attention to the possible induction of specific tardive dyskinesia is called for in the use of this drug.", "entity": "Gastrointestinal Diseases", "aliases": "Cholera Infantum Disease Gastrointestinal Diseases Disorder Functional Disorders", "definition": "Diseases in any segment of the GASTROINTESTINAL TRACT from ESOPHAGUS to RECTUM.\n    ", "id": "MESH:D005767"}
{"mention": "abnormal movements", "mention_text": "Abnormal involuntary movements appeared in the mouth, tongue, neck and abdomen of a 64-year-old male patient after he took metoclopramide for gastrointestinal disorder in a regimen of 30 mg per day for a total of about 260 days. The symptoms exacerbated to a maximum in a month. When the metoclopramide administration was discontinued, the abnormal movements gradually improved to a considerable extent. Attention to the possible induction of specific tardive dyskinesia is called for in the use of this drug.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "tardive dyskinesia", "mention_text": "Abnormal involuntary movements appeared in the mouth, tongue, neck and abdomen of a 64-year-old male patient after he took metoclopramide for gastrointestinal disorder in a regimen of 30 mg per day for a total of about 260 days. The symptoms exacerbated to a maximum in a month. When the metoclopramide administration was discontinued, the abnormal movements gradually improved to a considerable extent. Attention to the possible induction of specific tardive dyskinesia is called for in the use of this drug.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "amiodarone", "mention_text": "Further observations on the electrophysiologic effects of oral amiodarone therapy.", "entity": "Amiodarone", "aliases": "ASTA Medica Brand of Amiodarone Hydrochloride Alphapharm Amiobeta Amiodarex Amiodarona Amiohexal Aratac Armstrong Berenguer Infale Betapharm Braxan Corbionax Cordarex Cordarone G Gam Hexal Kordaron L 3428 L-3428 L3428 Leurquin Ortacrone Pharma Investi Rytmarone SKF 33134 A 33134-A 33134A Sanofi Winthrop Tachydaron Trangorex Wyeth", "definition": "An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.\n    ", "id": "MESH:D000638"}
{"mention": "intra-Hisian block", "mention_text": "A case is presented of a reversible intra-Hisian block occurring under amiodarone treatment for atrial tachycardia in a patient without clear intraventricular conduction abnormalities. His bundle recordings showed an atrial tachycardia with intermittent exit block and greatly prolonged BH and HV intervals (40 and 100 msec, respectively). Thirty days after amiodarone discontinuation, His bundle electrograms showed atrial flutter without intra-Hisian or infra-Hisian delay. Amiodarone should be used with caution during long-term oral therapy in patients with or without clear intraventricular conduction defects.", "entity": "Heart Block", "aliases": "A V Dissociation A-V Dissociations Atrioventricular Auriculo Ventricular Auriculo-Ventricular Block Heart Blocks", "definition": "Impaired conduction of cardiac impulse that can occur anywhere along the conduction pathway, such as between the SINOATRIAL NODE and the right atrium (SA block) or between atria and ventricles (AV block). Heart blocks can be classified by the duration, frequency, or completeness of conduction block. Reversibility depends on the degree of structural or functional defects.\n    ", "id": "MESH:D006327"}
{"mention": "amiodarone", "mention_text": "A case is presented of a reversible intra-Hisian block occurring under amiodarone treatment for atrial tachycardia in a patient without clear intraventricular conduction abnormalities. His bundle recordings showed an atrial tachycardia with intermittent exit block and greatly prolonged BH and HV intervals (40 and 100 msec, respectively). Thirty days after amiodarone discontinuation, His bundle electrograms showed atrial flutter without intra-Hisian or infra-Hisian delay. Amiodarone should be used with caution during long-term oral therapy in patients with or without clear intraventricular conduction defects.", "entity": "Amiodarone", "aliases": "ASTA Medica Brand of Amiodarone Hydrochloride Alphapharm Amiobeta Amiodarex Amiodarona Amiohexal Aratac Armstrong Berenguer Infale Betapharm Braxan Corbionax Cordarex Cordarone G Gam Hexal Kordaron L 3428 L-3428 L3428 Leurquin Ortacrone Pharma Investi Rytmarone SKF 33134 A 33134-A 33134A Sanofi Winthrop Tachydaron Trangorex Wyeth", "definition": "An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.\n    ", "id": "MESH:D000638"}
{"mention": "atrial tachycardia", "mention_text": "A case is presented of a reversible intra-Hisian block occurring under amiodarone treatment for atrial tachycardia in a patient without clear intraventricular conduction abnormalities. His bundle recordings showed an atrial tachycardia with intermittent exit block and greatly prolonged BH and HV intervals (40 and 100 msec, respectively). Thirty days after amiodarone discontinuation, His bundle electrograms showed atrial flutter without intra-Hisian or infra-Hisian delay. Amiodarone should be used with caution during long-term oral therapy in patients with or without clear intraventricular conduction defects.", "entity": "Tachycardia, Supraventricular", "aliases": "Supraventricular Tachycardia Tachycardias", "definition": "A generic expression for any tachycardia that originates above the BUNDLE OF HIS.\n    ", "id": "MESH:D013617"}
{"mention": "intraventricular conduction abnormalities", "mention_text": "A case is presented of a reversible intra-Hisian block occurring under amiodarone treatment for atrial tachycardia in a patient without clear intraventricular conduction abnormalities. His bundle recordings showed an atrial tachycardia with intermittent exit block and greatly prolonged BH and HV intervals (40 and 100 msec, respectively). Thirty days after amiodarone discontinuation, His bundle electrograms showed atrial flutter without intra-Hisian or infra-Hisian delay. Amiodarone should be used with caution during long-term oral therapy in patients with or without clear intraventricular conduction defects.", "entity": "Heart Septal Defects, Ventricular", "aliases": "Defect Intraventricular Septal Ventricular Defects Heart", "definition": "Developmental abnormalities in any portion of the VENTRICULAR SEPTUM resulting in abnormal communications between the two lower chambers of the heart. Classification of ventricular septal defects is based on location of the communication, such as perimembranous, inlet, outlet (infundibular), central muscular, marginal muscular, or apical muscular defect.\n    ", "id": "MESH:D006345"}
{"mention": "atrial flutter", "mention_text": "A case is presented of a reversible intra-Hisian block occurring under amiodarone treatment for atrial tachycardia in a patient without clear intraventricular conduction abnormalities. His bundle recordings showed an atrial tachycardia with intermittent exit block and greatly prolonged BH and HV intervals (40 and 100 msec, respectively). Thirty days after amiodarone discontinuation, His bundle electrograms showed atrial flutter without intra-Hisian or infra-Hisian delay. Amiodarone should be used with caution during long-term oral therapy in patients with or without clear intraventricular conduction defects.", "entity": "Atrial Flutter", "aliases": "Atrial Flutter Flutters Auricular", "definition": "Rapid, irregular atrial contractions caused by a block of electrical impulse conduction in the right atrium and a reentrant wave front traveling up the inter-atrial septum and down the right atrial free wall or vice versa. Unlike ATRIAL FIBRILLATION which is caused by abnormal impulse generation, typical atrial flutter is caused by abnormal impulse conduction. As in atrial fibrillation, patients with atrial flutter cannot effectively pump blood into the lower chambers of the heart (HEART VENTRICLES).\n    ", "id": "MESH:D001282"}
{"mention": "Amiodarone", "mention_text": "A case is presented of a reversible intra-Hisian block occurring under amiodarone treatment for atrial tachycardia in a patient without clear intraventricular conduction abnormalities. His bundle recordings showed an atrial tachycardia with intermittent exit block and greatly prolonged BH and HV intervals (40 and 100 msec, respectively). Thirty days after amiodarone discontinuation, His bundle electrograms showed atrial flutter without intra-Hisian or infra-Hisian delay. Amiodarone should be used with caution during long-term oral therapy in patients with or without clear intraventricular conduction defects.", "entity": "Amiodarone", "aliases": "ASTA Medica Brand of Amiodarone Hydrochloride Alphapharm Amiobeta Amiodarex Amiodarona Amiohexal Aratac Armstrong Berenguer Infale Betapharm Braxan Corbionax Cordarex Cordarone G Gam Hexal Kordaron L 3428 L-3428 L3428 Leurquin Ortacrone Pharma Investi Rytmarone SKF 33134 A 33134-A 33134A Sanofi Winthrop Tachydaron Trangorex Wyeth", "definition": "An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.\n    ", "id": "MESH:D000638"}
{"mention": "Busulfan", "mention_text": "Busulfan-induced hemorrhagic cystitis.", "entity": "Busulfan", "aliases": "Busulfan GlaxoSmithKline Brand Orphan Wellcome Busulfex Busulphan Glaxo of Glyzophrol Myelosan Mylecytan Myleran Myléran n-Butane-1,3-di(methylsulfonate)", "definition": "An alkylating agent having a selective immunosuppressive effect on BONE MARROW. It has been used in the palliative treatment of chronic myeloid leukemia (MYELOID LEUKEMIA, CHRONIC), but although symptomatic relief is provided, no permanent remission is brought about. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), busulfan is listed as a known carcinogen.\n    ", "id": "MESH:D002066"}
{"mention": "hemorrhagic", "mention_text": "Busulfan-induced hemorrhagic cystitis.", "entity": "Hemorrhage", "aliases": "Bleeding Hemorrhage Hemorrhages", "definition": "Bleeding or escape of blood from a vessel.\n    ", "id": "MESH:D006470"}
{"mention": "cystitis", "mention_text": "Busulfan-induced hemorrhagic cystitis.", "entity": "Cystitis", "aliases": "Cystitides Cystitis", "definition": "Inflammation of the URINARY BLADDER, either from bacterial or non-bacterial causes. Cystitis is usually associated with painful urination (dysuria), increased frequency, urgency, and suprapubic pain.\n    ", "id": "MESH:D003556"}
{"mention": "busulfan", "mention_text": "A case of a busulfan-induced hemorrhage cystitis is reported. Spontaneous resolution occurred following cessation of the drug. The similarity between the histologic appearances of busulfan cystitis and both radiation and cyclophosphamide-induced cystitis is discussed and the world literature reviewed. In view of the known tendency of busulfan to induce cellular atypia and carcinoma in other sites, periodic urinary cytology is suggested in patients on long-term therapy.", "entity": "Busulfan", "aliases": "Busulfan GlaxoSmithKline Brand Orphan Wellcome Busulfex Busulphan Glaxo of Glyzophrol Myelosan Mylecytan Myleran Myléran n-Butane-1,3-di(methylsulfonate)", "definition": "An alkylating agent having a selective immunosuppressive effect on BONE MARROW. It has been used in the palliative treatment of chronic myeloid leukemia (MYELOID LEUKEMIA, CHRONIC), but although symptomatic relief is provided, no permanent remission is brought about. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), busulfan is listed as a known carcinogen.\n    ", "id": "MESH:D002066"}
{"mention": "hemorrhage", "mention_text": "A case of a busulfan-induced hemorrhage cystitis is reported. Spontaneous resolution occurred following cessation of the drug. The similarity between the histologic appearances of busulfan cystitis and both radiation and cyclophosphamide-induced cystitis is discussed and the world literature reviewed. In view of the known tendency of busulfan to induce cellular atypia and carcinoma in other sites, periodic urinary cytology is suggested in patients on long-term therapy.", "entity": "Hemorrhage", "aliases": "Bleeding Hemorrhage Hemorrhages", "definition": "Bleeding or escape of blood from a vessel.\n    ", "id": "MESH:D006470"}
{"mention": "cystitis", "mention_text": "A case of a busulfan-induced hemorrhage cystitis is reported. Spontaneous resolution occurred following cessation of the drug. The similarity between the histologic appearances of busulfan cystitis and both radiation and cyclophosphamide-induced cystitis is discussed and the world literature reviewed. In view of the known tendency of busulfan to induce cellular atypia and carcinoma in other sites, periodic urinary cytology is suggested in patients on long-term therapy.", "entity": "Cystitis", "aliases": "Cystitides Cystitis", "definition": "Inflammation of the URINARY BLADDER, either from bacterial or non-bacterial causes. Cystitis is usually associated with painful urination (dysuria), increased frequency, urgency, and suprapubic pain.\n    ", "id": "MESH:D003556"}
{"mention": "cyclophosphamide", "mention_text": "A case of a busulfan-induced hemorrhage cystitis is reported. Spontaneous resolution occurred following cessation of the drug. The similarity between the histologic appearances of busulfan cystitis and both radiation and cyclophosphamide-induced cystitis is discussed and the world literature reviewed. In view of the known tendency of busulfan to induce cellular atypia and carcinoma in other sites, periodic urinary cytology is suggested in patients on long-term therapy.", "entity": "Cyclophosphamide", "aliases": "Anhydrous Cyclophosphamide B 518 B-518 B518 Monohydrate (R)-Isomer (S)-Isomer Cyclophosphane Cytophosphan Cytophosphane Cytoxan Endoxan NSC 26271 NSC-26271 NSC26271 Neosar Procytox Sendoxan", "definition": "Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.\n    ", "id": "MESH:D003520"}
{"mention": "carcinoma", "mention_text": "A case of a busulfan-induced hemorrhage cystitis is reported. Spontaneous resolution occurred following cessation of the drug. The similarity between the histologic appearances of busulfan cystitis and both radiation and cyclophosphamide-induced cystitis is discussed and the world literature reviewed. In view of the known tendency of busulfan to induce cellular atypia and carcinoma in other sites, periodic urinary cytology is suggested in patients on long-term therapy.", "entity": "Carcinoma", "aliases": "Anaplastic Carcinoma Carcinomas Spindle Cell Spindle-Cell Undifferentiated Carcinomatoses Carcinomatosis Epithelial Neoplasm Malignant Neoplasms Tumor Tumors Epithelioma Epitheliomas", "definition": "A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm but is often wrongly used as a synonym for \"cancer.\" (From Dorland, 27th ed)\n    ", "id": "MESH:D002277"}
{"mention": "hypertensive", "mention_text": "Rebound hypertensive after sodium nitroprusside prevented by saralasin in rats.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "sodium nitroprusside", "mention_text": "Rebound hypertensive after sodium nitroprusside prevented by saralasin in rats.", "entity": "Nitroprusside", "aliases": "Abbott Brand of Sodium Nitroprusside Bayer Cyanonitrosylferrate Disodium Salt Faulding Fides Ecopharma Ketostix Naniprus Nipride Nipruton Nitriate Nitroferricyanide Nitropress Nitroprussiat Dihydrate Roche SERB", "definition": "A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.\n    ", "id": "MESH:D009599"}
{"mention": "saralasin", "mention_text": "Rebound hypertensive after sodium nitroprusside prevented by saralasin in rats.", "entity": "Saralasin", "aliases": "(Sar(1),Ala(8))ANGII (Sar1,Val5,Ala8)Angiotensin II 1 Sar 8 Ala Angiotensin Sarcosine Alanine 1-Sar-8-Ala 1-Sarcosine-8-Alanine Sar(1)-Ala(8)- Sarcosyl(1)-Alanine(8)- Anhydrous Saralasin Acetate Hydrated Sar-Arg-Val-Tyr-Val-His-Pro-Ala", "definition": "An octapeptide analog of angiotensin II (bovine) with amino acids 1 and 8 replaced with sarcosine and alanine, respectively. It is a highly specific competitive inhibitor of angiotensin II that is used in the diagnosis of HYPERTENSION.\n    ", "id": "MESH:D012504"}
{"mention": "angiotensin", "mention_text": "The role of the renin--angiotensin system in the maintenance of blood pressure during halothane anesthesia and sodium nitroprusside (SNP)-induced hypotension was evaluated. Control rats received halothane anesthesia (1 MAC) for one hour, followed by SNP infusion, 40 microgram/kg/min, for 30 min, followed by a 30-min recovery period. A second group of rats was treated identically and, in addition, received an infusion of saralasin (a competitive inhibitor of angiotensin II) throughout the experimental period. In each group, SNP infusion resulted in an initial decrease in blood pressure from 86 torr and 83 torr, respectively, to 48 torr. During the SNP infusion the control animals demonstrated a progressive increase in blood pressure to 61 torr, whereas the saralasin-treated animals showed no change. Following discontinuation of SNP, blood pressure in the control animals rebounded to 94 torr, as compared with 78 torr in the saralasin-treated rats. This study indicates that with stable halothane anesthesia, the partial recovery of blood pressure during SNP infusion and the post-SNP rebound of blood pressure can be completely blocked by saralasin. This demonstrates the participation of the renin--angiotensin system in antagonizing the combined hypotensive effects of halothane and SNP.", "entity": "Angiotensins", "aliases": "Angiotensin Angiotensins", "definition": "Oligopeptides which are important in the regulation of blood pressure (VASOCONSTRICTION) and fluid homeostasis via the RENIN-ANGIOTENSIN SYSTEM. These include angiotensins derived naturally from precursor ANGIOTENSINOGEN, and those synthesized.\n    ", "id": "MESH:D000809"}
{"mention": "halothane", "mention_text": "The role of the renin--angiotensin system in the maintenance of blood pressure during halothane anesthesia and sodium nitroprusside (SNP)-induced hypotension was evaluated. Control rats received halothane anesthesia (1 MAC) for one hour, followed by SNP infusion, 40 microgram/kg/min, for 30 min, followed by a 30-min recovery period. A second group of rats was treated identically and, in addition, received an infusion of saralasin (a competitive inhibitor of angiotensin II) throughout the experimental period. In each group, SNP infusion resulted in an initial decrease in blood pressure from 86 torr and 83 torr, respectively, to 48 torr. During the SNP infusion the control animals demonstrated a progressive increase in blood pressure to 61 torr, whereas the saralasin-treated animals showed no change. Following discontinuation of SNP, blood pressure in the control animals rebounded to 94 torr, as compared with 78 torr in the saralasin-treated rats. This study indicates that with stable halothane anesthesia, the partial recovery of blood pressure during SNP infusion and the post-SNP rebound of blood pressure can be completely blocked by saralasin. This demonstrates the participation of the renin--angiotensin system in antagonizing the combined hypotensive effects of halothane and SNP.", "entity": "Halothane", "aliases": "1,1,1-Trifluoro-2-Chloro-2-Bromoethane Fluothane Ftorotan Halothane Narcotan", "definition": "A nonflammable, halogenated, hydrocarbon anesthetic that provides relatively rapid induction with little or no excitement. Analgesia may not be adequate. NITROUS OXIDE is often given concomitantly. Because halothane may not produce sufficient muscle relaxation, supplemental neuromuscular blocking agents may be required. (From AMA Drug Evaluations Annual, 1994, p178)\n    ", "id": "MESH:D006221"}
{"mention": "sodium nitroprusside", "mention_text": "The role of the renin--angiotensin system in the maintenance of blood pressure during halothane anesthesia and sodium nitroprusside (SNP)-induced hypotension was evaluated. Control rats received halothane anesthesia (1 MAC) for one hour, followed by SNP infusion, 40 microgram/kg/min, for 30 min, followed by a 30-min recovery period. A second group of rats was treated identically and, in addition, received an infusion of saralasin (a competitive inhibitor of angiotensin II) throughout the experimental period. In each group, SNP infusion resulted in an initial decrease in blood pressure from 86 torr and 83 torr, respectively, to 48 torr. During the SNP infusion the control animals demonstrated a progressive increase in blood pressure to 61 torr, whereas the saralasin-treated animals showed no change. Following discontinuation of SNP, blood pressure in the control animals rebounded to 94 torr, as compared with 78 torr in the saralasin-treated rats. This study indicates that with stable halothane anesthesia, the partial recovery of blood pressure during SNP infusion and the post-SNP rebound of blood pressure can be completely blocked by saralasin. This demonstrates the participation of the renin--angiotensin system in antagonizing the combined hypotensive effects of halothane and SNP.", "entity": "Nitroprusside", "aliases": "Abbott Brand of Sodium Nitroprusside Bayer Cyanonitrosylferrate Disodium Salt Faulding Fides Ecopharma Ketostix Naniprus Nipride Nipruton Nitriate Nitroferricyanide Nitropress Nitroprussiat Dihydrate Roche SERB", "definition": "A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.\n    ", "id": "MESH:D009599"}
{"mention": "SNP", "mention_text": "The role of the renin--angiotensin system in the maintenance of blood pressure during halothane anesthesia and sodium nitroprusside (SNP)-induced hypotension was evaluated. Control rats received halothane anesthesia (1 MAC) for one hour, followed by SNP infusion, 40 microgram/kg/min, for 30 min, followed by a 30-min recovery period. A second group of rats was treated identically and, in addition, received an infusion of saralasin (a competitive inhibitor of angiotensin II) throughout the experimental period. In each group, SNP infusion resulted in an initial decrease in blood pressure from 86 torr and 83 torr, respectively, to 48 torr. During the SNP infusion the control animals demonstrated a progressive increase in blood pressure to 61 torr, whereas the saralasin-treated animals showed no change. Following discontinuation of SNP, blood pressure in the control animals rebounded to 94 torr, as compared with 78 torr in the saralasin-treated rats. This study indicates that with stable halothane anesthesia, the partial recovery of blood pressure during SNP infusion and the post-SNP rebound of blood pressure can be completely blocked by saralasin. This demonstrates the participation of the renin--angiotensin system in antagonizing the combined hypotensive effects of halothane and SNP.", "entity": "Nitroprusside", "aliases": "Abbott Brand of Sodium Nitroprusside Bayer Cyanonitrosylferrate Disodium Salt Faulding Fides Ecopharma Ketostix Naniprus Nipride Nipruton Nitriate Nitroferricyanide Nitropress Nitroprussiat Dihydrate Roche SERB", "definition": "A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.\n    ", "id": "MESH:D009599"}
{"mention": "hypotension", "mention_text": "The role of the renin--angiotensin system in the maintenance of blood pressure during halothane anesthesia and sodium nitroprusside (SNP)-induced hypotension was evaluated. Control rats received halothane anesthesia (1 MAC) for one hour, followed by SNP infusion, 40 microgram/kg/min, for 30 min, followed by a 30-min recovery period. A second group of rats was treated identically and, in addition, received an infusion of saralasin (a competitive inhibitor of angiotensin II) throughout the experimental period. In each group, SNP infusion resulted in an initial decrease in blood pressure from 86 torr and 83 torr, respectively, to 48 torr. During the SNP infusion the control animals demonstrated a progressive increase in blood pressure to 61 torr, whereas the saralasin-treated animals showed no change. Following discontinuation of SNP, blood pressure in the control animals rebounded to 94 torr, as compared with 78 torr in the saralasin-treated rats. This study indicates that with stable halothane anesthesia, the partial recovery of blood pressure during SNP infusion and the post-SNP rebound of blood pressure can be completely blocked by saralasin. This demonstrates the participation of the renin--angiotensin system in antagonizing the combined hypotensive effects of halothane and SNP.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "saralasin", "mention_text": "The role of the renin--angiotensin system in the maintenance of blood pressure during halothane anesthesia and sodium nitroprusside (SNP)-induced hypotension was evaluated. Control rats received halothane anesthesia (1 MAC) for one hour, followed by SNP infusion, 40 microgram/kg/min, for 30 min, followed by a 30-min recovery period. A second group of rats was treated identically and, in addition, received an infusion of saralasin (a competitive inhibitor of angiotensin II) throughout the experimental period. In each group, SNP infusion resulted in an initial decrease in blood pressure from 86 torr and 83 torr, respectively, to 48 torr. During the SNP infusion the control animals demonstrated a progressive increase in blood pressure to 61 torr, whereas the saralasin-treated animals showed no change. Following discontinuation of SNP, blood pressure in the control animals rebounded to 94 torr, as compared with 78 torr in the saralasin-treated rats. This study indicates that with stable halothane anesthesia, the partial recovery of blood pressure during SNP infusion and the post-SNP rebound of blood pressure can be completely blocked by saralasin. This demonstrates the participation of the renin--angiotensin system in antagonizing the combined hypotensive effects of halothane and SNP.", "entity": "Saralasin", "aliases": "(Sar(1),Ala(8))ANGII (Sar1,Val5,Ala8)Angiotensin II 1 Sar 8 Ala Angiotensin Sarcosine Alanine 1-Sar-8-Ala 1-Sarcosine-8-Alanine Sar(1)-Ala(8)- Sarcosyl(1)-Alanine(8)- Anhydrous Saralasin Acetate Hydrated Sar-Arg-Val-Tyr-Val-His-Pro-Ala", "definition": "An octapeptide analog of angiotensin II (bovine) with amino acids 1 and 8 replaced with sarcosine and alanine, respectively. It is a highly specific competitive inhibitor of angiotensin II that is used in the diagnosis of HYPERTENSION.\n    ", "id": "MESH:D012504"}
{"mention": "angiotensin II", "mention_text": "The role of the renin--angiotensin system in the maintenance of blood pressure during halothane anesthesia and sodium nitroprusside (SNP)-induced hypotension was evaluated. Control rats received halothane anesthesia (1 MAC) for one hour, followed by SNP infusion, 40 microgram/kg/min, for 30 min, followed by a 30-min recovery period. A second group of rats was treated identically and, in addition, received an infusion of saralasin (a competitive inhibitor of angiotensin II) throughout the experimental period. In each group, SNP infusion resulted in an initial decrease in blood pressure from 86 torr and 83 torr, respectively, to 48 torr. During the SNP infusion the control animals demonstrated a progressive increase in blood pressure to 61 torr, whereas the saralasin-treated animals showed no change. Following discontinuation of SNP, blood pressure in the control animals rebounded to 94 torr, as compared with 78 torr in the saralasin-treated rats. This study indicates that with stable halothane anesthesia, the partial recovery of blood pressure during SNP infusion and the post-SNP rebound of blood pressure can be completely blocked by saralasin. This demonstrates the participation of the renin--angiotensin system in antagonizing the combined hypotensive effects of halothane and SNP.", "entity": "Angiotensin II", "aliases": "5 L Isoleucine Angiotensin II 5-L-Isoleucine ANG-(1-8)Octapeptide Ile(5)- Isoleucine(5)- Val(5)- Valine(5)- Angiotensin-(1-8) Octapeptide Isoleucine(5)-Angiotensin Isoleucyl(5)-Angiotensin Valyl(5)-Angiotensin", "definition": "An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.\n    ", "id": "MESH:D000804"}
{"mention": "increase in blood pressure", "mention_text": "The role of the renin--angiotensin system in the maintenance of blood pressure during halothane anesthesia and sodium nitroprusside (SNP)-induced hypotension was evaluated. Control rats received halothane anesthesia (1 MAC) for one hour, followed by SNP infusion, 40 microgram/kg/min, for 30 min, followed by a 30-min recovery period. A second group of rats was treated identically and, in addition, received an infusion of saralasin (a competitive inhibitor of angiotensin II) throughout the experimental period. In each group, SNP infusion resulted in an initial decrease in blood pressure from 86 torr and 83 torr, respectively, to 48 torr. During the SNP infusion the control animals demonstrated a progressive increase in blood pressure to 61 torr, whereas the saralasin-treated animals showed no change. Following discontinuation of SNP, blood pressure in the control animals rebounded to 94 torr, as compared with 78 torr in the saralasin-treated rats. This study indicates that with stable halothane anesthesia, the partial recovery of blood pressure during SNP infusion and the post-SNP rebound of blood pressure can be completely blocked by saralasin. This demonstrates the participation of the renin--angiotensin system in antagonizing the combined hypotensive effects of halothane and SNP.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "hypotensive", "mention_text": "The role of the renin--angiotensin system in the maintenance of blood pressure during halothane anesthesia and sodium nitroprusside (SNP)-induced hypotension was evaluated. Control rats received halothane anesthesia (1 MAC) for one hour, followed by SNP infusion, 40 microgram/kg/min, for 30 min, followed by a 30-min recovery period. A second group of rats was treated identically and, in addition, received an infusion of saralasin (a competitive inhibitor of angiotensin II) throughout the experimental period. In each group, SNP infusion resulted in an initial decrease in blood pressure from 86 torr and 83 torr, respectively, to 48 torr. During the SNP infusion the control animals demonstrated a progressive increase in blood pressure to 61 torr, whereas the saralasin-treated animals showed no change. Following discontinuation of SNP, blood pressure in the control animals rebounded to 94 torr, as compared with 78 torr in the saralasin-treated rats. This study indicates that with stable halothane anesthesia, the partial recovery of blood pressure during SNP infusion and the post-SNP rebound of blood pressure can be completely blocked by saralasin. This demonstrates the participation of the renin--angiotensin system in antagonizing the combined hypotensive effects of halothane and SNP.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "Toxic hepatitis", "mention_text": "Toxic hepatitis induced by antithyroid drugs: four cases including one with cross-reactivity between carbimazole and benzylthiouracil.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "carbimazole", "mention_text": "Toxic hepatitis induced by antithyroid drugs: four cases including one with cross-reactivity between carbimazole and benzylthiouracil.", "entity": "Carbimazole", "aliases": "Carbimazole Henning Berlin Brand of Herbrand Neo Tomizol Neo-Mercazole Neo-Thyreostat Neomercazole Roche Sanofi Synthelabo Tarbis", "definition": "An imidazole antithyroid agent. Carbimazole is metabolized to METHIMAZOLE, which is responsible for the antithyroid activity.\n    ", "id": "MESH:D002231"}
{"mention": "benzylthiouracil", "mention_text": "Toxic hepatitis induced by antithyroid drugs: four cases including one with cross-reactivity between carbimazole and benzylthiouracil.", "entity": "benzylthiouracil", "aliases": "6-benzyl-2-thiouracil Basdène Hexaspray benzylthiouracil", "definition": "", "id": "MESH:C019269"}
{"mention": "hepatic adverse effects", "mention_text": "OBJECTIVE: This study was conducted to assess the occurrence of hepatic adverse effects encountered with antithyroid drugs. METHODS: Retrospective review of medical records of 236 patients with hyperthyroidism admitted in our department (in- or out-patients) from 1986 to 1992. RESULTS: Four patients (1.7%) were identified with toxic hepatitis which could reasonably be attributed to the use of antithyroid agent. Two patients had a cholestatic hepatitis induced by carbimazole (N  omercazole). Two others had a mixed (cholestatic and cytolytic) hepatitis following carbimazole. One of the latter two patients further experienced a cytolytic hepatitis which appeared after Benzylthiouracil (Basd  ne) had replaced carbimazole. Biological features of hepatitis disappeared in all cases after cessation of the incriminated drug, while biliary, viral and immunological searches were negative. Only 2 patients of our retrospective study experienced a mild or severe neutropenia. CONCLUSION: Toxic hepatitis is a potential adverse effect of antithyroid drugs which warrants, as for haematological disturbances, a pre-therapeutic determination and a careful follow-up of relevant biological markers. Moreover, hepatotoxicity may not be restricted to one class of antithyroid agents.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "hyperthyroidism", "mention_text": "OBJECTIVE: This study was conducted to assess the occurrence of hepatic adverse effects encountered with antithyroid drugs. METHODS: Retrospective review of medical records of 236 patients with hyperthyroidism admitted in our department (in- or out-patients) from 1986 to 1992. RESULTS: Four patients (1.7%) were identified with toxic hepatitis which could reasonably be attributed to the use of antithyroid agent. Two patients had a cholestatic hepatitis induced by carbimazole (N  omercazole). Two others had a mixed (cholestatic and cytolytic) hepatitis following carbimazole. One of the latter two patients further experienced a cytolytic hepatitis which appeared after Benzylthiouracil (Basd  ne) had replaced carbimazole. Biological features of hepatitis disappeared in all cases after cessation of the incriminated drug, while biliary, viral and immunological searches were negative. Only 2 patients of our retrospective study experienced a mild or severe neutropenia. CONCLUSION: Toxic hepatitis is a potential adverse effect of antithyroid drugs which warrants, as for haematological disturbances, a pre-therapeutic determination and a careful follow-up of relevant biological markers. Moreover, hepatotoxicity may not be restricted to one class of antithyroid agents.", "entity": "Hyperthyroidism", "aliases": "Hyperthyroidism Primary Hyperthyroidisms", "definition": "Hypersecretion of THYROID HORMONES from the THYROID GLAND. Elevated levels of thyroid hormones increase BASAL METABOLIC RATE.\n    ", "id": "MESH:D006980"}
{"mention": "toxic hepatitis", "mention_text": "OBJECTIVE: This study was conducted to assess the occurrence of hepatic adverse effects encountered with antithyroid drugs. METHODS: Retrospective review of medical records of 236 patients with hyperthyroidism admitted in our department (in- or out-patients) from 1986 to 1992. RESULTS: Four patients (1.7%) were identified with toxic hepatitis which could reasonably be attributed to the use of antithyroid agent. Two patients had a cholestatic hepatitis induced by carbimazole (N  omercazole). Two others had a mixed (cholestatic and cytolytic) hepatitis following carbimazole. One of the latter two patients further experienced a cytolytic hepatitis which appeared after Benzylthiouracil (Basd  ne) had replaced carbimazole. Biological features of hepatitis disappeared in all cases after cessation of the incriminated drug, while biliary, viral and immunological searches were negative. Only 2 patients of our retrospective study experienced a mild or severe neutropenia. CONCLUSION: Toxic hepatitis is a potential adverse effect of antithyroid drugs which warrants, as for haematological disturbances, a pre-therapeutic determination and a careful follow-up of relevant biological markers. Moreover, hepatotoxicity may not be restricted to one class of antithyroid agents.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "cholestatic", "mention_text": "OBJECTIVE: This study was conducted to assess the occurrence of hepatic adverse effects encountered with antithyroid drugs. METHODS: Retrospective review of medical records of 236 patients with hyperthyroidism admitted in our department (in- or out-patients) from 1986 to 1992. RESULTS: Four patients (1.7%) were identified with toxic hepatitis which could reasonably be attributed to the use of antithyroid agent. Two patients had a cholestatic hepatitis induced by carbimazole (N  omercazole). Two others had a mixed (cholestatic and cytolytic) hepatitis following carbimazole. One of the latter two patients further experienced a cytolytic hepatitis which appeared after Benzylthiouracil (Basd  ne) had replaced carbimazole. Biological features of hepatitis disappeared in all cases after cessation of the incriminated drug, while biliary, viral and immunological searches were negative. Only 2 patients of our retrospective study experienced a mild or severe neutropenia. CONCLUSION: Toxic hepatitis is a potential adverse effect of antithyroid drugs which warrants, as for haematological disturbances, a pre-therapeutic determination and a careful follow-up of relevant biological markers. Moreover, hepatotoxicity may not be restricted to one class of antithyroid agents.", "entity": "Cholestasis", "aliases": "Bile Duct Obstruction Obstructions Biliary Stases Stasis Cholestases Cholestasis", "definition": "Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).\n    ", "id": "MESH:D002779"}
{"mention": "hepatitis", "mention_text": "OBJECTIVE: This study was conducted to assess the occurrence of hepatic adverse effects encountered with antithyroid drugs. METHODS: Retrospective review of medical records of 236 patients with hyperthyroidism admitted in our department (in- or out-patients) from 1986 to 1992. RESULTS: Four patients (1.7%) were identified with toxic hepatitis which could reasonably be attributed to the use of antithyroid agent. Two patients had a cholestatic hepatitis induced by carbimazole (N  omercazole). Two others had a mixed (cholestatic and cytolytic) hepatitis following carbimazole. One of the latter two patients further experienced a cytolytic hepatitis which appeared after Benzylthiouracil (Basd  ne) had replaced carbimazole. Biological features of hepatitis disappeared in all cases after cessation of the incriminated drug, while biliary, viral and immunological searches were negative. Only 2 patients of our retrospective study experienced a mild or severe neutropenia. CONCLUSION: Toxic hepatitis is a potential adverse effect of antithyroid drugs which warrants, as for haematological disturbances, a pre-therapeutic determination and a careful follow-up of relevant biological markers. Moreover, hepatotoxicity may not be restricted to one class of antithyroid agents.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "carbimazole", "mention_text": "OBJECTIVE: This study was conducted to assess the occurrence of hepatic adverse effects encountered with antithyroid drugs. METHODS: Retrospective review of medical records of 236 patients with hyperthyroidism admitted in our department (in- or out-patients) from 1986 to 1992. RESULTS: Four patients (1.7%) were identified with toxic hepatitis which could reasonably be attributed to the use of antithyroid agent. Two patients had a cholestatic hepatitis induced by carbimazole (N  omercazole). Two others had a mixed (cholestatic and cytolytic) hepatitis following carbimazole. One of the latter two patients further experienced a cytolytic hepatitis which appeared after Benzylthiouracil (Basd  ne) had replaced carbimazole. Biological features of hepatitis disappeared in all cases after cessation of the incriminated drug, while biliary, viral and immunological searches were negative. Only 2 patients of our retrospective study experienced a mild or severe neutropenia. CONCLUSION: Toxic hepatitis is a potential adverse effect of antithyroid drugs which warrants, as for haematological disturbances, a pre-therapeutic determination and a careful follow-up of relevant biological markers. Moreover, hepatotoxicity may not be restricted to one class of antithyroid agents.", "entity": "Carbimazole", "aliases": "Carbimazole Henning Berlin Brand of Herbrand Neo Tomizol Neo-Mercazole Neo-Thyreostat Neomercazole Roche Sanofi Synthelabo Tarbis", "definition": "An imidazole antithyroid agent. Carbimazole is metabolized to METHIMAZOLE, which is responsible for the antithyroid activity.\n    ", "id": "MESH:D002231"}
{"mention": "N  omercazole", "mention_text": "OBJECTIVE: This study was conducted to assess the occurrence of hepatic adverse effects encountered with antithyroid drugs. METHODS: Retrospective review of medical records of 236 patients with hyperthyroidism admitted in our department (in- or out-patients) from 1986 to 1992. RESULTS: Four patients (1.7%) were identified with toxic hepatitis which could reasonably be attributed to the use of antithyroid agent. Two patients had a cholestatic hepatitis induced by carbimazole (N  omercazole). Two others had a mixed (cholestatic and cytolytic) hepatitis following carbimazole. One of the latter two patients further experienced a cytolytic hepatitis which appeared after Benzylthiouracil (Basd  ne) had replaced carbimazole. Biological features of hepatitis disappeared in all cases after cessation of the incriminated drug, while biliary, viral and immunological searches were negative. Only 2 patients of our retrospective study experienced a mild or severe neutropenia. CONCLUSION: Toxic hepatitis is a potential adverse effect of antithyroid drugs which warrants, as for haematological disturbances, a pre-therapeutic determination and a careful follow-up of relevant biological markers. Moreover, hepatotoxicity may not be restricted to one class of antithyroid agents.", "entity": "Carbimazole", "aliases": "Carbimazole Henning Berlin Brand of Herbrand Neo Tomizol Neo-Mercazole Neo-Thyreostat Neomercazole Roche Sanofi Synthelabo Tarbis", "definition": "An imidazole antithyroid agent. Carbimazole is metabolized to METHIMAZOLE, which is responsible for the antithyroid activity.\n    ", "id": "MESH:D002231"}
{"mention": "Benzylthiouracil", "mention_text": "OBJECTIVE: This study was conducted to assess the occurrence of hepatic adverse effects encountered with antithyroid drugs. METHODS: Retrospective review of medical records of 236 patients with hyperthyroidism admitted in our department (in- or out-patients) from 1986 to 1992. RESULTS: Four patients (1.7%) were identified with toxic hepatitis which could reasonably be attributed to the use of antithyroid agent. Two patients had a cholestatic hepatitis induced by carbimazole (N  omercazole). Two others had a mixed (cholestatic and cytolytic) hepatitis following carbimazole. One of the latter two patients further experienced a cytolytic hepatitis which appeared after Benzylthiouracil (Basd  ne) had replaced carbimazole. Biological features of hepatitis disappeared in all cases after cessation of the incriminated drug, while biliary, viral and immunological searches were negative. Only 2 patients of our retrospective study experienced a mild or severe neutropenia. CONCLUSION: Toxic hepatitis is a potential adverse effect of antithyroid drugs which warrants, as for haematological disturbances, a pre-therapeutic determination and a careful follow-up of relevant biological markers. Moreover, hepatotoxicity may not be restricted to one class of antithyroid agents.", "entity": "benzylthiouracil", "aliases": "6-benzyl-2-thiouracil Basdène Hexaspray benzylthiouracil", "definition": "", "id": "MESH:C019269"}
{"mention": "Basd  ne", "mention_text": "OBJECTIVE: This study was conducted to assess the occurrence of hepatic adverse effects encountered with antithyroid drugs. METHODS: Retrospective review of medical records of 236 patients with hyperthyroidism admitted in our department (in- or out-patients) from 1986 to 1992. RESULTS: Four patients (1.7%) were identified with toxic hepatitis which could reasonably be attributed to the use of antithyroid agent. Two patients had a cholestatic hepatitis induced by carbimazole (N  omercazole). Two others had a mixed (cholestatic and cytolytic) hepatitis following carbimazole. One of the latter two patients further experienced a cytolytic hepatitis which appeared after Benzylthiouracil (Basd  ne) had replaced carbimazole. Biological features of hepatitis disappeared in all cases after cessation of the incriminated drug, while biliary, viral and immunological searches were negative. Only 2 patients of our retrospective study experienced a mild or severe neutropenia. CONCLUSION: Toxic hepatitis is a potential adverse effect of antithyroid drugs which warrants, as for haematological disturbances, a pre-therapeutic determination and a careful follow-up of relevant biological markers. Moreover, hepatotoxicity may not be restricted to one class of antithyroid agents.", "entity": "benzylthiouracil", "aliases": "6-benzyl-2-thiouracil Basdène Hexaspray benzylthiouracil", "definition": "", "id": "MESH:C019269"}
{"mention": "neutropenia", "mention_text": "OBJECTIVE: This study was conducted to assess the occurrence of hepatic adverse effects encountered with antithyroid drugs. METHODS: Retrospective review of medical records of 236 patients with hyperthyroidism admitted in our department (in- or out-patients) from 1986 to 1992. RESULTS: Four patients (1.7%) were identified with toxic hepatitis which could reasonably be attributed to the use of antithyroid agent. Two patients had a cholestatic hepatitis induced by carbimazole (N  omercazole). Two others had a mixed (cholestatic and cytolytic) hepatitis following carbimazole. One of the latter two patients further experienced a cytolytic hepatitis which appeared after Benzylthiouracil (Basd  ne) had replaced carbimazole. Biological features of hepatitis disappeared in all cases after cessation of the incriminated drug, while biliary, viral and immunological searches were negative. Only 2 patients of our retrospective study experienced a mild or severe neutropenia. CONCLUSION: Toxic hepatitis is a potential adverse effect of antithyroid drugs which warrants, as for haematological disturbances, a pre-therapeutic determination and a careful follow-up of relevant biological markers. Moreover, hepatotoxicity may not be restricted to one class of antithyroid agents.", "entity": "Neutropenia", "aliases": "Neutropenia Neutropenias", "definition": "A decrease in the number of NEUTROPHILS found in the blood.\n    ", "id": "MESH:D009503"}
{"mention": "Toxic hepatitis", "mention_text": "OBJECTIVE: This study was conducted to assess the occurrence of hepatic adverse effects encountered with antithyroid drugs. METHODS: Retrospective review of medical records of 236 patients with hyperthyroidism admitted in our department (in- or out-patients) from 1986 to 1992. RESULTS: Four patients (1.7%) were identified with toxic hepatitis which could reasonably be attributed to the use of antithyroid agent. Two patients had a cholestatic hepatitis induced by carbimazole (N  omercazole). Two others had a mixed (cholestatic and cytolytic) hepatitis following carbimazole. One of the latter two patients further experienced a cytolytic hepatitis which appeared after Benzylthiouracil (Basd  ne) had replaced carbimazole. Biological features of hepatitis disappeared in all cases after cessation of the incriminated drug, while biliary, viral and immunological searches were negative. Only 2 patients of our retrospective study experienced a mild or severe neutropenia. CONCLUSION: Toxic hepatitis is a potential adverse effect of antithyroid drugs which warrants, as for haematological disturbances, a pre-therapeutic determination and a careful follow-up of relevant biological markers. Moreover, hepatotoxicity may not be restricted to one class of antithyroid agents.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "hepatotoxicity", "mention_text": "OBJECTIVE: This study was conducted to assess the occurrence of hepatic adverse effects encountered with antithyroid drugs. METHODS: Retrospective review of medical records of 236 patients with hyperthyroidism admitted in our department (in- or out-patients) from 1986 to 1992. RESULTS: Four patients (1.7%) were identified with toxic hepatitis which could reasonably be attributed to the use of antithyroid agent. Two patients had a cholestatic hepatitis induced by carbimazole (N  omercazole). Two others had a mixed (cholestatic and cytolytic) hepatitis following carbimazole. One of the latter two patients further experienced a cytolytic hepatitis which appeared after Benzylthiouracil (Basd  ne) had replaced carbimazole. Biological features of hepatitis disappeared in all cases after cessation of the incriminated drug, while biliary, viral and immunological searches were negative. Only 2 patients of our retrospective study experienced a mild or severe neutropenia. CONCLUSION: Toxic hepatitis is a potential adverse effect of antithyroid drugs which warrants, as for haematological disturbances, a pre-therapeutic determination and a careful follow-up of relevant biological markers. Moreover, hepatotoxicity may not be restricted to one class of antithyroid agents.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "vitamin B12", "mention_text": "Study of the role of vitamin B12 and folinic acid supplementation in preventing hematologic toxicity of zidovudine.", "entity": "Vitamin B 12", "aliases": "B 12 Vitamin B12 Cobalamin Cobalamins Cyanocobalamin Eritron", "definition": "A cobalt-containing coordination compound produced by intestinal micro-organisms and found also in soil and water. Higher plants do not concentrate vitamin B 12 from the soil and so are a poor source of the substance as compared with animal tissues. INTRINSIC FACTOR is important for the assimilation of vitamin B 12.\n    ", "id": "MESH:D014805"}
{"mention": "folinic acid", "mention_text": "Study of the role of vitamin B12 and folinic acid supplementation in preventing hematologic toxicity of zidovudine.", "entity": "Leucovorin", "aliases": "5 Formyltetrahydrofolate Formyltetrahydropteroylglutamate 5-Formyltetrahydrofolate 5-Formyltetrahydropteroylglutamate Acid Folinic Calcium Folinate Leucovorin Citrovorum Factor SF Acid-SF (D)-Isomer (DL)-Isomer (R)-Isomer (1:1) Salt Pentahydrate Monosodium Leukovorin Leukovorum N(5)-Formyltetrahydrofolate Wellcovorin", "definition": "The active metabolite of FOLIC ACID. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid.\n    ", "id": "MESH:D002955"}
{"mention": "toxicity", "mention_text": "Study of the role of vitamin B12 and folinic acid supplementation in preventing hematologic toxicity of zidovudine.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "zidovudine", "mention_text": "Study of the role of vitamin B12 and folinic acid supplementation in preventing hematologic toxicity of zidovudine.", "entity": "Zidovudine", "aliases": "3' Azido 2',3' Dideoxythymidine deoxythymidine 3'-Azido-2',3'-Dideoxythymidine 3'-Azido-3'-deoxythymidine AZT (Antiviral) Antiviral Azidothymidine BW A509U BWA 509U BWA-509U BWA509U Retrovir Zidovudine", "definition": "A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.\n    ", "id": "MESH:D015215"}
{"mention": "vitamin B12", "mention_text": "A prospective, randomized study was conducted to evaluate the role of vitamin B12 and folinic acid supplementation in preventing zidovudine (ZDV)-induced bone marrow suppression. Seventy-five human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts < 500/mm3 were randomized to receive either ZDV (500 mg daily) alone (group I, n = 38) or in combination with folinic acid (15 mg daily) and intramascular vitamin B12 (1000 micrograms monthly) (group II, n = 37). Finally, 15 patients were excluded from the study (noncompliance 14, death 1); thus, 60 patients (31 in group I and 29 in group II) were eligible for analysis. No significant differences between groups were found at enrollment. During the study, vitamin B12 and folate levels were significantly higher in group II patients; however, no differences in hemoglobin, hematocrit, mean corpuscular volume, and white-cell, neutrophil and platelet counts were observed between groups at 3, 6, 9 and 12 months. Severe hematologic toxicity (neutrophil count < 1000/mm3 and/or hemoglobin < 8 g/dl) occurred in 4 patients assigned to group I and 7 assigned to group II. There was no correlation between vitamin B12 or folate levels and development of myelosuppression. Vitamin B12 and folinic acid supplementation of ZDV therapy does not seem useful in preventing or reducing ZDV-induced myelotoxicity in the overall treated population, although a beneficial effect in certain subgroups of patients cannot be excluded.", "entity": "Vitamin B 12", "aliases": "B 12 Vitamin B12 Cobalamin Cobalamins Cyanocobalamin Eritron", "definition": "A cobalt-containing coordination compound produced by intestinal micro-organisms and found also in soil and water. Higher plants do not concentrate vitamin B 12 from the soil and so are a poor source of the substance as compared with animal tissues. INTRINSIC FACTOR is important for the assimilation of vitamin B 12.\n    ", "id": "MESH:D014805"}
{"mention": "folinic acid", "mention_text": "A prospective, randomized study was conducted to evaluate the role of vitamin B12 and folinic acid supplementation in preventing zidovudine (ZDV)-induced bone marrow suppression. Seventy-five human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts < 500/mm3 were randomized to receive either ZDV (500 mg daily) alone (group I, n = 38) or in combination with folinic acid (15 mg daily) and intramascular vitamin B12 (1000 micrograms monthly) (group II, n = 37). Finally, 15 patients were excluded from the study (noncompliance 14, death 1); thus, 60 patients (31 in group I and 29 in group II) were eligible for analysis. No significant differences between groups were found at enrollment. During the study, vitamin B12 and folate levels were significantly higher in group II patients; however, no differences in hemoglobin, hematocrit, mean corpuscular volume, and white-cell, neutrophil and platelet counts were observed between groups at 3, 6, 9 and 12 months. Severe hematologic toxicity (neutrophil count < 1000/mm3 and/or hemoglobin < 8 g/dl) occurred in 4 patients assigned to group I and 7 assigned to group II. There was no correlation between vitamin B12 or folate levels and development of myelosuppression. Vitamin B12 and folinic acid supplementation of ZDV therapy does not seem useful in preventing or reducing ZDV-induced myelotoxicity in the overall treated population, although a beneficial effect in certain subgroups of patients cannot be excluded.", "entity": "Leucovorin", "aliases": "5 Formyltetrahydrofolate Formyltetrahydropteroylglutamate 5-Formyltetrahydrofolate 5-Formyltetrahydropteroylglutamate Acid Folinic Calcium Folinate Leucovorin Citrovorum Factor SF Acid-SF (D)-Isomer (DL)-Isomer (R)-Isomer (1:1) Salt Pentahydrate Monosodium Leukovorin Leukovorum N(5)-Formyltetrahydrofolate Wellcovorin", "definition": "The active metabolite of FOLIC ACID. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid.\n    ", "id": "MESH:D002955"}
{"mention": "zidovudine", "mention_text": "A prospective, randomized study was conducted to evaluate the role of vitamin B12 and folinic acid supplementation in preventing zidovudine (ZDV)-induced bone marrow suppression. Seventy-five human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts < 500/mm3 were randomized to receive either ZDV (500 mg daily) alone (group I, n = 38) or in combination with folinic acid (15 mg daily) and intramascular vitamin B12 (1000 micrograms monthly) (group II, n = 37). Finally, 15 patients were excluded from the study (noncompliance 14, death 1); thus, 60 patients (31 in group I and 29 in group II) were eligible for analysis. No significant differences between groups were found at enrollment. During the study, vitamin B12 and folate levels were significantly higher in group II patients; however, no differences in hemoglobin, hematocrit, mean corpuscular volume, and white-cell, neutrophil and platelet counts were observed between groups at 3, 6, 9 and 12 months. Severe hematologic toxicity (neutrophil count < 1000/mm3 and/or hemoglobin < 8 g/dl) occurred in 4 patients assigned to group I and 7 assigned to group II. There was no correlation between vitamin B12 or folate levels and development of myelosuppression. Vitamin B12 and folinic acid supplementation of ZDV therapy does not seem useful in preventing or reducing ZDV-induced myelotoxicity in the overall treated population, although a beneficial effect in certain subgroups of patients cannot be excluded.", "entity": "Zidovudine", "aliases": "3' Azido 2',3' Dideoxythymidine deoxythymidine 3'-Azido-2',3'-Dideoxythymidine 3'-Azido-3'-deoxythymidine AZT (Antiviral) Antiviral Azidothymidine BW A509U BWA 509U BWA-509U BWA509U Retrovir Zidovudine", "definition": "A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.\n    ", "id": "MESH:D015215"}
{"mention": "ZDV", "mention_text": "A prospective, randomized study was conducted to evaluate the role of vitamin B12 and folinic acid supplementation in preventing zidovudine (ZDV)-induced bone marrow suppression. Seventy-five human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts < 500/mm3 were randomized to receive either ZDV (500 mg daily) alone (group I, n = 38) or in combination with folinic acid (15 mg daily) and intramascular vitamin B12 (1000 micrograms monthly) (group II, n = 37). Finally, 15 patients were excluded from the study (noncompliance 14, death 1); thus, 60 patients (31 in group I and 29 in group II) were eligible for analysis. No significant differences between groups were found at enrollment. During the study, vitamin B12 and folate levels were significantly higher in group II patients; however, no differences in hemoglobin, hematocrit, mean corpuscular volume, and white-cell, neutrophil and platelet counts were observed between groups at 3, 6, 9 and 12 months. Severe hematologic toxicity (neutrophil count < 1000/mm3 and/or hemoglobin < 8 g/dl) occurred in 4 patients assigned to group I and 7 assigned to group II. There was no correlation between vitamin B12 or folate levels and development of myelosuppression. Vitamin B12 and folinic acid supplementation of ZDV therapy does not seem useful in preventing or reducing ZDV-induced myelotoxicity in the overall treated population, although a beneficial effect in certain subgroups of patients cannot be excluded.", "entity": "Zidovudine", "aliases": "3' Azido 2',3' Dideoxythymidine deoxythymidine 3'-Azido-2',3'-Dideoxythymidine 3'-Azido-3'-deoxythymidine AZT (Antiviral) Antiviral Azidothymidine BW A509U BWA 509U BWA-509U BWA509U Retrovir Zidovudine", "definition": "A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.\n    ", "id": "MESH:D015215"}
{"mention": "bone marrow suppression", "mention_text": "A prospective, randomized study was conducted to evaluate the role of vitamin B12 and folinic acid supplementation in preventing zidovudine (ZDV)-induced bone marrow suppression. Seventy-five human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts < 500/mm3 were randomized to receive either ZDV (500 mg daily) alone (group I, n = 38) or in combination with folinic acid (15 mg daily) and intramascular vitamin B12 (1000 micrograms monthly) (group II, n = 37). Finally, 15 patients were excluded from the study (noncompliance 14, death 1); thus, 60 patients (31 in group I and 29 in group II) were eligible for analysis. No significant differences between groups were found at enrollment. During the study, vitamin B12 and folate levels were significantly higher in group II patients; however, no differences in hemoglobin, hematocrit, mean corpuscular volume, and white-cell, neutrophil and platelet counts were observed between groups at 3, 6, 9 and 12 months. Severe hematologic toxicity (neutrophil count < 1000/mm3 and/or hemoglobin < 8 g/dl) occurred in 4 patients assigned to group I and 7 assigned to group II. There was no correlation between vitamin B12 or folate levels and development of myelosuppression. Vitamin B12 and folinic acid supplementation of ZDV therapy does not seem useful in preventing or reducing ZDV-induced myelotoxicity in the overall treated population, although a beneficial effect in certain subgroups of patients cannot be excluded.", "entity": "Bone Marrow Diseases", "aliases": "Bone Marrow Disease Diseases", "definition": "", "id": "MESH:D001855"}
{"mention": "human immunodeficiency virus (HIV)-infected", "mention_text": "A prospective, randomized study was conducted to evaluate the role of vitamin B12 and folinic acid supplementation in preventing zidovudine (ZDV)-induced bone marrow suppression. Seventy-five human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts < 500/mm3 were randomized to receive either ZDV (500 mg daily) alone (group I, n = 38) or in combination with folinic acid (15 mg daily) and intramascular vitamin B12 (1000 micrograms monthly) (group II, n = 37). Finally, 15 patients were excluded from the study (noncompliance 14, death 1); thus, 60 patients (31 in group I and 29 in group II) were eligible for analysis. No significant differences between groups were found at enrollment. During the study, vitamin B12 and folate levels were significantly higher in group II patients; however, no differences in hemoglobin, hematocrit, mean corpuscular volume, and white-cell, neutrophil and platelet counts were observed between groups at 3, 6, 9 and 12 months. Severe hematologic toxicity (neutrophil count < 1000/mm3 and/or hemoglobin < 8 g/dl) occurred in 4 patients assigned to group I and 7 assigned to group II. There was no correlation between vitamin B12 or folate levels and development of myelosuppression. Vitamin B12 and folinic acid supplementation of ZDV therapy does not seem useful in preventing or reducing ZDV-induced myelotoxicity in the overall treated population, although a beneficial effect in certain subgroups of patients cannot be excluded.", "entity": "HIV Infections", "aliases": "HIV Infection Infections HTLV III LAV HTLV-III HTLV-III-LAV T Lymphotropic Virus Type Human T-Lymphotropic", "definition": "Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).\n    ", "id": "MESH:D015658"}
{"mention": "death", "mention_text": "A prospective, randomized study was conducted to evaluate the role of vitamin B12 and folinic acid supplementation in preventing zidovudine (ZDV)-induced bone marrow suppression. Seventy-five human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts < 500/mm3 were randomized to receive either ZDV (500 mg daily) alone (group I, n = 38) or in combination with folinic acid (15 mg daily) and intramascular vitamin B12 (1000 micrograms monthly) (group II, n = 37). Finally, 15 patients were excluded from the study (noncompliance 14, death 1); thus, 60 patients (31 in group I and 29 in group II) were eligible for analysis. No significant differences between groups were found at enrollment. During the study, vitamin B12 and folate levels were significantly higher in group II patients; however, no differences in hemoglobin, hematocrit, mean corpuscular volume, and white-cell, neutrophil and platelet counts were observed between groups at 3, 6, 9 and 12 months. Severe hematologic toxicity (neutrophil count < 1000/mm3 and/or hemoglobin < 8 g/dl) occurred in 4 patients assigned to group I and 7 assigned to group II. There was no correlation between vitamin B12 or folate levels and development of myelosuppression. Vitamin B12 and folinic acid supplementation of ZDV therapy does not seem useful in preventing or reducing ZDV-induced myelotoxicity in the overall treated population, although a beneficial effect in certain subgroups of patients cannot be excluded.", "entity": "Death", "aliases": "Cardiac Death Determination of Near-Death Experience", "definition": "Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.\n    ", "id": "MESH:D003643"}
{"mention": "folate", "mention_text": "A prospective, randomized study was conducted to evaluate the role of vitamin B12 and folinic acid supplementation in preventing zidovudine (ZDV)-induced bone marrow suppression. Seventy-five human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts < 500/mm3 were randomized to receive either ZDV (500 mg daily) alone (group I, n = 38) or in combination with folinic acid (15 mg daily) and intramascular vitamin B12 (1000 micrograms monthly) (group II, n = 37). Finally, 15 patients were excluded from the study (noncompliance 14, death 1); thus, 60 patients (31 in group I and 29 in group II) were eligible for analysis. No significant differences between groups were found at enrollment. During the study, vitamin B12 and folate levels were significantly higher in group II patients; however, no differences in hemoglobin, hematocrit, mean corpuscular volume, and white-cell, neutrophil and platelet counts were observed between groups at 3, 6, 9 and 12 months. Severe hematologic toxicity (neutrophil count < 1000/mm3 and/or hemoglobin < 8 g/dl) occurred in 4 patients assigned to group I and 7 assigned to group II. There was no correlation between vitamin B12 or folate levels and development of myelosuppression. Vitamin B12 and folinic acid supplementation of ZDV therapy does not seem useful in preventing or reducing ZDV-induced myelotoxicity in the overall treated population, although a beneficial effect in certain subgroups of patients cannot be excluded.", "entity": "Folic Acid", "aliases": "B9 Vitamin Folacin Folate Folic Acid (D)-Isomer (DL)-Isomer Calcium Salt (1:1) Monopotassium Monosodium Potassium Sodium Folvite Pteroylglutamic M", "definition": "A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses (POACEAE). Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia.\n    ", "id": "MESH:D005492"}
{"mention": "toxicity", "mention_text": "A prospective, randomized study was conducted to evaluate the role of vitamin B12 and folinic acid supplementation in preventing zidovudine (ZDV)-induced bone marrow suppression. Seventy-five human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts < 500/mm3 were randomized to receive either ZDV (500 mg daily) alone (group I, n = 38) or in combination with folinic acid (15 mg daily) and intramascular vitamin B12 (1000 micrograms monthly) (group II, n = 37). Finally, 15 patients were excluded from the study (noncompliance 14, death 1); thus, 60 patients (31 in group I and 29 in group II) were eligible for analysis. No significant differences between groups were found at enrollment. During the study, vitamin B12 and folate levels were significantly higher in group II patients; however, no differences in hemoglobin, hematocrit, mean corpuscular volume, and white-cell, neutrophil and platelet counts were observed between groups at 3, 6, 9 and 12 months. Severe hematologic toxicity (neutrophil count < 1000/mm3 and/or hemoglobin < 8 g/dl) occurred in 4 patients assigned to group I and 7 assigned to group II. There was no correlation between vitamin B12 or folate levels and development of myelosuppression. Vitamin B12 and folinic acid supplementation of ZDV therapy does not seem useful in preventing or reducing ZDV-induced myelotoxicity in the overall treated population, although a beneficial effect in certain subgroups of patients cannot be excluded.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "myelosuppression", "mention_text": "A prospective, randomized study was conducted to evaluate the role of vitamin B12 and folinic acid supplementation in preventing zidovudine (ZDV)-induced bone marrow suppression. Seventy-five human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts < 500/mm3 were randomized to receive either ZDV (500 mg daily) alone (group I, n = 38) or in combination with folinic acid (15 mg daily) and intramascular vitamin B12 (1000 micrograms monthly) (group II, n = 37). Finally, 15 patients were excluded from the study (noncompliance 14, death 1); thus, 60 patients (31 in group I and 29 in group II) were eligible for analysis. No significant differences between groups were found at enrollment. During the study, vitamin B12 and folate levels were significantly higher in group II patients; however, no differences in hemoglobin, hematocrit, mean corpuscular volume, and white-cell, neutrophil and platelet counts were observed between groups at 3, 6, 9 and 12 months. Severe hematologic toxicity (neutrophil count < 1000/mm3 and/or hemoglobin < 8 g/dl) occurred in 4 patients assigned to group I and 7 assigned to group II. There was no correlation between vitamin B12 or folate levels and development of myelosuppression. Vitamin B12 and folinic acid supplementation of ZDV therapy does not seem useful in preventing or reducing ZDV-induced myelotoxicity in the overall treated population, although a beneficial effect in certain subgroups of patients cannot be excluded.", "entity": "Bone Marrow Diseases", "aliases": "Bone Marrow Disease Diseases", "definition": "", "id": "MESH:D001855"}
{"mention": "Vitamin B12", "mention_text": "A prospective, randomized study was conducted to evaluate the role of vitamin B12 and folinic acid supplementation in preventing zidovudine (ZDV)-induced bone marrow suppression. Seventy-five human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts < 500/mm3 were randomized to receive either ZDV (500 mg daily) alone (group I, n = 38) or in combination with folinic acid (15 mg daily) and intramascular vitamin B12 (1000 micrograms monthly) (group II, n = 37). Finally, 15 patients were excluded from the study (noncompliance 14, death 1); thus, 60 patients (31 in group I and 29 in group II) were eligible for analysis. No significant differences between groups were found at enrollment. During the study, vitamin B12 and folate levels were significantly higher in group II patients; however, no differences in hemoglobin, hematocrit, mean corpuscular volume, and white-cell, neutrophil and platelet counts were observed between groups at 3, 6, 9 and 12 months. Severe hematologic toxicity (neutrophil count < 1000/mm3 and/or hemoglobin < 8 g/dl) occurred in 4 patients assigned to group I and 7 assigned to group II. There was no correlation between vitamin B12 or folate levels and development of myelosuppression. Vitamin B12 and folinic acid supplementation of ZDV therapy does not seem useful in preventing or reducing ZDV-induced myelotoxicity in the overall treated population, although a beneficial effect in certain subgroups of patients cannot be excluded.", "entity": "Vitamin B 12", "aliases": "B 12 Vitamin B12 Cobalamin Cobalamins Cyanocobalamin Eritron", "definition": "A cobalt-containing coordination compound produced by intestinal micro-organisms and found also in soil and water. Higher plants do not concentrate vitamin B 12 from the soil and so are a poor source of the substance as compared with animal tissues. INTRINSIC FACTOR is important for the assimilation of vitamin B 12.\n    ", "id": "MESH:D014805"}
{"mention": "myelotoxicity", "mention_text": "A prospective, randomized study was conducted to evaluate the role of vitamin B12 and folinic acid supplementation in preventing zidovudine (ZDV)-induced bone marrow suppression. Seventy-five human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts < 500/mm3 were randomized to receive either ZDV (500 mg daily) alone (group I, n = 38) or in combination with folinic acid (15 mg daily) and intramascular vitamin B12 (1000 micrograms monthly) (group II, n = 37). Finally, 15 patients were excluded from the study (noncompliance 14, death 1); thus, 60 patients (31 in group I and 29 in group II) were eligible for analysis. No significant differences between groups were found at enrollment. During the study, vitamin B12 and folate levels were significantly higher in group II patients; however, no differences in hemoglobin, hematocrit, mean corpuscular volume, and white-cell, neutrophil and platelet counts were observed between groups at 3, 6, 9 and 12 months. Severe hematologic toxicity (neutrophil count < 1000/mm3 and/or hemoglobin < 8 g/dl) occurred in 4 patients assigned to group I and 7 assigned to group II. There was no correlation between vitamin B12 or folate levels and development of myelosuppression. Vitamin B12 and folinic acid supplementation of ZDV therapy does not seem useful in preventing or reducing ZDV-induced myelotoxicity in the overall treated population, although a beneficial effect in certain subgroups of patients cannot be excluded.", "entity": "Bone Marrow Diseases", "aliases": "Bone Marrow Disease Diseases", "definition": "", "id": "MESH:D001855"}
{"mention": "confusion", "mention_text": "Acute confusion induced by a high-dose infusion of 5-fluorouracil and folinic acid.", "entity": "Confusion", "aliases": "Bewilderment Confusion Post Ictal Post-Ictal Reactive Confusional State States Disorientation", "definition": "A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation.\n    ", "id": "MESH:D003221"}
{"mention": "5-fluorouracil", "mention_text": "Acute confusion induced by a high-dose infusion of 5-fluorouracil and folinic acid.", "entity": "Fluorouracil", "aliases": "5 FU Lederle medac Fluorouracil biosyn HU Hexal 5-FU 5-Fluorouracil 5-Fluorouracil-biosyn 5-HU 5FU Adrucil Allergan Brand of CSP Carac Dakota Fluorouracile Dermatech Dermik Efudex Efudix Ferrer Fluoro Uracile ICN Fluoro-Uracile Fluoroplex GRY Mononitrate Monopotassium Salt Monosodium Potassium Teva Fluorouracil-GRY Fluorouracilo Far Fluoruracil Fluracedyl Flurodex Gry Haemato fu Haemato-fu Neocorp Neofluor Onkofluor Onkoworks Pharmachemie Ribofluor Riemser Roche ribosepharm", "definition": "A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.\n    ", "id": "MESH:D005472"}
{"mention": "folinic acid", "mention_text": "Acute confusion induced by a high-dose infusion of 5-fluorouracil and folinic acid.", "entity": "Leucovorin", "aliases": "5 Formyltetrahydrofolate Formyltetrahydropteroylglutamate 5-Formyltetrahydrofolate 5-Formyltetrahydropteroylglutamate Acid Folinic Calcium Folinate Leucovorin Citrovorum Factor SF Acid-SF (D)-Isomer (DL)-Isomer (R)-Isomer (1:1) Salt Pentahydrate Monosodium Leukovorin Leukovorum N(5)-Formyltetrahydrofolate Wellcovorin", "definition": "The active metabolite of FOLIC ACID. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid.\n    ", "id": "MESH:D002955"}
{"mention": "cisplatinum", "mention_text": "A 61-year-old man was treated with combination chemotherapy incorporating cisplatinum, etoposide, high-dose 5-fluorouracil (2,250 mg/m2/24 hours) and folinic acid for an inoperable gastric adenocarcinoma. He developed acute neurologic symptoms of mental confusion, disorientation and irritability, and then lapsed into a deep coma, lasting for approximately 40 hours during the first dose (day 2) of 5-fluorouracil and folinic acid infusion. This complication reappeared on day 25 during the second dose of 5-fluorouracil and folinic acid, which were then the only drugs given. Because folinic acid was unlikely to be associated with this condition, neurotoxicity due to high-dose 5-fluorouracil was highly suspected. The pathogenesis of 5-fluorouracil neurotoxicity may be due to a Krebs cycle blockade by fluoroacetate and fluorocitrate, thiamine deficiency, or dihydrouracil dehydrogenase deficiency. High-dose 5-fluorouracil/folinic acid infusion therapy has recently become a popular regimen for various cancers. It is necessary that both oncologists and neurologists be fully aware of this unusual complication.", "entity": "Cisplatin", "aliases": "Biocisplatinum Cisplatin Diamminodichloride Platinum Dichlorodiammineplatinum NSC-119875 Platidiam Platino Platinol cis Diamminedichloroplatinum cis-Diamminedichloroplatinum cis-Diamminedichloroplatinum(II) cis-Dichlorodiammineplatinum(II) cis-Platinum", "definition": "An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.\n    ", "id": "MESH:D002945"}
{"mention": "etoposide", "mention_text": "A 61-year-old man was treated with combination chemotherapy incorporating cisplatinum, etoposide, high-dose 5-fluorouracil (2,250 mg/m2/24 hours) and folinic acid for an inoperable gastric adenocarcinoma. He developed acute neurologic symptoms of mental confusion, disorientation and irritability, and then lapsed into a deep coma, lasting for approximately 40 hours during the first dose (day 2) of 5-fluorouracil and folinic acid infusion. This complication reappeared on day 25 during the second dose of 5-fluorouracil and folinic acid, which were then the only drugs given. Because folinic acid was unlikely to be associated with this condition, neurotoxicity due to high-dose 5-fluorouracil was highly suspected. The pathogenesis of 5-fluorouracil neurotoxicity may be due to a Krebs cycle blockade by fluoroacetate and fluorocitrate, thiamine deficiency, or dihydrouracil dehydrogenase deficiency. High-dose 5-fluorouracil/folinic acid infusion therapy has recently become a popular regimen for various cancers. It is necessary that both oncologists and neurologists be fully aware of this unusual complication.", "entity": "Etoposide", "aliases": "Baxter Brand of Etoposide Oncology Bristol Myers Squibb Bristol-Myers Celltop Demethyl Epipodophyllotoxin Ethylidine Glucoside Eposide Eposin Eto GRY Eto-GRY Etomedac Etopos Pierre Fabre Teva (5S)-Isomer (5a alpha)-Isomer alpha,9 alpha D Glucopyranosyl Isomer alpha-D-Glucopyranosyl Etoposido Ferrer Farma Exitop Gry Lastet Lemery Medac NSC 141540 NSC-141540 NSC141540 Novartis Onkoposid Onkoworks Pharmachemie Prasfarma Riboposid Sanfer Tedec Meiji Toposar VP 16 213 16-213 16213 VP-16 VP16 Vepesid ", "definition": "A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.\n    ", "id": "MESH:D005047"}
{"mention": "5-fluorouracil", "mention_text": "A 61-year-old man was treated with combination chemotherapy incorporating cisplatinum, etoposide, high-dose 5-fluorouracil (2,250 mg/m2/24 hours) and folinic acid for an inoperable gastric adenocarcinoma. He developed acute neurologic symptoms of mental confusion, disorientation and irritability, and then lapsed into a deep coma, lasting for approximately 40 hours during the first dose (day 2) of 5-fluorouracil and folinic acid infusion. This complication reappeared on day 25 during the second dose of 5-fluorouracil and folinic acid, which were then the only drugs given. Because folinic acid was unlikely to be associated with this condition, neurotoxicity due to high-dose 5-fluorouracil was highly suspected. The pathogenesis of 5-fluorouracil neurotoxicity may be due to a Krebs cycle blockade by fluoroacetate and fluorocitrate, thiamine deficiency, or dihydrouracil dehydrogenase deficiency. High-dose 5-fluorouracil/folinic acid infusion therapy has recently become a popular regimen for various cancers. It is necessary that both oncologists and neurologists be fully aware of this unusual complication.", "entity": "Fluorouracil", "aliases": "5 FU Lederle medac Fluorouracil biosyn HU Hexal 5-FU 5-Fluorouracil 5-Fluorouracil-biosyn 5-HU 5FU Adrucil Allergan Brand of CSP Carac Dakota Fluorouracile Dermatech Dermik Efudex Efudix Ferrer Fluoro Uracile ICN Fluoro-Uracile Fluoroplex GRY Mononitrate Monopotassium Salt Monosodium Potassium Teva Fluorouracil-GRY Fluorouracilo Far Fluoruracil Fluracedyl Flurodex Gry Haemato fu Haemato-fu Neocorp Neofluor Onkofluor Onkoworks Pharmachemie Ribofluor Riemser Roche ribosepharm", "definition": "A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.\n    ", "id": "MESH:D005472"}
{"mention": "folinic acid", "mention_text": "A 61-year-old man was treated with combination chemotherapy incorporating cisplatinum, etoposide, high-dose 5-fluorouracil (2,250 mg/m2/24 hours) and folinic acid for an inoperable gastric adenocarcinoma. He developed acute neurologic symptoms of mental confusion, disorientation and irritability, and then lapsed into a deep coma, lasting for approximately 40 hours during the first dose (day 2) of 5-fluorouracil and folinic acid infusion. This complication reappeared on day 25 during the second dose of 5-fluorouracil and folinic acid, which were then the only drugs given. Because folinic acid was unlikely to be associated with this condition, neurotoxicity due to high-dose 5-fluorouracil was highly suspected. The pathogenesis of 5-fluorouracil neurotoxicity may be due to a Krebs cycle blockade by fluoroacetate and fluorocitrate, thiamine deficiency, or dihydrouracil dehydrogenase deficiency. High-dose 5-fluorouracil/folinic acid infusion therapy has recently become a popular regimen for various cancers. It is necessary that both oncologists and neurologists be fully aware of this unusual complication.", "entity": "Leucovorin", "aliases": "5 Formyltetrahydrofolate Formyltetrahydropteroylglutamate 5-Formyltetrahydrofolate 5-Formyltetrahydropteroylglutamate Acid Folinic Calcium Folinate Leucovorin Citrovorum Factor SF Acid-SF (D)-Isomer (DL)-Isomer (R)-Isomer (1:1) Salt Pentahydrate Monosodium Leukovorin Leukovorum N(5)-Formyltetrahydrofolate Wellcovorin", "definition": "The active metabolite of FOLIC ACID. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid.\n    ", "id": "MESH:D002955"}
{"mention": "gastric adenocarcinoma", "mention_text": "A 61-year-old man was treated with combination chemotherapy incorporating cisplatinum, etoposide, high-dose 5-fluorouracil (2,250 mg/m2/24 hours) and folinic acid for an inoperable gastric adenocarcinoma. He developed acute neurologic symptoms of mental confusion, disorientation and irritability, and then lapsed into a deep coma, lasting for approximately 40 hours during the first dose (day 2) of 5-fluorouracil and folinic acid infusion. This complication reappeared on day 25 during the second dose of 5-fluorouracil and folinic acid, which were then the only drugs given. Because folinic acid was unlikely to be associated with this condition, neurotoxicity due to high-dose 5-fluorouracil was highly suspected. The pathogenesis of 5-fluorouracil neurotoxicity may be due to a Krebs cycle blockade by fluoroacetate and fluorocitrate, thiamine deficiency, or dihydrouracil dehydrogenase deficiency. High-dose 5-fluorouracil/folinic acid infusion therapy has recently become a popular regimen for various cancers. It is necessary that both oncologists and neurologists be fully aware of this unusual complication.", "entity": "Stomach Neoplasms", "aliases": "Cancer of Stomach the Gastric Cancers Familial Diffuse Neoplasm Neoplasms", "definition": "Tumors or cancer of the STOMACH.\n    ", "id": "MESH:D013274"}
{"mention": "confusion", "mention_text": "A 61-year-old man was treated with combination chemotherapy incorporating cisplatinum, etoposide, high-dose 5-fluorouracil (2,250 mg/m2/24 hours) and folinic acid for an inoperable gastric adenocarcinoma. He developed acute neurologic symptoms of mental confusion, disorientation and irritability, and then lapsed into a deep coma, lasting for approximately 40 hours during the first dose (day 2) of 5-fluorouracil and folinic acid infusion. This complication reappeared on day 25 during the second dose of 5-fluorouracil and folinic acid, which were then the only drugs given. Because folinic acid was unlikely to be associated with this condition, neurotoxicity due to high-dose 5-fluorouracil was highly suspected. The pathogenesis of 5-fluorouracil neurotoxicity may be due to a Krebs cycle blockade by fluoroacetate and fluorocitrate, thiamine deficiency, or dihydrouracil dehydrogenase deficiency. High-dose 5-fluorouracil/folinic acid infusion therapy has recently become a popular regimen for various cancers. It is necessary that both oncologists and neurologists be fully aware of this unusual complication.", "entity": "Confusion", "aliases": "Bewilderment Confusion Post Ictal Post-Ictal Reactive Confusional State States Disorientation", "definition": "A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation.\n    ", "id": "MESH:D003221"}
{"mention": "disorientation", "mention_text": "A 61-year-old man was treated with combination chemotherapy incorporating cisplatinum, etoposide, high-dose 5-fluorouracil (2,250 mg/m2/24 hours) and folinic acid for an inoperable gastric adenocarcinoma. He developed acute neurologic symptoms of mental confusion, disorientation and irritability, and then lapsed into a deep coma, lasting for approximately 40 hours during the first dose (day 2) of 5-fluorouracil and folinic acid infusion. This complication reappeared on day 25 during the second dose of 5-fluorouracil and folinic acid, which were then the only drugs given. Because folinic acid was unlikely to be associated with this condition, neurotoxicity due to high-dose 5-fluorouracil was highly suspected. The pathogenesis of 5-fluorouracil neurotoxicity may be due to a Krebs cycle blockade by fluoroacetate and fluorocitrate, thiamine deficiency, or dihydrouracil dehydrogenase deficiency. High-dose 5-fluorouracil/folinic acid infusion therapy has recently become a popular regimen for various cancers. It is necessary that both oncologists and neurologists be fully aware of this unusual complication.", "entity": "Confusion", "aliases": "Bewilderment Confusion Post Ictal Post-Ictal Reactive Confusional State States Disorientation", "definition": "A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation.\n    ", "id": "MESH:D003221"}
{"mention": "irritability", "mention_text": "A 61-year-old man was treated with combination chemotherapy incorporating cisplatinum, etoposide, high-dose 5-fluorouracil (2,250 mg/m2/24 hours) and folinic acid for an inoperable gastric adenocarcinoma. He developed acute neurologic symptoms of mental confusion, disorientation and irritability, and then lapsed into a deep coma, lasting for approximately 40 hours during the first dose (day 2) of 5-fluorouracil and folinic acid infusion. This complication reappeared on day 25 during the second dose of 5-fluorouracil and folinic acid, which were then the only drugs given. Because folinic acid was unlikely to be associated with this condition, neurotoxicity due to high-dose 5-fluorouracil was highly suspected. The pathogenesis of 5-fluorouracil neurotoxicity may be due to a Krebs cycle blockade by fluoroacetate and fluorocitrate, thiamine deficiency, or dihydrouracil dehydrogenase deficiency. High-dose 5-fluorouracil/folinic acid infusion therapy has recently become a popular regimen for various cancers. It is necessary that both oncologists and neurologists be fully aware of this unusual complication.", "entity": "Mental Disorders", "aliases": "Behavior Disorders Diagnosis Psychiatric Disorder Mental", "definition": "Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.\n    ", "id": "MESH:D001523"}
{"mention": "coma", "mention_text": "A 61-year-old man was treated with combination chemotherapy incorporating cisplatinum, etoposide, high-dose 5-fluorouracil (2,250 mg/m2/24 hours) and folinic acid for an inoperable gastric adenocarcinoma. He developed acute neurologic symptoms of mental confusion, disorientation and irritability, and then lapsed into a deep coma, lasting for approximately 40 hours during the first dose (day 2) of 5-fluorouracil and folinic acid infusion. This complication reappeared on day 25 during the second dose of 5-fluorouracil and folinic acid, which were then the only drugs given. Because folinic acid was unlikely to be associated with this condition, neurotoxicity due to high-dose 5-fluorouracil was highly suspected. The pathogenesis of 5-fluorouracil neurotoxicity may be due to a Krebs cycle blockade by fluoroacetate and fluorocitrate, thiamine deficiency, or dihydrouracil dehydrogenase deficiency. High-dose 5-fluorouracil/folinic acid infusion therapy has recently become a popular regimen for various cancers. It is necessary that both oncologists and neurologists be fully aware of this unusual complication.", "entity": "Coma", "aliases": "Coma Comas Comatose Pseudocoma Pseudocomas", "definition": "A profound state of unconsciousness associated with depressed cerebral activity from which the individual cannot be aroused. Coma generally occurs when there is dysfunction or injury involving both cerebral hemispheres or the brain stem RETICULAR FORMATION.\n    ", "id": "MESH:D003128"}
{"mention": "neurotoxicity", "mention_text": "A 61-year-old man was treated with combination chemotherapy incorporating cisplatinum, etoposide, high-dose 5-fluorouracil (2,250 mg/m2/24 hours) and folinic acid for an inoperable gastric adenocarcinoma. He developed acute neurologic symptoms of mental confusion, disorientation and irritability, and then lapsed into a deep coma, lasting for approximately 40 hours during the first dose (day 2) of 5-fluorouracil and folinic acid infusion. This complication reappeared on day 25 during the second dose of 5-fluorouracil and folinic acid, which were then the only drugs given. Because folinic acid was unlikely to be associated with this condition, neurotoxicity due to high-dose 5-fluorouracil was highly suspected. The pathogenesis of 5-fluorouracil neurotoxicity may be due to a Krebs cycle blockade by fluoroacetate and fluorocitrate, thiamine deficiency, or dihydrouracil dehydrogenase deficiency. High-dose 5-fluorouracil/folinic acid infusion therapy has recently become a popular regimen for various cancers. It is necessary that both oncologists and neurologists be fully aware of this unusual complication.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "fluoroacetate", "mention_text": "A 61-year-old man was treated with combination chemotherapy incorporating cisplatinum, etoposide, high-dose 5-fluorouracil (2,250 mg/m2/24 hours) and folinic acid for an inoperable gastric adenocarcinoma. He developed acute neurologic symptoms of mental confusion, disorientation and irritability, and then lapsed into a deep coma, lasting for approximately 40 hours during the first dose (day 2) of 5-fluorouracil and folinic acid infusion. This complication reappeared on day 25 during the second dose of 5-fluorouracil and folinic acid, which were then the only drugs given. Because folinic acid was unlikely to be associated with this condition, neurotoxicity due to high-dose 5-fluorouracil was highly suspected. The pathogenesis of 5-fluorouracil neurotoxicity may be due to a Krebs cycle blockade by fluoroacetate and fluorocitrate, thiamine deficiency, or dihydrouracil dehydrogenase deficiency. High-dose 5-fluorouracil/folinic acid infusion therapy has recently become a popular regimen for various cancers. It is necessary that both oncologists and neurologists be fully aware of this unusual complication.", "entity": "Fluoroacetates", "aliases": "Fluoroacetates", "definition": "Derivatives of acetic acid with one or more fluorines attached. They are almost odorless, difficult to detect chemically, and very stable. The acid itself, as well as the derivatives that are broken down in the body to the acid, are highly toxic substances, behaving as convulsant poisons with a delayed action. (From Miall's Dictionary of Chemistry, 5th ed)\n    ", "id": "MESH:D005463"}
{"mention": "fluorocitrate", "mention_text": "A 61-year-old man was treated with combination chemotherapy incorporating cisplatinum, etoposide, high-dose 5-fluorouracil (2,250 mg/m2/24 hours) and folinic acid for an inoperable gastric adenocarcinoma. He developed acute neurologic symptoms of mental confusion, disorientation and irritability, and then lapsed into a deep coma, lasting for approximately 40 hours during the first dose (day 2) of 5-fluorouracil and folinic acid infusion. This complication reappeared on day 25 during the second dose of 5-fluorouracil and folinic acid, which were then the only drugs given. Because folinic acid was unlikely to be associated with this condition, neurotoxicity due to high-dose 5-fluorouracil was highly suspected. The pathogenesis of 5-fluorouracil neurotoxicity may be due to a Krebs cycle blockade by fluoroacetate and fluorocitrate, thiamine deficiency, or dihydrouracil dehydrogenase deficiency. High-dose 5-fluorouracil/folinic acid infusion therapy has recently become a popular regimen for various cancers. It is necessary that both oncologists and neurologists be fully aware of this unusual complication.", "entity": "fluorocitrate", "aliases": "2-fluoro-L-erythro-citrate erythrofluorocitrate (isomer) fluorocitrate mono-sodium salt sodium (erythro-DL)-isomer (erythro-D)-isomer (threo-L)-isomer", "definition": "", "id": "MESH:C007744"}
{"mention": "thiamine", "mention_text": "A 61-year-old man was treated with combination chemotherapy incorporating cisplatinum, etoposide, high-dose 5-fluorouracil (2,250 mg/m2/24 hours) and folinic acid for an inoperable gastric adenocarcinoma. He developed acute neurologic symptoms of mental confusion, disorientation and irritability, and then lapsed into a deep coma, lasting for approximately 40 hours during the first dose (day 2) of 5-fluorouracil and folinic acid infusion. This complication reappeared on day 25 during the second dose of 5-fluorouracil and folinic acid, which were then the only drugs given. Because folinic acid was unlikely to be associated with this condition, neurotoxicity due to high-dose 5-fluorouracil was highly suspected. The pathogenesis of 5-fluorouracil neurotoxicity may be due to a Krebs cycle blockade by fluoroacetate and fluorocitrate, thiamine deficiency, or dihydrouracil dehydrogenase deficiency. High-dose 5-fluorouracil/folinic acid infusion therapy has recently become a popular regimen for various cancers. It is necessary that both oncologists and neurologists be fully aware of this unusual complication.", "entity": "Thiamine", "aliases": "Aneurin Mononitrate Thiamine Vitamin B 1 B1", "definition": "3-((4-Amino-2-methyl-5-pyrimidinyl)methyl)-5-(2- hydroxyethyl)-4-methylthiazolium chloride.\n    ", "id": "MESH:D013831"}
{"mention": "dihydrouracil", "mention_text": "A 61-year-old man was treated with combination chemotherapy incorporating cisplatinum, etoposide, high-dose 5-fluorouracil (2,250 mg/m2/24 hours) and folinic acid for an inoperable gastric adenocarcinoma. He developed acute neurologic symptoms of mental confusion, disorientation and irritability, and then lapsed into a deep coma, lasting for approximately 40 hours during the first dose (day 2) of 5-fluorouracil and folinic acid infusion. This complication reappeared on day 25 during the second dose of 5-fluorouracil and folinic acid, which were then the only drugs given. Because folinic acid was unlikely to be associated with this condition, neurotoxicity due to high-dose 5-fluorouracil was highly suspected. The pathogenesis of 5-fluorouracil neurotoxicity may be due to a Krebs cycle blockade by fluoroacetate and fluorocitrate, thiamine deficiency, or dihydrouracil dehydrogenase deficiency. High-dose 5-fluorouracil/folinic acid infusion therapy has recently become a popular regimen for various cancers. It is necessary that both oncologists and neurologists be fully aware of this unusual complication.", "entity": "dihydrouracil", "aliases": "dihydrouracil", "definition": "", "id": "MESH:C007419"}
{"mention": "cancers", "mention_text": "A 61-year-old man was treated with combination chemotherapy incorporating cisplatinum, etoposide, high-dose 5-fluorouracil (2,250 mg/m2/24 hours) and folinic acid for an inoperable gastric adenocarcinoma. He developed acute neurologic symptoms of mental confusion, disorientation and irritability, and then lapsed into a deep coma, lasting for approximately 40 hours during the first dose (day 2) of 5-fluorouracil and folinic acid infusion. This complication reappeared on day 25 during the second dose of 5-fluorouracil and folinic acid, which were then the only drugs given. Because folinic acid was unlikely to be associated with this condition, neurotoxicity due to high-dose 5-fluorouracil was highly suspected. The pathogenesis of 5-fluorouracil neurotoxicity may be due to a Krebs cycle blockade by fluoroacetate and fluorocitrate, thiamine deficiency, or dihydrouracil dehydrogenase deficiency. High-dose 5-fluorouracil/folinic acid infusion therapy has recently become a popular regimen for various cancers. It is necessary that both oncologists and neurologists be fully aware of this unusual complication.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "carbamazepine", "mention_text": "Effect of switching carbamazepine to oxcarbazepine on the plasma levels of neuroleptics. A case report.", "entity": "Carbamazepine", "aliases": "Amizepine Carbamazepine Acetate Anhydrous Dihydrate Hydrochloride L-Tartrate (4:1) Phosphate Sulfate (2:1) Carbazepin Epitol Finlepsin Neurotol Tegretol", "definition": "An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of PHENYTOIN; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar.\n    ", "id": "MESH:D002220"}
{"mention": "oxcarbazepine", "mention_text": "Effect of switching carbamazepine to oxcarbazepine on the plasma levels of neuroleptics. A case report.", "entity": "oxcarbazepine", "aliases": "Desitin brand of oxcarbazepine GP 47680 Novartis Timox Trileptal", "definition": "", "id": "MESH:C036006"}
{"mention": "Carbamazepine", "mention_text": "Carbamazepine was switched to its 10-keto analogue oxcarbazepine among six difficult-to-treat schizophrenic or organic psychotic patients using concomitantly haloperidol, chlorpromazine or clozapine. This change resulted within 2-4 weeks in the 50-200% increase in the plasma levels of these neuroleptics and the appearance of extrapyramidal symptoms. None of the patients showed any clinical deteriotation during the following 3-6 months. The results of this case report support the idea that in contrast with carbamazepine oxcarbazepine does not induce the hepatic microsomal enzyme systems regulating the inactivation of antipsychotic drugs.", "entity": "Carbamazepine", "aliases": "Amizepine Carbamazepine Acetate Anhydrous Dihydrate Hydrochloride L-Tartrate (4:1) Phosphate Sulfate (2:1) Carbazepin Epitol Finlepsin Neurotol Tegretol", "definition": "An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of PHENYTOIN; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar.\n    ", "id": "MESH:D002220"}
{"mention": "oxcarbazepine", "mention_text": "Carbamazepine was switched to its 10-keto analogue oxcarbazepine among six difficult-to-treat schizophrenic or organic psychotic patients using concomitantly haloperidol, chlorpromazine or clozapine. This change resulted within 2-4 weeks in the 50-200% increase in the plasma levels of these neuroleptics and the appearance of extrapyramidal symptoms. None of the patients showed any clinical deteriotation during the following 3-6 months. The results of this case report support the idea that in contrast with carbamazepine oxcarbazepine does not induce the hepatic microsomal enzyme systems regulating the inactivation of antipsychotic drugs.", "entity": "oxcarbazepine", "aliases": "Desitin brand of oxcarbazepine GP 47680 Novartis Timox Trileptal", "definition": "", "id": "MESH:C036006"}
{"mention": "schizophrenic", "mention_text": "Carbamazepine was switched to its 10-keto analogue oxcarbazepine among six difficult-to-treat schizophrenic or organic psychotic patients using concomitantly haloperidol, chlorpromazine or clozapine. This change resulted within 2-4 weeks in the 50-200% increase in the plasma levels of these neuroleptics and the appearance of extrapyramidal symptoms. None of the patients showed any clinical deteriotation during the following 3-6 months. The results of this case report support the idea that in contrast with carbamazepine oxcarbazepine does not induce the hepatic microsomal enzyme systems regulating the inactivation of antipsychotic drugs.", "entity": "Schizophrenia", "aliases": "Dementia Praecox Disorder Schizophrenic Disorders Schizophrenia Schizophrenias", "definition": "A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior.\n    ", "id": "MESH:D012559"}
{"mention": "organic psychotic", "mention_text": "Carbamazepine was switched to its 10-keto analogue oxcarbazepine among six difficult-to-treat schizophrenic or organic psychotic patients using concomitantly haloperidol, chlorpromazine or clozapine. This change resulted within 2-4 weeks in the 50-200% increase in the plasma levels of these neuroleptics and the appearance of extrapyramidal symptoms. None of the patients showed any clinical deteriotation during the following 3-6 months. The results of this case report support the idea that in contrast with carbamazepine oxcarbazepine does not induce the hepatic microsomal enzyme systems regulating the inactivation of antipsychotic drugs.", "entity": "Delirium, Dementia, Amnestic, Cognitive Disorders", "aliases": "Clerambault Syndrome Delirium Dementia Amnestic Cognitive Disorders Organic Mental Kandinsky Disorder Nonpsychotic Brain Psychotic Psychoses Traumatic", "definition": "Cognitive disorders including delirium, dementia, and other cognitive disorders. These may be the result of substance use, trauma, or other causes.\n    ", "id": "MESH:D019965"}
{"mention": "haloperidol", "mention_text": "Carbamazepine was switched to its 10-keto analogue oxcarbazepine among six difficult-to-treat schizophrenic or organic psychotic patients using concomitantly haloperidol, chlorpromazine or clozapine. This change resulted within 2-4 weeks in the 50-200% increase in the plasma levels of these neuroleptics and the appearance of extrapyramidal symptoms. None of the patients showed any clinical deteriotation during the following 3-6 months. The results of this case report support the idea that in contrast with carbamazepine oxcarbazepine does not induce the hepatic microsomal enzyme systems regulating the inactivation of antipsychotic drugs.", "entity": "Haloperidol", "aliases": "Haldol Haloperidol", "definition": "A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)\n    ", "id": "MESH:D006220"}
{"mention": "chlorpromazine", "mention_text": "Carbamazepine was switched to its 10-keto analogue oxcarbazepine among six difficult-to-treat schizophrenic or organic psychotic patients using concomitantly haloperidol, chlorpromazine or clozapine. This change resulted within 2-4 weeks in the 50-200% increase in the plasma levels of these neuroleptics and the appearance of extrapyramidal symptoms. None of the patients showed any clinical deteriotation during the following 3-6 months. The results of this case report support the idea that in contrast with carbamazepine oxcarbazepine does not induce the hepatic microsomal enzyme systems regulating the inactivation of antipsychotic drugs.", "entity": "Chlorpromazine", "aliases": "Aminazine Chlorazine Chlordelazine Chlorpromazine Hydrochloride Contomin Fenactil Largactil Propaphenin Thorazine", "definition": "The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking DOPAMINE RECEPTORS. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup.\n    ", "id": "MESH:D002746"}
{"mention": "clozapine", "mention_text": "Carbamazepine was switched to its 10-keto analogue oxcarbazepine among six difficult-to-treat schizophrenic or organic psychotic patients using concomitantly haloperidol, chlorpromazine or clozapine. This change resulted within 2-4 weeks in the 50-200% increase in the plasma levels of these neuroleptics and the appearance of extrapyramidal symptoms. None of the patients showed any clinical deteriotation during the following 3-6 months. The results of this case report support the idea that in contrast with carbamazepine oxcarbazepine does not induce the hepatic microsomal enzyme systems regulating the inactivation of antipsychotic drugs.", "entity": "Clozapine", "aliases": "Clozapine Clozaril Leponex", "definition": "A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.\n    ", "id": "MESH:D003024"}
{"mention": "extrapyramidal symptoms", "mention_text": "Carbamazepine was switched to its 10-keto analogue oxcarbazepine among six difficult-to-treat schizophrenic or organic psychotic patients using concomitantly haloperidol, chlorpromazine or clozapine. This change resulted within 2-4 weeks in the 50-200% increase in the plasma levels of these neuroleptics and the appearance of extrapyramidal symptoms. None of the patients showed any clinical deteriotation during the following 3-6 months. The results of this case report support the idea that in contrast with carbamazepine oxcarbazepine does not induce the hepatic microsomal enzyme systems regulating the inactivation of antipsychotic drugs.", "entity": "Basal Ganglia Diseases", "aliases": "Basal Ganglia Disease Diseases Disorder Disorders Extrapyramidal Lenticulostriate", "definition": "Diseases of the BASAL GANGLIA including the PUTAMEN; GLOBUS PALLIDUS; claustrum; AMYGDALA; and CAUDATE NUCLEUS. DYSKINESIAS (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include CEREBROVASCULAR DISORDERS; NEURODEGENERATIVE DISEASES; and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D001480"}
{"mention": "carbamazepine", "mention_text": "Carbamazepine was switched to its 10-keto analogue oxcarbazepine among six difficult-to-treat schizophrenic or organic psychotic patients using concomitantly haloperidol, chlorpromazine or clozapine. This change resulted within 2-4 weeks in the 50-200% increase in the plasma levels of these neuroleptics and the appearance of extrapyramidal symptoms. None of the patients showed any clinical deteriotation during the following 3-6 months. The results of this case report support the idea that in contrast with carbamazepine oxcarbazepine does not induce the hepatic microsomal enzyme systems regulating the inactivation of antipsychotic drugs.", "entity": "Carbamazepine", "aliases": "Amizepine Carbamazepine Acetate Anhydrous Dihydrate Hydrochloride L-Tartrate (4:1) Phosphate Sulfate (2:1) Carbazepin Epitol Finlepsin Neurotol Tegretol", "definition": "An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of PHENYTOIN; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar.\n    ", "id": "MESH:D002220"}
{"mention": "Erythema multiforme", "mention_text": "Erythema multiforme and hypersensitivity myocarditis caused by ampicillin.", "entity": "Erythema Multiforme", "aliases": "Erythema Multiforme", "definition": "A skin and mucous membrane disease characterized by an eruption of macules, papules, nodules, vesicles, and/or bullae with characteristic \"bull's-eye\" lesions usually occurring on the dorsal aspect of the hands and forearms.\n    ", "id": "MESH:D004892"}
{"mention": "hypersensitivity myocarditis", "mention_text": "Erythema multiforme and hypersensitivity myocarditis caused by ampicillin.", "entity": "Myocarditis", "aliases": "Carditis Myocarditides Myocarditis", "definition": "Inflammatory processes of the muscular walls of the heart (MYOCARDIUM) which result in injury to the cardiac muscle cells (MYOCYTES, CARDIAC). Manifestations range from subclinical to sudden death (DEATH, SUDDEN). Myocarditis in association with cardiac dysfunction is classified as inflammatory CARDIOMYOPATHY usually caused by INFECTION, autoimmune diseases, or responses to toxic substances. Myocarditis is also a common cause of DILATED CARDIOMYOPATHY and other cardiomyopathies.\n    ", "id": "MESH:D009205"}
{"mention": "ampicillin", "mention_text": "Erythema multiforme and hypersensitivity myocarditis caused by ampicillin.", "entity": "Ampicillin", "aliases": "Amcill Aminobenzyl Penicillin Aminobenzylpenicillin Ampicillin Sodium Trihydrate Antibiotic KS R1 KS-R1 Omnipen Pentrexyl Polycillin Ukapen", "definition": "Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic.\n    ", "id": "MESH:D000667"}
{"mention": "erythema multiforme", "mention_text": "OBJECTIVE: To report a case of erythema multiforme and hypersensitivity myocarditis caused by ampicillin. CASE SUMMARY: A 13-year-old boy was treated with ampicillin and gentamicin because of suspected septicemia. Medications were discontinued when erythema multiforme and congestive heart failure caused by myocarditis occurred. The patient was treated with methylprednisolone and gradually improved. Macrophage-migration inhibition (MIF) test with ampicillin was positive. DISCUSSION: After most infections causing erythema multiforme and myocarditis were ruled out, a drug-induced allergic reaction was suspected. Positive MIF test for ampicillin showed sensitization of the patient's lymphocytes to ampicillin. CONCLUSIONS: Hypersensitivity myocarditis is a rare and dangerous manifestation of allergy to penicillins.", "entity": "Erythema Multiforme", "aliases": "Erythema Multiforme", "definition": "A skin and mucous membrane disease characterized by an eruption of macules, papules, nodules, vesicles, and/or bullae with characteristic \"bull's-eye\" lesions usually occurring on the dorsal aspect of the hands and forearms.\n    ", "id": "MESH:D004892"}
{"mention": "hypersensitivity myocarditis", "mention_text": "OBJECTIVE: To report a case of erythema multiforme and hypersensitivity myocarditis caused by ampicillin. CASE SUMMARY: A 13-year-old boy was treated with ampicillin and gentamicin because of suspected septicemia. Medications were discontinued when erythema multiforme and congestive heart failure caused by myocarditis occurred. The patient was treated with methylprednisolone and gradually improved. Macrophage-migration inhibition (MIF) test with ampicillin was positive. DISCUSSION: After most infections causing erythema multiforme and myocarditis were ruled out, a drug-induced allergic reaction was suspected. Positive MIF test for ampicillin showed sensitization of the patient's lymphocytes to ampicillin. CONCLUSIONS: Hypersensitivity myocarditis is a rare and dangerous manifestation of allergy to penicillins.", "entity": "Myocarditis", "aliases": "Carditis Myocarditides Myocarditis", "definition": "Inflammatory processes of the muscular walls of the heart (MYOCARDIUM) which result in injury to the cardiac muscle cells (MYOCYTES, CARDIAC). Manifestations range from subclinical to sudden death (DEATH, SUDDEN). Myocarditis in association with cardiac dysfunction is classified as inflammatory CARDIOMYOPATHY usually caused by INFECTION, autoimmune diseases, or responses to toxic substances. Myocarditis is also a common cause of DILATED CARDIOMYOPATHY and other cardiomyopathies.\n    ", "id": "MESH:D009205"}
{"mention": "ampicillin", "mention_text": "OBJECTIVE: To report a case of erythema multiforme and hypersensitivity myocarditis caused by ampicillin. CASE SUMMARY: A 13-year-old boy was treated with ampicillin and gentamicin because of suspected septicemia. Medications were discontinued when erythema multiforme and congestive heart failure caused by myocarditis occurred. The patient was treated with methylprednisolone and gradually improved. Macrophage-migration inhibition (MIF) test with ampicillin was positive. DISCUSSION: After most infections causing erythema multiforme and myocarditis were ruled out, a drug-induced allergic reaction was suspected. Positive MIF test for ampicillin showed sensitization of the patient's lymphocytes to ampicillin. CONCLUSIONS: Hypersensitivity myocarditis is a rare and dangerous manifestation of allergy to penicillins.", "entity": "Ampicillin", "aliases": "Amcill Aminobenzyl Penicillin Aminobenzylpenicillin Ampicillin Sodium Trihydrate Antibiotic KS R1 KS-R1 Omnipen Pentrexyl Polycillin Ukapen", "definition": "Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic.\n    ", "id": "MESH:D000667"}
{"mention": "gentamicin", "mention_text": "OBJECTIVE: To report a case of erythema multiforme and hypersensitivity myocarditis caused by ampicillin. CASE SUMMARY: A 13-year-old boy was treated with ampicillin and gentamicin because of suspected septicemia. Medications were discontinued when erythema multiforme and congestive heart failure caused by myocarditis occurred. The patient was treated with methylprednisolone and gradually improved. Macrophage-migration inhibition (MIF) test with ampicillin was positive. DISCUSSION: After most infections causing erythema multiforme and myocarditis were ruled out, a drug-induced allergic reaction was suspected. Positive MIF test for ampicillin showed sensitization of the patient's lymphocytes to ampicillin. CONCLUSIONS: Hypersensitivity myocarditis is a rare and dangerous manifestation of allergy to penicillins.", "entity": "Gentamicins", "aliases": "G Myticin G-Myticin GMyticin Garamycin Gentacycol Gentamicin Sulfate (USP) Gentamicins Gentamycin Gentamycins Gentavet Genticin", "definition": "A complex of closely related aminoglycosides obtained from MICROMONOSPORA purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit PROTEIN BIOSYNTHESIS.\n    ", "id": "MESH:D005839"}
{"mention": "septicemia", "mention_text": "OBJECTIVE: To report a case of erythema multiforme and hypersensitivity myocarditis caused by ampicillin. CASE SUMMARY: A 13-year-old boy was treated with ampicillin and gentamicin because of suspected septicemia. Medications were discontinued when erythema multiforme and congestive heart failure caused by myocarditis occurred. The patient was treated with methylprednisolone and gradually improved. Macrophage-migration inhibition (MIF) test with ampicillin was positive. DISCUSSION: After most infections causing erythema multiforme and myocarditis were ruled out, a drug-induced allergic reaction was suspected. Positive MIF test for ampicillin showed sensitization of the patient's lymphocytes to ampicillin. CONCLUSIONS: Hypersensitivity myocarditis is a rare and dangerous manifestation of allergy to penicillins.", "entity": "Sepsis", "aliases": "Blood Poisoning Poisonings Pyaemia Pyaemias Pyemia Pyemias Pyohemia Pyohemias Sepsis Severe Septicemia Septicemias", "definition": "Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by HYPOTENSION despite adequate fluid infusion, it is called SEPTIC SHOCK.\n    ", "id": "MESH:D018805"}
{"mention": "congestive heart failure", "mention_text": "OBJECTIVE: To report a case of erythema multiforme and hypersensitivity myocarditis caused by ampicillin. CASE SUMMARY: A 13-year-old boy was treated with ampicillin and gentamicin because of suspected septicemia. Medications were discontinued when erythema multiforme and congestive heart failure caused by myocarditis occurred. The patient was treated with methylprednisolone and gradually improved. Macrophage-migration inhibition (MIF) test with ampicillin was positive. DISCUSSION: After most infections causing erythema multiforme and myocarditis were ruled out, a drug-induced allergic reaction was suspected. Positive MIF test for ampicillin showed sensitization of the patient's lymphocytes to ampicillin. CONCLUSIONS: Hypersensitivity myocarditis is a rare and dangerous manifestation of allergy to penicillins.", "entity": "Heart Failure", "aliases": "Cardiac Failure Congestive Heart Decompensation Left Sided Left-Sided Right Right-Sided Myocardial", "definition": "A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.\n    ", "id": "MESH:D006333"}
{"mention": "myocarditis", "mention_text": "OBJECTIVE: To report a case of erythema multiforme and hypersensitivity myocarditis caused by ampicillin. CASE SUMMARY: A 13-year-old boy was treated with ampicillin and gentamicin because of suspected septicemia. Medications were discontinued when erythema multiforme and congestive heart failure caused by myocarditis occurred. The patient was treated with methylprednisolone and gradually improved. Macrophage-migration inhibition (MIF) test with ampicillin was positive. DISCUSSION: After most infections causing erythema multiforme and myocarditis were ruled out, a drug-induced allergic reaction was suspected. Positive MIF test for ampicillin showed sensitization of the patient's lymphocytes to ampicillin. CONCLUSIONS: Hypersensitivity myocarditis is a rare and dangerous manifestation of allergy to penicillins.", "entity": "Myocarditis", "aliases": "Carditis Myocarditides Myocarditis", "definition": "Inflammatory processes of the muscular walls of the heart (MYOCARDIUM) which result in injury to the cardiac muscle cells (MYOCYTES, CARDIAC). Manifestations range from subclinical to sudden death (DEATH, SUDDEN). Myocarditis in association with cardiac dysfunction is classified as inflammatory CARDIOMYOPATHY usually caused by INFECTION, autoimmune diseases, or responses to toxic substances. Myocarditis is also a common cause of DILATED CARDIOMYOPATHY and other cardiomyopathies.\n    ", "id": "MESH:D009205"}
{"mention": "methylprednisolone", "mention_text": "OBJECTIVE: To report a case of erythema multiforme and hypersensitivity myocarditis caused by ampicillin. CASE SUMMARY: A 13-year-old boy was treated with ampicillin and gentamicin because of suspected septicemia. Medications were discontinued when erythema multiforme and congestive heart failure caused by myocarditis occurred. The patient was treated with methylprednisolone and gradually improved. Macrophage-migration inhibition (MIF) test with ampicillin was positive. DISCUSSION: After most infections causing erythema multiforme and myocarditis were ruled out, a drug-induced allergic reaction was suspected. Positive MIF test for ampicillin showed sensitization of the patient's lymphocytes to ampicillin. CONCLUSIONS: Hypersensitivity myocarditis is a rare and dangerous manifestation of allergy to penicillins.", "entity": "Methylprednisolone", "aliases": "6 Methylprednisolone 6-Methylprednisolone Medrol Metipred Urbason", "definition": "A PREDNISOLONE derivative with similar anti-inflammatory action.\n    ", "id": "MESH:D008775"}
{"mention": "infections", "mention_text": "OBJECTIVE: To report a case of erythema multiforme and hypersensitivity myocarditis caused by ampicillin. CASE SUMMARY: A 13-year-old boy was treated with ampicillin and gentamicin because of suspected septicemia. Medications were discontinued when erythema multiforme and congestive heart failure caused by myocarditis occurred. The patient was treated with methylprednisolone and gradually improved. Macrophage-migration inhibition (MIF) test with ampicillin was positive. DISCUSSION: After most infections causing erythema multiforme and myocarditis were ruled out, a drug-induced allergic reaction was suspected. Positive MIF test for ampicillin showed sensitization of the patient's lymphocytes to ampicillin. CONCLUSIONS: Hypersensitivity myocarditis is a rare and dangerous manifestation of allergy to penicillins.", "entity": "Infection", "aliases": "Infection Infections", "definition": "Invasion of the host organism by microorganisms that can cause pathological conditions or diseases.\n    ", "id": "MESH:D007239"}
{"mention": "drug-induced allergic reaction", "mention_text": "OBJECTIVE: To report a case of erythema multiforme and hypersensitivity myocarditis caused by ampicillin. CASE SUMMARY: A 13-year-old boy was treated with ampicillin and gentamicin because of suspected septicemia. Medications were discontinued when erythema multiforme and congestive heart failure caused by myocarditis occurred. The patient was treated with methylprednisolone and gradually improved. Macrophage-migration inhibition (MIF) test with ampicillin was positive. DISCUSSION: After most infections causing erythema multiforme and myocarditis were ruled out, a drug-induced allergic reaction was suspected. Positive MIF test for ampicillin showed sensitization of the patient's lymphocytes to ampicillin. CONCLUSIONS: Hypersensitivity myocarditis is a rare and dangerous manifestation of allergy to penicillins.", "entity": "Drug Hypersensitivity", "aliases": "Allergies Drug Allergy Hypersensitivities Hypersensitivity", "definition": "Immunologically mediated adverse reactions to medicinal substances used legally or illegally.\n    ", "id": "MESH:D004342"}
{"mention": "Hypersensitivity myocarditis", "mention_text": "OBJECTIVE: To report a case of erythema multiforme and hypersensitivity myocarditis caused by ampicillin. CASE SUMMARY: A 13-year-old boy was treated with ampicillin and gentamicin because of suspected septicemia. Medications were discontinued when erythema multiforme and congestive heart failure caused by myocarditis occurred. The patient was treated with methylprednisolone and gradually improved. Macrophage-migration inhibition (MIF) test with ampicillin was positive. DISCUSSION: After most infections causing erythema multiforme and myocarditis were ruled out, a drug-induced allergic reaction was suspected. Positive MIF test for ampicillin showed sensitization of the patient's lymphocytes to ampicillin. CONCLUSIONS: Hypersensitivity myocarditis is a rare and dangerous manifestation of allergy to penicillins.", "entity": "Myocarditis", "aliases": "Carditis Myocarditides Myocarditis", "definition": "Inflammatory processes of the muscular walls of the heart (MYOCARDIUM) which result in injury to the cardiac muscle cells (MYOCYTES, CARDIAC). Manifestations range from subclinical to sudden death (DEATH, SUDDEN). Myocarditis in association with cardiac dysfunction is classified as inflammatory CARDIOMYOPATHY usually caused by INFECTION, autoimmune diseases, or responses to toxic substances. Myocarditis is also a common cause of DILATED CARDIOMYOPATHY and other cardiomyopathies.\n    ", "id": "MESH:D009205"}
{"mention": "allergy", "mention_text": "OBJECTIVE: To report a case of erythema multiforme and hypersensitivity myocarditis caused by ampicillin. CASE SUMMARY: A 13-year-old boy was treated with ampicillin and gentamicin because of suspected septicemia. Medications were discontinued when erythema multiforme and congestive heart failure caused by myocarditis occurred. The patient was treated with methylprednisolone and gradually improved. Macrophage-migration inhibition (MIF) test with ampicillin was positive. DISCUSSION: After most infections causing erythema multiforme and myocarditis were ruled out, a drug-induced allergic reaction was suspected. Positive MIF test for ampicillin showed sensitization of the patient's lymphocytes to ampicillin. CONCLUSIONS: Hypersensitivity myocarditis is a rare and dangerous manifestation of allergy to penicillins.", "entity": "Drug Hypersensitivity", "aliases": "Allergies Drug Allergy Hypersensitivities Hypersensitivity", "definition": "Immunologically mediated adverse reactions to medicinal substances used legally or illegally.\n    ", "id": "MESH:D004342"}
{"mention": "penicillins", "mention_text": "OBJECTIVE: To report a case of erythema multiforme and hypersensitivity myocarditis caused by ampicillin. CASE SUMMARY: A 13-year-old boy was treated with ampicillin and gentamicin because of suspected septicemia. Medications were discontinued when erythema multiforme and congestive heart failure caused by myocarditis occurred. The patient was treated with methylprednisolone and gradually improved. Macrophage-migration inhibition (MIF) test with ampicillin was positive. DISCUSSION: After most infections causing erythema multiforme and myocarditis were ruled out, a drug-induced allergic reaction was suspected. Positive MIF test for ampicillin showed sensitization of the patient's lymphocytes to ampicillin. CONCLUSIONS: Hypersensitivity myocarditis is a rare and dangerous manifestation of allergy to penicillins.", "entity": "Penicillins", "aliases": "Antibiotics Penicillin Penicillins", "definition": "A group of antibiotics that contain 6-aminopenicillanic acid with a side chain attached to the 6-amino group. The penicillin nucleus is the chief structural requirement for biological activity. The side-chain structure determines many of the antibacterial and pharmacological characteristics. (Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1065)\n    ", "id": "MESH:D010406"}
{"mention": "allergic reactions", "mention_text": "Immediate allergic reactions to amoxicillin.", "entity": "Drug Hypersensitivity", "aliases": "Allergies Drug Allergy Hypersensitivities Hypersensitivity", "definition": "Immunologically mediated adverse reactions to medicinal substances used legally or illegally.\n    ", "id": "MESH:D004342"}
{"mention": "amoxicillin", "mention_text": "Immediate allergic reactions to amoxicillin.", "entity": "Amoxicillin", "aliases": "Actimoxi Amoxicillin Anhydrous Clariana Brand Monopotassium Salt Monosodium Sodium Trihydrate (R*)-Isomer Amoxicilline Amoxil Amoxycillin BRL 2333 BRL-2333 BRL2333 Clamoxyl G.A. parenteral of Hydroxyampicillin Penamox Pfizer Polymox SmithKline Beecham Trimox Wymox", "definition": "A broad-spectrum semisynthetic antibiotic similar to AMPICILLIN except that its resistance to gastric acid permits higher serum levels with oral administration.\n    ", "id": "MESH:D000658"}
{"mention": "allergic reactions", "mention_text": "A large group of patients with suspected allergic reactions to beta-lactam antibiotics was evaluated. A detailed clinical history, together with skin tests, RAST (radioallergosorbent test), and controlled challenge tests, was used to establish whether patients allergic to beta-lactam antibiotics had selective immediate allergic responses to amoxicillin (AX) or were cross-reacting with other penicillin derivatives. Skin tests were performed with benzylpenicilloyl-poly-L-lysine (BPO-PLL), benzylpenicilloate, benzylpenicillin (PG), ampicillin (AMP), and AX. RAST for BPO-PLL and AX-PLL was done. When both skin test and RAST for BPO were negative, single-blind, placebo-controlled challenge tests were done to ensure tolerance of PG or sensitivity to AX. A total of 177 patients were diagnosed as allergic to beta-lactam antibiotics. We selected the 54 (30.5%) cases of immediate AX allergy with good tolerance of PG. Anaphylaxis was seen in 37 patients (69%), the other 17 (31%) having urticaria and/or angioedema. All the patients were skin test negative to BPO; 49 of 51 (96%) were also negative to MDM, and 44 of 46 (96%) to PG. Skin tests with AX were positive in 34 (63%) patients. RAST was positive for AX in 22 patients (41%) and to BPO in just 5 (9%). None of the sera with negative RAST for AX were positive to BPO. Challenge tests with AX were performed in 23 subjects (43%) to establish the diagnosis of immediate allergic reaction to AX, and in 15 cases (28%) both skin test and RAST for AX were negative. PG was well tolerated by all 54 patients. We describe the largest group of AX-allergic patients who have tolerated PG reported so far. Diagnosis of these patients can be achieved only if specific AX-related reagents are employed. Further studies are necessary to determine the exact extent of this problem and to improve the efficacy of diagnostic methods.", "entity": "Drug Hypersensitivity", "aliases": "Allergies Drug Allergy Hypersensitivities Hypersensitivity", "definition": "Immunologically mediated adverse reactions to medicinal substances used legally or illegally.\n    ", "id": "MESH:D004342"}
{"mention": "beta-lactam", "mention_text": "A large group of patients with suspected allergic reactions to beta-lactam antibiotics was evaluated. A detailed clinical history, together with skin tests, RAST (radioallergosorbent test), and controlled challenge tests, was used to establish whether patients allergic to beta-lactam antibiotics had selective immediate allergic responses to amoxicillin (AX) or were cross-reacting with other penicillin derivatives. Skin tests were performed with benzylpenicilloyl-poly-L-lysine (BPO-PLL), benzylpenicilloate, benzylpenicillin (PG), ampicillin (AMP), and AX. RAST for BPO-PLL and AX-PLL was done. When both skin test and RAST for BPO were negative, single-blind, placebo-controlled challenge tests were done to ensure tolerance of PG or sensitivity to AX. A total of 177 patients were diagnosed as allergic to beta-lactam antibiotics. We selected the 54 (30.5%) cases of immediate AX allergy with good tolerance of PG. Anaphylaxis was seen in 37 patients (69%), the other 17 (31%) having urticaria and/or angioedema. All the patients were skin test negative to BPO; 49 of 51 (96%) were also negative to MDM, and 44 of 46 (96%) to PG. Skin tests with AX were positive in 34 (63%) patients. RAST was positive for AX in 22 patients (41%) and to BPO in just 5 (9%). None of the sera with negative RAST for AX were positive to BPO. Challenge tests with AX were performed in 23 subjects (43%) to establish the diagnosis of immediate allergic reaction to AX, and in 15 cases (28%) both skin test and RAST for AX were negative. PG was well tolerated by all 54 patients. We describe the largest group of AX-allergic patients who have tolerated PG reported so far. Diagnosis of these patients can be achieved only if specific AX-related reagents are employed. Further studies are necessary to determine the exact extent of this problem and to improve the efficacy of diagnostic methods.", "entity": "beta-Lactams", "aliases": "4-Thia-1-Azabicyclo(3.2.0)Heptanes 4-Thia-1-Azabicyclo(4.2.0)Octanes beta Lactams beta-Lactams", "definition": "Four-membered cyclic AMIDES, best known for the PENICILLINS based on a bicyclo-thiazolidine, as well as the CEPHALOSPORINS based on a bicyclo-thiazine, and including monocyclic MONOBACTAMS. The BETA-LACTAMASES hydrolyze the beta lactam ring, accounting for BETA-LACTAM RESISTANCE of infective bacteria.\n    ", "id": "MESH:D047090"}
{"mention": "allergic", "mention_text": "A large group of patients with suspected allergic reactions to beta-lactam antibiotics was evaluated. A detailed clinical history, together with skin tests, RAST (radioallergosorbent test), and controlled challenge tests, was used to establish whether patients allergic to beta-lactam antibiotics had selective immediate allergic responses to amoxicillin (AX) or were cross-reacting with other penicillin derivatives. Skin tests were performed with benzylpenicilloyl-poly-L-lysine (BPO-PLL), benzylpenicilloate, benzylpenicillin (PG), ampicillin (AMP), and AX. RAST for BPO-PLL and AX-PLL was done. When both skin test and RAST for BPO were negative, single-blind, placebo-controlled challenge tests were done to ensure tolerance of PG or sensitivity to AX. A total of 177 patients were diagnosed as allergic to beta-lactam antibiotics. We selected the 54 (30.5%) cases of immediate AX allergy with good tolerance of PG. Anaphylaxis was seen in 37 patients (69%), the other 17 (31%) having urticaria and/or angioedema. All the patients were skin test negative to BPO; 49 of 51 (96%) were also negative to MDM, and 44 of 46 (96%) to PG. Skin tests with AX were positive in 34 (63%) patients. RAST was positive for AX in 22 patients (41%) and to BPO in just 5 (9%). None of the sera with negative RAST for AX were positive to BPO. Challenge tests with AX were performed in 23 subjects (43%) to establish the diagnosis of immediate allergic reaction to AX, and in 15 cases (28%) both skin test and RAST for AX were negative. PG was well tolerated by all 54 patients. We describe the largest group of AX-allergic patients who have tolerated PG reported so far. Diagnosis of these patients can be achieved only if specific AX-related reagents are employed. Further studies are necessary to determine the exact extent of this problem and to improve the efficacy of diagnostic methods.", "entity": "Drug Hypersensitivity", "aliases": "Allergies Drug Allergy Hypersensitivities Hypersensitivity", "definition": "Immunologically mediated adverse reactions to medicinal substances used legally or illegally.\n    ", "id": "MESH:D004342"}
{"mention": "amoxicillin", "mention_text": "A large group of patients with suspected allergic reactions to beta-lactam antibiotics was evaluated. A detailed clinical history, together with skin tests, RAST (radioallergosorbent test), and controlled challenge tests, was used to establish whether patients allergic to beta-lactam antibiotics had selective immediate allergic responses to amoxicillin (AX) or were cross-reacting with other penicillin derivatives. Skin tests were performed with benzylpenicilloyl-poly-L-lysine (BPO-PLL), benzylpenicilloate, benzylpenicillin (PG), ampicillin (AMP), and AX. RAST for BPO-PLL and AX-PLL was done. When both skin test and RAST for BPO were negative, single-blind, placebo-controlled challenge tests were done to ensure tolerance of PG or sensitivity to AX. A total of 177 patients were diagnosed as allergic to beta-lactam antibiotics. We selected the 54 (30.5%) cases of immediate AX allergy with good tolerance of PG. Anaphylaxis was seen in 37 patients (69%), the other 17 (31%) having urticaria and/or angioedema. All the patients were skin test negative to BPO; 49 of 51 (96%) were also negative to MDM, and 44 of 46 (96%) to PG. Skin tests with AX were positive in 34 (63%) patients. RAST was positive for AX in 22 patients (41%) and to BPO in just 5 (9%). None of the sera with negative RAST for AX were positive to BPO. Challenge tests with AX were performed in 23 subjects (43%) to establish the diagnosis of immediate allergic reaction to AX, and in 15 cases (28%) both skin test and RAST for AX were negative. PG was well tolerated by all 54 patients. We describe the largest group of AX-allergic patients who have tolerated PG reported so far. Diagnosis of these patients can be achieved only if specific AX-related reagents are employed. Further studies are necessary to determine the exact extent of this problem and to improve the efficacy of diagnostic methods.", "entity": "Amoxicillin", "aliases": "Actimoxi Amoxicillin Anhydrous Clariana Brand Monopotassium Salt Monosodium Sodium Trihydrate (R*)-Isomer Amoxicilline Amoxil Amoxycillin BRL 2333 BRL-2333 BRL2333 Clamoxyl G.A. parenteral of Hydroxyampicillin Penamox Pfizer Polymox SmithKline Beecham Trimox Wymox", "definition": "A broad-spectrum semisynthetic antibiotic similar to AMPICILLIN except that its resistance to gastric acid permits higher serum levels with oral administration.\n    ", "id": "MESH:D000658"}
{"mention": "AX", "mention_text": "A large group of patients with suspected allergic reactions to beta-lactam antibiotics was evaluated. A detailed clinical history, together with skin tests, RAST (radioallergosorbent test), and controlled challenge tests, was used to establish whether patients allergic to beta-lactam antibiotics had selective immediate allergic responses to amoxicillin (AX) or were cross-reacting with other penicillin derivatives. Skin tests were performed with benzylpenicilloyl-poly-L-lysine (BPO-PLL), benzylpenicilloate, benzylpenicillin (PG), ampicillin (AMP), and AX. RAST for BPO-PLL and AX-PLL was done. When both skin test and RAST for BPO were negative, single-blind, placebo-controlled challenge tests were done to ensure tolerance of PG or sensitivity to AX. A total of 177 patients were diagnosed as allergic to beta-lactam antibiotics. We selected the 54 (30.5%) cases of immediate AX allergy with good tolerance of PG. Anaphylaxis was seen in 37 patients (69%), the other 17 (31%) having urticaria and/or angioedema. All the patients were skin test negative to BPO; 49 of 51 (96%) were also negative to MDM, and 44 of 46 (96%) to PG. Skin tests with AX were positive in 34 (63%) patients. RAST was positive for AX in 22 patients (41%) and to BPO in just 5 (9%). None of the sera with negative RAST for AX were positive to BPO. Challenge tests with AX were performed in 23 subjects (43%) to establish the diagnosis of immediate allergic reaction to AX, and in 15 cases (28%) both skin test and RAST for AX were negative. PG was well tolerated by all 54 patients. We describe the largest group of AX-allergic patients who have tolerated PG reported so far. Diagnosis of these patients can be achieved only if specific AX-related reagents are employed. Further studies are necessary to determine the exact extent of this problem and to improve the efficacy of diagnostic methods.", "entity": "Amoxicillin", "aliases": "Actimoxi Amoxicillin Anhydrous Clariana Brand Monopotassium Salt Monosodium Sodium Trihydrate (R*)-Isomer Amoxicilline Amoxil Amoxycillin BRL 2333 BRL-2333 BRL2333 Clamoxyl G.A. parenteral of Hydroxyampicillin Penamox Pfizer Polymox SmithKline Beecham Trimox Wymox", "definition": "A broad-spectrum semisynthetic antibiotic similar to AMPICILLIN except that its resistance to gastric acid permits higher serum levels with oral administration.\n    ", "id": "MESH:D000658"}
{"mention": "penicillin", "mention_text": "A large group of patients with suspected allergic reactions to beta-lactam antibiotics was evaluated. A detailed clinical history, together with skin tests, RAST (radioallergosorbent test), and controlled challenge tests, was used to establish whether patients allergic to beta-lactam antibiotics had selective immediate allergic responses to amoxicillin (AX) or were cross-reacting with other penicillin derivatives. Skin tests were performed with benzylpenicilloyl-poly-L-lysine (BPO-PLL), benzylpenicilloate, benzylpenicillin (PG), ampicillin (AMP), and AX. RAST for BPO-PLL and AX-PLL was done. When both skin test and RAST for BPO were negative, single-blind, placebo-controlled challenge tests were done to ensure tolerance of PG or sensitivity to AX. A total of 177 patients were diagnosed as allergic to beta-lactam antibiotics. We selected the 54 (30.5%) cases of immediate AX allergy with good tolerance of PG. Anaphylaxis was seen in 37 patients (69%), the other 17 (31%) having urticaria and/or angioedema. All the patients were skin test negative to BPO; 49 of 51 (96%) were also negative to MDM, and 44 of 46 (96%) to PG. Skin tests with AX were positive in 34 (63%) patients. RAST was positive for AX in 22 patients (41%) and to BPO in just 5 (9%). None of the sera with negative RAST for AX were positive to BPO. Challenge tests with AX were performed in 23 subjects (43%) to establish the diagnosis of immediate allergic reaction to AX, and in 15 cases (28%) both skin test and RAST for AX were negative. PG was well tolerated by all 54 patients. We describe the largest group of AX-allergic patients who have tolerated PG reported so far. Diagnosis of these patients can be achieved only if specific AX-related reagents are employed. Further studies are necessary to determine the exact extent of this problem and to improve the efficacy of diagnostic methods.", "entity": "Penicillins", "aliases": "Antibiotics Penicillin Penicillins", "definition": "A group of antibiotics that contain 6-aminopenicillanic acid with a side chain attached to the 6-amino group. The penicillin nucleus is the chief structural requirement for biological activity. The side-chain structure determines many of the antibacterial and pharmacological characteristics. (Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1065)\n    ", "id": "MESH:D010406"}
{"mention": "benzylpenicillin", "mention_text": "A large group of patients with suspected allergic reactions to beta-lactam antibiotics was evaluated. A detailed clinical history, together with skin tests, RAST (radioallergosorbent test), and controlled challenge tests, was used to establish whether patients allergic to beta-lactam antibiotics had selective immediate allergic responses to amoxicillin (AX) or were cross-reacting with other penicillin derivatives. Skin tests were performed with benzylpenicilloyl-poly-L-lysine (BPO-PLL), benzylpenicilloate, benzylpenicillin (PG), ampicillin (AMP), and AX. RAST for BPO-PLL and AX-PLL was done. When both skin test and RAST for BPO were negative, single-blind, placebo-controlled challenge tests were done to ensure tolerance of PG or sensitivity to AX. A total of 177 patients were diagnosed as allergic to beta-lactam antibiotics. We selected the 54 (30.5%) cases of immediate AX allergy with good tolerance of PG. Anaphylaxis was seen in 37 patients (69%), the other 17 (31%) having urticaria and/or angioedema. All the patients were skin test negative to BPO; 49 of 51 (96%) were also negative to MDM, and 44 of 46 (96%) to PG. Skin tests with AX were positive in 34 (63%) patients. RAST was positive for AX in 22 patients (41%) and to BPO in just 5 (9%). None of the sera with negative RAST for AX were positive to BPO. Challenge tests with AX were performed in 23 subjects (43%) to establish the diagnosis of immediate allergic reaction to AX, and in 15 cases (28%) both skin test and RAST for AX were negative. PG was well tolerated by all 54 patients. We describe the largest group of AX-allergic patients who have tolerated PG reported so far. Diagnosis of these patients can be achieved only if specific AX-related reagents are employed. Further studies are necessary to determine the exact extent of this problem and to improve the efficacy of diagnostic methods.", "entity": "Penicillin G", "aliases": "Antibioticos Brand of Penicillin G Sodium Benpen Benzylpenicillin Potassium Bioniche Britannia CEPA CSL Clonmel Coliriocilina Crystapen Ern Grünenthal Jenapharm Lakeside Llorente Medical Normon Or-pen Ortega Parcillin Parmed Pekamin Pengesod Penibiot Penicilina Penilevel Peniroger Pfizer Pfizerpen Sodiopen Sodipen UCB Unicilina Ursopen Van-Pen-G Vangard", "definition": "A penicillin derivative commonly used in the form of its sodium or potassium salts in the treatment of a variety of infections. It is effective against most gram-positive bacteria and against gram-negative cocci. It has also been used as an experimental convulsant because of its actions on GAMMA-AMINOBUTYRIC ACID mediated synaptic transmission.\n    ", "id": "MESH:D010400"}
{"mention": "PG", "mention_text": "A large group of patients with suspected allergic reactions to beta-lactam antibiotics was evaluated. A detailed clinical history, together with skin tests, RAST (radioallergosorbent test), and controlled challenge tests, was used to establish whether patients allergic to beta-lactam antibiotics had selective immediate allergic responses to amoxicillin (AX) or were cross-reacting with other penicillin derivatives. Skin tests were performed with benzylpenicilloyl-poly-L-lysine (BPO-PLL), benzylpenicilloate, benzylpenicillin (PG), ampicillin (AMP), and AX. RAST for BPO-PLL and AX-PLL was done. When both skin test and RAST for BPO were negative, single-blind, placebo-controlled challenge tests were done to ensure tolerance of PG or sensitivity to AX. A total of 177 patients were diagnosed as allergic to beta-lactam antibiotics. We selected the 54 (30.5%) cases of immediate AX allergy with good tolerance of PG. Anaphylaxis was seen in 37 patients (69%), the other 17 (31%) having urticaria and/or angioedema. All the patients were skin test negative to BPO; 49 of 51 (96%) were also negative to MDM, and 44 of 46 (96%) to PG. Skin tests with AX were positive in 34 (63%) patients. RAST was positive for AX in 22 patients (41%) and to BPO in just 5 (9%). None of the sera with negative RAST for AX were positive to BPO. Challenge tests with AX were performed in 23 subjects (43%) to establish the diagnosis of immediate allergic reaction to AX, and in 15 cases (28%) both skin test and RAST for AX were negative. PG was well tolerated by all 54 patients. We describe the largest group of AX-allergic patients who have tolerated PG reported so far. Diagnosis of these patients can be achieved only if specific AX-related reagents are employed. Further studies are necessary to determine the exact extent of this problem and to improve the efficacy of diagnostic methods.", "entity": "Penicillin G", "aliases": "Antibioticos Brand of Penicillin G Sodium Benpen Benzylpenicillin Potassium Bioniche Britannia CEPA CSL Clonmel Coliriocilina Crystapen Ern Grünenthal Jenapharm Lakeside Llorente Medical Normon Or-pen Ortega Parcillin Parmed Pekamin Pengesod Penibiot Penicilina Penilevel Peniroger Pfizer Pfizerpen Sodiopen Sodipen UCB Unicilina Ursopen Van-Pen-G Vangard", "definition": "A penicillin derivative commonly used in the form of its sodium or potassium salts in the treatment of a variety of infections. It is effective against most gram-positive bacteria and against gram-negative cocci. It has also been used as an experimental convulsant because of its actions on GAMMA-AMINOBUTYRIC ACID mediated synaptic transmission.\n    ", "id": "MESH:D010400"}
{"mention": "ampicillin", "mention_text": "A large group of patients with suspected allergic reactions to beta-lactam antibiotics was evaluated. A detailed clinical history, together with skin tests, RAST (radioallergosorbent test), and controlled challenge tests, was used to establish whether patients allergic to beta-lactam antibiotics had selective immediate allergic responses to amoxicillin (AX) or were cross-reacting with other penicillin derivatives. Skin tests were performed with benzylpenicilloyl-poly-L-lysine (BPO-PLL), benzylpenicilloate, benzylpenicillin (PG), ampicillin (AMP), and AX. RAST for BPO-PLL and AX-PLL was done. When both skin test and RAST for BPO were negative, single-blind, placebo-controlled challenge tests were done to ensure tolerance of PG or sensitivity to AX. A total of 177 patients were diagnosed as allergic to beta-lactam antibiotics. We selected the 54 (30.5%) cases of immediate AX allergy with good tolerance of PG. Anaphylaxis was seen in 37 patients (69%), the other 17 (31%) having urticaria and/or angioedema. All the patients were skin test negative to BPO; 49 of 51 (96%) were also negative to MDM, and 44 of 46 (96%) to PG. Skin tests with AX were positive in 34 (63%) patients. RAST was positive for AX in 22 patients (41%) and to BPO in just 5 (9%). None of the sera with negative RAST for AX were positive to BPO. Challenge tests with AX were performed in 23 subjects (43%) to establish the diagnosis of immediate allergic reaction to AX, and in 15 cases (28%) both skin test and RAST for AX were negative. PG was well tolerated by all 54 patients. We describe the largest group of AX-allergic patients who have tolerated PG reported so far. Diagnosis of these patients can be achieved only if specific AX-related reagents are employed. Further studies are necessary to determine the exact extent of this problem and to improve the efficacy of diagnostic methods.", "entity": "Ampicillin", "aliases": "Amcill Aminobenzyl Penicillin Aminobenzylpenicillin Ampicillin Sodium Trihydrate Antibiotic KS R1 KS-R1 Omnipen Pentrexyl Polycillin Ukapen", "definition": "Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic.\n    ", "id": "MESH:D000667"}
{"mention": "AMP", "mention_text": "A large group of patients with suspected allergic reactions to beta-lactam antibiotics was evaluated. A detailed clinical history, together with skin tests, RAST (radioallergosorbent test), and controlled challenge tests, was used to establish whether patients allergic to beta-lactam antibiotics had selective immediate allergic responses to amoxicillin (AX) or were cross-reacting with other penicillin derivatives. Skin tests were performed with benzylpenicilloyl-poly-L-lysine (BPO-PLL), benzylpenicilloate, benzylpenicillin (PG), ampicillin (AMP), and AX. RAST for BPO-PLL and AX-PLL was done. When both skin test and RAST for BPO were negative, single-blind, placebo-controlled challenge tests were done to ensure tolerance of PG or sensitivity to AX. A total of 177 patients were diagnosed as allergic to beta-lactam antibiotics. We selected the 54 (30.5%) cases of immediate AX allergy with good tolerance of PG. Anaphylaxis was seen in 37 patients (69%), the other 17 (31%) having urticaria and/or angioedema. All the patients were skin test negative to BPO; 49 of 51 (96%) were also negative to MDM, and 44 of 46 (96%) to PG. Skin tests with AX were positive in 34 (63%) patients. RAST was positive for AX in 22 patients (41%) and to BPO in just 5 (9%). None of the sera with negative RAST for AX were positive to BPO. Challenge tests with AX were performed in 23 subjects (43%) to establish the diagnosis of immediate allergic reaction to AX, and in 15 cases (28%) both skin test and RAST for AX were negative. PG was well tolerated by all 54 patients. We describe the largest group of AX-allergic patients who have tolerated PG reported so far. Diagnosis of these patients can be achieved only if specific AX-related reagents are employed. Further studies are necessary to determine the exact extent of this problem and to improve the efficacy of diagnostic methods.", "entity": "Ampicillin", "aliases": "Amcill Aminobenzyl Penicillin Aminobenzylpenicillin Ampicillin Sodium Trihydrate Antibiotic KS R1 KS-R1 Omnipen Pentrexyl Polycillin Ukapen", "definition": "Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic.\n    ", "id": "MESH:D000667"}
{"mention": "allergy", "mention_text": "A large group of patients with suspected allergic reactions to beta-lactam antibiotics was evaluated. A detailed clinical history, together with skin tests, RAST (radioallergosorbent test), and controlled challenge tests, was used to establish whether patients allergic to beta-lactam antibiotics had selective immediate allergic responses to amoxicillin (AX) or were cross-reacting with other penicillin derivatives. Skin tests were performed with benzylpenicilloyl-poly-L-lysine (BPO-PLL), benzylpenicilloate, benzylpenicillin (PG), ampicillin (AMP), and AX. RAST for BPO-PLL and AX-PLL was done. When both skin test and RAST for BPO were negative, single-blind, placebo-controlled challenge tests were done to ensure tolerance of PG or sensitivity to AX. A total of 177 patients were diagnosed as allergic to beta-lactam antibiotics. We selected the 54 (30.5%) cases of immediate AX allergy with good tolerance of PG. Anaphylaxis was seen in 37 patients (69%), the other 17 (31%) having urticaria and/or angioedema. All the patients were skin test negative to BPO; 49 of 51 (96%) were also negative to MDM, and 44 of 46 (96%) to PG. Skin tests with AX were positive in 34 (63%) patients. RAST was positive for AX in 22 patients (41%) and to BPO in just 5 (9%). None of the sera with negative RAST for AX were positive to BPO. Challenge tests with AX were performed in 23 subjects (43%) to establish the diagnosis of immediate allergic reaction to AX, and in 15 cases (28%) both skin test and RAST for AX were negative. PG was well tolerated by all 54 patients. We describe the largest group of AX-allergic patients who have tolerated PG reported so far. Diagnosis of these patients can be achieved only if specific AX-related reagents are employed. Further studies are necessary to determine the exact extent of this problem and to improve the efficacy of diagnostic methods.", "entity": "Drug Hypersensitivity", "aliases": "Allergies Drug Allergy Hypersensitivities Hypersensitivity", "definition": "Immunologically mediated adverse reactions to medicinal substances used legally or illegally.\n    ", "id": "MESH:D004342"}
{"mention": "Anaphylaxis", "mention_text": "A large group of patients with suspected allergic reactions to beta-lactam antibiotics was evaluated. A detailed clinical history, together with skin tests, RAST (radioallergosorbent test), and controlled challenge tests, was used to establish whether patients allergic to beta-lactam antibiotics had selective immediate allergic responses to amoxicillin (AX) or were cross-reacting with other penicillin derivatives. Skin tests were performed with benzylpenicilloyl-poly-L-lysine (BPO-PLL), benzylpenicilloate, benzylpenicillin (PG), ampicillin (AMP), and AX. RAST for BPO-PLL and AX-PLL was done. When both skin test and RAST for BPO were negative, single-blind, placebo-controlled challenge tests were done to ensure tolerance of PG or sensitivity to AX. A total of 177 patients were diagnosed as allergic to beta-lactam antibiotics. We selected the 54 (30.5%) cases of immediate AX allergy with good tolerance of PG. Anaphylaxis was seen in 37 patients (69%), the other 17 (31%) having urticaria and/or angioedema. All the patients were skin test negative to BPO; 49 of 51 (96%) were also negative to MDM, and 44 of 46 (96%) to PG. Skin tests with AX were positive in 34 (63%) patients. RAST was positive for AX in 22 patients (41%) and to BPO in just 5 (9%). None of the sera with negative RAST for AX were positive to BPO. Challenge tests with AX were performed in 23 subjects (43%) to establish the diagnosis of immediate allergic reaction to AX, and in 15 cases (28%) both skin test and RAST for AX were negative. PG was well tolerated by all 54 patients. We describe the largest group of AX-allergic patients who have tolerated PG reported so far. Diagnosis of these patients can be achieved only if specific AX-related reagents are employed. Further studies are necessary to determine the exact extent of this problem and to improve the efficacy of diagnostic methods.", "entity": "Anaphylaxis", "aliases": "Anaphylactic Reaction Reactions Shock Anaphylaxis", "definition": "An acute hypersensitivity reaction due to exposure to a previously encountered ANTIGEN. The reaction may include rapidly progressing URTICARIA, respiratory distress, vascular collapse, systemic SHOCK, and death.\n    ", "id": "MESH:D000707"}
{"mention": "urticaria", "mention_text": "A large group of patients with suspected allergic reactions to beta-lactam antibiotics was evaluated. A detailed clinical history, together with skin tests, RAST (radioallergosorbent test), and controlled challenge tests, was used to establish whether patients allergic to beta-lactam antibiotics had selective immediate allergic responses to amoxicillin (AX) or were cross-reacting with other penicillin derivatives. Skin tests were performed with benzylpenicilloyl-poly-L-lysine (BPO-PLL), benzylpenicilloate, benzylpenicillin (PG), ampicillin (AMP), and AX. RAST for BPO-PLL and AX-PLL was done. When both skin test and RAST for BPO were negative, single-blind, placebo-controlled challenge tests were done to ensure tolerance of PG or sensitivity to AX. A total of 177 patients were diagnosed as allergic to beta-lactam antibiotics. We selected the 54 (30.5%) cases of immediate AX allergy with good tolerance of PG. Anaphylaxis was seen in 37 patients (69%), the other 17 (31%) having urticaria and/or angioedema. All the patients were skin test negative to BPO; 49 of 51 (96%) were also negative to MDM, and 44 of 46 (96%) to PG. Skin tests with AX were positive in 34 (63%) patients. RAST was positive for AX in 22 patients (41%) and to BPO in just 5 (9%). None of the sera with negative RAST for AX were positive to BPO. Challenge tests with AX were performed in 23 subjects (43%) to establish the diagnosis of immediate allergic reaction to AX, and in 15 cases (28%) both skin test and RAST for AX were negative. PG was well tolerated by all 54 patients. We describe the largest group of AX-allergic patients who have tolerated PG reported so far. Diagnosis of these patients can be achieved only if specific AX-related reagents are employed. Further studies are necessary to determine the exact extent of this problem and to improve the efficacy of diagnostic methods.", "entity": "Urticaria", "aliases": "Hives Urticaria Urticarias", "definition": "A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress.\n    ", "id": "MESH:D014581"}
{"mention": "angioedema", "mention_text": "A large group of patients with suspected allergic reactions to beta-lactam antibiotics was evaluated. A detailed clinical history, together with skin tests, RAST (radioallergosorbent test), and controlled challenge tests, was used to establish whether patients allergic to beta-lactam antibiotics had selective immediate allergic responses to amoxicillin (AX) or were cross-reacting with other penicillin derivatives. Skin tests were performed with benzylpenicilloyl-poly-L-lysine (BPO-PLL), benzylpenicilloate, benzylpenicillin (PG), ampicillin (AMP), and AX. RAST for BPO-PLL and AX-PLL was done. When both skin test and RAST for BPO were negative, single-blind, placebo-controlled challenge tests were done to ensure tolerance of PG or sensitivity to AX. A total of 177 patients were diagnosed as allergic to beta-lactam antibiotics. We selected the 54 (30.5%) cases of immediate AX allergy with good tolerance of PG. Anaphylaxis was seen in 37 patients (69%), the other 17 (31%) having urticaria and/or angioedema. All the patients were skin test negative to BPO; 49 of 51 (96%) were also negative to MDM, and 44 of 46 (96%) to PG. Skin tests with AX were positive in 34 (63%) patients. RAST was positive for AX in 22 patients (41%) and to BPO in just 5 (9%). None of the sera with negative RAST for AX were positive to BPO. Challenge tests with AX were performed in 23 subjects (43%) to establish the diagnosis of immediate allergic reaction to AX, and in 15 cases (28%) both skin test and RAST for AX were negative. PG was well tolerated by all 54 patients. We describe the largest group of AX-allergic patients who have tolerated PG reported so far. Diagnosis of these patients can be achieved only if specific AX-related reagents are employed. Further studies are necessary to determine the exact extent of this problem and to improve the efficacy of diagnostic methods.", "entity": "Angioedema", "aliases": "Angioedema Angioedemas Angioneurotic Edema Edemas Quincke's Giant Urticaria Urticarias Quincke Quinckes", "definition": "Swelling involving the deep DERMIS, subcutaneous, or submucosal tissues, representing localized EDEMA. Angioedema often occurs in the face, lips, tongue, and larynx.\n    ", "id": "MESH:D000799"}
{"mention": "MDM", "mention_text": "A large group of patients with suspected allergic reactions to beta-lactam antibiotics was evaluated. A detailed clinical history, together with skin tests, RAST (radioallergosorbent test), and controlled challenge tests, was used to establish whether patients allergic to beta-lactam antibiotics had selective immediate allergic responses to amoxicillin (AX) or were cross-reacting with other penicillin derivatives. Skin tests were performed with benzylpenicilloyl-poly-L-lysine (BPO-PLL), benzylpenicilloate, benzylpenicillin (PG), ampicillin (AMP), and AX. RAST for BPO-PLL and AX-PLL was done. When both skin test and RAST for BPO were negative, single-blind, placebo-controlled challenge tests were done to ensure tolerance of PG or sensitivity to AX. A total of 177 patients were diagnosed as allergic to beta-lactam antibiotics. We selected the 54 (30.5%) cases of immediate AX allergy with good tolerance of PG. Anaphylaxis was seen in 37 patients (69%), the other 17 (31%) having urticaria and/or angioedema. All the patients were skin test negative to BPO; 49 of 51 (96%) were also negative to MDM, and 44 of 46 (96%) to PG. Skin tests with AX were positive in 34 (63%) patients. RAST was positive for AX in 22 patients (41%) and to BPO in just 5 (9%). None of the sera with negative RAST for AX were positive to BPO. Challenge tests with AX were performed in 23 subjects (43%) to establish the diagnosis of immediate allergic reaction to AX, and in 15 cases (28%) both skin test and RAST for AX were negative. PG was well tolerated by all 54 patients. We describe the largest group of AX-allergic patients who have tolerated PG reported so far. Diagnosis of these patients can be achieved only if specific AX-related reagents are employed. Further studies are necessary to determine the exact extent of this problem and to improve the efficacy of diagnostic methods.", "entity": "Keratoderma, Palmoplantar", "aliases": "Disease Meleda Hyperkeratosis Palmaris et Plantaris Keratoderma Palmoplantar Keratodermas Keratoses Keratosis Palmoplantaris Transgradiens of Siemens Mal de", "definition": "Group of mostly hereditary disorders characterized by thickening of the palms and soles as a result of excessive keratin formation leading to hypertrophy of the stratum corneum (hyperkeratosis).\n    ", "id": "MESH:D007645"}
{"mention": "allergic reaction", "mention_text": "A large group of patients with suspected allergic reactions to beta-lactam antibiotics was evaluated. A detailed clinical history, together with skin tests, RAST (radioallergosorbent test), and controlled challenge tests, was used to establish whether patients allergic to beta-lactam antibiotics had selective immediate allergic responses to amoxicillin (AX) or were cross-reacting with other penicillin derivatives. Skin tests were performed with benzylpenicilloyl-poly-L-lysine (BPO-PLL), benzylpenicilloate, benzylpenicillin (PG), ampicillin (AMP), and AX. RAST for BPO-PLL and AX-PLL was done. When both skin test and RAST for BPO were negative, single-blind, placebo-controlled challenge tests were done to ensure tolerance of PG or sensitivity to AX. A total of 177 patients were diagnosed as allergic to beta-lactam antibiotics. We selected the 54 (30.5%) cases of immediate AX allergy with good tolerance of PG. Anaphylaxis was seen in 37 patients (69%), the other 17 (31%) having urticaria and/or angioedema. All the patients were skin test negative to BPO; 49 of 51 (96%) were also negative to MDM, and 44 of 46 (96%) to PG. Skin tests with AX were positive in 34 (63%) patients. RAST was positive for AX in 22 patients (41%) and to BPO in just 5 (9%). None of the sera with negative RAST for AX were positive to BPO. Challenge tests with AX were performed in 23 subjects (43%) to establish the diagnosis of immediate allergic reaction to AX, and in 15 cases (28%) both skin test and RAST for AX were negative. PG was well tolerated by all 54 patients. We describe the largest group of AX-allergic patients who have tolerated PG reported so far. Diagnosis of these patients can be achieved only if specific AX-related reagents are employed. Further studies are necessary to determine the exact extent of this problem and to improve the efficacy of diagnostic methods.", "entity": "Drug Hypersensitivity", "aliases": "Allergies Drug Allergy Hypersensitivities Hypersensitivity", "definition": "Immunologically mediated adverse reactions to medicinal substances used legally or illegally.\n    ", "id": "MESH:D004342"}
{"mention": "paralysis", "mention_text": "Persistent paralysis after prolonged use of atracurium in the absence of corticosteroids.", "entity": "Paralysis", "aliases": "Palsies Palsy Paralyses Paralysis Todd Todd's Plegia Plegias Todds", "definition": "A general term most often used to describe severe or complete loss of muscle strength due to motor system disease from the level of the cerebral cortex to the muscle fiber. This term may also occasionally refer to a loss of sensory function. (From Adams et al., Principles of Neurology, 6th ed, p45)\n    ", "id": "MESH:D010243"}
{"mention": "atracurium", "mention_text": "Persistent paralysis after prolonged use of atracurium in the absence of corticosteroids.", "entity": "Atracurium", "aliases": "33 A 74 Atracurium Besilate Besylate Dibesylate BW 33A BW-33A BW33A Glaxo Wellcome Brand of Pisa Relatrac Tracrium", "definition": "A non-depolarizing neuromuscular blocking agent with short duration of action. Its lack of significant cardiovascular effects and its lack of dependence on good kidney function for elimination provide clinical advantage over alternate non-depolarizing neuromuscular blocking agents.\n    ", "id": "MESH:D001279"}
{"mention": "paralysis", "mention_text": "Neuromuscular blocking agents (NMBAs) are often used for patients requiring prolonged mechanical ventilation. Reports of persistent paralysis after the discontinuance of these drugs have most often involved aminosteroid-based NMBAs such as vecuronium bromide, especially when used in conjunction with corticosteroids. Atracurium besylate, a short-acting benzylisoquinolinium NMBA that is eliminated independently of renal or hepatic function, has also been associated with persistent paralysis, but only when used with corticosteroids. We report a case of atracurium-related paralysis persisting for approximately 50 hours in a patient who was not treated with corticosteroids.", "entity": "Paralysis", "aliases": "Palsies Palsy Paralyses Paralysis Todd Todd's Plegia Plegias Todds", "definition": "A general term most often used to describe severe or complete loss of muscle strength due to motor system disease from the level of the cerebral cortex to the muscle fiber. This term may also occasionally refer to a loss of sensory function. (From Adams et al., Principles of Neurology, 6th ed, p45)\n    ", "id": "MESH:D010243"}
{"mention": "vecuronium bromide", "mention_text": "Neuromuscular blocking agents (NMBAs) are often used for patients requiring prolonged mechanical ventilation. Reports of persistent paralysis after the discontinuance of these drugs have most often involved aminosteroid-based NMBAs such as vecuronium bromide, especially when used in conjunction with corticosteroids. Atracurium besylate, a short-acting benzylisoquinolinium NMBA that is eliminated independently of renal or hepatic function, has also been associated with persistent paralysis, but only when used with corticosteroids. We report a case of atracurium-related paralysis persisting for approximately 50 hours in a patient who was not treated with corticosteroids.", "entity": "Vecuronium Bromide", "aliases": "Bromide Vecuronium Citrate Hydrobromide Hydrochloride Maleate NC 45 NC-45 NC45 Norcuron ORG ORG-NC ORG-NC-45 ORG-NC45 ORGNC ORGNC45 Phosphate Quaternary Ion", "definition": "Monoquaternary homolog of PANCURONIUM. A non-depolarizing neuromuscular blocking agent with shorter duration of action than pancuronium. Its lack of significant cardiovascular effects and lack of dependence on good kidney function for elimination as well as its short duration of action and easy reversibility provide advantages over, or alternatives to, other established neuromuscular blocking agents.\n    ", "id": "MESH:D014673"}
{"mention": "Atracurium besylate", "mention_text": "Neuromuscular blocking agents (NMBAs) are often used for patients requiring prolonged mechanical ventilation. Reports of persistent paralysis after the discontinuance of these drugs have most often involved aminosteroid-based NMBAs such as vecuronium bromide, especially when used in conjunction with corticosteroids. Atracurium besylate, a short-acting benzylisoquinolinium NMBA that is eliminated independently of renal or hepatic function, has also been associated with persistent paralysis, but only when used with corticosteroids. We report a case of atracurium-related paralysis persisting for approximately 50 hours in a patient who was not treated with corticosteroids.", "entity": "Atracurium", "aliases": "33 A 74 Atracurium Besilate Besylate Dibesylate BW 33A BW-33A BW33A Glaxo Wellcome Brand of Pisa Relatrac Tracrium", "definition": "A non-depolarizing neuromuscular blocking agent with short duration of action. Its lack of significant cardiovascular effects and its lack of dependence on good kidney function for elimination provide clinical advantage over alternate non-depolarizing neuromuscular blocking agents.\n    ", "id": "MESH:D001279"}
{"mention": "atracurium", "mention_text": "Neuromuscular blocking agents (NMBAs) are often used for patients requiring prolonged mechanical ventilation. Reports of persistent paralysis after the discontinuance of these drugs have most often involved aminosteroid-based NMBAs such as vecuronium bromide, especially when used in conjunction with corticosteroids. Atracurium besylate, a short-acting benzylisoquinolinium NMBA that is eliminated independently of renal or hepatic function, has also been associated with persistent paralysis, but only when used with corticosteroids. We report a case of atracurium-related paralysis persisting for approximately 50 hours in a patient who was not treated with corticosteroids.", "entity": "Atracurium", "aliases": "33 A 74 Atracurium Besilate Besylate Dibesylate BW 33A BW-33A BW33A Glaxo Wellcome Brand of Pisa Relatrac Tracrium", "definition": "A non-depolarizing neuromuscular blocking agent with short duration of action. Its lack of significant cardiovascular effects and its lack of dependence on good kidney function for elimination provide clinical advantage over alternate non-depolarizing neuromuscular blocking agents.\n    ", "id": "MESH:D001279"}
{"mention": "acetaminophen", "mention_text": "Habitual use of acetaminophen as a risk factor for chronic renal failure: a comparison with phenacetin.", "entity": "Acetaminophen", "aliases": "APAP Acamol Acephen Acetaco Acetamidophenol Acetaminophen Acetominophen Algotropyl Anacin 3 Anacin-3 Anacin3 Datril Hydroxyacetanilide N-(4-Hydroxyphenyl)acetanilide N-Acetyl-p-aminophenol Panadol Paracetamol Tylenol p-Acetamidophenol p-Hydroxyacetanilide", "definition": "Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.\n    ", "id": "MESH:D000082"}
{"mention": "chronic renal failure", "mention_text": "Habitual use of acetaminophen as a risk factor for chronic renal failure: a comparison with phenacetin.", "entity": "Kidney Failure, Chronic", "aliases": "Chronic Kidney Failure Renal Disease End-Stage ESRD End Stage", "definition": "The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.\n    ", "id": "MESH:D007676"}
{"mention": "phenacetin", "mention_text": "Habitual use of acetaminophen as a risk factor for chronic renal failure: a comparison with phenacetin.", "entity": "Phenacetin", "aliases": "Acetophenetidin Phenacetin", "definition": "A phenylacetamide that was formerly used in ANALGESICS but nephropathy and METHEMOGLOBINEMIA led to its withdrawal from the market. (From Smith and Reynard, Textbook of Pharmacology,1991, p431)\n    ", "id": "MESH:D010615"}
{"mention": "phenacetin", "mention_text": "Six epidemiologic studies in the United States and Europe indicate that habitual use of phenacetin is associated with the development of chronic renal failure and end-stage renal disease (ESRD), with a relative risk in the range of 4 to 19. As a result of these and other studies, phenacetin has now been withdrawn from the market in most countries. However, three case control studies, one each in North Carolina, northern Maryland, and West Berlin, Germany, showed that habitual use of acetaminophen is also associated with chronic renal failure and ESRD, with a relative risk in the range of 2 to 4. These studies suggest that both phenacetin and acetaminophen may contribute to the burden of ESRD, with the risk of the latter being somewhat less than that of the former. This apparent difference in risk may not be due to differences in nephrotoxic potential of the drugs themselves. A lower relative risk would be expected for acetaminophen if the risk of both drugs in combination with other analgesics was higher than the risk of either agent alone. Thus, acetaminophen has been used both as a single agent and in combination with other analgesics, whereas phenacetin was available only in combinations. The possibility that habitual use of acetaminophen alone increases the risk of ESRD has not been clearly demonstrated, but cannot be dismissed.", "entity": "Phenacetin", "aliases": "Acetophenetidin Phenacetin", "definition": "A phenylacetamide that was formerly used in ANALGESICS but nephropathy and METHEMOGLOBINEMIA led to its withdrawal from the market. (From Smith and Reynard, Textbook of Pharmacology,1991, p431)\n    ", "id": "MESH:D010615"}
{"mention": "chronic renal failure", "mention_text": "Six epidemiologic studies in the United States and Europe indicate that habitual use of phenacetin is associated with the development of chronic renal failure and end-stage renal disease (ESRD), with a relative risk in the range of 4 to 19. As a result of these and other studies, phenacetin has now been withdrawn from the market in most countries. However, three case control studies, one each in North Carolina, northern Maryland, and West Berlin, Germany, showed that habitual use of acetaminophen is also associated with chronic renal failure and ESRD, with a relative risk in the range of 2 to 4. These studies suggest that both phenacetin and acetaminophen may contribute to the burden of ESRD, with the risk of the latter being somewhat less than that of the former. This apparent difference in risk may not be due to differences in nephrotoxic potential of the drugs themselves. A lower relative risk would be expected for acetaminophen if the risk of both drugs in combination with other analgesics was higher than the risk of either agent alone. Thus, acetaminophen has been used both as a single agent and in combination with other analgesics, whereas phenacetin was available only in combinations. The possibility that habitual use of acetaminophen alone increases the risk of ESRD has not been clearly demonstrated, but cannot be dismissed.", "entity": "Kidney Failure, Chronic", "aliases": "Chronic Kidney Failure Renal Disease End-Stage ESRD End Stage", "definition": "The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.\n    ", "id": "MESH:D007676"}
{"mention": "end-stage renal disease", "mention_text": "Six epidemiologic studies in the United States and Europe indicate that habitual use of phenacetin is associated with the development of chronic renal failure and end-stage renal disease (ESRD), with a relative risk in the range of 4 to 19. As a result of these and other studies, phenacetin has now been withdrawn from the market in most countries. However, three case control studies, one each in North Carolina, northern Maryland, and West Berlin, Germany, showed that habitual use of acetaminophen is also associated with chronic renal failure and ESRD, with a relative risk in the range of 2 to 4. These studies suggest that both phenacetin and acetaminophen may contribute to the burden of ESRD, with the risk of the latter being somewhat less than that of the former. This apparent difference in risk may not be due to differences in nephrotoxic potential of the drugs themselves. A lower relative risk would be expected for acetaminophen if the risk of both drugs in combination with other analgesics was higher than the risk of either agent alone. Thus, acetaminophen has been used both as a single agent and in combination with other analgesics, whereas phenacetin was available only in combinations. The possibility that habitual use of acetaminophen alone increases the risk of ESRD has not been clearly demonstrated, but cannot be dismissed.", "entity": "Kidney Failure, Chronic", "aliases": "Chronic Kidney Failure Renal Disease End-Stage ESRD End Stage", "definition": "The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.\n    ", "id": "MESH:D007676"}
{"mention": "ESRD", "mention_text": "Six epidemiologic studies in the United States and Europe indicate that habitual use of phenacetin is associated with the development of chronic renal failure and end-stage renal disease (ESRD), with a relative risk in the range of 4 to 19. As a result of these and other studies, phenacetin has now been withdrawn from the market in most countries. However, three case control studies, one each in North Carolina, northern Maryland, and West Berlin, Germany, showed that habitual use of acetaminophen is also associated with chronic renal failure and ESRD, with a relative risk in the range of 2 to 4. These studies suggest that both phenacetin and acetaminophen may contribute to the burden of ESRD, with the risk of the latter being somewhat less than that of the former. This apparent difference in risk may not be due to differences in nephrotoxic potential of the drugs themselves. A lower relative risk would be expected for acetaminophen if the risk of both drugs in combination with other analgesics was higher than the risk of either agent alone. Thus, acetaminophen has been used both as a single agent and in combination with other analgesics, whereas phenacetin was available only in combinations. The possibility that habitual use of acetaminophen alone increases the risk of ESRD has not been clearly demonstrated, but cannot be dismissed.", "entity": "Kidney Failure, Chronic", "aliases": "Chronic Kidney Failure Renal Disease End-Stage ESRD End Stage", "definition": "The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.\n    ", "id": "MESH:D007676"}
{"mention": "acetaminophen", "mention_text": "Six epidemiologic studies in the United States and Europe indicate that habitual use of phenacetin is associated with the development of chronic renal failure and end-stage renal disease (ESRD), with a relative risk in the range of 4 to 19. As a result of these and other studies, phenacetin has now been withdrawn from the market in most countries. However, three case control studies, one each in North Carolina, northern Maryland, and West Berlin, Germany, showed that habitual use of acetaminophen is also associated with chronic renal failure and ESRD, with a relative risk in the range of 2 to 4. These studies suggest that both phenacetin and acetaminophen may contribute to the burden of ESRD, with the risk of the latter being somewhat less than that of the former. This apparent difference in risk may not be due to differences in nephrotoxic potential of the drugs themselves. A lower relative risk would be expected for acetaminophen if the risk of both drugs in combination with other analgesics was higher than the risk of either agent alone. Thus, acetaminophen has been used both as a single agent and in combination with other analgesics, whereas phenacetin was available only in combinations. The possibility that habitual use of acetaminophen alone increases the risk of ESRD has not been clearly demonstrated, but cannot be dismissed.", "entity": "Acetaminophen", "aliases": "APAP Acamol Acephen Acetaco Acetamidophenol Acetaminophen Acetominophen Algotropyl Anacin 3 Anacin-3 Anacin3 Datril Hydroxyacetanilide N-(4-Hydroxyphenyl)acetanilide N-Acetyl-p-aminophenol Panadol Paracetamol Tylenol p-Acetamidophenol p-Hydroxyacetanilide", "definition": "Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.\n    ", "id": "MESH:D000082"}
{"mention": "nephrotoxic", "mention_text": "Six epidemiologic studies in the United States and Europe indicate that habitual use of phenacetin is associated with the development of chronic renal failure and end-stage renal disease (ESRD), with a relative risk in the range of 4 to 19. As a result of these and other studies, phenacetin has now been withdrawn from the market in most countries. However, three case control studies, one each in North Carolina, northern Maryland, and West Berlin, Germany, showed that habitual use of acetaminophen is also associated with chronic renal failure and ESRD, with a relative risk in the range of 2 to 4. These studies suggest that both phenacetin and acetaminophen may contribute to the burden of ESRD, with the risk of the latter being somewhat less than that of the former. This apparent difference in risk may not be due to differences in nephrotoxic potential of the drugs themselves. A lower relative risk would be expected for acetaminophen if the risk of both drugs in combination with other analgesics was higher than the risk of either agent alone. Thus, acetaminophen has been used both as a single agent and in combination with other analgesics, whereas phenacetin was available only in combinations. The possibility that habitual use of acetaminophen alone increases the risk of ESRD has not been clearly demonstrated, but cannot be dismissed.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "heparan sulphate", "mention_text": "Reduction of heparan sulphate-associated anionic sites in the glomerular basement membrane of rats with streptozotocin-induced diabetic nephropathy.", "entity": "Heparitin Sulfate", "aliases": "Heparan Sulfate Heparitin", "definition": "A heteropolysaccharide that is similar in structure to HEPARIN. It accumulates in individuals with MUCOPOLYSACCHARIDOSIS.\n    ", "id": "MESH:D006497"}
{"mention": "streptozotocin", "mention_text": "Reduction of heparan sulphate-associated anionic sites in the glomerular basement membrane of rats with streptozotocin-induced diabetic nephropathy.", "entity": "Streptozocin", "aliases": "2-Deoxy-2-((methylnitrosoamino)carbonyl)amino-D-glucose Streptozocin Teva Brand Streptozotocin Streptozotocine of Zanosar", "definition": "An antibiotic that is produced by Stretomyces achromogenes. It is used as an antineoplastic agent and to induce diabetes in experimental animals.\n    ", "id": "MESH:D013311"}
{"mention": "diabetic nephropathy", "mention_text": "Reduction of heparan sulphate-associated anionic sites in the glomerular basement membrane of rats with streptozotocin-induced diabetic nephropathy.", "entity": "Diabetic Nephropathies", "aliases": "Diabetic Glomerulosclerosis Kidney Disease Diseases Nephropathies Nephropathy Nodular Intracapillary Kimmelstiel Wilson Syndrome Kimmelstiel-Wilson", "definition": "KIDNEY injuries associated with diabetes mellitus and affecting KIDNEY GLOMERULUS; ARTERIOLES; KIDNEY TUBULES; and the interstitium. Clinical signs include persistent PROTEINURIA, from microalbuminuria progressing to ALBUMINURIA of greater than 300 mg/24 h, leading to reduced GLOMERULAR FILTRATION RATE and END-STAGE RENAL DISEASE.\n    ", "id": "MESH:D003928"}
{"mention": "Heparan sulphate", "mention_text": "Heparan sulphate-associated anionic sites in the glomerular basement membrane were studied in rats 8 months after induction of diabetes by streptozotocin and in age- adn sex-matched control rats, employing the cationic dye cuprolinic blue. Morphometric analysis at the ultrastructural level was performed using a computerized image processor. The heparan sulphate specificity of the cuprolinic blue staining was demonstrated by glycosaminoglycan-degrading enzymes, showing that pretreatment of the sections with heparitinase abolished all staining, whereas chondroitinase ABC had no effect. The majority of anionic sites (74% in diabetic and 81% in control rats) were found within the lamina rara externa of the glomerular basement membrane. A minority of anionic sites were scattered throughout the lamina densa and lamina rara interna, and were significantly smaller than those in the lamina rara externa of the glomerular basement membrane (p<0.001 and p<0.01 for diabetic and control rats, respectively). Diabetic rats progressively developed albuminuria reaching 40.3 (32.2-62.0) mg/24 h after 8 months in contrast to the control animals (0.8 (0.2-0.9) mg/24 h, p<0.002). At the same time, the number of heparan sulphate anionic sites and the total anionic site surface (number of anionic sites x mean anionic site surface) in the lamina rara externa of the glomerular basement membrane was reduced by 19% (p<0.021) and by 26% (p<0.02), respectively. Number and total anionic site surface in the remaining part of the glomerular basement membrane (lamina densa and lamina rara interna) were not significantly changed. We conclude that in streptozotocin-diabetic rats with an increased urinary albumin excretion, a reduced heparan sulphate charge barrier/density is found at the lamina rara externa of the glomerular basement membrane.", "entity": "Heparitin Sulfate", "aliases": "Heparan Sulfate Heparitin", "definition": "A heteropolysaccharide that is similar in structure to HEPARIN. It accumulates in individuals with MUCOPOLYSACCHARIDOSIS.\n    ", "id": "MESH:D006497"}
{"mention": "diabetes", "mention_text": "Heparan sulphate-associated anionic sites in the glomerular basement membrane were studied in rats 8 months after induction of diabetes by streptozotocin and in age- adn sex-matched control rats, employing the cationic dye cuprolinic blue. Morphometric analysis at the ultrastructural level was performed using a computerized image processor. The heparan sulphate specificity of the cuprolinic blue staining was demonstrated by glycosaminoglycan-degrading enzymes, showing that pretreatment of the sections with heparitinase abolished all staining, whereas chondroitinase ABC had no effect. The majority of anionic sites (74% in diabetic and 81% in control rats) were found within the lamina rara externa of the glomerular basement membrane. A minority of anionic sites were scattered throughout the lamina densa and lamina rara interna, and were significantly smaller than those in the lamina rara externa of the glomerular basement membrane (p<0.001 and p<0.01 for diabetic and control rats, respectively). Diabetic rats progressively developed albuminuria reaching 40.3 (32.2-62.0) mg/24 h after 8 months in contrast to the control animals (0.8 (0.2-0.9) mg/24 h, p<0.002). At the same time, the number of heparan sulphate anionic sites and the total anionic site surface (number of anionic sites x mean anionic site surface) in the lamina rara externa of the glomerular basement membrane was reduced by 19% (p<0.021) and by 26% (p<0.02), respectively. Number and total anionic site surface in the remaining part of the glomerular basement membrane (lamina densa and lamina rara interna) were not significantly changed. We conclude that in streptozotocin-diabetic rats with an increased urinary albumin excretion, a reduced heparan sulphate charge barrier/density is found at the lamina rara externa of the glomerular basement membrane.", "entity": "Diabetes Mellitus", "aliases": "Diabetes Mellitus", "definition": "A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.\n    ", "id": "MESH:D003920"}
{"mention": "streptozotocin", "mention_text": "Heparan sulphate-associated anionic sites in the glomerular basement membrane were studied in rats 8 months after induction of diabetes by streptozotocin and in age- adn sex-matched control rats, employing the cationic dye cuprolinic blue. Morphometric analysis at the ultrastructural level was performed using a computerized image processor. The heparan sulphate specificity of the cuprolinic blue staining was demonstrated by glycosaminoglycan-degrading enzymes, showing that pretreatment of the sections with heparitinase abolished all staining, whereas chondroitinase ABC had no effect. The majority of anionic sites (74% in diabetic and 81% in control rats) were found within the lamina rara externa of the glomerular basement membrane. A minority of anionic sites were scattered throughout the lamina densa and lamina rara interna, and were significantly smaller than those in the lamina rara externa of the glomerular basement membrane (p<0.001 and p<0.01 for diabetic and control rats, respectively). Diabetic rats progressively developed albuminuria reaching 40.3 (32.2-62.0) mg/24 h after 8 months in contrast to the control animals (0.8 (0.2-0.9) mg/24 h, p<0.002). At the same time, the number of heparan sulphate anionic sites and the total anionic site surface (number of anionic sites x mean anionic site surface) in the lamina rara externa of the glomerular basement membrane was reduced by 19% (p<0.021) and by 26% (p<0.02), respectively. Number and total anionic site surface in the remaining part of the glomerular basement membrane (lamina densa and lamina rara interna) were not significantly changed. We conclude that in streptozotocin-diabetic rats with an increased urinary albumin excretion, a reduced heparan sulphate charge barrier/density is found at the lamina rara externa of the glomerular basement membrane.", "entity": "Streptozocin", "aliases": "2-Deoxy-2-((methylnitrosoamino)carbonyl)amino-D-glucose Streptozocin Teva Brand Streptozotocin Streptozotocine of Zanosar", "definition": "An antibiotic that is produced by Stretomyces achromogenes. It is used as an antineoplastic agent and to induce diabetes in experimental animals.\n    ", "id": "MESH:D013311"}
{"mention": "cuprolinic blue", "mention_text": "Heparan sulphate-associated anionic sites in the glomerular basement membrane were studied in rats 8 months after induction of diabetes by streptozotocin and in age- adn sex-matched control rats, employing the cationic dye cuprolinic blue. Morphometric analysis at the ultrastructural level was performed using a computerized image processor. The heparan sulphate specificity of the cuprolinic blue staining was demonstrated by glycosaminoglycan-degrading enzymes, showing that pretreatment of the sections with heparitinase abolished all staining, whereas chondroitinase ABC had no effect. The majority of anionic sites (74% in diabetic and 81% in control rats) were found within the lamina rara externa of the glomerular basement membrane. A minority of anionic sites were scattered throughout the lamina densa and lamina rara interna, and were significantly smaller than those in the lamina rara externa of the glomerular basement membrane (p<0.001 and p<0.01 for diabetic and control rats, respectively). Diabetic rats progressively developed albuminuria reaching 40.3 (32.2-62.0) mg/24 h after 8 months in contrast to the control animals (0.8 (0.2-0.9) mg/24 h, p<0.002). At the same time, the number of heparan sulphate anionic sites and the total anionic site surface (number of anionic sites x mean anionic site surface) in the lamina rara externa of the glomerular basement membrane was reduced by 19% (p<0.021) and by 26% (p<0.02), respectively. Number and total anionic site surface in the remaining part of the glomerular basement membrane (lamina densa and lamina rara interna) were not significantly changed. We conclude that in streptozotocin-diabetic rats with an increased urinary albumin excretion, a reduced heparan sulphate charge barrier/density is found at the lamina rara externa of the glomerular basement membrane.", "entity": "copper phthalocyanine", "aliases": "Monastral Blue B Fast blue dye copper phthalocyanine cuprolinic cupromeronic", "definition": "", "id": "MESH:C015445"}
{"mention": "heparan sulphate", "mention_text": "Heparan sulphate-associated anionic sites in the glomerular basement membrane were studied in rats 8 months after induction of diabetes by streptozotocin and in age- adn sex-matched control rats, employing the cationic dye cuprolinic blue. Morphometric analysis at the ultrastructural level was performed using a computerized image processor. The heparan sulphate specificity of the cuprolinic blue staining was demonstrated by glycosaminoglycan-degrading enzymes, showing that pretreatment of the sections with heparitinase abolished all staining, whereas chondroitinase ABC had no effect. The majority of anionic sites (74% in diabetic and 81% in control rats) were found within the lamina rara externa of the glomerular basement membrane. A minority of anionic sites were scattered throughout the lamina densa and lamina rara interna, and were significantly smaller than those in the lamina rara externa of the glomerular basement membrane (p<0.001 and p<0.01 for diabetic and control rats, respectively). Diabetic rats progressively developed albuminuria reaching 40.3 (32.2-62.0) mg/24 h after 8 months in contrast to the control animals (0.8 (0.2-0.9) mg/24 h, p<0.002). At the same time, the number of heparan sulphate anionic sites and the total anionic site surface (number of anionic sites x mean anionic site surface) in the lamina rara externa of the glomerular basement membrane was reduced by 19% (p<0.021) and by 26% (p<0.02), respectively. Number and total anionic site surface in the remaining part of the glomerular basement membrane (lamina densa and lamina rara interna) were not significantly changed. We conclude that in streptozotocin-diabetic rats with an increased urinary albumin excretion, a reduced heparan sulphate charge barrier/density is found at the lamina rara externa of the glomerular basement membrane.", "entity": "Heparitin Sulfate", "aliases": "Heparan Sulfate Heparitin", "definition": "A heteropolysaccharide that is similar in structure to HEPARIN. It accumulates in individuals with MUCOPOLYSACCHARIDOSIS.\n    ", "id": "MESH:D006497"}
{"mention": "glycosaminoglycan", "mention_text": "Heparan sulphate-associated anionic sites in the glomerular basement membrane were studied in rats 8 months after induction of diabetes by streptozotocin and in age- adn sex-matched control rats, employing the cationic dye cuprolinic blue. Morphometric analysis at the ultrastructural level was performed using a computerized image processor. The heparan sulphate specificity of the cuprolinic blue staining was demonstrated by glycosaminoglycan-degrading enzymes, showing that pretreatment of the sections with heparitinase abolished all staining, whereas chondroitinase ABC had no effect. The majority of anionic sites (74% in diabetic and 81% in control rats) were found within the lamina rara externa of the glomerular basement membrane. A minority of anionic sites were scattered throughout the lamina densa and lamina rara interna, and were significantly smaller than those in the lamina rara externa of the glomerular basement membrane (p<0.001 and p<0.01 for diabetic and control rats, respectively). Diabetic rats progressively developed albuminuria reaching 40.3 (32.2-62.0) mg/24 h after 8 months in contrast to the control animals (0.8 (0.2-0.9) mg/24 h, p<0.002). At the same time, the number of heparan sulphate anionic sites and the total anionic site surface (number of anionic sites x mean anionic site surface) in the lamina rara externa of the glomerular basement membrane was reduced by 19% (p<0.021) and by 26% (p<0.02), respectively. Number and total anionic site surface in the remaining part of the glomerular basement membrane (lamina densa and lamina rara interna) were not significantly changed. We conclude that in streptozotocin-diabetic rats with an increased urinary albumin excretion, a reduced heparan sulphate charge barrier/density is found at the lamina rara externa of the glomerular basement membrane.", "entity": "Glycosaminoglycans", "aliases": "Glycosaminoglycans Mucopolysaccharides", "definition": "Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or N-acetylgalactosamine.\n    ", "id": "MESH:D006025"}
{"mention": "diabetic", "mention_text": "Heparan sulphate-associated anionic sites in the glomerular basement membrane were studied in rats 8 months after induction of diabetes by streptozotocin and in age- adn sex-matched control rats, employing the cationic dye cuprolinic blue. Morphometric analysis at the ultrastructural level was performed using a computerized image processor. The heparan sulphate specificity of the cuprolinic blue staining was demonstrated by glycosaminoglycan-degrading enzymes, showing that pretreatment of the sections with heparitinase abolished all staining, whereas chondroitinase ABC had no effect. The majority of anionic sites (74% in diabetic and 81% in control rats) were found within the lamina rara externa of the glomerular basement membrane. A minority of anionic sites were scattered throughout the lamina densa and lamina rara interna, and were significantly smaller than those in the lamina rara externa of the glomerular basement membrane (p<0.001 and p<0.01 for diabetic and control rats, respectively). Diabetic rats progressively developed albuminuria reaching 40.3 (32.2-62.0) mg/24 h after 8 months in contrast to the control animals (0.8 (0.2-0.9) mg/24 h, p<0.002). At the same time, the number of heparan sulphate anionic sites and the total anionic site surface (number of anionic sites x mean anionic site surface) in the lamina rara externa of the glomerular basement membrane was reduced by 19% (p<0.021) and by 26% (p<0.02), respectively. Number and total anionic site surface in the remaining part of the glomerular basement membrane (lamina densa and lamina rara interna) were not significantly changed. We conclude that in streptozotocin-diabetic rats with an increased urinary albumin excretion, a reduced heparan sulphate charge barrier/density is found at the lamina rara externa of the glomerular basement membrane.", "entity": "Diabetes Mellitus", "aliases": "Diabetes Mellitus", "definition": "A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.\n    ", "id": "MESH:D003920"}
{"mention": "Diabetic", "mention_text": "Heparan sulphate-associated anionic sites in the glomerular basement membrane were studied in rats 8 months after induction of diabetes by streptozotocin and in age- adn sex-matched control rats, employing the cationic dye cuprolinic blue. Morphometric analysis at the ultrastructural level was performed using a computerized image processor. The heparan sulphate specificity of the cuprolinic blue staining was demonstrated by glycosaminoglycan-degrading enzymes, showing that pretreatment of the sections with heparitinase abolished all staining, whereas chondroitinase ABC had no effect. The majority of anionic sites (74% in diabetic and 81% in control rats) were found within the lamina rara externa of the glomerular basement membrane. A minority of anionic sites were scattered throughout the lamina densa and lamina rara interna, and were significantly smaller than those in the lamina rara externa of the glomerular basement membrane (p<0.001 and p<0.01 for diabetic and control rats, respectively). Diabetic rats progressively developed albuminuria reaching 40.3 (32.2-62.0) mg/24 h after 8 months in contrast to the control animals (0.8 (0.2-0.9) mg/24 h, p<0.002). At the same time, the number of heparan sulphate anionic sites and the total anionic site surface (number of anionic sites x mean anionic site surface) in the lamina rara externa of the glomerular basement membrane was reduced by 19% (p<0.021) and by 26% (p<0.02), respectively. Number and total anionic site surface in the remaining part of the glomerular basement membrane (lamina densa and lamina rara interna) were not significantly changed. We conclude that in streptozotocin-diabetic rats with an increased urinary albumin excretion, a reduced heparan sulphate charge barrier/density is found at the lamina rara externa of the glomerular basement membrane.", "entity": "Diabetes Mellitus", "aliases": "Diabetes Mellitus", "definition": "A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.\n    ", "id": "MESH:D003920"}
{"mention": "albuminuria", "mention_text": "Heparan sulphate-associated anionic sites in the glomerular basement membrane were studied in rats 8 months after induction of diabetes by streptozotocin and in age- adn sex-matched control rats, employing the cationic dye cuprolinic blue. Morphometric analysis at the ultrastructural level was performed using a computerized image processor. The heparan sulphate specificity of the cuprolinic blue staining was demonstrated by glycosaminoglycan-degrading enzymes, showing that pretreatment of the sections with heparitinase abolished all staining, whereas chondroitinase ABC had no effect. The majority of anionic sites (74% in diabetic and 81% in control rats) were found within the lamina rara externa of the glomerular basement membrane. A minority of anionic sites were scattered throughout the lamina densa and lamina rara interna, and were significantly smaller than those in the lamina rara externa of the glomerular basement membrane (p<0.001 and p<0.01 for diabetic and control rats, respectively). Diabetic rats progressively developed albuminuria reaching 40.3 (32.2-62.0) mg/24 h after 8 months in contrast to the control animals (0.8 (0.2-0.9) mg/24 h, p<0.002). At the same time, the number of heparan sulphate anionic sites and the total anionic site surface (number of anionic sites x mean anionic site surface) in the lamina rara externa of the glomerular basement membrane was reduced by 19% (p<0.021) and by 26% (p<0.02), respectively. Number and total anionic site surface in the remaining part of the glomerular basement membrane (lamina densa and lamina rara interna) were not significantly changed. We conclude that in streptozotocin-diabetic rats with an increased urinary albumin excretion, a reduced heparan sulphate charge barrier/density is found at the lamina rara externa of the glomerular basement membrane.", "entity": "Albuminuria", "aliases": "Albuminuria Albuminurias", "definition": "The presence of albumin in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D000419"}
{"mention": "renal toxicity", "mention_text": "Effect of some anticancer drugs and combined chemotherapy on renal toxicity.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "nephrotoxic", "mention_text": "The nephrotoxic action of anticancer drugs such as nitrogranulogen (NG), methotrexate (MTX), 5-fluorouracil (5-FU) and cyclophosphamide (CY) administered alone or in combination [MTX + 5-FU + CY (CMF)] was evaluated in experiments on Wistar rats. After drug administration, creatinine concentrations in the plasma and in the urine of the rats were determined, as well as creatinine clearance. Histopathologic evaluation of the kidneys was also performed. After MTX administration a significant increase (p = 0.0228) in the plasma creatinine concentration and a significant (p = 0.0001) decrease in creatinine clearance was noted compared to controls. After the administration of NG, 5-FU and CY neither a statistically significant increase in creatinine concentration nor an increase in creatinine clearance was observed compared to the group receiving no cytostatics. Following polytherapy according to the CMF regimen, a statistically significant decrease (p = 0.0343) in creatinine clearance was found, but creatinine concentration did not increase significantly compared to controls. CY caused hemorrhagic cystitis in 40% of rats, but it did not cause this complication when combined with 5-FU and MTX. Histologic changes were found in rat kidneys after administration of MTX, CY and NG, while no such change was observed after 5-FU and joint administration of MTX + 5-FU + CY compared to controls. Our studies indicate that nephrotoxicity of MTX + 5-FU + CY administered jointly is lower than in monotherapy.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "nitrogranulogen", "mention_text": "The nephrotoxic action of anticancer drugs such as nitrogranulogen (NG), methotrexate (MTX), 5-fluorouracil (5-FU) and cyclophosphamide (CY) administered alone or in combination [MTX + 5-FU + CY (CMF)] was evaluated in experiments on Wistar rats. After drug administration, creatinine concentrations in the plasma and in the urine of the rats were determined, as well as creatinine clearance. Histopathologic evaluation of the kidneys was also performed. After MTX administration a significant increase (p = 0.0228) in the plasma creatinine concentration and a significant (p = 0.0001) decrease in creatinine clearance was noted compared to controls. After the administration of NG, 5-FU and CY neither a statistically significant increase in creatinine concentration nor an increase in creatinine clearance was observed compared to the group receiving no cytostatics. Following polytherapy according to the CMF regimen, a statistically significant decrease (p = 0.0343) in creatinine clearance was found, but creatinine concentration did not increase significantly compared to controls. CY caused hemorrhagic cystitis in 40% of rats, but it did not cause this complication when combined with 5-FU and MTX. Histologic changes were found in rat kidneys after administration of MTX, CY and NG, while no such change was observed after 5-FU and joint administration of MTX + 5-FU + CY compared to controls. Our studies indicate that nephrotoxicity of MTX + 5-FU + CY administered jointly is lower than in monotherapy.", "entity": "Mechlorethamine", "aliases": "Bis(2-chloroethyl)methylamine Caryolysine Chlorethazine Chlormethine Cloramin Embichin Genopharm Brand of Mechlorethamine Hydrochloride N-Oxide N Oxide Merck Frosst Methylchlorethamine Mitomen Mustargen Mustine Nitrogen Mustard NSC 10107 762 NSC-10107 NSC-762 NSC10107 NSC762 Nitrogranulogen Nitromin", "definition": "A vesicant and necrotizing irritant destructive to mucous membranes. It was formerly used as a war gas. The hydrochloride is used as an antineoplastic in Hodgkin's disease and lymphomas. It causes severe gastrointestinal and bone marrow damage.\n    ", "id": "MESH:D008466"}
{"mention": "NG", "mention_text": "The nephrotoxic action of anticancer drugs such as nitrogranulogen (NG), methotrexate (MTX), 5-fluorouracil (5-FU) and cyclophosphamide (CY) administered alone or in combination [MTX + 5-FU + CY (CMF)] was evaluated in experiments on Wistar rats. After drug administration, creatinine concentrations in the plasma and in the urine of the rats were determined, as well as creatinine clearance. Histopathologic evaluation of the kidneys was also performed. After MTX administration a significant increase (p = 0.0228) in the plasma creatinine concentration and a significant (p = 0.0001) decrease in creatinine clearance was noted compared to controls. After the administration of NG, 5-FU and CY neither a statistically significant increase in creatinine concentration nor an increase in creatinine clearance was observed compared to the group receiving no cytostatics. Following polytherapy according to the CMF regimen, a statistically significant decrease (p = 0.0343) in creatinine clearance was found, but creatinine concentration did not increase significantly compared to controls. CY caused hemorrhagic cystitis in 40% of rats, but it did not cause this complication when combined with 5-FU and MTX. Histologic changes were found in rat kidneys after administration of MTX, CY and NG, while no such change was observed after 5-FU and joint administration of MTX + 5-FU + CY compared to controls. Our studies indicate that nephrotoxicity of MTX + 5-FU + CY administered jointly is lower than in monotherapy.", "entity": "Mechlorethamine", "aliases": "Bis(2-chloroethyl)methylamine Caryolysine Chlorethazine Chlormethine Cloramin Embichin Genopharm Brand of Mechlorethamine Hydrochloride N-Oxide N Oxide Merck Frosst Methylchlorethamine Mitomen Mustargen Mustine Nitrogen Mustard NSC 10107 762 NSC-10107 NSC-762 NSC10107 NSC762 Nitrogranulogen Nitromin", "definition": "A vesicant and necrotizing irritant destructive to mucous membranes. It was formerly used as a war gas. The hydrochloride is used as an antineoplastic in Hodgkin's disease and lymphomas. It causes severe gastrointestinal and bone marrow damage.\n    ", "id": "MESH:D008466"}
{"mention": "methotrexate", "mention_text": "The nephrotoxic action of anticancer drugs such as nitrogranulogen (NG), methotrexate (MTX), 5-fluorouracil (5-FU) and cyclophosphamide (CY) administered alone or in combination [MTX + 5-FU + CY (CMF)] was evaluated in experiments on Wistar rats. After drug administration, creatinine concentrations in the plasma and in the urine of the rats were determined, as well as creatinine clearance. Histopathologic evaluation of the kidneys was also performed. After MTX administration a significant increase (p = 0.0228) in the plasma creatinine concentration and a significant (p = 0.0001) decrease in creatinine clearance was noted compared to controls. After the administration of NG, 5-FU and CY neither a statistically significant increase in creatinine concentration nor an increase in creatinine clearance was observed compared to the group receiving no cytostatics. Following polytherapy according to the CMF regimen, a statistically significant decrease (p = 0.0343) in creatinine clearance was found, but creatinine concentration did not increase significantly compared to controls. CY caused hemorrhagic cystitis in 40% of rats, but it did not cause this complication when combined with 5-FU and MTX. Histologic changes were found in rat kidneys after administration of MTX, CY and NG, while no such change was observed after 5-FU and joint administration of MTX + 5-FU + CY compared to controls. Our studies indicate that nephrotoxicity of MTX + 5-FU + CY administered jointly is lower than in monotherapy.", "entity": "Methotrexate", "aliases": "Amethopterin Dicesium Salt Methotrexate Hydrate Sodium (D)-Isomer (DL)-Isomer Disodium Mexate", "definition": "An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.\n    ", "id": "MESH:D008727"}
{"mention": "MTX", "mention_text": "The nephrotoxic action of anticancer drugs such as nitrogranulogen (NG), methotrexate (MTX), 5-fluorouracil (5-FU) and cyclophosphamide (CY) administered alone or in combination [MTX + 5-FU + CY (CMF)] was evaluated in experiments on Wistar rats. After drug administration, creatinine concentrations in the plasma and in the urine of the rats were determined, as well as creatinine clearance. Histopathologic evaluation of the kidneys was also performed. After MTX administration a significant increase (p = 0.0228) in the plasma creatinine concentration and a significant (p = 0.0001) decrease in creatinine clearance was noted compared to controls. After the administration of NG, 5-FU and CY neither a statistically significant increase in creatinine concentration nor an increase in creatinine clearance was observed compared to the group receiving no cytostatics. Following polytherapy according to the CMF regimen, a statistically significant decrease (p = 0.0343) in creatinine clearance was found, but creatinine concentration did not increase significantly compared to controls. CY caused hemorrhagic cystitis in 40% of rats, but it did not cause this complication when combined with 5-FU and MTX. Histologic changes were found in rat kidneys after administration of MTX, CY and NG, while no such change was observed after 5-FU and joint administration of MTX + 5-FU + CY compared to controls. Our studies indicate that nephrotoxicity of MTX + 5-FU + CY administered jointly is lower than in monotherapy.", "entity": "Methotrexate", "aliases": "Amethopterin Dicesium Salt Methotrexate Hydrate Sodium (D)-Isomer (DL)-Isomer Disodium Mexate", "definition": "An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.\n    ", "id": "MESH:D008727"}
{"mention": "5-fluorouracil", "mention_text": "The nephrotoxic action of anticancer drugs such as nitrogranulogen (NG), methotrexate (MTX), 5-fluorouracil (5-FU) and cyclophosphamide (CY) administered alone or in combination [MTX + 5-FU + CY (CMF)] was evaluated in experiments on Wistar rats. After drug administration, creatinine concentrations in the plasma and in the urine of the rats were determined, as well as creatinine clearance. Histopathologic evaluation of the kidneys was also performed. After MTX administration a significant increase (p = 0.0228) in the plasma creatinine concentration and a significant (p = 0.0001) decrease in creatinine clearance was noted compared to controls. After the administration of NG, 5-FU and CY neither a statistically significant increase in creatinine concentration nor an increase in creatinine clearance was observed compared to the group receiving no cytostatics. Following polytherapy according to the CMF regimen, a statistically significant decrease (p = 0.0343) in creatinine clearance was found, but creatinine concentration did not increase significantly compared to controls. CY caused hemorrhagic cystitis in 40% of rats, but it did not cause this complication when combined with 5-FU and MTX. Histologic changes were found in rat kidneys after administration of MTX, CY and NG, while no such change was observed after 5-FU and joint administration of MTX + 5-FU + CY compared to controls. Our studies indicate that nephrotoxicity of MTX + 5-FU + CY administered jointly is lower than in monotherapy.", "entity": "Fluorouracil", "aliases": "5 FU Lederle medac Fluorouracil biosyn HU Hexal 5-FU 5-Fluorouracil 5-Fluorouracil-biosyn 5-HU 5FU Adrucil Allergan Brand of CSP Carac Dakota Fluorouracile Dermatech Dermik Efudex Efudix Ferrer Fluoro Uracile ICN Fluoro-Uracile Fluoroplex GRY Mononitrate Monopotassium Salt Monosodium Potassium Teva Fluorouracil-GRY Fluorouracilo Far Fluoruracil Fluracedyl Flurodex Gry Haemato fu Haemato-fu Neocorp Neofluor Onkofluor Onkoworks Pharmachemie Ribofluor Riemser Roche ribosepharm", "definition": "A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.\n    ", "id": "MESH:D005472"}
{"mention": "5-FU", "mention_text": "The nephrotoxic action of anticancer drugs such as nitrogranulogen (NG), methotrexate (MTX), 5-fluorouracil (5-FU) and cyclophosphamide (CY) administered alone or in combination [MTX + 5-FU + CY (CMF)] was evaluated in experiments on Wistar rats. After drug administration, creatinine concentrations in the plasma and in the urine of the rats were determined, as well as creatinine clearance. Histopathologic evaluation of the kidneys was also performed. After MTX administration a significant increase (p = 0.0228) in the plasma creatinine concentration and a significant (p = 0.0001) decrease in creatinine clearance was noted compared to controls. After the administration of NG, 5-FU and CY neither a statistically significant increase in creatinine concentration nor an increase in creatinine clearance was observed compared to the group receiving no cytostatics. Following polytherapy according to the CMF regimen, a statistically significant decrease (p = 0.0343) in creatinine clearance was found, but creatinine concentration did not increase significantly compared to controls. CY caused hemorrhagic cystitis in 40% of rats, but it did not cause this complication when combined with 5-FU and MTX. Histologic changes were found in rat kidneys after administration of MTX, CY and NG, while no such change was observed after 5-FU and joint administration of MTX + 5-FU + CY compared to controls. Our studies indicate that nephrotoxicity of MTX + 5-FU + CY administered jointly is lower than in monotherapy.", "entity": "Fluorouracil", "aliases": "5 FU Lederle medac Fluorouracil biosyn HU Hexal 5-FU 5-Fluorouracil 5-Fluorouracil-biosyn 5-HU 5FU Adrucil Allergan Brand of CSP Carac Dakota Fluorouracile Dermatech Dermik Efudex Efudix Ferrer Fluoro Uracile ICN Fluoro-Uracile Fluoroplex GRY Mononitrate Monopotassium Salt Monosodium Potassium Teva Fluorouracil-GRY Fluorouracilo Far Fluoruracil Fluracedyl Flurodex Gry Haemato fu Haemato-fu Neocorp Neofluor Onkofluor Onkoworks Pharmachemie Ribofluor Riemser Roche ribosepharm", "definition": "A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.\n    ", "id": "MESH:D005472"}
{"mention": "cyclophosphamide", "mention_text": "The nephrotoxic action of anticancer drugs such as nitrogranulogen (NG), methotrexate (MTX), 5-fluorouracil (5-FU) and cyclophosphamide (CY) administered alone or in combination [MTX + 5-FU + CY (CMF)] was evaluated in experiments on Wistar rats. After drug administration, creatinine concentrations in the plasma and in the urine of the rats were determined, as well as creatinine clearance. Histopathologic evaluation of the kidneys was also performed. After MTX administration a significant increase (p = 0.0228) in the plasma creatinine concentration and a significant (p = 0.0001) decrease in creatinine clearance was noted compared to controls. After the administration of NG, 5-FU and CY neither a statistically significant increase in creatinine concentration nor an increase in creatinine clearance was observed compared to the group receiving no cytostatics. Following polytherapy according to the CMF regimen, a statistically significant decrease (p = 0.0343) in creatinine clearance was found, but creatinine concentration did not increase significantly compared to controls. CY caused hemorrhagic cystitis in 40% of rats, but it did not cause this complication when combined with 5-FU and MTX. Histologic changes were found in rat kidneys after administration of MTX, CY and NG, while no such change was observed after 5-FU and joint administration of MTX + 5-FU + CY compared to controls. Our studies indicate that nephrotoxicity of MTX + 5-FU + CY administered jointly is lower than in monotherapy.", "entity": "Cyclophosphamide", "aliases": "Anhydrous Cyclophosphamide B 518 B-518 B518 Monohydrate (R)-Isomer (S)-Isomer Cyclophosphane Cytophosphan Cytophosphane Cytoxan Endoxan NSC 26271 NSC-26271 NSC26271 Neosar Procytox Sendoxan", "definition": "Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.\n    ", "id": "MESH:D003520"}
{"mention": "CY", "mention_text": "The nephrotoxic action of anticancer drugs such as nitrogranulogen (NG), methotrexate (MTX), 5-fluorouracil (5-FU) and cyclophosphamide (CY) administered alone or in combination [MTX + 5-FU + CY (CMF)] was evaluated in experiments on Wistar rats. After drug administration, creatinine concentrations in the plasma and in the urine of the rats were determined, as well as creatinine clearance. Histopathologic evaluation of the kidneys was also performed. After MTX administration a significant increase (p = 0.0228) in the plasma creatinine concentration and a significant (p = 0.0001) decrease in creatinine clearance was noted compared to controls. After the administration of NG, 5-FU and CY neither a statistically significant increase in creatinine concentration nor an increase in creatinine clearance was observed compared to the group receiving no cytostatics. Following polytherapy according to the CMF regimen, a statistically significant decrease (p = 0.0343) in creatinine clearance was found, but creatinine concentration did not increase significantly compared to controls. CY caused hemorrhagic cystitis in 40% of rats, but it did not cause this complication when combined with 5-FU and MTX. Histologic changes were found in rat kidneys after administration of MTX, CY and NG, while no such change was observed after 5-FU and joint administration of MTX + 5-FU + CY compared to controls. Our studies indicate that nephrotoxicity of MTX + 5-FU + CY administered jointly is lower than in monotherapy.", "entity": "Cyclophosphamide", "aliases": "Anhydrous Cyclophosphamide B 518 B-518 B518 Monohydrate (R)-Isomer (S)-Isomer Cyclophosphane Cytophosphan Cytophosphane Cytoxan Endoxan NSC 26271 NSC-26271 NSC26271 Neosar Procytox Sendoxan", "definition": "Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.\n    ", "id": "MESH:D003520"}
{"mention": "creatinine", "mention_text": "The nephrotoxic action of anticancer drugs such as nitrogranulogen (NG), methotrexate (MTX), 5-fluorouracil (5-FU) and cyclophosphamide (CY) administered alone or in combination [MTX + 5-FU + CY (CMF)] was evaluated in experiments on Wistar rats. After drug administration, creatinine concentrations in the plasma and in the urine of the rats were determined, as well as creatinine clearance. Histopathologic evaluation of the kidneys was also performed. After MTX administration a significant increase (p = 0.0228) in the plasma creatinine concentration and a significant (p = 0.0001) decrease in creatinine clearance was noted compared to controls. After the administration of NG, 5-FU and CY neither a statistically significant increase in creatinine concentration nor an increase in creatinine clearance was observed compared to the group receiving no cytostatics. Following polytherapy according to the CMF regimen, a statistically significant decrease (p = 0.0343) in creatinine clearance was found, but creatinine concentration did not increase significantly compared to controls. CY caused hemorrhagic cystitis in 40% of rats, but it did not cause this complication when combined with 5-FU and MTX. Histologic changes were found in rat kidneys after administration of MTX, CY and NG, while no such change was observed after 5-FU and joint administration of MTX + 5-FU + CY compared to controls. Our studies indicate that nephrotoxicity of MTX + 5-FU + CY administered jointly is lower than in monotherapy.", "entity": "Creatinine", "aliases": "Creatinine Sulfate Salt Krebiozen", "definition": "", "id": "MESH:D003404"}
{"mention": "hemorrhagic", "mention_text": "The nephrotoxic action of anticancer drugs such as nitrogranulogen (NG), methotrexate (MTX), 5-fluorouracil (5-FU) and cyclophosphamide (CY) administered alone or in combination [MTX + 5-FU + CY (CMF)] was evaluated in experiments on Wistar rats. After drug administration, creatinine concentrations in the plasma and in the urine of the rats were determined, as well as creatinine clearance. Histopathologic evaluation of the kidneys was also performed. After MTX administration a significant increase (p = 0.0228) in the plasma creatinine concentration and a significant (p = 0.0001) decrease in creatinine clearance was noted compared to controls. After the administration of NG, 5-FU and CY neither a statistically significant increase in creatinine concentration nor an increase in creatinine clearance was observed compared to the group receiving no cytostatics. Following polytherapy according to the CMF regimen, a statistically significant decrease (p = 0.0343) in creatinine clearance was found, but creatinine concentration did not increase significantly compared to controls. CY caused hemorrhagic cystitis in 40% of rats, but it did not cause this complication when combined with 5-FU and MTX. Histologic changes were found in rat kidneys after administration of MTX, CY and NG, while no such change was observed after 5-FU and joint administration of MTX + 5-FU + CY compared to controls. Our studies indicate that nephrotoxicity of MTX + 5-FU + CY administered jointly is lower than in monotherapy.", "entity": "Hemorrhage", "aliases": "Bleeding Hemorrhage Hemorrhages", "definition": "Bleeding or escape of blood from a vessel.\n    ", "id": "MESH:D006470"}
{"mention": "cystitis", "mention_text": "The nephrotoxic action of anticancer drugs such as nitrogranulogen (NG), methotrexate (MTX), 5-fluorouracil (5-FU) and cyclophosphamide (CY) administered alone or in combination [MTX + 5-FU + CY (CMF)] was evaluated in experiments on Wistar rats. After drug administration, creatinine concentrations in the plasma and in the urine of the rats were determined, as well as creatinine clearance. Histopathologic evaluation of the kidneys was also performed. After MTX administration a significant increase (p = 0.0228) in the plasma creatinine concentration and a significant (p = 0.0001) decrease in creatinine clearance was noted compared to controls. After the administration of NG, 5-FU and CY neither a statistically significant increase in creatinine concentration nor an increase in creatinine clearance was observed compared to the group receiving no cytostatics. Following polytherapy according to the CMF regimen, a statistically significant decrease (p = 0.0343) in creatinine clearance was found, but creatinine concentration did not increase significantly compared to controls. CY caused hemorrhagic cystitis in 40% of rats, but it did not cause this complication when combined with 5-FU and MTX. Histologic changes were found in rat kidneys after administration of MTX, CY and NG, while no such change was observed after 5-FU and joint administration of MTX + 5-FU + CY compared to controls. Our studies indicate that nephrotoxicity of MTX + 5-FU + CY administered jointly is lower than in monotherapy.", "entity": "Cystitis", "aliases": "Cystitides Cystitis", "definition": "Inflammation of the URINARY BLADDER, either from bacterial or non-bacterial causes. Cystitis is usually associated with painful urination (dysuria), increased frequency, urgency, and suprapubic pain.\n    ", "id": "MESH:D003556"}
{"mention": "nephrotoxicity", "mention_text": "The nephrotoxic action of anticancer drugs such as nitrogranulogen (NG), methotrexate (MTX), 5-fluorouracil (5-FU) and cyclophosphamide (CY) administered alone or in combination [MTX + 5-FU + CY (CMF)] was evaluated in experiments on Wistar rats. After drug administration, creatinine concentrations in the plasma and in the urine of the rats were determined, as well as creatinine clearance. Histopathologic evaluation of the kidneys was also performed. After MTX administration a significant increase (p = 0.0228) in the plasma creatinine concentration and a significant (p = 0.0001) decrease in creatinine clearance was noted compared to controls. After the administration of NG, 5-FU and CY neither a statistically significant increase in creatinine concentration nor an increase in creatinine clearance was observed compared to the group receiving no cytostatics. Following polytherapy according to the CMF regimen, a statistically significant decrease (p = 0.0343) in creatinine clearance was found, but creatinine concentration did not increase significantly compared to controls. CY caused hemorrhagic cystitis in 40% of rats, but it did not cause this complication when combined with 5-FU and MTX. Histologic changes were found in rat kidneys after administration of MTX, CY and NG, while no such change was observed after 5-FU and joint administration of MTX + 5-FU + CY compared to controls. Our studies indicate that nephrotoxicity of MTX + 5-FU + CY administered jointly is lower than in monotherapy.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "Lithium", "mention_text": "Lithium-associated cognitive and functional deficits reduced by a switch to divalproex sodium: a case series.", "entity": "Lithium", "aliases": "Lithium", "definition": "An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.\n    ", "id": "MESH:D008094"}
{"mention": "cognitive and functional deficits", "mention_text": "Lithium-associated cognitive and functional deficits reduced by a switch to divalproex sodium: a case series.", "entity": "Cognition Disorders", "aliases": "Cognition Disorders Disorder Overinclusion", "definition": "Disturbances in the mental process related to thinking, reasoning, and judgment.\n    ", "id": "MESH:D003072"}
{"mention": "divalproex sodium", "mention_text": "Lithium-associated cognitive and functional deficits reduced by a switch to divalproex sodium: a case series.", "entity": "Valproic Acid", "aliases": "2 Propylpentanoic Acid 2-Propylpentanoic Acetate Dipropyl Propylisopropylacetic Valproic Calcium Valproate Convulsofin Depakene Depakine Depakote Divalproex Sodium Ergenyl Magnesium Semisodium Salt (2:1) Vupral", "definition": "A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.\n    ", "id": "MESH:D014635"}
{"mention": "Lithium", "mention_text": "BACKGROUND: Lithium remains a first-line treatment for the acute and maintenance treatment of bipolar disorder. Although much has been written about the management of the more common adverse effects of lithium, such as polyuria and tremor, more subtle lithium side effects such as cognitive deficits, loss of creativity, and functional impairments remain understudied. This report summarizes our experience in switching bipolar patients from lithium to divalproex sodium to alleviate such cognitive and functional impairments. METHOD: Open, case series design. RESULTS: We report seven cases where substitution of lithium, either fully or partially, with divalproex sodium was extremely helpful in reducing the cognitive, motivational, or creative deficits attributed to lithium in our bipolar patients. CONCLUSION: In this preliminary report, divalproex sodium was a superior alternative to lithium in bipolar patients experiencing cognitive deficits, loss of creativity, and functional impairments.", "entity": "Lithium", "aliases": "Lithium", "definition": "An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.\n    ", "id": "MESH:D008094"}
{"mention": "bipolar disorder", "mention_text": "BACKGROUND: Lithium remains a first-line treatment for the acute and maintenance treatment of bipolar disorder. Although much has been written about the management of the more common adverse effects of lithium, such as polyuria and tremor, more subtle lithium side effects such as cognitive deficits, loss of creativity, and functional impairments remain understudied. This report summarizes our experience in switching bipolar patients from lithium to divalproex sodium to alleviate such cognitive and functional impairments. METHOD: Open, case series design. RESULTS: We report seven cases where substitution of lithium, either fully or partially, with divalproex sodium was extremely helpful in reducing the cognitive, motivational, or creative deficits attributed to lithium in our bipolar patients. CONCLUSION: In this preliminary report, divalproex sodium was a superior alternative to lithium in bipolar patients experiencing cognitive deficits, loss of creativity, and functional impairments.", "entity": "Bipolar Disorder", "aliases": "Affective Psychosis Bipolar Depression Disorder Disorders Manic Mania Manias Depressive State States Manic-Depressive Psychoses", "definition": "A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.\n    ", "id": "MESH:D001714"}
{"mention": "lithium", "mention_text": "BACKGROUND: Lithium remains a first-line treatment for the acute and maintenance treatment of bipolar disorder. Although much has been written about the management of the more common adverse effects of lithium, such as polyuria and tremor, more subtle lithium side effects such as cognitive deficits, loss of creativity, and functional impairments remain understudied. This report summarizes our experience in switching bipolar patients from lithium to divalproex sodium to alleviate such cognitive and functional impairments. METHOD: Open, case series design. RESULTS: We report seven cases where substitution of lithium, either fully or partially, with divalproex sodium was extremely helpful in reducing the cognitive, motivational, or creative deficits attributed to lithium in our bipolar patients. CONCLUSION: In this preliminary report, divalproex sodium was a superior alternative to lithium in bipolar patients experiencing cognitive deficits, loss of creativity, and functional impairments.", "entity": "Lithium", "aliases": "Lithium", "definition": "An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.\n    ", "id": "MESH:D008094"}
{"mention": "polyuria", "mention_text": "BACKGROUND: Lithium remains a first-line treatment for the acute and maintenance treatment of bipolar disorder. Although much has been written about the management of the more common adverse effects of lithium, such as polyuria and tremor, more subtle lithium side effects such as cognitive deficits, loss of creativity, and functional impairments remain understudied. This report summarizes our experience in switching bipolar patients from lithium to divalproex sodium to alleviate such cognitive and functional impairments. METHOD: Open, case series design. RESULTS: We report seven cases where substitution of lithium, either fully or partially, with divalproex sodium was extremely helpful in reducing the cognitive, motivational, or creative deficits attributed to lithium in our bipolar patients. CONCLUSION: In this preliminary report, divalproex sodium was a superior alternative to lithium in bipolar patients experiencing cognitive deficits, loss of creativity, and functional impairments.", "entity": "Polyuria", "aliases": "Polyuria Polyurias", "definition": "Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes (DIABETES MELLITUS; DIABETES INSIPIDUS).\n    ", "id": "MESH:D011141"}
{"mention": "tremor", "mention_text": "BACKGROUND: Lithium remains a first-line treatment for the acute and maintenance treatment of bipolar disorder. Although much has been written about the management of the more common adverse effects of lithium, such as polyuria and tremor, more subtle lithium side effects such as cognitive deficits, loss of creativity, and functional impairments remain understudied. This report summarizes our experience in switching bipolar patients from lithium to divalproex sodium to alleviate such cognitive and functional impairments. METHOD: Open, case series design. RESULTS: We report seven cases where substitution of lithium, either fully or partially, with divalproex sodium was extremely helpful in reducing the cognitive, motivational, or creative deficits attributed to lithium in our bipolar patients. CONCLUSION: In this preliminary report, divalproex sodium was a superior alternative to lithium in bipolar patients experiencing cognitive deficits, loss of creativity, and functional impairments.", "entity": "Tremor", "aliases": "Action Tremor Tremors Coarse Continuous Darkness Fine Intention Intermittent Involuntary Quiver Quivers Limb Massive Muscle Neonatal Nerve Passive Perioral Persistent Pill Rolling Rest Resting Saturnine Semirhythmic Senile Static", "definition": "Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of CEREBELLAR DISEASES, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of PARKINSON DISEASE.\n    ", "id": "MESH:D014202"}
{"mention": "cognitive deficits", "mention_text": "BACKGROUND: Lithium remains a first-line treatment for the acute and maintenance treatment of bipolar disorder. Although much has been written about the management of the more common adverse effects of lithium, such as polyuria and tremor, more subtle lithium side effects such as cognitive deficits, loss of creativity, and functional impairments remain understudied. This report summarizes our experience in switching bipolar patients from lithium to divalproex sodium to alleviate such cognitive and functional impairments. METHOD: Open, case series design. RESULTS: We report seven cases where substitution of lithium, either fully or partially, with divalproex sodium was extremely helpful in reducing the cognitive, motivational, or creative deficits attributed to lithium in our bipolar patients. CONCLUSION: In this preliminary report, divalproex sodium was a superior alternative to lithium in bipolar patients experiencing cognitive deficits, loss of creativity, and functional impairments.", "entity": "Cognition Disorders", "aliases": "Cognition Disorders Disorder Overinclusion", "definition": "Disturbances in the mental process related to thinking, reasoning, and judgment.\n    ", "id": "MESH:D003072"}
{"mention": "loss of creativity", "mention_text": "BACKGROUND: Lithium remains a first-line treatment for the acute and maintenance treatment of bipolar disorder. Although much has been written about the management of the more common adverse effects of lithium, such as polyuria and tremor, more subtle lithium side effects such as cognitive deficits, loss of creativity, and functional impairments remain understudied. This report summarizes our experience in switching bipolar patients from lithium to divalproex sodium to alleviate such cognitive and functional impairments. METHOD: Open, case series design. RESULTS: We report seven cases where substitution of lithium, either fully or partially, with divalproex sodium was extremely helpful in reducing the cognitive, motivational, or creative deficits attributed to lithium in our bipolar patients. CONCLUSION: In this preliminary report, divalproex sodium was a superior alternative to lithium in bipolar patients experiencing cognitive deficits, loss of creativity, and functional impairments.", "entity": "Cognition Disorders", "aliases": "Cognition Disorders Disorder Overinclusion", "definition": "Disturbances in the mental process related to thinking, reasoning, and judgment.\n    ", "id": "MESH:D003072"}
{"mention": "functional impairments", "mention_text": "BACKGROUND: Lithium remains a first-line treatment for the acute and maintenance treatment of bipolar disorder. Although much has been written about the management of the more common adverse effects of lithium, such as polyuria and tremor, more subtle lithium side effects such as cognitive deficits, loss of creativity, and functional impairments remain understudied. This report summarizes our experience in switching bipolar patients from lithium to divalproex sodium to alleviate such cognitive and functional impairments. METHOD: Open, case series design. RESULTS: We report seven cases where substitution of lithium, either fully or partially, with divalproex sodium was extremely helpful in reducing the cognitive, motivational, or creative deficits attributed to lithium in our bipolar patients. CONCLUSION: In this preliminary report, divalproex sodium was a superior alternative to lithium in bipolar patients experiencing cognitive deficits, loss of creativity, and functional impairments.", "entity": "Cognition Disorders", "aliases": "Cognition Disorders Disorder Overinclusion", "definition": "Disturbances in the mental process related to thinking, reasoning, and judgment.\n    ", "id": "MESH:D003072"}
{"mention": "bipolar", "mention_text": "BACKGROUND: Lithium remains a first-line treatment for the acute and maintenance treatment of bipolar disorder. Although much has been written about the management of the more common adverse effects of lithium, such as polyuria and tremor, more subtle lithium side effects such as cognitive deficits, loss of creativity, and functional impairments remain understudied. This report summarizes our experience in switching bipolar patients from lithium to divalproex sodium to alleviate such cognitive and functional impairments. METHOD: Open, case series design. RESULTS: We report seven cases where substitution of lithium, either fully or partially, with divalproex sodium was extremely helpful in reducing the cognitive, motivational, or creative deficits attributed to lithium in our bipolar patients. CONCLUSION: In this preliminary report, divalproex sodium was a superior alternative to lithium in bipolar patients experiencing cognitive deficits, loss of creativity, and functional impairments.", "entity": "Bipolar Disorder", "aliases": "Affective Psychosis Bipolar Depression Disorder Disorders Manic Mania Manias Depressive State States Manic-Depressive Psychoses", "definition": "A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.\n    ", "id": "MESH:D001714"}
{"mention": "divalproex sodium", "mention_text": "BACKGROUND: Lithium remains a first-line treatment for the acute and maintenance treatment of bipolar disorder. Although much has been written about the management of the more common adverse effects of lithium, such as polyuria and tremor, more subtle lithium side effects such as cognitive deficits, loss of creativity, and functional impairments remain understudied. This report summarizes our experience in switching bipolar patients from lithium to divalproex sodium to alleviate such cognitive and functional impairments. METHOD: Open, case series design. RESULTS: We report seven cases where substitution of lithium, either fully or partially, with divalproex sodium was extremely helpful in reducing the cognitive, motivational, or creative deficits attributed to lithium in our bipolar patients. CONCLUSION: In this preliminary report, divalproex sodium was a superior alternative to lithium in bipolar patients experiencing cognitive deficits, loss of creativity, and functional impairments.", "entity": "Valproic Acid", "aliases": "2 Propylpentanoic Acid 2-Propylpentanoic Acetate Dipropyl Propylisopropylacetic Valproic Calcium Valproate Convulsofin Depakene Depakine Depakote Divalproex Sodium Ergenyl Magnesium Semisodium Salt (2:1) Vupral", "definition": "A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.\n    ", "id": "MESH:D014635"}
{"mention": "cognitive and functional impairments", "mention_text": "BACKGROUND: Lithium remains a first-line treatment for the acute and maintenance treatment of bipolar disorder. Although much has been written about the management of the more common adverse effects of lithium, such as polyuria and tremor, more subtle lithium side effects such as cognitive deficits, loss of creativity, and functional impairments remain understudied. This report summarizes our experience in switching bipolar patients from lithium to divalproex sodium to alleviate such cognitive and functional impairments. METHOD: Open, case series design. RESULTS: We report seven cases where substitution of lithium, either fully or partially, with divalproex sodium was extremely helpful in reducing the cognitive, motivational, or creative deficits attributed to lithium in our bipolar patients. CONCLUSION: In this preliminary report, divalproex sodium was a superior alternative to lithium in bipolar patients experiencing cognitive deficits, loss of creativity, and functional impairments.", "entity": "Cognition Disorders", "aliases": "Cognition Disorders Disorder Overinclusion", "definition": "Disturbances in the mental process related to thinking, reasoning, and judgment.\n    ", "id": "MESH:D003072"}
{"mention": "cognitive, motivational, or creative deficits", "mention_text": "BACKGROUND: Lithium remains a first-line treatment for the acute and maintenance treatment of bipolar disorder. Although much has been written about the management of the more common adverse effects of lithium, such as polyuria and tremor, more subtle lithium side effects such as cognitive deficits, loss of creativity, and functional impairments remain understudied. This report summarizes our experience in switching bipolar patients from lithium to divalproex sodium to alleviate such cognitive and functional impairments. METHOD: Open, case series design. RESULTS: We report seven cases where substitution of lithium, either fully or partially, with divalproex sodium was extremely helpful in reducing the cognitive, motivational, or creative deficits attributed to lithium in our bipolar patients. CONCLUSION: In this preliminary report, divalproex sodium was a superior alternative to lithium in bipolar patients experiencing cognitive deficits, loss of creativity, and functional impairments.", "entity": "Cognition Disorders", "aliases": "Cognition Disorders Disorder Overinclusion", "definition": "Disturbances in the mental process related to thinking, reasoning, and judgment.\n    ", "id": "MESH:D003072"}
{"mention": "breast cancer", "mention_text": "Treatment of previously treated metastatic breast cancer by mitoxantrone and 48-hour continuous infusion of high-dose 5-FU and leucovorin (MFL): low palliative benefit and high treatment-related toxicity.", "entity": "Breast Neoplasms", "aliases": "Breast Cancer Carcinoma Neoplasm Neoplasms Tumor Tumors of the Human Mammary Carcinomas Malignant", "definition": "Tumors or cancer of the human BREAST.\n    ", "id": "MESH:D001943"}
{"mention": "mitoxantrone", "mention_text": "Treatment of previously treated metastatic breast cancer by mitoxantrone and 48-hour continuous infusion of high-dose 5-FU and leucovorin (MFL): low palliative benefit and high treatment-related toxicity.", "entity": "Mitoxantrone", "aliases": "AHP Brand of Mitoxantrone Hydrochloride ASTA Medica Acetate Amgen Baxter Oncology CL 232325 CL-232325 CL232325 Columbia DHAQ Inibsa Lederle Mitozantrone Mitroxone NSC 279836 287836 299195 301739 301739D NSC-279836 NSC-287836 NSC-299195 NSC-301739 NSC-301739D NSC279836 NSC287836 NSC299195 NSC301739 NSC301739D Novantron Novantrone Onkotrone Pralifan Ralenova Wyeth", "definition": "An anthracenedione-derived antineoplastic agent.\n    ", "id": "MESH:D008942"}
{"mention": "5-FU", "mention_text": "Treatment of previously treated metastatic breast cancer by mitoxantrone and 48-hour continuous infusion of high-dose 5-FU and leucovorin (MFL): low palliative benefit and high treatment-related toxicity.", "entity": "Fluorouracil", "aliases": "5 FU Lederle medac Fluorouracil biosyn HU Hexal 5-FU 5-Fluorouracil 5-Fluorouracil-biosyn 5-HU 5FU Adrucil Allergan Brand of CSP Carac Dakota Fluorouracile Dermatech Dermik Efudex Efudix Ferrer Fluoro Uracile ICN Fluoro-Uracile Fluoroplex GRY Mononitrate Monopotassium Salt Monosodium Potassium Teva Fluorouracil-GRY Fluorouracilo Far Fluoruracil Fluracedyl Flurodex Gry Haemato fu Haemato-fu Neocorp Neofluor Onkofluor Onkoworks Pharmachemie Ribofluor Riemser Roche ribosepharm", "definition": "A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.\n    ", "id": "MESH:D005472"}
{"mention": "leucovorin", "mention_text": "Treatment of previously treated metastatic breast cancer by mitoxantrone and 48-hour continuous infusion of high-dose 5-FU and leucovorin (MFL): low palliative benefit and high treatment-related toxicity.", "entity": "Leucovorin", "aliases": "5 Formyltetrahydrofolate Formyltetrahydropteroylglutamate 5-Formyltetrahydrofolate 5-Formyltetrahydropteroylglutamate Acid Folinic Calcium Folinate Leucovorin Citrovorum Factor SF Acid-SF (D)-Isomer (DL)-Isomer (R)-Isomer (1:1) Salt Pentahydrate Monosodium Leukovorin Leukovorum N(5)-Formyltetrahydrofolate Wellcovorin", "definition": "The active metabolite of FOLIC ACID. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid.\n    ", "id": "MESH:D002955"}
{"mention": "MFL", "mention_text": "Treatment of previously treated metastatic breast cancer by mitoxantrone and 48-hour continuous infusion of high-dose 5-FU and leucovorin (MFL): low palliative benefit and high treatment-related toxicity.", "entity": "MFL combination", "aliases": "MFL combination NFL regimen", "definition": "", "id": "MESH:C085788"}
{"mention": "toxicity", "mention_text": "Treatment of previously treated metastatic breast cancer by mitoxantrone and 48-hour continuous infusion of high-dose 5-FU and leucovorin (MFL): low palliative benefit and high treatment-related toxicity.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "breast cancer", "mention_text": "For previously treated advanced breast cancer, there is no standard second-line therapy. Combination chemotherapy with mitoxantrone, high-dose 5-fluorouracil (5-FU) and leucovorin (MFL regimen) had been reported as an effective and well tolerated regimen. From October 1993 to November 1995, we treated 13 patients with previously chemotherapy-treated metastatic breast cancer by mitoxantrone, 12 mg/m2, on day 1 and continuous infusion of 5-FU, 3000 mg/m2, together with leucovorin, 300 mg/m2, for 48 h from day 1 to 2. Each course of chemotherapy was given every 4 weeks. Most of these patients had more than two metastatic sites, with lung metastasis predominant. Seven patients had been treated with anthracycline. Seven patients had previously received radiotherapy and seven had received hormone therapy. Median number of courses of MFL regimen given was six and the median cumulative dose of mitoxantrone was 68.35 mg/m2. One patient had complete response, seven had stable disease, none had partial response and five had progressive disease. The overall objective response rate was 7.6%. The median follow-up period was 14 months. Median survival was 16 months. Median progression-free survival was 5 months. A complete responder had relapse-free survival up to 17 months. Major toxicities were cardiotoxicity and leukopenia. Eight patients were dead in the last follow-up; two of them died of treatment-related toxicity. The MFL regimen achieves little palliative benefit and induces severe toxicity at a fairly high rate. Administration of this regimen to breast cancer patients who have been treated by chemotherapy and those with impaired heart function requires careful attention.", "entity": "Breast Neoplasms", "aliases": "Breast Cancer Carcinoma Neoplasm Neoplasms Tumor Tumors of the Human Mammary Carcinomas Malignant", "definition": "Tumors or cancer of the human BREAST.\n    ", "id": "MESH:D001943"}
{"mention": "mitoxantrone", "mention_text": "For previously treated advanced breast cancer, there is no standard second-line therapy. Combination chemotherapy with mitoxantrone, high-dose 5-fluorouracil (5-FU) and leucovorin (MFL regimen) had been reported as an effective and well tolerated regimen. From October 1993 to November 1995, we treated 13 patients with previously chemotherapy-treated metastatic breast cancer by mitoxantrone, 12 mg/m2, on day 1 and continuous infusion of 5-FU, 3000 mg/m2, together with leucovorin, 300 mg/m2, for 48 h from day 1 to 2. Each course of chemotherapy was given every 4 weeks. Most of these patients had more than two metastatic sites, with lung metastasis predominant. Seven patients had been treated with anthracycline. Seven patients had previously received radiotherapy and seven had received hormone therapy. Median number of courses of MFL regimen given was six and the median cumulative dose of mitoxantrone was 68.35 mg/m2. One patient had complete response, seven had stable disease, none had partial response and five had progressive disease. The overall objective response rate was 7.6%. The median follow-up period was 14 months. Median survival was 16 months. Median progression-free survival was 5 months. A complete responder had relapse-free survival up to 17 months. Major toxicities were cardiotoxicity and leukopenia. Eight patients were dead in the last follow-up; two of them died of treatment-related toxicity. The MFL regimen achieves little palliative benefit and induces severe toxicity at a fairly high rate. Administration of this regimen to breast cancer patients who have been treated by chemotherapy and those with impaired heart function requires careful attention.", "entity": "Mitoxantrone", "aliases": "AHP Brand of Mitoxantrone Hydrochloride ASTA Medica Acetate Amgen Baxter Oncology CL 232325 CL-232325 CL232325 Columbia DHAQ Inibsa Lederle Mitozantrone Mitroxone NSC 279836 287836 299195 301739 301739D NSC-279836 NSC-287836 NSC-299195 NSC-301739 NSC-301739D NSC279836 NSC287836 NSC299195 NSC301739 NSC301739D Novantron Novantrone Onkotrone Pralifan Ralenova Wyeth", "definition": "An anthracenedione-derived antineoplastic agent.\n    ", "id": "MESH:D008942"}
{"mention": "5-fluorouracil", "mention_text": "For previously treated advanced breast cancer, there is no standard second-line therapy. Combination chemotherapy with mitoxantrone, high-dose 5-fluorouracil (5-FU) and leucovorin (MFL regimen) had been reported as an effective and well tolerated regimen. From October 1993 to November 1995, we treated 13 patients with previously chemotherapy-treated metastatic breast cancer by mitoxantrone, 12 mg/m2, on day 1 and continuous infusion of 5-FU, 3000 mg/m2, together with leucovorin, 300 mg/m2, for 48 h from day 1 to 2. Each course of chemotherapy was given every 4 weeks. Most of these patients had more than two metastatic sites, with lung metastasis predominant. Seven patients had been treated with anthracycline. Seven patients had previously received radiotherapy and seven had received hormone therapy. Median number of courses of MFL regimen given was six and the median cumulative dose of mitoxantrone was 68.35 mg/m2. One patient had complete response, seven had stable disease, none had partial response and five had progressive disease. The overall objective response rate was 7.6%. The median follow-up period was 14 months. Median survival was 16 months. Median progression-free survival was 5 months. A complete responder had relapse-free survival up to 17 months. Major toxicities were cardiotoxicity and leukopenia. Eight patients were dead in the last follow-up; two of them died of treatment-related toxicity. The MFL regimen achieves little palliative benefit and induces severe toxicity at a fairly high rate. Administration of this regimen to breast cancer patients who have been treated by chemotherapy and those with impaired heart function requires careful attention.", "entity": "Fluorouracil", "aliases": "5 FU Lederle medac Fluorouracil biosyn HU Hexal 5-FU 5-Fluorouracil 5-Fluorouracil-biosyn 5-HU 5FU Adrucil Allergan Brand of CSP Carac Dakota Fluorouracile Dermatech Dermik Efudex Efudix Ferrer Fluoro Uracile ICN Fluoro-Uracile Fluoroplex GRY Mononitrate Monopotassium Salt Monosodium Potassium Teva Fluorouracil-GRY Fluorouracilo Far Fluoruracil Fluracedyl Flurodex Gry Haemato fu Haemato-fu Neocorp Neofluor Onkofluor Onkoworks Pharmachemie Ribofluor Riemser Roche ribosepharm", "definition": "A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.\n    ", "id": "MESH:D005472"}
{"mention": "5-FU", "mention_text": "For previously treated advanced breast cancer, there is no standard second-line therapy. Combination chemotherapy with mitoxantrone, high-dose 5-fluorouracil (5-FU) and leucovorin (MFL regimen) had been reported as an effective and well tolerated regimen. From October 1993 to November 1995, we treated 13 patients with previously chemotherapy-treated metastatic breast cancer by mitoxantrone, 12 mg/m2, on day 1 and continuous infusion of 5-FU, 3000 mg/m2, together with leucovorin, 300 mg/m2, for 48 h from day 1 to 2. Each course of chemotherapy was given every 4 weeks. Most of these patients had more than two metastatic sites, with lung metastasis predominant. Seven patients had been treated with anthracycline. Seven patients had previously received radiotherapy and seven had received hormone therapy. Median number of courses of MFL regimen given was six and the median cumulative dose of mitoxantrone was 68.35 mg/m2. One patient had complete response, seven had stable disease, none had partial response and five had progressive disease. The overall objective response rate was 7.6%. The median follow-up period was 14 months. Median survival was 16 months. Median progression-free survival was 5 months. A complete responder had relapse-free survival up to 17 months. Major toxicities were cardiotoxicity and leukopenia. Eight patients were dead in the last follow-up; two of them died of treatment-related toxicity. The MFL regimen achieves little palliative benefit and induces severe toxicity at a fairly high rate. Administration of this regimen to breast cancer patients who have been treated by chemotherapy and those with impaired heart function requires careful attention.", "entity": "Fluorouracil", "aliases": "5 FU Lederle medac Fluorouracil biosyn HU Hexal 5-FU 5-Fluorouracil 5-Fluorouracil-biosyn 5-HU 5FU Adrucil Allergan Brand of CSP Carac Dakota Fluorouracile Dermatech Dermik Efudex Efudix Ferrer Fluoro Uracile ICN Fluoro-Uracile Fluoroplex GRY Mononitrate Monopotassium Salt Monosodium Potassium Teva Fluorouracil-GRY Fluorouracilo Far Fluoruracil Fluracedyl Flurodex Gry Haemato fu Haemato-fu Neocorp Neofluor Onkofluor Onkoworks Pharmachemie Ribofluor Riemser Roche ribosepharm", "definition": "A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.\n    ", "id": "MESH:D005472"}
{"mention": "leucovorin", "mention_text": "For previously treated advanced breast cancer, there is no standard second-line therapy. Combination chemotherapy with mitoxantrone, high-dose 5-fluorouracil (5-FU) and leucovorin (MFL regimen) had been reported as an effective and well tolerated regimen. From October 1993 to November 1995, we treated 13 patients with previously chemotherapy-treated metastatic breast cancer by mitoxantrone, 12 mg/m2, on day 1 and continuous infusion of 5-FU, 3000 mg/m2, together with leucovorin, 300 mg/m2, for 48 h from day 1 to 2. Each course of chemotherapy was given every 4 weeks. Most of these patients had more than two metastatic sites, with lung metastasis predominant. Seven patients had been treated with anthracycline. Seven patients had previously received radiotherapy and seven had received hormone therapy. Median number of courses of MFL regimen given was six and the median cumulative dose of mitoxantrone was 68.35 mg/m2. One patient had complete response, seven had stable disease, none had partial response and five had progressive disease. The overall objective response rate was 7.6%. The median follow-up period was 14 months. Median survival was 16 months. Median progression-free survival was 5 months. A complete responder had relapse-free survival up to 17 months. Major toxicities were cardiotoxicity and leukopenia. Eight patients were dead in the last follow-up; two of them died of treatment-related toxicity. The MFL regimen achieves little palliative benefit and induces severe toxicity at a fairly high rate. Administration of this regimen to breast cancer patients who have been treated by chemotherapy and those with impaired heart function requires careful attention.", "entity": "Leucovorin", "aliases": "5 Formyltetrahydrofolate Formyltetrahydropteroylglutamate 5-Formyltetrahydrofolate 5-Formyltetrahydropteroylglutamate Acid Folinic Calcium Folinate Leucovorin Citrovorum Factor SF Acid-SF (D)-Isomer (DL)-Isomer (R)-Isomer (1:1) Salt Pentahydrate Monosodium Leukovorin Leukovorum N(5)-Formyltetrahydrofolate Wellcovorin", "definition": "The active metabolite of FOLIC ACID. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid.\n    ", "id": "MESH:D002955"}
{"mention": "MFL regimen", "mention_text": "For previously treated advanced breast cancer, there is no standard second-line therapy. Combination chemotherapy with mitoxantrone, high-dose 5-fluorouracil (5-FU) and leucovorin (MFL regimen) had been reported as an effective and well tolerated regimen. From October 1993 to November 1995, we treated 13 patients with previously chemotherapy-treated metastatic breast cancer by mitoxantrone, 12 mg/m2, on day 1 and continuous infusion of 5-FU, 3000 mg/m2, together with leucovorin, 300 mg/m2, for 48 h from day 1 to 2. Each course of chemotherapy was given every 4 weeks. Most of these patients had more than two metastatic sites, with lung metastasis predominant. Seven patients had been treated with anthracycline. Seven patients had previously received radiotherapy and seven had received hormone therapy. Median number of courses of MFL regimen given was six and the median cumulative dose of mitoxantrone was 68.35 mg/m2. One patient had complete response, seven had stable disease, none had partial response and five had progressive disease. The overall objective response rate was 7.6%. The median follow-up period was 14 months. Median survival was 16 months. Median progression-free survival was 5 months. A complete responder had relapse-free survival up to 17 months. Major toxicities were cardiotoxicity and leukopenia. Eight patients were dead in the last follow-up; two of them died of treatment-related toxicity. The MFL regimen achieves little palliative benefit and induces severe toxicity at a fairly high rate. Administration of this regimen to breast cancer patients who have been treated by chemotherapy and those with impaired heart function requires careful attention.", "entity": "MFL combination", "aliases": "MFL combination NFL regimen", "definition": "", "id": "MESH:C085788"}
{"mention": "anthracycline", "mention_text": "For previously treated advanced breast cancer, there is no standard second-line therapy. Combination chemotherapy with mitoxantrone, high-dose 5-fluorouracil (5-FU) and leucovorin (MFL regimen) had been reported as an effective and well tolerated regimen. From October 1993 to November 1995, we treated 13 patients with previously chemotherapy-treated metastatic breast cancer by mitoxantrone, 12 mg/m2, on day 1 and continuous infusion of 5-FU, 3000 mg/m2, together with leucovorin, 300 mg/m2, for 48 h from day 1 to 2. Each course of chemotherapy was given every 4 weeks. Most of these patients had more than two metastatic sites, with lung metastasis predominant. Seven patients had been treated with anthracycline. Seven patients had previously received radiotherapy and seven had received hormone therapy. Median number of courses of MFL regimen given was six and the median cumulative dose of mitoxantrone was 68.35 mg/m2. One patient had complete response, seven had stable disease, none had partial response and five had progressive disease. The overall objective response rate was 7.6%. The median follow-up period was 14 months. Median survival was 16 months. Median progression-free survival was 5 months. A complete responder had relapse-free survival up to 17 months. Major toxicities were cardiotoxicity and leukopenia. Eight patients were dead in the last follow-up; two of them died of treatment-related toxicity. The MFL regimen achieves little palliative benefit and induces severe toxicity at a fairly high rate. Administration of this regimen to breast cancer patients who have been treated by chemotherapy and those with impaired heart function requires careful attention.", "entity": "Anthracyclines", "aliases": "Anthracyclines", "definition": "Organic compounds that have a tetrahydronaphthacenedione ring structure attached by a glycosidic linkage to the amino sugar daunosamine.\n    ", "id": "MESH:D018943"}
{"mention": "toxicities", "mention_text": "For previously treated advanced breast cancer, there is no standard second-line therapy. Combination chemotherapy with mitoxantrone, high-dose 5-fluorouracil (5-FU) and leucovorin (MFL regimen) had been reported as an effective and well tolerated regimen. From October 1993 to November 1995, we treated 13 patients with previously chemotherapy-treated metastatic breast cancer by mitoxantrone, 12 mg/m2, on day 1 and continuous infusion of 5-FU, 3000 mg/m2, together with leucovorin, 300 mg/m2, for 48 h from day 1 to 2. Each course of chemotherapy was given every 4 weeks. Most of these patients had more than two metastatic sites, with lung metastasis predominant. Seven patients had been treated with anthracycline. Seven patients had previously received radiotherapy and seven had received hormone therapy. Median number of courses of MFL regimen given was six and the median cumulative dose of mitoxantrone was 68.35 mg/m2. One patient had complete response, seven had stable disease, none had partial response and five had progressive disease. The overall objective response rate was 7.6%. The median follow-up period was 14 months. Median survival was 16 months. Median progression-free survival was 5 months. A complete responder had relapse-free survival up to 17 months. Major toxicities were cardiotoxicity and leukopenia. Eight patients were dead in the last follow-up; two of them died of treatment-related toxicity. The MFL regimen achieves little palliative benefit and induces severe toxicity at a fairly high rate. Administration of this regimen to breast cancer patients who have been treated by chemotherapy and those with impaired heart function requires careful attention.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "cardiotoxicity", "mention_text": "For previously treated advanced breast cancer, there is no standard second-line therapy. Combination chemotherapy with mitoxantrone, high-dose 5-fluorouracil (5-FU) and leucovorin (MFL regimen) had been reported as an effective and well tolerated regimen. From October 1993 to November 1995, we treated 13 patients with previously chemotherapy-treated metastatic breast cancer by mitoxantrone, 12 mg/m2, on day 1 and continuous infusion of 5-FU, 3000 mg/m2, together with leucovorin, 300 mg/m2, for 48 h from day 1 to 2. Each course of chemotherapy was given every 4 weeks. Most of these patients had more than two metastatic sites, with lung metastasis predominant. Seven patients had been treated with anthracycline. Seven patients had previously received radiotherapy and seven had received hormone therapy. Median number of courses of MFL regimen given was six and the median cumulative dose of mitoxantrone was 68.35 mg/m2. One patient had complete response, seven had stable disease, none had partial response and five had progressive disease. The overall objective response rate was 7.6%. The median follow-up period was 14 months. Median survival was 16 months. Median progression-free survival was 5 months. A complete responder had relapse-free survival up to 17 months. Major toxicities were cardiotoxicity and leukopenia. Eight patients were dead in the last follow-up; two of them died of treatment-related toxicity. The MFL regimen achieves little palliative benefit and induces severe toxicity at a fairly high rate. Administration of this regimen to breast cancer patients who have been treated by chemotherapy and those with impaired heart function requires careful attention.", "entity": "Cardiotoxicity", "aliases": "Cardiac Toxicities Toxicity Cardiotoxicities Cardiotoxicity", "definition": "Damage to the heart or its function secondary to exposure to toxic substances such as drugs used in CHEMOTHERAPY; IMMUNOTHERAPY; or RADIATION.\n    ", "id": "MESH:D066126"}
{"mention": "leukopenia", "mention_text": "For previously treated advanced breast cancer, there is no standard second-line therapy. Combination chemotherapy with mitoxantrone, high-dose 5-fluorouracil (5-FU) and leucovorin (MFL regimen) had been reported as an effective and well tolerated regimen. From October 1993 to November 1995, we treated 13 patients with previously chemotherapy-treated metastatic breast cancer by mitoxantrone, 12 mg/m2, on day 1 and continuous infusion of 5-FU, 3000 mg/m2, together with leucovorin, 300 mg/m2, for 48 h from day 1 to 2. Each course of chemotherapy was given every 4 weeks. Most of these patients had more than two metastatic sites, with lung metastasis predominant. Seven patients had been treated with anthracycline. Seven patients had previously received radiotherapy and seven had received hormone therapy. Median number of courses of MFL regimen given was six and the median cumulative dose of mitoxantrone was 68.35 mg/m2. One patient had complete response, seven had stable disease, none had partial response and five had progressive disease. The overall objective response rate was 7.6%. The median follow-up period was 14 months. Median survival was 16 months. Median progression-free survival was 5 months. A complete responder had relapse-free survival up to 17 months. Major toxicities were cardiotoxicity and leukopenia. Eight patients were dead in the last follow-up; two of them died of treatment-related toxicity. The MFL regimen achieves little palliative benefit and induces severe toxicity at a fairly high rate. Administration of this regimen to breast cancer patients who have been treated by chemotherapy and those with impaired heart function requires careful attention.", "entity": "Leukopenia", "aliases": "Leukocytopenia Leukocytopenias Leukopenia Leukopenias", "definition": "", "id": "MESH:D007970"}
{"mention": "toxicity", "mention_text": "For previously treated advanced breast cancer, there is no standard second-line therapy. Combination chemotherapy with mitoxantrone, high-dose 5-fluorouracil (5-FU) and leucovorin (MFL regimen) had been reported as an effective and well tolerated regimen. From October 1993 to November 1995, we treated 13 patients with previously chemotherapy-treated metastatic breast cancer by mitoxantrone, 12 mg/m2, on day 1 and continuous infusion of 5-FU, 3000 mg/m2, together with leucovorin, 300 mg/m2, for 48 h from day 1 to 2. Each course of chemotherapy was given every 4 weeks. Most of these patients had more than two metastatic sites, with lung metastasis predominant. Seven patients had been treated with anthracycline. Seven patients had previously received radiotherapy and seven had received hormone therapy. Median number of courses of MFL regimen given was six and the median cumulative dose of mitoxantrone was 68.35 mg/m2. One patient had complete response, seven had stable disease, none had partial response and five had progressive disease. The overall objective response rate was 7.6%. The median follow-up period was 14 months. Median survival was 16 months. Median progression-free survival was 5 months. A complete responder had relapse-free survival up to 17 months. Major toxicities were cardiotoxicity and leukopenia. Eight patients were dead in the last follow-up; two of them died of treatment-related toxicity. The MFL regimen achieves little palliative benefit and induces severe toxicity at a fairly high rate. Administration of this regimen to breast cancer patients who have been treated by chemotherapy and those with impaired heart function requires careful attention.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "impaired heart function", "mention_text": "For previously treated advanced breast cancer, there is no standard second-line therapy. Combination chemotherapy with mitoxantrone, high-dose 5-fluorouracil (5-FU) and leucovorin (MFL regimen) had been reported as an effective and well tolerated regimen. From October 1993 to November 1995, we treated 13 patients with previously chemotherapy-treated metastatic breast cancer by mitoxantrone, 12 mg/m2, on day 1 and continuous infusion of 5-FU, 3000 mg/m2, together with leucovorin, 300 mg/m2, for 48 h from day 1 to 2. Each course of chemotherapy was given every 4 weeks. Most of these patients had more than two metastatic sites, with lung metastasis predominant. Seven patients had been treated with anthracycline. Seven patients had previously received radiotherapy and seven had received hormone therapy. Median number of courses of MFL regimen given was six and the median cumulative dose of mitoxantrone was 68.35 mg/m2. One patient had complete response, seven had stable disease, none had partial response and five had progressive disease. The overall objective response rate was 7.6%. The median follow-up period was 14 months. Median survival was 16 months. Median progression-free survival was 5 months. A complete responder had relapse-free survival up to 17 months. Major toxicities were cardiotoxicity and leukopenia. Eight patients were dead in the last follow-up; two of them died of treatment-related toxicity. The MFL regimen achieves little palliative benefit and induces severe toxicity at a fairly high rate. Administration of this regimen to breast cancer patients who have been treated by chemotherapy and those with impaired heart function requires careful attention.", "entity": "Heart Diseases", "aliases": "Cardiac Disease Diseases Heart", "definition": "Pathological conditions involving the HEART including its structural and functional abnormalities.\n    ", "id": "MESH:D006331"}
{"mention": "vasopressin", "mention_text": "Upregulation of the expression of vasopressin gene in the paraventricular and supraoptic nuclei of the lithium-induced diabetes insipidus rat.", "entity": "Vasopressins", "aliases": "American Pharmaceutical Brand of Vasopressin Regent Antidiuretic Hormones Monarch Parke-Davis (USP) Pitressin Vasopressins beta Hypophamine beta-Hypophamine", "definition": "Antidiuretic hormones released by the NEUROHYPOPHYSIS of all vertebrates (structure varies with species) to regulate water balance and OSMOLARITY. In general, vasopressin is a nonapeptide consisting of a six-amino-acid ring with a cysteine 1 to cysteine 6 disulfide bridge or an octapeptide containing a CYSTINE. All mammals have arginine vasopressin except the pig with a lysine at position 8. Vasopressin, a vasoconstrictor, acts on the KIDNEY COLLECTING DUCTS to increase water reabsorption, increase blood volume and blood pressure.\n    ", "id": "MESH:D014667"}
{"mention": "lithium", "mention_text": "Upregulation of the expression of vasopressin gene in the paraventricular and supraoptic nuclei of the lithium-induced diabetes insipidus rat.", "entity": "Lithium", "aliases": "Lithium", "definition": "An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.\n    ", "id": "MESH:D008094"}
{"mention": "diabetes insipidus", "mention_text": "Upregulation of the expression of vasopressin gene in the paraventricular and supraoptic nuclei of the lithium-induced diabetes insipidus rat.", "entity": "Diabetes Insipidus", "aliases": "Diabetes Insipidus", "definition": "A disease that is characterized by frequent urination, excretion of large amounts of dilute URINE, and excessive THIRST. Etiologies of diabetes insipidus include deficiency of antidiuretic hormone (also known as ADH or VASOPRESSIN) secreted by the NEUROHYPOPHYSIS, impaired KIDNEY response to ADH, and impaired hypothalamic regulation of thirst.\n    ", "id": "MESH:D003919"}
{"mention": "arginine vasopressin", "mention_text": "The expression of arginine vasopressin (AVP) gene in the paraventricular (PVN) and supraoptic nuclei (SON) was investigated in rats with lithium (Li)-induced polyuria, using in situ hybridization histochemistry and radioimmunoassay. The male Wistar rats consuming a diet that contained LiCl (60 mmol/kg) for 4 weeks developed marked polyuria. The Li-treated rats produced a large volume of hypotonic urine with low ionic concentrations. Plasma sodium concentrations were found to be slightly increased in the Li-treated rats compared with those in controls. Plasma concentration of AVP and transcripts of AVP gene in the PVN and SON were significantly increased in the Li-treated rats compared with controls. These results suggest that dehydration and/or the activation of visceral afferent inputs may contribute to the elevation of plasma AVP and the upregulation of AVP gene expression in the PVN and the SON of the Li-induced diabetes insipidus rat.", "entity": "Arginine Vasopressin", "aliases": "Arg Vasopressin Arg-Vasopressin Arginine Argipressin Tannate", "definition": "The predominant form of mammalian antidiuretic hormone. It is a nonapeptide containing an ARGININE at residue 8 and two disulfide-linked cysteines at residues of 1 and 6. Arg-vasopressin is used to treat DIABETES INSIPIDUS or to improve vasomotor tone and BLOOD PRESSURE.\n    ", "id": "MESH:D001127"}
{"mention": "AVP", "mention_text": "The expression of arginine vasopressin (AVP) gene in the paraventricular (PVN) and supraoptic nuclei (SON) was investigated in rats with lithium (Li)-induced polyuria, using in situ hybridization histochemistry and radioimmunoassay. The male Wistar rats consuming a diet that contained LiCl (60 mmol/kg) for 4 weeks developed marked polyuria. The Li-treated rats produced a large volume of hypotonic urine with low ionic concentrations. Plasma sodium concentrations were found to be slightly increased in the Li-treated rats compared with those in controls. Plasma concentration of AVP and transcripts of AVP gene in the PVN and SON were significantly increased in the Li-treated rats compared with controls. These results suggest that dehydration and/or the activation of visceral afferent inputs may contribute to the elevation of plasma AVP and the upregulation of AVP gene expression in the PVN and the SON of the Li-induced diabetes insipidus rat.", "entity": "Arginine Vasopressin", "aliases": "Arg Vasopressin Arg-Vasopressin Arginine Argipressin Tannate", "definition": "The predominant form of mammalian antidiuretic hormone. It is a nonapeptide containing an ARGININE at residue 8 and two disulfide-linked cysteines at residues of 1 and 6. Arg-vasopressin is used to treat DIABETES INSIPIDUS or to improve vasomotor tone and BLOOD PRESSURE.\n    ", "id": "MESH:D001127"}
{"mention": "lithium", "mention_text": "The expression of arginine vasopressin (AVP) gene in the paraventricular (PVN) and supraoptic nuclei (SON) was investigated in rats with lithium (Li)-induced polyuria, using in situ hybridization histochemistry and radioimmunoassay. The male Wistar rats consuming a diet that contained LiCl (60 mmol/kg) for 4 weeks developed marked polyuria. The Li-treated rats produced a large volume of hypotonic urine with low ionic concentrations. Plasma sodium concentrations were found to be slightly increased in the Li-treated rats compared with those in controls. Plasma concentration of AVP and transcripts of AVP gene in the PVN and SON were significantly increased in the Li-treated rats compared with controls. These results suggest that dehydration and/or the activation of visceral afferent inputs may contribute to the elevation of plasma AVP and the upregulation of AVP gene expression in the PVN and the SON of the Li-induced diabetes insipidus rat.", "entity": "Lithium", "aliases": "Lithium", "definition": "An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.\n    ", "id": "MESH:D008094"}
{"mention": "Li", "mention_text": "The expression of arginine vasopressin (AVP) gene in the paraventricular (PVN) and supraoptic nuclei (SON) was investigated in rats with lithium (Li)-induced polyuria, using in situ hybridization histochemistry and radioimmunoassay. The male Wistar rats consuming a diet that contained LiCl (60 mmol/kg) for 4 weeks developed marked polyuria. The Li-treated rats produced a large volume of hypotonic urine with low ionic concentrations. Plasma sodium concentrations were found to be slightly increased in the Li-treated rats compared with those in controls. Plasma concentration of AVP and transcripts of AVP gene in the PVN and SON were significantly increased in the Li-treated rats compared with controls. These results suggest that dehydration and/or the activation of visceral afferent inputs may contribute to the elevation of plasma AVP and the upregulation of AVP gene expression in the PVN and the SON of the Li-induced diabetes insipidus rat.", "entity": "Lithium", "aliases": "Lithium", "definition": "An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.\n    ", "id": "MESH:D008094"}
{"mention": "polyuria", "mention_text": "The expression of arginine vasopressin (AVP) gene in the paraventricular (PVN) and supraoptic nuclei (SON) was investigated in rats with lithium (Li)-induced polyuria, using in situ hybridization histochemistry and radioimmunoassay. The male Wistar rats consuming a diet that contained LiCl (60 mmol/kg) for 4 weeks developed marked polyuria. The Li-treated rats produced a large volume of hypotonic urine with low ionic concentrations. Plasma sodium concentrations were found to be slightly increased in the Li-treated rats compared with those in controls. Plasma concentration of AVP and transcripts of AVP gene in the PVN and SON were significantly increased in the Li-treated rats compared with controls. These results suggest that dehydration and/or the activation of visceral afferent inputs may contribute to the elevation of plasma AVP and the upregulation of AVP gene expression in the PVN and the SON of the Li-induced diabetes insipidus rat.", "entity": "Polyuria", "aliases": "Polyuria Polyurias", "definition": "Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes (DIABETES MELLITUS; DIABETES INSIPIDUS).\n    ", "id": "MESH:D011141"}
{"mention": "LiCl", "mention_text": "The expression of arginine vasopressin (AVP) gene in the paraventricular (PVN) and supraoptic nuclei (SON) was investigated in rats with lithium (Li)-induced polyuria, using in situ hybridization histochemistry and radioimmunoassay. The male Wistar rats consuming a diet that contained LiCl (60 mmol/kg) for 4 weeks developed marked polyuria. The Li-treated rats produced a large volume of hypotonic urine with low ionic concentrations. Plasma sodium concentrations were found to be slightly increased in the Li-treated rats compared with those in controls. Plasma concentration of AVP and transcripts of AVP gene in the PVN and SON were significantly increased in the Li-treated rats compared with controls. These results suggest that dehydration and/or the activation of visceral afferent inputs may contribute to the elevation of plasma AVP and the upregulation of AVP gene expression in the PVN and the SON of the Li-induced diabetes insipidus rat.", "entity": "Lithium Chloride", "aliases": "Chloride Lithium", "definition": "A salt of lithium that has been used experimentally as an immunomodulator.\n    ", "id": "MESH:D018021"}
{"mention": "sodium", "mention_text": "The expression of arginine vasopressin (AVP) gene in the paraventricular (PVN) and supraoptic nuclei (SON) was investigated in rats with lithium (Li)-induced polyuria, using in situ hybridization histochemistry and radioimmunoassay. The male Wistar rats consuming a diet that contained LiCl (60 mmol/kg) for 4 weeks developed marked polyuria. The Li-treated rats produced a large volume of hypotonic urine with low ionic concentrations. Plasma sodium concentrations were found to be slightly increased in the Li-treated rats compared with those in controls. Plasma concentration of AVP and transcripts of AVP gene in the PVN and SON were significantly increased in the Li-treated rats compared with controls. These results suggest that dehydration and/or the activation of visceral afferent inputs may contribute to the elevation of plasma AVP and the upregulation of AVP gene expression in the PVN and the SON of the Li-induced diabetes insipidus rat.", "entity": "Sodium", "aliases": "Ion Level Sodium", "definition": "A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.\n    ", "id": "MESH:D012964"}
{"mention": "dehydration", "mention_text": "The expression of arginine vasopressin (AVP) gene in the paraventricular (PVN) and supraoptic nuclei (SON) was investigated in rats with lithium (Li)-induced polyuria, using in situ hybridization histochemistry and radioimmunoassay. The male Wistar rats consuming a diet that contained LiCl (60 mmol/kg) for 4 weeks developed marked polyuria. The Li-treated rats produced a large volume of hypotonic urine with low ionic concentrations. Plasma sodium concentrations were found to be slightly increased in the Li-treated rats compared with those in controls. Plasma concentration of AVP and transcripts of AVP gene in the PVN and SON were significantly increased in the Li-treated rats compared with controls. These results suggest that dehydration and/or the activation of visceral afferent inputs may contribute to the elevation of plasma AVP and the upregulation of AVP gene expression in the PVN and the SON of the Li-induced diabetes insipidus rat.", "entity": "Dehydration", "aliases": "Dehydration Stress Water", "definition": "The condition that results from excessive loss of water from a living organism.\n    ", "id": "MESH:D003681"}
{"mention": "diabetes insipidus", "mention_text": "The expression of arginine vasopressin (AVP) gene in the paraventricular (PVN) and supraoptic nuclei (SON) was investigated in rats with lithium (Li)-induced polyuria, using in situ hybridization histochemistry and radioimmunoassay. The male Wistar rats consuming a diet that contained LiCl (60 mmol/kg) for 4 weeks developed marked polyuria. The Li-treated rats produced a large volume of hypotonic urine with low ionic concentrations. Plasma sodium concentrations were found to be slightly increased in the Li-treated rats compared with those in controls. Plasma concentration of AVP and transcripts of AVP gene in the PVN and SON were significantly increased in the Li-treated rats compared with controls. These results suggest that dehydration and/or the activation of visceral afferent inputs may contribute to the elevation of plasma AVP and the upregulation of AVP gene expression in the PVN and the SON of the Li-induced diabetes insipidus rat.", "entity": "Diabetes Insipidus", "aliases": "Diabetes Insipidus", "definition": "A disease that is characterized by frequent urination, excretion of large amounts of dilute URINE, and excessive THIRST. Etiologies of diabetes insipidus include deficiency of antidiuretic hormone (also known as ADH or VASOPRESSIN) secreted by the NEUROHYPOPHYSIS, impaired KIDNEY response to ADH, and impaired hypothalamic regulation of thirst.\n    ", "id": "MESH:D003919"}
{"mention": "Suxamethonium", "mention_text": "Suxamethonium-induced cardiac arrest and death following 5 days of immobilization.", "entity": "Succinylcholine", "aliases": "Anectine Bromide Suxamethonium Celocurine Dibromide Succinylcholine Dichloride Diiodide Diperchlorate Ditilin Listenon Lysthenon Myorelaxin Quelicin Succicuran Chloride Di H2O Di-H2O Iodide Succinyldicholine", "definition": "A quaternary skeletal muscle relaxant usually used in the form of its bromide, chloride, or iodide. It is a depolarizing relaxant, acting in about 30 seconds and with a duration of effect averaging three to five minutes. Succinylcholine is used in surgical, anesthetic, and other procedures in which a brief period of muscle relaxation is called for.\n    ", "id": "MESH:D013390"}
{"mention": "cardiac arrest", "mention_text": "Suxamethonium-induced cardiac arrest and death following 5 days of immobilization.", "entity": "Heart Arrest", "aliases": "Arrest Cardiac Cardiopulmonary Heart Asystole Asystoles", "definition": "Cessation of heart beat or MYOCARDIAL CONTRACTION. If it is treated within a few minutes, heart arrest can be reversed in most cases to normal cardiac rhythm and effective circulation.\n    ", "id": "MESH:D006323"}
{"mention": "death", "mention_text": "Suxamethonium-induced cardiac arrest and death following 5 days of immobilization.", "entity": "Death", "aliases": "Cardiac Death Determination of Near-Death Experience", "definition": "Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.\n    ", "id": "MESH:D003643"}
{"mention": "cardiac arrest", "mention_text": "The present report describes a case of cardiac arrest and subsequent death as a result of hyperkalaemia following the use of suxamethonium in a 23-year-old Malawian woman. Five days after the onset of the symptoms of meningitis, the patient aspirated stomach contents and needed endotracheal intubation. Forty seconds after injection of suxamethonium, bradycardia and cardiac arrest occurred. Attempts to resuscitate the patient were not successful. The serum level of potassium was observed to be 8.4 mequiv L-1. Apart from the reduction in the patient's level of consciousness, there were no signs of motor neurone damage or of any of the other known predisposing conditions for hyperkalaemia following the administration of suxamethonium. It is postulated that her death was caused by hypersensitivity to suxamethonium, associated with her 5-day immobilization.", "entity": "Heart Arrest", "aliases": "Arrest Cardiac Cardiopulmonary Heart Asystole Asystoles", "definition": "Cessation of heart beat or MYOCARDIAL CONTRACTION. If it is treated within a few minutes, heart arrest can be reversed in most cases to normal cardiac rhythm and effective circulation.\n    ", "id": "MESH:D006323"}
{"mention": "death", "mention_text": "The present report describes a case of cardiac arrest and subsequent death as a result of hyperkalaemia following the use of suxamethonium in a 23-year-old Malawian woman. Five days after the onset of the symptoms of meningitis, the patient aspirated stomach contents and needed endotracheal intubation. Forty seconds after injection of suxamethonium, bradycardia and cardiac arrest occurred. Attempts to resuscitate the patient were not successful. The serum level of potassium was observed to be 8.4 mequiv L-1. Apart from the reduction in the patient's level of consciousness, there were no signs of motor neurone damage or of any of the other known predisposing conditions for hyperkalaemia following the administration of suxamethonium. It is postulated that her death was caused by hypersensitivity to suxamethonium, associated with her 5-day immobilization.", "entity": "Death", "aliases": "Cardiac Death Determination of Near-Death Experience", "definition": "Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.\n    ", "id": "MESH:D003643"}
{"mention": "hyperkalaemia", "mention_text": "The present report describes a case of cardiac arrest and subsequent death as a result of hyperkalaemia following the use of suxamethonium in a 23-year-old Malawian woman. Five days after the onset of the symptoms of meningitis, the patient aspirated stomach contents and needed endotracheal intubation. Forty seconds after injection of suxamethonium, bradycardia and cardiac arrest occurred. Attempts to resuscitate the patient were not successful. The serum level of potassium was observed to be 8.4 mequiv L-1. Apart from the reduction in the patient's level of consciousness, there were no signs of motor neurone damage or of any of the other known predisposing conditions for hyperkalaemia following the administration of suxamethonium. It is postulated that her death was caused by hypersensitivity to suxamethonium, associated with her 5-day immobilization.", "entity": "Hyperkalemia", "aliases": "Hyperkalemia Hyperkalemias Hyperpotassemia Hyperpotassemias", "definition": "Abnormally high potassium concentration in the blood, most often due to defective renal excretion. It is characterized clinically by electrocardiographic abnormalities (elevated T waves and depressed P waves, and eventually by atrial asystole). In severe cases, weakness and flaccid paralysis may occur. (Dorland, 27th ed)\n    ", "id": "MESH:D006947"}
{"mention": "suxamethonium", "mention_text": "The present report describes a case of cardiac arrest and subsequent death as a result of hyperkalaemia following the use of suxamethonium in a 23-year-old Malawian woman. Five days after the onset of the symptoms of meningitis, the patient aspirated stomach contents and needed endotracheal intubation. Forty seconds after injection of suxamethonium, bradycardia and cardiac arrest occurred. Attempts to resuscitate the patient were not successful. The serum level of potassium was observed to be 8.4 mequiv L-1. Apart from the reduction in the patient's level of consciousness, there were no signs of motor neurone damage or of any of the other known predisposing conditions for hyperkalaemia following the administration of suxamethonium. It is postulated that her death was caused by hypersensitivity to suxamethonium, associated with her 5-day immobilization.", "entity": "Succinylcholine", "aliases": "Anectine Bromide Suxamethonium Celocurine Dibromide Succinylcholine Dichloride Diiodide Diperchlorate Ditilin Listenon Lysthenon Myorelaxin Quelicin Succicuran Chloride Di H2O Di-H2O Iodide Succinyldicholine", "definition": "A quaternary skeletal muscle relaxant usually used in the form of its bromide, chloride, or iodide. It is a depolarizing relaxant, acting in about 30 seconds and with a duration of effect averaging three to five minutes. Succinylcholine is used in surgical, anesthetic, and other procedures in which a brief period of muscle relaxation is called for.\n    ", "id": "MESH:D013390"}
{"mention": "meningitis", "mention_text": "The present report describes a case of cardiac arrest and subsequent death as a result of hyperkalaemia following the use of suxamethonium in a 23-year-old Malawian woman. Five days after the onset of the symptoms of meningitis, the patient aspirated stomach contents and needed endotracheal intubation. Forty seconds after injection of suxamethonium, bradycardia and cardiac arrest occurred. Attempts to resuscitate the patient were not successful. The serum level of potassium was observed to be 8.4 mequiv L-1. Apart from the reduction in the patient's level of consciousness, there were no signs of motor neurone damage or of any of the other known predisposing conditions for hyperkalaemia following the administration of suxamethonium. It is postulated that her death was caused by hypersensitivity to suxamethonium, associated with her 5-day immobilization.", "entity": "Meningitis", "aliases": "Meningitides Meningitis Pachymeningitides Pachymeningitis", "definition": "Inflammation of the coverings of the brain and/or spinal cord, which consist of the PIA MATER; ARACHNOID; and DURA MATER. Infections (viral, bacterial, and fungal) are the most common causes of this condition, but subarachnoid hemorrhage (HEMORRHAGES, SUBARACHNOID), chemical irritation (chemical MENINGITIS), granulomatous conditions, neoplastic conditions (CARCINOMATOUS MENINGITIS), and other inflammatory conditions may produce this syndrome. (From Joynt, Clinical Neurology, 1994, Ch24, p6)\n    ", "id": "MESH:D008581"}
{"mention": "bradycardia", "mention_text": "The present report describes a case of cardiac arrest and subsequent death as a result of hyperkalaemia following the use of suxamethonium in a 23-year-old Malawian woman. Five days after the onset of the symptoms of meningitis, the patient aspirated stomach contents and needed endotracheal intubation. Forty seconds after injection of suxamethonium, bradycardia and cardiac arrest occurred. Attempts to resuscitate the patient were not successful. The serum level of potassium was observed to be 8.4 mequiv L-1. Apart from the reduction in the patient's level of consciousness, there were no signs of motor neurone damage or of any of the other known predisposing conditions for hyperkalaemia following the administration of suxamethonium. It is postulated that her death was caused by hypersensitivity to suxamethonium, associated with her 5-day immobilization.", "entity": "Bradycardia", "aliases": "Bradyarrhythmia Bradyarrhythmias Bradycardia Bradycardias", "definition": "Cardiac arrhythmias that are characterized by excessively slow HEART RATE, usually below 50 beats per minute in human adults. They can be classified broadly into SINOATRIAL NODE dysfunction and ATRIOVENTRICULAR BLOCK.\n    ", "id": "MESH:D001919"}
{"mention": "potassium", "mention_text": "The present report describes a case of cardiac arrest and subsequent death as a result of hyperkalaemia following the use of suxamethonium in a 23-year-old Malawian woman. Five days after the onset of the symptoms of meningitis, the patient aspirated stomach contents and needed endotracheal intubation. Forty seconds after injection of suxamethonium, bradycardia and cardiac arrest occurred. Attempts to resuscitate the patient were not successful. The serum level of potassium was observed to be 8.4 mequiv L-1. Apart from the reduction in the patient's level of consciousness, there were no signs of motor neurone damage or of any of the other known predisposing conditions for hyperkalaemia following the administration of suxamethonium. It is postulated that her death was caused by hypersensitivity to suxamethonium, associated with her 5-day immobilization.", "entity": "Potassium", "aliases": "Potassium", "definition": "An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.\n    ", "id": "MESH:D011188"}
{"mention": "hypersensitivity", "mention_text": "The present report describes a case of cardiac arrest and subsequent death as a result of hyperkalaemia following the use of suxamethonium in a 23-year-old Malawian woman. Five days after the onset of the symptoms of meningitis, the patient aspirated stomach contents and needed endotracheal intubation. Forty seconds after injection of suxamethonium, bradycardia and cardiac arrest occurred. Attempts to resuscitate the patient were not successful. The serum level of potassium was observed to be 8.4 mequiv L-1. Apart from the reduction in the patient's level of consciousness, there were no signs of motor neurone damage or of any of the other known predisposing conditions for hyperkalaemia following the administration of suxamethonium. It is postulated that her death was caused by hypersensitivity to suxamethonium, associated with her 5-day immobilization.", "entity": "Drug Hypersensitivity", "aliases": "Allergies Drug Allergy Hypersensitivities Hypersensitivity", "definition": "Immunologically mediated adverse reactions to medicinal substances used legally or illegally.\n    ", "id": "MESH:D004342"}
{"mention": "mepivacaine", "mention_text": "An unusual toxic reaction to axillary block by mepivacaine with adrenaline.", "entity": "Mepivacaine", "aliases": "3M Brand of Mepivacaine Hydrochloride Abbott Astra AstraZeneca Aventis Braun Mepivicaine Mepivacaina Carbocaine Carbocaïne Clarben Dentsply Hexal Inibsa Isocaine Isogaine Meaverin Mecain Mepihexal Mepivacain Injektopas Mepivacain-Injektopas Monohydrochloride Mepivastesin Novocol Pascoe Polocaine Sanofi Scandicain Scandicaine Scandinibsa Scandonest curasan", "definition": "A local anesthetic that is chemically related to BUPIVACAINE but pharmacologically related to LIDOCAINE. It is indicated for infiltration, nerve block, and epidural anesthesia. Mepivacaine is effective topically only in large doses and therefore should not be used by this route. (From AMA Drug Evaluations, 1994, p168)\n    ", "id": "MESH:D008619"}
{"mention": "adrenaline", "mention_text": "An unusual toxic reaction to axillary block by mepivacaine with adrenaline.", "entity": "Epinephrine", "aliases": "4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-benzenediol Acetate Epinephrine Adrenaline Acid Tartrate Bitartrate Hydrochloride Allergan Brand of Epifrin Hydrogen Epitrate Lyophrin Medihaler-Epi", "definition": "The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.\n    ", "id": "MESH:D004837"}
{"mention": "increase in blood pressure", "mention_text": "An increase in blood pressure, accompanied by atrial fibrillation, agitation, incomprehensible shouts and loss of consciousness, was observed in an elderly, ASA classification group II, cardiovascularly medicated male, 12 min after performance of axillary block with mepivacaine 850 mg containing adrenaline 0.225 mg, for correction of Dupuytren's contracture. After intravenous administration of labetalol, metoprolol and midazolam the patient's condition improved, and 15 min later he woke up. The block was successful and surgery was conducted as scheduled despite persisting atrial fibrillation. Postoperatively, the patient refused DC cardioversion and was treated medically. Both the temporal relationship of events and the response to treatment suggest that a rapid systemic absorption of mepivacaine with adrenaline and/or interaction of these drugs with the patient's cardiovascular medications were responsible for the perioperative complications.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "atrial fibrillation", "mention_text": "An increase in blood pressure, accompanied by atrial fibrillation, agitation, incomprehensible shouts and loss of consciousness, was observed in an elderly, ASA classification group II, cardiovascularly medicated male, 12 min after performance of axillary block with mepivacaine 850 mg containing adrenaline 0.225 mg, for correction of Dupuytren's contracture. After intravenous administration of labetalol, metoprolol and midazolam the patient's condition improved, and 15 min later he woke up. The block was successful and surgery was conducted as scheduled despite persisting atrial fibrillation. Postoperatively, the patient refused DC cardioversion and was treated medically. Both the temporal relationship of events and the response to treatment suggest that a rapid systemic absorption of mepivacaine with adrenaline and/or interaction of these drugs with the patient's cardiovascular medications were responsible for the perioperative complications.", "entity": "Atrial Fibrillation", "aliases": "Atrial Fibrillation Fibrillations Auricular Familial", "definition": "Abnormal cardiac rhythm that is characterized by rapid, uncoordinated firing of electrical impulses in the upper chambers of the heart (HEART ATRIA). In such case, blood cannot be effectively pumped into the lower chambers of the heart (HEART VENTRICLES). It is caused by abnormal impulse generation.\n    ", "id": "MESH:D001281"}
{"mention": "agitation", "mention_text": "An increase in blood pressure, accompanied by atrial fibrillation, agitation, incomprehensible shouts and loss of consciousness, was observed in an elderly, ASA classification group II, cardiovascularly medicated male, 12 min after performance of axillary block with mepivacaine 850 mg containing adrenaline 0.225 mg, for correction of Dupuytren's contracture. After intravenous administration of labetalol, metoprolol and midazolam the patient's condition improved, and 15 min later he woke up. The block was successful and surgery was conducted as scheduled despite persisting atrial fibrillation. Postoperatively, the patient refused DC cardioversion and was treated medically. Both the temporal relationship of events and the response to treatment suggest that a rapid systemic absorption of mepivacaine with adrenaline and/or interaction of these drugs with the patient's cardiovascular medications were responsible for the perioperative complications.", "entity": "Psychomotor Agitation", "aliases": "Agitation Psychomotor Akathisia Excitement Hyperactivity Restlessness", "definition": "A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions.\n    ", "id": "MESH:D011595"}
{"mention": "incomprehensible shouts", "mention_text": "An increase in blood pressure, accompanied by atrial fibrillation, agitation, incomprehensible shouts and loss of consciousness, was observed in an elderly, ASA classification group II, cardiovascularly medicated male, 12 min after performance of axillary block with mepivacaine 850 mg containing adrenaline 0.225 mg, for correction of Dupuytren's contracture. After intravenous administration of labetalol, metoprolol and midazolam the patient's condition improved, and 15 min later he woke up. The block was successful and surgery was conducted as scheduled despite persisting atrial fibrillation. Postoperatively, the patient refused DC cardioversion and was treated medically. Both the temporal relationship of events and the response to treatment suggest that a rapid systemic absorption of mepivacaine with adrenaline and/or interaction of these drugs with the patient's cardiovascular medications were responsible for the perioperative complications.", "entity": "Neurobehavioral Manifestations", "aliases": "Cognitive Manifestation Manifestations Symptom Symptoms Neurobehavioral Signs and", "definition": "Signs and symptoms of higher cortical dysfunction caused by organic conditions. These include certain behavioral alterations and impairments of skills involved in the acquisition, processing, and utilization of knowledge or information.\n    ", "id": "MESH:D019954"}
{"mention": "loss of consciousness", "mention_text": "An increase in blood pressure, accompanied by atrial fibrillation, agitation, incomprehensible shouts and loss of consciousness, was observed in an elderly, ASA classification group II, cardiovascularly medicated male, 12 min after performance of axillary block with mepivacaine 850 mg containing adrenaline 0.225 mg, for correction of Dupuytren's contracture. After intravenous administration of labetalol, metoprolol and midazolam the patient's condition improved, and 15 min later he woke up. The block was successful and surgery was conducted as scheduled despite persisting atrial fibrillation. Postoperatively, the patient refused DC cardioversion and was treated medically. Both the temporal relationship of events and the response to treatment suggest that a rapid systemic absorption of mepivacaine with adrenaline and/or interaction of these drugs with the patient's cardiovascular medications were responsible for the perioperative complications.", "entity": "Unconsciousness", "aliases": "Consciousness Loss of State Unconscious States Unconsciousness", "definition": "Loss of the ability to maintain awareness of self and environment combined with markedly reduced responsiveness to environmental stimuli. (From Adams et al., Principles of Neurology, 6th ed, pp344-5)\n    ", "id": "MESH:D014474"}
{"mention": "mepivacaine", "mention_text": "An increase in blood pressure, accompanied by atrial fibrillation, agitation, incomprehensible shouts and loss of consciousness, was observed in an elderly, ASA classification group II, cardiovascularly medicated male, 12 min after performance of axillary block with mepivacaine 850 mg containing adrenaline 0.225 mg, for correction of Dupuytren's contracture. After intravenous administration of labetalol, metoprolol and midazolam the patient's condition improved, and 15 min later he woke up. The block was successful and surgery was conducted as scheduled despite persisting atrial fibrillation. Postoperatively, the patient refused DC cardioversion and was treated medically. Both the temporal relationship of events and the response to treatment suggest that a rapid systemic absorption of mepivacaine with adrenaline and/or interaction of these drugs with the patient's cardiovascular medications were responsible for the perioperative complications.", "entity": "Mepivacaine", "aliases": "3M Brand of Mepivacaine Hydrochloride Abbott Astra AstraZeneca Aventis Braun Mepivicaine Mepivacaina Carbocaine Carbocaïne Clarben Dentsply Hexal Inibsa Isocaine Isogaine Meaverin Mecain Mepihexal Mepivacain Injektopas Mepivacain-Injektopas Monohydrochloride Mepivastesin Novocol Pascoe Polocaine Sanofi Scandicain Scandicaine Scandinibsa Scandonest curasan", "definition": "A local anesthetic that is chemically related to BUPIVACAINE but pharmacologically related to LIDOCAINE. It is indicated for infiltration, nerve block, and epidural anesthesia. Mepivacaine is effective topically only in large doses and therefore should not be used by this route. (From AMA Drug Evaluations, 1994, p168)\n    ", "id": "MESH:D008619"}
{"mention": "adrenaline", "mention_text": "An increase in blood pressure, accompanied by atrial fibrillation, agitation, incomprehensible shouts and loss of consciousness, was observed in an elderly, ASA classification group II, cardiovascularly medicated male, 12 min after performance of axillary block with mepivacaine 850 mg containing adrenaline 0.225 mg, for correction of Dupuytren's contracture. After intravenous administration of labetalol, metoprolol and midazolam the patient's condition improved, and 15 min later he woke up. The block was successful and surgery was conducted as scheduled despite persisting atrial fibrillation. Postoperatively, the patient refused DC cardioversion and was treated medically. Both the temporal relationship of events and the response to treatment suggest that a rapid systemic absorption of mepivacaine with adrenaline and/or interaction of these drugs with the patient's cardiovascular medications were responsible for the perioperative complications.", "entity": "Epinephrine", "aliases": "4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-benzenediol Acetate Epinephrine Adrenaline Acid Tartrate Bitartrate Hydrochloride Allergan Brand of Epifrin Hydrogen Epitrate Lyophrin Medihaler-Epi", "definition": "The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.\n    ", "id": "MESH:D004837"}
{"mention": "Dupuytren's contracture", "mention_text": "An increase in blood pressure, accompanied by atrial fibrillation, agitation, incomprehensible shouts and loss of consciousness, was observed in an elderly, ASA classification group II, cardiovascularly medicated male, 12 min after performance of axillary block with mepivacaine 850 mg containing adrenaline 0.225 mg, for correction of Dupuytren's contracture. After intravenous administration of labetalol, metoprolol and midazolam the patient's condition improved, and 15 min later he woke up. The block was successful and surgery was conducted as scheduled despite persisting atrial fibrillation. Postoperatively, the patient refused DC cardioversion and was treated medically. Both the temporal relationship of events and the response to treatment suggest that a rapid systemic absorption of mepivacaine with adrenaline and/or interaction of these drugs with the patient's cardiovascular medications were responsible for the perioperative complications.", "entity": "Dupuytren Contracture", "aliases": "Contracture Dupuytren Dupuytren's Disease Dupuytrens", "definition": "A fibromatosis of the palmar fascia characterized by thickening and contracture of the fibrous bands on the palmar surfaces of the hand and fingers. It arises most commonly in men between the ages of 30 and 50.\n    ", "id": "MESH:D004387"}
{"mention": "labetalol", "mention_text": "An increase in blood pressure, accompanied by atrial fibrillation, agitation, incomprehensible shouts and loss of consciousness, was observed in an elderly, ASA classification group II, cardiovascularly medicated male, 12 min after performance of axillary block with mepivacaine 850 mg containing adrenaline 0.225 mg, for correction of Dupuytren's contracture. After intravenous administration of labetalol, metoprolol and midazolam the patient's condition improved, and 15 min later he woke up. The block was successful and surgery was conducted as scheduled despite persisting atrial fibrillation. Postoperatively, the patient refused DC cardioversion and was treated medically. Both the temporal relationship of events and the response to treatment suggest that a rapid systemic absorption of mepivacaine with adrenaline and/or interaction of these drugs with the patient's cardiovascular medications were responsible for the perioperative complications.", "entity": "Labetalol", "aliases": "AH 5158 AH-5158 AH5158 Albetol Alphapharm Brand of Labetalol Hydrochloride Apo Apo-Labetalol ApoLabetalol Apotex Celltech Dilevalol Faro Glaxo Wellcome GlaxoSmithKline Kern (R,R)-Isomer Labetolol Leiras Normodyne Presolol R,R R,R-Labetalol SCH 19927 SCH-19927 SCH19927 Schering Shire Sigma Trandate", "definition": "A salicylamide derivative that is a non-cardioselective blocker of BETA-ADRENERGIC RECEPTORS and ALPHA-1 ADRENERGIC RECEPTORS.\n    ", "id": "MESH:D007741"}
{"mention": "metoprolol", "mention_text": "An increase in blood pressure, accompanied by atrial fibrillation, agitation, incomprehensible shouts and loss of consciousness, was observed in an elderly, ASA classification group II, cardiovascularly medicated male, 12 min after performance of axillary block with mepivacaine 850 mg containing adrenaline 0.225 mg, for correction of Dupuytren's contracture. After intravenous administration of labetalol, metoprolol and midazolam the patient's condition improved, and 15 min later he woke up. The block was successful and surgery was conducted as scheduled despite persisting atrial fibrillation. Postoperatively, the patient refused DC cardioversion and was treated medically. Both the temporal relationship of events and the response to treatment suggest that a rapid systemic absorption of mepivacaine with adrenaline and/or interaction of these drugs with the patient's cardiovascular medications were responsible for the perioperative complications.", "entity": "Metoprolol", "aliases": "AstraZeneca Brand of Metaoprolol Tartrate Seloken Beloc Duriles Beloc-Duriles BelocDuriles Betaloc Astra Betaloc-Astra BetalocAstra Betalok CGP 2175 CGP-2175 CGP2175 H 93 26 93-26 9326 Leiras Metoprolol Succinate or Metoprolol Lopressor Novartis Metprolol Spesicor Spesikor", "definition": "A selective adrenergic beta-1 blocking agent that is commonly used to treat ANGINA PECTORIS; HYPERTENSION; and CARDIAC ARRHYTHMIAS.\n    ", "id": "MESH:D008790"}
{"mention": "midazolam", "mention_text": "An increase in blood pressure, accompanied by atrial fibrillation, agitation, incomprehensible shouts and loss of consciousness, was observed in an elderly, ASA classification group II, cardiovascularly medicated male, 12 min after performance of axillary block with mepivacaine 850 mg containing adrenaline 0.225 mg, for correction of Dupuytren's contracture. After intravenous administration of labetalol, metoprolol and midazolam the patient's condition improved, and 15 min later he woke up. The block was successful and surgery was conducted as scheduled despite persisting atrial fibrillation. Postoperatively, the patient refused DC cardioversion and was treated medically. Both the temporal relationship of events and the response to treatment suggest that a rapid systemic absorption of mepivacaine with adrenaline and/or interaction of these drugs with the patient's cardiovascular medications were responsible for the perioperative complications.", "entity": "Midazolam", "aliases": "Dormicum Hydrochloride Midazolam Maleate Ro 21 3981 21-3981 213981 Versed", "definition": "A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH.\n    ", "id": "MESH:D008874"}
{"mention": "tacrolimus", "mention_text": "Clinical and histopathologic examination of renal allografts treated with tacrolimus (FK506) for at least one year.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "FK506", "mention_text": "Clinical and histopathologic examination of renal allografts treated with tacrolimus (FK506) for at least one year.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "tacrolimus", "mention_text": "BACKGROUND: We clinically and pathologically analyzed renal allografts from 1 9 renal transplant patients treated with tacrolimus (FK506) for more than 1 year. METHODS: Twenty-six renal allograft biopsy specimens from 1 9 renal transplant patients who underwent transplantations between 1991 and 1993 were evaluated. Thirteen biopsies were performed from stable functioning renal allografts with informed consent (nonepisode biopsy) and the other 13 were from dysfunctional renal allografts with a clinical indication for biopsy (episode biopsy). RESULTS: The main pathologic diagnoses (some overlap) were acute rejection (AR; n = 4), chronic rejection (CR; n=5), AR+CR (n =4), recurrent IgA nephropathy (n =5), normal findings (n =2), minimal-type chronic FK506 nephropathy (n = 9), and mild-type FK506 nephropathy (n = 11). Of the nonepisode biopsies, 7 and 4 biopsies showed minimal-type and mild-type chronic FK506 nephropathy, respectively. Chronic FK506 nephropathy consisted of rough and foamy tubular vacuolization (5 biopsies), arteriolopathy (angiodegeneration of the arteriolar wall; 20 biopsies), focal segmental glomerulosclerosis (4 biopsies) and the striped form of interstitial fibrosis (11 biopsies). The serum creatinine levels of patients in the mild-type chronic FK506 nephropathy group, which included 7 episode biopsies, were statistically higher than those in the minimum-type chronic FK506-nephropathy group (P< 0.001). CONCLUSIONS: This study demonstrates that chronic FK506 nephropathy consists primarily of arteriolopathy manifesting as insudative hyalinosis of the arteriolar wall, and suggests that mild-type chronic FK506 nephropathy is a condition which may lead to deterioration of renal allograft function.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "FK506", "mention_text": "BACKGROUND: We clinically and pathologically analyzed renal allografts from 1 9 renal transplant patients treated with tacrolimus (FK506) for more than 1 year. METHODS: Twenty-six renal allograft biopsy specimens from 1 9 renal transplant patients who underwent transplantations between 1991 and 1993 were evaluated. Thirteen biopsies were performed from stable functioning renal allografts with informed consent (nonepisode biopsy) and the other 13 were from dysfunctional renal allografts with a clinical indication for biopsy (episode biopsy). RESULTS: The main pathologic diagnoses (some overlap) were acute rejection (AR; n = 4), chronic rejection (CR; n=5), AR+CR (n =4), recurrent IgA nephropathy (n =5), normal findings (n =2), minimal-type chronic FK506 nephropathy (n = 9), and mild-type FK506 nephropathy (n = 11). Of the nonepisode biopsies, 7 and 4 biopsies showed minimal-type and mild-type chronic FK506 nephropathy, respectively. Chronic FK506 nephropathy consisted of rough and foamy tubular vacuolization (5 biopsies), arteriolopathy (angiodegeneration of the arteriolar wall; 20 biopsies), focal segmental glomerulosclerosis (4 biopsies) and the striped form of interstitial fibrosis (11 biopsies). The serum creatinine levels of patients in the mild-type chronic FK506 nephropathy group, which included 7 episode biopsies, were statistically higher than those in the minimum-type chronic FK506-nephropathy group (P< 0.001). CONCLUSIONS: This study demonstrates that chronic FK506 nephropathy consists primarily of arteriolopathy manifesting as insudative hyalinosis of the arteriolar wall, and suggests that mild-type chronic FK506 nephropathy is a condition which may lead to deterioration of renal allograft function.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "IgA nephropathy", "mention_text": "BACKGROUND: We clinically and pathologically analyzed renal allografts from 1 9 renal transplant patients treated with tacrolimus (FK506) for more than 1 year. METHODS: Twenty-six renal allograft biopsy specimens from 1 9 renal transplant patients who underwent transplantations between 1991 and 1993 were evaluated. Thirteen biopsies were performed from stable functioning renal allografts with informed consent (nonepisode biopsy) and the other 13 were from dysfunctional renal allografts with a clinical indication for biopsy (episode biopsy). RESULTS: The main pathologic diagnoses (some overlap) were acute rejection (AR; n = 4), chronic rejection (CR; n=5), AR+CR (n =4), recurrent IgA nephropathy (n =5), normal findings (n =2), minimal-type chronic FK506 nephropathy (n = 9), and mild-type FK506 nephropathy (n = 11). Of the nonepisode biopsies, 7 and 4 biopsies showed minimal-type and mild-type chronic FK506 nephropathy, respectively. Chronic FK506 nephropathy consisted of rough and foamy tubular vacuolization (5 biopsies), arteriolopathy (angiodegeneration of the arteriolar wall; 20 biopsies), focal segmental glomerulosclerosis (4 biopsies) and the striped form of interstitial fibrosis (11 biopsies). The serum creatinine levels of patients in the mild-type chronic FK506 nephropathy group, which included 7 episode biopsies, were statistically higher than those in the minimum-type chronic FK506-nephropathy group (P< 0.001). CONCLUSIONS: This study demonstrates that chronic FK506 nephropathy consists primarily of arteriolopathy manifesting as insudative hyalinosis of the arteriolar wall, and suggests that mild-type chronic FK506 nephropathy is a condition which may lead to deterioration of renal allograft function.", "entity": "Glomerulonephritis, IGA", "aliases": "Berger Disease Berger's Bergers Glomerulonephritides IGA Glomerulonephritis Nephropathy Type Nephritis Iga 1 Immunoglobulin A", "definition": "A chronic form of glomerulonephritis characterized by deposits of predominantly IMMUNOGLOBULIN A in the mesangial area (GLOMERULAR MESANGIUM). Deposits of COMPLEMENT C3 and IMMUNOGLOBULIN G are also often found. Clinical features may progress from asymptomatic HEMATURIA to END-STAGE KIDNEY DISEASE.\n    ", "id": "MESH:D005922"}
{"mention": "nephropathy", "mention_text": "BACKGROUND: We clinically and pathologically analyzed renal allografts from 1 9 renal transplant patients treated with tacrolimus (FK506) for more than 1 year. METHODS: Twenty-six renal allograft biopsy specimens from 1 9 renal transplant patients who underwent transplantations between 1991 and 1993 were evaluated. Thirteen biopsies were performed from stable functioning renal allografts with informed consent (nonepisode biopsy) and the other 13 were from dysfunctional renal allografts with a clinical indication for biopsy (episode biopsy). RESULTS: The main pathologic diagnoses (some overlap) were acute rejection (AR; n = 4), chronic rejection (CR; n=5), AR+CR (n =4), recurrent IgA nephropathy (n =5), normal findings (n =2), minimal-type chronic FK506 nephropathy (n = 9), and mild-type FK506 nephropathy (n = 11). Of the nonepisode biopsies, 7 and 4 biopsies showed minimal-type and mild-type chronic FK506 nephropathy, respectively. Chronic FK506 nephropathy consisted of rough and foamy tubular vacuolization (5 biopsies), arteriolopathy (angiodegeneration of the arteriolar wall; 20 biopsies), focal segmental glomerulosclerosis (4 biopsies) and the striped form of interstitial fibrosis (11 biopsies). The serum creatinine levels of patients in the mild-type chronic FK506 nephropathy group, which included 7 episode biopsies, were statistically higher than those in the minimum-type chronic FK506-nephropathy group (P< 0.001). CONCLUSIONS: This study demonstrates that chronic FK506 nephropathy consists primarily of arteriolopathy manifesting as insudative hyalinosis of the arteriolar wall, and suggests that mild-type chronic FK506 nephropathy is a condition which may lead to deterioration of renal allograft function.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "focal segmental glomerulosclerosis", "mention_text": "BACKGROUND: We clinically and pathologically analyzed renal allografts from 1 9 renal transplant patients treated with tacrolimus (FK506) for more than 1 year. METHODS: Twenty-six renal allograft biopsy specimens from 1 9 renal transplant patients who underwent transplantations between 1991 and 1993 were evaluated. Thirteen biopsies were performed from stable functioning renal allografts with informed consent (nonepisode biopsy) and the other 13 were from dysfunctional renal allografts with a clinical indication for biopsy (episode biopsy). RESULTS: The main pathologic diagnoses (some overlap) were acute rejection (AR; n = 4), chronic rejection (CR; n=5), AR+CR (n =4), recurrent IgA nephropathy (n =5), normal findings (n =2), minimal-type chronic FK506 nephropathy (n = 9), and mild-type FK506 nephropathy (n = 11). Of the nonepisode biopsies, 7 and 4 biopsies showed minimal-type and mild-type chronic FK506 nephropathy, respectively. Chronic FK506 nephropathy consisted of rough and foamy tubular vacuolization (5 biopsies), arteriolopathy (angiodegeneration of the arteriolar wall; 20 biopsies), focal segmental glomerulosclerosis (4 biopsies) and the striped form of interstitial fibrosis (11 biopsies). The serum creatinine levels of patients in the mild-type chronic FK506 nephropathy group, which included 7 episode biopsies, were statistically higher than those in the minimum-type chronic FK506-nephropathy group (P< 0.001). CONCLUSIONS: This study demonstrates that chronic FK506 nephropathy consists primarily of arteriolopathy manifesting as insudative hyalinosis of the arteriolar wall, and suggests that mild-type chronic FK506 nephropathy is a condition which may lead to deterioration of renal allograft function.", "entity": "Glomerulosclerosis, Focal Segmental", "aliases": "Focal Glomerulosclerosis Sclerosing Glomerulonephritides Glomerulonephritis Segmental Glomerular Hyalinosis", "definition": "A clinicopathological syndrome or diagnostic term for a type of glomerular injury that has multiple causes, primary or secondary. Clinical features include PROTEINURIA, reduced GLOMERULAR FILTRATION RATE, and EDEMA. Kidney biopsy initially indicates focal segmental glomerular consolidation (hyalinosis) or scarring which can progress to globally sclerotic glomeruli leading to eventual KIDNEY FAILURE.\n    ", "id": "MESH:D005923"}
{"mention": "interstitial fibrosis", "mention_text": "BACKGROUND: We clinically and pathologically analyzed renal allografts from 1 9 renal transplant patients treated with tacrolimus (FK506) for more than 1 year. METHODS: Twenty-six renal allograft biopsy specimens from 1 9 renal transplant patients who underwent transplantations between 1991 and 1993 were evaluated. Thirteen biopsies were performed from stable functioning renal allografts with informed consent (nonepisode biopsy) and the other 13 were from dysfunctional renal allografts with a clinical indication for biopsy (episode biopsy). RESULTS: The main pathologic diagnoses (some overlap) were acute rejection (AR; n = 4), chronic rejection (CR; n=5), AR+CR (n =4), recurrent IgA nephropathy (n =5), normal findings (n =2), minimal-type chronic FK506 nephropathy (n = 9), and mild-type FK506 nephropathy (n = 11). Of the nonepisode biopsies, 7 and 4 biopsies showed minimal-type and mild-type chronic FK506 nephropathy, respectively. Chronic FK506 nephropathy consisted of rough and foamy tubular vacuolization (5 biopsies), arteriolopathy (angiodegeneration of the arteriolar wall; 20 biopsies), focal segmental glomerulosclerosis (4 biopsies) and the striped form of interstitial fibrosis (11 biopsies). The serum creatinine levels of patients in the mild-type chronic FK506 nephropathy group, which included 7 episode biopsies, were statistically higher than those in the minimum-type chronic FK506-nephropathy group (P< 0.001). CONCLUSIONS: This study demonstrates that chronic FK506 nephropathy consists primarily of arteriolopathy manifesting as insudative hyalinosis of the arteriolar wall, and suggests that mild-type chronic FK506 nephropathy is a condition which may lead to deterioration of renal allograft function.", "entity": "Fibrosis", "aliases": "Cirrhosis Fibroses Fibrosis", "definition": "Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.\n    ", "id": "MESH:D005355"}
{"mention": "creatinine", "mention_text": "BACKGROUND: We clinically and pathologically analyzed renal allografts from 1 9 renal transplant patients treated with tacrolimus (FK506) for more than 1 year. METHODS: Twenty-six renal allograft biopsy specimens from 1 9 renal transplant patients who underwent transplantations between 1991 and 1993 were evaluated. Thirteen biopsies were performed from stable functioning renal allografts with informed consent (nonepisode biopsy) and the other 13 were from dysfunctional renal allografts with a clinical indication for biopsy (episode biopsy). RESULTS: The main pathologic diagnoses (some overlap) were acute rejection (AR; n = 4), chronic rejection (CR; n=5), AR+CR (n =4), recurrent IgA nephropathy (n =5), normal findings (n =2), minimal-type chronic FK506 nephropathy (n = 9), and mild-type FK506 nephropathy (n = 11). Of the nonepisode biopsies, 7 and 4 biopsies showed minimal-type and mild-type chronic FK506 nephropathy, respectively. Chronic FK506 nephropathy consisted of rough and foamy tubular vacuolization (5 biopsies), arteriolopathy (angiodegeneration of the arteriolar wall; 20 biopsies), focal segmental glomerulosclerosis (4 biopsies) and the striped form of interstitial fibrosis (11 biopsies). The serum creatinine levels of patients in the mild-type chronic FK506 nephropathy group, which included 7 episode biopsies, were statistically higher than those in the minimum-type chronic FK506-nephropathy group (P< 0.001). CONCLUSIONS: This study demonstrates that chronic FK506 nephropathy consists primarily of arteriolopathy manifesting as insudative hyalinosis of the arteriolar wall, and suggests that mild-type chronic FK506 nephropathy is a condition which may lead to deterioration of renal allograft function.", "entity": "Creatinine", "aliases": "Creatinine Sulfate Salt Krebiozen", "definition": "", "id": "MESH:D003404"}
{"mention": "acetylcholine", "mention_text": "Memory facilitation and stimulation of endogenous nerve growth factor synthesis by the acetylcholine releaser PG-9.", "entity": "Acetylcholine", "aliases": "2-(Acetyloxy)-N,N,N-trimethylethanaminium Acetilcolina Cusi Acetylcholine Bromide Chloride Fluoride Hydroxide Iodide L Tartrate L-Tartrate Perchlorate Picrate (1:1) Sulfate Alcon Brand of Bournonville Bromoacetylcholine Chloroacetylcholine Ciba Vision Iolab Miochol", "definition": "A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.\n    ", "id": "MESH:D000109"}
{"mention": "PG-9", "mention_text": "Memory facilitation and stimulation of endogenous nerve growth factor synthesis by the acetylcholine releaser PG-9.", "entity": "N-methyltropan-3-yl 2-(4-bromophenyl)propionate", "aliases": "N-methyltropan-3-yl 2-(4-bromophenyl)propionate (+)-stereoisomer (+-)-stereoisomer NMT-3-BPP PG 9 cpd PG-9", "definition": "", "id": "MESH:C087567"}
{"mention": "PG-9", "mention_text": "The effects of PG-9 (3alpha-tropyl 2-(p-bromophenyl)propionate), the acetylcholine releaser, on memory processes and nerve growth factor (NGF) synthesis were evaluated. In the mouse passive-avoidance test, PG-9 (10-30 mg/kg, i.p.), administered 20 min before the training session, prevented amnesia induced by both the non selective antimuscarinic drug scopolamine and the M1-selective antagonist S-(-)-ET-126. In the same experimental conditions, PG-9 (5-20 microg per mouse, i.c.v.) was also able to prevent antimuscarine-induced amnesia, demonstrating a central localization of the activity. At the highest effective doses, PG-9 did not produce any collateral symptoms as revealed by the Irwin test, and it did not modify spontaneous motility and inspection activity, as revealed by the hole-board test. PG-9 was also able to increase the amount of NGF secreted in vitro by astrocytes in a dose-dependent manner. The maximal NGF contents obtained by PG-9 were 17.6-fold of the control value. During culture, no morphological changes were found at effective concentrations of PG-9. The current work indicates the ability of PG-9 to induce beneficial effects on cognitive processes and stimulate activity of NGF synthesis in astroglial cells. Therefore, PG-9 could represent a potential useful drug able to improve the function of impaired cognitive processes.", "entity": "N-methyltropan-3-yl 2-(4-bromophenyl)propionate", "aliases": "N-methyltropan-3-yl 2-(4-bromophenyl)propionate (+)-stereoisomer (+-)-stereoisomer NMT-3-BPP PG 9 cpd PG-9", "definition": "", "id": "MESH:C087567"}
{"mention": "3alpha-tropyl 2-(p-bromophenyl)propionate", "mention_text": "The effects of PG-9 (3alpha-tropyl 2-(p-bromophenyl)propionate), the acetylcholine releaser, on memory processes and nerve growth factor (NGF) synthesis were evaluated. In the mouse passive-avoidance test, PG-9 (10-30 mg/kg, i.p.), administered 20 min before the training session, prevented amnesia induced by both the non selective antimuscarinic drug scopolamine and the M1-selective antagonist S-(-)-ET-126. In the same experimental conditions, PG-9 (5-20 microg per mouse, i.c.v.) was also able to prevent antimuscarine-induced amnesia, demonstrating a central localization of the activity. At the highest effective doses, PG-9 did not produce any collateral symptoms as revealed by the Irwin test, and it did not modify spontaneous motility and inspection activity, as revealed by the hole-board test. PG-9 was also able to increase the amount of NGF secreted in vitro by astrocytes in a dose-dependent manner. The maximal NGF contents obtained by PG-9 were 17.6-fold of the control value. During culture, no morphological changes were found at effective concentrations of PG-9. The current work indicates the ability of PG-9 to induce beneficial effects on cognitive processes and stimulate activity of NGF synthesis in astroglial cells. Therefore, PG-9 could represent a potential useful drug able to improve the function of impaired cognitive processes.", "entity": "N-methyltropan-3-yl 2-(4-bromophenyl)propionate", "aliases": "N-methyltropan-3-yl 2-(4-bromophenyl)propionate (+)-stereoisomer (+-)-stereoisomer NMT-3-BPP PG 9 cpd PG-9", "definition": "", "id": "MESH:C087567"}
{"mention": "acetylcholine", "mention_text": "The effects of PG-9 (3alpha-tropyl 2-(p-bromophenyl)propionate), the acetylcholine releaser, on memory processes and nerve growth factor (NGF) synthesis were evaluated. In the mouse passive-avoidance test, PG-9 (10-30 mg/kg, i.p.), administered 20 min before the training session, prevented amnesia induced by both the non selective antimuscarinic drug scopolamine and the M1-selective antagonist S-(-)-ET-126. In the same experimental conditions, PG-9 (5-20 microg per mouse, i.c.v.) was also able to prevent antimuscarine-induced amnesia, demonstrating a central localization of the activity. At the highest effective doses, PG-9 did not produce any collateral symptoms as revealed by the Irwin test, and it did not modify spontaneous motility and inspection activity, as revealed by the hole-board test. PG-9 was also able to increase the amount of NGF secreted in vitro by astrocytes in a dose-dependent manner. The maximal NGF contents obtained by PG-9 were 17.6-fold of the control value. During culture, no morphological changes were found at effective concentrations of PG-9. The current work indicates the ability of PG-9 to induce beneficial effects on cognitive processes and stimulate activity of NGF synthesis in astroglial cells. Therefore, PG-9 could represent a potential useful drug able to improve the function of impaired cognitive processes.", "entity": "Acetylcholine", "aliases": "2-(Acetyloxy)-N,N,N-trimethylethanaminium Acetilcolina Cusi Acetylcholine Bromide Chloride Fluoride Hydroxide Iodide L Tartrate L-Tartrate Perchlorate Picrate (1:1) Sulfate Alcon Brand of Bournonville Bromoacetylcholine Chloroacetylcholine Ciba Vision Iolab Miochol", "definition": "A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.\n    ", "id": "MESH:D000109"}
{"mention": "amnesia", "mention_text": "The effects of PG-9 (3alpha-tropyl 2-(p-bromophenyl)propionate), the acetylcholine releaser, on memory processes and nerve growth factor (NGF) synthesis were evaluated. In the mouse passive-avoidance test, PG-9 (10-30 mg/kg, i.p.), administered 20 min before the training session, prevented amnesia induced by both the non selective antimuscarinic drug scopolamine and the M1-selective antagonist S-(-)-ET-126. In the same experimental conditions, PG-9 (5-20 microg per mouse, i.c.v.) was also able to prevent antimuscarine-induced amnesia, demonstrating a central localization of the activity. At the highest effective doses, PG-9 did not produce any collateral symptoms as revealed by the Irwin test, and it did not modify spontaneous motility and inspection activity, as revealed by the hole-board test. PG-9 was also able to increase the amount of NGF secreted in vitro by astrocytes in a dose-dependent manner. The maximal NGF contents obtained by PG-9 were 17.6-fold of the control value. During culture, no morphological changes were found at effective concentrations of PG-9. The current work indicates the ability of PG-9 to induce beneficial effects on cognitive processes and stimulate activity of NGF synthesis in astroglial cells. Therefore, PG-9 could represent a potential useful drug able to improve the function of impaired cognitive processes.", "entity": "Amnesia", "aliases": "Amnesia Memory Loss Dissociative Global Hysterical Tactile Temporary Amnesia-Memory Losses Amnesias Amnestic State States", "definition": "Pathologic partial or complete loss of the ability to recall past experiences (AMNESIA, RETROGRADE) or to form new memories (AMNESIA, ANTEROGRADE). This condition may be of organic or psychologic origin. Organic forms of amnesia are usually associated with dysfunction of the DIENCEPHALON or HIPPOCAMPUS. (From Adams et al., Principles of Neurology, 6th ed, pp426-7)\n    ", "id": "MESH:D000647"}
{"mention": "scopolamine", "mention_text": "The effects of PG-9 (3alpha-tropyl 2-(p-bromophenyl)propionate), the acetylcholine releaser, on memory processes and nerve growth factor (NGF) synthesis were evaluated. In the mouse passive-avoidance test, PG-9 (10-30 mg/kg, i.p.), administered 20 min before the training session, prevented amnesia induced by both the non selective antimuscarinic drug scopolamine and the M1-selective antagonist S-(-)-ET-126. In the same experimental conditions, PG-9 (5-20 microg per mouse, i.c.v.) was also able to prevent antimuscarine-induced amnesia, demonstrating a central localization of the activity. At the highest effective doses, PG-9 did not produce any collateral symptoms as revealed by the Irwin test, and it did not modify spontaneous motility and inspection activity, as revealed by the hole-board test. PG-9 was also able to increase the amount of NGF secreted in vitro by astrocytes in a dose-dependent manner. The maximal NGF contents obtained by PG-9 were 17.6-fold of the control value. During culture, no morphological changes were found at effective concentrations of PG-9. The current work indicates the ability of PG-9 to induce beneficial effects on cognitive processes and stimulate activity of NGF synthesis in astroglial cells. Therefore, PG-9 could represent a potential useful drug able to improve the function of impaired cognitive processes.", "entity": "Scopolamine Hydrobromide", "aliases": "Alcon Brand of Scopolamine Hydrobromide Boro Scopol Boro-Scopol BoroScopol Bull Cooper Hamilton Hope Hyoscine Inibisa Isopto Kwells Novartis Consumer Health Renaudin Roche Scoburen Scopace Scopoderm TTS Transderm Scop V Transderm-V Travacalm HO Vorigeno Winzer Borate", "definition": "An alkaloid from SOLANACEAE, especially DATURA and SCOPOLIA. Scopolamine and its quaternary derivatives act as antimuscarinics like ATROPINE, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in URINARY INCONTINENCE, in MOTION SICKNESS, as an antispasmodic, and as a mydriatic and cycloplegic.\n    ", "id": "MESH:D012601"}
{"mention": "S-(-)-ET-126", "mention_text": "The effects of PG-9 (3alpha-tropyl 2-(p-bromophenyl)propionate), the acetylcholine releaser, on memory processes and nerve growth factor (NGF) synthesis were evaluated. In the mouse passive-avoidance test, PG-9 (10-30 mg/kg, i.p.), administered 20 min before the training session, prevented amnesia induced by both the non selective antimuscarinic drug scopolamine and the M1-selective antagonist S-(-)-ET-126. In the same experimental conditions, PG-9 (5-20 microg per mouse, i.c.v.) was also able to prevent antimuscarine-induced amnesia, demonstrating a central localization of the activity. At the highest effective doses, PG-9 did not produce any collateral symptoms as revealed by the Irwin test, and it did not modify spontaneous motility and inspection activity, as revealed by the hole-board test. PG-9 was also able to increase the amount of NGF secreted in vitro by astrocytes in a dose-dependent manner. The maximal NGF contents obtained by PG-9 were 17.6-fold of the control value. During culture, no morphological changes were found at effective concentrations of PG-9. The current work indicates the ability of PG-9 to induce beneficial effects on cognitive processes and stimulate activity of NGF synthesis in astroglial cells. Therefore, PG-9 could represent a potential useful drug able to improve the function of impaired cognitive processes.", "entity": "ET 126", "aliases": "ET 126 ET-126 S-(-)-ET S-(-)-alpha-(hydroxymethyl)benzeneacetic acid 1-methyl-4-piperidinyl ester", "definition": "", "id": "MESH:C098725"}
{"mention": "Angioedema", "mention_text": "Angioedema due to ACE inhibitors: common and inadequately diagnosed.", "entity": "Angioedema", "aliases": "Angioedema Angioedemas Angioneurotic Edema Edemas Quincke's Giant Urticaria Urticarias Quincke Quinckes", "definition": "Swelling involving the deep DERMIS, subcutaneous, or submucosal tissues, representing localized EDEMA. Angioedema often occurs in the face, lips, tongue, and larynx.\n    ", "id": "MESH:D000799"}
{"mention": "ACE inhibitors", "mention_text": "Angioedema due to ACE inhibitors: common and inadequately diagnosed.", "entity": "Angiotensin-Converting Enzyme Inhibitors", "aliases": "ACE Inhibitors Angiotensin Converting Enzyme Antagonists I I-Converting Angiotensin-Converting Kininase II", "definition": "A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility.\n    ", "id": "MESH:D000806"}
{"mention": "angioedema", "mention_text": "The estimated incidence of angioedema during angiotensin-converting enzyme (ACE) inhibitor treatment is between 1 and 7 per thousand patients. This potentially serious adverse effect is often preceded by minor manifestations that may serve as a warning.", "entity": "Angioedema", "aliases": "Angioedema Angioedemas Angioneurotic Edema Edemas Quincke's Giant Urticaria Urticarias Quincke Quinckes", "definition": "Swelling involving the deep DERMIS, subcutaneous, or submucosal tissues, representing localized EDEMA. Angioedema often occurs in the face, lips, tongue, and larynx.\n    ", "id": "MESH:D000799"}
{"mention": "angiotensin-converting enzyme (ACE) inhibitor", "mention_text": "The estimated incidence of angioedema during angiotensin-converting enzyme (ACE) inhibitor treatment is between 1 and 7 per thousand patients. This potentially serious adverse effect is often preceded by minor manifestations that may serve as a warning.", "entity": "Angiotensin-Converting Enzyme Inhibitors", "aliases": "ACE Inhibitors Angiotensin Converting Enzyme Antagonists I I-Converting Angiotensin-Converting Kininase II", "definition": "A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility.\n    ", "id": "MESH:D000806"}
{"mention": "atracurium", "mention_text": "A case of recurarization in the recovery room is reported. Accumulation of atracurium in the intravenous line led to recurarization after flushing the line in the recovery room. A respiratory arrest with severe desaturation and bradycardia occurred. Circumstances leading to this event and the mechanisms enabling a neuromuscular blockade to occur, following the administration of a small dose of relaxant, are discussed.", "entity": "Atracurium", "aliases": "33 A 74 Atracurium Besilate Besylate Dibesylate BW 33A BW-33A BW33A Glaxo Wellcome Brand of Pisa Relatrac Tracrium", "definition": "A non-depolarizing neuromuscular blocking agent with short duration of action. Its lack of significant cardiovascular effects and its lack of dependence on good kidney function for elimination provide clinical advantage over alternate non-depolarizing neuromuscular blocking agents.\n    ", "id": "MESH:D001279"}
{"mention": "respiratory arrest", "mention_text": "A case of recurarization in the recovery room is reported. Accumulation of atracurium in the intravenous line led to recurarization after flushing the line in the recovery room. A respiratory arrest with severe desaturation and bradycardia occurred. Circumstances leading to this event and the mechanisms enabling a neuromuscular blockade to occur, following the administration of a small dose of relaxant, are discussed.", "entity": "Respiratory Insufficiency", "aliases": "Depressions Ventilatory Respiratory Depression Failure Insufficiency", "definition": "Failure to adequately provide oxygen to cells of the body and to remove excess carbon dioxide from them. (Stedman, 25th ed)\n    ", "id": "MESH:D012131"}
{"mention": "desaturation", "mention_text": "A case of recurarization in the recovery room is reported. Accumulation of atracurium in the intravenous line led to recurarization after flushing the line in the recovery room. A respiratory arrest with severe desaturation and bradycardia occurred. Circumstances leading to this event and the mechanisms enabling a neuromuscular blockade to occur, following the administration of a small dose of relaxant, are discussed.", "entity": "Apnea", "aliases": "Apnea Apneas", "definition": "A transient absence of spontaneous respiration.\n    ", "id": "MESH:D001049"}
{"mention": "bradycardia", "mention_text": "A case of recurarization in the recovery room is reported. Accumulation of atracurium in the intravenous line led to recurarization after flushing the line in the recovery room. A respiratory arrest with severe desaturation and bradycardia occurred. Circumstances leading to this event and the mechanisms enabling a neuromuscular blockade to occur, following the administration of a small dose of relaxant, are discussed.", "entity": "Bradycardia", "aliases": "Bradyarrhythmia Bradyarrhythmias Bradycardia Bradycardias", "definition": "Cardiac arrhythmias that are characterized by excessively slow HEART RATE, usually below 50 beats per minute in human adults. They can be classified broadly into SINOATRIAL NODE dysfunction and ATRIOVENTRICULAR BLOCK.\n    ", "id": "MESH:D001919"}
{"mention": "neuromuscular blockade", "mention_text": "A case of recurarization in the recovery room is reported. Accumulation of atracurium in the intravenous line led to recurarization after flushing the line in the recovery room. A respiratory arrest with severe desaturation and bradycardia occurred. Circumstances leading to this event and the mechanisms enabling a neuromuscular blockade to occur, following the administration of a small dose of relaxant, are discussed.", "entity": "Neuromuscular Manifestations", "aliases": "Disease Manifestation Muscle Manifestations Neuromuscular Signs and Symptoms", "definition": "Signs and symptoms associated with diseases of the muscle, neuromuscular junction, or peripheral nerves.\n    ", "id": "MESH:D020879"}
{"mention": "oral contraceptives", "mention_text": "Recurrent use of newer oral contraceptives and the risk of venous thromboembolism.", "entity": "Contraceptives, Oral", "aliases": "Contraceptives Low-Dose Oral Phasic Low Dose", "definition": "Compounds, usually hormonal, taken orally in order to block ovulation and prevent the occurrence of pregnancy. The hormones are generally estrogen or progesterone or both.\n    ", "id": "MESH:D003276"}
{"mention": "venous thromboembolism", "mention_text": "Recurrent use of newer oral contraceptives and the risk of venous thromboembolism.", "entity": "Venous Thromboembolism", "aliases": "Thromboembolism Venous", "definition": "Obstruction of a vein or VEINS (embolism) by a blood clot (THROMBUS) in the blood stream.\n    ", "id": "MESH:D054556"}
{"mention": "venous thromboembolism", "mention_text": "The epidemiological studies that assessed the risk of venous thromboembolism (VTE) associated with newer oral contraceptives (OC) did not distinguish between patterns of OC use, namely first-time users, repeaters and switchers. Data from a Transnational case-control study were used to assess the risk of VTE for the latter patterns of use, while accounting for duration of use. Over the period 1993-1996, 551 cases of VTE were identified in Germany and the UK along with 2066 controls. Totals of 128 cases and 650 controls were analysed for repeat use and 135 cases and 622 controls for switching patterns. The adjusted rate ratio of VTE for repeat users of third generation OC was 0.6 (95% CI:0.3-1.2) relative to repeat users of second generation pills, whereas it was 1.3 (95% CI:0.7-2.4) for switchers from second to third generation pills relative to switchers from third to second generation pills. We conclude that second and third generation agents are associated with equivalent risks of VTE when the same agent is used repeatedly after interruption periods or when users are switched between the two generations of pills. These analyses suggest that the higher risk observed for the newer OC in other studies may be the result of inadequate comparisons of pill users with different patterns of pill use.", "entity": "Venous Thromboembolism", "aliases": "Thromboembolism Venous", "definition": "Obstruction of a vein or VEINS (embolism) by a blood clot (THROMBUS) in the blood stream.\n    ", "id": "MESH:D054556"}
{"mention": "VTE", "mention_text": "The epidemiological studies that assessed the risk of venous thromboembolism (VTE) associated with newer oral contraceptives (OC) did not distinguish between patterns of OC use, namely first-time users, repeaters and switchers. Data from a Transnational case-control study were used to assess the risk of VTE for the latter patterns of use, while accounting for duration of use. Over the period 1993-1996, 551 cases of VTE were identified in Germany and the UK along with 2066 controls. Totals of 128 cases and 650 controls were analysed for repeat use and 135 cases and 622 controls for switching patterns. The adjusted rate ratio of VTE for repeat users of third generation OC was 0.6 (95% CI:0.3-1.2) relative to repeat users of second generation pills, whereas it was 1.3 (95% CI:0.7-2.4) for switchers from second to third generation pills relative to switchers from third to second generation pills. We conclude that second and third generation agents are associated with equivalent risks of VTE when the same agent is used repeatedly after interruption periods or when users are switched between the two generations of pills. These analyses suggest that the higher risk observed for the newer OC in other studies may be the result of inadequate comparisons of pill users with different patterns of pill use.", "entity": "Venous Thromboembolism", "aliases": "Thromboembolism Venous", "definition": "Obstruction of a vein or VEINS (embolism) by a blood clot (THROMBUS) in the blood stream.\n    ", "id": "MESH:D054556"}
{"mention": "oral contraceptives", "mention_text": "The epidemiological studies that assessed the risk of venous thromboembolism (VTE) associated with newer oral contraceptives (OC) did not distinguish between patterns of OC use, namely first-time users, repeaters and switchers. Data from a Transnational case-control study were used to assess the risk of VTE for the latter patterns of use, while accounting for duration of use. Over the period 1993-1996, 551 cases of VTE were identified in Germany and the UK along with 2066 controls. Totals of 128 cases and 650 controls were analysed for repeat use and 135 cases and 622 controls for switching patterns. The adjusted rate ratio of VTE for repeat users of third generation OC was 0.6 (95% CI:0.3-1.2) relative to repeat users of second generation pills, whereas it was 1.3 (95% CI:0.7-2.4) for switchers from second to third generation pills relative to switchers from third to second generation pills. We conclude that second and third generation agents are associated with equivalent risks of VTE when the same agent is used repeatedly after interruption periods or when users are switched between the two generations of pills. These analyses suggest that the higher risk observed for the newer OC in other studies may be the result of inadequate comparisons of pill users with different patterns of pill use.", "entity": "Contraceptives, Oral", "aliases": "Contraceptives Low-Dose Oral Phasic Low Dose", "definition": "Compounds, usually hormonal, taken orally in order to block ovulation and prevent the occurrence of pregnancy. The hormones are generally estrogen or progesterone or both.\n    ", "id": "MESH:D003276"}
{"mention": "OC", "mention_text": "The epidemiological studies that assessed the risk of venous thromboembolism (VTE) associated with newer oral contraceptives (OC) did not distinguish between patterns of OC use, namely first-time users, repeaters and switchers. Data from a Transnational case-control study were used to assess the risk of VTE for the latter patterns of use, while accounting for duration of use. Over the period 1993-1996, 551 cases of VTE were identified in Germany and the UK along with 2066 controls. Totals of 128 cases and 650 controls were analysed for repeat use and 135 cases and 622 controls for switching patterns. The adjusted rate ratio of VTE for repeat users of third generation OC was 0.6 (95% CI:0.3-1.2) relative to repeat users of second generation pills, whereas it was 1.3 (95% CI:0.7-2.4) for switchers from second to third generation pills relative to switchers from third to second generation pills. We conclude that second and third generation agents are associated with equivalent risks of VTE when the same agent is used repeatedly after interruption periods or when users are switched between the two generations of pills. These analyses suggest that the higher risk observed for the newer OC in other studies may be the result of inadequate comparisons of pill users with different patterns of pill use.", "entity": "Contraceptives, Oral", "aliases": "Contraceptives Low-Dose Oral Phasic Low Dose", "definition": "Compounds, usually hormonal, taken orally in order to block ovulation and prevent the occurrence of pregnancy. The hormones are generally estrogen or progesterone or both.\n    ", "id": "MESH:D003276"}
{"mention": "apomorphine", "mention_text": "Development of apomorphine-induced aggressive behavior: comparison of adult male and female Wistar rats.", "entity": "Apomorphine", "aliases": "Aguettant Brand of Apomorphine Hydrochloride Anhydrous Apokinon Apomorphin Teclapharm Apomorphin-Teclapharm ApomorphinTeclapharm Chloride Hemihydrate Britaject Britannia", "definition": "A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use.\n    ", "id": "MESH:D001058"}
{"mention": "aggressive behavior", "mention_text": "Development of apomorphine-induced aggressive behavior: comparison of adult male and female Wistar rats.", "entity": "Personality Disorders", "aliases": "As If Personality Avoidant Disorder Disorders Impulse Ridden Impulse-Ridden Inadequate Narcissistic", "definition": "A major deviation from normal patterns of behavior.\n    ", "id": "MESH:D010554"}
{"mention": "apomorphine", "mention_text": "The development of apomorphine-induced (1.0 mg/kg s.c. once daily) aggressive behavior of adult male and female Wistar rats obtained from the same breeder was studied in two consecutive sets. In male animals, repeated apomorphine treatment induced a gradual development of aggressive behavior as evidenced by the increased intensity of aggressiveness and shortened latency before the first attack toward the opponent. In female rats, only a weak tendency toward aggressiveness was found. In conclusion, the present study demonstrates gender differences in the development of the apomorphine-induced aggressive behavior and indicates that the female rats do not fill the validation criteria for use in this method.", "entity": "Apomorphine", "aliases": "Aguettant Brand of Apomorphine Hydrochloride Anhydrous Apokinon Apomorphin Teclapharm Apomorphin-Teclapharm ApomorphinTeclapharm Chloride Hemihydrate Britaject Britannia", "definition": "A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use.\n    ", "id": "MESH:D001058"}
{"mention": "aggressive behavior", "mention_text": "The development of apomorphine-induced (1.0 mg/kg s.c. once daily) aggressive behavior of adult male and female Wistar rats obtained from the same breeder was studied in two consecutive sets. In male animals, repeated apomorphine treatment induced a gradual development of aggressive behavior as evidenced by the increased intensity of aggressiveness and shortened latency before the first attack toward the opponent. In female rats, only a weak tendency toward aggressiveness was found. In conclusion, the present study demonstrates gender differences in the development of the apomorphine-induced aggressive behavior and indicates that the female rats do not fill the validation criteria for use in this method.", "entity": "Personality Disorders", "aliases": "As If Personality Avoidant Disorder Disorders Impulse Ridden Impulse-Ridden Inadequate Narcissistic", "definition": "A major deviation from normal patterns of behavior.\n    ", "id": "MESH:D010554"}
{"mention": "aggressiveness", "mention_text": "The development of apomorphine-induced (1.0 mg/kg s.c. once daily) aggressive behavior of adult male and female Wistar rats obtained from the same breeder was studied in two consecutive sets. In male animals, repeated apomorphine treatment induced a gradual development of aggressive behavior as evidenced by the increased intensity of aggressiveness and shortened latency before the first attack toward the opponent. In female rats, only a weak tendency toward aggressiveness was found. In conclusion, the present study demonstrates gender differences in the development of the apomorphine-induced aggressive behavior and indicates that the female rats do not fill the validation criteria for use in this method.", "entity": "Personality Disorders", "aliases": "As If Personality Avoidant Disorder Disorders Impulse Ridden Impulse-Ridden Inadequate Narcissistic", "definition": "A major deviation from normal patterns of behavior.\n    ", "id": "MESH:D010554"}
{"mention": "Serotonergic antidepressants", "mention_text": "Serotonergic antidepressants and urinary incontinence.", "entity": "Serotonin Agents", "aliases": "Agents Serotonergic Serotonin Drugs Effect Serotoninergic Effects", "definition": "Drugs used for their effects on serotonergic systems. Among these are drugs that affect serotonin receptors, the life cycle of serotonin, and the survival of serotonergic neurons.\n    ", "id": "MESH:D018490"}
{"mention": "urinary incontinence", "mention_text": "Serotonergic antidepressants and urinary incontinence.", "entity": "Urinary Incontinence", "aliases": "Incontinence Urinary", "definition": "Involuntary loss of URINE, such as leaking of urine. It is a symptom of various underlying pathological processes. Major types of incontinence include URINARY URGE INCONTINENCE and URINARY STRESS INCONTINENCE.\n    ", "id": "MESH:D014549"}
{"mention": "serotonergic antidepressants", "mention_text": "Many new serotonergic antidepressants have been introduced over the past decade. Although urinary incontinence is listed as one side effect of these drugs in their package inserts there is only one report in the literature. This concerns 2 male patients who experienced incontinence while taking venlafaxine. In the present paper the authors describe 2 female patients who developed incontinence secondary to the selective serotonin reuptake inhibitors paroxetine and sertraline, as well as a third who developed this side effect on venlafaxine. In 2 of the 3 cases the patients were also taking lithium carbonate and beta-blockers, both of which could have contributed to the incontinence. Animal studies suggest that incontinence secondary to serotonergic antidepressants could be mediated by the 5HT4 receptors found on the bladder. Further research is needed to delineate the frequency of this troubling side effect and how best to treat it.", "entity": "Serotonin Agents", "aliases": "Agents Serotonergic Serotonin Drugs Effect Serotoninergic Effects", "definition": "Drugs used for their effects on serotonergic systems. Among these are drugs that affect serotonin receptors, the life cycle of serotonin, and the survival of serotonergic neurons.\n    ", "id": "MESH:D018490"}
{"mention": "urinary incontinence", "mention_text": "Many new serotonergic antidepressants have been introduced over the past decade. Although urinary incontinence is listed as one side effect of these drugs in their package inserts there is only one report in the literature. This concerns 2 male patients who experienced incontinence while taking venlafaxine. In the present paper the authors describe 2 female patients who developed incontinence secondary to the selective serotonin reuptake inhibitors paroxetine and sertraline, as well as a third who developed this side effect on venlafaxine. In 2 of the 3 cases the patients were also taking lithium carbonate and beta-blockers, both of which could have contributed to the incontinence. Animal studies suggest that incontinence secondary to serotonergic antidepressants could be mediated by the 5HT4 receptors found on the bladder. Further research is needed to delineate the frequency of this troubling side effect and how best to treat it.", "entity": "Urinary Incontinence", "aliases": "Incontinence Urinary", "definition": "Involuntary loss of URINE, such as leaking of urine. It is a symptom of various underlying pathological processes. Major types of incontinence include URINARY URGE INCONTINENCE and URINARY STRESS INCONTINENCE.\n    ", "id": "MESH:D014549"}
{"mention": "incontinence", "mention_text": "Many new serotonergic antidepressants have been introduced over the past decade. Although urinary incontinence is listed as one side effect of these drugs in their package inserts there is only one report in the literature. This concerns 2 male patients who experienced incontinence while taking venlafaxine. In the present paper the authors describe 2 female patients who developed incontinence secondary to the selective serotonin reuptake inhibitors paroxetine and sertraline, as well as a third who developed this side effect on venlafaxine. In 2 of the 3 cases the patients were also taking lithium carbonate and beta-blockers, both of which could have contributed to the incontinence. Animal studies suggest that incontinence secondary to serotonergic antidepressants could be mediated by the 5HT4 receptors found on the bladder. Further research is needed to delineate the frequency of this troubling side effect and how best to treat it.", "entity": "Urinary Incontinence", "aliases": "Incontinence Urinary", "definition": "Involuntary loss of URINE, such as leaking of urine. It is a symptom of various underlying pathological processes. Major types of incontinence include URINARY URGE INCONTINENCE and URINARY STRESS INCONTINENCE.\n    ", "id": "MESH:D014549"}
{"mention": "venlafaxine", "mention_text": "Many new serotonergic antidepressants have been introduced over the past decade. Although urinary incontinence is listed as one side effect of these drugs in their package inserts there is only one report in the literature. This concerns 2 male patients who experienced incontinence while taking venlafaxine. In the present paper the authors describe 2 female patients who developed incontinence secondary to the selective serotonin reuptake inhibitors paroxetine and sertraline, as well as a third who developed this side effect on venlafaxine. In 2 of the 3 cases the patients were also taking lithium carbonate and beta-blockers, both of which could have contributed to the incontinence. Animal studies suggest that incontinence secondary to serotonergic antidepressants could be mediated by the 5HT4 receptors found on the bladder. Further research is needed to delineate the frequency of this troubling side effect and how best to treat it.", "entity": "venlafaxine", "aliases": "1-(2-(dimethylamino)-1-(4-methoxyphenyl)ethyl)cyclohexanol HCl Cyclohexanol 1-(2-(dimethylamino)-1-(4-methoxyphenyl)ethyl)- hydrochloride Dobupal Efexor Effexor Trevilor Vandral Wy 45030 Wy-45,030 Wy-45030 sila-venlafaxine venlafaxine", "definition": "", "id": "MESH:C047426"}
{"mention": "serotonin", "mention_text": "Many new serotonergic antidepressants have been introduced over the past decade. Although urinary incontinence is listed as one side effect of these drugs in their package inserts there is only one report in the literature. This concerns 2 male patients who experienced incontinence while taking venlafaxine. In the present paper the authors describe 2 female patients who developed incontinence secondary to the selective serotonin reuptake inhibitors paroxetine and sertraline, as well as a third who developed this side effect on venlafaxine. In 2 of the 3 cases the patients were also taking lithium carbonate and beta-blockers, both of which could have contributed to the incontinence. Animal studies suggest that incontinence secondary to serotonergic antidepressants could be mediated by the 5HT4 receptors found on the bladder. Further research is needed to delineate the frequency of this troubling side effect and how best to treat it.", "entity": "Serotonin", "aliases": "3-(2-Aminoethyl)-1H-indol-5-ol 5 Hydroxytryptamine 5-HT 5-Hydroxytryptamine Enteramine Hippophaine Serotonin", "definition": "A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.\n    ", "id": "MESH:D012701"}
{"mention": "paroxetine", "mention_text": "Many new serotonergic antidepressants have been introduced over the past decade. Although urinary incontinence is listed as one side effect of these drugs in their package inserts there is only one report in the literature. This concerns 2 male patients who experienced incontinence while taking venlafaxine. In the present paper the authors describe 2 female patients who developed incontinence secondary to the selective serotonin reuptake inhibitors paroxetine and sertraline, as well as a third who developed this side effect on venlafaxine. In 2 of the 3 cases the patients were also taking lithium carbonate and beta-blockers, both of which could have contributed to the incontinence. Animal studies suggest that incontinence secondary to serotonergic antidepressants could be mediated by the 5HT4 receptors found on the bladder. Further research is needed to delineate the frequency of this troubling side effect and how best to treat it.", "entity": "Paroxetine", "aliases": "Acetate Paroxetine Anhydrous Hydrochloride Aropax BRL 29060 BRL-29060 BRL29060 FG 7051 FG-7051 FG7051 Hemihydrate Maleate cis-(+)-Isomer cis-(-)-Isomer trans-(+)-Isomer Paxil Seroxat", "definition": "A serotonin uptake inhibitor that is effective in the treatment of depression.\n    ", "id": "MESH:D017374"}
{"mention": "sertraline", "mention_text": "Many new serotonergic antidepressants have been introduced over the past decade. Although urinary incontinence is listed as one side effect of these drugs in their package inserts there is only one report in the literature. This concerns 2 male patients who experienced incontinence while taking venlafaxine. In the present paper the authors describe 2 female patients who developed incontinence secondary to the selective serotonin reuptake inhibitors paroxetine and sertraline, as well as a third who developed this side effect on venlafaxine. In 2 of the 3 cases the patients were also taking lithium carbonate and beta-blockers, both of which could have contributed to the incontinence. Animal studies suggest that incontinence secondary to serotonergic antidepressants could be mediated by the 5HT4 receptors found on the bladder. Further research is needed to delineate the frequency of this troubling side effect and how best to treat it.", "entity": "Sertraline", "aliases": "Altruline Apo Sertraline Apo-Sertraline Apotex Brand of Hydrochloride Aremis Besitran Boehringer Ingelheim Esteve Gen Gen-Sertraline Genpharm Gladem Lacer Lustral Novo Novo-Sertraline Novopharm Parke Davis Pfizer Ratiopharm Rhoxal sertraline Rhoxal-sertraline Rhoxalpharma Roerig Sealdin (1S-cis)-Isomer Zoloft ratio ratio-Sertraline", "definition": "A selective serotonin uptake inhibitor that is used in the treatment of depression.\n    ", "id": "MESH:D020280"}
{"mention": "lithium carbonate", "mention_text": "Many new serotonergic antidepressants have been introduced over the past decade. Although urinary incontinence is listed as one side effect of these drugs in their package inserts there is only one report in the literature. This concerns 2 male patients who experienced incontinence while taking venlafaxine. In the present paper the authors describe 2 female patients who developed incontinence secondary to the selective serotonin reuptake inhibitors paroxetine and sertraline, as well as a third who developed this side effect on venlafaxine. In 2 of the 3 cases the patients were also taking lithium carbonate and beta-blockers, both of which could have contributed to the incontinence. Animal studies suggest that incontinence secondary to serotonergic antidepressants could be mediated by the 5HT4 receptors found on the bladder. Further research is needed to delineate the frequency of this troubling side effect and how best to treat it.", "entity": "Lithium Carbonate", "aliases": "Bicarbonate Lithium CP 15,467 61 CP-15,467-61 CP15,46761 Carbonate Dilithium Eskalith Lithane Lithobid Lithonate Lithotabs Micalith NSC 16895 NSC-16895 NSC16895 Priadel Quilinorm retard Quilinorm-retard Quilinormretard", "definition": "A lithium salt, classified as a mood-stabilizing agent. Lithium ion alters the metabolism of BIOGENIC MONOAMINES in the CENTRAL NERVOUS SYSTEM, and affects multiple neurotransmission systems.\n    ", "id": "MESH:D016651"}
{"mention": "Hypotension", "mention_text": "Hypotension following the initiation of tizanidine in a patient treated with an angiotensin converting enzyme inhibitor for chronic hypertension.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "tizanidine", "mention_text": "Hypotension following the initiation of tizanidine in a patient treated with an angiotensin converting enzyme inhibitor for chronic hypertension.", "entity": "tizanidine", "aliases": "5-chloro-4-(2-imidazolin-2-yl-amino)-2,1,3-benzothiadiazole Acorda brand of tizanidine hydrochloride DS 103-282 Novartis Sanofi Synthelabo Sirdalud Zanaflex monohydrochloride", "definition": "", "id": "MESH:C023754"}
{"mention": "angiotensin", "mention_text": "Hypotension following the initiation of tizanidine in a patient treated with an angiotensin converting enzyme inhibitor for chronic hypertension.", "entity": "Angiotensins", "aliases": "Angiotensin Angiotensins", "definition": "Oligopeptides which are important in the regulation of blood pressure (VASOCONSTRICTION) and fluid homeostasis via the RENIN-ANGIOTENSIN SYSTEM. These include angiotensins derived naturally from precursor ANGIOTENSINOGEN, and those synthesized.\n    ", "id": "MESH:D000809"}
{"mention": "hypertension", "mention_text": "Hypotension following the initiation of tizanidine in a patient treated with an angiotensin converting enzyme inhibitor for chronic hypertension.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "spasticity", "mention_text": "Centrally acting alpha-2 adrenergic agonists are one of several pharmacologic agents used in the treatment of spasticity related to disorders of the central nervous system. In addition to their effects on spasticity, certain adverse cardiorespiratory effects have been reported. Adults chronically treated with angiotensin converting enzyme inhibitors may have a limited ability to respond to hypotension when the sympathetic response is simultaneously blocked. The authors present a 10-year-old boy chronically treated with lisinopril, an angiotensin converting enzyme inhibitor, to control hypertension who developed hypotension following the addition of tizanidine, an alpha-2 agonist, for the treatment of spasticity. The possible interaction of tizanidine and other antihypertensive agents should be kept in mind when prescribing therapy to treat either hypertension or spasticity in such patients.", "entity": "Muscle Spasticity", "aliases": "Clasp Knife Spasticity Clasp-Knife Muscle Spastic", "definition": "A form of muscle hypertonia associated with upper MOTOR NEURON DISEASE. Resistance to passive stretch of a spastic muscle results in minimal initial resistance (a \"free interval\") followed by an incremental increase in muscle tone. Tone increases in proportion to the velocity of stretch. Spasticity is usually accompanied by HYPERREFLEXIA and variable degrees of MUSCLE WEAKNESS. (From Adams et al., Principles of Neurology, 6th ed, p54)\n    ", "id": "MESH:D009128"}
{"mention": "disorders of the central nervous system", "mention_text": "Centrally acting alpha-2 adrenergic agonists are one of several pharmacologic agents used in the treatment of spasticity related to disorders of the central nervous system. In addition to their effects on spasticity, certain adverse cardiorespiratory effects have been reported. Adults chronically treated with angiotensin converting enzyme inhibitors may have a limited ability to respond to hypotension when the sympathetic response is simultaneously blocked. The authors present a 10-year-old boy chronically treated with lisinopril, an angiotensin converting enzyme inhibitor, to control hypertension who developed hypotension following the addition of tizanidine, an alpha-2 agonist, for the treatment of spasticity. The possible interaction of tizanidine and other antihypertensive agents should be kept in mind when prescribing therapy to treat either hypertension or spasticity in such patients.", "entity": "Central Nervous System Diseases", "aliases": "CNS Disease Diseases Central Nervous System Disorders", "definition": "Diseases of any component of the brain (including the cerebral hemispheres, diencephalon, brain stem, and cerebellum) or the spinal cord.\n    ", "id": "MESH:D002493"}
{"mention": "angiotensin", "mention_text": "Centrally acting alpha-2 adrenergic agonists are one of several pharmacologic agents used in the treatment of spasticity related to disorders of the central nervous system. In addition to their effects on spasticity, certain adverse cardiorespiratory effects have been reported. Adults chronically treated with angiotensin converting enzyme inhibitors may have a limited ability to respond to hypotension when the sympathetic response is simultaneously blocked. The authors present a 10-year-old boy chronically treated with lisinopril, an angiotensin converting enzyme inhibitor, to control hypertension who developed hypotension following the addition of tizanidine, an alpha-2 agonist, for the treatment of spasticity. The possible interaction of tizanidine and other antihypertensive agents should be kept in mind when prescribing therapy to treat either hypertension or spasticity in such patients.", "entity": "Angiotensins", "aliases": "Angiotensin Angiotensins", "definition": "Oligopeptides which are important in the regulation of blood pressure (VASOCONSTRICTION) and fluid homeostasis via the RENIN-ANGIOTENSIN SYSTEM. These include angiotensins derived naturally from precursor ANGIOTENSINOGEN, and those synthesized.\n    ", "id": "MESH:D000809"}
{"mention": "hypotension", "mention_text": "Centrally acting alpha-2 adrenergic agonists are one of several pharmacologic agents used in the treatment of spasticity related to disorders of the central nervous system. In addition to their effects on spasticity, certain adverse cardiorespiratory effects have been reported. Adults chronically treated with angiotensin converting enzyme inhibitors may have a limited ability to respond to hypotension when the sympathetic response is simultaneously blocked. The authors present a 10-year-old boy chronically treated with lisinopril, an angiotensin converting enzyme inhibitor, to control hypertension who developed hypotension following the addition of tizanidine, an alpha-2 agonist, for the treatment of spasticity. The possible interaction of tizanidine and other antihypertensive agents should be kept in mind when prescribing therapy to treat either hypertension or spasticity in such patients.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "lisinopril", "mention_text": "Centrally acting alpha-2 adrenergic agonists are one of several pharmacologic agents used in the treatment of spasticity related to disorders of the central nervous system. In addition to their effects on spasticity, certain adverse cardiorespiratory effects have been reported. Adults chronically treated with angiotensin converting enzyme inhibitors may have a limited ability to respond to hypotension when the sympathetic response is simultaneously blocked. The authors present a 10-year-old boy chronically treated with lisinopril, an angiotensin converting enzyme inhibitor, to control hypertension who developed hypotension following the addition of tizanidine, an alpha-2 agonist, for the treatment of spasticity. The possible interaction of tizanidine and other antihypertensive agents should be kept in mind when prescribing therapy to treat either hypertension or spasticity in such patients.", "entity": "Lisinopril", "aliases": "Lisinopril Maleate (1:1) Sulfate (1:2) Lysinopril MK-521 Prinivil Zestril", "definition": "One of the ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACE inhibitors), orally active, that has been used in the treatment of hypertension and congestive heart failure.\n    ", "id": "MESH:D017706"}
{"mention": "hypertension", "mention_text": "Centrally acting alpha-2 adrenergic agonists are one of several pharmacologic agents used in the treatment of spasticity related to disorders of the central nervous system. In addition to their effects on spasticity, certain adverse cardiorespiratory effects have been reported. Adults chronically treated with angiotensin converting enzyme inhibitors may have a limited ability to respond to hypotension when the sympathetic response is simultaneously blocked. The authors present a 10-year-old boy chronically treated with lisinopril, an angiotensin converting enzyme inhibitor, to control hypertension who developed hypotension following the addition of tizanidine, an alpha-2 agonist, for the treatment of spasticity. The possible interaction of tizanidine and other antihypertensive agents should be kept in mind when prescribing therapy to treat either hypertension or spasticity in such patients.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "tizanidine", "mention_text": "Centrally acting alpha-2 adrenergic agonists are one of several pharmacologic agents used in the treatment of spasticity related to disorders of the central nervous system. In addition to their effects on spasticity, certain adverse cardiorespiratory effects have been reported. Adults chronically treated with angiotensin converting enzyme inhibitors may have a limited ability to respond to hypotension when the sympathetic response is simultaneously blocked. The authors present a 10-year-old boy chronically treated with lisinopril, an angiotensin converting enzyme inhibitor, to control hypertension who developed hypotension following the addition of tizanidine, an alpha-2 agonist, for the treatment of spasticity. The possible interaction of tizanidine and other antihypertensive agents should be kept in mind when prescribing therapy to treat either hypertension or spasticity in such patients.", "entity": "tizanidine", "aliases": "5-chloro-4-(2-imidazolin-2-yl-amino)-2,1,3-benzothiadiazole Acorda brand of tizanidine hydrochloride DS 103-282 Novartis Sanofi Synthelabo Sirdalud Zanaflex monohydrochloride", "definition": "", "id": "MESH:C023754"}
{"mention": "kidney disease", "mention_text": "Peritubular capillary basement membrane reduplication in allografts and native kidney disease: a clinicopathologic study of 278 consecutive renal specimens.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "transplant glomerulopathy", "mention_text": "BACKGROUND: An association has been found between transplant glomerulopathy (TG) and reduplication of peritubular capillary basement membranes (PTCR). Although such an association is of practical and theoretical importance, only one prospective study has tried to confirm it. METHODS: We examined 278 consecutive renal specimens (from 135 transplants and 143 native kidneys) for ultrastructural evidence of PTCR. In addition to renal allografts with TG, we also examined grafts with acute rejection, recurrent glomerulonephritis, chronic allograft nephropathy and stable grafts (\"protocol biopsies\"). Native kidney specimens included a wide range of glomerulopathies as well as cases of thrombotic microangiopathy, malignant hypertension, acute interstitial nephritis, and acute tubular necrosis. RESULTS: We found PTCR in 14 of 15 cases of TG, in 7 transplant biopsy specimens without TG, and in 13 of 143 native kidney biopsy specimens. These 13 included cases of malignant hypertension, thrombotic microangiopathy, lupus nephritis, Henoch-Schonlein nephritis, crescentic glomerulonephritis, and cocaine-related acute renal failure. Mild PTCR in allografts without TG did not predict renal failure or significant proteinuria after follow-up periods of between 3 months and 1 year. CONCLUSIONS: We conclude that in transplants, there is a strong association between well-developed PTCR and TG, while the significance of mild PTCR and its predictive value in the absence of TG is unclear. PTCR also occurs in certain native kidney diseases, though the association is not as strong as that for TG. We suggest that repeated endothelial injury, including immunologic injury, may be the cause of this lesion both in allografts and native kidneys.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "TG", "mention_text": "BACKGROUND: An association has been found between transplant glomerulopathy (TG) and reduplication of peritubular capillary basement membranes (PTCR). Although such an association is of practical and theoretical importance, only one prospective study has tried to confirm it. METHODS: We examined 278 consecutive renal specimens (from 135 transplants and 143 native kidneys) for ultrastructural evidence of PTCR. In addition to renal allografts with TG, we also examined grafts with acute rejection, recurrent glomerulonephritis, chronic allograft nephropathy and stable grafts (\"protocol biopsies\"). Native kidney specimens included a wide range of glomerulopathies as well as cases of thrombotic microangiopathy, malignant hypertension, acute interstitial nephritis, and acute tubular necrosis. RESULTS: We found PTCR in 14 of 15 cases of TG, in 7 transplant biopsy specimens without TG, and in 13 of 143 native kidney biopsy specimens. These 13 included cases of malignant hypertension, thrombotic microangiopathy, lupus nephritis, Henoch-Schonlein nephritis, crescentic glomerulonephritis, and cocaine-related acute renal failure. Mild PTCR in allografts without TG did not predict renal failure or significant proteinuria after follow-up periods of between 3 months and 1 year. CONCLUSIONS: We conclude that in transplants, there is a strong association between well-developed PTCR and TG, while the significance of mild PTCR and its predictive value in the absence of TG is unclear. PTCR also occurs in certain native kidney diseases, though the association is not as strong as that for TG. We suggest that repeated endothelial injury, including immunologic injury, may be the cause of this lesion both in allografts and native kidneys.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "glomerulonephritis", "mention_text": "BACKGROUND: An association has been found between transplant glomerulopathy (TG) and reduplication of peritubular capillary basement membranes (PTCR). Although such an association is of practical and theoretical importance, only one prospective study has tried to confirm it. METHODS: We examined 278 consecutive renal specimens (from 135 transplants and 143 native kidneys) for ultrastructural evidence of PTCR. In addition to renal allografts with TG, we also examined grafts with acute rejection, recurrent glomerulonephritis, chronic allograft nephropathy and stable grafts (\"protocol biopsies\"). Native kidney specimens included a wide range of glomerulopathies as well as cases of thrombotic microangiopathy, malignant hypertension, acute interstitial nephritis, and acute tubular necrosis. RESULTS: We found PTCR in 14 of 15 cases of TG, in 7 transplant biopsy specimens without TG, and in 13 of 143 native kidney biopsy specimens. These 13 included cases of malignant hypertension, thrombotic microangiopathy, lupus nephritis, Henoch-Schonlein nephritis, crescentic glomerulonephritis, and cocaine-related acute renal failure. Mild PTCR in allografts without TG did not predict renal failure or significant proteinuria after follow-up periods of between 3 months and 1 year. CONCLUSIONS: We conclude that in transplants, there is a strong association between well-developed PTCR and TG, while the significance of mild PTCR and its predictive value in the absence of TG is unclear. PTCR also occurs in certain native kidney diseases, though the association is not as strong as that for TG. We suggest that repeated endothelial injury, including immunologic injury, may be the cause of this lesion both in allografts and native kidneys.", "entity": "Glomerulonephritis", "aliases": "Bright Disease Glomerulonephritides Glomerulonephritis", "definition": "Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.\n    ", "id": "MESH:D005921"}
{"mention": "chronic allograft nephropathy", "mention_text": "BACKGROUND: An association has been found between transplant glomerulopathy (TG) and reduplication of peritubular capillary basement membranes (PTCR). Although such an association is of practical and theoretical importance, only one prospective study has tried to confirm it. METHODS: We examined 278 consecutive renal specimens (from 135 transplants and 143 native kidneys) for ultrastructural evidence of PTCR. In addition to renal allografts with TG, we also examined grafts with acute rejection, recurrent glomerulonephritis, chronic allograft nephropathy and stable grafts (\"protocol biopsies\"). Native kidney specimens included a wide range of glomerulopathies as well as cases of thrombotic microangiopathy, malignant hypertension, acute interstitial nephritis, and acute tubular necrosis. RESULTS: We found PTCR in 14 of 15 cases of TG, in 7 transplant biopsy specimens without TG, and in 13 of 143 native kidney biopsy specimens. These 13 included cases of malignant hypertension, thrombotic microangiopathy, lupus nephritis, Henoch-Schonlein nephritis, crescentic glomerulonephritis, and cocaine-related acute renal failure. Mild PTCR in allografts without TG did not predict renal failure or significant proteinuria after follow-up periods of between 3 months and 1 year. CONCLUSIONS: We conclude that in transplants, there is a strong association between well-developed PTCR and TG, while the significance of mild PTCR and its predictive value in the absence of TG is unclear. PTCR also occurs in certain native kidney diseases, though the association is not as strong as that for TG. We suggest that repeated endothelial injury, including immunologic injury, may be the cause of this lesion both in allografts and native kidneys.", "entity": "Renal Insufficiency, Chronic", "aliases": "Chronic Kidney Disease Diseases Insufficiencies Insufficiency Renal", "definition": "Conditions in which the KIDNEYS perform below the normal level for more than three months. Chronic kidney insufficiency is classified by five stages according to the decline in GLOMERULAR FILTRATION RATE and the degree of kidney damage (as measured by the level of PROTEINURIA). The most severe form is the end-stage renal disease (CHRONIC KIDNEY FAILURE). (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002)\n    ", "id": "MESH:D051436"}
{"mention": "glomerulopathies", "mention_text": "BACKGROUND: An association has been found between transplant glomerulopathy (TG) and reduplication of peritubular capillary basement membranes (PTCR). Although such an association is of practical and theoretical importance, only one prospective study has tried to confirm it. METHODS: We examined 278 consecutive renal specimens (from 135 transplants and 143 native kidneys) for ultrastructural evidence of PTCR. In addition to renal allografts with TG, we also examined grafts with acute rejection, recurrent glomerulonephritis, chronic allograft nephropathy and stable grafts (\"protocol biopsies\"). Native kidney specimens included a wide range of glomerulopathies as well as cases of thrombotic microangiopathy, malignant hypertension, acute interstitial nephritis, and acute tubular necrosis. RESULTS: We found PTCR in 14 of 15 cases of TG, in 7 transplant biopsy specimens without TG, and in 13 of 143 native kidney biopsy specimens. These 13 included cases of malignant hypertension, thrombotic microangiopathy, lupus nephritis, Henoch-Schonlein nephritis, crescentic glomerulonephritis, and cocaine-related acute renal failure. Mild PTCR in allografts without TG did not predict renal failure or significant proteinuria after follow-up periods of between 3 months and 1 year. CONCLUSIONS: We conclude that in transplants, there is a strong association between well-developed PTCR and TG, while the significance of mild PTCR and its predictive value in the absence of TG is unclear. PTCR also occurs in certain native kidney diseases, though the association is not as strong as that for TG. We suggest that repeated endothelial injury, including immunologic injury, may be the cause of this lesion both in allografts and native kidneys.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "thrombotic microangiopathy", "mention_text": "BACKGROUND: An association has been found between transplant glomerulopathy (TG) and reduplication of peritubular capillary basement membranes (PTCR). Although such an association is of practical and theoretical importance, only one prospective study has tried to confirm it. METHODS: We examined 278 consecutive renal specimens (from 135 transplants and 143 native kidneys) for ultrastructural evidence of PTCR. In addition to renal allografts with TG, we also examined grafts with acute rejection, recurrent glomerulonephritis, chronic allograft nephropathy and stable grafts (\"protocol biopsies\"). Native kidney specimens included a wide range of glomerulopathies as well as cases of thrombotic microangiopathy, malignant hypertension, acute interstitial nephritis, and acute tubular necrosis. RESULTS: We found PTCR in 14 of 15 cases of TG, in 7 transplant biopsy specimens without TG, and in 13 of 143 native kidney biopsy specimens. These 13 included cases of malignant hypertension, thrombotic microangiopathy, lupus nephritis, Henoch-Schonlein nephritis, crescentic glomerulonephritis, and cocaine-related acute renal failure. Mild PTCR in allografts without TG did not predict renal failure or significant proteinuria after follow-up periods of between 3 months and 1 year. CONCLUSIONS: We conclude that in transplants, there is a strong association between well-developed PTCR and TG, while the significance of mild PTCR and its predictive value in the absence of TG is unclear. PTCR also occurs in certain native kidney diseases, though the association is not as strong as that for TG. We suggest that repeated endothelial injury, including immunologic injury, may be the cause of this lesion both in allografts and native kidneys.", "entity": "Thrombotic Microangiopathies", "aliases": "Microangiopathies Thrombotic Microangiopathy", "definition": "Diseases that result in THROMBOSIS in MICROVASCULATURE. The two most prominent diseases are PURPURA, THROMBOTIC THROMBOCYTOPENIC; and HEMOLYTIC-UREMIC SYNDROME. Multiple etiological factors include VASCULAR ENDOTHELIAL CELL damage due to SHIGA TOXIN; FACTOR H deficiency; and aberrant VON WILLEBRAND FACTOR formation.\n    ", "id": "MESH:D057049"}
{"mention": "malignant hypertension", "mention_text": "BACKGROUND: An association has been found between transplant glomerulopathy (TG) and reduplication of peritubular capillary basement membranes (PTCR). Although such an association is of practical and theoretical importance, only one prospective study has tried to confirm it. METHODS: We examined 278 consecutive renal specimens (from 135 transplants and 143 native kidneys) for ultrastructural evidence of PTCR. In addition to renal allografts with TG, we also examined grafts with acute rejection, recurrent glomerulonephritis, chronic allograft nephropathy and stable grafts (\"protocol biopsies\"). Native kidney specimens included a wide range of glomerulopathies as well as cases of thrombotic microangiopathy, malignant hypertension, acute interstitial nephritis, and acute tubular necrosis. RESULTS: We found PTCR in 14 of 15 cases of TG, in 7 transplant biopsy specimens without TG, and in 13 of 143 native kidney biopsy specimens. These 13 included cases of malignant hypertension, thrombotic microangiopathy, lupus nephritis, Henoch-Schonlein nephritis, crescentic glomerulonephritis, and cocaine-related acute renal failure. Mild PTCR in allografts without TG did not predict renal failure or significant proteinuria after follow-up periods of between 3 months and 1 year. CONCLUSIONS: We conclude that in transplants, there is a strong association between well-developed PTCR and TG, while the significance of mild PTCR and its predictive value in the absence of TG is unclear. PTCR also occurs in certain native kidney diseases, though the association is not as strong as that for TG. We suggest that repeated endothelial injury, including immunologic injury, may be the cause of this lesion both in allografts and native kidneys.", "entity": "Hypertension, Malignant", "aliases": "Hypertension Malignant", "definition": "A condition of markedly elevated BLOOD PRESSURE with DIASTOLIC PRESSURE usually greater than 120 mm Hg. Malignant hypertension is characterized by widespread vascular damage, PAPILLEDEMA, retinopathy, HYPERTENSIVE ENCEPHALOPATHY, and renal dysfunction.\n    ", "id": "MESH:D006974"}
{"mention": "interstitial nephritis", "mention_text": "BACKGROUND: An association has been found between transplant glomerulopathy (TG) and reduplication of peritubular capillary basement membranes (PTCR). Although such an association is of practical and theoretical importance, only one prospective study has tried to confirm it. METHODS: We examined 278 consecutive renal specimens (from 135 transplants and 143 native kidneys) for ultrastructural evidence of PTCR. In addition to renal allografts with TG, we also examined grafts with acute rejection, recurrent glomerulonephritis, chronic allograft nephropathy and stable grafts (\"protocol biopsies\"). Native kidney specimens included a wide range of glomerulopathies as well as cases of thrombotic microangiopathy, malignant hypertension, acute interstitial nephritis, and acute tubular necrosis. RESULTS: We found PTCR in 14 of 15 cases of TG, in 7 transplant biopsy specimens without TG, and in 13 of 143 native kidney biopsy specimens. These 13 included cases of malignant hypertension, thrombotic microangiopathy, lupus nephritis, Henoch-Schonlein nephritis, crescentic glomerulonephritis, and cocaine-related acute renal failure. Mild PTCR in allografts without TG did not predict renal failure or significant proteinuria after follow-up periods of between 3 months and 1 year. CONCLUSIONS: We conclude that in transplants, there is a strong association between well-developed PTCR and TG, while the significance of mild PTCR and its predictive value in the absence of TG is unclear. PTCR also occurs in certain native kidney diseases, though the association is not as strong as that for TG. We suggest that repeated endothelial injury, including immunologic injury, may be the cause of this lesion both in allografts and native kidneys.", "entity": "Nephritis, Interstitial", "aliases": "Interstitial Nephritides Nephritis Tubulointerstitial", "definition": "Inflammation of the interstitial tissue of the kidney. This term is generally used for primary inflammation of KIDNEY TUBULES and/or surrounding interstitium. For primary inflammation of glomerular interstitium, see GLOMERULONEPHRITIS. Infiltration of the inflammatory cells into the interstitial compartment results in EDEMA, increased spaces between the tubules, and tubular renal dysfunction.\n    ", "id": "MESH:D009395"}
{"mention": "acute tubular necrosis", "mention_text": "BACKGROUND: An association has been found between transplant glomerulopathy (TG) and reduplication of peritubular capillary basement membranes (PTCR). Although such an association is of practical and theoretical importance, only one prospective study has tried to confirm it. METHODS: We examined 278 consecutive renal specimens (from 135 transplants and 143 native kidneys) for ultrastructural evidence of PTCR. In addition to renal allografts with TG, we also examined grafts with acute rejection, recurrent glomerulonephritis, chronic allograft nephropathy and stable grafts (\"protocol biopsies\"). Native kidney specimens included a wide range of glomerulopathies as well as cases of thrombotic microangiopathy, malignant hypertension, acute interstitial nephritis, and acute tubular necrosis. RESULTS: We found PTCR in 14 of 15 cases of TG, in 7 transplant biopsy specimens without TG, and in 13 of 143 native kidney biopsy specimens. These 13 included cases of malignant hypertension, thrombotic microangiopathy, lupus nephritis, Henoch-Schonlein nephritis, crescentic glomerulonephritis, and cocaine-related acute renal failure. Mild PTCR in allografts without TG did not predict renal failure or significant proteinuria after follow-up periods of between 3 months and 1 year. CONCLUSIONS: We conclude that in transplants, there is a strong association between well-developed PTCR and TG, while the significance of mild PTCR and its predictive value in the absence of TG is unclear. PTCR also occurs in certain native kidney diseases, though the association is not as strong as that for TG. We suggest that repeated endothelial injury, including immunologic injury, may be the cause of this lesion both in allografts and native kidneys.", "entity": "Kidney Tubular Necrosis, Acute", "aliases": "Acute Kidney Tubular Necrosis Lower Nephron Nephroses Nephrosis", "definition": "Acute kidney failure resulting from destruction of EPITHELIAL CELLS of the KIDNEY TUBULES. It is commonly attributed to exposure to toxic agents or renal ISCHEMIA following severe TRAUMA.\n    ", "id": "MESH:D007683"}
{"mention": "lupus nephritis", "mention_text": "BACKGROUND: An association has been found between transplant glomerulopathy (TG) and reduplication of peritubular capillary basement membranes (PTCR). Although such an association is of practical and theoretical importance, only one prospective study has tried to confirm it. METHODS: We examined 278 consecutive renal specimens (from 135 transplants and 143 native kidneys) for ultrastructural evidence of PTCR. In addition to renal allografts with TG, we also examined grafts with acute rejection, recurrent glomerulonephritis, chronic allograft nephropathy and stable grafts (\"protocol biopsies\"). Native kidney specimens included a wide range of glomerulopathies as well as cases of thrombotic microangiopathy, malignant hypertension, acute interstitial nephritis, and acute tubular necrosis. RESULTS: We found PTCR in 14 of 15 cases of TG, in 7 transplant biopsy specimens without TG, and in 13 of 143 native kidney biopsy specimens. These 13 included cases of malignant hypertension, thrombotic microangiopathy, lupus nephritis, Henoch-Schonlein nephritis, crescentic glomerulonephritis, and cocaine-related acute renal failure. Mild PTCR in allografts without TG did not predict renal failure or significant proteinuria after follow-up periods of between 3 months and 1 year. CONCLUSIONS: We conclude that in transplants, there is a strong association between well-developed PTCR and TG, while the significance of mild PTCR and its predictive value in the absence of TG is unclear. PTCR also occurs in certain native kidney diseases, though the association is not as strong as that for TG. We suggest that repeated endothelial injury, including immunologic injury, may be the cause of this lesion both in allografts and native kidneys.", "entity": "Lupus Nephritis", "aliases": "Glomerulonephritides Lupus Glomerulonephritis Nephritides Nephritis", "definition": "Glomerulonephritis associated with autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Lupus nephritis is histologically classified into 6 classes: class I - normal glomeruli, class II - pure mesangial alterations, class III - focal segmental glomerulonephritis, class IV - diffuse glomerulonephritis, class V - diffuse membranous glomerulonephritis, and class VI - advanced sclerosing glomerulonephritis (The World Health Organization classification 1982).\n    ", "id": "MESH:D008181"}
{"mention": "Henoch-Schonlein nephritis", "mention_text": "BACKGROUND: An association has been found between transplant glomerulopathy (TG) and reduplication of peritubular capillary basement membranes (PTCR). Although such an association is of practical and theoretical importance, only one prospective study has tried to confirm it. METHODS: We examined 278 consecutive renal specimens (from 135 transplants and 143 native kidneys) for ultrastructural evidence of PTCR. In addition to renal allografts with TG, we also examined grafts with acute rejection, recurrent glomerulonephritis, chronic allograft nephropathy and stable grafts (\"protocol biopsies\"). Native kidney specimens included a wide range of glomerulopathies as well as cases of thrombotic microangiopathy, malignant hypertension, acute interstitial nephritis, and acute tubular necrosis. RESULTS: We found PTCR in 14 of 15 cases of TG, in 7 transplant biopsy specimens without TG, and in 13 of 143 native kidney biopsy specimens. These 13 included cases of malignant hypertension, thrombotic microangiopathy, lupus nephritis, Henoch-Schonlein nephritis, crescentic glomerulonephritis, and cocaine-related acute renal failure. Mild PTCR in allografts without TG did not predict renal failure or significant proteinuria after follow-up periods of between 3 months and 1 year. CONCLUSIONS: We conclude that in transplants, there is a strong association between well-developed PTCR and TG, while the significance of mild PTCR and its predictive value in the absence of TG is unclear. PTCR also occurs in certain native kidney diseases, though the association is not as strong as that for TG. We suggest that repeated endothelial injury, including immunologic injury, may be the cause of this lesion both in allografts and native kidneys.", "entity": "Purpura, Schoenlein-Henoch", "aliases": "Allergic Purpura Anaphylactoid Hemorrhagic Vasculitis Hemorrhagica Henoch Schoenlein Schonlein Purpuras Henoch-Schoenlein Henoch-Schonlein Nonthrombocytopenic Nonthrombopenic Rheumatoid Schoenlein-Henoch Schonlein-Henoch", "definition": "A systemic non-thrombocytopenic purpura caused by HYPERSENSITIVITY VASCULITIS and deposition of IGA-containing IMMUNE COMPLEXES within the blood vessels throughout the body, including those in the kidney (KIDNEY GLOMERULUS). Clinical symptoms include URTICARIA; ERYTHEMA; ARTHRITIS; GASTROINTESTINAL HEMORRHAGE; and renal involvement. Most cases are seen in children after acute upper respiratory infections.\n    ", "id": "MESH:D011695"}
{"mention": "cocaine", "mention_text": "BACKGROUND: An association has been found between transplant glomerulopathy (TG) and reduplication of peritubular capillary basement membranes (PTCR). Although such an association is of practical and theoretical importance, only one prospective study has tried to confirm it. METHODS: We examined 278 consecutive renal specimens (from 135 transplants and 143 native kidneys) for ultrastructural evidence of PTCR. In addition to renal allografts with TG, we also examined grafts with acute rejection, recurrent glomerulonephritis, chronic allograft nephropathy and stable grafts (\"protocol biopsies\"). Native kidney specimens included a wide range of glomerulopathies as well as cases of thrombotic microangiopathy, malignant hypertension, acute interstitial nephritis, and acute tubular necrosis. RESULTS: We found PTCR in 14 of 15 cases of TG, in 7 transplant biopsy specimens without TG, and in 13 of 143 native kidney biopsy specimens. These 13 included cases of malignant hypertension, thrombotic microangiopathy, lupus nephritis, Henoch-Schonlein nephritis, crescentic glomerulonephritis, and cocaine-related acute renal failure. Mild PTCR in allografts without TG did not predict renal failure or significant proteinuria after follow-up periods of between 3 months and 1 year. CONCLUSIONS: We conclude that in transplants, there is a strong association between well-developed PTCR and TG, while the significance of mild PTCR and its predictive value in the absence of TG is unclear. PTCR also occurs in certain native kidney diseases, though the association is not as strong as that for TG. We suggest that repeated endothelial injury, including immunologic injury, may be the cause of this lesion both in allografts and native kidneys.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "acute renal failure", "mention_text": "BACKGROUND: An association has been found between transplant glomerulopathy (TG) and reduplication of peritubular capillary basement membranes (PTCR). Although such an association is of practical and theoretical importance, only one prospective study has tried to confirm it. METHODS: We examined 278 consecutive renal specimens (from 135 transplants and 143 native kidneys) for ultrastructural evidence of PTCR. In addition to renal allografts with TG, we also examined grafts with acute rejection, recurrent glomerulonephritis, chronic allograft nephropathy and stable grafts (\"protocol biopsies\"). Native kidney specimens included a wide range of glomerulopathies as well as cases of thrombotic microangiopathy, malignant hypertension, acute interstitial nephritis, and acute tubular necrosis. RESULTS: We found PTCR in 14 of 15 cases of TG, in 7 transplant biopsy specimens without TG, and in 13 of 143 native kidney biopsy specimens. These 13 included cases of malignant hypertension, thrombotic microangiopathy, lupus nephritis, Henoch-Schonlein nephritis, crescentic glomerulonephritis, and cocaine-related acute renal failure. Mild PTCR in allografts without TG did not predict renal failure or significant proteinuria after follow-up periods of between 3 months and 1 year. CONCLUSIONS: We conclude that in transplants, there is a strong association between well-developed PTCR and TG, while the significance of mild PTCR and its predictive value in the absence of TG is unclear. PTCR also occurs in certain native kidney diseases, though the association is not as strong as that for TG. We suggest that repeated endothelial injury, including immunologic injury, may be the cause of this lesion both in allografts and native kidneys.", "entity": "Acute Kidney Injury", "aliases": "Acute Kidney Failure Failures Injuries Injury Insufficiencies Insufficiency Renal", "definition": "Abrupt reduction in kidney function. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions.\n    ", "id": "MESH:D058186"}
{"mention": "renal failure", "mention_text": "BACKGROUND: An association has been found between transplant glomerulopathy (TG) and reduplication of peritubular capillary basement membranes (PTCR). Although such an association is of practical and theoretical importance, only one prospective study has tried to confirm it. METHODS: We examined 278 consecutive renal specimens (from 135 transplants and 143 native kidneys) for ultrastructural evidence of PTCR. In addition to renal allografts with TG, we also examined grafts with acute rejection, recurrent glomerulonephritis, chronic allograft nephropathy and stable grafts (\"protocol biopsies\"). Native kidney specimens included a wide range of glomerulopathies as well as cases of thrombotic microangiopathy, malignant hypertension, acute interstitial nephritis, and acute tubular necrosis. RESULTS: We found PTCR in 14 of 15 cases of TG, in 7 transplant biopsy specimens without TG, and in 13 of 143 native kidney biopsy specimens. These 13 included cases of malignant hypertension, thrombotic microangiopathy, lupus nephritis, Henoch-Schonlein nephritis, crescentic glomerulonephritis, and cocaine-related acute renal failure. Mild PTCR in allografts without TG did not predict renal failure or significant proteinuria after follow-up periods of between 3 months and 1 year. CONCLUSIONS: We conclude that in transplants, there is a strong association between well-developed PTCR and TG, while the significance of mild PTCR and its predictive value in the absence of TG is unclear. PTCR also occurs in certain native kidney diseases, though the association is not as strong as that for TG. We suggest that repeated endothelial injury, including immunologic injury, may be the cause of this lesion both in allografts and native kidneys.", "entity": "Renal Insufficiency", "aliases": "Failure Kidney Renal Failures Insufficiency Insufficiencies", "definition": "Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.\n    ", "id": "MESH:D051437"}
{"mention": "proteinuria", "mention_text": "BACKGROUND: An association has been found between transplant glomerulopathy (TG) and reduplication of peritubular capillary basement membranes (PTCR). Although such an association is of practical and theoretical importance, only one prospective study has tried to confirm it. METHODS: We examined 278 consecutive renal specimens (from 135 transplants and 143 native kidneys) for ultrastructural evidence of PTCR. In addition to renal allografts with TG, we also examined grafts with acute rejection, recurrent glomerulonephritis, chronic allograft nephropathy and stable grafts (\"protocol biopsies\"). Native kidney specimens included a wide range of glomerulopathies as well as cases of thrombotic microangiopathy, malignant hypertension, acute interstitial nephritis, and acute tubular necrosis. RESULTS: We found PTCR in 14 of 15 cases of TG, in 7 transplant biopsy specimens without TG, and in 13 of 143 native kidney biopsy specimens. These 13 included cases of malignant hypertension, thrombotic microangiopathy, lupus nephritis, Henoch-Schonlein nephritis, crescentic glomerulonephritis, and cocaine-related acute renal failure. Mild PTCR in allografts without TG did not predict renal failure or significant proteinuria after follow-up periods of between 3 months and 1 year. CONCLUSIONS: We conclude that in transplants, there is a strong association between well-developed PTCR and TG, while the significance of mild PTCR and its predictive value in the absence of TG is unclear. PTCR also occurs in certain native kidney diseases, though the association is not as strong as that for TG. We suggest that repeated endothelial injury, including immunologic injury, may be the cause of this lesion both in allografts and native kidneys.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "kidney diseases", "mention_text": "BACKGROUND: An association has been found between transplant glomerulopathy (TG) and reduplication of peritubular capillary basement membranes (PTCR). Although such an association is of practical and theoretical importance, only one prospective study has tried to confirm it. METHODS: We examined 278 consecutive renal specimens (from 135 transplants and 143 native kidneys) for ultrastructural evidence of PTCR. In addition to renal allografts with TG, we also examined grafts with acute rejection, recurrent glomerulonephritis, chronic allograft nephropathy and stable grafts (\"protocol biopsies\"). Native kidney specimens included a wide range of glomerulopathies as well as cases of thrombotic microangiopathy, malignant hypertension, acute interstitial nephritis, and acute tubular necrosis. RESULTS: We found PTCR in 14 of 15 cases of TG, in 7 transplant biopsy specimens without TG, and in 13 of 143 native kidney biopsy specimens. These 13 included cases of malignant hypertension, thrombotic microangiopathy, lupus nephritis, Henoch-Schonlein nephritis, crescentic glomerulonephritis, and cocaine-related acute renal failure. Mild PTCR in allografts without TG did not predict renal failure or significant proteinuria after follow-up periods of between 3 months and 1 year. CONCLUSIONS: We conclude that in transplants, there is a strong association between well-developed PTCR and TG, while the significance of mild PTCR and its predictive value in the absence of TG is unclear. PTCR also occurs in certain native kidney diseases, though the association is not as strong as that for TG. We suggest that repeated endothelial injury, including immunologic injury, may be the cause of this lesion both in allografts and native kidneys.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "endothelial injury", "mention_text": "BACKGROUND: An association has been found between transplant glomerulopathy (TG) and reduplication of peritubular capillary basement membranes (PTCR). Although such an association is of practical and theoretical importance, only one prospective study has tried to confirm it. METHODS: We examined 278 consecutive renal specimens (from 135 transplants and 143 native kidneys) for ultrastructural evidence of PTCR. In addition to renal allografts with TG, we also examined grafts with acute rejection, recurrent glomerulonephritis, chronic allograft nephropathy and stable grafts (\"protocol biopsies\"). Native kidney specimens included a wide range of glomerulopathies as well as cases of thrombotic microangiopathy, malignant hypertension, acute interstitial nephritis, and acute tubular necrosis. RESULTS: We found PTCR in 14 of 15 cases of TG, in 7 transplant biopsy specimens without TG, and in 13 of 143 native kidney biopsy specimens. These 13 included cases of malignant hypertension, thrombotic microangiopathy, lupus nephritis, Henoch-Schonlein nephritis, crescentic glomerulonephritis, and cocaine-related acute renal failure. Mild PTCR in allografts without TG did not predict renal failure or significant proteinuria after follow-up periods of between 3 months and 1 year. CONCLUSIONS: We conclude that in transplants, there is a strong association between well-developed PTCR and TG, while the significance of mild PTCR and its predictive value in the absence of TG is unclear. PTCR also occurs in certain native kidney diseases, though the association is not as strong as that for TG. We suggest that repeated endothelial injury, including immunologic injury, may be the cause of this lesion both in allografts and native kidneys.", "entity": "Wounds and Injuries", "aliases": "Injuries and Wounds Injury Trauma Traumas Wound", "definition": "Damage inflicted on the body as the direct or indirect result of an external force, with or without disruption of structural continuity.\n    ", "id": "MESH:D014947"}
{"mention": "immunologic injury", "mention_text": "BACKGROUND: An association has been found between transplant glomerulopathy (TG) and reduplication of peritubular capillary basement membranes (PTCR). Although such an association is of practical and theoretical importance, only one prospective study has tried to confirm it. METHODS: We examined 278 consecutive renal specimens (from 135 transplants and 143 native kidneys) for ultrastructural evidence of PTCR. In addition to renal allografts with TG, we also examined grafts with acute rejection, recurrent glomerulonephritis, chronic allograft nephropathy and stable grafts (\"protocol biopsies\"). Native kidney specimens included a wide range of glomerulopathies as well as cases of thrombotic microangiopathy, malignant hypertension, acute interstitial nephritis, and acute tubular necrosis. RESULTS: We found PTCR in 14 of 15 cases of TG, in 7 transplant biopsy specimens without TG, and in 13 of 143 native kidney biopsy specimens. These 13 included cases of malignant hypertension, thrombotic microangiopathy, lupus nephritis, Henoch-Schonlein nephritis, crescentic glomerulonephritis, and cocaine-related acute renal failure. Mild PTCR in allografts without TG did not predict renal failure or significant proteinuria after follow-up periods of between 3 months and 1 year. CONCLUSIONS: We conclude that in transplants, there is a strong association between well-developed PTCR and TG, while the significance of mild PTCR and its predictive value in the absence of TG is unclear. PTCR also occurs in certain native kidney diseases, though the association is not as strong as that for TG. We suggest that repeated endothelial injury, including immunologic injury, may be the cause of this lesion both in allografts and native kidneys.", "entity": "Immune System Diseases", "aliases": "Disease Immune System Immunologic Immunological Diseases of Disorder Disorders", "definition": "Disorders caused by abnormal or absent immunologic mechanisms, whether humoral, cell-mediated, or both.\n    ", "id": "MESH:D007154"}
{"mention": "BD1008", "mention_text": "Conformationally restricted analogs of BD1008 and an antisense oligodeoxynucleotide targeting sigma1 receptors produce anti-cocaine effects in mice.", "entity": "BD 1008", "aliases": "BD 1008 BD-1008 BD1008 DEMPEA N-(2-(3,4-dichlorophenyl)ethyl)-N-methyl-2-(1-pyrrolidinyl)ethylamine", "definition": "", "id": "MESH:C085527"}
{"mention": "oligodeoxynucleotide", "mention_text": "Conformationally restricted analogs of BD1008 and an antisense oligodeoxynucleotide targeting sigma1 receptors produce anti-cocaine effects in mice.", "entity": "Oligodeoxyribonucleotides", "aliases": "Oligodeoxynucleotides Oligodeoxyribonucleotides", "definition": "A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.\n    ", "id": "MESH:D009838"}
{"mention": "cocaine", "mention_text": "Conformationally restricted analogs of BD1008 and an antisense oligodeoxynucleotide targeting sigma1 receptors produce anti-cocaine effects in mice.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "Cocaine", "mention_text": "Cocaine's ability to interact with sigma receptors suggests that these proteins mediate some of its behavioral effects. Therefore, three novel sigma receptor ligands with antagonist activity were evaluated in Swiss Webster mice: BD1018 (3S-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane), BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine), and LR132 (1R,2S-(+)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl)cyclohexylamine). Competition binding assays demonstrated that all three compounds have high affinities for sigma1 receptors. The three compounds vary in their affinities for sigma2 receptors and exhibit negligible affinities for dopamine, opioid, GABA(A) and NMDA receptors. In behavioral studies, pre-treatment of mice with BD1018, BD1063, or LR132 significantly attenuated cocaine-induced convulsions and lethality. Moreover, post-treatment with LR132 prevented cocaine-induced lethality in a significant proportion of animals. In contrast to the protection provided by the putative antagonists, the well-characterized sigma receptor agonist di-o-tolylguanidine (DTG) and the novel sigma receptor agonist BD1031 (3R-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane) each worsened the behavioral toxicity of cocaine. At doses where alone, they produced no significant effects on locomotion, BD1018, BD1063 and LR132 significantly attenuated the locomotor stimulatory effects of cocaine. To further validate the hypothesis that the anti-cocaine effects of the novel ligands involved antagonism of sigma receptors, an antisense oligodeoxynucleotide against sigma1 receptors was also shown to significantly attenuate the convulsive and locomotor stimulatory effects of cocaine. Together, the data suggests that functional antagonism of sigma receptors is capable of attenuating a number of cocaine-induced behaviors.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "BD1063", "mention_text": "Cocaine's ability to interact with sigma receptors suggests that these proteins mediate some of its behavioral effects. Therefore, three novel sigma receptor ligands with antagonist activity were evaluated in Swiss Webster mice: BD1018 (3S-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane), BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine), and LR132 (1R,2S-(+)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl)cyclohexylamine). Competition binding assays demonstrated that all three compounds have high affinities for sigma1 receptors. The three compounds vary in their affinities for sigma2 receptors and exhibit negligible affinities for dopamine, opioid, GABA(A) and NMDA receptors. In behavioral studies, pre-treatment of mice with BD1018, BD1063, or LR132 significantly attenuated cocaine-induced convulsions and lethality. Moreover, post-treatment with LR132 prevented cocaine-induced lethality in a significant proportion of animals. In contrast to the protection provided by the putative antagonists, the well-characterized sigma receptor agonist di-o-tolylguanidine (DTG) and the novel sigma receptor agonist BD1031 (3R-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane) each worsened the behavioral toxicity of cocaine. At doses where alone, they produced no significant effects on locomotion, BD1018, BD1063 and LR132 significantly attenuated the locomotor stimulatory effects of cocaine. To further validate the hypothesis that the anti-cocaine effects of the novel ligands involved antagonism of sigma receptors, an antisense oligodeoxynucleotide against sigma1 receptors was also shown to significantly attenuate the convulsive and locomotor stimulatory effects of cocaine. Together, the data suggests that functional antagonism of sigma receptors is capable of attenuating a number of cocaine-induced behaviors.", "entity": "1-(2-(3,4-dichlorophenyl)ethyl)-4-methylpiperazine", "aliases": "1-(2-(3,4-dichlorophenyl)ethyl)-4-methylpiperazine BD 1063 BD-1063", "definition": "", "id": "MESH:C093337"}
{"mention": "1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine", "mention_text": "Cocaine's ability to interact with sigma receptors suggests that these proteins mediate some of its behavioral effects. Therefore, three novel sigma receptor ligands with antagonist activity were evaluated in Swiss Webster mice: BD1018 (3S-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane), BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine), and LR132 (1R,2S-(+)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl)cyclohexylamine). Competition binding assays demonstrated that all three compounds have high affinities for sigma1 receptors. The three compounds vary in their affinities for sigma2 receptors and exhibit negligible affinities for dopamine, opioid, GABA(A) and NMDA receptors. In behavioral studies, pre-treatment of mice with BD1018, BD1063, or LR132 significantly attenuated cocaine-induced convulsions and lethality. Moreover, post-treatment with LR132 prevented cocaine-induced lethality in a significant proportion of animals. In contrast to the protection provided by the putative antagonists, the well-characterized sigma receptor agonist di-o-tolylguanidine (DTG) and the novel sigma receptor agonist BD1031 (3R-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane) each worsened the behavioral toxicity of cocaine. At doses where alone, they produced no significant effects on locomotion, BD1018, BD1063 and LR132 significantly attenuated the locomotor stimulatory effects of cocaine. To further validate the hypothesis that the anti-cocaine effects of the novel ligands involved antagonism of sigma receptors, an antisense oligodeoxynucleotide against sigma1 receptors was also shown to significantly attenuate the convulsive and locomotor stimulatory effects of cocaine. Together, the data suggests that functional antagonism of sigma receptors is capable of attenuating a number of cocaine-induced behaviors.", "entity": "1-(2-(3,4-dichlorophenyl)ethyl)-4-methylpiperazine", "aliases": "1-(2-(3,4-dichlorophenyl)ethyl)-4-methylpiperazine BD 1063 BD-1063", "definition": "", "id": "MESH:C093337"}
{"mention": "dopamine", "mention_text": "Cocaine's ability to interact with sigma receptors suggests that these proteins mediate some of its behavioral effects. Therefore, three novel sigma receptor ligands with antagonist activity were evaluated in Swiss Webster mice: BD1018 (3S-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane), BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine), and LR132 (1R,2S-(+)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl)cyclohexylamine). Competition binding assays demonstrated that all three compounds have high affinities for sigma1 receptors. The three compounds vary in their affinities for sigma2 receptors and exhibit negligible affinities for dopamine, opioid, GABA(A) and NMDA receptors. In behavioral studies, pre-treatment of mice with BD1018, BD1063, or LR132 significantly attenuated cocaine-induced convulsions and lethality. Moreover, post-treatment with LR132 prevented cocaine-induced lethality in a significant proportion of animals. In contrast to the protection provided by the putative antagonists, the well-characterized sigma receptor agonist di-o-tolylguanidine (DTG) and the novel sigma receptor agonist BD1031 (3R-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane) each worsened the behavioral toxicity of cocaine. At doses where alone, they produced no significant effects on locomotion, BD1018, BD1063 and LR132 significantly attenuated the locomotor stimulatory effects of cocaine. To further validate the hypothesis that the anti-cocaine effects of the novel ligands involved antagonism of sigma receptors, an antisense oligodeoxynucleotide against sigma1 receptors was also shown to significantly attenuate the convulsive and locomotor stimulatory effects of cocaine. Together, the data suggests that functional antagonism of sigma receptors is capable of attenuating a number of cocaine-induced behaviors.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "GABA", "mention_text": "Cocaine's ability to interact with sigma receptors suggests that these proteins mediate some of its behavioral effects. Therefore, three novel sigma receptor ligands with antagonist activity were evaluated in Swiss Webster mice: BD1018 (3S-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane), BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine), and LR132 (1R,2S-(+)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl)cyclohexylamine). Competition binding assays demonstrated that all three compounds have high affinities for sigma1 receptors. The three compounds vary in their affinities for sigma2 receptors and exhibit negligible affinities for dopamine, opioid, GABA(A) and NMDA receptors. In behavioral studies, pre-treatment of mice with BD1018, BD1063, or LR132 significantly attenuated cocaine-induced convulsions and lethality. Moreover, post-treatment with LR132 prevented cocaine-induced lethality in a significant proportion of animals. In contrast to the protection provided by the putative antagonists, the well-characterized sigma receptor agonist di-o-tolylguanidine (DTG) and the novel sigma receptor agonist BD1031 (3R-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane) each worsened the behavioral toxicity of cocaine. At doses where alone, they produced no significant effects on locomotion, BD1018, BD1063 and LR132 significantly attenuated the locomotor stimulatory effects of cocaine. To further validate the hypothesis that the anti-cocaine effects of the novel ligands involved antagonism of sigma receptors, an antisense oligodeoxynucleotide against sigma1 receptors was also shown to significantly attenuate the convulsive and locomotor stimulatory effects of cocaine. Together, the data suggests that functional antagonism of sigma receptors is capable of attenuating a number of cocaine-induced behaviors.", "entity": "gamma-Aminobutyric Acid", "aliases": "4 Aminobutanoic Acid Aminobutyric 4-Aminobutanoic 4-Aminobutyric Hydrochloride gamma-Aminobutyric Aminalon Aminalone GABA Lithium Gammalon gamma Monolithium Salt Monosodium Calcium (2:1) Zinc", "definition": "The most common inhibitory neurotransmitter in the central nervous system.\n    ", "id": "MESH:D005680"}
{"mention": "NMDA", "mention_text": "Cocaine's ability to interact with sigma receptors suggests that these proteins mediate some of its behavioral effects. Therefore, three novel sigma receptor ligands with antagonist activity were evaluated in Swiss Webster mice: BD1018 (3S-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane), BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine), and LR132 (1R,2S-(+)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl)cyclohexylamine). Competition binding assays demonstrated that all three compounds have high affinities for sigma1 receptors. The three compounds vary in their affinities for sigma2 receptors and exhibit negligible affinities for dopamine, opioid, GABA(A) and NMDA receptors. In behavioral studies, pre-treatment of mice with BD1018, BD1063, or LR132 significantly attenuated cocaine-induced convulsions and lethality. Moreover, post-treatment with LR132 prevented cocaine-induced lethality in a significant proportion of animals. In contrast to the protection provided by the putative antagonists, the well-characterized sigma receptor agonist di-o-tolylguanidine (DTG) and the novel sigma receptor agonist BD1031 (3R-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane) each worsened the behavioral toxicity of cocaine. At doses where alone, they produced no significant effects on locomotion, BD1018, BD1063 and LR132 significantly attenuated the locomotor stimulatory effects of cocaine. To further validate the hypothesis that the anti-cocaine effects of the novel ligands involved antagonism of sigma receptors, an antisense oligodeoxynucleotide against sigma1 receptors was also shown to significantly attenuate the convulsive and locomotor stimulatory effects of cocaine. Together, the data suggests that functional antagonism of sigma receptors is capable of attenuating a number of cocaine-induced behaviors.", "entity": "N-Methylaspartate", "aliases": "Acid N-Methyl-D-aspartic N Methyl D aspartate aspartic Methylaspartate N-Methyl-D-aspartate N-Methylaspartate NMDA", "definition": "An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).\n    ", "id": "MESH:D016202"}
{"mention": "cocaine", "mention_text": "Cocaine's ability to interact with sigma receptors suggests that these proteins mediate some of its behavioral effects. Therefore, three novel sigma receptor ligands with antagonist activity were evaluated in Swiss Webster mice: BD1018 (3S-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane), BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine), and LR132 (1R,2S-(+)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl)cyclohexylamine). Competition binding assays demonstrated that all three compounds have high affinities for sigma1 receptors. The three compounds vary in their affinities for sigma2 receptors and exhibit negligible affinities for dopamine, opioid, GABA(A) and NMDA receptors. In behavioral studies, pre-treatment of mice with BD1018, BD1063, or LR132 significantly attenuated cocaine-induced convulsions and lethality. Moreover, post-treatment with LR132 prevented cocaine-induced lethality in a significant proportion of animals. In contrast to the protection provided by the putative antagonists, the well-characterized sigma receptor agonist di-o-tolylguanidine (DTG) and the novel sigma receptor agonist BD1031 (3R-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane) each worsened the behavioral toxicity of cocaine. At doses where alone, they produced no significant effects on locomotion, BD1018, BD1063 and LR132 significantly attenuated the locomotor stimulatory effects of cocaine. To further validate the hypothesis that the anti-cocaine effects of the novel ligands involved antagonism of sigma receptors, an antisense oligodeoxynucleotide against sigma1 receptors was also shown to significantly attenuate the convulsive and locomotor stimulatory effects of cocaine. Together, the data suggests that functional antagonism of sigma receptors is capable of attenuating a number of cocaine-induced behaviors.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "convulsions", "mention_text": "Cocaine's ability to interact with sigma receptors suggests that these proteins mediate some of its behavioral effects. Therefore, three novel sigma receptor ligands with antagonist activity were evaluated in Swiss Webster mice: BD1018 (3S-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane), BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine), and LR132 (1R,2S-(+)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl)cyclohexylamine). Competition binding assays demonstrated that all three compounds have high affinities for sigma1 receptors. The three compounds vary in their affinities for sigma2 receptors and exhibit negligible affinities for dopamine, opioid, GABA(A) and NMDA receptors. In behavioral studies, pre-treatment of mice with BD1018, BD1063, or LR132 significantly attenuated cocaine-induced convulsions and lethality. Moreover, post-treatment with LR132 prevented cocaine-induced lethality in a significant proportion of animals. In contrast to the protection provided by the putative antagonists, the well-characterized sigma receptor agonist di-o-tolylguanidine (DTG) and the novel sigma receptor agonist BD1031 (3R-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane) each worsened the behavioral toxicity of cocaine. At doses where alone, they produced no significant effects on locomotion, BD1018, BD1063 and LR132 significantly attenuated the locomotor stimulatory effects of cocaine. To further validate the hypothesis that the anti-cocaine effects of the novel ligands involved antagonism of sigma receptors, an antisense oligodeoxynucleotide against sigma1 receptors was also shown to significantly attenuate the convulsive and locomotor stimulatory effects of cocaine. Together, the data suggests that functional antagonism of sigma receptors is capable of attenuating a number of cocaine-induced behaviors.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "di-o-tolylguanidine", "mention_text": "Cocaine's ability to interact with sigma receptors suggests that these proteins mediate some of its behavioral effects. Therefore, three novel sigma receptor ligands with antagonist activity were evaluated in Swiss Webster mice: BD1018 (3S-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane), BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine), and LR132 (1R,2S-(+)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl)cyclohexylamine). Competition binding assays demonstrated that all three compounds have high affinities for sigma1 receptors. The three compounds vary in their affinities for sigma2 receptors and exhibit negligible affinities for dopamine, opioid, GABA(A) and NMDA receptors. In behavioral studies, pre-treatment of mice with BD1018, BD1063, or LR132 significantly attenuated cocaine-induced convulsions and lethality. Moreover, post-treatment with LR132 prevented cocaine-induced lethality in a significant proportion of animals. In contrast to the protection provided by the putative antagonists, the well-characterized sigma receptor agonist di-o-tolylguanidine (DTG) and the novel sigma receptor agonist BD1031 (3R-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane) each worsened the behavioral toxicity of cocaine. At doses where alone, they produced no significant effects on locomotion, BD1018, BD1063 and LR132 significantly attenuated the locomotor stimulatory effects of cocaine. To further validate the hypothesis that the anti-cocaine effects of the novel ligands involved antagonism of sigma receptors, an antisense oligodeoxynucleotide against sigma1 receptors was also shown to significantly attenuate the convulsive and locomotor stimulatory effects of cocaine. Together, the data suggests that functional antagonism of sigma receptors is capable of attenuating a number of cocaine-induced behaviors.", "entity": "1,3-ditolylguanidine", "aliases": "1,3-di-(2-tolyl)guanidine 1,3-di-o-tolylguanidine 1,3-di-ortho-tolyl-guanidine 1,3-ditolylguanidine hydrochloride N,N'-bis(2-methylphenyl)guanidine", "definition": "", "id": "MESH:C050232"}
{"mention": "DTG", "mention_text": "Cocaine's ability to interact with sigma receptors suggests that these proteins mediate some of its behavioral effects. Therefore, three novel sigma receptor ligands with antagonist activity were evaluated in Swiss Webster mice: BD1018 (3S-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane), BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine), and LR132 (1R,2S-(+)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl)cyclohexylamine). Competition binding assays demonstrated that all three compounds have high affinities for sigma1 receptors. The three compounds vary in their affinities for sigma2 receptors and exhibit negligible affinities for dopamine, opioid, GABA(A) and NMDA receptors. In behavioral studies, pre-treatment of mice with BD1018, BD1063, or LR132 significantly attenuated cocaine-induced convulsions and lethality. Moreover, post-treatment with LR132 prevented cocaine-induced lethality in a significant proportion of animals. In contrast to the protection provided by the putative antagonists, the well-characterized sigma receptor agonist di-o-tolylguanidine (DTG) and the novel sigma receptor agonist BD1031 (3R-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane) each worsened the behavioral toxicity of cocaine. At doses where alone, they produced no significant effects on locomotion, BD1018, BD1063 and LR132 significantly attenuated the locomotor stimulatory effects of cocaine. To further validate the hypothesis that the anti-cocaine effects of the novel ligands involved antagonism of sigma receptors, an antisense oligodeoxynucleotide against sigma1 receptors was also shown to significantly attenuate the convulsive and locomotor stimulatory effects of cocaine. Together, the data suggests that functional antagonism of sigma receptors is capable of attenuating a number of cocaine-induced behaviors.", "entity": "1,3-ditolylguanidine", "aliases": "1,3-di-(2-tolyl)guanidine 1,3-di-o-tolylguanidine 1,3-di-ortho-tolyl-guanidine 1,3-ditolylguanidine hydrochloride N,N'-bis(2-methylphenyl)guanidine", "definition": "", "id": "MESH:C050232"}
{"mention": "toxicity", "mention_text": "Cocaine's ability to interact with sigma receptors suggests that these proteins mediate some of its behavioral effects. Therefore, three novel sigma receptor ligands with antagonist activity were evaluated in Swiss Webster mice: BD1018 (3S-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane), BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine), and LR132 (1R,2S-(+)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl)cyclohexylamine). Competition binding assays demonstrated that all three compounds have high affinities for sigma1 receptors. The three compounds vary in their affinities for sigma2 receptors and exhibit negligible affinities for dopamine, opioid, GABA(A) and NMDA receptors. In behavioral studies, pre-treatment of mice with BD1018, BD1063, or LR132 significantly attenuated cocaine-induced convulsions and lethality. Moreover, post-treatment with LR132 prevented cocaine-induced lethality in a significant proportion of animals. In contrast to the protection provided by the putative antagonists, the well-characterized sigma receptor agonist di-o-tolylguanidine (DTG) and the novel sigma receptor agonist BD1031 (3R-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane) each worsened the behavioral toxicity of cocaine. At doses where alone, they produced no significant effects on locomotion, BD1018, BD1063 and LR132 significantly attenuated the locomotor stimulatory effects of cocaine. To further validate the hypothesis that the anti-cocaine effects of the novel ligands involved antagonism of sigma receptors, an antisense oligodeoxynucleotide against sigma1 receptors was also shown to significantly attenuate the convulsive and locomotor stimulatory effects of cocaine. Together, the data suggests that functional antagonism of sigma receptors is capable of attenuating a number of cocaine-induced behaviors.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "oligodeoxynucleotide", "mention_text": "Cocaine's ability to interact with sigma receptors suggests that these proteins mediate some of its behavioral effects. Therefore, three novel sigma receptor ligands with antagonist activity were evaluated in Swiss Webster mice: BD1018 (3S-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane), BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine), and LR132 (1R,2S-(+)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl)cyclohexylamine). Competition binding assays demonstrated that all three compounds have high affinities for sigma1 receptors. The three compounds vary in their affinities for sigma2 receptors and exhibit negligible affinities for dopamine, opioid, GABA(A) and NMDA receptors. In behavioral studies, pre-treatment of mice with BD1018, BD1063, or LR132 significantly attenuated cocaine-induced convulsions and lethality. Moreover, post-treatment with LR132 prevented cocaine-induced lethality in a significant proportion of animals. In contrast to the protection provided by the putative antagonists, the well-characterized sigma receptor agonist di-o-tolylguanidine (DTG) and the novel sigma receptor agonist BD1031 (3R-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane) each worsened the behavioral toxicity of cocaine. At doses where alone, they produced no significant effects on locomotion, BD1018, BD1063 and LR132 significantly attenuated the locomotor stimulatory effects of cocaine. To further validate the hypothesis that the anti-cocaine effects of the novel ligands involved antagonism of sigma receptors, an antisense oligodeoxynucleotide against sigma1 receptors was also shown to significantly attenuate the convulsive and locomotor stimulatory effects of cocaine. Together, the data suggests that functional antagonism of sigma receptors is capable of attenuating a number of cocaine-induced behaviors.", "entity": "Oligodeoxyribonucleotides", "aliases": "Oligodeoxynucleotides Oligodeoxyribonucleotides", "definition": "A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.\n    ", "id": "MESH:D009838"}
{"mention": "convulsive", "mention_text": "Cocaine's ability to interact with sigma receptors suggests that these proteins mediate some of its behavioral effects. Therefore, three novel sigma receptor ligands with antagonist activity were evaluated in Swiss Webster mice: BD1018 (3S-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane), BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine), and LR132 (1R,2S-(+)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl)cyclohexylamine). Competition binding assays demonstrated that all three compounds have high affinities for sigma1 receptors. The three compounds vary in their affinities for sigma2 receptors and exhibit negligible affinities for dopamine, opioid, GABA(A) and NMDA receptors. In behavioral studies, pre-treatment of mice with BD1018, BD1063, or LR132 significantly attenuated cocaine-induced convulsions and lethality. Moreover, post-treatment with LR132 prevented cocaine-induced lethality in a significant proportion of animals. In contrast to the protection provided by the putative antagonists, the well-characterized sigma receptor agonist di-o-tolylguanidine (DTG) and the novel sigma receptor agonist BD1031 (3R-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane) each worsened the behavioral toxicity of cocaine. At doses where alone, they produced no significant effects on locomotion, BD1018, BD1063 and LR132 significantly attenuated the locomotor stimulatory effects of cocaine. To further validate the hypothesis that the anti-cocaine effects of the novel ligands involved antagonism of sigma receptors, an antisense oligodeoxynucleotide against sigma1 receptors was also shown to significantly attenuate the convulsive and locomotor stimulatory effects of cocaine. Together, the data suggests that functional antagonism of sigma receptors is capable of attenuating a number of cocaine-induced behaviors.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "E4031", "mention_text": "Pharmacokinetic/pharmacodynamic assessment of the effects of E4031, cisapride, terfenadine and terodiline on monophasic action potential duration in dog.", "entity": "E 4031", "aliases": "2-methyl-6-(2-(4-(4-methylsulfonylamino)benzoylpiperidin-1-yl)ethyl)pyridine E 4031 E-4031", "definition": "", "id": "MESH:C063968"}
{"mention": "cisapride", "mention_text": "Pharmacokinetic/pharmacodynamic assessment of the effects of E4031, cisapride, terfenadine and terodiline on monophasic action potential duration in dog.", "entity": "Cisapride", "aliases": "Cisapride Propulsid R 51619 R-51619 R51619", "definition": "A substituted benzamide used for its prokinetic properties. It is used in the management of gastroesophageal reflux disease, functional dyspepsia, and other disorders associated with impaired gastrointestinal motility. (Martindale The Extra Pharmacopoeia, 31st ed)\n    ", "id": "MESH:D020117"}
{"mention": "terfenadine", "mention_text": "Pharmacokinetic/pharmacodynamic assessment of the effects of E4031, cisapride, terfenadine and terodiline on monophasic action potential duration in dog.", "entity": "Terfenadine", "aliases": "Aliud Brand of Terfenadine Balkis Saft Spezial Bial Cantabria Cyater Dolorgiet Heumann Hisfedin Hoechst Merck dura Mundipharma RMI 9918 RMI-9918 RMI9918 Rapidal Seldane Sigma Tau Sigma-Tau Stadapharm Teldane Terfedura Terfemundin Terfenadin AL Stada Terfenadin-ratiopharm Terfenidine Ternadin Triludan Wolff alpha-(4-(1,1-Dimethylethyl)phenyl)-4-(hydroxydiphenylmethyl)-1-piperdinebutanol ct Arzneimittel ct-Arzneimittel ratiopharm terfenadin von", "definition": "A selective histamine H1-receptor antagonist devoid of central nervous system depressant activity. The drug was used for ALLERGY but withdrawn due to causing LONG QT SYNDROME.\n    ", "id": "MESH:D016593"}
{"mention": "terodiline", "mention_text": "Pharmacokinetic/pharmacodynamic assessment of the effects of E4031, cisapride, terfenadine and terodiline on monophasic action potential duration in dog.", "entity": "terodiline", "aliases": "N-tert-butyl-1-methyl-3,3-diphenylpropylamine N-tert-butyl-3,3-diphenyl-1-methylpropylamine TD 758 TD-758 terodiline hydrochloride", "definition": "", "id": "MESH:C010637"}
{"mention": "Torsades de pointes", "mention_text": "1. Torsades de pointes (TDP) is a potentially fatal ventricular tachycardia associated with increases in QT interval and monophasic action potential duration (MAPD). TDP is a side-effect that has led to withdrawal of several drugs from the market (e.g. terfenadine and terodiline). 2. The potential of compounds to cause TDP was evaluated by monitoring their effects on MAPD in dog. Four compounds known to increase QT interval and cause TDP were investigated: terfenadine, terodiline, cisapride and E4031. On the basis that only free drug in the systemic circulation will elicit a pharmacological response target, free concentrations in plasma were selected to mimic the free drug exposures in man. Infusion regimens were designed that rapidly achieved and maintained target-free concentrations of these drugs in plasma and data on the relationship between free concentration and changes in MAPD were obtained for these compounds. 3. These data indicate that the free ED50 in plasma for terfenadine (1.9 nM), terodiline (76 nM), cisapride (11 nM) and E4031 (1.9 nM) closely correlate with the free concentration in man causing QT effects. For compounds that have shown TDP in the clinic (terfenadine, terodiline, cisapride) there is little differentiation between the dog ED50 and the efficacious free plasma concentrations in man (< 10-fold) reflecting their limited safety margins. These data underline the need to maximize the therapeutic ratio with respect to TDP in potential development candidates and the importance of using free drug concentrations in pharmacokinetic/pharmacodynamic studies.", "entity": "Torsades de Pointes", "aliases": "Pointes Torsade de Torsades", "definition": "A malignant form of polymorphic ventricular tachycardia that is characterized by HEART RATE between 200 and 250 beats per minute, and QRS complexes with changing amplitude and twisting of the points. The term also describes the syndrome of tachycardia with prolonged ventricular repolarization, long QT intervals exceeding 500 milliseconds or BRADYCARDIA. Torsades de pointes may be self-limited or may progress to VENTRICULAR FIBRILLATION.\n    ", "id": "MESH:D016171"}
{"mention": "TDP", "mention_text": "1. Torsades de pointes (TDP) is a potentially fatal ventricular tachycardia associated with increases in QT interval and monophasic action potential duration (MAPD). TDP is a side-effect that has led to withdrawal of several drugs from the market (e.g. terfenadine and terodiline). 2. The potential of compounds to cause TDP was evaluated by monitoring their effects on MAPD in dog. Four compounds known to increase QT interval and cause TDP were investigated: terfenadine, terodiline, cisapride and E4031. On the basis that only free drug in the systemic circulation will elicit a pharmacological response target, free concentrations in plasma were selected to mimic the free drug exposures in man. Infusion regimens were designed that rapidly achieved and maintained target-free concentrations of these drugs in plasma and data on the relationship between free concentration and changes in MAPD were obtained for these compounds. 3. These data indicate that the free ED50 in plasma for terfenadine (1.9 nM), terodiline (76 nM), cisapride (11 nM) and E4031 (1.9 nM) closely correlate with the free concentration in man causing QT effects. For compounds that have shown TDP in the clinic (terfenadine, terodiline, cisapride) there is little differentiation between the dog ED50 and the efficacious free plasma concentrations in man (< 10-fold) reflecting their limited safety margins. These data underline the need to maximize the therapeutic ratio with respect to TDP in potential development candidates and the importance of using free drug concentrations in pharmacokinetic/pharmacodynamic studies.", "entity": "Torsades de Pointes", "aliases": "Pointes Torsade de Torsades", "definition": "A malignant form of polymorphic ventricular tachycardia that is characterized by HEART RATE between 200 and 250 beats per minute, and QRS complexes with changing amplitude and twisting of the points. The term also describes the syndrome of tachycardia with prolonged ventricular repolarization, long QT intervals exceeding 500 milliseconds or BRADYCARDIA. Torsades de pointes may be self-limited or may progress to VENTRICULAR FIBRILLATION.\n    ", "id": "MESH:D016171"}
{"mention": "ventricular tachycardia", "mention_text": "1. Torsades de pointes (TDP) is a potentially fatal ventricular tachycardia associated with increases in QT interval and monophasic action potential duration (MAPD). TDP is a side-effect that has led to withdrawal of several drugs from the market (e.g. terfenadine and terodiline). 2. The potential of compounds to cause TDP was evaluated by monitoring their effects on MAPD in dog. Four compounds known to increase QT interval and cause TDP were investigated: terfenadine, terodiline, cisapride and E4031. On the basis that only free drug in the systemic circulation will elicit a pharmacological response target, free concentrations in plasma were selected to mimic the free drug exposures in man. Infusion regimens were designed that rapidly achieved and maintained target-free concentrations of these drugs in plasma and data on the relationship between free concentration and changes in MAPD were obtained for these compounds. 3. These data indicate that the free ED50 in plasma for terfenadine (1.9 nM), terodiline (76 nM), cisapride (11 nM) and E4031 (1.9 nM) closely correlate with the free concentration in man causing QT effects. For compounds that have shown TDP in the clinic (terfenadine, terodiline, cisapride) there is little differentiation between the dog ED50 and the efficacious free plasma concentrations in man (< 10-fold) reflecting their limited safety margins. These data underline the need to maximize the therapeutic ratio with respect to TDP in potential development candidates and the importance of using free drug concentrations in pharmacokinetic/pharmacodynamic studies.", "entity": "Tachycardia, Ventricular", "aliases": "Tachycardia Ventricular Tachycardias", "definition": "An abnormally rapid ventricular rhythm usually in excess of 150 beats per minute. It is generated within the ventricle below the BUNDLE OF HIS, either as autonomic impulse formation or reentrant impulse conduction. Depending on the etiology, onset of ventricular tachycardia can be paroxysmal (sudden) or nonparoxysmal, its wide QRS complexes can be uniform or polymorphic, and the ventricular beating may be independent of the atrial beating (AV dissociation).\n    ", "id": "MESH:D017180"}
{"mention": "terfenadine", "mention_text": "1. Torsades de pointes (TDP) is a potentially fatal ventricular tachycardia associated with increases in QT interval and monophasic action potential duration (MAPD). TDP is a side-effect that has led to withdrawal of several drugs from the market (e.g. terfenadine and terodiline). 2. The potential of compounds to cause TDP was evaluated by monitoring their effects on MAPD in dog. Four compounds known to increase QT interval and cause TDP were investigated: terfenadine, terodiline, cisapride and E4031. On the basis that only free drug in the systemic circulation will elicit a pharmacological response target, free concentrations in plasma were selected to mimic the free drug exposures in man. Infusion regimens were designed that rapidly achieved and maintained target-free concentrations of these drugs in plasma and data on the relationship between free concentration and changes in MAPD were obtained for these compounds. 3. These data indicate that the free ED50 in plasma for terfenadine (1.9 nM), terodiline (76 nM), cisapride (11 nM) and E4031 (1.9 nM) closely correlate with the free concentration in man causing QT effects. For compounds that have shown TDP in the clinic (terfenadine, terodiline, cisapride) there is little differentiation between the dog ED50 and the efficacious free plasma concentrations in man (< 10-fold) reflecting their limited safety margins. These data underline the need to maximize the therapeutic ratio with respect to TDP in potential development candidates and the importance of using free drug concentrations in pharmacokinetic/pharmacodynamic studies.", "entity": "Terfenadine", "aliases": "Aliud Brand of Terfenadine Balkis Saft Spezial Bial Cantabria Cyater Dolorgiet Heumann Hisfedin Hoechst Merck dura Mundipharma RMI 9918 RMI-9918 RMI9918 Rapidal Seldane Sigma Tau Sigma-Tau Stadapharm Teldane Terfedura Terfemundin Terfenadin AL Stada Terfenadin-ratiopharm Terfenidine Ternadin Triludan Wolff alpha-(4-(1,1-Dimethylethyl)phenyl)-4-(hydroxydiphenylmethyl)-1-piperdinebutanol ct Arzneimittel ct-Arzneimittel ratiopharm terfenadin von", "definition": "A selective histamine H1-receptor antagonist devoid of central nervous system depressant activity. The drug was used for ALLERGY but withdrawn due to causing LONG QT SYNDROME.\n    ", "id": "MESH:D016593"}
{"mention": "terodiline", "mention_text": "1. Torsades de pointes (TDP) is a potentially fatal ventricular tachycardia associated with increases in QT interval and monophasic action potential duration (MAPD). TDP is a side-effect that has led to withdrawal of several drugs from the market (e.g. terfenadine and terodiline). 2. The potential of compounds to cause TDP was evaluated by monitoring their effects on MAPD in dog. Four compounds known to increase QT interval and cause TDP were investigated: terfenadine, terodiline, cisapride and E4031. On the basis that only free drug in the systemic circulation will elicit a pharmacological response target, free concentrations in plasma were selected to mimic the free drug exposures in man. Infusion regimens were designed that rapidly achieved and maintained target-free concentrations of these drugs in plasma and data on the relationship between free concentration and changes in MAPD were obtained for these compounds. 3. These data indicate that the free ED50 in plasma for terfenadine (1.9 nM), terodiline (76 nM), cisapride (11 nM) and E4031 (1.9 nM) closely correlate with the free concentration in man causing QT effects. For compounds that have shown TDP in the clinic (terfenadine, terodiline, cisapride) there is little differentiation between the dog ED50 and the efficacious free plasma concentrations in man (< 10-fold) reflecting their limited safety margins. These data underline the need to maximize the therapeutic ratio with respect to TDP in potential development candidates and the importance of using free drug concentrations in pharmacokinetic/pharmacodynamic studies.", "entity": "terodiline", "aliases": "N-tert-butyl-1-methyl-3,3-diphenylpropylamine N-tert-butyl-3,3-diphenyl-1-methylpropylamine TD 758 TD-758 terodiline hydrochloride", "definition": "", "id": "MESH:C010637"}
{"mention": "cisapride", "mention_text": "1. Torsades de pointes (TDP) is a potentially fatal ventricular tachycardia associated with increases in QT interval and monophasic action potential duration (MAPD). TDP is a side-effect that has led to withdrawal of several drugs from the market (e.g. terfenadine and terodiline). 2. The potential of compounds to cause TDP was evaluated by monitoring their effects on MAPD in dog. Four compounds known to increase QT interval and cause TDP were investigated: terfenadine, terodiline, cisapride and E4031. On the basis that only free drug in the systemic circulation will elicit a pharmacological response target, free concentrations in plasma were selected to mimic the free drug exposures in man. Infusion regimens were designed that rapidly achieved and maintained target-free concentrations of these drugs in plasma and data on the relationship between free concentration and changes in MAPD were obtained for these compounds. 3. These data indicate that the free ED50 in plasma for terfenadine (1.9 nM), terodiline (76 nM), cisapride (11 nM) and E4031 (1.9 nM) closely correlate with the free concentration in man causing QT effects. For compounds that have shown TDP in the clinic (terfenadine, terodiline, cisapride) there is little differentiation between the dog ED50 and the efficacious free plasma concentrations in man (< 10-fold) reflecting their limited safety margins. These data underline the need to maximize the therapeutic ratio with respect to TDP in potential development candidates and the importance of using free drug concentrations in pharmacokinetic/pharmacodynamic studies.", "entity": "Cisapride", "aliases": "Cisapride Propulsid R 51619 R-51619 R51619", "definition": "A substituted benzamide used for its prokinetic properties. It is used in the management of gastroesophageal reflux disease, functional dyspepsia, and other disorders associated with impaired gastrointestinal motility. (Martindale The Extra Pharmacopoeia, 31st ed)\n    ", "id": "MESH:D020117"}
{"mention": "E4031", "mention_text": "1. Torsades de pointes (TDP) is a potentially fatal ventricular tachycardia associated with increases in QT interval and monophasic action potential duration (MAPD). TDP is a side-effect that has led to withdrawal of several drugs from the market (e.g. terfenadine and terodiline). 2. The potential of compounds to cause TDP was evaluated by monitoring their effects on MAPD in dog. Four compounds known to increase QT interval and cause TDP were investigated: terfenadine, terodiline, cisapride and E4031. On the basis that only free drug in the systemic circulation will elicit a pharmacological response target, free concentrations in plasma were selected to mimic the free drug exposures in man. Infusion regimens were designed that rapidly achieved and maintained target-free concentrations of these drugs in plasma and data on the relationship between free concentration and changes in MAPD were obtained for these compounds. 3. These data indicate that the free ED50 in plasma for terfenadine (1.9 nM), terodiline (76 nM), cisapride (11 nM) and E4031 (1.9 nM) closely correlate with the free concentration in man causing QT effects. For compounds that have shown TDP in the clinic (terfenadine, terodiline, cisapride) there is little differentiation between the dog ED50 and the efficacious free plasma concentrations in man (< 10-fold) reflecting their limited safety margins. These data underline the need to maximize the therapeutic ratio with respect to TDP in potential development candidates and the importance of using free drug concentrations in pharmacokinetic/pharmacodynamic studies.", "entity": "E 4031", "aliases": "2-methyl-6-(2-(4-(4-methylsulfonylamino)benzoylpiperidin-1-yl)ethyl)pyridine E 4031 E-4031", "definition": "", "id": "MESH:C063968"}
{"mention": "myeloencephalopathy", "mention_text": "Fatal myeloencephalopathy due to accidental intrathecal vincristin administration: a report of two cases.", "entity": "Brain Diseases", "aliases": "Brain Disease Diseases Disorder Disorders CNS Intracranial Central Nervous System Encephalon", "definition": "Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.\n    ", "id": "MESH:D001927"}
{"mention": "vincristin", "mention_text": "Fatal myeloencephalopathy due to accidental intrathecal vincristin administration: a report of two cases.", "entity": "Vincristine", "aliases": "Bristol-Myers Squibb Brand of Vincristine Sulfate Citomid Columbia EG Labo Farmistin Irisfarma Lemery Leurocristine Lilly Oncovin Oncovine Onkocristin Onkoworks PFS Vincasar Pfizer Teva Vincristin Bristol Liquid medac Vincrisul Vintec cell pharm cellcristin", "definition": "Antitumor alkaloid isolated from Vinca Rosea. (Merck, 11th ed.)\n    ", "id": "MESH:D014750"}
{"mention": "vincristine", "mention_text": "We report on two fatal cases of accidental intrathecal vincristine instillation in a 5-year old girl with recurrent acute lymphoblastic leucemia and a 57-year old man with lymphoblastic lymphoma. The girl died seven days, the man four weeks after intrathecal injection of vincristine. Clinically, the onset was characterized by the signs of opistothonus, sensory and motor dysfunction and ascending paralysis. Histological and immunohistochemical investigations (HE-LFB, CD-68, Neurofilament) revealed degeneration of myelin and axons as well as pseudocystic transformation in areas exposed to vincristine, accompanied by secondary changes with numerous prominent macrophages. The clinical course and histopathological results of the two cases are presented. A review of all reported cases in the literature is given. A better controlled regimen for administering vincristine and intrathecal chemotherapy is recommended.", "entity": "Vincristine", "aliases": "Bristol-Myers Squibb Brand of Vincristine Sulfate Citomid Columbia EG Labo Farmistin Irisfarma Lemery Leurocristine Lilly Oncovin Oncovine Onkocristin Onkoworks PFS Vincasar Pfizer Teva Vincristin Bristol Liquid medac Vincrisul Vintec cell pharm cellcristin", "definition": "Antitumor alkaloid isolated from Vinca Rosea. (Merck, 11th ed.)\n    ", "id": "MESH:D014750"}
{"mention": "acute lymphoblastic leucemia", "mention_text": "We report on two fatal cases of accidental intrathecal vincristine instillation in a 5-year old girl with recurrent acute lymphoblastic leucemia and a 57-year old man with lymphoblastic lymphoma. The girl died seven days, the man four weeks after intrathecal injection of vincristine. Clinically, the onset was characterized by the signs of opistothonus, sensory and motor dysfunction and ascending paralysis. Histological and immunohistochemical investigations (HE-LFB, CD-68, Neurofilament) revealed degeneration of myelin and axons as well as pseudocystic transformation in areas exposed to vincristine, accompanied by secondary changes with numerous prominent macrophages. The clinical course and histopathological results of the two cases are presented. A review of all reported cases in the literature is given. A better controlled regimen for administering vincristine and intrathecal chemotherapy is recommended.", "entity": "Precursor Cell Lymphoblastic Leukemia-Lymphoma", "aliases": "ALL Childhood Acute Lymphoblastic Leukemia Lymphocytic Lymphoid L1 L2 Philadelphia-Positive Adult Lymphoma Precursor Cell Leukemia-Lymphoma", "definition": "A neoplasm characterized by abnormalities of the lymphoid cell precursors leading to excessive lymphoblasts in the marrow and other organs. It is the most common cancer in children and accounts for the vast majority of all childhood leukemias.\n    ", "id": "MESH:D054198"}
{"mention": "lymphoblastic lymphoma", "mention_text": "We report on two fatal cases of accidental intrathecal vincristine instillation in a 5-year old girl with recurrent acute lymphoblastic leucemia and a 57-year old man with lymphoblastic lymphoma. The girl died seven days, the man four weeks after intrathecal injection of vincristine. Clinically, the onset was characterized by the signs of opistothonus, sensory and motor dysfunction and ascending paralysis. Histological and immunohistochemical investigations (HE-LFB, CD-68, Neurofilament) revealed degeneration of myelin and axons as well as pseudocystic transformation in areas exposed to vincristine, accompanied by secondary changes with numerous prominent macrophages. The clinical course and histopathological results of the two cases are presented. A review of all reported cases in the literature is given. A better controlled regimen for administering vincristine and intrathecal chemotherapy is recommended.", "entity": "Precursor Cell Lymphoblastic Leukemia-Lymphoma", "aliases": "ALL Childhood Acute Lymphoblastic Leukemia Lymphocytic Lymphoid L1 L2 Philadelphia-Positive Adult Lymphoma Precursor Cell Leukemia-Lymphoma", "definition": "A neoplasm characterized by abnormalities of the lymphoid cell precursors leading to excessive lymphoblasts in the marrow and other organs. It is the most common cancer in children and accounts for the vast majority of all childhood leukemias.\n    ", "id": "MESH:D054198"}
{"mention": "motor dysfunction", "mention_text": "We report on two fatal cases of accidental intrathecal vincristine instillation in a 5-year old girl with recurrent acute lymphoblastic leucemia and a 57-year old man with lymphoblastic lymphoma. The girl died seven days, the man four weeks after intrathecal injection of vincristine. Clinically, the onset was characterized by the signs of opistothonus, sensory and motor dysfunction and ascending paralysis. Histological and immunohistochemical investigations (HE-LFB, CD-68, Neurofilament) revealed degeneration of myelin and axons as well as pseudocystic transformation in areas exposed to vincristine, accompanied by secondary changes with numerous prominent macrophages. The clinical course and histopathological results of the two cases are presented. A review of all reported cases in the literature is given. A better controlled regimen for administering vincristine and intrathecal chemotherapy is recommended.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "paralysis", "mention_text": "We report on two fatal cases of accidental intrathecal vincristine instillation in a 5-year old girl with recurrent acute lymphoblastic leucemia and a 57-year old man with lymphoblastic lymphoma. The girl died seven days, the man four weeks after intrathecal injection of vincristine. Clinically, the onset was characterized by the signs of opistothonus, sensory and motor dysfunction and ascending paralysis. Histological and immunohistochemical investigations (HE-LFB, CD-68, Neurofilament) revealed degeneration of myelin and axons as well as pseudocystic transformation in areas exposed to vincristine, accompanied by secondary changes with numerous prominent macrophages. The clinical course and histopathological results of the two cases are presented. A review of all reported cases in the literature is given. A better controlled regimen for administering vincristine and intrathecal chemotherapy is recommended.", "entity": "Paralysis", "aliases": "Palsies Palsy Paralyses Paralysis Todd Todd's Plegia Plegias Todds", "definition": "A general term most often used to describe severe or complete loss of muscle strength due to motor system disease from the level of the cerebral cortex to the muscle fiber. This term may also occasionally refer to a loss of sensory function. (From Adams et al., Principles of Neurology, 6th ed, p45)\n    ", "id": "MESH:D010243"}
{"mention": "degeneration of myelin", "mention_text": "We report on two fatal cases of accidental intrathecal vincristine instillation in a 5-year old girl with recurrent acute lymphoblastic leucemia and a 57-year old man with lymphoblastic lymphoma. The girl died seven days, the man four weeks after intrathecal injection of vincristine. Clinically, the onset was characterized by the signs of opistothonus, sensory and motor dysfunction and ascending paralysis. Histological and immunohistochemical investigations (HE-LFB, CD-68, Neurofilament) revealed degeneration of myelin and axons as well as pseudocystic transformation in areas exposed to vincristine, accompanied by secondary changes with numerous prominent macrophages. The clinical course and histopathological results of the two cases are presented. A review of all reported cases in the literature is given. A better controlled regimen for administering vincristine and intrathecal chemotherapy is recommended.", "entity": "Demyelinating Diseases", "aliases": "Clinically Isolated CNS Demyelinating Syndrome Disease Diseases Disorder Disorders Demyelination Demyelinations", "definition": "Diseases characterized by loss or dysfunction of myelin in the central or peripheral nervous system.\n    ", "id": "MESH:D003711"}
{"mention": "prochlorperazine", "mention_text": "Intravenous administration of prochlorperazine by 15-minute infusion versus 2-minute bolus does not affect the incidence of akathisia: a prospective, randomized, controlled trial.", "entity": "Prochlorperazine", "aliases": "Compazine Edisylate Salt Prochlorperazine Maleate", "definition": "A phenothiazine antipsychotic used principally in the treatment of NAUSEA; VOMITING; and VERTIGO. It is more likely than CHLORPROMAZINE to cause EXTRAPYRAMIDAL DISORDERS. (From Martindale, The Extra Pharmacopoeia, 30th ed, p612)\n    ", "id": "MESH:D011346"}
{"mention": "akathisia", "mention_text": "Intravenous administration of prochlorperazine by 15-minute infusion versus 2-minute bolus does not affect the incidence of akathisia: a prospective, randomized, controlled trial.", "entity": "Akathisia, Drug-Induced", "aliases": "Acathisia Drug Induced Drug-Induced Akathisia Tardive Pseudoakathisia", "definition": "A condition associated with the use of certain medications and characterized by an internal sense of motor restlessness often described as an inability to resist the urge to move.\n    ", "id": "MESH:D017109"}
{"mention": "akathisia", "mention_text": "STUDY OBJECTIVE: We sought to compare the rate of akathisia after administration of intravenous prochlorperazine as a 2-minute bolus or 15-minute infusion. METHODS: We conducted a prospective, randomized, double-blind study in the emergency department of a central-city teaching hospital. Patients aged 18 years or older treated with prochlorperazine for headache, nausea, or vomiting were eligible for inclusion. Study participants were randomized to receive 10 mg of prochlorperazine administered intravenously by means of 2-minute push (bolus group) or 10 mg diluted in 50 mL of normal saline solution administered by means of intravenous infusion during a 15-minute period (infusion group). The main outcome was the number of study participants experiencing akathisia within 60 minutes of administration. Akathisia was defined as either a spontaneous report of restlessness or agitation or a change of 2 or more in the patient-reported akathisia rating scale and a change of at least 1 in the investigator-observed akathisia rating scale. The intensity of headache and nausea was measured with a 100-mm visual analog scale. RESULTS: One hundred patients were enrolled. One study participant was excluded after protocol violation. Seventy-three percent (73/99) of the study participants were treated for headache and 70% (70/99) for nausea. In the bolus group, 26.0% (13/50) had akathisia compared with 32.7% (16/49) in the infusion group (Delta=-6.7%; 95% confidence interval [CI] -24.6% to 11.2%). The difference between the bolus and infusion groups in the percentage of participants who saw a 50% reduction in their headache intensity within 30 minutes was 11.8% (95% CI -9.6% to 33.3%). The difference in the percentage of patients with a 50% reduction in their nausea was 12.6% (95% CI -4.6% to 29.8%). CONCLUSION: A 50% reduction in the incidence of akathisia when prochlorperazine was administered by means of 15-minute intravenous infusion versus a 2-minute intravenous push was not detected. The efficacy of prochlorperazine in the treatment of headache and nausea likewise did not appear to be affected by the rate of administration, although no formal statistical comparisons were made.", "entity": "Akathisia, Drug-Induced", "aliases": "Acathisia Drug Induced Drug-Induced Akathisia Tardive Pseudoakathisia", "definition": "A condition associated with the use of certain medications and characterized by an internal sense of motor restlessness often described as an inability to resist the urge to move.\n    ", "id": "MESH:D017109"}
{"mention": "prochlorperazine", "mention_text": "STUDY OBJECTIVE: We sought to compare the rate of akathisia after administration of intravenous prochlorperazine as a 2-minute bolus or 15-minute infusion. METHODS: We conducted a prospective, randomized, double-blind study in the emergency department of a central-city teaching hospital. Patients aged 18 years or older treated with prochlorperazine for headache, nausea, or vomiting were eligible for inclusion. Study participants were randomized to receive 10 mg of prochlorperazine administered intravenously by means of 2-minute push (bolus group) or 10 mg diluted in 50 mL of normal saline solution administered by means of intravenous infusion during a 15-minute period (infusion group). The main outcome was the number of study participants experiencing akathisia within 60 minutes of administration. Akathisia was defined as either a spontaneous report of restlessness or agitation or a change of 2 or more in the patient-reported akathisia rating scale and a change of at least 1 in the investigator-observed akathisia rating scale. The intensity of headache and nausea was measured with a 100-mm visual analog scale. RESULTS: One hundred patients were enrolled. One study participant was excluded after protocol violation. Seventy-three percent (73/99) of the study participants were treated for headache and 70% (70/99) for nausea. In the bolus group, 26.0% (13/50) had akathisia compared with 32.7% (16/49) in the infusion group (Delta=-6.7%; 95% confidence interval [CI] -24.6% to 11.2%). The difference between the bolus and infusion groups in the percentage of participants who saw a 50% reduction in their headache intensity within 30 minutes was 11.8% (95% CI -9.6% to 33.3%). The difference in the percentage of patients with a 50% reduction in their nausea was 12.6% (95% CI -4.6% to 29.8%). CONCLUSION: A 50% reduction in the incidence of akathisia when prochlorperazine was administered by means of 15-minute intravenous infusion versus a 2-minute intravenous push was not detected. The efficacy of prochlorperazine in the treatment of headache and nausea likewise did not appear to be affected by the rate of administration, although no formal statistical comparisons were made.", "entity": "Prochlorperazine", "aliases": "Compazine Edisylate Salt Prochlorperazine Maleate", "definition": "A phenothiazine antipsychotic used principally in the treatment of NAUSEA; VOMITING; and VERTIGO. It is more likely than CHLORPROMAZINE to cause EXTRAPYRAMIDAL DISORDERS. (From Martindale, The Extra Pharmacopoeia, 30th ed, p612)\n    ", "id": "MESH:D011346"}
{"mention": "headache", "mention_text": "STUDY OBJECTIVE: We sought to compare the rate of akathisia after administration of intravenous prochlorperazine as a 2-minute bolus or 15-minute infusion. METHODS: We conducted a prospective, randomized, double-blind study in the emergency department of a central-city teaching hospital. Patients aged 18 years or older treated with prochlorperazine for headache, nausea, or vomiting were eligible for inclusion. Study participants were randomized to receive 10 mg of prochlorperazine administered intravenously by means of 2-minute push (bolus group) or 10 mg diluted in 50 mL of normal saline solution administered by means of intravenous infusion during a 15-minute period (infusion group). The main outcome was the number of study participants experiencing akathisia within 60 minutes of administration. Akathisia was defined as either a spontaneous report of restlessness or agitation or a change of 2 or more in the patient-reported akathisia rating scale and a change of at least 1 in the investigator-observed akathisia rating scale. The intensity of headache and nausea was measured with a 100-mm visual analog scale. RESULTS: One hundred patients were enrolled. One study participant was excluded after protocol violation. Seventy-three percent (73/99) of the study participants were treated for headache and 70% (70/99) for nausea. In the bolus group, 26.0% (13/50) had akathisia compared with 32.7% (16/49) in the infusion group (Delta=-6.7%; 95% confidence interval [CI] -24.6% to 11.2%). The difference between the bolus and infusion groups in the percentage of participants who saw a 50% reduction in their headache intensity within 30 minutes was 11.8% (95% CI -9.6% to 33.3%). The difference in the percentage of patients with a 50% reduction in their nausea was 12.6% (95% CI -4.6% to 29.8%). CONCLUSION: A 50% reduction in the incidence of akathisia when prochlorperazine was administered by means of 15-minute intravenous infusion versus a 2-minute intravenous push was not detected. The efficacy of prochlorperazine in the treatment of headache and nausea likewise did not appear to be affected by the rate of administration, although no formal statistical comparisons were made.", "entity": "Headache", "aliases": "Bilateral Headache Headaches Cephalalgia Cephalalgias Cephalgia Cephalgias Cephalodynia Cephalodynias Cranial Pain Pains Generalized Head Ocular Orthostatic Periorbital Retro-Ocular Sharp Throbbing Unilateral Vertex Hemicrania Retro", "definition": "The symptom of PAIN in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of HEADACHE DISORDERS.\n    ", "id": "MESH:D006261"}
{"mention": "nausea", "mention_text": "STUDY OBJECTIVE: We sought to compare the rate of akathisia after administration of intravenous prochlorperazine as a 2-minute bolus or 15-minute infusion. METHODS: We conducted a prospective, randomized, double-blind study in the emergency department of a central-city teaching hospital. Patients aged 18 years or older treated with prochlorperazine for headache, nausea, or vomiting were eligible for inclusion. Study participants were randomized to receive 10 mg of prochlorperazine administered intravenously by means of 2-minute push (bolus group) or 10 mg diluted in 50 mL of normal saline solution administered by means of intravenous infusion during a 15-minute period (infusion group). The main outcome was the number of study participants experiencing akathisia within 60 minutes of administration. Akathisia was defined as either a spontaneous report of restlessness or agitation or a change of 2 or more in the patient-reported akathisia rating scale and a change of at least 1 in the investigator-observed akathisia rating scale. The intensity of headache and nausea was measured with a 100-mm visual analog scale. RESULTS: One hundred patients were enrolled. One study participant was excluded after protocol violation. Seventy-three percent (73/99) of the study participants were treated for headache and 70% (70/99) for nausea. In the bolus group, 26.0% (13/50) had akathisia compared with 32.7% (16/49) in the infusion group (Delta=-6.7%; 95% confidence interval [CI] -24.6% to 11.2%). The difference between the bolus and infusion groups in the percentage of participants who saw a 50% reduction in their headache intensity within 30 minutes was 11.8% (95% CI -9.6% to 33.3%). The difference in the percentage of patients with a 50% reduction in their nausea was 12.6% (95% CI -4.6% to 29.8%). CONCLUSION: A 50% reduction in the incidence of akathisia when prochlorperazine was administered by means of 15-minute intravenous infusion versus a 2-minute intravenous push was not detected. The efficacy of prochlorperazine in the treatment of headache and nausea likewise did not appear to be affected by the rate of administration, although no formal statistical comparisons were made.", "entity": "Nausea", "aliases": "Nausea", "definition": "An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.\n    ", "id": "MESH:D009325"}
{"mention": "vomiting", "mention_text": "STUDY OBJECTIVE: We sought to compare the rate of akathisia after administration of intravenous prochlorperazine as a 2-minute bolus or 15-minute infusion. METHODS: We conducted a prospective, randomized, double-blind study in the emergency department of a central-city teaching hospital. Patients aged 18 years or older treated with prochlorperazine for headache, nausea, or vomiting were eligible for inclusion. Study participants were randomized to receive 10 mg of prochlorperazine administered intravenously by means of 2-minute push (bolus group) or 10 mg diluted in 50 mL of normal saline solution administered by means of intravenous infusion during a 15-minute period (infusion group). The main outcome was the number of study participants experiencing akathisia within 60 minutes of administration. Akathisia was defined as either a spontaneous report of restlessness or agitation or a change of 2 or more in the patient-reported akathisia rating scale and a change of at least 1 in the investigator-observed akathisia rating scale. The intensity of headache and nausea was measured with a 100-mm visual analog scale. RESULTS: One hundred patients were enrolled. One study participant was excluded after protocol violation. Seventy-three percent (73/99) of the study participants were treated for headache and 70% (70/99) for nausea. In the bolus group, 26.0% (13/50) had akathisia compared with 32.7% (16/49) in the infusion group (Delta=-6.7%; 95% confidence interval [CI] -24.6% to 11.2%). The difference between the bolus and infusion groups in the percentage of participants who saw a 50% reduction in their headache intensity within 30 minutes was 11.8% (95% CI -9.6% to 33.3%). The difference in the percentage of patients with a 50% reduction in their nausea was 12.6% (95% CI -4.6% to 29.8%). CONCLUSION: A 50% reduction in the incidence of akathisia when prochlorperazine was administered by means of 15-minute intravenous infusion versus a 2-minute intravenous push was not detected. The efficacy of prochlorperazine in the treatment of headache and nausea likewise did not appear to be affected by the rate of administration, although no formal statistical comparisons were made.", "entity": "Vomiting", "aliases": "Emesis Vomiting", "definition": "The forcible expulsion of the contents of the STOMACH through the MOUTH.\n    ", "id": "MESH:D014839"}
{"mention": "agitation", "mention_text": "STUDY OBJECTIVE: We sought to compare the rate of akathisia after administration of intravenous prochlorperazine as a 2-minute bolus or 15-minute infusion. METHODS: We conducted a prospective, randomized, double-blind study in the emergency department of a central-city teaching hospital. Patients aged 18 years or older treated with prochlorperazine for headache, nausea, or vomiting were eligible for inclusion. Study participants were randomized to receive 10 mg of prochlorperazine administered intravenously by means of 2-minute push (bolus group) or 10 mg diluted in 50 mL of normal saline solution administered by means of intravenous infusion during a 15-minute period (infusion group). The main outcome was the number of study participants experiencing akathisia within 60 minutes of administration. Akathisia was defined as either a spontaneous report of restlessness or agitation or a change of 2 or more in the patient-reported akathisia rating scale and a change of at least 1 in the investigator-observed akathisia rating scale. The intensity of headache and nausea was measured with a 100-mm visual analog scale. RESULTS: One hundred patients were enrolled. One study participant was excluded after protocol violation. Seventy-three percent (73/99) of the study participants were treated for headache and 70% (70/99) for nausea. In the bolus group, 26.0% (13/50) had akathisia compared with 32.7% (16/49) in the infusion group (Delta=-6.7%; 95% confidence interval [CI] -24.6% to 11.2%). The difference between the bolus and infusion groups in the percentage of participants who saw a 50% reduction in their headache intensity within 30 minutes was 11.8% (95% CI -9.6% to 33.3%). The difference in the percentage of patients with a 50% reduction in their nausea was 12.6% (95% CI -4.6% to 29.8%). CONCLUSION: A 50% reduction in the incidence of akathisia when prochlorperazine was administered by means of 15-minute intravenous infusion versus a 2-minute intravenous push was not detected. The efficacy of prochlorperazine in the treatment of headache and nausea likewise did not appear to be affected by the rate of administration, although no formal statistical comparisons were made.", "entity": "Psychomotor Agitation", "aliases": "Agitation Psychomotor Akathisia Excitement Hyperactivity Restlessness", "definition": "A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions.\n    ", "id": "MESH:D011595"}
{"mention": "Antithymocyte globulin", "mention_text": "Antithymocyte globulin in the treatment of D-penicillamine-induced aplastic anemia.", "entity": "Antilymphocyte Serum", "aliases": "ATGAM Anti Thymocyte Globulin Anti-Thymocyte Globulins Antibodies Antilymphocyte Lymphocytotoxic Antibody Antilymphoblast Immunoglobulin Immunoglobulins Serum Serums Antithymocyte Antithymoglobulin Antithymoglobulins Lymphocyte Immune (Equine) Pressimmune", "definition": "Serum containing GAMMA-GLOBULINS which are antibodies for lymphocyte ANTIGENS. It is used both as a test for HISTOCOMPATIBILITY and therapeutically in TRANSPLANTATION.\n    ", "id": "MESH:D000961"}
{"mention": "D-penicillamine", "mention_text": "Antithymocyte globulin in the treatment of D-penicillamine-induced aplastic anemia.", "entity": "Penicillamine", "aliases": "Copper Penicillaminate Cuprenil Cuprimine D 3 Mercaptovaline Penicillamine D-3-Mercaptovaline D-Penicillamine Dimethylcysteine Metalcaptase beta,beta beta,beta-Dimethylcysteine", "definition": "3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease.\n    ", "id": "MESH:D010396"}
{"mention": "aplastic anemia", "mention_text": "Antithymocyte globulin in the treatment of D-penicillamine-induced aplastic anemia.", "entity": "Anemia, Aplastic", "aliases": "Anemia Aplastic Hypoplastic Anemias", "definition": "A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements.\n    ", "id": "MESH:D000741"}
{"mention": "antithymocyte globulin", "mention_text": "A patient who received antithymocyte globulin therapy for aplastic anemia due to D-penicillamine therapy is described. Bone marrow recovery and peripheral blood recovery were complete 1 month and 3 months, respectively, after treatment, and blood transfusion or other therapies were not necessary in a follow-up period of more than 2 years. Use of antithymocyte globulin may be the optimal treatment of D-penicillamine-induced aplastic anemia.", "entity": "Antilymphocyte Serum", "aliases": "ATGAM Anti Thymocyte Globulin Anti-Thymocyte Globulins Antibodies Antilymphocyte Lymphocytotoxic Antibody Antilymphoblast Immunoglobulin Immunoglobulins Serum Serums Antithymocyte Antithymoglobulin Antithymoglobulins Lymphocyte Immune (Equine) Pressimmune", "definition": "Serum containing GAMMA-GLOBULINS which are antibodies for lymphocyte ANTIGENS. It is used both as a test for HISTOCOMPATIBILITY and therapeutically in TRANSPLANTATION.\n    ", "id": "MESH:D000961"}
{"mention": "aplastic anemia", "mention_text": "A patient who received antithymocyte globulin therapy for aplastic anemia due to D-penicillamine therapy is described. Bone marrow recovery and peripheral blood recovery were complete 1 month and 3 months, respectively, after treatment, and blood transfusion or other therapies were not necessary in a follow-up period of more than 2 years. Use of antithymocyte globulin may be the optimal treatment of D-penicillamine-induced aplastic anemia.", "entity": "Anemia, Aplastic", "aliases": "Anemia Aplastic Hypoplastic Anemias", "definition": "A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements.\n    ", "id": "MESH:D000741"}
{"mention": "D-penicillamine", "mention_text": "A patient who received antithymocyte globulin therapy for aplastic anemia due to D-penicillamine therapy is described. Bone marrow recovery and peripheral blood recovery were complete 1 month and 3 months, respectively, after treatment, and blood transfusion or other therapies were not necessary in a follow-up period of more than 2 years. Use of antithymocyte globulin may be the optimal treatment of D-penicillamine-induced aplastic anemia.", "entity": "Penicillamine", "aliases": "Copper Penicillaminate Cuprenil Cuprimine D 3 Mercaptovaline Penicillamine D-3-Mercaptovaline D-Penicillamine Dimethylcysteine Metalcaptase beta,beta beta,beta-Dimethylcysteine", "definition": "3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease.\n    ", "id": "MESH:D010396"}
{"mention": "acetylcholine", "mention_text": "The relationship between hippocampal acetylcholine release and cholinergic convulsant sensitivity in withdrawal seizure-prone and withdrawal seizure-resistant selected mouse lines.", "entity": "Acetylcholine", "aliases": "2-(Acetyloxy)-N,N,N-trimethylethanaminium Acetilcolina Cusi Acetylcholine Bromide Chloride Fluoride Hydroxide Iodide L Tartrate L-Tartrate Perchlorate Picrate (1:1) Sulfate Alcon Brand of Bournonville Bromoacetylcholine Chloroacetylcholine Ciba Vision Iolab Miochol", "definition": "A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.\n    ", "id": "MESH:D000109"}
{"mention": "seizure", "mention_text": "The relationship between hippocampal acetylcholine release and cholinergic convulsant sensitivity in withdrawal seizure-prone and withdrawal seizure-resistant selected mouse lines.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "alcohol", "mention_text": "BACKGROUND: The septo-hippocampal cholinergic pathway has been implicated in epileptogenesis, and genetic factors influence the response to cholinergic agents, but limited data are available on cholinergic involvement in alcohol withdrawal severity. Thus, the relationship between cholinergic activity and responsiveness and alcohol withdrawal was investigated in a genetic animal model of ethanol withdrawal severity. METHODS: Cholinergic convulsant sensitivity was examined in alcohol-na  ve Withdrawal Seizure-Prone (WSP) and-Resistant (WSR) mice. Animals were administered nicotine, carbachol, or neostigmine via timed tail vein infusion, and the latencies to onset of tremor and clonus were recorded and converted to threshold dose. We also used microdialysis to measure basal and potassium-stimulated acetylcholine (ACh) release in the CA1 region of the hippocampus. Potassium was applied by reverse dialysis twice, separated by 75 min. Hippocampal ACh also was measured during testing for handling-induced convulsions. RESULTS: Sensitivity to several convulsion endpoints induced by nicotine, carbachol, and neostigmine were significantly greater in WSR versus WSP mice. In microdialysis experiments, the lines did not differ in basal release of ACh, and 50 mM KCl increased ACh output in both lines of mice. However, the increase in release of ACh produced by the first application of KCl was 2-fold higher in WSP versus WSR mice. When hippocampal ACh was measured during testing for handling-induced convulsions, extracellular ACh was significantly elevated (192%) in WSP mice, but was nonsignificantly elevated (59%) in WSR mice. CONCLUSIONS: These results suggest that differences in cholinergic activity and postsynaptic sensitivity to cholinergic convulsants may be associated with ethanol withdrawal severity and implicate cholinergic mechanisms in alcohol withdrawal. Specifically, WSP mice may have lower sensitivity to cholinergic convulsants compared with WSR because of postsynaptic receptor desensitization brought on by higher activity of cholinergic neurons.", "entity": "Ethanol", "aliases": "Absolute Alcohol Ethyl Grain Ethanol", "definition": "A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.\n    ", "id": "MESH:D000431"}
{"mention": "ethanol", "mention_text": "BACKGROUND: The septo-hippocampal cholinergic pathway has been implicated in epileptogenesis, and genetic factors influence the response to cholinergic agents, but limited data are available on cholinergic involvement in alcohol withdrawal severity. Thus, the relationship between cholinergic activity and responsiveness and alcohol withdrawal was investigated in a genetic animal model of ethanol withdrawal severity. METHODS: Cholinergic convulsant sensitivity was examined in alcohol-na  ve Withdrawal Seizure-Prone (WSP) and-Resistant (WSR) mice. Animals were administered nicotine, carbachol, or neostigmine via timed tail vein infusion, and the latencies to onset of tremor and clonus were recorded and converted to threshold dose. We also used microdialysis to measure basal and potassium-stimulated acetylcholine (ACh) release in the CA1 region of the hippocampus. Potassium was applied by reverse dialysis twice, separated by 75 min. Hippocampal ACh also was measured during testing for handling-induced convulsions. RESULTS: Sensitivity to several convulsion endpoints induced by nicotine, carbachol, and neostigmine were significantly greater in WSR versus WSP mice. In microdialysis experiments, the lines did not differ in basal release of ACh, and 50 mM KCl increased ACh output in both lines of mice. However, the increase in release of ACh produced by the first application of KCl was 2-fold higher in WSP versus WSR mice. When hippocampal ACh was measured during testing for handling-induced convulsions, extracellular ACh was significantly elevated (192%) in WSP mice, but was nonsignificantly elevated (59%) in WSR mice. CONCLUSIONS: These results suggest that differences in cholinergic activity and postsynaptic sensitivity to cholinergic convulsants may be associated with ethanol withdrawal severity and implicate cholinergic mechanisms in alcohol withdrawal. Specifically, WSP mice may have lower sensitivity to cholinergic convulsants compared with WSR because of postsynaptic receptor desensitization brought on by higher activity of cholinergic neurons.", "entity": "Ethanol", "aliases": "Absolute Alcohol Ethyl Grain Ethanol", "definition": "A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.\n    ", "id": "MESH:D000431"}
{"mention": "Seizure", "mention_text": "BACKGROUND: The septo-hippocampal cholinergic pathway has been implicated in epileptogenesis, and genetic factors influence the response to cholinergic agents, but limited data are available on cholinergic involvement in alcohol withdrawal severity. Thus, the relationship between cholinergic activity and responsiveness and alcohol withdrawal was investigated in a genetic animal model of ethanol withdrawal severity. METHODS: Cholinergic convulsant sensitivity was examined in alcohol-na  ve Withdrawal Seizure-Prone (WSP) and-Resistant (WSR) mice. Animals were administered nicotine, carbachol, or neostigmine via timed tail vein infusion, and the latencies to onset of tremor and clonus were recorded and converted to threshold dose. We also used microdialysis to measure basal and potassium-stimulated acetylcholine (ACh) release in the CA1 region of the hippocampus. Potassium was applied by reverse dialysis twice, separated by 75 min. Hippocampal ACh also was measured during testing for handling-induced convulsions. RESULTS: Sensitivity to several convulsion endpoints induced by nicotine, carbachol, and neostigmine were significantly greater in WSR versus WSP mice. In microdialysis experiments, the lines did not differ in basal release of ACh, and 50 mM KCl increased ACh output in both lines of mice. However, the increase in release of ACh produced by the first application of KCl was 2-fold higher in WSP versus WSR mice. When hippocampal ACh was measured during testing for handling-induced convulsions, extracellular ACh was significantly elevated (192%) in WSP mice, but was nonsignificantly elevated (59%) in WSR mice. CONCLUSIONS: These results suggest that differences in cholinergic activity and postsynaptic sensitivity to cholinergic convulsants may be associated with ethanol withdrawal severity and implicate cholinergic mechanisms in alcohol withdrawal. Specifically, WSP mice may have lower sensitivity to cholinergic convulsants compared with WSR because of postsynaptic receptor desensitization brought on by higher activity of cholinergic neurons.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "nicotine", "mention_text": "BACKGROUND: The septo-hippocampal cholinergic pathway has been implicated in epileptogenesis, and genetic factors influence the response to cholinergic agents, but limited data are available on cholinergic involvement in alcohol withdrawal severity. Thus, the relationship between cholinergic activity and responsiveness and alcohol withdrawal was investigated in a genetic animal model of ethanol withdrawal severity. METHODS: Cholinergic convulsant sensitivity was examined in alcohol-na  ve Withdrawal Seizure-Prone (WSP) and-Resistant (WSR) mice. Animals were administered nicotine, carbachol, or neostigmine via timed tail vein infusion, and the latencies to onset of tremor and clonus were recorded and converted to threshold dose. We also used microdialysis to measure basal and potassium-stimulated acetylcholine (ACh) release in the CA1 region of the hippocampus. Potassium was applied by reverse dialysis twice, separated by 75 min. Hippocampal ACh also was measured during testing for handling-induced convulsions. RESULTS: Sensitivity to several convulsion endpoints induced by nicotine, carbachol, and neostigmine were significantly greater in WSR versus WSP mice. In microdialysis experiments, the lines did not differ in basal release of ACh, and 50 mM KCl increased ACh output in both lines of mice. However, the increase in release of ACh produced by the first application of KCl was 2-fold higher in WSP versus WSR mice. When hippocampal ACh was measured during testing for handling-induced convulsions, extracellular ACh was significantly elevated (192%) in WSP mice, but was nonsignificantly elevated (59%) in WSR mice. CONCLUSIONS: These results suggest that differences in cholinergic activity and postsynaptic sensitivity to cholinergic convulsants may be associated with ethanol withdrawal severity and implicate cholinergic mechanisms in alcohol withdrawal. Specifically, WSP mice may have lower sensitivity to cholinergic convulsants compared with WSR because of postsynaptic receptor desensitization brought on by higher activity of cholinergic neurons.", "entity": "Nicotine", "aliases": "Bitartrate Nicotine Tartrate", "definition": "Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.\n    ", "id": "MESH:D009538"}
{"mention": "carbachol", "mention_text": "BACKGROUND: The septo-hippocampal cholinergic pathway has been implicated in epileptogenesis, and genetic factors influence the response to cholinergic agents, but limited data are available on cholinergic involvement in alcohol withdrawal severity. Thus, the relationship between cholinergic activity and responsiveness and alcohol withdrawal was investigated in a genetic animal model of ethanol withdrawal severity. METHODS: Cholinergic convulsant sensitivity was examined in alcohol-na  ve Withdrawal Seizure-Prone (WSP) and-Resistant (WSR) mice. Animals were administered nicotine, carbachol, or neostigmine via timed tail vein infusion, and the latencies to onset of tremor and clonus were recorded and converted to threshold dose. We also used microdialysis to measure basal and potassium-stimulated acetylcholine (ACh) release in the CA1 region of the hippocampus. Potassium was applied by reverse dialysis twice, separated by 75 min. Hippocampal ACh also was measured during testing for handling-induced convulsions. RESULTS: Sensitivity to several convulsion endpoints induced by nicotine, carbachol, and neostigmine were significantly greater in WSR versus WSP mice. In microdialysis experiments, the lines did not differ in basal release of ACh, and 50 mM KCl increased ACh output in both lines of mice. However, the increase in release of ACh produced by the first application of KCl was 2-fold higher in WSP versus WSR mice. When hippocampal ACh was measured during testing for handling-induced convulsions, extracellular ACh was significantly elevated (192%) in WSP mice, but was nonsignificantly elevated (59%) in WSR mice. CONCLUSIONS: These results suggest that differences in cholinergic activity and postsynaptic sensitivity to cholinergic convulsants may be associated with ethanol withdrawal severity and implicate cholinergic mechanisms in alcohol withdrawal. Specifically, WSP mice may have lower sensitivity to cholinergic convulsants compared with WSR because of postsynaptic receptor desensitization brought on by higher activity of cholinergic neurons.", "entity": "Carbachol", "aliases": "Alcon Brand 1 of Carbachol 2 Allphar Bioniche Bipharma Isopto Carbacholine Carbamann Carbamoylcholine Carbamylcholine Carbastat Carbocholine Carboptic Chauvin Doryl Jestryl Mann Merck Miostat Novartis NutraMax Optopics", "definition": "A slowly hydrolyzed cholinergic agonist that acts at both muscarinic and nicotinic receptors.\n    ", "id": "MESH:D002217"}
{"mention": "neostigmine", "mention_text": "BACKGROUND: The septo-hippocampal cholinergic pathway has been implicated in epileptogenesis, and genetic factors influence the response to cholinergic agents, but limited data are available on cholinergic involvement in alcohol withdrawal severity. Thus, the relationship between cholinergic activity and responsiveness and alcohol withdrawal was investigated in a genetic animal model of ethanol withdrawal severity. METHODS: Cholinergic convulsant sensitivity was examined in alcohol-na  ve Withdrawal Seizure-Prone (WSP) and-Resistant (WSR) mice. Animals were administered nicotine, carbachol, or neostigmine via timed tail vein infusion, and the latencies to onset of tremor and clonus were recorded and converted to threshold dose. We also used microdialysis to measure basal and potassium-stimulated acetylcholine (ACh) release in the CA1 region of the hippocampus. Potassium was applied by reverse dialysis twice, separated by 75 min. Hippocampal ACh also was measured during testing for handling-induced convulsions. RESULTS: Sensitivity to several convulsion endpoints induced by nicotine, carbachol, and neostigmine were significantly greater in WSR versus WSP mice. In microdialysis experiments, the lines did not differ in basal release of ACh, and 50 mM KCl increased ACh output in both lines of mice. However, the increase in release of ACh produced by the first application of KCl was 2-fold higher in WSP versus WSR mice. When hippocampal ACh was measured during testing for handling-induced convulsions, extracellular ACh was significantly elevated (192%) in WSP mice, but was nonsignificantly elevated (59%) in WSR mice. CONCLUSIONS: These results suggest that differences in cholinergic activity and postsynaptic sensitivity to cholinergic convulsants may be associated with ethanol withdrawal severity and implicate cholinergic mechanisms in alcohol withdrawal. Specifically, WSP mice may have lower sensitivity to cholinergic convulsants compared with WSR because of postsynaptic receptor desensitization brought on by higher activity of cholinergic neurons.", "entity": "Neostigmine", "aliases": "Bromide Neostigmine Methylsulfate Polstigmine Proserine Prostigmin Prostigmine Prozerin Synstigmin Syntostigmine", "definition": "A cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine. Neostigmine, unlike PHYSOSTIGMINE, does not cross the blood-brain barrier.\n    ", "id": "MESH:D009388"}
{"mention": "tremor", "mention_text": "BACKGROUND: The septo-hippocampal cholinergic pathway has been implicated in epileptogenesis, and genetic factors influence the response to cholinergic agents, but limited data are available on cholinergic involvement in alcohol withdrawal severity. Thus, the relationship between cholinergic activity and responsiveness and alcohol withdrawal was investigated in a genetic animal model of ethanol withdrawal severity. METHODS: Cholinergic convulsant sensitivity was examined in alcohol-na  ve Withdrawal Seizure-Prone (WSP) and-Resistant (WSR) mice. Animals were administered nicotine, carbachol, or neostigmine via timed tail vein infusion, and the latencies to onset of tremor and clonus were recorded and converted to threshold dose. We also used microdialysis to measure basal and potassium-stimulated acetylcholine (ACh) release in the CA1 region of the hippocampus. Potassium was applied by reverse dialysis twice, separated by 75 min. Hippocampal ACh also was measured during testing for handling-induced convulsions. RESULTS: Sensitivity to several convulsion endpoints induced by nicotine, carbachol, and neostigmine were significantly greater in WSR versus WSP mice. In microdialysis experiments, the lines did not differ in basal release of ACh, and 50 mM KCl increased ACh output in both lines of mice. However, the increase in release of ACh produced by the first application of KCl was 2-fold higher in WSP versus WSR mice. When hippocampal ACh was measured during testing for handling-induced convulsions, extracellular ACh was significantly elevated (192%) in WSP mice, but was nonsignificantly elevated (59%) in WSR mice. CONCLUSIONS: These results suggest that differences in cholinergic activity and postsynaptic sensitivity to cholinergic convulsants may be associated with ethanol withdrawal severity and implicate cholinergic mechanisms in alcohol withdrawal. Specifically, WSP mice may have lower sensitivity to cholinergic convulsants compared with WSR because of postsynaptic receptor desensitization brought on by higher activity of cholinergic neurons.", "entity": "Tremor", "aliases": "Action Tremor Tremors Coarse Continuous Darkness Fine Intention Intermittent Involuntary Quiver Quivers Limb Massive Muscle Neonatal Nerve Passive Perioral Persistent Pill Rolling Rest Resting Saturnine Semirhythmic Senile Static", "definition": "Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of CEREBELLAR DISEASES, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of PARKINSON DISEASE.\n    ", "id": "MESH:D014202"}
{"mention": "potassium", "mention_text": "BACKGROUND: The septo-hippocampal cholinergic pathway has been implicated in epileptogenesis, and genetic factors influence the response to cholinergic agents, but limited data are available on cholinergic involvement in alcohol withdrawal severity. Thus, the relationship between cholinergic activity and responsiveness and alcohol withdrawal was investigated in a genetic animal model of ethanol withdrawal severity. METHODS: Cholinergic convulsant sensitivity was examined in alcohol-na  ve Withdrawal Seizure-Prone (WSP) and-Resistant (WSR) mice. Animals were administered nicotine, carbachol, or neostigmine via timed tail vein infusion, and the latencies to onset of tremor and clonus were recorded and converted to threshold dose. We also used microdialysis to measure basal and potassium-stimulated acetylcholine (ACh) release in the CA1 region of the hippocampus. Potassium was applied by reverse dialysis twice, separated by 75 min. Hippocampal ACh also was measured during testing for handling-induced convulsions. RESULTS: Sensitivity to several convulsion endpoints induced by nicotine, carbachol, and neostigmine were significantly greater in WSR versus WSP mice. In microdialysis experiments, the lines did not differ in basal release of ACh, and 50 mM KCl increased ACh output in both lines of mice. However, the increase in release of ACh produced by the first application of KCl was 2-fold higher in WSP versus WSR mice. When hippocampal ACh was measured during testing for handling-induced convulsions, extracellular ACh was significantly elevated (192%) in WSP mice, but was nonsignificantly elevated (59%) in WSR mice. CONCLUSIONS: These results suggest that differences in cholinergic activity and postsynaptic sensitivity to cholinergic convulsants may be associated with ethanol withdrawal severity and implicate cholinergic mechanisms in alcohol withdrawal. Specifically, WSP mice may have lower sensitivity to cholinergic convulsants compared with WSR because of postsynaptic receptor desensitization brought on by higher activity of cholinergic neurons.", "entity": "Potassium", "aliases": "Potassium", "definition": "An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.\n    ", "id": "MESH:D011188"}
{"mention": "acetylcholine", "mention_text": "BACKGROUND: The septo-hippocampal cholinergic pathway has been implicated in epileptogenesis, and genetic factors influence the response to cholinergic agents, but limited data are available on cholinergic involvement in alcohol withdrawal severity. Thus, the relationship between cholinergic activity and responsiveness and alcohol withdrawal was investigated in a genetic animal model of ethanol withdrawal severity. METHODS: Cholinergic convulsant sensitivity was examined in alcohol-na  ve Withdrawal Seizure-Prone (WSP) and-Resistant (WSR) mice. Animals were administered nicotine, carbachol, or neostigmine via timed tail vein infusion, and the latencies to onset of tremor and clonus were recorded and converted to threshold dose. We also used microdialysis to measure basal and potassium-stimulated acetylcholine (ACh) release in the CA1 region of the hippocampus. Potassium was applied by reverse dialysis twice, separated by 75 min. Hippocampal ACh also was measured during testing for handling-induced convulsions. RESULTS: Sensitivity to several convulsion endpoints induced by nicotine, carbachol, and neostigmine were significantly greater in WSR versus WSP mice. In microdialysis experiments, the lines did not differ in basal release of ACh, and 50 mM KCl increased ACh output in both lines of mice. However, the increase in release of ACh produced by the first application of KCl was 2-fold higher in WSP versus WSR mice. When hippocampal ACh was measured during testing for handling-induced convulsions, extracellular ACh was significantly elevated (192%) in WSP mice, but was nonsignificantly elevated (59%) in WSR mice. CONCLUSIONS: These results suggest that differences in cholinergic activity and postsynaptic sensitivity to cholinergic convulsants may be associated with ethanol withdrawal severity and implicate cholinergic mechanisms in alcohol withdrawal. Specifically, WSP mice may have lower sensitivity to cholinergic convulsants compared with WSR because of postsynaptic receptor desensitization brought on by higher activity of cholinergic neurons.", "entity": "Acetylcholine", "aliases": "2-(Acetyloxy)-N,N,N-trimethylethanaminium Acetilcolina Cusi Acetylcholine Bromide Chloride Fluoride Hydroxide Iodide L Tartrate L-Tartrate Perchlorate Picrate (1:1) Sulfate Alcon Brand of Bournonville Bromoacetylcholine Chloroacetylcholine Ciba Vision Iolab Miochol", "definition": "A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.\n    ", "id": "MESH:D000109"}
{"mention": "ACh", "mention_text": "BACKGROUND: The septo-hippocampal cholinergic pathway has been implicated in epileptogenesis, and genetic factors influence the response to cholinergic agents, but limited data are available on cholinergic involvement in alcohol withdrawal severity. Thus, the relationship between cholinergic activity and responsiveness and alcohol withdrawal was investigated in a genetic animal model of ethanol withdrawal severity. METHODS: Cholinergic convulsant sensitivity was examined in alcohol-na  ve Withdrawal Seizure-Prone (WSP) and-Resistant (WSR) mice. Animals were administered nicotine, carbachol, or neostigmine via timed tail vein infusion, and the latencies to onset of tremor and clonus were recorded and converted to threshold dose. We also used microdialysis to measure basal and potassium-stimulated acetylcholine (ACh) release in the CA1 region of the hippocampus. Potassium was applied by reverse dialysis twice, separated by 75 min. Hippocampal ACh also was measured during testing for handling-induced convulsions. RESULTS: Sensitivity to several convulsion endpoints induced by nicotine, carbachol, and neostigmine were significantly greater in WSR versus WSP mice. In microdialysis experiments, the lines did not differ in basal release of ACh, and 50 mM KCl increased ACh output in both lines of mice. However, the increase in release of ACh produced by the first application of KCl was 2-fold higher in WSP versus WSR mice. When hippocampal ACh was measured during testing for handling-induced convulsions, extracellular ACh was significantly elevated (192%) in WSP mice, but was nonsignificantly elevated (59%) in WSR mice. CONCLUSIONS: These results suggest that differences in cholinergic activity and postsynaptic sensitivity to cholinergic convulsants may be associated with ethanol withdrawal severity and implicate cholinergic mechanisms in alcohol withdrawal. Specifically, WSP mice may have lower sensitivity to cholinergic convulsants compared with WSR because of postsynaptic receptor desensitization brought on by higher activity of cholinergic neurons.", "entity": "Acetylcholine", "aliases": "2-(Acetyloxy)-N,N,N-trimethylethanaminium Acetilcolina Cusi Acetylcholine Bromide Chloride Fluoride Hydroxide Iodide L Tartrate L-Tartrate Perchlorate Picrate (1:1) Sulfate Alcon Brand of Bournonville Bromoacetylcholine Chloroacetylcholine Ciba Vision Iolab Miochol", "definition": "A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.\n    ", "id": "MESH:D000109"}
{"mention": "Potassium", "mention_text": "BACKGROUND: The septo-hippocampal cholinergic pathway has been implicated in epileptogenesis, and genetic factors influence the response to cholinergic agents, but limited data are available on cholinergic involvement in alcohol withdrawal severity. Thus, the relationship between cholinergic activity and responsiveness and alcohol withdrawal was investigated in a genetic animal model of ethanol withdrawal severity. METHODS: Cholinergic convulsant sensitivity was examined in alcohol-na  ve Withdrawal Seizure-Prone (WSP) and-Resistant (WSR) mice. Animals were administered nicotine, carbachol, or neostigmine via timed tail vein infusion, and the latencies to onset of tremor and clonus were recorded and converted to threshold dose. We also used microdialysis to measure basal and potassium-stimulated acetylcholine (ACh) release in the CA1 region of the hippocampus. Potassium was applied by reverse dialysis twice, separated by 75 min. Hippocampal ACh also was measured during testing for handling-induced convulsions. RESULTS: Sensitivity to several convulsion endpoints induced by nicotine, carbachol, and neostigmine were significantly greater in WSR versus WSP mice. In microdialysis experiments, the lines did not differ in basal release of ACh, and 50 mM KCl increased ACh output in both lines of mice. However, the increase in release of ACh produced by the first application of KCl was 2-fold higher in WSP versus WSR mice. When hippocampal ACh was measured during testing for handling-induced convulsions, extracellular ACh was significantly elevated (192%) in WSP mice, but was nonsignificantly elevated (59%) in WSR mice. CONCLUSIONS: These results suggest that differences in cholinergic activity and postsynaptic sensitivity to cholinergic convulsants may be associated with ethanol withdrawal severity and implicate cholinergic mechanisms in alcohol withdrawal. Specifically, WSP mice may have lower sensitivity to cholinergic convulsants compared with WSR because of postsynaptic receptor desensitization brought on by higher activity of cholinergic neurons.", "entity": "Potassium", "aliases": "Potassium", "definition": "An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.\n    ", "id": "MESH:D011188"}
{"mention": "convulsions", "mention_text": "BACKGROUND: The septo-hippocampal cholinergic pathway has been implicated in epileptogenesis, and genetic factors influence the response to cholinergic agents, but limited data are available on cholinergic involvement in alcohol withdrawal severity. Thus, the relationship between cholinergic activity and responsiveness and alcohol withdrawal was investigated in a genetic animal model of ethanol withdrawal severity. METHODS: Cholinergic convulsant sensitivity was examined in alcohol-na  ve Withdrawal Seizure-Prone (WSP) and-Resistant (WSR) mice. Animals were administered nicotine, carbachol, or neostigmine via timed tail vein infusion, and the latencies to onset of tremor and clonus were recorded and converted to threshold dose. We also used microdialysis to measure basal and potassium-stimulated acetylcholine (ACh) release in the CA1 region of the hippocampus. Potassium was applied by reverse dialysis twice, separated by 75 min. Hippocampal ACh also was measured during testing for handling-induced convulsions. RESULTS: Sensitivity to several convulsion endpoints induced by nicotine, carbachol, and neostigmine were significantly greater in WSR versus WSP mice. In microdialysis experiments, the lines did not differ in basal release of ACh, and 50 mM KCl increased ACh output in both lines of mice. However, the increase in release of ACh produced by the first application of KCl was 2-fold higher in WSP versus WSR mice. When hippocampal ACh was measured during testing for handling-induced convulsions, extracellular ACh was significantly elevated (192%) in WSP mice, but was nonsignificantly elevated (59%) in WSR mice. CONCLUSIONS: These results suggest that differences in cholinergic activity and postsynaptic sensitivity to cholinergic convulsants may be associated with ethanol withdrawal severity and implicate cholinergic mechanisms in alcohol withdrawal. Specifically, WSP mice may have lower sensitivity to cholinergic convulsants compared with WSR because of postsynaptic receptor desensitization brought on by higher activity of cholinergic neurons.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "convulsion", "mention_text": "BACKGROUND: The septo-hippocampal cholinergic pathway has been implicated in epileptogenesis, and genetic factors influence the response to cholinergic agents, but limited data are available on cholinergic involvement in alcohol withdrawal severity. Thus, the relationship between cholinergic activity and responsiveness and alcohol withdrawal was investigated in a genetic animal model of ethanol withdrawal severity. METHODS: Cholinergic convulsant sensitivity was examined in alcohol-na  ve Withdrawal Seizure-Prone (WSP) and-Resistant (WSR) mice. Animals were administered nicotine, carbachol, or neostigmine via timed tail vein infusion, and the latencies to onset of tremor and clonus were recorded and converted to threshold dose. We also used microdialysis to measure basal and potassium-stimulated acetylcholine (ACh) release in the CA1 region of the hippocampus. Potassium was applied by reverse dialysis twice, separated by 75 min. Hippocampal ACh also was measured during testing for handling-induced convulsions. RESULTS: Sensitivity to several convulsion endpoints induced by nicotine, carbachol, and neostigmine were significantly greater in WSR versus WSP mice. In microdialysis experiments, the lines did not differ in basal release of ACh, and 50 mM KCl increased ACh output in both lines of mice. However, the increase in release of ACh produced by the first application of KCl was 2-fold higher in WSP versus WSR mice. When hippocampal ACh was measured during testing for handling-induced convulsions, extracellular ACh was significantly elevated (192%) in WSP mice, but was nonsignificantly elevated (59%) in WSR mice. CONCLUSIONS: These results suggest that differences in cholinergic activity and postsynaptic sensitivity to cholinergic convulsants may be associated with ethanol withdrawal severity and implicate cholinergic mechanisms in alcohol withdrawal. Specifically, WSP mice may have lower sensitivity to cholinergic convulsants compared with WSR because of postsynaptic receptor desensitization brought on by higher activity of cholinergic neurons.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "KCl", "mention_text": "BACKGROUND: The septo-hippocampal cholinergic pathway has been implicated in epileptogenesis, and genetic factors influence the response to cholinergic agents, but limited data are available on cholinergic involvement in alcohol withdrawal severity. Thus, the relationship between cholinergic activity and responsiveness and alcohol withdrawal was investigated in a genetic animal model of ethanol withdrawal severity. METHODS: Cholinergic convulsant sensitivity was examined in alcohol-na  ve Withdrawal Seizure-Prone (WSP) and-Resistant (WSR) mice. Animals were administered nicotine, carbachol, or neostigmine via timed tail vein infusion, and the latencies to onset of tremor and clonus were recorded and converted to threshold dose. We also used microdialysis to measure basal and potassium-stimulated acetylcholine (ACh) release in the CA1 region of the hippocampus. Potassium was applied by reverse dialysis twice, separated by 75 min. Hippocampal ACh also was measured during testing for handling-induced convulsions. RESULTS: Sensitivity to several convulsion endpoints induced by nicotine, carbachol, and neostigmine were significantly greater in WSR versus WSP mice. In microdialysis experiments, the lines did not differ in basal release of ACh, and 50 mM KCl increased ACh output in both lines of mice. However, the increase in release of ACh produced by the first application of KCl was 2-fold higher in WSP versus WSR mice. When hippocampal ACh was measured during testing for handling-induced convulsions, extracellular ACh was significantly elevated (192%) in WSP mice, but was nonsignificantly elevated (59%) in WSR mice. CONCLUSIONS: These results suggest that differences in cholinergic activity and postsynaptic sensitivity to cholinergic convulsants may be associated with ethanol withdrawal severity and implicate cholinergic mechanisms in alcohol withdrawal. Specifically, WSP mice may have lower sensitivity to cholinergic convulsants compared with WSR because of postsynaptic receptor desensitization brought on by higher activity of cholinergic neurons.", "entity": "KCL compound", "aliases": "KCL compound", "definition": "", "id": "MESH:C522374"}
{"mention": "convulsants", "mention_text": "BACKGROUND: The septo-hippocampal cholinergic pathway has been implicated in epileptogenesis, and genetic factors influence the response to cholinergic agents, but limited data are available on cholinergic involvement in alcohol withdrawal severity. Thus, the relationship between cholinergic activity and responsiveness and alcohol withdrawal was investigated in a genetic animal model of ethanol withdrawal severity. METHODS: Cholinergic convulsant sensitivity was examined in alcohol-na  ve Withdrawal Seizure-Prone (WSP) and-Resistant (WSR) mice. Animals were administered nicotine, carbachol, or neostigmine via timed tail vein infusion, and the latencies to onset of tremor and clonus were recorded and converted to threshold dose. We also used microdialysis to measure basal and potassium-stimulated acetylcholine (ACh) release in the CA1 region of the hippocampus. Potassium was applied by reverse dialysis twice, separated by 75 min. Hippocampal ACh also was measured during testing for handling-induced convulsions. RESULTS: Sensitivity to several convulsion endpoints induced by nicotine, carbachol, and neostigmine were significantly greater in WSR versus WSP mice. In microdialysis experiments, the lines did not differ in basal release of ACh, and 50 mM KCl increased ACh output in both lines of mice. However, the increase in release of ACh produced by the first application of KCl was 2-fold higher in WSP versus WSR mice. When hippocampal ACh was measured during testing for handling-induced convulsions, extracellular ACh was significantly elevated (192%) in WSP mice, but was nonsignificantly elevated (59%) in WSR mice. CONCLUSIONS: These results suggest that differences in cholinergic activity and postsynaptic sensitivity to cholinergic convulsants may be associated with ethanol withdrawal severity and implicate cholinergic mechanisms in alcohol withdrawal. Specifically, WSP mice may have lower sensitivity to cholinergic convulsants compared with WSR because of postsynaptic receptor desensitization brought on by higher activity of cholinergic neurons.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "dexamethasone", "mention_text": "Prenatal dexamethasone programs hypertension and renal injury in the rat.", "entity": "Dexamethasone", "aliases": "Alcon Brand of Dexamethasone Decaject L.A. Decaject-L.A. Decameth Decaspray Dexasone Dexpak ECR Foy Hexadecadrol Hexadrol ICN Maxidex Merck Merz 1 2 Methylfluorprednisolone Millicorten Oradexon", "definition": "An anti-inflammatory 9-fluoro-glucocorticoid.\n    ", "id": "MESH:D003907"}
{"mention": "hypertension", "mention_text": "Prenatal dexamethasone programs hypertension and renal injury in the rat.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "renal injury", "mention_text": "Prenatal dexamethasone programs hypertension and renal injury in the rat.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "dexamethasone", "mention_text": "Dexamethasone is frequently administered to the developing fetus to accelerate pulmonary development. The purpose of the present study was to determine if prenatal dexamethasone programmed a progressive increase in blood pressure and renal injury in rats. Pregnant rats were given either vehicle or 2 daily intraperitoneal injections of dexamethasone (0.2 mg/kg body weight) on gestational days 11 and 12, 13 and 14, 15 and 16, 17 and 18, or 19 and 20. Offspring of rats administered dexamethasone on days 15 and 16 gestation had a 20% reduction in glomerular number compared with control at 6 to 9 months of age (22 527+/-509 versus 28 050+/-561, P<0.05), which was comparable to the percent reduction in glomeruli measured at 3 weeks of age. Six- to 9-month old rats receiving prenatal dexamethasone on days 17 and 18 of gestation had a 17% reduction in glomeruli (23 380+/-587) compared with control rats (P<0.05). Male rats that received prenatal dexamethasone on days 15 and 16, 17 and 18, and 13 and 14 of gestation had elevated blood pressures at 6 months of age; the latter group did not have a reduction in glomerular number. Adult rats given dexamethasone on days 15 and 16 of gestation had more glomeruli with glomerulosclerosis than control rats. This study shows that prenatal dexamethasone in rats results in a reduction in glomerular number, glomerulosclerosis, and hypertension when administered at specific points during gestation. Hypertension was observed in animals that had a reduction in glomeruli as well as in a group that did not have a reduction in glomerular number, suggesting that a reduction in glomerular number is not the sole cause for the development of hypertension.", "entity": "Dexamethasone", "aliases": "Alcon Brand of Dexamethasone Decaject L.A. Decaject-L.A. Decameth Decaspray Dexasone Dexpak ECR Foy Hexadecadrol Hexadrol ICN Maxidex Merck Merz 1 2 Methylfluorprednisolone Millicorten Oradexon", "definition": "An anti-inflammatory 9-fluoro-glucocorticoid.\n    ", "id": "MESH:D003907"}
{"mention": "increase in blood pressure", "mention_text": "Dexamethasone is frequently administered to the developing fetus to accelerate pulmonary development. The purpose of the present study was to determine if prenatal dexamethasone programmed a progressive increase in blood pressure and renal injury in rats. Pregnant rats were given either vehicle or 2 daily intraperitoneal injections of dexamethasone (0.2 mg/kg body weight) on gestational days 11 and 12, 13 and 14, 15 and 16, 17 and 18, or 19 and 20. Offspring of rats administered dexamethasone on days 15 and 16 gestation had a 20% reduction in glomerular number compared with control at 6 to 9 months of age (22 527+/-509 versus 28 050+/-561, P<0.05), which was comparable to the percent reduction in glomeruli measured at 3 weeks of age. Six- to 9-month old rats receiving prenatal dexamethasone on days 17 and 18 of gestation had a 17% reduction in glomeruli (23 380+/-587) compared with control rats (P<0.05). Male rats that received prenatal dexamethasone on days 15 and 16, 17 and 18, and 13 and 14 of gestation had elevated blood pressures at 6 months of age; the latter group did not have a reduction in glomerular number. Adult rats given dexamethasone on days 15 and 16 of gestation had more glomeruli with glomerulosclerosis than control rats. This study shows that prenatal dexamethasone in rats results in a reduction in glomerular number, glomerulosclerosis, and hypertension when administered at specific points during gestation. Hypertension was observed in animals that had a reduction in glomeruli as well as in a group that did not have a reduction in glomerular number, suggesting that a reduction in glomerular number is not the sole cause for the development of hypertension.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "renal injury", "mention_text": "Dexamethasone is frequently administered to the developing fetus to accelerate pulmonary development. The purpose of the present study was to determine if prenatal dexamethasone programmed a progressive increase in blood pressure and renal injury in rats. Pregnant rats were given either vehicle or 2 daily intraperitoneal injections of dexamethasone (0.2 mg/kg body weight) on gestational days 11 and 12, 13 and 14, 15 and 16, 17 and 18, or 19 and 20. Offspring of rats administered dexamethasone on days 15 and 16 gestation had a 20% reduction in glomerular number compared with control at 6 to 9 months of age (22 527+/-509 versus 28 050+/-561, P<0.05), which was comparable to the percent reduction in glomeruli measured at 3 weeks of age. Six- to 9-month old rats receiving prenatal dexamethasone on days 17 and 18 of gestation had a 17% reduction in glomeruli (23 380+/-587) compared with control rats (P<0.05). Male rats that received prenatal dexamethasone on days 15 and 16, 17 and 18, and 13 and 14 of gestation had elevated blood pressures at 6 months of age; the latter group did not have a reduction in glomerular number. Adult rats given dexamethasone on days 15 and 16 of gestation had more glomeruli with glomerulosclerosis than control rats. This study shows that prenatal dexamethasone in rats results in a reduction in glomerular number, glomerulosclerosis, and hypertension when administered at specific points during gestation. Hypertension was observed in animals that had a reduction in glomeruli as well as in a group that did not have a reduction in glomerular number, suggesting that a reduction in glomerular number is not the sole cause for the development of hypertension.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "reduction in glomerular number", "mention_text": "Dexamethasone is frequently administered to the developing fetus to accelerate pulmonary development. The purpose of the present study was to determine if prenatal dexamethasone programmed a progressive increase in blood pressure and renal injury in rats. Pregnant rats were given either vehicle or 2 daily intraperitoneal injections of dexamethasone (0.2 mg/kg body weight) on gestational days 11 and 12, 13 and 14, 15 and 16, 17 and 18, or 19 and 20. Offspring of rats administered dexamethasone on days 15 and 16 gestation had a 20% reduction in glomerular number compared with control at 6 to 9 months of age (22 527+/-509 versus 28 050+/-561, P<0.05), which was comparable to the percent reduction in glomeruli measured at 3 weeks of age. Six- to 9-month old rats receiving prenatal dexamethasone on days 17 and 18 of gestation had a 17% reduction in glomeruli (23 380+/-587) compared with control rats (P<0.05). Male rats that received prenatal dexamethasone on days 15 and 16, 17 and 18, and 13 and 14 of gestation had elevated blood pressures at 6 months of age; the latter group did not have a reduction in glomerular number. Adult rats given dexamethasone on days 15 and 16 of gestation had more glomeruli with glomerulosclerosis than control rats. This study shows that prenatal dexamethasone in rats results in a reduction in glomerular number, glomerulosclerosis, and hypertension when administered at specific points during gestation. Hypertension was observed in animals that had a reduction in glomeruli as well as in a group that did not have a reduction in glomerular number, suggesting that a reduction in glomerular number is not the sole cause for the development of hypertension.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "elevated blood pressures", "mention_text": "Dexamethasone is frequently administered to the developing fetus to accelerate pulmonary development. The purpose of the present study was to determine if prenatal dexamethasone programmed a progressive increase in blood pressure and renal injury in rats. Pregnant rats were given either vehicle or 2 daily intraperitoneal injections of dexamethasone (0.2 mg/kg body weight) on gestational days 11 and 12, 13 and 14, 15 and 16, 17 and 18, or 19 and 20. Offspring of rats administered dexamethasone on days 15 and 16 gestation had a 20% reduction in glomerular number compared with control at 6 to 9 months of age (22 527+/-509 versus 28 050+/-561, P<0.05), which was comparable to the percent reduction in glomeruli measured at 3 weeks of age. Six- to 9-month old rats receiving prenatal dexamethasone on days 17 and 18 of gestation had a 17% reduction in glomeruli (23 380+/-587) compared with control rats (P<0.05). Male rats that received prenatal dexamethasone on days 15 and 16, 17 and 18, and 13 and 14 of gestation had elevated blood pressures at 6 months of age; the latter group did not have a reduction in glomerular number. Adult rats given dexamethasone on days 15 and 16 of gestation had more glomeruli with glomerulosclerosis than control rats. This study shows that prenatal dexamethasone in rats results in a reduction in glomerular number, glomerulosclerosis, and hypertension when administered at specific points during gestation. Hypertension was observed in animals that had a reduction in glomeruli as well as in a group that did not have a reduction in glomerular number, suggesting that a reduction in glomerular number is not the sole cause for the development of hypertension.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "glomerulosclerosis", "mention_text": "Dexamethasone is frequently administered to the developing fetus to accelerate pulmonary development. The purpose of the present study was to determine if prenatal dexamethasone programmed a progressive increase in blood pressure and renal injury in rats. Pregnant rats were given either vehicle or 2 daily intraperitoneal injections of dexamethasone (0.2 mg/kg body weight) on gestational days 11 and 12, 13 and 14, 15 and 16, 17 and 18, or 19 and 20. Offspring of rats administered dexamethasone on days 15 and 16 gestation had a 20% reduction in glomerular number compared with control at 6 to 9 months of age (22 527+/-509 versus 28 050+/-561, P<0.05), which was comparable to the percent reduction in glomeruli measured at 3 weeks of age. Six- to 9-month old rats receiving prenatal dexamethasone on days 17 and 18 of gestation had a 17% reduction in glomeruli (23 380+/-587) compared with control rats (P<0.05). Male rats that received prenatal dexamethasone on days 15 and 16, 17 and 18, and 13 and 14 of gestation had elevated blood pressures at 6 months of age; the latter group did not have a reduction in glomerular number. Adult rats given dexamethasone on days 15 and 16 of gestation had more glomeruli with glomerulosclerosis than control rats. This study shows that prenatal dexamethasone in rats results in a reduction in glomerular number, glomerulosclerosis, and hypertension when administered at specific points during gestation. Hypertension was observed in animals that had a reduction in glomeruli as well as in a group that did not have a reduction in glomerular number, suggesting that a reduction in glomerular number is not the sole cause for the development of hypertension.", "entity": "Glomerulonephritis", "aliases": "Bright Disease Glomerulonephritides Glomerulonephritis", "definition": "Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.\n    ", "id": "MESH:D005921"}
{"mention": "hypertension", "mention_text": "Dexamethasone is frequently administered to the developing fetus to accelerate pulmonary development. The purpose of the present study was to determine if prenatal dexamethasone programmed a progressive increase in blood pressure and renal injury in rats. Pregnant rats were given either vehicle or 2 daily intraperitoneal injections of dexamethasone (0.2 mg/kg body weight) on gestational days 11 and 12, 13 and 14, 15 and 16, 17 and 18, or 19 and 20. Offspring of rats administered dexamethasone on days 15 and 16 gestation had a 20% reduction in glomerular number compared with control at 6 to 9 months of age (22 527+/-509 versus 28 050+/-561, P<0.05), which was comparable to the percent reduction in glomeruli measured at 3 weeks of age. Six- to 9-month old rats receiving prenatal dexamethasone on days 17 and 18 of gestation had a 17% reduction in glomeruli (23 380+/-587) compared with control rats (P<0.05). Male rats that received prenatal dexamethasone on days 15 and 16, 17 and 18, and 13 and 14 of gestation had elevated blood pressures at 6 months of age; the latter group did not have a reduction in glomerular number. Adult rats given dexamethasone on days 15 and 16 of gestation had more glomeruli with glomerulosclerosis than control rats. This study shows that prenatal dexamethasone in rats results in a reduction in glomerular number, glomerulosclerosis, and hypertension when administered at specific points during gestation. Hypertension was observed in animals that had a reduction in glomeruli as well as in a group that did not have a reduction in glomerular number, suggesting that a reduction in glomerular number is not the sole cause for the development of hypertension.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "Hypertension", "mention_text": "Dexamethasone is frequently administered to the developing fetus to accelerate pulmonary development. The purpose of the present study was to determine if prenatal dexamethasone programmed a progressive increase in blood pressure and renal injury in rats. Pregnant rats were given either vehicle or 2 daily intraperitoneal injections of dexamethasone (0.2 mg/kg body weight) on gestational days 11 and 12, 13 and 14, 15 and 16, 17 and 18, or 19 and 20. Offspring of rats administered dexamethasone on days 15 and 16 gestation had a 20% reduction in glomerular number compared with control at 6 to 9 months of age (22 527+/-509 versus 28 050+/-561, P<0.05), which was comparable to the percent reduction in glomeruli measured at 3 weeks of age. Six- to 9-month old rats receiving prenatal dexamethasone on days 17 and 18 of gestation had a 17% reduction in glomeruli (23 380+/-587) compared with control rats (P<0.05). Male rats that received prenatal dexamethasone on days 15 and 16, 17 and 18, and 13 and 14 of gestation had elevated blood pressures at 6 months of age; the latter group did not have a reduction in glomerular number. Adult rats given dexamethasone on days 15 and 16 of gestation had more glomeruli with glomerulosclerosis than control rats. This study shows that prenatal dexamethasone in rats results in a reduction in glomerular number, glomerulosclerosis, and hypertension when administered at specific points during gestation. Hypertension was observed in animals that had a reduction in glomeruli as well as in a group that did not have a reduction in glomerular number, suggesting that a reduction in glomerular number is not the sole cause for the development of hypertension.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "venous thromboembolism", "mention_text": "The risk of venous thromboembolism in women prescribed cyproterone acetate in combination with ethinyl estradiol: a nested cohort analysis and case-control study.", "entity": "Venous Thromboembolism", "aliases": "Thromboembolism Venous", "definition": "Obstruction of a vein or VEINS (embolism) by a blood clot (THROMBUS) in the blood stream.\n    ", "id": "MESH:D054556"}
{"mention": "cyproterone acetate", "mention_text": "The risk of venous thromboembolism in women prescribed cyproterone acetate in combination with ethinyl estradiol: a nested cohort analysis and case-control study.", "entity": "Cyproterone Acetate", "aliases": "Androcur Cyproterone Acetate (1 alpha,2 alpha)-Isomer alpha,9 beta,10 (17", "definition": "An agent with anti-androgen and progestational properties. It shows competitive binding with dihydrotestosterone at androgen receptor sites.\n    ", "id": "MESH:D017373"}
{"mention": "ethinyl estradiol", "mention_text": "The risk of venous thromboembolism in women prescribed cyproterone acetate in combination with ethinyl estradiol: a nested cohort analysis and case-control study.", "entity": "Ethinyl Estradiol", "aliases": "Effik Brand of Ethinyl Estradiol Estinyl Ethynyl Hemihydrate (8 alpha)-Isomer alpha,17 alpha,9 beta,13 alpha,14 beta)-Isomer (9 beta,17 Oestradiol Ethinyl-Oestradiol Ethinylestradiol Jenapharm Ethinyloestradiol Lynoral Microfollin Forte Organon Progynon C Schering Schering-Plough", "definition": "A semisynthetic alkylated ESTRADIOL with a 17-alpha-ethinyl substitution. It has high estrogenic potency when administered orally, and is often used as the estrogenic component in ORAL CONTRACEPTIVES.\n    ", "id": "MESH:D004997"}
{"mention": "Cyproterone acetate", "mention_text": "BACKGROUND: Cyproterone acetate combined with ethinyl estradiol (CPA/EE) is licensed in the UK for the treatment of women with acne and hirsutism and is also a treatment option for polycystic ovary syndrome (PCOS). Previous studies have demonstrated an increased risk of venous thromboembolism (VTE) associated with CPA/EE compared with conventional combined oral contraceptives (COCs). We believe the results of those studies may have been affected by residual confounding. METHODS: Using the General Practice Research Database we conducted a cohort analysis and case-control study nested within a population of women aged between 15 and 39 years with acne, hirsutism or PCOS to estimate the risk of VTE associated with CPA/EE. RESULTS: The age-adjusted incidence rate ratio for CPA/EE versus conventional COCs was 2.20 [95% confidence interval (CI) 1.35-3.58]. Using as the reference group women who were not using oral contraception, had no recent pregnancy or menopausal symptoms, the case-control analysis gave an adjusted odds ratio (OR(adj)) of 7.44 (95% CI 3.67-15.08) for CPA/EE use compared with an OR(adj) of 2.58 (95% CI 1.60-4.18) for use of conventional COCs. CONCLUSIONS: We have demonstrated an increased risk of VTE associated with the use of CPA/EE in women with acne, hirsutism or PCOS although residual confounding by indication cannot be excluded.", "entity": "Cyproterone Acetate", "aliases": "Androcur Cyproterone Acetate (1 alpha,2 alpha)-Isomer alpha,9 beta,10 (17", "definition": "An agent with anti-androgen and progestational properties. It shows competitive binding with dihydrotestosterone at androgen receptor sites.\n    ", "id": "MESH:D017373"}
{"mention": "ethinyl estradiol", "mention_text": "BACKGROUND: Cyproterone acetate combined with ethinyl estradiol (CPA/EE) is licensed in the UK for the treatment of women with acne and hirsutism and is also a treatment option for polycystic ovary syndrome (PCOS). Previous studies have demonstrated an increased risk of venous thromboembolism (VTE) associated with CPA/EE compared with conventional combined oral contraceptives (COCs). We believe the results of those studies may have been affected by residual confounding. METHODS: Using the General Practice Research Database we conducted a cohort analysis and case-control study nested within a population of women aged between 15 and 39 years with acne, hirsutism or PCOS to estimate the risk of VTE associated with CPA/EE. RESULTS: The age-adjusted incidence rate ratio for CPA/EE versus conventional COCs was 2.20 [95% confidence interval (CI) 1.35-3.58]. Using as the reference group women who were not using oral contraception, had no recent pregnancy or menopausal symptoms, the case-control analysis gave an adjusted odds ratio (OR(adj)) of 7.44 (95% CI 3.67-15.08) for CPA/EE use compared with an OR(adj) of 2.58 (95% CI 1.60-4.18) for use of conventional COCs. CONCLUSIONS: We have demonstrated an increased risk of VTE associated with the use of CPA/EE in women with acne, hirsutism or PCOS although residual confounding by indication cannot be excluded.", "entity": "Ethinyl Estradiol", "aliases": "Effik Brand of Ethinyl Estradiol Estinyl Ethynyl Hemihydrate (8 alpha)-Isomer alpha,17 alpha,9 beta,13 alpha,14 beta)-Isomer (9 beta,17 Oestradiol Ethinyl-Oestradiol Ethinylestradiol Jenapharm Ethinyloestradiol Lynoral Microfollin Forte Organon Progynon C Schering Schering-Plough", "definition": "A semisynthetic alkylated ESTRADIOL with a 17-alpha-ethinyl substitution. It has high estrogenic potency when administered orally, and is often used as the estrogenic component in ORAL CONTRACEPTIVES.\n    ", "id": "MESH:D004997"}
{"mention": "CPA", "mention_text": "BACKGROUND: Cyproterone acetate combined with ethinyl estradiol (CPA/EE) is licensed in the UK for the treatment of women with acne and hirsutism and is also a treatment option for polycystic ovary syndrome (PCOS). Previous studies have demonstrated an increased risk of venous thromboembolism (VTE) associated with CPA/EE compared with conventional combined oral contraceptives (COCs). We believe the results of those studies may have been affected by residual confounding. METHODS: Using the General Practice Research Database we conducted a cohort analysis and case-control study nested within a population of women aged between 15 and 39 years with acne, hirsutism or PCOS to estimate the risk of VTE associated with CPA/EE. RESULTS: The age-adjusted incidence rate ratio for CPA/EE versus conventional COCs was 2.20 [95% confidence interval (CI) 1.35-3.58]. Using as the reference group women who were not using oral contraception, had no recent pregnancy or menopausal symptoms, the case-control analysis gave an adjusted odds ratio (OR(adj)) of 7.44 (95% CI 3.67-15.08) for CPA/EE use compared with an OR(adj) of 2.58 (95% CI 1.60-4.18) for use of conventional COCs. CONCLUSIONS: We have demonstrated an increased risk of VTE associated with the use of CPA/EE in women with acne, hirsutism or PCOS although residual confounding by indication cannot be excluded.", "entity": "Cyproterone Acetate", "aliases": "Androcur Cyproterone Acetate (1 alpha,2 alpha)-Isomer alpha,9 beta,10 (17", "definition": "An agent with anti-androgen and progestational properties. It shows competitive binding with dihydrotestosterone at androgen receptor sites.\n    ", "id": "MESH:D017373"}
{"mention": "EE", "mention_text": "BACKGROUND: Cyproterone acetate combined with ethinyl estradiol (CPA/EE) is licensed in the UK for the treatment of women with acne and hirsutism and is also a treatment option for polycystic ovary syndrome (PCOS). Previous studies have demonstrated an increased risk of venous thromboembolism (VTE) associated with CPA/EE compared with conventional combined oral contraceptives (COCs). We believe the results of those studies may have been affected by residual confounding. METHODS: Using the General Practice Research Database we conducted a cohort analysis and case-control study nested within a population of women aged between 15 and 39 years with acne, hirsutism or PCOS to estimate the risk of VTE associated with CPA/EE. RESULTS: The age-adjusted incidence rate ratio for CPA/EE versus conventional COCs was 2.20 [95% confidence interval (CI) 1.35-3.58]. Using as the reference group women who were not using oral contraception, had no recent pregnancy or menopausal symptoms, the case-control analysis gave an adjusted odds ratio (OR(adj)) of 7.44 (95% CI 3.67-15.08) for CPA/EE use compared with an OR(adj) of 2.58 (95% CI 1.60-4.18) for use of conventional COCs. CONCLUSIONS: We have demonstrated an increased risk of VTE associated with the use of CPA/EE in women with acne, hirsutism or PCOS although residual confounding by indication cannot be excluded.", "entity": "Ethinyl Estradiol", "aliases": "Effik Brand of Ethinyl Estradiol Estinyl Ethynyl Hemihydrate (8 alpha)-Isomer alpha,17 alpha,9 beta,13 alpha,14 beta)-Isomer (9 beta,17 Oestradiol Ethinyl-Oestradiol Ethinylestradiol Jenapharm Ethinyloestradiol Lynoral Microfollin Forte Organon Progynon C Schering Schering-Plough", "definition": "A semisynthetic alkylated ESTRADIOL with a 17-alpha-ethinyl substitution. It has high estrogenic potency when administered orally, and is often used as the estrogenic component in ORAL CONTRACEPTIVES.\n    ", "id": "MESH:D004997"}
{"mention": "acne", "mention_text": "BACKGROUND: Cyproterone acetate combined with ethinyl estradiol (CPA/EE) is licensed in the UK for the treatment of women with acne and hirsutism and is also a treatment option for polycystic ovary syndrome (PCOS). Previous studies have demonstrated an increased risk of venous thromboembolism (VTE) associated with CPA/EE compared with conventional combined oral contraceptives (COCs). We believe the results of those studies may have been affected by residual confounding. METHODS: Using the General Practice Research Database we conducted a cohort analysis and case-control study nested within a population of women aged between 15 and 39 years with acne, hirsutism or PCOS to estimate the risk of VTE associated with CPA/EE. RESULTS: The age-adjusted incidence rate ratio for CPA/EE versus conventional COCs was 2.20 [95% confidence interval (CI) 1.35-3.58]. Using as the reference group women who were not using oral contraception, had no recent pregnancy or menopausal symptoms, the case-control analysis gave an adjusted odds ratio (OR(adj)) of 7.44 (95% CI 3.67-15.08) for CPA/EE use compared with an OR(adj) of 2.58 (95% CI 1.60-4.18) for use of conventional COCs. CONCLUSIONS: We have demonstrated an increased risk of VTE associated with the use of CPA/EE in women with acne, hirsutism or PCOS although residual confounding by indication cannot be excluded.", "entity": "Acne Vulgaris", "aliases": "Acne Vulgaris", "definition": "A chronic disorder of the pilosebaceous apparatus associated with an increase in sebum secretion. It is characterized by open comedones (blackheads), closed comedones (whiteheads), and pustular nodules. The cause is unknown, but heredity and age are predisposing factors.\n    ", "id": "MESH:D000152"}
{"mention": "hirsutism", "mention_text": "BACKGROUND: Cyproterone acetate combined with ethinyl estradiol (CPA/EE) is licensed in the UK for the treatment of women with acne and hirsutism and is also a treatment option for polycystic ovary syndrome (PCOS). Previous studies have demonstrated an increased risk of venous thromboembolism (VTE) associated with CPA/EE compared with conventional combined oral contraceptives (COCs). We believe the results of those studies may have been affected by residual confounding. METHODS: Using the General Practice Research Database we conducted a cohort analysis and case-control study nested within a population of women aged between 15 and 39 years with acne, hirsutism or PCOS to estimate the risk of VTE associated with CPA/EE. RESULTS: The age-adjusted incidence rate ratio for CPA/EE versus conventional COCs was 2.20 [95% confidence interval (CI) 1.35-3.58]. Using as the reference group women who were not using oral contraception, had no recent pregnancy or menopausal symptoms, the case-control analysis gave an adjusted odds ratio (OR(adj)) of 7.44 (95% CI 3.67-15.08) for CPA/EE use compared with an OR(adj) of 2.58 (95% CI 1.60-4.18) for use of conventional COCs. CONCLUSIONS: We have demonstrated an increased risk of VTE associated with the use of CPA/EE in women with acne, hirsutism or PCOS although residual confounding by indication cannot be excluded.", "entity": "Hirsutism", "aliases": "Hirsutism", "definition": "A condition observed in WOMEN and CHILDREN when there is excess coarse body hair of an adult male distribution pattern, such as facial and chest areas. It is the result of elevated ANDROGENS from the OVARIES, the ADRENAL GLANDS, or exogenous sources. The concept does not include HYPERTRICHOSIS, which is an androgen-independent excessive hair growth.\n    ", "id": "MESH:D006628"}
{"mention": "polycystic ovary syndrome", "mention_text": "BACKGROUND: Cyproterone acetate combined with ethinyl estradiol (CPA/EE) is licensed in the UK for the treatment of women with acne and hirsutism and is also a treatment option for polycystic ovary syndrome (PCOS). Previous studies have demonstrated an increased risk of venous thromboembolism (VTE) associated with CPA/EE compared with conventional combined oral contraceptives (COCs). We believe the results of those studies may have been affected by residual confounding. METHODS: Using the General Practice Research Database we conducted a cohort analysis and case-control study nested within a population of women aged between 15 and 39 years with acne, hirsutism or PCOS to estimate the risk of VTE associated with CPA/EE. RESULTS: The age-adjusted incidence rate ratio for CPA/EE versus conventional COCs was 2.20 [95% confidence interval (CI) 1.35-3.58]. Using as the reference group women who were not using oral contraception, had no recent pregnancy or menopausal symptoms, the case-control analysis gave an adjusted odds ratio (OR(adj)) of 7.44 (95% CI 3.67-15.08) for CPA/EE use compared with an OR(adj) of 2.58 (95% CI 1.60-4.18) for use of conventional COCs. CONCLUSIONS: We have demonstrated an increased risk of VTE associated with the use of CPA/EE in women with acne, hirsutism or PCOS although residual confounding by indication cannot be excluded.", "entity": "Polycystic Ovary Syndrome", "aliases": "Ovarian Degeneration Sclerocystic Syndrome Polycystic Ovary 1 Ovaries Stein Leventhal Stein-Leventhal", "definition": "A complex disorder characterized by infertility, HIRSUTISM; OBESITY; and various menstrual disturbances such as OLIGOMENORRHEA; AMENORRHEA; ANOVULATION. Polycystic ovary syndrome is usually associated with bilateral enlarged ovaries studded with atretic follicles, not with cysts. The term, polycystic ovary, is misleading.\n    ", "id": "MESH:D011085"}
{"mention": "PCOS", "mention_text": "BACKGROUND: Cyproterone acetate combined with ethinyl estradiol (CPA/EE) is licensed in the UK for the treatment of women with acne and hirsutism and is also a treatment option for polycystic ovary syndrome (PCOS). Previous studies have demonstrated an increased risk of venous thromboembolism (VTE) associated with CPA/EE compared with conventional combined oral contraceptives (COCs). We believe the results of those studies may have been affected by residual confounding. METHODS: Using the General Practice Research Database we conducted a cohort analysis and case-control study nested within a population of women aged between 15 and 39 years with acne, hirsutism or PCOS to estimate the risk of VTE associated with CPA/EE. RESULTS: The age-adjusted incidence rate ratio for CPA/EE versus conventional COCs was 2.20 [95% confidence interval (CI) 1.35-3.58]. Using as the reference group women who were not using oral contraception, had no recent pregnancy or menopausal symptoms, the case-control analysis gave an adjusted odds ratio (OR(adj)) of 7.44 (95% CI 3.67-15.08) for CPA/EE use compared with an OR(adj) of 2.58 (95% CI 1.60-4.18) for use of conventional COCs. CONCLUSIONS: We have demonstrated an increased risk of VTE associated with the use of CPA/EE in women with acne, hirsutism or PCOS although residual confounding by indication cannot be excluded.", "entity": "Polycystic Ovary Syndrome", "aliases": "Ovarian Degeneration Sclerocystic Syndrome Polycystic Ovary 1 Ovaries Stein Leventhal Stein-Leventhal", "definition": "A complex disorder characterized by infertility, HIRSUTISM; OBESITY; and various menstrual disturbances such as OLIGOMENORRHEA; AMENORRHEA; ANOVULATION. Polycystic ovary syndrome is usually associated with bilateral enlarged ovaries studded with atretic follicles, not with cysts. The term, polycystic ovary, is misleading.\n    ", "id": "MESH:D011085"}
{"mention": "venous thromboembolism", "mention_text": "BACKGROUND: Cyproterone acetate combined with ethinyl estradiol (CPA/EE) is licensed in the UK for the treatment of women with acne and hirsutism and is also a treatment option for polycystic ovary syndrome (PCOS). Previous studies have demonstrated an increased risk of venous thromboembolism (VTE) associated with CPA/EE compared with conventional combined oral contraceptives (COCs). We believe the results of those studies may have been affected by residual confounding. METHODS: Using the General Practice Research Database we conducted a cohort analysis and case-control study nested within a population of women aged between 15 and 39 years with acne, hirsutism or PCOS to estimate the risk of VTE associated with CPA/EE. RESULTS: The age-adjusted incidence rate ratio for CPA/EE versus conventional COCs was 2.20 [95% confidence interval (CI) 1.35-3.58]. Using as the reference group women who were not using oral contraception, had no recent pregnancy or menopausal symptoms, the case-control analysis gave an adjusted odds ratio (OR(adj)) of 7.44 (95% CI 3.67-15.08) for CPA/EE use compared with an OR(adj) of 2.58 (95% CI 1.60-4.18) for use of conventional COCs. CONCLUSIONS: We have demonstrated an increased risk of VTE associated with the use of CPA/EE in women with acne, hirsutism or PCOS although residual confounding by indication cannot be excluded.", "entity": "Venous Thromboembolism", "aliases": "Thromboembolism Venous", "definition": "Obstruction of a vein or VEINS (embolism) by a blood clot (THROMBUS) in the blood stream.\n    ", "id": "MESH:D054556"}
{"mention": "VTE", "mention_text": "BACKGROUND: Cyproterone acetate combined with ethinyl estradiol (CPA/EE) is licensed in the UK for the treatment of women with acne and hirsutism and is also a treatment option for polycystic ovary syndrome (PCOS). Previous studies have demonstrated an increased risk of venous thromboembolism (VTE) associated with CPA/EE compared with conventional combined oral contraceptives (COCs). We believe the results of those studies may have been affected by residual confounding. METHODS: Using the General Practice Research Database we conducted a cohort analysis and case-control study nested within a population of women aged between 15 and 39 years with acne, hirsutism or PCOS to estimate the risk of VTE associated with CPA/EE. RESULTS: The age-adjusted incidence rate ratio for CPA/EE versus conventional COCs was 2.20 [95% confidence interval (CI) 1.35-3.58]. Using as the reference group women who were not using oral contraception, had no recent pregnancy or menopausal symptoms, the case-control analysis gave an adjusted odds ratio (OR(adj)) of 7.44 (95% CI 3.67-15.08) for CPA/EE use compared with an OR(adj) of 2.58 (95% CI 1.60-4.18) for use of conventional COCs. CONCLUSIONS: We have demonstrated an increased risk of VTE associated with the use of CPA/EE in women with acne, hirsutism or PCOS although residual confounding by indication cannot be excluded.", "entity": "Venous Thromboembolism", "aliases": "Thromboembolism Venous", "definition": "Obstruction of a vein or VEINS (embolism) by a blood clot (THROMBUS) in the blood stream.\n    ", "id": "MESH:D054556"}
{"mention": "oral contraceptives", "mention_text": "BACKGROUND: Cyproterone acetate combined with ethinyl estradiol (CPA/EE) is licensed in the UK for the treatment of women with acne and hirsutism and is also a treatment option for polycystic ovary syndrome (PCOS). Previous studies have demonstrated an increased risk of venous thromboembolism (VTE) associated with CPA/EE compared with conventional combined oral contraceptives (COCs). We believe the results of those studies may have been affected by residual confounding. METHODS: Using the General Practice Research Database we conducted a cohort analysis and case-control study nested within a population of women aged between 15 and 39 years with acne, hirsutism or PCOS to estimate the risk of VTE associated with CPA/EE. RESULTS: The age-adjusted incidence rate ratio for CPA/EE versus conventional COCs was 2.20 [95% confidence interval (CI) 1.35-3.58]. Using as the reference group women who were not using oral contraception, had no recent pregnancy or menopausal symptoms, the case-control analysis gave an adjusted odds ratio (OR(adj)) of 7.44 (95% CI 3.67-15.08) for CPA/EE use compared with an OR(adj) of 2.58 (95% CI 1.60-4.18) for use of conventional COCs. CONCLUSIONS: We have demonstrated an increased risk of VTE associated with the use of CPA/EE in women with acne, hirsutism or PCOS although residual confounding by indication cannot be excluded.", "entity": "Contraceptives, Oral", "aliases": "Contraceptives Low-Dose Oral Phasic Low Dose", "definition": "Compounds, usually hormonal, taken orally in order to block ovulation and prevent the occurrence of pregnancy. The hormones are generally estrogen or progesterone or both.\n    ", "id": "MESH:D003276"}
{"mention": "Pseudoacromegaly", "mention_text": "Pseudoacromegaly induced by the long-term use of minoxidil.", "entity": "Disease", "aliases": "Disease Diseases", "definition": "A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.\n    ", "id": "MESH:D004194"}
{"mention": "minoxidil", "mention_text": "Pseudoacromegaly induced by the long-term use of minoxidil.", "entity": "Minoxidil", "aliases": "Loniten Minoxidil Pfizer Brand of Regaine Rogaine U 10858", "definition": "A potent direct-acting peripheral vasodilator (VASODILATOR AGENTS) that reduces peripheral resistance and produces a fall in BLOOD PRESSURE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p371)\n    ", "id": "MESH:D008914"}
{"mention": "Acromegaly", "mention_text": "Acromegaly is an endocrine disorder caused by chronic excessive growth hormone secretion from the anterior pituitary gland. Significant disfiguring changes occur as a result of bone, cartilage, and soft tissue hypertrophy, including the thickening of the skin, coarsening of facial features, and cutis verticis gyrata. Pseudoacromegaly, on the other hand, is the presence of similar acromegaloid features in the absence of elevated growth hormone or insulin-like growth factor levels. We present a patient with pseudoacromegaly that resulted from the long-term use of minoxidil at an unusually high dose. This is the first case report of pseudoacromegaly as a side effect of minoxidil use.", "entity": "Acromegaly", "aliases": "Acromegaly Hypersecretion Syndrome Somatotropin (Acromegaly) Syndromes Inappropriate GH Secretion Growth Hormone", "definition": "A condition caused by prolonged exposure to excessive HUMAN GROWTH HORMONE in adults. It is characterized by bony enlargement of the FACE; lower jaw (PROGNATHISM); hands; FEET; HEAD; and THORAX. The most common etiology is a GROWTH HORMONE-SECRETING PITUITARY ADENOMA. (From Joynt, Clinical Neurology, 1992, Ch36, pp79-80)\n    ", "id": "MESH:D000172"}
{"mention": "endocrine disorder", "mention_text": "Acromegaly is an endocrine disorder caused by chronic excessive growth hormone secretion from the anterior pituitary gland. Significant disfiguring changes occur as a result of bone, cartilage, and soft tissue hypertrophy, including the thickening of the skin, coarsening of facial features, and cutis verticis gyrata. Pseudoacromegaly, on the other hand, is the presence of similar acromegaloid features in the absence of elevated growth hormone or insulin-like growth factor levels. We present a patient with pseudoacromegaly that resulted from the long-term use of minoxidil at an unusually high dose. This is the first case report of pseudoacromegaly as a side effect of minoxidil use.", "entity": "Endocrine System Diseases", "aliases": "Disease Endocrine System Diseases of", "definition": "Pathological processes of the ENDOCRINE GLANDS, and diseases resulting from abnormal level of available HORMONES.\n    ", "id": "MESH:D004700"}
{"mention": "hypertrophy", "mention_text": "Acromegaly is an endocrine disorder caused by chronic excessive growth hormone secretion from the anterior pituitary gland. Significant disfiguring changes occur as a result of bone, cartilage, and soft tissue hypertrophy, including the thickening of the skin, coarsening of facial features, and cutis verticis gyrata. Pseudoacromegaly, on the other hand, is the presence of similar acromegaloid features in the absence of elevated growth hormone or insulin-like growth factor levels. We present a patient with pseudoacromegaly that resulted from the long-term use of minoxidil at an unusually high dose. This is the first case report of pseudoacromegaly as a side effect of minoxidil use.", "entity": "Hypertrophy", "aliases": "Hypertrophies Hypertrophy", "definition": "General increase in bulk of a part or organ due to CELL ENLARGEMENT and accumulation of FLUIDS AND SECRETIONS, not due to tumor formation, nor to an increase in the number of cells (HYPERPLASIA).\n    ", "id": "MESH:D006984"}
{"mention": "cutis verticis gyrata", "mention_text": "Acromegaly is an endocrine disorder caused by chronic excessive growth hormone secretion from the anterior pituitary gland. Significant disfiguring changes occur as a result of bone, cartilage, and soft tissue hypertrophy, including the thickening of the skin, coarsening of facial features, and cutis verticis gyrata. Pseudoacromegaly, on the other hand, is the presence of similar acromegaloid features in the absence of elevated growth hormone or insulin-like growth factor levels. We present a patient with pseudoacromegaly that resulted from the long-term use of minoxidil at an unusually high dose. This is the first case report of pseudoacromegaly as a side effect of minoxidil use.", "entity": "Akesson syndrome", "aliases": "Akesson syndrome Cutis Verticis Gyrata Thyroid Aplasia and Mental Retardation verticis gyrata thyroaplasia mental deficiency gyrata-thyroid aplasia-mental retardation", "definition": "", "id": "MESH:C535610"}
{"mention": "Pseudoacromegaly", "mention_text": "Acromegaly is an endocrine disorder caused by chronic excessive growth hormone secretion from the anterior pituitary gland. Significant disfiguring changes occur as a result of bone, cartilage, and soft tissue hypertrophy, including the thickening of the skin, coarsening of facial features, and cutis verticis gyrata. Pseudoacromegaly, on the other hand, is the presence of similar acromegaloid features in the absence of elevated growth hormone or insulin-like growth factor levels. We present a patient with pseudoacromegaly that resulted from the long-term use of minoxidil at an unusually high dose. This is the first case report of pseudoacromegaly as a side effect of minoxidil use.", "entity": "Disease", "aliases": "Disease Diseases", "definition": "A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.\n    ", "id": "MESH:D004194"}
{"mention": "pseudoacromegaly", "mention_text": "Acromegaly is an endocrine disorder caused by chronic excessive growth hormone secretion from the anterior pituitary gland. Significant disfiguring changes occur as a result of bone, cartilage, and soft tissue hypertrophy, including the thickening of the skin, coarsening of facial features, and cutis verticis gyrata. Pseudoacromegaly, on the other hand, is the presence of similar acromegaloid features in the absence of elevated growth hormone or insulin-like growth factor levels. We present a patient with pseudoacromegaly that resulted from the long-term use of minoxidil at an unusually high dose. This is the first case report of pseudoacromegaly as a side effect of minoxidil use.", "entity": "Disease", "aliases": "Disease Diseases", "definition": "A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.\n    ", "id": "MESH:D004194"}
{"mention": "minoxidil", "mention_text": "Acromegaly is an endocrine disorder caused by chronic excessive growth hormone secretion from the anterior pituitary gland. Significant disfiguring changes occur as a result of bone, cartilage, and soft tissue hypertrophy, including the thickening of the skin, coarsening of facial features, and cutis verticis gyrata. Pseudoacromegaly, on the other hand, is the presence of similar acromegaloid features in the absence of elevated growth hormone or insulin-like growth factor levels. We present a patient with pseudoacromegaly that resulted from the long-term use of minoxidil at an unusually high dose. This is the first case report of pseudoacromegaly as a side effect of minoxidil use.", "entity": "Minoxidil", "aliases": "Loniten Minoxidil Pfizer Brand of Regaine Rogaine U 10858", "definition": "A potent direct-acting peripheral vasodilator (VASODILATOR AGENTS) that reduces peripheral resistance and produces a fall in BLOOD PRESSURE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p371)\n    ", "id": "MESH:D008914"}
{"mention": "anemia", "mention_text": "Combined androgen blockade-induced anemia in prostate cancer patients without bone involvement.", "entity": "Anemia", "aliases": "Anemia Anemias", "definition": "A reduction in the number of circulating ERYTHROCYTES or in the quantity of HEMOGLOBIN.\n    ", "id": "MESH:D000740"}
{"mention": "prostate cancer", "mention_text": "Combined androgen blockade-induced anemia in prostate cancer patients without bone involvement.", "entity": "Prostatic Neoplasms", "aliases": "Cancer of Prostate the Prostatic Cancers Neoplasm Neoplasms", "definition": "Tumors or cancer of the PROSTATE.\n    ", "id": "MESH:D011471"}
{"mention": "anemia", "mention_text": "BACKGROUND: To determine the onset and extent of combined androgen blockade (CAB)-induced anemia in prostate cancer patients without bone involvement. PATIENTS AND METHODS: Forty-two patients with biopsy-proven prostatic adenocarcinoma [26 with stage C (T3N0M0) and 16 with stage D1 (T3N1M0)] were included in this study. All patients received CAB [leuprolide acetate (LHRH-A) 3.75 mg, intramuscularly, every 28 days plus 250 mg flutamide, tid, per Os] and were evaluated for anemia by physical examination and laboratory tests at baseline and 4 subsequent intervals (1, 2, 3 and 6 months post-CAB). Hb, PSA and Testosterone measurements were recorded. Patients with stage D2-3 disease, abnormal hemoglobin level or renal and liver function tests that were higher than the upper limits were excluded from the study. The duration of the study was six months. RESULTS: The mean hemoglobin (Hb) levels were significantly declined in all patients from baseline of 14.2 g/dl to 14.0 g/dl, 13.5 g/dl, 13.2 g/dl and 12.7 g/dl at 1, 2, 3 and 6 months post-CAB, respectively. Severe and clinically evident anemia of Hb < 11 g/dl with clinical symptoms was detected in 6 patients (14.3%). This CAB-induced anemia was normochromic and normocytic. At six months post-CAB, patients with severe anemia had a Hb mean value of 10.2 +/- 0.1 g/dl (X +/- SE), whereas the other patients had mild anemia with Hb mean value of 13.2 +/- 0.17 (X +/- SE). The development of severe anemia at 6 months post-CAB was predictable by the reduction of Hb baseline value of more than 2.5 g/dl after 3 months of CAB (p = 0.01). The development of severe CAB-induced anemia in prostate cancer patients did not correlate with T baseline values (T < 3 ng/ml versus T > or = 3 ng/ml), with age (< 76 yrs versus > or = 76 yrs), and clinical stage (stage C versus stage D1). Severe and clinically evident anemia was easily corrected by subcutaneous injections (3 times/week for 1 month) of recombinant erythropoietin (rHuEPO-beta). CONCLUSION: Our data suggest that rHuEPO-beta correctable CAB-induced anemia occurs in 14.3% of prostate cancer patients after 6 months of therapy.", "entity": "Anemia", "aliases": "Anemia Anemias", "definition": "A reduction in the number of circulating ERYTHROCYTES or in the quantity of HEMOGLOBIN.\n    ", "id": "MESH:D000740"}
{"mention": "prostate cancer", "mention_text": "BACKGROUND: To determine the onset and extent of combined androgen blockade (CAB)-induced anemia in prostate cancer patients without bone involvement. PATIENTS AND METHODS: Forty-two patients with biopsy-proven prostatic adenocarcinoma [26 with stage C (T3N0M0) and 16 with stage D1 (T3N1M0)] were included in this study. All patients received CAB [leuprolide acetate (LHRH-A) 3.75 mg, intramuscularly, every 28 days plus 250 mg flutamide, tid, per Os] and were evaluated for anemia by physical examination and laboratory tests at baseline and 4 subsequent intervals (1, 2, 3 and 6 months post-CAB). Hb, PSA and Testosterone measurements were recorded. Patients with stage D2-3 disease, abnormal hemoglobin level or renal and liver function tests that were higher than the upper limits were excluded from the study. The duration of the study was six months. RESULTS: The mean hemoglobin (Hb) levels were significantly declined in all patients from baseline of 14.2 g/dl to 14.0 g/dl, 13.5 g/dl, 13.2 g/dl and 12.7 g/dl at 1, 2, 3 and 6 months post-CAB, respectively. Severe and clinically evident anemia of Hb < 11 g/dl with clinical symptoms was detected in 6 patients (14.3%). This CAB-induced anemia was normochromic and normocytic. At six months post-CAB, patients with severe anemia had a Hb mean value of 10.2 +/- 0.1 g/dl (X +/- SE), whereas the other patients had mild anemia with Hb mean value of 13.2 +/- 0.17 (X +/- SE). The development of severe anemia at 6 months post-CAB was predictable by the reduction of Hb baseline value of more than 2.5 g/dl after 3 months of CAB (p = 0.01). The development of severe CAB-induced anemia in prostate cancer patients did not correlate with T baseline values (T < 3 ng/ml versus T > or = 3 ng/ml), with age (< 76 yrs versus > or = 76 yrs), and clinical stage (stage C versus stage D1). Severe and clinically evident anemia was easily corrected by subcutaneous injections (3 times/week for 1 month) of recombinant erythropoietin (rHuEPO-beta). CONCLUSION: Our data suggest that rHuEPO-beta correctable CAB-induced anemia occurs in 14.3% of prostate cancer patients after 6 months of therapy.", "entity": "Prostatic Neoplasms", "aliases": "Cancer of Prostate the Prostatic Cancers Neoplasm Neoplasms", "definition": "Tumors or cancer of the PROSTATE.\n    ", "id": "MESH:D011471"}
{"mention": "prostatic adenocarcinoma", "mention_text": "BACKGROUND: To determine the onset and extent of combined androgen blockade (CAB)-induced anemia in prostate cancer patients without bone involvement. PATIENTS AND METHODS: Forty-two patients with biopsy-proven prostatic adenocarcinoma [26 with stage C (T3N0M0) and 16 with stage D1 (T3N1M0)] were included in this study. All patients received CAB [leuprolide acetate (LHRH-A) 3.75 mg, intramuscularly, every 28 days plus 250 mg flutamide, tid, per Os] and were evaluated for anemia by physical examination and laboratory tests at baseline and 4 subsequent intervals (1, 2, 3 and 6 months post-CAB). Hb, PSA and Testosterone measurements were recorded. Patients with stage D2-3 disease, abnormal hemoglobin level or renal and liver function tests that were higher than the upper limits were excluded from the study. The duration of the study was six months. RESULTS: The mean hemoglobin (Hb) levels were significantly declined in all patients from baseline of 14.2 g/dl to 14.0 g/dl, 13.5 g/dl, 13.2 g/dl and 12.7 g/dl at 1, 2, 3 and 6 months post-CAB, respectively. Severe and clinically evident anemia of Hb < 11 g/dl with clinical symptoms was detected in 6 patients (14.3%). This CAB-induced anemia was normochromic and normocytic. At six months post-CAB, patients with severe anemia had a Hb mean value of 10.2 +/- 0.1 g/dl (X +/- SE), whereas the other patients had mild anemia with Hb mean value of 13.2 +/- 0.17 (X +/- SE). The development of severe anemia at 6 months post-CAB was predictable by the reduction of Hb baseline value of more than 2.5 g/dl after 3 months of CAB (p = 0.01). The development of severe CAB-induced anemia in prostate cancer patients did not correlate with T baseline values (T < 3 ng/ml versus T > or = 3 ng/ml), with age (< 76 yrs versus > or = 76 yrs), and clinical stage (stage C versus stage D1). Severe and clinically evident anemia was easily corrected by subcutaneous injections (3 times/week for 1 month) of recombinant erythropoietin (rHuEPO-beta). CONCLUSION: Our data suggest that rHuEPO-beta correctable CAB-induced anemia occurs in 14.3% of prostate cancer patients after 6 months of therapy.", "entity": "Adenocarcinoma", "aliases": "Adenocarcinoma Basal Cell Granular Oxyphilic Tubular Adenocarcinomas Adenoma Malignant Adenomas Carcinoma Cribriform Carcinomas", "definition": "A malignant epithelial tumor with a glandular organization.\n    ", "id": "MESH:D000230"}
{"mention": "leuprolide acetate", "mention_text": "BACKGROUND: To determine the onset and extent of combined androgen blockade (CAB)-induced anemia in prostate cancer patients without bone involvement. PATIENTS AND METHODS: Forty-two patients with biopsy-proven prostatic adenocarcinoma [26 with stage C (T3N0M0) and 16 with stage D1 (T3N1M0)] were included in this study. All patients received CAB [leuprolide acetate (LHRH-A) 3.75 mg, intramuscularly, every 28 days plus 250 mg flutamide, tid, per Os] and were evaluated for anemia by physical examination and laboratory tests at baseline and 4 subsequent intervals (1, 2, 3 and 6 months post-CAB). Hb, PSA and Testosterone measurements were recorded. Patients with stage D2-3 disease, abnormal hemoglobin level or renal and liver function tests that were higher than the upper limits were excluded from the study. The duration of the study was six months. RESULTS: The mean hemoglobin (Hb) levels were significantly declined in all patients from baseline of 14.2 g/dl to 14.0 g/dl, 13.5 g/dl, 13.2 g/dl and 12.7 g/dl at 1, 2, 3 and 6 months post-CAB, respectively. Severe and clinically evident anemia of Hb < 11 g/dl with clinical symptoms was detected in 6 patients (14.3%). This CAB-induced anemia was normochromic and normocytic. At six months post-CAB, patients with severe anemia had a Hb mean value of 10.2 +/- 0.1 g/dl (X +/- SE), whereas the other patients had mild anemia with Hb mean value of 13.2 +/- 0.17 (X +/- SE). The development of severe anemia at 6 months post-CAB was predictable by the reduction of Hb baseline value of more than 2.5 g/dl after 3 months of CAB (p = 0.01). The development of severe CAB-induced anemia in prostate cancer patients did not correlate with T baseline values (T < 3 ng/ml versus T > or = 3 ng/ml), with age (< 76 yrs versus > or = 76 yrs), and clinical stage (stage C versus stage D1). Severe and clinically evident anemia was easily corrected by subcutaneous injections (3 times/week for 1 month) of recombinant erythropoietin (rHuEPO-beta). CONCLUSION: Our data suggest that rHuEPO-beta correctable CAB-induced anemia occurs in 14.3% of prostate cancer patients after 6 months of therapy.", "entity": "Leuprolide", "aliases": "A 43818 A-43818 A43818 Acetate Leuprolide Enantone Monoacetate (DL-Leu)-Isomer (L-Leu)-Isomer Leuprorelin Lupron TAP 144 TAP-144 TAP144", "definition": "A potent synthetic long-acting agonist of GONADOTROPIN-RELEASING HORMONE that regulates the synthesis and release of pituitary gonadotropins, LUTEINIZING HORMONE and FOLLICLE STIMULATING HORMONE.\n    ", "id": "MESH:D016729"}
{"mention": "LHRH-A", "mention_text": "BACKGROUND: To determine the onset and extent of combined androgen blockade (CAB)-induced anemia in prostate cancer patients without bone involvement. PATIENTS AND METHODS: Forty-two patients with biopsy-proven prostatic adenocarcinoma [26 with stage C (T3N0M0) and 16 with stage D1 (T3N1M0)] were included in this study. All patients received CAB [leuprolide acetate (LHRH-A) 3.75 mg, intramuscularly, every 28 days plus 250 mg flutamide, tid, per Os] and were evaluated for anemia by physical examination and laboratory tests at baseline and 4 subsequent intervals (1, 2, 3 and 6 months post-CAB). Hb, PSA and Testosterone measurements were recorded. Patients with stage D2-3 disease, abnormal hemoglobin level or renal and liver function tests that were higher than the upper limits were excluded from the study. The duration of the study was six months. RESULTS: The mean hemoglobin (Hb) levels were significantly declined in all patients from baseline of 14.2 g/dl to 14.0 g/dl, 13.5 g/dl, 13.2 g/dl and 12.7 g/dl at 1, 2, 3 and 6 months post-CAB, respectively. Severe and clinically evident anemia of Hb < 11 g/dl with clinical symptoms was detected in 6 patients (14.3%). This CAB-induced anemia was normochromic and normocytic. At six months post-CAB, patients with severe anemia had a Hb mean value of 10.2 +/- 0.1 g/dl (X +/- SE), whereas the other patients had mild anemia with Hb mean value of 13.2 +/- 0.17 (X +/- SE). The development of severe anemia at 6 months post-CAB was predictable by the reduction of Hb baseline value of more than 2.5 g/dl after 3 months of CAB (p = 0.01). The development of severe CAB-induced anemia in prostate cancer patients did not correlate with T baseline values (T < 3 ng/ml versus T > or = 3 ng/ml), with age (< 76 yrs versus > or = 76 yrs), and clinical stage (stage C versus stage D1). Severe and clinically evident anemia was easily corrected by subcutaneous injections (3 times/week for 1 month) of recombinant erythropoietin (rHuEPO-beta). CONCLUSION: Our data suggest that rHuEPO-beta correctable CAB-induced anemia occurs in 14.3% of prostate cancer patients after 6 months of therapy.", "entity": "Leuprolide", "aliases": "A 43818 A-43818 A43818 Acetate Leuprolide Enantone Monoacetate (DL-Leu)-Isomer (L-Leu)-Isomer Leuprorelin Lupron TAP 144 TAP-144 TAP144", "definition": "A potent synthetic long-acting agonist of GONADOTROPIN-RELEASING HORMONE that regulates the synthesis and release of pituitary gonadotropins, LUTEINIZING HORMONE and FOLLICLE STIMULATING HORMONE.\n    ", "id": "MESH:D016729"}
{"mention": "flutamide", "mention_text": "BACKGROUND: To determine the onset and extent of combined androgen blockade (CAB)-induced anemia in prostate cancer patients without bone involvement. PATIENTS AND METHODS: Forty-two patients with biopsy-proven prostatic adenocarcinoma [26 with stage C (T3N0M0) and 16 with stage D1 (T3N1M0)] were included in this study. All patients received CAB [leuprolide acetate (LHRH-A) 3.75 mg, intramuscularly, every 28 days plus 250 mg flutamide, tid, per Os] and were evaluated for anemia by physical examination and laboratory tests at baseline and 4 subsequent intervals (1, 2, 3 and 6 months post-CAB). Hb, PSA and Testosterone measurements were recorded. Patients with stage D2-3 disease, abnormal hemoglobin level or renal and liver function tests that were higher than the upper limits were excluded from the study. The duration of the study was six months. RESULTS: The mean hemoglobin (Hb) levels were significantly declined in all patients from baseline of 14.2 g/dl to 14.0 g/dl, 13.5 g/dl, 13.2 g/dl and 12.7 g/dl at 1, 2, 3 and 6 months post-CAB, respectively. Severe and clinically evident anemia of Hb < 11 g/dl with clinical symptoms was detected in 6 patients (14.3%). This CAB-induced anemia was normochromic and normocytic. At six months post-CAB, patients with severe anemia had a Hb mean value of 10.2 +/- 0.1 g/dl (X +/- SE), whereas the other patients had mild anemia with Hb mean value of 13.2 +/- 0.17 (X +/- SE). The development of severe anemia at 6 months post-CAB was predictable by the reduction of Hb baseline value of more than 2.5 g/dl after 3 months of CAB (p = 0.01). The development of severe CAB-induced anemia in prostate cancer patients did not correlate with T baseline values (T < 3 ng/ml versus T > or = 3 ng/ml), with age (< 76 yrs versus > or = 76 yrs), and clinical stage (stage C versus stage D1). Severe and clinically evident anemia was easily corrected by subcutaneous injections (3 times/week for 1 month) of recombinant erythropoietin (rHuEPO-beta). CONCLUSION: Our data suggest that rHuEPO-beta correctable CAB-induced anemia occurs in 14.3% of prostate cancer patients after 6 months of therapy.", "entity": "Flutamide", "aliases": "1A Brand of Flutamide Alphapharm Apimid Apo Apo-Flutamide ApoFlutamide Apogepha Apotex Azupharma Chephasaar Chimax Chiron Ciclum Cytamid Drogenil Essex Euflex Eulexin Eulexine Fluken Flulem Flumid Fluta Pharma GRY cell Fluta-GRY Fluta-cell FlutaGRY Flutacell Flutamin Flutandrona Flutaplex Flutexin Fugerel Grisetin Gry Hexal Inibsa Ipsen Juta Kendrick Lemery Niftolid Niftolide Novo Novo-Flutamide NovoFlutamide Novopharm Oncosal PMS PMS-Flutamide Pharmascience Prasfarma Prostacur Prostica Prostoge", "definition": "An antiandrogen with about the same potency as cyproterone in rodent and canine species.\n    ", "id": "MESH:D005485"}
{"mention": "Testosterone", "mention_text": "BACKGROUND: To determine the onset and extent of combined androgen blockade (CAB)-induced anemia in prostate cancer patients without bone involvement. PATIENTS AND METHODS: Forty-two patients with biopsy-proven prostatic adenocarcinoma [26 with stage C (T3N0M0) and 16 with stage D1 (T3N1M0)] were included in this study. All patients received CAB [leuprolide acetate (LHRH-A) 3.75 mg, intramuscularly, every 28 days plus 250 mg flutamide, tid, per Os] and were evaluated for anemia by physical examination and laboratory tests at baseline and 4 subsequent intervals (1, 2, 3 and 6 months post-CAB). Hb, PSA and Testosterone measurements were recorded. Patients with stage D2-3 disease, abnormal hemoglobin level or renal and liver function tests that were higher than the upper limits were excluded from the study. The duration of the study was six months. RESULTS: The mean hemoglobin (Hb) levels were significantly declined in all patients from baseline of 14.2 g/dl to 14.0 g/dl, 13.5 g/dl, 13.2 g/dl and 12.7 g/dl at 1, 2, 3 and 6 months post-CAB, respectively. Severe and clinically evident anemia of Hb < 11 g/dl with clinical symptoms was detected in 6 patients (14.3%). This CAB-induced anemia was normochromic and normocytic. At six months post-CAB, patients with severe anemia had a Hb mean value of 10.2 +/- 0.1 g/dl (X +/- SE), whereas the other patients had mild anemia with Hb mean value of 13.2 +/- 0.17 (X +/- SE). The development of severe anemia at 6 months post-CAB was predictable by the reduction of Hb baseline value of more than 2.5 g/dl after 3 months of CAB (p = 0.01). The development of severe CAB-induced anemia in prostate cancer patients did not correlate with T baseline values (T < 3 ng/ml versus T > or = 3 ng/ml), with age (< 76 yrs versus > or = 76 yrs), and clinical stage (stage C versus stage D1). Severe and clinically evident anemia was easily corrected by subcutaneous injections (3 times/week for 1 month) of recombinant erythropoietin (rHuEPO-beta). CONCLUSION: Our data suggest that rHuEPO-beta correctable CAB-induced anemia occurs in 14.3% of prostate cancer patients after 6 months of therapy.", "entity": "Testosterone", "aliases": "17 beta Hydroxy 4 Androsten 3 one 8 alpha 17-beta-Hydroxy-4-Androsten-3-one 17-beta-Hydroxy-8 alpha-4-Androsten-3-one Isotestosterone 8-Isotestosterone AndroGel Androderm Andropatch Androtop AstraZeneca Brand of Testosterone Auxilium Pharmaceuticals Inc. Bartor CEPA Dr. Kade Faulding Ferring GlaxoSmithKline Hauck Histerone Ortho Paladin Pasadena Schering SmithKline Beecham Solvay Sterotate Sustanon Testim Testoderm Testolin Testopel Sulfate Ulmer Unimed Watson", "definition": "A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.\n    ", "id": "MESH:D013739"}
{"mention": "dilated cardiomyopathy", "mention_text": "Reversible dilated cardiomyopathy related to amphotericin B therapy.", "entity": "Cardiomyopathy, Dilated", "aliases": "1A Dilated cardiomyopathy 1As Cardiomyopathies Congestive Familial Idiopathic Cardiomyopathy 1a Autosomal Recessive CMD1A LMNA With Conduction Defect 1 with Deffect1", "definition": "A form of CARDIAC MUSCLE disease that is characterized by ventricular dilation, VENTRICULAR DYSFUNCTION, and HEART FAILURE. Risk factors include SMOKING; ALCOHOL DRINKING; HYPERTENSION; INFECTION; PREGNANCY; and mutations in the LMNA gene encoding LAMIN TYPE A, a NUCLEAR LAMINA protein.\n    ", "id": "MESH:D002311"}
{"mention": "amphotericin B", "mention_text": "Reversible dilated cardiomyopathy related to amphotericin B therapy.", "entity": "Amphotericin B", "aliases": "Amphocil Amphotericin B Cholesterol Dispersion Colloidal Fungizone", "definition": "Macrolide antifungal antibiotic produced by Streptomyces nodosus obtained from soil of the Orinoco river region of Venezuela.\n    ", "id": "MESH:D000666"}
{"mention": "dilated cardiomyopathy", "mention_text": "We describe a patient who developed dilated cardiomyopathy and clinical congestive heart failure after 2 months of therapy with amphotericin B (AmB) for disseminated coccidioidomycosis. His echocardiographic abnormalities and heart failure resolved after posaconazole was substituted for AmB. It is important to recognize the rare and potentially reversible toxicity of AmB.", "entity": "Cardiomyopathy, Dilated", "aliases": "1A Dilated cardiomyopathy 1As Cardiomyopathies Congestive Familial Idiopathic Cardiomyopathy 1a Autosomal Recessive CMD1A LMNA With Conduction Defect 1 with Deffect1", "definition": "A form of CARDIAC MUSCLE disease that is characterized by ventricular dilation, VENTRICULAR DYSFUNCTION, and HEART FAILURE. Risk factors include SMOKING; ALCOHOL DRINKING; HYPERTENSION; INFECTION; PREGNANCY; and mutations in the LMNA gene encoding LAMIN TYPE A, a NUCLEAR LAMINA protein.\n    ", "id": "MESH:D002311"}
{"mention": "heart failure", "mention_text": "We describe a patient who developed dilated cardiomyopathy and clinical congestive heart failure after 2 months of therapy with amphotericin B (AmB) for disseminated coccidioidomycosis. His echocardiographic abnormalities and heart failure resolved after posaconazole was substituted for AmB. It is important to recognize the rare and potentially reversible toxicity of AmB.", "entity": "Heart Failure", "aliases": "Cardiac Failure Congestive Heart Decompensation Left Sided Left-Sided Right Right-Sided Myocardial", "definition": "A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.\n    ", "id": "MESH:D006333"}
{"mention": "amphotericin B", "mention_text": "We describe a patient who developed dilated cardiomyopathy and clinical congestive heart failure after 2 months of therapy with amphotericin B (AmB) for disseminated coccidioidomycosis. His echocardiographic abnormalities and heart failure resolved after posaconazole was substituted for AmB. It is important to recognize the rare and potentially reversible toxicity of AmB.", "entity": "Amphotericin B", "aliases": "Amphocil Amphotericin B Cholesterol Dispersion Colloidal Fungizone", "definition": "Macrolide antifungal antibiotic produced by Streptomyces nodosus obtained from soil of the Orinoco river region of Venezuela.\n    ", "id": "MESH:D000666"}
{"mention": "AmB", "mention_text": "We describe a patient who developed dilated cardiomyopathy and clinical congestive heart failure after 2 months of therapy with amphotericin B (AmB) for disseminated coccidioidomycosis. His echocardiographic abnormalities and heart failure resolved after posaconazole was substituted for AmB. It is important to recognize the rare and potentially reversible toxicity of AmB.", "entity": "Amphotericin B", "aliases": "Amphocil Amphotericin B Cholesterol Dispersion Colloidal Fungizone", "definition": "Macrolide antifungal antibiotic produced by Streptomyces nodosus obtained from soil of the Orinoco river region of Venezuela.\n    ", "id": "MESH:D000666"}
{"mention": "coccidioidomycosis", "mention_text": "We describe a patient who developed dilated cardiomyopathy and clinical congestive heart failure after 2 months of therapy with amphotericin B (AmB) for disseminated coccidioidomycosis. His echocardiographic abnormalities and heart failure resolved after posaconazole was substituted for AmB. It is important to recognize the rare and potentially reversible toxicity of AmB.", "entity": "Coccidioidomycosis", "aliases": "Coccidioides immitis Infection Infections Coccidioidomycoses Coccidioidomycosis San Joaquin Valley Fever Fevers", "definition": "Infection with a fungus of the genus COCCIDIOIDES, endemic to the SOUTHWESTERN UNITED STATES. It is sometimes called valley fever but should not be confused with RIFT VALLEY FEVER. Infection is caused by inhalation of airborne, fungal particles known as arthroconidia, a form of FUNGAL SPORES. A primary form is an acute, benign, self-limited respiratory infection. A secondary form is a virulent, severe, chronic, progressive granulomatous disease with systemic involvement. It can be detected by use of COCCIDIOIDIN.\n    ", "id": "MESH:D003047"}
{"mention": "posaconazole", "mention_text": "We describe a patient who developed dilated cardiomyopathy and clinical congestive heart failure after 2 months of therapy with amphotericin B (AmB) for disseminated coccidioidomycosis. His echocardiographic abnormalities and heart failure resolved after posaconazole was substituted for AmB. It is important to recognize the rare and potentially reversible toxicity of AmB.", "entity": "posaconazole", "aliases": "Noxafil SCH 56592 SCH-56592 posaconazole", "definition": "", "id": "MESH:C101425"}
{"mention": "toxicity", "mention_text": "We describe a patient who developed dilated cardiomyopathy and clinical congestive heart failure after 2 months of therapy with amphotericin B (AmB) for disseminated coccidioidomycosis. His echocardiographic abnormalities and heart failure resolved after posaconazole was substituted for AmB. It is important to recognize the rare and potentially reversible toxicity of AmB.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "quinine", "mention_text": "Risks of the consumption of beverages containing quinine.", "entity": "Quinine", "aliases": "Alphapharm Brand of Quinine Sulfate Aventis Bisulfate Biquinate Fawns & McAllan Foy Hoechst Hydrochloride Innotech Lafran Legatrim Myoquin Odan Plough Prosana Quinamm Quinbisan Quinbisul Quindan Quinimax Sulphate Quinine-Odan Quinoctal Quinson Quinsul Strema Surquina", "definition": "An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood.\n    ", "id": "MESH:D011803"}
{"mention": "nocturnal leg cramps", "mention_text": "Although the United States Food and Drug Administration banned its use for nocturnal leg cramps due to lack of safety and efficacy, quinine is widely available in beverages including tonic water and bitter lemon. Numerous anecdotal reports suggest that products containing quinine may produce neurological complications, including confusion, altered mental status, seizures, and coma, particularly in older women. Psychologists need to inquire about consumption of quinine-containing beverages as part of an evaluation process.", "entity": "Sleep-Wake Transition Disorders", "aliases": "Cramp Nocturnal Leg Cramps Jactatio Capitis Nocturna Movement Disorders Rhythmic Sleep Head Banging Starts Talking Wake Transition Transitional Sleep-Wake Disorder Somnolescent", "definition": "Parasomnias characterized by behavioral abnormalities that occur during the transition between wakefulness and sleep (or between sleep and wakefulness).\n    ", "id": "MESH:D020922"}
{"mention": "quinine", "mention_text": "Although the United States Food and Drug Administration banned its use for nocturnal leg cramps due to lack of safety and efficacy, quinine is widely available in beverages including tonic water and bitter lemon. Numerous anecdotal reports suggest that products containing quinine may produce neurological complications, including confusion, altered mental status, seizures, and coma, particularly in older women. Psychologists need to inquire about consumption of quinine-containing beverages as part of an evaluation process.", "entity": "Quinine", "aliases": "Alphapharm Brand of Quinine Sulfate Aventis Bisulfate Biquinate Fawns & McAllan Foy Hoechst Hydrochloride Innotech Lafran Legatrim Myoquin Odan Plough Prosana Quinamm Quinbisan Quinbisul Quindan Quinimax Sulphate Quinine-Odan Quinoctal Quinson Quinsul Strema Surquina", "definition": "An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood.\n    ", "id": "MESH:D011803"}
{"mention": "neurological complications", "mention_text": "Although the United States Food and Drug Administration banned its use for nocturnal leg cramps due to lack of safety and efficacy, quinine is widely available in beverages including tonic water and bitter lemon. Numerous anecdotal reports suggest that products containing quinine may produce neurological complications, including confusion, altered mental status, seizures, and coma, particularly in older women. Psychologists need to inquire about consumption of quinine-containing beverages as part of an evaluation process.", "entity": "Central Nervous System Diseases", "aliases": "CNS Disease Diseases Central Nervous System Disorders", "definition": "Diseases of any component of the brain (including the cerebral hemispheres, diencephalon, brain stem, and cerebellum) or the spinal cord.\n    ", "id": "MESH:D002493"}
{"mention": "confusion", "mention_text": "Although the United States Food and Drug Administration banned its use for nocturnal leg cramps due to lack of safety and efficacy, quinine is widely available in beverages including tonic water and bitter lemon. Numerous anecdotal reports suggest that products containing quinine may produce neurological complications, including confusion, altered mental status, seizures, and coma, particularly in older women. Psychologists need to inquire about consumption of quinine-containing beverages as part of an evaluation process.", "entity": "Confusion", "aliases": "Bewilderment Confusion Post Ictal Post-Ictal Reactive Confusional State States Disorientation", "definition": "A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation.\n    ", "id": "MESH:D003221"}
{"mention": "seizures", "mention_text": "Although the United States Food and Drug Administration banned its use for nocturnal leg cramps due to lack of safety and efficacy, quinine is widely available in beverages including tonic water and bitter lemon. Numerous anecdotal reports suggest that products containing quinine may produce neurological complications, including confusion, altered mental status, seizures, and coma, particularly in older women. Psychologists need to inquire about consumption of quinine-containing beverages as part of an evaluation process.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "coma", "mention_text": "Although the United States Food and Drug Administration banned its use for nocturnal leg cramps due to lack of safety and efficacy, quinine is widely available in beverages including tonic water and bitter lemon. Numerous anecdotal reports suggest that products containing quinine may produce neurological complications, including confusion, altered mental status, seizures, and coma, particularly in older women. Psychologists need to inquire about consumption of quinine-containing beverages as part of an evaluation process.", "entity": "Coma", "aliases": "Coma Comas Comatose Pseudocoma Pseudocomas", "definition": "A profound state of unconsciousness associated with depressed cerebral activity from which the individual cannot be aroused. Coma generally occurs when there is dysfunction or injury involving both cerebral hemispheres or the brain stem RETICULAR FORMATION.\n    ", "id": "MESH:D003128"}
{"mention": "Organophosphate", "mention_text": "Organophosphate-induced convulsions and prevention of neuropathological damages.", "entity": "Organophosphates", "aliases": "Acid Esters Phosphoric Organic Phosphates Organophosphates Organopyrophosphates", "definition": "Carbon-containing phosphoric acid derivatives. Included under this heading are compounds that have CARBON atoms bound to one or more OXYGEN atoms of the P(=O)(O)3 structure. Note that several specific classes of endogenous phosphorus-containing compounds such as NUCLEOTIDES; PHOSPHOLIPIDS; and PHOSPHOPROTEINS are listed elsewhere.\n    ", "id": "MESH:D010755"}
{"mention": "convulsions", "mention_text": "Organophosphate-induced convulsions and prevention of neuropathological damages.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "neuropathological damages", "mention_text": "Organophosphate-induced convulsions and prevention of neuropathological damages.", "entity": "Disease", "aliases": "Disease Diseases", "definition": "A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.\n    ", "id": "MESH:D004194"}
{"mention": "organophosphorus", "mention_text": "Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.", "entity": "Organophosphates", "aliases": "Acid Esters Phosphoric Organic Phosphates Organophosphates Organopyrophosphates", "definition": "Carbon-containing phosphoric acid derivatives. Included under this heading are compounds that have CARBON atoms bound to one or more OXYGEN atoms of the P(=O)(O)3 structure. Note that several specific classes of endogenous phosphorus-containing compounds such as NUCLEOTIDES; PHOSPHOLIPIDS; and PHOSPHOPROTEINS are listed elsewhere.\n    ", "id": "MESH:D010755"}
{"mention": "OP", "mention_text": "Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.", "entity": "Organophosphates", "aliases": "Acid Esters Phosphoric Organic Phosphates Organophosphates Organopyrophosphates", "definition": "Carbon-containing phosphoric acid derivatives. Included under this heading are compounds that have CARBON atoms bound to one or more OXYGEN atoms of the P(=O)(O)3 structure. Note that several specific classes of endogenous phosphorus-containing compounds such as NUCLEOTIDES; PHOSPHOLIPIDS; and PHOSPHOPROTEINS are listed elsewhere.\n    ", "id": "MESH:D010755"}
{"mention": "diisopropylfluorophosphate", "mention_text": "Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.", "entity": "Isoflurophate", "aliases": "Bis(1-methylethyl) Phosphorofluoridate DFP Di isopropylphosphorofluoridate Di-isopropylphosphorofluoridate Diisopropylfluorophosphate Diisopropylphosphofluoridate Dyflos Floropryl Fluorostigmine Fluostigmine Isoflurophate Merck Brand of", "definition": "A di-isopropyl-fluorophosphate which is an irreversible cholinesterase inhibitor used to investigate the NERVOUS SYSTEM.\n    ", "id": "MESH:D007531"}
{"mention": "DFP", "mention_text": "Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.", "entity": "Isoflurophate", "aliases": "Bis(1-methylethyl) Phosphorofluoridate DFP Di isopropylphosphorofluoridate Di-isopropylphosphorofluoridate Diisopropylfluorophosphate Diisopropylphosphofluoridate Dyflos Floropryl Fluorostigmine Fluostigmine Isoflurophate Merck Brand of", "definition": "A di-isopropyl-fluorophosphate which is an irreversible cholinesterase inhibitor used to investigate the NERVOUS SYSTEM.\n    ", "id": "MESH:D007531"}
{"mention": "sarin", "mention_text": "Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.", "entity": "Sarin", "aliases": "Phosphonofluoridate o-Isopropylmethyl ortho-Isopropylmethyl Sarin o Isopropylmethyl ortho", "definition": "An organophosphorus ester compound that produces potent and irreversible inhibition of cholinesterase. It is toxic to the nervous system and is a chemical warfare agent.\n    ", "id": "MESH:D012524"}
{"mention": "soman", "mention_text": "Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.", "entity": "Soman", "aliases": "Methylphosphonofluoridate Pinacolyl Soman", "definition": "An organophosphorus compound that inhibits cholinesterase. It causes seizures and has been used as a chemical warfare agent.\n    ", "id": "MESH:D012999"}
{"mention": "toxicity", "mention_text": "Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "OPs", "mention_text": "Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.", "entity": "Organophosphates", "aliases": "Acid Esters Phosphoric Organic Phosphates Organophosphates Organopyrophosphates", "definition": "Carbon-containing phosphoric acid derivatives. Included under this heading are compounds that have CARBON atoms bound to one or more OXYGEN atoms of the P(=O)(O)3 structure. Note that several specific classes of endogenous phosphorus-containing compounds such as NUCLEOTIDES; PHOSPHOLIPIDS; and PHOSPHOPROTEINS are listed elsewhere.\n    ", "id": "MESH:D010755"}
{"mention": "acetylcholine", "mention_text": "Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.", "entity": "Acetylcholine", "aliases": "2-(Acetyloxy)-N,N,N-trimethylethanaminium Acetilcolina Cusi Acetylcholine Bromide Chloride Fluoride Hydroxide Iodide L Tartrate L-Tartrate Perchlorate Picrate (1:1) Sulfate Alcon Brand of Bournonville Bromoacetylcholine Chloroacetylcholine Ciba Vision Iolab Miochol", "definition": "A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.\n    ", "id": "MESH:D000109"}
{"mention": "ACh", "mention_text": "Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.", "entity": "Acetylcholine", "aliases": "2-(Acetyloxy)-N,N,N-trimethylethanaminium Acetilcolina Cusi Acetylcholine Bromide Chloride Fluoride Hydroxide Iodide L Tartrate L-Tartrate Perchlorate Picrate (1:1) Sulfate Alcon Brand of Bournonville Bromoacetylcholine Chloroacetylcholine Ciba Vision Iolab Miochol", "definition": "A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.\n    ", "id": "MESH:D000109"}
{"mention": "pralidoxime-2-chloride", "mention_text": "Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.", "entity": "Pralidoxime Compounds", "aliases": "2 PAM Compounds 2-PAM Pralidoxime Pyridine Aldoxime Methyl", "definition": "Various salts of a quaternary ammonium oxime that reconstitute inactivated acetylcholinesterase, especially at the neuromuscular junction, and may cause neuromuscular blockade. They are used as antidotes to organophosphorus poisoning as chlorides, iodides, methanesulfonates (mesylates), or other salts.\n    ", "id": "MESH:D011220"}
{"mention": "2PAM", "mention_text": "Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.", "entity": "Pralidoxime Compounds", "aliases": "2 PAM Compounds 2-PAM Pralidoxime Pyridine Aldoxime Methyl", "definition": "Various salts of a quaternary ammonium oxime that reconstitute inactivated acetylcholinesterase, especially at the neuromuscular junction, and may cause neuromuscular blockade. They are used as antidotes to organophosphorus poisoning as chlorides, iodides, methanesulfonates (mesylates), or other salts.\n    ", "id": "MESH:D011220"}
{"mention": "diazepam", "mention_text": "Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.", "entity": "Diazepam", "aliases": "7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one Apaurin Diazemuls Diazepam Faustan Relanium Seduxen Sibazon Stesolid Valium", "definition": "A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity.\n    ", "id": "MESH:D003975"}
{"mention": "adenosine", "mention_text": "Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.", "entity": "Adenosine", "aliases": "Adenocard Adenoscan Adenosine", "definition": "A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.\n    ", "id": "MESH:D000241"}
{"mention": "N(6)-cyclopentyl adenosine", "mention_text": "Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.", "entity": "N(6)-cyclopentyladenosine", "aliases": "N(6)-cyclopentyladenosine N6-cyclopentyladenosine", "definition": "", "id": "MESH:C048599"}
{"mention": "CPA", "mention_text": "Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.", "entity": "N(6)-cyclopentyladenosine", "aliases": "N(6)-cyclopentyladenosine N6-cyclopentyladenosine", "definition": "", "id": "MESH:C048599"}
{"mention": "NMDA", "mention_text": "Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.", "entity": "N-Methylaspartate", "aliases": "Acid N-Methyl-D-aspartic N Methyl D aspartate aspartic Methylaspartate N-Methyl-D-aspartate N-Methylaspartate NMDA", "definition": "An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).\n    ", "id": "MESH:D016202"}
{"mention": "dizocilpine maleate", "mention_text": "Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.", "entity": "Dizocilpine Maleate", "aliases": "Dizocilpine Maleate MK 801 MK-801 MK801", "definition": "A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects.\n    ", "id": "MESH:D016291"}
{"mention": "atropine sulfate", "mention_text": "Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.", "entity": "Atropine", "aliases": "Anhydrous Atropine Sulfate AtroPen Atropin Augenöl Chauvin Brand Winzer Atropinol of Survival Technology", "definition": "An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.\n    ", "id": "MESH:D001285"}
{"mention": "atropine", "mention_text": "Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.", "entity": "Atropine", "aliases": "Anhydrous Atropine Sulfate AtroPen Atropin Augenöl Chauvin Brand Winzer Atropinol of Survival Technology", "definition": "An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.\n    ", "id": "MESH:D001285"}
{"mention": "poisoning", "mention_text": "Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.", "entity": "Poisoning", "aliases": "Poisoning Poisonings", "definition": "A condition or physical state produced by the ingestion, injection, inhalation of or exposure to a deleterious agent.\n    ", "id": "MESH:D011041"}
{"mention": "Atropine", "mention_text": "Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.", "entity": "Atropine", "aliases": "Anhydrous Atropine Sulfate AtroPen Atropin Augenöl Chauvin Brand Winzer Atropinol of Survival Technology", "definition": "An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.\n    ", "id": "MESH:D001285"}
{"mention": "MK801", "mention_text": "Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.", "entity": "Dizocilpine Maleate", "aliases": "Dizocilpine Maleate MK 801 MK-801 MK801", "definition": "A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects.\n    ", "id": "MESH:D016291"}
{"mention": "estrogen", "mention_text": "Differential modulation by estrogen of alpha2-adrenergic and I1-imidazoline receptor-mediated hypotension in female rats.", "entity": "Estrogens", "aliases": "Agents Estrogenic Agonists Estrogen Receptor Compounds Effects Effect Estrogens", "definition": "Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds.\n    ", "id": "MESH:D004967"}
{"mention": "imidazoline", "mention_text": "Differential modulation by estrogen of alpha2-adrenergic and I1-imidazoline receptor-mediated hypotension in female rats.", "entity": "Imidazolines", "aliases": "Imidazolines", "definition": "Compounds based on reduced IMIDAZOLES containing a single double bond.\n    ", "id": "MESH:D048288"}
{"mention": "hypotension", "mention_text": "Differential modulation by estrogen of alpha2-adrenergic and I1-imidazoline receptor-mediated hypotension in female rats.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "estrogen", "mention_text": "We have recently shown that estrogen negatively modulates the hypotensive effect of clonidine (mixed alpha2-/I1-receptor agonist) in female rats and implicates the cardiovascular autonomic control in this interaction. The present study investigated whether this effect of estrogen involves interaction with alpha2- and/or I1-receptors. Changes evoked by a single intraperitoneal injection of rilmenidine (600 microg/kg) or alpha-methyldopa (100 mg/kg), selective I1- and alpha2-receptor agonists, respectively, in blood pressure, hemodynamic variability, and locomotor activity were assessed in radiotelemetered sham-operated and ovariectomized (Ovx) Sprague-Dawley female rats with or without 12-wk estrogen replacement. Three time domain indexes of hemodynamic variability were employed: the standard deviation of mean arterial pressure as a measure of blood pressure variability and the standard deviation of beat-to-beat intervals (SDRR) and the root mean square of successive differences in R-wave-to-R-wave intervals as measures of heart rate variability. In sham-operated rats, rilmenidine or alpha-methyldopa elicited similar hypotension that lasted at least 5 h and was associated with reductions in standard deviation of mean arterial pressure. SDRR was reduced only by alpha-methyldopa. Ovx significantly enhanced the hypotensive response to alpha-methyldopa, in contrast to no effect on rilmenidine hypotension. The enhanced alpha-methyldopa hypotension in Ovx rats was paralleled with further reduction in SDRR and a reduced locomotor activity. Estrogen replacement (17beta-estradiol subcutaneous pellet, 14.2 microg/day, 12 wk) of Ovx rats restored the hemodynamic and locomotor effects of alpha-methyldopa to sham-operated levels. These findings suggest that estrogen downregulates alpha2- but not I1-receptor-mediated hypotension and highlight a role for the cardiac autonomic control in alpha-methyldopa-estrogen interaction.", "entity": "Estrogens", "aliases": "Agents Estrogenic Agonists Estrogen Receptor Compounds Effects Effect Estrogens", "definition": "Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds.\n    ", "id": "MESH:D004967"}
{"mention": "hypotensive", "mention_text": "We have recently shown that estrogen negatively modulates the hypotensive effect of clonidine (mixed alpha2-/I1-receptor agonist) in female rats and implicates the cardiovascular autonomic control in this interaction. The present study investigated whether this effect of estrogen involves interaction with alpha2- and/or I1-receptors. Changes evoked by a single intraperitoneal injection of rilmenidine (600 microg/kg) or alpha-methyldopa (100 mg/kg), selective I1- and alpha2-receptor agonists, respectively, in blood pressure, hemodynamic variability, and locomotor activity were assessed in radiotelemetered sham-operated and ovariectomized (Ovx) Sprague-Dawley female rats with or without 12-wk estrogen replacement. Three time domain indexes of hemodynamic variability were employed: the standard deviation of mean arterial pressure as a measure of blood pressure variability and the standard deviation of beat-to-beat intervals (SDRR) and the root mean square of successive differences in R-wave-to-R-wave intervals as measures of heart rate variability. In sham-operated rats, rilmenidine or alpha-methyldopa elicited similar hypotension that lasted at least 5 h and was associated with reductions in standard deviation of mean arterial pressure. SDRR was reduced only by alpha-methyldopa. Ovx significantly enhanced the hypotensive response to alpha-methyldopa, in contrast to no effect on rilmenidine hypotension. The enhanced alpha-methyldopa hypotension in Ovx rats was paralleled with further reduction in SDRR and a reduced locomotor activity. Estrogen replacement (17beta-estradiol subcutaneous pellet, 14.2 microg/day, 12 wk) of Ovx rats restored the hemodynamic and locomotor effects of alpha-methyldopa to sham-operated levels. These findings suggest that estrogen downregulates alpha2- but not I1-receptor-mediated hypotension and highlight a role for the cardiac autonomic control in alpha-methyldopa-estrogen interaction.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "clonidine", "mention_text": "We have recently shown that estrogen negatively modulates the hypotensive effect of clonidine (mixed alpha2-/I1-receptor agonist) in female rats and implicates the cardiovascular autonomic control in this interaction. The present study investigated whether this effect of estrogen involves interaction with alpha2- and/or I1-receptors. Changes evoked by a single intraperitoneal injection of rilmenidine (600 microg/kg) or alpha-methyldopa (100 mg/kg), selective I1- and alpha2-receptor agonists, respectively, in blood pressure, hemodynamic variability, and locomotor activity were assessed in radiotelemetered sham-operated and ovariectomized (Ovx) Sprague-Dawley female rats with or without 12-wk estrogen replacement. Three time domain indexes of hemodynamic variability were employed: the standard deviation of mean arterial pressure as a measure of blood pressure variability and the standard deviation of beat-to-beat intervals (SDRR) and the root mean square of successive differences in R-wave-to-R-wave intervals as measures of heart rate variability. In sham-operated rats, rilmenidine or alpha-methyldopa elicited similar hypotension that lasted at least 5 h and was associated with reductions in standard deviation of mean arterial pressure. SDRR was reduced only by alpha-methyldopa. Ovx significantly enhanced the hypotensive response to alpha-methyldopa, in contrast to no effect on rilmenidine hypotension. The enhanced alpha-methyldopa hypotension in Ovx rats was paralleled with further reduction in SDRR and a reduced locomotor activity. Estrogen replacement (17beta-estradiol subcutaneous pellet, 14.2 microg/day, 12 wk) of Ovx rats restored the hemodynamic and locomotor effects of alpha-methyldopa to sham-operated levels. These findings suggest that estrogen downregulates alpha2- but not I1-receptor-mediated hypotension and highlight a role for the cardiac autonomic control in alpha-methyldopa-estrogen interaction.", "entity": "Clonidine", "aliases": "Boehringer Ingelheim Brand of Clonidine Hydrochloride Catapres Catapresan Catapressan Chlophazolin Clofelin Clofenil Dihydrochloride Monohydrobromide Monohydrochloride Clopheline Dixarit Gemiton Hemiton Isoglaucon Klofelin Klofenil M 5041T M-5041T M5041T ST 155 ST-155 ST155", "definition": "An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.\n    ", "id": "MESH:D003000"}
{"mention": "rilmenidine", "mention_text": "We have recently shown that estrogen negatively modulates the hypotensive effect of clonidine (mixed alpha2-/I1-receptor agonist) in female rats and implicates the cardiovascular autonomic control in this interaction. The present study investigated whether this effect of estrogen involves interaction with alpha2- and/or I1-receptors. Changes evoked by a single intraperitoneal injection of rilmenidine (600 microg/kg) or alpha-methyldopa (100 mg/kg), selective I1- and alpha2-receptor agonists, respectively, in blood pressure, hemodynamic variability, and locomotor activity were assessed in radiotelemetered sham-operated and ovariectomized (Ovx) Sprague-Dawley female rats with or without 12-wk estrogen replacement. Three time domain indexes of hemodynamic variability were employed: the standard deviation of mean arterial pressure as a measure of blood pressure variability and the standard deviation of beat-to-beat intervals (SDRR) and the root mean square of successive differences in R-wave-to-R-wave intervals as measures of heart rate variability. In sham-operated rats, rilmenidine or alpha-methyldopa elicited similar hypotension that lasted at least 5 h and was associated with reductions in standard deviation of mean arterial pressure. SDRR was reduced only by alpha-methyldopa. Ovx significantly enhanced the hypotensive response to alpha-methyldopa, in contrast to no effect on rilmenidine hypotension. The enhanced alpha-methyldopa hypotension in Ovx rats was paralleled with further reduction in SDRR and a reduced locomotor activity. Estrogen replacement (17beta-estradiol subcutaneous pellet, 14.2 microg/day, 12 wk) of Ovx rats restored the hemodynamic and locomotor effects of alpha-methyldopa to sham-operated levels. These findings suggest that estrogen downregulates alpha2- but not I1-receptor-mediated hypotension and highlight a role for the cardiac autonomic control in alpha-methyldopa-estrogen interaction.", "entity": "rilmenidine", "aliases": "2-(N-(dicyclopropylmethyl)amino)oxazoline phosphate salt Hyperium S 3341 S-3341 S-3341-3 S3341 oxaminozoline rilmenidine", "definition": "", "id": "MESH:C032302"}
{"mention": "alpha-methyldopa", "mention_text": "We have recently shown that estrogen negatively modulates the hypotensive effect of clonidine (mixed alpha2-/I1-receptor agonist) in female rats and implicates the cardiovascular autonomic control in this interaction. The present study investigated whether this effect of estrogen involves interaction with alpha2- and/or I1-receptors. Changes evoked by a single intraperitoneal injection of rilmenidine (600 microg/kg) or alpha-methyldopa (100 mg/kg), selective I1- and alpha2-receptor agonists, respectively, in blood pressure, hemodynamic variability, and locomotor activity were assessed in radiotelemetered sham-operated and ovariectomized (Ovx) Sprague-Dawley female rats with or without 12-wk estrogen replacement. Three time domain indexes of hemodynamic variability were employed: the standard deviation of mean arterial pressure as a measure of blood pressure variability and the standard deviation of beat-to-beat intervals (SDRR) and the root mean square of successive differences in R-wave-to-R-wave intervals as measures of heart rate variability. In sham-operated rats, rilmenidine or alpha-methyldopa elicited similar hypotension that lasted at least 5 h and was associated with reductions in standard deviation of mean arterial pressure. SDRR was reduced only by alpha-methyldopa. Ovx significantly enhanced the hypotensive response to alpha-methyldopa, in contrast to no effect on rilmenidine hypotension. The enhanced alpha-methyldopa hypotension in Ovx rats was paralleled with further reduction in SDRR and a reduced locomotor activity. Estrogen replacement (17beta-estradiol subcutaneous pellet, 14.2 microg/day, 12 wk) of Ovx rats restored the hemodynamic and locomotor effects of alpha-methyldopa to sham-operated levels. These findings suggest that estrogen downregulates alpha2- but not I1-receptor-mediated hypotension and highlight a role for the cardiac autonomic control in alpha-methyldopa-estrogen interaction.", "entity": "Methyldopa", "aliases": "Aldomet Alphamethyldopa Alphapharm Brand of Methyldopa Apo Apo-Methyldopa Apotex Biopat Cahill May Roberts Clonmel Dopamet Dopegit Dopegyt Dopergit Hydopa Meldopa Merck Sharp & Dohme Nu-Pharm Orion Methyldopate Nu Medopa Pharm Nu-Medopa Rhône Poulenc Rorer Rhône-Poulenc Sembrina alpha Methyl L Dopa alpha-Methyl-L-Dopa alpha-Methyldopa", "definition": "An alpha-2 adrenergic agonist that has both central and peripheral nervous system effects. Its primary clinical use is as an antihypertensive agent.\n    ", "id": "MESH:D008750"}
{"mention": "hypotension", "mention_text": "We have recently shown that estrogen negatively modulates the hypotensive effect of clonidine (mixed alpha2-/I1-receptor agonist) in female rats and implicates the cardiovascular autonomic control in this interaction. The present study investigated whether this effect of estrogen involves interaction with alpha2- and/or I1-receptors. Changes evoked by a single intraperitoneal injection of rilmenidine (600 microg/kg) or alpha-methyldopa (100 mg/kg), selective I1- and alpha2-receptor agonists, respectively, in blood pressure, hemodynamic variability, and locomotor activity were assessed in radiotelemetered sham-operated and ovariectomized (Ovx) Sprague-Dawley female rats with or without 12-wk estrogen replacement. Three time domain indexes of hemodynamic variability were employed: the standard deviation of mean arterial pressure as a measure of blood pressure variability and the standard deviation of beat-to-beat intervals (SDRR) and the root mean square of successive differences in R-wave-to-R-wave intervals as measures of heart rate variability. In sham-operated rats, rilmenidine or alpha-methyldopa elicited similar hypotension that lasted at least 5 h and was associated with reductions in standard deviation of mean arterial pressure. SDRR was reduced only by alpha-methyldopa. Ovx significantly enhanced the hypotensive response to alpha-methyldopa, in contrast to no effect on rilmenidine hypotension. The enhanced alpha-methyldopa hypotension in Ovx rats was paralleled with further reduction in SDRR and a reduced locomotor activity. Estrogen replacement (17beta-estradiol subcutaneous pellet, 14.2 microg/day, 12 wk) of Ovx rats restored the hemodynamic and locomotor effects of alpha-methyldopa to sham-operated levels. These findings suggest that estrogen downregulates alpha2- but not I1-receptor-mediated hypotension and highlight a role for the cardiac autonomic control in alpha-methyldopa-estrogen interaction.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "a reduced locomotor activity", "mention_text": "We have recently shown that estrogen negatively modulates the hypotensive effect of clonidine (mixed alpha2-/I1-receptor agonist) in female rats and implicates the cardiovascular autonomic control in this interaction. The present study investigated whether this effect of estrogen involves interaction with alpha2- and/or I1-receptors. Changes evoked by a single intraperitoneal injection of rilmenidine (600 microg/kg) or alpha-methyldopa (100 mg/kg), selective I1- and alpha2-receptor agonists, respectively, in blood pressure, hemodynamic variability, and locomotor activity were assessed in radiotelemetered sham-operated and ovariectomized (Ovx) Sprague-Dawley female rats with or without 12-wk estrogen replacement. Three time domain indexes of hemodynamic variability were employed: the standard deviation of mean arterial pressure as a measure of blood pressure variability and the standard deviation of beat-to-beat intervals (SDRR) and the root mean square of successive differences in R-wave-to-R-wave intervals as measures of heart rate variability. In sham-operated rats, rilmenidine or alpha-methyldopa elicited similar hypotension that lasted at least 5 h and was associated with reductions in standard deviation of mean arterial pressure. SDRR was reduced only by alpha-methyldopa. Ovx significantly enhanced the hypotensive response to alpha-methyldopa, in contrast to no effect on rilmenidine hypotension. The enhanced alpha-methyldopa hypotension in Ovx rats was paralleled with further reduction in SDRR and a reduced locomotor activity. Estrogen replacement (17beta-estradiol subcutaneous pellet, 14.2 microg/day, 12 wk) of Ovx rats restored the hemodynamic and locomotor effects of alpha-methyldopa to sham-operated levels. These findings suggest that estrogen downregulates alpha2- but not I1-receptor-mediated hypotension and highlight a role for the cardiac autonomic control in alpha-methyldopa-estrogen interaction.", "entity": "Mental Disorders", "aliases": "Behavior Disorders Diagnosis Psychiatric Disorder Mental", "definition": "Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.\n    ", "id": "MESH:D001523"}
{"mention": "17beta-estradiol", "mention_text": "We have recently shown that estrogen negatively modulates the hypotensive effect of clonidine (mixed alpha2-/I1-receptor agonist) in female rats and implicates the cardiovascular autonomic control in this interaction. The present study investigated whether this effect of estrogen involves interaction with alpha2- and/or I1-receptors. Changes evoked by a single intraperitoneal injection of rilmenidine (600 microg/kg) or alpha-methyldopa (100 mg/kg), selective I1- and alpha2-receptor agonists, respectively, in blood pressure, hemodynamic variability, and locomotor activity were assessed in radiotelemetered sham-operated and ovariectomized (Ovx) Sprague-Dawley female rats with or without 12-wk estrogen replacement. Three time domain indexes of hemodynamic variability were employed: the standard deviation of mean arterial pressure as a measure of blood pressure variability and the standard deviation of beat-to-beat intervals (SDRR) and the root mean square of successive differences in R-wave-to-R-wave intervals as measures of heart rate variability. In sham-operated rats, rilmenidine or alpha-methyldopa elicited similar hypotension that lasted at least 5 h and was associated with reductions in standard deviation of mean arterial pressure. SDRR was reduced only by alpha-methyldopa. Ovx significantly enhanced the hypotensive response to alpha-methyldopa, in contrast to no effect on rilmenidine hypotension. The enhanced alpha-methyldopa hypotension in Ovx rats was paralleled with further reduction in SDRR and a reduced locomotor activity. Estrogen replacement (17beta-estradiol subcutaneous pellet, 14.2 microg/day, 12 wk) of Ovx rats restored the hemodynamic and locomotor effects of alpha-methyldopa to sham-operated levels. These findings suggest that estrogen downregulates alpha2- but not I1-receptor-mediated hypotension and highlight a role for the cardiac autonomic control in alpha-methyldopa-estrogen interaction.", "entity": "Estradiol", "aliases": "17 beta Estradiol Oestradiol beta-Estradiol beta-Oestradiol Aerodiol Estrace Estraderm TTS alpha 17beta Anhydrous Hemihydrate (17 alpha)-Isomer Monohydrate Orion Brand (+-)-Isomer (-)-Isomer (16 alpha,17 beta)-Isomer (17-alpha)-Isomer (8 beta)-(+-)-Isomer (9 beta,17 Monosodium Salt Sodium Estradiol-17 Estradiol-17beta Novartis Pharmaceuticals of Ovocyclin Vivelle", "definition": "The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.\n    ", "id": "MESH:D004958"}
{"mention": "tincture of Crataegus", "mention_text": "Cardioprotective effect of tincture of Crataegus on isoproterenol-induced myocardial infarction in rats.", "entity": "crataegus extract", "aliases": "Crataegutt crataegus extract", "definition": "", "id": "MESH:C007145"}
{"mention": "isoproterenol", "mention_text": "Cardioprotective effect of tincture of Crataegus on isoproterenol-induced myocardial infarction in rats.", "entity": "Isoproterenol", "aliases": "4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol Euspiran Hydrochloride Isoproterenol Isadrin Isadrine Isoprenaline Isopropyl Noradrenaline Isopropylarterenol Isopropylnoradrenaline Isopropylnorepinephrine Sulfate Isuprel Izadrin Norisodrine Novodrin", "definition": "Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.\n    ", "id": "MESH:D007545"}
{"mention": "myocardial infarction", "mention_text": "Cardioprotective effect of tincture of Crataegus on isoproterenol-induced myocardial infarction in rats.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "Tincture of Crataegus", "mention_text": "Tincture of Crataegus (TCR), an alcoholic extract of the berries of hawthorn (Crataegus oxycantha), is used in herbal and homeopathic medicine. The present study was done to investigate the protective effect of TCR on experimentally induced myocardial infarction in rats. Pretreatment of TCR, at a dose of 0.5 mL/100 g bodyweight per day, orally for 30 days, prevented the increase in lipid peroxidation and activity of marker enzymes observed in isoproterenol-induced rats (85 mg kg(-1) s. c. for 2 days at an interval of 24 h). TCR prevented the isoproterenol-induced decrease in antioxidant enzymes in the heart and increased the rate of ADP-stimulated oxygen uptake and respiratory coupling ratio. TCR protected against pathological changes induced by isoproterenol in rat heart. The results show that pretreatment with TCR may be useful in preventing the damage induced by isoproterenol in rat heart.", "entity": "crataegus extract", "aliases": "Crataegutt crataegus extract", "definition": "", "id": "MESH:C007145"}
{"mention": "TCR", "mention_text": "Tincture of Crataegus (TCR), an alcoholic extract of the berries of hawthorn (Crataegus oxycantha), is used in herbal and homeopathic medicine. The present study was done to investigate the protective effect of TCR on experimentally induced myocardial infarction in rats. Pretreatment of TCR, at a dose of 0.5 mL/100 g bodyweight per day, orally for 30 days, prevented the increase in lipid peroxidation and activity of marker enzymes observed in isoproterenol-induced rats (85 mg kg(-1) s. c. for 2 days at an interval of 24 h). TCR prevented the isoproterenol-induced decrease in antioxidant enzymes in the heart and increased the rate of ADP-stimulated oxygen uptake and respiratory coupling ratio. TCR protected against pathological changes induced by isoproterenol in rat heart. The results show that pretreatment with TCR may be useful in preventing the damage induced by isoproterenol in rat heart.", "entity": "crataegus extract", "aliases": "Crataegutt crataegus extract", "definition": "", "id": "MESH:C007145"}
{"mention": "alcoholic extract of the berries of hawthorn", "mention_text": "Tincture of Crataegus (TCR), an alcoholic extract of the berries of hawthorn (Crataegus oxycantha), is used in herbal and homeopathic medicine. The present study was done to investigate the protective effect of TCR on experimentally induced myocardial infarction in rats. Pretreatment of TCR, at a dose of 0.5 mL/100 g bodyweight per day, orally for 30 days, prevented the increase in lipid peroxidation and activity of marker enzymes observed in isoproterenol-induced rats (85 mg kg(-1) s. c. for 2 days at an interval of 24 h). TCR prevented the isoproterenol-induced decrease in antioxidant enzymes in the heart and increased the rate of ADP-stimulated oxygen uptake and respiratory coupling ratio. TCR protected against pathological changes induced by isoproterenol in rat heart. The results show that pretreatment with TCR may be useful in preventing the damage induced by isoproterenol in rat heart.", "entity": "crataegus extract", "aliases": "Crataegutt crataegus extract", "definition": "", "id": "MESH:C007145"}
{"mention": "Crataegus oxycantha", "mention_text": "Tincture of Crataegus (TCR), an alcoholic extract of the berries of hawthorn (Crataegus oxycantha), is used in herbal and homeopathic medicine. The present study was done to investigate the protective effect of TCR on experimentally induced myocardial infarction in rats. Pretreatment of TCR, at a dose of 0.5 mL/100 g bodyweight per day, orally for 30 days, prevented the increase in lipid peroxidation and activity of marker enzymes observed in isoproterenol-induced rats (85 mg kg(-1) s. c. for 2 days at an interval of 24 h). TCR prevented the isoproterenol-induced decrease in antioxidant enzymes in the heart and increased the rate of ADP-stimulated oxygen uptake and respiratory coupling ratio. TCR protected against pathological changes induced by isoproterenol in rat heart. The results show that pretreatment with TCR may be useful in preventing the damage induced by isoproterenol in rat heart.", "entity": "crataegus extract", "aliases": "Crataegutt crataegus extract", "definition": "", "id": "MESH:C007145"}
{"mention": "myocardial infarction", "mention_text": "Tincture of Crataegus (TCR), an alcoholic extract of the berries of hawthorn (Crataegus oxycantha), is used in herbal and homeopathic medicine. The present study was done to investigate the protective effect of TCR on experimentally induced myocardial infarction in rats. Pretreatment of TCR, at a dose of 0.5 mL/100 g bodyweight per day, orally for 30 days, prevented the increase in lipid peroxidation and activity of marker enzymes observed in isoproterenol-induced rats (85 mg kg(-1) s. c. for 2 days at an interval of 24 h). TCR prevented the isoproterenol-induced decrease in antioxidant enzymes in the heart and increased the rate of ADP-stimulated oxygen uptake and respiratory coupling ratio. TCR protected against pathological changes induced by isoproterenol in rat heart. The results show that pretreatment with TCR may be useful in preventing the damage induced by isoproterenol in rat heart.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "isoproterenol", "mention_text": "Tincture of Crataegus (TCR), an alcoholic extract of the berries of hawthorn (Crataegus oxycantha), is used in herbal and homeopathic medicine. The present study was done to investigate the protective effect of TCR on experimentally induced myocardial infarction in rats. Pretreatment of TCR, at a dose of 0.5 mL/100 g bodyweight per day, orally for 30 days, prevented the increase in lipid peroxidation and activity of marker enzymes observed in isoproterenol-induced rats (85 mg kg(-1) s. c. for 2 days at an interval of 24 h). TCR prevented the isoproterenol-induced decrease in antioxidant enzymes in the heart and increased the rate of ADP-stimulated oxygen uptake and respiratory coupling ratio. TCR protected against pathological changes induced by isoproterenol in rat heart. The results show that pretreatment with TCR may be useful in preventing the damage induced by isoproterenol in rat heart.", "entity": "Isoproterenol", "aliases": "4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol Euspiran Hydrochloride Isoproterenol Isadrin Isadrine Isoprenaline Isopropyl Noradrenaline Isopropylarterenol Isopropylnoradrenaline Isopropylnorepinephrine Sulfate Isuprel Izadrin Norisodrine Novodrin", "definition": "Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.\n    ", "id": "MESH:D007545"}
{"mention": "ADP", "mention_text": "Tincture of Crataegus (TCR), an alcoholic extract of the berries of hawthorn (Crataegus oxycantha), is used in herbal and homeopathic medicine. The present study was done to investigate the protective effect of TCR on experimentally induced myocardial infarction in rats. Pretreatment of TCR, at a dose of 0.5 mL/100 g bodyweight per day, orally for 30 days, prevented the increase in lipid peroxidation and activity of marker enzymes observed in isoproterenol-induced rats (85 mg kg(-1) s. c. for 2 days at an interval of 24 h). TCR prevented the isoproterenol-induced decrease in antioxidant enzymes in the heart and increased the rate of ADP-stimulated oxygen uptake and respiratory coupling ratio. TCR protected against pathological changes induced by isoproterenol in rat heart. The results show that pretreatment with TCR may be useful in preventing the damage induced by isoproterenol in rat heart.", "entity": "Adenosine Diphosphate", "aliases": "5'-Pyrophosphate Adenosine ADP Magnesium 5' Pyrophosphate Diphosphate MgADP", "definition": "Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.\n    ", "id": "MESH:D000244"}
{"mention": "oxygen", "mention_text": "Tincture of Crataegus (TCR), an alcoholic extract of the berries of hawthorn (Crataegus oxycantha), is used in herbal and homeopathic medicine. The present study was done to investigate the protective effect of TCR on experimentally induced myocardial infarction in rats. Pretreatment of TCR, at a dose of 0.5 mL/100 g bodyweight per day, orally for 30 days, prevented the increase in lipid peroxidation and activity of marker enzymes observed in isoproterenol-induced rats (85 mg kg(-1) s. c. for 2 days at an interval of 24 h). TCR prevented the isoproterenol-induced decrease in antioxidant enzymes in the heart and increased the rate of ADP-stimulated oxygen uptake and respiratory coupling ratio. TCR protected against pathological changes induced by isoproterenol in rat heart. The results show that pretreatment with TCR may be useful in preventing the damage induced by isoproterenol in rat heart.", "entity": "Oxygen", "aliases": "Dioxygen Oxygen", "definition": "An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.\n    ", "id": "MESH:D010100"}
{"mention": "raloxifene", "mention_text": "Safety and adverse effects associated with raloxifene: multiple outcomes of raloxifene evaluation.", "entity": "Raloxifene", "aliases": "ELi Lilly Brand of Raloxifene Evista Keoxifene Hydrochloride LY 139481 156758 LY-139481 LY-156758 LY139481 LY156758", "definition": "A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue.\n    ", "id": "MESH:D020849"}
{"mention": "raloxifene", "mention_text": "OBJECTIVE: To examine the effect of raloxifene on major adverse events that occur with postmenopausal estrogen therapy or tamoxifen. METHODS: The Multiple Outcomes of Raloxifene Evaluation, a multicenter, randomized, double-blind trial, enrolled 7,705 postmenopausal women with osteoporosis. Women were randomly assigned to raloxifene 60 mg/d or 120 mg/d or placebo. Outcomes included venous thromboembolism, cataracts, gallbladder disease, and endometrial hyperplasia or cancer. RESULTS: During a mean follow-up of 3.3 years, raloxifene was associated with an increased risk for venous thromboembolism (relative risk [RR] 2.1; 95% confidence interval [CI] 1.2-3.8). The excess event rate was 1.8 per 1,000 woman-years (95% CI -0.5-4.1), and the number needed to treat to cause 1 event was 170 (95% CI 100-582) over 3.3 years. Risk in the raloxifene group was higher than in the placebo group for the first 2 years, but decreased to about the same rate as in the placebo group thereafter. Raloxifene did not increase risk for cataracts (RR 0.9; 95% CI 0.8-1.1), gallbladder disease (RR 1.0; 95% CI 0.7-1.3), endometrial hyperplasia (RR 1.3; 95% CI 0.4-5.1), or endometrial cancer (RR 0.9; 95% CI 0.3-2.7). CONCLUSION: Raloxifene was associated with an increased risk for venous thromboembolism, but there was no increased risk for cataracts, gallbladder disease, endometrial hyperplasia, or endometrial cancer. LEVEL OF EVIDENCE: I", "entity": "Raloxifene", "aliases": "ELi Lilly Brand of Raloxifene Evista Keoxifene Hydrochloride LY 139481 156758 LY-139481 LY-156758 LY139481 LY156758", "definition": "A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue.\n    ", "id": "MESH:D020849"}
{"mention": "estrogen", "mention_text": "OBJECTIVE: To examine the effect of raloxifene on major adverse events that occur with postmenopausal estrogen therapy or tamoxifen. METHODS: The Multiple Outcomes of Raloxifene Evaluation, a multicenter, randomized, double-blind trial, enrolled 7,705 postmenopausal women with osteoporosis. Women were randomly assigned to raloxifene 60 mg/d or 120 mg/d or placebo. Outcomes included venous thromboembolism, cataracts, gallbladder disease, and endometrial hyperplasia or cancer. RESULTS: During a mean follow-up of 3.3 years, raloxifene was associated with an increased risk for venous thromboembolism (relative risk [RR] 2.1; 95% confidence interval [CI] 1.2-3.8). The excess event rate was 1.8 per 1,000 woman-years (95% CI -0.5-4.1), and the number needed to treat to cause 1 event was 170 (95% CI 100-582) over 3.3 years. Risk in the raloxifene group was higher than in the placebo group for the first 2 years, but decreased to about the same rate as in the placebo group thereafter. Raloxifene did not increase risk for cataracts (RR 0.9; 95% CI 0.8-1.1), gallbladder disease (RR 1.0; 95% CI 0.7-1.3), endometrial hyperplasia (RR 1.3; 95% CI 0.4-5.1), or endometrial cancer (RR 0.9; 95% CI 0.3-2.7). CONCLUSION: Raloxifene was associated with an increased risk for venous thromboembolism, but there was no increased risk for cataracts, gallbladder disease, endometrial hyperplasia, or endometrial cancer. LEVEL OF EVIDENCE: I", "entity": "Estrogens", "aliases": "Agents Estrogenic Agonists Estrogen Receptor Compounds Effects Effect Estrogens", "definition": "Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds.\n    ", "id": "MESH:D004967"}
{"mention": "tamoxifen", "mention_text": "OBJECTIVE: To examine the effect of raloxifene on major adverse events that occur with postmenopausal estrogen therapy or tamoxifen. METHODS: The Multiple Outcomes of Raloxifene Evaluation, a multicenter, randomized, double-blind trial, enrolled 7,705 postmenopausal women with osteoporosis. Women were randomly assigned to raloxifene 60 mg/d or 120 mg/d or placebo. Outcomes included venous thromboembolism, cataracts, gallbladder disease, and endometrial hyperplasia or cancer. RESULTS: During a mean follow-up of 3.3 years, raloxifene was associated with an increased risk for venous thromboembolism (relative risk [RR] 2.1; 95% confidence interval [CI] 1.2-3.8). The excess event rate was 1.8 per 1,000 woman-years (95% CI -0.5-4.1), and the number needed to treat to cause 1 event was 170 (95% CI 100-582) over 3.3 years. Risk in the raloxifene group was higher than in the placebo group for the first 2 years, but decreased to about the same rate as in the placebo group thereafter. Raloxifene did not increase risk for cataracts (RR 0.9; 95% CI 0.8-1.1), gallbladder disease (RR 1.0; 95% CI 0.7-1.3), endometrial hyperplasia (RR 1.3; 95% CI 0.4-5.1), or endometrial cancer (RR 0.9; 95% CI 0.3-2.7). CONCLUSION: Raloxifene was associated with an increased risk for venous thromboembolism, but there was no increased risk for cataracts, gallbladder disease, endometrial hyperplasia, or endometrial cancer. LEVEL OF EVIDENCE: I", "entity": "Tamoxifen", "aliases": "Citrate Tamoxifen ICI 46,474 46474 47699 ICI-46,474 ICI-46474 ICI-47699 ICI46,474 ICI46474 ICI47699 Nolvadex Novaldex Savient brand of Soltamox Tomaxithen Zitazonium", "definition": "One of the SELECTIVE ESTROGEN RECEPTOR MODULATORS with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the ENDOMETRIUM.\n    ", "id": "MESH:D013629"}
{"mention": "Raloxifene", "mention_text": "OBJECTIVE: To examine the effect of raloxifene on major adverse events that occur with postmenopausal estrogen therapy or tamoxifen. METHODS: The Multiple Outcomes of Raloxifene Evaluation, a multicenter, randomized, double-blind trial, enrolled 7,705 postmenopausal women with osteoporosis. Women were randomly assigned to raloxifene 60 mg/d or 120 mg/d or placebo. Outcomes included venous thromboembolism, cataracts, gallbladder disease, and endometrial hyperplasia or cancer. RESULTS: During a mean follow-up of 3.3 years, raloxifene was associated with an increased risk for venous thromboembolism (relative risk [RR] 2.1; 95% confidence interval [CI] 1.2-3.8). The excess event rate was 1.8 per 1,000 woman-years (95% CI -0.5-4.1), and the number needed to treat to cause 1 event was 170 (95% CI 100-582) over 3.3 years. Risk in the raloxifene group was higher than in the placebo group for the first 2 years, but decreased to about the same rate as in the placebo group thereafter. Raloxifene did not increase risk for cataracts (RR 0.9; 95% CI 0.8-1.1), gallbladder disease (RR 1.0; 95% CI 0.7-1.3), endometrial hyperplasia (RR 1.3; 95% CI 0.4-5.1), or endometrial cancer (RR 0.9; 95% CI 0.3-2.7). CONCLUSION: Raloxifene was associated with an increased risk for venous thromboembolism, but there was no increased risk for cataracts, gallbladder disease, endometrial hyperplasia, or endometrial cancer. LEVEL OF EVIDENCE: I", "entity": "Raloxifene", "aliases": "ELi Lilly Brand of Raloxifene Evista Keoxifene Hydrochloride LY 139481 156758 LY-139481 LY-156758 LY139481 LY156758", "definition": "A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue.\n    ", "id": "MESH:D020849"}
{"mention": "osteoporosis", "mention_text": "OBJECTIVE: To examine the effect of raloxifene on major adverse events that occur with postmenopausal estrogen therapy or tamoxifen. METHODS: The Multiple Outcomes of Raloxifene Evaluation, a multicenter, randomized, double-blind trial, enrolled 7,705 postmenopausal women with osteoporosis. Women were randomly assigned to raloxifene 60 mg/d or 120 mg/d or placebo. Outcomes included venous thromboembolism, cataracts, gallbladder disease, and endometrial hyperplasia or cancer. RESULTS: During a mean follow-up of 3.3 years, raloxifene was associated with an increased risk for venous thromboembolism (relative risk [RR] 2.1; 95% confidence interval [CI] 1.2-3.8). The excess event rate was 1.8 per 1,000 woman-years (95% CI -0.5-4.1), and the number needed to treat to cause 1 event was 170 (95% CI 100-582) over 3.3 years. Risk in the raloxifene group was higher than in the placebo group for the first 2 years, but decreased to about the same rate as in the placebo group thereafter. Raloxifene did not increase risk for cataracts (RR 0.9; 95% CI 0.8-1.1), gallbladder disease (RR 1.0; 95% CI 0.7-1.3), endometrial hyperplasia (RR 1.3; 95% CI 0.4-5.1), or endometrial cancer (RR 0.9; 95% CI 0.3-2.7). CONCLUSION: Raloxifene was associated with an increased risk for venous thromboembolism, but there was no increased risk for cataracts, gallbladder disease, endometrial hyperplasia, or endometrial cancer. LEVEL OF EVIDENCE: I", "entity": "Osteoporosis", "aliases": "Age Related Osteoporosis Age-Related Bone Loss Losses Osteoporoses Senile Involutional Post Traumatic Post-Traumatic", "definition": "Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis (OSTEOPOROSIS, POSTMENOPAUSAL) and age-related or senile osteoporosis.\n    ", "id": "MESH:D010024"}
{"mention": "venous thromboembolism", "mention_text": "OBJECTIVE: To examine the effect of raloxifene on major adverse events that occur with postmenopausal estrogen therapy or tamoxifen. METHODS: The Multiple Outcomes of Raloxifene Evaluation, a multicenter, randomized, double-blind trial, enrolled 7,705 postmenopausal women with osteoporosis. Women were randomly assigned to raloxifene 60 mg/d or 120 mg/d or placebo. Outcomes included venous thromboembolism, cataracts, gallbladder disease, and endometrial hyperplasia or cancer. RESULTS: During a mean follow-up of 3.3 years, raloxifene was associated with an increased risk for venous thromboembolism (relative risk [RR] 2.1; 95% confidence interval [CI] 1.2-3.8). The excess event rate was 1.8 per 1,000 woman-years (95% CI -0.5-4.1), and the number needed to treat to cause 1 event was 170 (95% CI 100-582) over 3.3 years. Risk in the raloxifene group was higher than in the placebo group for the first 2 years, but decreased to about the same rate as in the placebo group thereafter. Raloxifene did not increase risk for cataracts (RR 0.9; 95% CI 0.8-1.1), gallbladder disease (RR 1.0; 95% CI 0.7-1.3), endometrial hyperplasia (RR 1.3; 95% CI 0.4-5.1), or endometrial cancer (RR 0.9; 95% CI 0.3-2.7). CONCLUSION: Raloxifene was associated with an increased risk for venous thromboembolism, but there was no increased risk for cataracts, gallbladder disease, endometrial hyperplasia, or endometrial cancer. LEVEL OF EVIDENCE: I", "entity": "Venous Thromboembolism", "aliases": "Thromboembolism Venous", "definition": "Obstruction of a vein or VEINS (embolism) by a blood clot (THROMBUS) in the blood stream.\n    ", "id": "MESH:D054556"}
{"mention": "cataracts", "mention_text": "OBJECTIVE: To examine the effect of raloxifene on major adverse events that occur with postmenopausal estrogen therapy or tamoxifen. METHODS: The Multiple Outcomes of Raloxifene Evaluation, a multicenter, randomized, double-blind trial, enrolled 7,705 postmenopausal women with osteoporosis. Women were randomly assigned to raloxifene 60 mg/d or 120 mg/d or placebo. Outcomes included venous thromboembolism, cataracts, gallbladder disease, and endometrial hyperplasia or cancer. RESULTS: During a mean follow-up of 3.3 years, raloxifene was associated with an increased risk for venous thromboembolism (relative risk [RR] 2.1; 95% confidence interval [CI] 1.2-3.8). The excess event rate was 1.8 per 1,000 woman-years (95% CI -0.5-4.1), and the number needed to treat to cause 1 event was 170 (95% CI 100-582) over 3.3 years. Risk in the raloxifene group was higher than in the placebo group for the first 2 years, but decreased to about the same rate as in the placebo group thereafter. Raloxifene did not increase risk for cataracts (RR 0.9; 95% CI 0.8-1.1), gallbladder disease (RR 1.0; 95% CI 0.7-1.3), endometrial hyperplasia (RR 1.3; 95% CI 0.4-5.1), or endometrial cancer (RR 0.9; 95% CI 0.3-2.7). CONCLUSION: Raloxifene was associated with an increased risk for venous thromboembolism, but there was no increased risk for cataracts, gallbladder disease, endometrial hyperplasia, or endometrial cancer. LEVEL OF EVIDENCE: I", "entity": "Cataract", "aliases": "Cataract Membranous Cataracts Lens Opacities Opacity Pseudoaphakia Pseudoaphakias", "definition": "Partial or complete opacity on or in the lens or capsule of one or both eyes, impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). (Dorland, 27th ed)\n    ", "id": "MESH:D002386"}
{"mention": "gallbladder disease", "mention_text": "OBJECTIVE: To examine the effect of raloxifene on major adverse events that occur with postmenopausal estrogen therapy or tamoxifen. METHODS: The Multiple Outcomes of Raloxifene Evaluation, a multicenter, randomized, double-blind trial, enrolled 7,705 postmenopausal women with osteoporosis. Women were randomly assigned to raloxifene 60 mg/d or 120 mg/d or placebo. Outcomes included venous thromboembolism, cataracts, gallbladder disease, and endometrial hyperplasia or cancer. RESULTS: During a mean follow-up of 3.3 years, raloxifene was associated with an increased risk for venous thromboembolism (relative risk [RR] 2.1; 95% confidence interval [CI] 1.2-3.8). The excess event rate was 1.8 per 1,000 woman-years (95% CI -0.5-4.1), and the number needed to treat to cause 1 event was 170 (95% CI 100-582) over 3.3 years. Risk in the raloxifene group was higher than in the placebo group for the first 2 years, but decreased to about the same rate as in the placebo group thereafter. Raloxifene did not increase risk for cataracts (RR 0.9; 95% CI 0.8-1.1), gallbladder disease (RR 1.0; 95% CI 0.7-1.3), endometrial hyperplasia (RR 1.3; 95% CI 0.4-5.1), or endometrial cancer (RR 0.9; 95% CI 0.3-2.7). CONCLUSION: Raloxifene was associated with an increased risk for venous thromboembolism, but there was no increased risk for cataracts, gallbladder disease, endometrial hyperplasia, or endometrial cancer. LEVEL OF EVIDENCE: I", "entity": "Gallbladder Diseases", "aliases": "Bladder Disease Gall Diseases Gallbladder", "definition": "Diseases of the GALLBLADDER. They generally involve the impairment of BILE flow, GALLSTONES in the BILIARY TRACT, infections, neoplasms, or other diseases.\n    ", "id": "MESH:D005705"}
{"mention": "endometrial hyperplasia", "mention_text": "OBJECTIVE: To examine the effect of raloxifene on major adverse events that occur with postmenopausal estrogen therapy or tamoxifen. METHODS: The Multiple Outcomes of Raloxifene Evaluation, a multicenter, randomized, double-blind trial, enrolled 7,705 postmenopausal women with osteoporosis. Women were randomly assigned to raloxifene 60 mg/d or 120 mg/d or placebo. Outcomes included venous thromboembolism, cataracts, gallbladder disease, and endometrial hyperplasia or cancer. RESULTS: During a mean follow-up of 3.3 years, raloxifene was associated with an increased risk for venous thromboembolism (relative risk [RR] 2.1; 95% confidence interval [CI] 1.2-3.8). The excess event rate was 1.8 per 1,000 woman-years (95% CI -0.5-4.1), and the number needed to treat to cause 1 event was 170 (95% CI 100-582) over 3.3 years. Risk in the raloxifene group was higher than in the placebo group for the first 2 years, but decreased to about the same rate as in the placebo group thereafter. Raloxifene did not increase risk for cataracts (RR 0.9; 95% CI 0.8-1.1), gallbladder disease (RR 1.0; 95% CI 0.7-1.3), endometrial hyperplasia (RR 1.3; 95% CI 0.4-5.1), or endometrial cancer (RR 0.9; 95% CI 0.3-2.7). CONCLUSION: Raloxifene was associated with an increased risk for venous thromboembolism, but there was no increased risk for cataracts, gallbladder disease, endometrial hyperplasia, or endometrial cancer. LEVEL OF EVIDENCE: I", "entity": "Endometrial Hyperplasia", "aliases": "Atypical Endometrial Hyperplasia Hyperplasias Complex Simple", "definition": "Benign proliferation of the ENDOMETRIUM in the UTERUS. Endometrial hyperplasia is classified by its cytology and glandular tissue. There are simple, complex (adenomatous without atypia), and atypical hyperplasia representing also the ascending risk of becoming malignant.\n    ", "id": "MESH:D004714"}
{"mention": "endometrial cancer", "mention_text": "OBJECTIVE: To examine the effect of raloxifene on major adverse events that occur with postmenopausal estrogen therapy or tamoxifen. METHODS: The Multiple Outcomes of Raloxifene Evaluation, a multicenter, randomized, double-blind trial, enrolled 7,705 postmenopausal women with osteoporosis. Women were randomly assigned to raloxifene 60 mg/d or 120 mg/d or placebo. Outcomes included venous thromboembolism, cataracts, gallbladder disease, and endometrial hyperplasia or cancer. RESULTS: During a mean follow-up of 3.3 years, raloxifene was associated with an increased risk for venous thromboembolism (relative risk [RR] 2.1; 95% confidence interval [CI] 1.2-3.8). The excess event rate was 1.8 per 1,000 woman-years (95% CI -0.5-4.1), and the number needed to treat to cause 1 event was 170 (95% CI 100-582) over 3.3 years. Risk in the raloxifene group was higher than in the placebo group for the first 2 years, but decreased to about the same rate as in the placebo group thereafter. Raloxifene did not increase risk for cataracts (RR 0.9; 95% CI 0.8-1.1), gallbladder disease (RR 1.0; 95% CI 0.7-1.3), endometrial hyperplasia (RR 1.3; 95% CI 0.4-5.1), or endometrial cancer (RR 0.9; 95% CI 0.3-2.7). CONCLUSION: Raloxifene was associated with an increased risk for venous thromboembolism, but there was no increased risk for cataracts, gallbladder disease, endometrial hyperplasia, or endometrial cancer. LEVEL OF EVIDENCE: I", "entity": "Endometrial Neoplasms", "aliases": "Cancer of Endometrium the Endometrial Cancers Carcinoma Carcinomas Neoplasm Neoplasms", "definition": "Tumors or cancer of ENDOMETRIUM, the mucous lining of the UTERUS. These neoplasms can be benign or malignant. Their classification and grading are based on the various cell types and the percent of undifferentiated cells.\n    ", "id": "MESH:D016889"}
{"mention": "Ceftriaxone", "mention_text": "Ceftriaxone-associated biliary pseudolithiasis in paediatric surgical patients.", "entity": "Ceftriaxone", "aliases": "Anhydrous Ceftriaxone Sodium Benaxona Boehringer Mannheim Brand of Cefatriaxone Cefaxona Ceftrex Ceftriaxon Curamed Hexal Ceftriaxona Andreu LDP Torlan Irex Disodium Salt Hemiheptahydrate Columbia Fustery Galen Hoffman La Roche Hoffman-La Inibsa Lendacin Longacef Longaceph Pisa Ro 13 9904 13-9904 139904 Ro-13-9904 Ro13 Ro13-9904 Ro139904 Rocefalin Rocefin Rocephin Rocephine Syntex Tacex Terbac", "definition": "A broad-spectrum cephalosporin antibiotic with a very long half-life and high penetrability to meninges, eyes and inner ears.\n    ", "id": "MESH:D002443"}
{"mention": "biliary pseudolithiasis", "mention_text": "Ceftriaxone-associated biliary pseudolithiasis in paediatric surgical patients.", "entity": "Biliary Tract Diseases", "aliases": "Biliary Tract Disease Diseases", "definition": "Diseases in any part of the BILIARY TRACT including the BILE DUCTS and the GALLBLADDER.\n    ", "id": "MESH:D001660"}
{"mention": "ceftriaxone", "mention_text": "It is well known that ceftriaxone leads to pseudolithiasis in some patients. Clinical and experimental studies also suggest that situations causing gallbladder dysfunction, such as fasting, may have a role for the development of pseudolithiasis. In this study, we prospectively evaluated the incidence and clinical importance of pseudolithiasis in paediatric surgical patients receiving ceftriaxone treatment, who often had to fast in the post-operative period. Fifty children who were given ceftriaxone were evaluated by serial abdominal sonograms. Of those, 13 (26%) developed biliary pathology. Comparison of the patients with or without pseudolithiasis revealed no significant difference with respect to age, sex, duration of the treatment and starvation variables. After cessation of the treatment, pseudolithiasis resolved spontaneously within a short period. The incidence of pseudolithiasis is not affected by fasting.", "entity": "Ceftriaxone", "aliases": "Anhydrous Ceftriaxone Sodium Benaxona Boehringer Mannheim Brand of Cefatriaxone Cefaxona Ceftrex Ceftriaxon Curamed Hexal Ceftriaxona Andreu LDP Torlan Irex Disodium Salt Hemiheptahydrate Columbia Fustery Galen Hoffman La Roche Hoffman-La Inibsa Lendacin Longacef Longaceph Pisa Ro 13 9904 13-9904 139904 Ro-13-9904 Ro13 Ro13-9904 Ro139904 Rocefalin Rocefin Rocephin Rocephine Syntex Tacex Terbac", "definition": "A broad-spectrum cephalosporin antibiotic with a very long half-life and high penetrability to meninges, eyes and inner ears.\n    ", "id": "MESH:D002443"}
{"mention": "pseudolithiasis", "mention_text": "It is well known that ceftriaxone leads to pseudolithiasis in some patients. Clinical and experimental studies also suggest that situations causing gallbladder dysfunction, such as fasting, may have a role for the development of pseudolithiasis. In this study, we prospectively evaluated the incidence and clinical importance of pseudolithiasis in paediatric surgical patients receiving ceftriaxone treatment, who often had to fast in the post-operative period. Fifty children who were given ceftriaxone were evaluated by serial abdominal sonograms. Of those, 13 (26%) developed biliary pathology. Comparison of the patients with or without pseudolithiasis revealed no significant difference with respect to age, sex, duration of the treatment and starvation variables. After cessation of the treatment, pseudolithiasis resolved spontaneously within a short period. The incidence of pseudolithiasis is not affected by fasting.", "entity": "Biliary Tract Diseases", "aliases": "Biliary Tract Disease Diseases", "definition": "Diseases in any part of the BILIARY TRACT including the BILE DUCTS and the GALLBLADDER.\n    ", "id": "MESH:D001660"}
{"mention": "gallbladder dysfunction", "mention_text": "It is well known that ceftriaxone leads to pseudolithiasis in some patients. Clinical and experimental studies also suggest that situations causing gallbladder dysfunction, such as fasting, may have a role for the development of pseudolithiasis. In this study, we prospectively evaluated the incidence and clinical importance of pseudolithiasis in paediatric surgical patients receiving ceftriaxone treatment, who often had to fast in the post-operative period. Fifty children who were given ceftriaxone were evaluated by serial abdominal sonograms. Of those, 13 (26%) developed biliary pathology. Comparison of the patients with or without pseudolithiasis revealed no significant difference with respect to age, sex, duration of the treatment and starvation variables. After cessation of the treatment, pseudolithiasis resolved spontaneously within a short period. The incidence of pseudolithiasis is not affected by fasting.", "entity": "Gallbladder Diseases", "aliases": "Bladder Disease Gall Diseases Gallbladder", "definition": "Diseases of the GALLBLADDER. They generally involve the impairment of BILE flow, GALLSTONES in the BILIARY TRACT, infections, neoplasms, or other diseases.\n    ", "id": "MESH:D005705"}
{"mention": "cocaine overdose", "mention_text": "Evaluation of the anticocaine monoclonal antibody GNC92H2 as an immunotherapy for cocaine overdose.", "entity": "Drug Overdose", "aliases": "Drug Overdose Overdoses", "definition": "Accidental or deliberate use of a medication or street drug in excess of normal dosage.\n    ", "id": "MESH:D062787"}
{"mention": "cocaine", "mention_text": "The illicit use of cocaine continues in epidemic proportions and treatment for cocaine overdose remains elusive. Current protein-based technology offers a new therapeutic venue by which antibodies bind the drug in the blood stream, inactivating its toxic effects. The therapeutic potential of the anticocaine antibody GNC92H2 was examined using a model of cocaine overdose. Swiss albino mice prepared with intrajugular catheters were tested in photocell cages after administration of 93 mg/kg (LD50) of cocaine and GNC92H2 infusions ranging from 30 to 190 mg/kg. GNC92H2 was delivered 30 min before, concomitantly or 3 min after cocaine treatment. Significant blockade of cocaine toxicity was observed with the higher dose of GNC92H2 (190 mg/kg), where premorbid behaviors were reduced up to 40%, seizures up to 77% and death by 72%. Importantly, GNC92H2 prevented death even post-cocaine injection. The results support the important potential of GNC92H2 as a therapeutic tool against cocaine overdose.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "cocaine overdose", "mention_text": "The illicit use of cocaine continues in epidemic proportions and treatment for cocaine overdose remains elusive. Current protein-based technology offers a new therapeutic venue by which antibodies bind the drug in the blood stream, inactivating its toxic effects. The therapeutic potential of the anticocaine antibody GNC92H2 was examined using a model of cocaine overdose. Swiss albino mice prepared with intrajugular catheters were tested in photocell cages after administration of 93 mg/kg (LD50) of cocaine and GNC92H2 infusions ranging from 30 to 190 mg/kg. GNC92H2 was delivered 30 min before, concomitantly or 3 min after cocaine treatment. Significant blockade of cocaine toxicity was observed with the higher dose of GNC92H2 (190 mg/kg), where premorbid behaviors were reduced up to 40%, seizures up to 77% and death by 72%. Importantly, GNC92H2 prevented death even post-cocaine injection. The results support the important potential of GNC92H2 as a therapeutic tool against cocaine overdose.", "entity": "Drug Overdose", "aliases": "Drug Overdose Overdoses", "definition": "Accidental or deliberate use of a medication or street drug in excess of normal dosage.\n    ", "id": "MESH:D062787"}
{"mention": "toxicity", "mention_text": "The illicit use of cocaine continues in epidemic proportions and treatment for cocaine overdose remains elusive. Current protein-based technology offers a new therapeutic venue by which antibodies bind the drug in the blood stream, inactivating its toxic effects. The therapeutic potential of the anticocaine antibody GNC92H2 was examined using a model of cocaine overdose. Swiss albino mice prepared with intrajugular catheters were tested in photocell cages after administration of 93 mg/kg (LD50) of cocaine and GNC92H2 infusions ranging from 30 to 190 mg/kg. GNC92H2 was delivered 30 min before, concomitantly or 3 min after cocaine treatment. Significant blockade of cocaine toxicity was observed with the higher dose of GNC92H2 (190 mg/kg), where premorbid behaviors were reduced up to 40%, seizures up to 77% and death by 72%. Importantly, GNC92H2 prevented death even post-cocaine injection. The results support the important potential of GNC92H2 as a therapeutic tool against cocaine overdose.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "seizures", "mention_text": "The illicit use of cocaine continues in epidemic proportions and treatment for cocaine overdose remains elusive. Current protein-based technology offers a new therapeutic venue by which antibodies bind the drug in the blood stream, inactivating its toxic effects. The therapeutic potential of the anticocaine antibody GNC92H2 was examined using a model of cocaine overdose. Swiss albino mice prepared with intrajugular catheters were tested in photocell cages after administration of 93 mg/kg (LD50) of cocaine and GNC92H2 infusions ranging from 30 to 190 mg/kg. GNC92H2 was delivered 30 min before, concomitantly or 3 min after cocaine treatment. Significant blockade of cocaine toxicity was observed with the higher dose of GNC92H2 (190 mg/kg), where premorbid behaviors were reduced up to 40%, seizures up to 77% and death by 72%. Importantly, GNC92H2 prevented death even post-cocaine injection. The results support the important potential of GNC92H2 as a therapeutic tool against cocaine overdose.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "death", "mention_text": "The illicit use of cocaine continues in epidemic proportions and treatment for cocaine overdose remains elusive. Current protein-based technology offers a new therapeutic venue by which antibodies bind the drug in the blood stream, inactivating its toxic effects. The therapeutic potential of the anticocaine antibody GNC92H2 was examined using a model of cocaine overdose. Swiss albino mice prepared with intrajugular catheters were tested in photocell cages after administration of 93 mg/kg (LD50) of cocaine and GNC92H2 infusions ranging from 30 to 190 mg/kg. GNC92H2 was delivered 30 min before, concomitantly or 3 min after cocaine treatment. Significant blockade of cocaine toxicity was observed with the higher dose of GNC92H2 (190 mg/kg), where premorbid behaviors were reduced up to 40%, seizures up to 77% and death by 72%. Importantly, GNC92H2 prevented death even post-cocaine injection. The results support the important potential of GNC92H2 as a therapeutic tool against cocaine overdose.", "entity": "Death", "aliases": "Cardiac Death Determination of Near-Death Experience", "definition": "Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.\n    ", "id": "MESH:D003643"}
{"mention": "raloxifene", "mention_text": "The effects of short-term raloxifene therapy on fibrinolysis markers: TAFI, tPA, and PAI-1.", "entity": "Raloxifene", "aliases": "ELi Lilly Brand of Raloxifene Evista Keoxifene Hydrochloride LY 139481 156758 LY-139481 LY-156758 LY139481 LY156758", "definition": "A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue.\n    ", "id": "MESH:D020849"}
{"mention": "raloxifene", "mention_text": "BACKGROUND: Markers of fibrinolysis, thrombin-activatable fibrinolysis inhibitor (TAFI), tissue-type plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) levels were studied for the evaluation of short-term effects of raloxifene administration in postmenopausal women. METHODS: Thirty-nine postmenopausal women with osteopenia or osteoporosis were included in this prospective, controlled clinical study. Twenty-five women were given raloxifene hydrochloride (60 mg/day) plus calcium (500 mg/day). Age-matched controls (n = 14) were given only calcium. Plasma TAFI, tPA, and PAI-1 antigen levels were measured at baseline and after 3 months of treatment by commercially available ELISA kits. Variations of individuals were assessed by Wilcoxon's test. Relationship between those markers and demographic characteristics were investigated. RESULTS: Three months of raloxifene treatment was associated with a significant decrease in the plasma TAFI antigen concentrations (16% change, P < 0.01), and a significant increase in tPA antigen concentrations (25% change, P < 0.05). A significant correlation was found between baseline TAFI antigen concentrations and the duration of amenorrhea (P < 0.05; r = 0.33). CONCLUSION: We suggest that the increased risk of venous thromboembolism due to raloxifene treatment may be related to increased tPA levels, but not TAFI levels.", "entity": "Raloxifene", "aliases": "ELi Lilly Brand of Raloxifene Evista Keoxifene Hydrochloride LY 139481 156758 LY-139481 LY-156758 LY139481 LY156758", "definition": "A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue.\n    ", "id": "MESH:D020849"}
{"mention": "osteopenia", "mention_text": "BACKGROUND: Markers of fibrinolysis, thrombin-activatable fibrinolysis inhibitor (TAFI), tissue-type plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) levels were studied for the evaluation of short-term effects of raloxifene administration in postmenopausal women. METHODS: Thirty-nine postmenopausal women with osteopenia or osteoporosis were included in this prospective, controlled clinical study. Twenty-five women were given raloxifene hydrochloride (60 mg/day) plus calcium (500 mg/day). Age-matched controls (n = 14) were given only calcium. Plasma TAFI, tPA, and PAI-1 antigen levels were measured at baseline and after 3 months of treatment by commercially available ELISA kits. Variations of individuals were assessed by Wilcoxon's test. Relationship between those markers and demographic characteristics were investigated. RESULTS: Three months of raloxifene treatment was associated with a significant decrease in the plasma TAFI antigen concentrations (16% change, P < 0.01), and a significant increase in tPA antigen concentrations (25% change, P < 0.05). A significant correlation was found between baseline TAFI antigen concentrations and the duration of amenorrhea (P < 0.05; r = 0.33). CONCLUSION: We suggest that the increased risk of venous thromboembolism due to raloxifene treatment may be related to increased tPA levels, but not TAFI levels.", "entity": "Bone Diseases, Metabolic", "aliases": "Bone Disease Metabolic Diseases Osteopenia Osteopenias", "definition": "", "id": "MESH:D001851"}
{"mention": "osteoporosis", "mention_text": "BACKGROUND: Markers of fibrinolysis, thrombin-activatable fibrinolysis inhibitor (TAFI), tissue-type plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) levels were studied for the evaluation of short-term effects of raloxifene administration in postmenopausal women. METHODS: Thirty-nine postmenopausal women with osteopenia or osteoporosis were included in this prospective, controlled clinical study. Twenty-five women were given raloxifene hydrochloride (60 mg/day) plus calcium (500 mg/day). Age-matched controls (n = 14) were given only calcium. Plasma TAFI, tPA, and PAI-1 antigen levels were measured at baseline and after 3 months of treatment by commercially available ELISA kits. Variations of individuals were assessed by Wilcoxon's test. Relationship between those markers and demographic characteristics were investigated. RESULTS: Three months of raloxifene treatment was associated with a significant decrease in the plasma TAFI antigen concentrations (16% change, P < 0.01), and a significant increase in tPA antigen concentrations (25% change, P < 0.05). A significant correlation was found between baseline TAFI antigen concentrations and the duration of amenorrhea (P < 0.05; r = 0.33). CONCLUSION: We suggest that the increased risk of venous thromboembolism due to raloxifene treatment may be related to increased tPA levels, but not TAFI levels.", "entity": "Osteoporosis", "aliases": "Age Related Osteoporosis Age-Related Bone Loss Losses Osteoporoses Senile Involutional Post Traumatic Post-Traumatic", "definition": "Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis (OSTEOPOROSIS, POSTMENOPAUSAL) and age-related or senile osteoporosis.\n    ", "id": "MESH:D010024"}
{"mention": "raloxifene hydrochloride", "mention_text": "BACKGROUND: Markers of fibrinolysis, thrombin-activatable fibrinolysis inhibitor (TAFI), tissue-type plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) levels were studied for the evaluation of short-term effects of raloxifene administration in postmenopausal women. METHODS: Thirty-nine postmenopausal women with osteopenia or osteoporosis were included in this prospective, controlled clinical study. Twenty-five women were given raloxifene hydrochloride (60 mg/day) plus calcium (500 mg/day). Age-matched controls (n = 14) were given only calcium. Plasma TAFI, tPA, and PAI-1 antigen levels were measured at baseline and after 3 months of treatment by commercially available ELISA kits. Variations of individuals were assessed by Wilcoxon's test. Relationship between those markers and demographic characteristics were investigated. RESULTS: Three months of raloxifene treatment was associated with a significant decrease in the plasma TAFI antigen concentrations (16% change, P < 0.01), and a significant increase in tPA antigen concentrations (25% change, P < 0.05). A significant correlation was found between baseline TAFI antigen concentrations and the duration of amenorrhea (P < 0.05; r = 0.33). CONCLUSION: We suggest that the increased risk of venous thromboembolism due to raloxifene treatment may be related to increased tPA levels, but not TAFI levels.", "entity": "Raloxifene", "aliases": "ELi Lilly Brand of Raloxifene Evista Keoxifene Hydrochloride LY 139481 156758 LY-139481 LY-156758 LY139481 LY156758", "definition": "A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue.\n    ", "id": "MESH:D020849"}
{"mention": "calcium", "mention_text": "BACKGROUND: Markers of fibrinolysis, thrombin-activatable fibrinolysis inhibitor (TAFI), tissue-type plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) levels were studied for the evaluation of short-term effects of raloxifene administration in postmenopausal women. METHODS: Thirty-nine postmenopausal women with osteopenia or osteoporosis were included in this prospective, controlled clinical study. Twenty-five women were given raloxifene hydrochloride (60 mg/day) plus calcium (500 mg/day). Age-matched controls (n = 14) were given only calcium. Plasma TAFI, tPA, and PAI-1 antigen levels were measured at baseline and after 3 months of treatment by commercially available ELISA kits. Variations of individuals were assessed by Wilcoxon's test. Relationship between those markers and demographic characteristics were investigated. RESULTS: Three months of raloxifene treatment was associated with a significant decrease in the plasma TAFI antigen concentrations (16% change, P < 0.01), and a significant increase in tPA antigen concentrations (25% change, P < 0.05). A significant correlation was found between baseline TAFI antigen concentrations and the duration of amenorrhea (P < 0.05; r = 0.33). CONCLUSION: We suggest that the increased risk of venous thromboembolism due to raloxifene treatment may be related to increased tPA levels, but not TAFI levels.", "entity": "Calcium", "aliases": "Blood Coagulation Factor IV Calcium", "definition": "A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.\n    ", "id": "MESH:D002118"}
{"mention": "amenorrhea", "mention_text": "BACKGROUND: Markers of fibrinolysis, thrombin-activatable fibrinolysis inhibitor (TAFI), tissue-type plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) levels were studied for the evaluation of short-term effects of raloxifene administration in postmenopausal women. METHODS: Thirty-nine postmenopausal women with osteopenia or osteoporosis were included in this prospective, controlled clinical study. Twenty-five women were given raloxifene hydrochloride (60 mg/day) plus calcium (500 mg/day). Age-matched controls (n = 14) were given only calcium. Plasma TAFI, tPA, and PAI-1 antigen levels were measured at baseline and after 3 months of treatment by commercially available ELISA kits. Variations of individuals were assessed by Wilcoxon's test. Relationship between those markers and demographic characteristics were investigated. RESULTS: Three months of raloxifene treatment was associated with a significant decrease in the plasma TAFI antigen concentrations (16% change, P < 0.01), and a significant increase in tPA antigen concentrations (25% change, P < 0.05). A significant correlation was found between baseline TAFI antigen concentrations and the duration of amenorrhea (P < 0.05; r = 0.33). CONCLUSION: We suggest that the increased risk of venous thromboembolism due to raloxifene treatment may be related to increased tPA levels, but not TAFI levels.", "entity": "Amenorrhea", "aliases": "Amenorrhea Postpartum Amenorrheas", "definition": "Absence of menstruation.\n    ", "id": "MESH:D000568"}
{"mention": "venous thromboembolism", "mention_text": "BACKGROUND: Markers of fibrinolysis, thrombin-activatable fibrinolysis inhibitor (TAFI), tissue-type plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) levels were studied for the evaluation of short-term effects of raloxifene administration in postmenopausal women. METHODS: Thirty-nine postmenopausal women with osteopenia or osteoporosis were included in this prospective, controlled clinical study. Twenty-five women were given raloxifene hydrochloride (60 mg/day) plus calcium (500 mg/day). Age-matched controls (n = 14) were given only calcium. Plasma TAFI, tPA, and PAI-1 antigen levels were measured at baseline and after 3 months of treatment by commercially available ELISA kits. Variations of individuals were assessed by Wilcoxon's test. Relationship between those markers and demographic characteristics were investigated. RESULTS: Three months of raloxifene treatment was associated with a significant decrease in the plasma TAFI antigen concentrations (16% change, P < 0.01), and a significant increase in tPA antigen concentrations (25% change, P < 0.05). A significant correlation was found between baseline TAFI antigen concentrations and the duration of amenorrhea (P < 0.05; r = 0.33). CONCLUSION: We suggest that the increased risk of venous thromboembolism due to raloxifene treatment may be related to increased tPA levels, but not TAFI levels.", "entity": "Venous Thromboembolism", "aliases": "Thromboembolism Venous", "definition": "Obstruction of a vein or VEINS (embolism) by a blood clot (THROMBUS) in the blood stream.\n    ", "id": "MESH:D054556"}
{"mention": "Ketoconazole", "mention_text": "Ketoconazole induced torsades de pointes without concomitant use of QT interval-prolonging drug.", "entity": "Ketoconazole", "aliases": "Janssen Brand of Ketoconazole Nizoral R 41400 R-41400 R41,400 R41400", "definition": "Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.\n    ", "id": "MESH:D007654"}
{"mention": "torsades de pointes", "mention_text": "Ketoconazole induced torsades de pointes without concomitant use of QT interval-prolonging drug.", "entity": "Torsades de Pointes", "aliases": "Pointes Torsade de Torsades", "definition": "A malignant form of polymorphic ventricular tachycardia that is characterized by HEART RATE between 200 and 250 beats per minute, and QRS complexes with changing amplitude and twisting of the points. The term also describes the syndrome of tachycardia with prolonged ventricular repolarization, long QT intervals exceeding 500 milliseconds or BRADYCARDIA. Torsades de pointes may be self-limited or may progress to VENTRICULAR FIBRILLATION.\n    ", "id": "MESH:D016171"}
{"mention": "Ketoconazole", "mention_text": "Ketoconazole is not known to be proarrhythmic without concomitant use of QT interval-prolonging drugs. We report a woman with coronary artery disease who developed a markedly prolonged QT interval and torsades de pointes (TdP) after taking ketoconazole for treatment of fungal infection. Her QT interval returned to normal upon withdrawal of ketoconazole. Genetic study did not find any mutation in her genes that encode cardiac IKr channel proteins. We postulate that by virtue of its direct blocking action on IKr, ketoconazole alone may prolong QT interval and induce TdP. This calls for attention when ketoconazole is administered to patients with risk factors for acquired long QT syndrome.", "entity": "Ketoconazole", "aliases": "Janssen Brand of Ketoconazole Nizoral R 41400 R-41400 R41,400 R41400", "definition": "Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.\n    ", "id": "MESH:D007654"}
{"mention": "coronary artery disease", "mention_text": "Ketoconazole is not known to be proarrhythmic without concomitant use of QT interval-prolonging drugs. We report a woman with coronary artery disease who developed a markedly prolonged QT interval and torsades de pointes (TdP) after taking ketoconazole for treatment of fungal infection. Her QT interval returned to normal upon withdrawal of ketoconazole. Genetic study did not find any mutation in her genes that encode cardiac IKr channel proteins. We postulate that by virtue of its direct blocking action on IKr, ketoconazole alone may prolong QT interval and induce TdP. This calls for attention when ketoconazole is administered to patients with risk factors for acquired long QT syndrome.", "entity": "Coronary Artery Disease", "aliases": "Arterioscleroses Coronary Arteriosclerosis Artery Disease Diseases Atheroscleroses Atherosclerosis", "definition": "Pathological processes of CORONARY ARTERIES that may derive from a congenital abnormality, atherosclerotic, or non-atherosclerotic cause.\n    ", "id": "MESH:D003324"}
{"mention": "prolonged QT interval", "mention_text": "Ketoconazole is not known to be proarrhythmic without concomitant use of QT interval-prolonging drugs. We report a woman with coronary artery disease who developed a markedly prolonged QT interval and torsades de pointes (TdP) after taking ketoconazole for treatment of fungal infection. Her QT interval returned to normal upon withdrawal of ketoconazole. Genetic study did not find any mutation in her genes that encode cardiac IKr channel proteins. We postulate that by virtue of its direct blocking action on IKr, ketoconazole alone may prolong QT interval and induce TdP. This calls for attention when ketoconazole is administered to patients with risk factors for acquired long QT syndrome.", "entity": "Long QT Syndrome", "aliases": "Long QT Syndrome", "definition": "A condition that is characterized by episodes of fainting (SYNCOPE) and varying degree of ventricular arrhythmia as indicated by the prolonged QT interval. The inherited forms are caused by mutation of genes encoding cardiac ion channel proteins. The two major forms are ROMANO-WARD SYNDROME and JERVELL-LANGE NIELSEN SYNDROME.\n    ", "id": "MESH:D008133"}
{"mention": "torsades de pointes", "mention_text": "Ketoconazole is not known to be proarrhythmic without concomitant use of QT interval-prolonging drugs. We report a woman with coronary artery disease who developed a markedly prolonged QT interval and torsades de pointes (TdP) after taking ketoconazole for treatment of fungal infection. Her QT interval returned to normal upon withdrawal of ketoconazole. Genetic study did not find any mutation in her genes that encode cardiac IKr channel proteins. We postulate that by virtue of its direct blocking action on IKr, ketoconazole alone may prolong QT interval and induce TdP. This calls for attention when ketoconazole is administered to patients with risk factors for acquired long QT syndrome.", "entity": "Torsades de Pointes", "aliases": "Pointes Torsade de Torsades", "definition": "A malignant form of polymorphic ventricular tachycardia that is characterized by HEART RATE between 200 and 250 beats per minute, and QRS complexes with changing amplitude and twisting of the points. The term also describes the syndrome of tachycardia with prolonged ventricular repolarization, long QT intervals exceeding 500 milliseconds or BRADYCARDIA. Torsades de pointes may be self-limited or may progress to VENTRICULAR FIBRILLATION.\n    ", "id": "MESH:D016171"}
{"mention": "TdP", "mention_text": "Ketoconazole is not known to be proarrhythmic without concomitant use of QT interval-prolonging drugs. We report a woman with coronary artery disease who developed a markedly prolonged QT interval and torsades de pointes (TdP) after taking ketoconazole for treatment of fungal infection. Her QT interval returned to normal upon withdrawal of ketoconazole. Genetic study did not find any mutation in her genes that encode cardiac IKr channel proteins. We postulate that by virtue of its direct blocking action on IKr, ketoconazole alone may prolong QT interval and induce TdP. This calls for attention when ketoconazole is administered to patients with risk factors for acquired long QT syndrome.", "entity": "Torsades de Pointes", "aliases": "Pointes Torsade de Torsades", "definition": "A malignant form of polymorphic ventricular tachycardia that is characterized by HEART RATE between 200 and 250 beats per minute, and QRS complexes with changing amplitude and twisting of the points. The term also describes the syndrome of tachycardia with prolonged ventricular repolarization, long QT intervals exceeding 500 milliseconds or BRADYCARDIA. Torsades de pointes may be self-limited or may progress to VENTRICULAR FIBRILLATION.\n    ", "id": "MESH:D016171"}
{"mention": "ketoconazole", "mention_text": "Ketoconazole is not known to be proarrhythmic without concomitant use of QT interval-prolonging drugs. We report a woman with coronary artery disease who developed a markedly prolonged QT interval and torsades de pointes (TdP) after taking ketoconazole for treatment of fungal infection. Her QT interval returned to normal upon withdrawal of ketoconazole. Genetic study did not find any mutation in her genes that encode cardiac IKr channel proteins. We postulate that by virtue of its direct blocking action on IKr, ketoconazole alone may prolong QT interval and induce TdP. This calls for attention when ketoconazole is administered to patients with risk factors for acquired long QT syndrome.", "entity": "Ketoconazole", "aliases": "Janssen Brand of Ketoconazole Nizoral R 41400 R-41400 R41,400 R41400", "definition": "Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.\n    ", "id": "MESH:D007654"}
{"mention": "fungal infection", "mention_text": "Ketoconazole is not known to be proarrhythmic without concomitant use of QT interval-prolonging drugs. We report a woman with coronary artery disease who developed a markedly prolonged QT interval and torsades de pointes (TdP) after taking ketoconazole for treatment of fungal infection. Her QT interval returned to normal upon withdrawal of ketoconazole. Genetic study did not find any mutation in her genes that encode cardiac IKr channel proteins. We postulate that by virtue of its direct blocking action on IKr, ketoconazole alone may prolong QT interval and induce TdP. This calls for attention when ketoconazole is administered to patients with risk factors for acquired long QT syndrome.", "entity": "Mycoses", "aliases": "Disease Fungus Diseases Mycoses", "definition": "", "id": "MESH:D009181"}
{"mention": "long QT syndrome", "mention_text": "Ketoconazole is not known to be proarrhythmic without concomitant use of QT interval-prolonging drugs. We report a woman with coronary artery disease who developed a markedly prolonged QT interval and torsades de pointes (TdP) after taking ketoconazole for treatment of fungal infection. Her QT interval returned to normal upon withdrawal of ketoconazole. Genetic study did not find any mutation in her genes that encode cardiac IKr channel proteins. We postulate that by virtue of its direct blocking action on IKr, ketoconazole alone may prolong QT interval and induce TdP. This calls for attention when ketoconazole is administered to patients with risk factors for acquired long QT syndrome.", "entity": "Long QT Syndrome", "aliases": "Long QT Syndrome", "definition": "A condition that is characterized by episodes of fainting (SYNCOPE) and varying degree of ventricular arrhythmia as indicated by the prolonged QT interval. The inherited forms are caused by mutation of genes encoding cardiac ion channel proteins. The two major forms are ROMANO-WARD SYNDROME and JERVELL-LANGE NIELSEN SYNDROME.\n    ", "id": "MESH:D008133"}
{"mention": "cognitive dysfunctions", "mention_text": "Pharmacological evidence for the potential of Daucus carota in the management of cognitive dysfunctions.", "entity": "Cognition Disorders", "aliases": "Cognition Disorders Disorder Overinclusion", "definition": "Disturbances in the mental process related to thinking, reasoning, and judgment.\n    ", "id": "MESH:D003072"}
{"mention": "cholesterol", "mention_text": "The present study was aimed at investigating the effects of Daucus carota seeds on cognitive functions, total serum cholesterol levels and brain cholinesterase activity in mice. The ethanolic extract of Daucus carota seeds (DCE) was administered orally in three doses (100, 200, 400 mg/kg) for seven successive days to different groups of young and aged mice. Elevated plus maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam-, scopolamine- and ageing-induced amnesia served as the interoceptive behavioral models. DCE (200, 400 mg/kg, p.o.) showed significant improvement in memory scores of young and aged mice. The extent of memory improvement evoked by DCE was 23% at the dose of 200 mg/kg and 35% at the dose of 400 mg/kg in young mice using elevated plus maze. Similarly, significant improvements in memory scores were observed using passive avoidance apparatus and aged mice. Furthermore, DCE reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Daucus carota extract (200, 400 mg/kg, p.o.) reduced significantly the brain acetylcholinesterase activity and cholesterol levels in young and aged mice. The extent of inhibition of brain cholinesterase activity evoked by DCE at the dose of 400 mg/kg was 22% in young and 19% in aged mice. There was a remarkable reduction in total cholesterol level as well, to the extent of 23% in young and 21% in aged animals with this dose of DCE. Therefore, DCE may prove to be a useful remedy for the management of cognitive dysfunctions on account of its multifarious beneficial effects such as, memory improving property, cholesterol lowering property and anticholinesterase activity.", "entity": "Cholesterol", "aliases": "Cholesterol Epicholesterol", "definition": "The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.\n    ", "id": "MESH:D002784"}
{"mention": "extract of Daucus carota seeds", "mention_text": "The present study was aimed at investigating the effects of Daucus carota seeds on cognitive functions, total serum cholesterol levels and brain cholinesterase activity in mice. The ethanolic extract of Daucus carota seeds (DCE) was administered orally in three doses (100, 200, 400 mg/kg) for seven successive days to different groups of young and aged mice. Elevated plus maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam-, scopolamine- and ageing-induced amnesia served as the interoceptive behavioral models. DCE (200, 400 mg/kg, p.o.) showed significant improvement in memory scores of young and aged mice. The extent of memory improvement evoked by DCE was 23% at the dose of 200 mg/kg and 35% at the dose of 400 mg/kg in young mice using elevated plus maze. Similarly, significant improvements in memory scores were observed using passive avoidance apparatus and aged mice. Furthermore, DCE reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Daucus carota extract (200, 400 mg/kg, p.o.) reduced significantly the brain acetylcholinesterase activity and cholesterol levels in young and aged mice. The extent of inhibition of brain cholinesterase activity evoked by DCE at the dose of 400 mg/kg was 22% in young and 19% in aged mice. There was a remarkable reduction in total cholesterol level as well, to the extent of 23% in young and 21% in aged animals with this dose of DCE. Therefore, DCE may prove to be a useful remedy for the management of cognitive dysfunctions on account of its multifarious beneficial effects such as, memory improving property, cholesterol lowering property and anticholinesterase activity.", "entity": "Plant Extracts", "aliases": "Extracts Plant", "definition": "Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.\n    ", "id": "MESH:D010936"}
{"mention": "DCE", "mention_text": "The present study was aimed at investigating the effects of Daucus carota seeds on cognitive functions, total serum cholesterol levels and brain cholinesterase activity in mice. The ethanolic extract of Daucus carota seeds (DCE) was administered orally in three doses (100, 200, 400 mg/kg) for seven successive days to different groups of young and aged mice. Elevated plus maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam-, scopolamine- and ageing-induced amnesia served as the interoceptive behavioral models. DCE (200, 400 mg/kg, p.o.) showed significant improvement in memory scores of young and aged mice. The extent of memory improvement evoked by DCE was 23% at the dose of 200 mg/kg and 35% at the dose of 400 mg/kg in young mice using elevated plus maze. Similarly, significant improvements in memory scores were observed using passive avoidance apparatus and aged mice. Furthermore, DCE reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Daucus carota extract (200, 400 mg/kg, p.o.) reduced significantly the brain acetylcholinesterase activity and cholesterol levels in young and aged mice. The extent of inhibition of brain cholinesterase activity evoked by DCE at the dose of 400 mg/kg was 22% in young and 19% in aged mice. There was a remarkable reduction in total cholesterol level as well, to the extent of 23% in young and 21% in aged animals with this dose of DCE. Therefore, DCE may prove to be a useful remedy for the management of cognitive dysfunctions on account of its multifarious beneficial effects such as, memory improving property, cholesterol lowering property and anticholinesterase activity.", "entity": "Plant Extracts", "aliases": "Extracts Plant", "definition": "Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.\n    ", "id": "MESH:D010936"}
{"mention": "Diazepam", "mention_text": "The present study was aimed at investigating the effects of Daucus carota seeds on cognitive functions, total serum cholesterol levels and brain cholinesterase activity in mice. The ethanolic extract of Daucus carota seeds (DCE) was administered orally in three doses (100, 200, 400 mg/kg) for seven successive days to different groups of young and aged mice. Elevated plus maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam-, scopolamine- and ageing-induced amnesia served as the interoceptive behavioral models. DCE (200, 400 mg/kg, p.o.) showed significant improvement in memory scores of young and aged mice. The extent of memory improvement evoked by DCE was 23% at the dose of 200 mg/kg and 35% at the dose of 400 mg/kg in young mice using elevated plus maze. Similarly, significant improvements in memory scores were observed using passive avoidance apparatus and aged mice. Furthermore, DCE reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Daucus carota extract (200, 400 mg/kg, p.o.) reduced significantly the brain acetylcholinesterase activity and cholesterol levels in young and aged mice. The extent of inhibition of brain cholinesterase activity evoked by DCE at the dose of 400 mg/kg was 22% in young and 19% in aged mice. There was a remarkable reduction in total cholesterol level as well, to the extent of 23% in young and 21% in aged animals with this dose of DCE. Therefore, DCE may prove to be a useful remedy for the management of cognitive dysfunctions on account of its multifarious beneficial effects such as, memory improving property, cholesterol lowering property and anticholinesterase activity.", "entity": "Diazepam", "aliases": "7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one Apaurin Diazemuls Diazepam Faustan Relanium Seduxen Sibazon Stesolid Valium", "definition": "A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity.\n    ", "id": "MESH:D003975"}
{"mention": "scopolamine", "mention_text": "The present study was aimed at investigating the effects of Daucus carota seeds on cognitive functions, total serum cholesterol levels and brain cholinesterase activity in mice. The ethanolic extract of Daucus carota seeds (DCE) was administered orally in three doses (100, 200, 400 mg/kg) for seven successive days to different groups of young and aged mice. Elevated plus maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam-, scopolamine- and ageing-induced amnesia served as the interoceptive behavioral models. DCE (200, 400 mg/kg, p.o.) showed significant improvement in memory scores of young and aged mice. The extent of memory improvement evoked by DCE was 23% at the dose of 200 mg/kg and 35% at the dose of 400 mg/kg in young mice using elevated plus maze. Similarly, significant improvements in memory scores were observed using passive avoidance apparatus and aged mice. Furthermore, DCE reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Daucus carota extract (200, 400 mg/kg, p.o.) reduced significantly the brain acetylcholinesterase activity and cholesterol levels in young and aged mice. The extent of inhibition of brain cholinesterase activity evoked by DCE at the dose of 400 mg/kg was 22% in young and 19% in aged mice. There was a remarkable reduction in total cholesterol level as well, to the extent of 23% in young and 21% in aged animals with this dose of DCE. Therefore, DCE may prove to be a useful remedy for the management of cognitive dysfunctions on account of its multifarious beneficial effects such as, memory improving property, cholesterol lowering property and anticholinesterase activity.", "entity": "Scopolamine Hydrobromide", "aliases": "Alcon Brand of Scopolamine Hydrobromide Boro Scopol Boro-Scopol BoroScopol Bull Cooper Hamilton Hope Hyoscine Inibisa Isopto Kwells Novartis Consumer Health Renaudin Roche Scoburen Scopace Scopoderm TTS Transderm Scop V Transderm-V Travacalm HO Vorigeno Winzer Borate", "definition": "An alkaloid from SOLANACEAE, especially DATURA and SCOPOLIA. Scopolamine and its quaternary derivatives act as antimuscarinics like ATROPINE, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in URINARY INCONTINENCE, in MOTION SICKNESS, as an antispasmodic, and as a mydriatic and cycloplegic.\n    ", "id": "MESH:D012601"}
{"mention": "amnesia", "mention_text": "The present study was aimed at investigating the effects of Daucus carota seeds on cognitive functions, total serum cholesterol levels and brain cholinesterase activity in mice. The ethanolic extract of Daucus carota seeds (DCE) was administered orally in three doses (100, 200, 400 mg/kg) for seven successive days to different groups of young and aged mice. Elevated plus maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam-, scopolamine- and ageing-induced amnesia served as the interoceptive behavioral models. DCE (200, 400 mg/kg, p.o.) showed significant improvement in memory scores of young and aged mice. The extent of memory improvement evoked by DCE was 23% at the dose of 200 mg/kg and 35% at the dose of 400 mg/kg in young mice using elevated plus maze. Similarly, significant improvements in memory scores were observed using passive avoidance apparatus and aged mice. Furthermore, DCE reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Daucus carota extract (200, 400 mg/kg, p.o.) reduced significantly the brain acetylcholinesterase activity and cholesterol levels in young and aged mice. The extent of inhibition of brain cholinesterase activity evoked by DCE at the dose of 400 mg/kg was 22% in young and 19% in aged mice. There was a remarkable reduction in total cholesterol level as well, to the extent of 23% in young and 21% in aged animals with this dose of DCE. Therefore, DCE may prove to be a useful remedy for the management of cognitive dysfunctions on account of its multifarious beneficial effects such as, memory improving property, cholesterol lowering property and anticholinesterase activity.", "entity": "Amnesia", "aliases": "Amnesia Memory Loss Dissociative Global Hysterical Tactile Temporary Amnesia-Memory Losses Amnesias Amnestic State States", "definition": "Pathologic partial or complete loss of the ability to recall past experiences (AMNESIA, RETROGRADE) or to form new memories (AMNESIA, ANTEROGRADE). This condition may be of organic or psychologic origin. Organic forms of amnesia are usually associated with dysfunction of the DIENCEPHALON or HIPPOCAMPUS. (From Adams et al., Principles of Neurology, 6th ed, pp426-7)\n    ", "id": "MESH:D000647"}
{"mention": "diazepam", "mention_text": "The present study was aimed at investigating the effects of Daucus carota seeds on cognitive functions, total serum cholesterol levels and brain cholinesterase activity in mice. The ethanolic extract of Daucus carota seeds (DCE) was administered orally in three doses (100, 200, 400 mg/kg) for seven successive days to different groups of young and aged mice. Elevated plus maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam-, scopolamine- and ageing-induced amnesia served as the interoceptive behavioral models. DCE (200, 400 mg/kg, p.o.) showed significant improvement in memory scores of young and aged mice. The extent of memory improvement evoked by DCE was 23% at the dose of 200 mg/kg and 35% at the dose of 400 mg/kg in young mice using elevated plus maze. Similarly, significant improvements in memory scores were observed using passive avoidance apparatus and aged mice. Furthermore, DCE reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Daucus carota extract (200, 400 mg/kg, p.o.) reduced significantly the brain acetylcholinesterase activity and cholesterol levels in young and aged mice. The extent of inhibition of brain cholinesterase activity evoked by DCE at the dose of 400 mg/kg was 22% in young and 19% in aged mice. There was a remarkable reduction in total cholesterol level as well, to the extent of 23% in young and 21% in aged animals with this dose of DCE. Therefore, DCE may prove to be a useful remedy for the management of cognitive dysfunctions on account of its multifarious beneficial effects such as, memory improving property, cholesterol lowering property and anticholinesterase activity.", "entity": "Diazepam", "aliases": "7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one Apaurin Diazemuls Diazepam Faustan Relanium Seduxen Sibazon Stesolid Valium", "definition": "A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity.\n    ", "id": "MESH:D003975"}
{"mention": "Daucus carota extract", "mention_text": "The present study was aimed at investigating the effects of Daucus carota seeds on cognitive functions, total serum cholesterol levels and brain cholinesterase activity in mice. The ethanolic extract of Daucus carota seeds (DCE) was administered orally in three doses (100, 200, 400 mg/kg) for seven successive days to different groups of young and aged mice. Elevated plus maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam-, scopolamine- and ageing-induced amnesia served as the interoceptive behavioral models. DCE (200, 400 mg/kg, p.o.) showed significant improvement in memory scores of young and aged mice. The extent of memory improvement evoked by DCE was 23% at the dose of 200 mg/kg and 35% at the dose of 400 mg/kg in young mice using elevated plus maze. Similarly, significant improvements in memory scores were observed using passive avoidance apparatus and aged mice. Furthermore, DCE reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Daucus carota extract (200, 400 mg/kg, p.o.) reduced significantly the brain acetylcholinesterase activity and cholesterol levels in young and aged mice. The extent of inhibition of brain cholinesterase activity evoked by DCE at the dose of 400 mg/kg was 22% in young and 19% in aged mice. There was a remarkable reduction in total cholesterol level as well, to the extent of 23% in young and 21% in aged animals with this dose of DCE. Therefore, DCE may prove to be a useful remedy for the management of cognitive dysfunctions on account of its multifarious beneficial effects such as, memory improving property, cholesterol lowering property and anticholinesterase activity.", "entity": "Plant Extracts", "aliases": "Extracts Plant", "definition": "Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.\n    ", "id": "MESH:D010936"}
{"mention": "cognitive dysfunctions", "mention_text": "The present study was aimed at investigating the effects of Daucus carota seeds on cognitive functions, total serum cholesterol levels and brain cholinesterase activity in mice. The ethanolic extract of Daucus carota seeds (DCE) was administered orally in three doses (100, 200, 400 mg/kg) for seven successive days to different groups of young and aged mice. Elevated plus maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam-, scopolamine- and ageing-induced amnesia served as the interoceptive behavioral models. DCE (200, 400 mg/kg, p.o.) showed significant improvement in memory scores of young and aged mice. The extent of memory improvement evoked by DCE was 23% at the dose of 200 mg/kg and 35% at the dose of 400 mg/kg in young mice using elevated plus maze. Similarly, significant improvements in memory scores were observed using passive avoidance apparatus and aged mice. Furthermore, DCE reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Daucus carota extract (200, 400 mg/kg, p.o.) reduced significantly the brain acetylcholinesterase activity and cholesterol levels in young and aged mice. The extent of inhibition of brain cholinesterase activity evoked by DCE at the dose of 400 mg/kg was 22% in young and 19% in aged mice. There was a remarkable reduction in total cholesterol level as well, to the extent of 23% in young and 21% in aged animals with this dose of DCE. Therefore, DCE may prove to be a useful remedy for the management of cognitive dysfunctions on account of its multifarious beneficial effects such as, memory improving property, cholesterol lowering property and anticholinesterase activity.", "entity": "Cognition Disorders", "aliases": "Cognition Disorders Disorder Overinclusion", "definition": "Disturbances in the mental process related to thinking, reasoning, and judgment.\n    ", "id": "MESH:D003072"}
{"mention": "Cauda equina syndrome", "mention_text": "Cauda equina syndrome after epidural steroid injection: a case report.", "entity": "Polyradiculopathy", "aliases": "Abdominal Polyradiculopathies Polyradiculopathy Cauda Equina Syndrome Syndromes Polyradiculitides Polyradiculitis", "definition": "Disease or injury involving multiple SPINAL NERVE ROOTS. Polyradiculitis refers to inflammation of multiple spinal nerve roots.\n    ", "id": "MESH:D011128"}
{"mention": "steroid", "mention_text": "Cauda equina syndrome after epidural steroid injection: a case report.", "entity": "Steroids", "aliases": "Catatoxic Steroids", "definition": "A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)\n    ", "id": "MESH:D013256"}
{"mention": "radiculopathy", "mention_text": "OBJECTIVE: Conventional treatment methods of lumbusacral radiculopathy are physical therapy, epidural steroid injections, oral medications, and spinal manipulative therapy. Cauda equina syndrome is a rare complication of epidural anesthesia. The following case is a report of cauda equina syndrome possibly caused by epidural injection of triamcinolone and bupivacaine. CLINICAL FEATURES: A 50-year-old woman with low back and right leg pain was scheduled for epidural steroid injection. INTERVENTION AND OUTCOME: An 18-gauge Touhy needle was inserted until loss of resistance occurred at the L4-5 level. Spread of the contrast medium within the epidural space was determined by radiographic imaging. After verifying the epidural space, bupivacaine and triamcinolone diacetate were injected. After the injection, there was a reduction in radicular symptoms. Three hours later, she complained of perineal numbness and lower extremity weakness. The neurologic evaluation revealed loss of sensation in the saddle area and medial aspect of her right leg. There was a decrease in the perception of pinprick test. Deep-tendon reflexes were decreased especially in the right leg. She was unable to urinate. The patient's symptoms improved slightly over the next few hours. She had a gradual return of motor function and ability of feeling Foley catheter. All of the symptoms were completely resolved over the next 8 hours. CONCLUSION: Complications associated with epidural steroid injections are rare. Clinical examination and continued vigilance for neurologic deterioration after epidural steroid injections is important.", "entity": "Radiculopathy", "aliases": "Avulsion Nerve Root Avulsions Cervical Radiculopathies Radiculopathy Compression Compressions Inflammation Disorder Disorders Inflammations Radiculitides Radiculitis", "definition": "Disease involving a spinal nerve root (see SPINAL NERVE ROOTS) which may result from compression related to INTERVERTEBRAL DISK DISPLACEMENT; SPINAL CORD INJURIES; SPINAL DISEASES; and other conditions. Clinical manifestations include radicular pain, weakness, and sensory loss referable to structures innervated by the involved nerve root.\n    ", "id": "MESH:D011843"}
{"mention": "steroid", "mention_text": "OBJECTIVE: Conventional treatment methods of lumbusacral radiculopathy are physical therapy, epidural steroid injections, oral medications, and spinal manipulative therapy. Cauda equina syndrome is a rare complication of epidural anesthesia. The following case is a report of cauda equina syndrome possibly caused by epidural injection of triamcinolone and bupivacaine. CLINICAL FEATURES: A 50-year-old woman with low back and right leg pain was scheduled for epidural steroid injection. INTERVENTION AND OUTCOME: An 18-gauge Touhy needle was inserted until loss of resistance occurred at the L4-5 level. Spread of the contrast medium within the epidural space was determined by radiographic imaging. After verifying the epidural space, bupivacaine and triamcinolone diacetate were injected. After the injection, there was a reduction in radicular symptoms. Three hours later, she complained of perineal numbness and lower extremity weakness. The neurologic evaluation revealed loss of sensation in the saddle area and medial aspect of her right leg. There was a decrease in the perception of pinprick test. Deep-tendon reflexes were decreased especially in the right leg. She was unable to urinate. The patient's symptoms improved slightly over the next few hours. She had a gradual return of motor function and ability of feeling Foley catheter. All of the symptoms were completely resolved over the next 8 hours. CONCLUSION: Complications associated with epidural steroid injections are rare. Clinical examination and continued vigilance for neurologic deterioration after epidural steroid injections is important.", "entity": "Steroids", "aliases": "Catatoxic Steroids", "definition": "A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)\n    ", "id": "MESH:D013256"}
{"mention": "Cauda equina syndrome", "mention_text": "OBJECTIVE: Conventional treatment methods of lumbusacral radiculopathy are physical therapy, epidural steroid injections, oral medications, and spinal manipulative therapy. Cauda equina syndrome is a rare complication of epidural anesthesia. The following case is a report of cauda equina syndrome possibly caused by epidural injection of triamcinolone and bupivacaine. CLINICAL FEATURES: A 50-year-old woman with low back and right leg pain was scheduled for epidural steroid injection. INTERVENTION AND OUTCOME: An 18-gauge Touhy needle was inserted until loss of resistance occurred at the L4-5 level. Spread of the contrast medium within the epidural space was determined by radiographic imaging. After verifying the epidural space, bupivacaine and triamcinolone diacetate were injected. After the injection, there was a reduction in radicular symptoms. Three hours later, she complained of perineal numbness and lower extremity weakness. The neurologic evaluation revealed loss of sensation in the saddle area and medial aspect of her right leg. There was a decrease in the perception of pinprick test. Deep-tendon reflexes were decreased especially in the right leg. She was unable to urinate. The patient's symptoms improved slightly over the next few hours. She had a gradual return of motor function and ability of feeling Foley catheter. All of the symptoms were completely resolved over the next 8 hours. CONCLUSION: Complications associated with epidural steroid injections are rare. Clinical examination and continued vigilance for neurologic deterioration after epidural steroid injections is important.", "entity": "Polyradiculopathy", "aliases": "Abdominal Polyradiculopathies Polyradiculopathy Cauda Equina Syndrome Syndromes Polyradiculitides Polyradiculitis", "definition": "Disease or injury involving multiple SPINAL NERVE ROOTS. Polyradiculitis refers to inflammation of multiple spinal nerve roots.\n    ", "id": "MESH:D011128"}
{"mention": "cauda equina syndrome", "mention_text": "OBJECTIVE: Conventional treatment methods of lumbusacral radiculopathy are physical therapy, epidural steroid injections, oral medications, and spinal manipulative therapy. Cauda equina syndrome is a rare complication of epidural anesthesia. The following case is a report of cauda equina syndrome possibly caused by epidural injection of triamcinolone and bupivacaine. CLINICAL FEATURES: A 50-year-old woman with low back and right leg pain was scheduled for epidural steroid injection. INTERVENTION AND OUTCOME: An 18-gauge Touhy needle was inserted until loss of resistance occurred at the L4-5 level. Spread of the contrast medium within the epidural space was determined by radiographic imaging. After verifying the epidural space, bupivacaine and triamcinolone diacetate were injected. After the injection, there was a reduction in radicular symptoms. Three hours later, she complained of perineal numbness and lower extremity weakness. The neurologic evaluation revealed loss of sensation in the saddle area and medial aspect of her right leg. There was a decrease in the perception of pinprick test. Deep-tendon reflexes were decreased especially in the right leg. She was unable to urinate. The patient's symptoms improved slightly over the next few hours. She had a gradual return of motor function and ability of feeling Foley catheter. All of the symptoms were completely resolved over the next 8 hours. CONCLUSION: Complications associated with epidural steroid injections are rare. Clinical examination and continued vigilance for neurologic deterioration after epidural steroid injections is important.", "entity": "Polyradiculopathy", "aliases": "Abdominal Polyradiculopathies Polyradiculopathy Cauda Equina Syndrome Syndromes Polyradiculitides Polyradiculitis", "definition": "Disease or injury involving multiple SPINAL NERVE ROOTS. Polyradiculitis refers to inflammation of multiple spinal nerve roots.\n    ", "id": "MESH:D011128"}
{"mention": "triamcinolone", "mention_text": "OBJECTIVE: Conventional treatment methods of lumbusacral radiculopathy are physical therapy, epidural steroid injections, oral medications, and spinal manipulative therapy. Cauda equina syndrome is a rare complication of epidural anesthesia. The following case is a report of cauda equina syndrome possibly caused by epidural injection of triamcinolone and bupivacaine. CLINICAL FEATURES: A 50-year-old woman with low back and right leg pain was scheduled for epidural steroid injection. INTERVENTION AND OUTCOME: An 18-gauge Touhy needle was inserted until loss of resistance occurred at the L4-5 level. Spread of the contrast medium within the epidural space was determined by radiographic imaging. After verifying the epidural space, bupivacaine and triamcinolone diacetate were injected. After the injection, there was a reduction in radicular symptoms. Three hours later, she complained of perineal numbness and lower extremity weakness. The neurologic evaluation revealed loss of sensation in the saddle area and medial aspect of her right leg. There was a decrease in the perception of pinprick test. Deep-tendon reflexes were decreased especially in the right leg. She was unable to urinate. The patient's symptoms improved slightly over the next few hours. She had a gradual return of motor function and ability of feeling Foley catheter. All of the symptoms were completely resolved over the next 8 hours. CONCLUSION: Complications associated with epidural steroid injections are rare. Clinical examination and continued vigilance for neurologic deterioration after epidural steroid injections is important.", "entity": "Triamcinolone", "aliases": "Aristocort Triamcinolone Volon", "definition": "A glucocorticoid given, as the free alcohol or in esterified form, orally, intramuscularly, by local injection, by inhalation, or applied topically in the management of various disorders in which corticosteroids are indicated. (From Martindale, The Extra Pharmacopoeia, 30th ed, p739)\n    ", "id": "MESH:D014221"}
{"mention": "bupivacaine", "mention_text": "OBJECTIVE: Conventional treatment methods of lumbusacral radiculopathy are physical therapy, epidural steroid injections, oral medications, and spinal manipulative therapy. Cauda equina syndrome is a rare complication of epidural anesthesia. The following case is a report of cauda equina syndrome possibly caused by epidural injection of triamcinolone and bupivacaine. CLINICAL FEATURES: A 50-year-old woman with low back and right leg pain was scheduled for epidural steroid injection. INTERVENTION AND OUTCOME: An 18-gauge Touhy needle was inserted until loss of resistance occurred at the L4-5 level. Spread of the contrast medium within the epidural space was determined by radiographic imaging. After verifying the epidural space, bupivacaine and triamcinolone diacetate were injected. After the injection, there was a reduction in radicular symptoms. Three hours later, she complained of perineal numbness and lower extremity weakness. The neurologic evaluation revealed loss of sensation in the saddle area and medial aspect of her right leg. There was a decrease in the perception of pinprick test. Deep-tendon reflexes were decreased especially in the right leg. She was unable to urinate. The patient's symptoms improved slightly over the next few hours. She had a gradual return of motor function and ability of feeling Foley catheter. All of the symptoms were completely resolved over the next 8 hours. CONCLUSION: Complications associated with epidural steroid injections are rare. Clinical examination and continued vigilance for neurologic deterioration after epidural steroid injections is important.", "entity": "Bupivacaine", "aliases": "1-Butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide Abbott Brand of Bupivacaine Hydrochloride Anhydrous Astra AstraZeneca Aventis Braun Bupivacaina Bupivacain Janapharm RPR Bupivacain-RPR Carbonate Monohydrochloride Monohydrate Buvacaina Carbostesin Dolanaest Inibsa Jenapharm Marcain Marcaine Pisa Sensorcaine Strathmann Svedocain Sin Vasoconstr", "definition": "A widely used local anesthetic agent.\n    ", "id": "MESH:D002045"}
{"mention": "pain", "mention_text": "OBJECTIVE: Conventional treatment methods of lumbusacral radiculopathy are physical therapy, epidural steroid injections, oral medications, and spinal manipulative therapy. Cauda equina syndrome is a rare complication of epidural anesthesia. The following case is a report of cauda equina syndrome possibly caused by epidural injection of triamcinolone and bupivacaine. CLINICAL FEATURES: A 50-year-old woman with low back and right leg pain was scheduled for epidural steroid injection. INTERVENTION AND OUTCOME: An 18-gauge Touhy needle was inserted until loss of resistance occurred at the L4-5 level. Spread of the contrast medium within the epidural space was determined by radiographic imaging. After verifying the epidural space, bupivacaine and triamcinolone diacetate were injected. After the injection, there was a reduction in radicular symptoms. Three hours later, she complained of perineal numbness and lower extremity weakness. The neurologic evaluation revealed loss of sensation in the saddle area and medial aspect of her right leg. There was a decrease in the perception of pinprick test. Deep-tendon reflexes were decreased especially in the right leg. She was unable to urinate. The patient's symptoms improved slightly over the next few hours. She had a gradual return of motor function and ability of feeling Foley catheter. All of the symptoms were completely resolved over the next 8 hours. CONCLUSION: Complications associated with epidural steroid injections are rare. Clinical examination and continued vigilance for neurologic deterioration after epidural steroid injections is important.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "triamcinolone diacetate", "mention_text": "OBJECTIVE: Conventional treatment methods of lumbusacral radiculopathy are physical therapy, epidural steroid injections, oral medications, and spinal manipulative therapy. Cauda equina syndrome is a rare complication of epidural anesthesia. The following case is a report of cauda equina syndrome possibly caused by epidural injection of triamcinolone and bupivacaine. CLINICAL FEATURES: A 50-year-old woman with low back and right leg pain was scheduled for epidural steroid injection. INTERVENTION AND OUTCOME: An 18-gauge Touhy needle was inserted until loss of resistance occurred at the L4-5 level. Spread of the contrast medium within the epidural space was determined by radiographic imaging. After verifying the epidural space, bupivacaine and triamcinolone diacetate were injected. After the injection, there was a reduction in radicular symptoms. Three hours later, she complained of perineal numbness and lower extremity weakness. The neurologic evaluation revealed loss of sensation in the saddle area and medial aspect of her right leg. There was a decrease in the perception of pinprick test. Deep-tendon reflexes were decreased especially in the right leg. She was unable to urinate. The patient's symptoms improved slightly over the next few hours. She had a gradual return of motor function and ability of feeling Foley catheter. All of the symptoms were completely resolved over the next 8 hours. CONCLUSION: Complications associated with epidural steroid injections are rare. Clinical examination and continued vigilance for neurologic deterioration after epidural steroid injections is important.", "entity": "triamcinolone diacetate", "aliases": "Polcartolone Polcortolon triamcinolone diacetate", "definition": "", "id": "MESH:C030262"}
{"mention": "numbness", "mention_text": "OBJECTIVE: Conventional treatment methods of lumbusacral radiculopathy are physical therapy, epidural steroid injections, oral medications, and spinal manipulative therapy. Cauda equina syndrome is a rare complication of epidural anesthesia. The following case is a report of cauda equina syndrome possibly caused by epidural injection of triamcinolone and bupivacaine. CLINICAL FEATURES: A 50-year-old woman with low back and right leg pain was scheduled for epidural steroid injection. INTERVENTION AND OUTCOME: An 18-gauge Touhy needle was inserted until loss of resistance occurred at the L4-5 level. Spread of the contrast medium within the epidural space was determined by radiographic imaging. After verifying the epidural space, bupivacaine and triamcinolone diacetate were injected. After the injection, there was a reduction in radicular symptoms. Three hours later, she complained of perineal numbness and lower extremity weakness. The neurologic evaluation revealed loss of sensation in the saddle area and medial aspect of her right leg. There was a decrease in the perception of pinprick test. Deep-tendon reflexes were decreased especially in the right leg. She was unable to urinate. The patient's symptoms improved slightly over the next few hours. She had a gradual return of motor function and ability of feeling Foley catheter. All of the symptoms were completely resolved over the next 8 hours. CONCLUSION: Complications associated with epidural steroid injections are rare. Clinical examination and continued vigilance for neurologic deterioration after epidural steroid injections is important.", "entity": "Hypesthesia", "aliases": "Hypesthesia Tactile Thermal Hypesthesias Hypoesthesia Hypoesthesias Impaired Sensation Sensations Numbness Reduced", "definition": "Absent or reduced sensitivity to cutaneous stimulation.\n    ", "id": "MESH:D006987"}
{"mention": "lower extremity weakness", "mention_text": "OBJECTIVE: Conventional treatment methods of lumbusacral radiculopathy are physical therapy, epidural steroid injections, oral medications, and spinal manipulative therapy. Cauda equina syndrome is a rare complication of epidural anesthesia. The following case is a report of cauda equina syndrome possibly caused by epidural injection of triamcinolone and bupivacaine. CLINICAL FEATURES: A 50-year-old woman with low back and right leg pain was scheduled for epidural steroid injection. INTERVENTION AND OUTCOME: An 18-gauge Touhy needle was inserted until loss of resistance occurred at the L4-5 level. Spread of the contrast medium within the epidural space was determined by radiographic imaging. After verifying the epidural space, bupivacaine and triamcinolone diacetate were injected. After the injection, there was a reduction in radicular symptoms. Three hours later, she complained of perineal numbness and lower extremity weakness. The neurologic evaluation revealed loss of sensation in the saddle area and medial aspect of her right leg. There was a decrease in the perception of pinprick test. Deep-tendon reflexes were decreased especially in the right leg. She was unable to urinate. The patient's symptoms improved slightly over the next few hours. She had a gradual return of motor function and ability of feeling Foley catheter. All of the symptoms were completely resolved over the next 8 hours. CONCLUSION: Complications associated with epidural steroid injections are rare. Clinical examination and continued vigilance for neurologic deterioration after epidural steroid injections is important.", "entity": "Paraparesis", "aliases": "Cerebral Paraparesis Chronic Progressive Hypotonic Parapareses Spinal", "definition": "Mild to moderate loss of bilateral lower extremity motor function, which may be a manifestation of SPINAL CORD DISEASES; PERIPHERAL NERVOUS SYSTEM DISEASES; MUSCULAR DISEASES; INTRACRANIAL HYPERTENSION; parasagittal brain lesions; and other conditions.\n    ", "id": "MESH:D020335"}
{"mention": "loss of sensation", "mention_text": "OBJECTIVE: Conventional treatment methods of lumbusacral radiculopathy are physical therapy, epidural steroid injections, oral medications, and spinal manipulative therapy. Cauda equina syndrome is a rare complication of epidural anesthesia. The following case is a report of cauda equina syndrome possibly caused by epidural injection of triamcinolone and bupivacaine. CLINICAL FEATURES: A 50-year-old woman with low back and right leg pain was scheduled for epidural steroid injection. INTERVENTION AND OUTCOME: An 18-gauge Touhy needle was inserted until loss of resistance occurred at the L4-5 level. Spread of the contrast medium within the epidural space was determined by radiographic imaging. After verifying the epidural space, bupivacaine and triamcinolone diacetate were injected. After the injection, there was a reduction in radicular symptoms. Three hours later, she complained of perineal numbness and lower extremity weakness. The neurologic evaluation revealed loss of sensation in the saddle area and medial aspect of her right leg. There was a decrease in the perception of pinprick test. Deep-tendon reflexes were decreased especially in the right leg. She was unable to urinate. The patient's symptoms improved slightly over the next few hours. She had a gradual return of motor function and ability of feeling Foley catheter. All of the symptoms were completely resolved over the next 8 hours. CONCLUSION: Complications associated with epidural steroid injections are rare. Clinical examination and continued vigilance for neurologic deterioration after epidural steroid injections is important.", "entity": "Hypesthesia", "aliases": "Hypesthesia Tactile Thermal Hypesthesias Hypoesthesia Hypoesthesias Impaired Sensation Sensations Numbness Reduced", "definition": "Absent or reduced sensitivity to cutaneous stimulation.\n    ", "id": "MESH:D006987"}
{"mention": "neurologic deterioration", "mention_text": "OBJECTIVE: Conventional treatment methods of lumbusacral radiculopathy are physical therapy, epidural steroid injections, oral medications, and spinal manipulative therapy. Cauda equina syndrome is a rare complication of epidural anesthesia. The following case is a report of cauda equina syndrome possibly caused by epidural injection of triamcinolone and bupivacaine. CLINICAL FEATURES: A 50-year-old woman with low back and right leg pain was scheduled for epidural steroid injection. INTERVENTION AND OUTCOME: An 18-gauge Touhy needle was inserted until loss of resistance occurred at the L4-5 level. Spread of the contrast medium within the epidural space was determined by radiographic imaging. After verifying the epidural space, bupivacaine and triamcinolone diacetate were injected. After the injection, there was a reduction in radicular symptoms. Three hours later, she complained of perineal numbness and lower extremity weakness. The neurologic evaluation revealed loss of sensation in the saddle area and medial aspect of her right leg. There was a decrease in the perception of pinprick test. Deep-tendon reflexes were decreased especially in the right leg. She was unable to urinate. The patient's symptoms improved slightly over the next few hours. She had a gradual return of motor function and ability of feeling Foley catheter. All of the symptoms were completely resolved over the next 8 hours. CONCLUSION: Complications associated with epidural steroid injections are rare. Clinical examination and continued vigilance for neurologic deterioration after epidural steroid injections is important.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "testosterone", "mention_text": "High-dose testosterone is associated with atherosclerosis in postmenopausal women.", "entity": "Testosterone", "aliases": "17 beta Hydroxy 4 Androsten 3 one 8 alpha 17-beta-Hydroxy-4-Androsten-3-one 17-beta-Hydroxy-8 alpha-4-Androsten-3-one Isotestosterone 8-Isotestosterone AndroGel Androderm Andropatch Androtop AstraZeneca Brand of Testosterone Auxilium Pharmaceuticals Inc. Bartor CEPA Dr. Kade Faulding Ferring GlaxoSmithKline Hauck Histerone Ortho Paladin Pasadena Schering SmithKline Beecham Solvay Sterotate Sustanon Testim Testoderm Testolin Testopel Sulfate Ulmer Unimed Watson", "definition": "A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.\n    ", "id": "MESH:D013739"}
{"mention": "atherosclerosis", "mention_text": "High-dose testosterone is associated with atherosclerosis in postmenopausal women.", "entity": "Atherosclerosis", "aliases": "Atherogenesis Atheroscleroses Atherosclerosis", "definition": "A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA.\n    ", "id": "MESH:D050197"}
{"mention": "atherosclerosis", "mention_text": "OBJECTIVES: To study the long-term effects of androgen treatment on atherosclerosis in postmenopausal women. METHODS: In a population-based study in 513 naturally postmenopausal women aged 54-67 years, we studied the association between self-reported intramuscularly administered high-dose estrogen-testosterone therapy (estradiol- and testosterone esters) and aortic atherosclerosis. Aortic atherosclerosis was diagnosed by radiographic detection of calcified deposits in the abdominal aorta, which have been shown to reflect intima atherosclerosis. Hormone therapy users were compared with never users. RESULTS: Intramuscular hormone therapy use for 1 year or longer was reported by 25 women. In almost half of these women severe atherosclerosis of the aorta was present (n=11), while in women without hormone use severe atherosclerosis of the aorta was present in less than 20% (OR 3.1; 95% CI, 1.1-8.5, adjusted for age, years since menopause, smoking, and body mass index). The association remained after additional adjustment for diabetes, cholesterol level, systolic blood pressure, or alcohol use. No association was found for hormone use less than 1 year. CONCLUSION: Our results suggest that high-dose testosterone therapy may adversely affect atherosclerosis in postmenopausal women and indicate that androgen replacement in these women may not be harmless.", "entity": "Atherosclerosis", "aliases": "Atherogenesis Atheroscleroses Atherosclerosis", "definition": "A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA.\n    ", "id": "MESH:D050197"}
{"mention": "estrogen", "mention_text": "OBJECTIVES: To study the long-term effects of androgen treatment on atherosclerosis in postmenopausal women. METHODS: In a population-based study in 513 naturally postmenopausal women aged 54-67 years, we studied the association between self-reported intramuscularly administered high-dose estrogen-testosterone therapy (estradiol- and testosterone esters) and aortic atherosclerosis. Aortic atherosclerosis was diagnosed by radiographic detection of calcified deposits in the abdominal aorta, which have been shown to reflect intima atherosclerosis. Hormone therapy users were compared with never users. RESULTS: Intramuscular hormone therapy use for 1 year or longer was reported by 25 women. In almost half of these women severe atherosclerosis of the aorta was present (n=11), while in women without hormone use severe atherosclerosis of the aorta was present in less than 20% (OR 3.1; 95% CI, 1.1-8.5, adjusted for age, years since menopause, smoking, and body mass index). The association remained after additional adjustment for diabetes, cholesterol level, systolic blood pressure, or alcohol use. No association was found for hormone use less than 1 year. CONCLUSION: Our results suggest that high-dose testosterone therapy may adversely affect atherosclerosis in postmenopausal women and indicate that androgen replacement in these women may not be harmless.", "entity": "Estrogens", "aliases": "Agents Estrogenic Agonists Estrogen Receptor Compounds Effects Effect Estrogens", "definition": "Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds.\n    ", "id": "MESH:D004967"}
{"mention": "testosterone", "mention_text": "OBJECTIVES: To study the long-term effects of androgen treatment on atherosclerosis in postmenopausal women. METHODS: In a population-based study in 513 naturally postmenopausal women aged 54-67 years, we studied the association between self-reported intramuscularly administered high-dose estrogen-testosterone therapy (estradiol- and testosterone esters) and aortic atherosclerosis. Aortic atherosclerosis was diagnosed by radiographic detection of calcified deposits in the abdominal aorta, which have been shown to reflect intima atherosclerosis. Hormone therapy users were compared with never users. RESULTS: Intramuscular hormone therapy use for 1 year or longer was reported by 25 women. In almost half of these women severe atherosclerosis of the aorta was present (n=11), while in women without hormone use severe atherosclerosis of the aorta was present in less than 20% (OR 3.1; 95% CI, 1.1-8.5, adjusted for age, years since menopause, smoking, and body mass index). The association remained after additional adjustment for diabetes, cholesterol level, systolic blood pressure, or alcohol use. No association was found for hormone use less than 1 year. CONCLUSION: Our results suggest that high-dose testosterone therapy may adversely affect atherosclerosis in postmenopausal women and indicate that androgen replacement in these women may not be harmless.", "entity": "Testosterone", "aliases": "17 beta Hydroxy 4 Androsten 3 one 8 alpha 17-beta-Hydroxy-4-Androsten-3-one 17-beta-Hydroxy-8 alpha-4-Androsten-3-one Isotestosterone 8-Isotestosterone AndroGel Androderm Andropatch Androtop AstraZeneca Brand of Testosterone Auxilium Pharmaceuticals Inc. Bartor CEPA Dr. Kade Faulding Ferring GlaxoSmithKline Hauck Histerone Ortho Paladin Pasadena Schering SmithKline Beecham Solvay Sterotate Sustanon Testim Testoderm Testolin Testopel Sulfate Ulmer Unimed Watson", "definition": "A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.\n    ", "id": "MESH:D013739"}
{"mention": "estradiol- and testosterone esters", "mention_text": "OBJECTIVES: To study the long-term effects of androgen treatment on atherosclerosis in postmenopausal women. METHODS: In a population-based study in 513 naturally postmenopausal women aged 54-67 years, we studied the association between self-reported intramuscularly administered high-dose estrogen-testosterone therapy (estradiol- and testosterone esters) and aortic atherosclerosis. Aortic atherosclerosis was diagnosed by radiographic detection of calcified deposits in the abdominal aorta, which have been shown to reflect intima atherosclerosis. Hormone therapy users were compared with never users. RESULTS: Intramuscular hormone therapy use for 1 year or longer was reported by 25 women. In almost half of these women severe atherosclerosis of the aorta was present (n=11), while in women without hormone use severe atherosclerosis of the aorta was present in less than 20% (OR 3.1; 95% CI, 1.1-8.5, adjusted for age, years since menopause, smoking, and body mass index). The association remained after additional adjustment for diabetes, cholesterol level, systolic blood pressure, or alcohol use. No association was found for hormone use less than 1 year. CONCLUSION: Our results suggest that high-dose testosterone therapy may adversely affect atherosclerosis in postmenopausal women and indicate that androgen replacement in these women may not be harmless.", "entity": "ethynodiol testosterone ester", "aliases": "dimeric ethynodiol-testosterone ethynodiol testosterone ester", "definition": "", "id": "MESH:C032109"}
{"mention": "diabetes", "mention_text": "OBJECTIVES: To study the long-term effects of androgen treatment on atherosclerosis in postmenopausal women. METHODS: In a population-based study in 513 naturally postmenopausal women aged 54-67 years, we studied the association between self-reported intramuscularly administered high-dose estrogen-testosterone therapy (estradiol- and testosterone esters) and aortic atherosclerosis. Aortic atherosclerosis was diagnosed by radiographic detection of calcified deposits in the abdominal aorta, which have been shown to reflect intima atherosclerosis. Hormone therapy users were compared with never users. RESULTS: Intramuscular hormone therapy use for 1 year or longer was reported by 25 women. In almost half of these women severe atherosclerosis of the aorta was present (n=11), while in women without hormone use severe atherosclerosis of the aorta was present in less than 20% (OR 3.1; 95% CI, 1.1-8.5, adjusted for age, years since menopause, smoking, and body mass index). The association remained after additional adjustment for diabetes, cholesterol level, systolic blood pressure, or alcohol use. No association was found for hormone use less than 1 year. CONCLUSION: Our results suggest that high-dose testosterone therapy may adversely affect atherosclerosis in postmenopausal women and indicate that androgen replacement in these women may not be harmless.", "entity": "Diabetes Mellitus", "aliases": "Diabetes Mellitus", "definition": "A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.\n    ", "id": "MESH:D003920"}
{"mention": "cholesterol", "mention_text": "OBJECTIVES: To study the long-term effects of androgen treatment on atherosclerosis in postmenopausal women. METHODS: In a population-based study in 513 naturally postmenopausal women aged 54-67 years, we studied the association between self-reported intramuscularly administered high-dose estrogen-testosterone therapy (estradiol- and testosterone esters) and aortic atherosclerosis. Aortic atherosclerosis was diagnosed by radiographic detection of calcified deposits in the abdominal aorta, which have been shown to reflect intima atherosclerosis. Hormone therapy users were compared with never users. RESULTS: Intramuscular hormone therapy use for 1 year or longer was reported by 25 women. In almost half of these women severe atherosclerosis of the aorta was present (n=11), while in women without hormone use severe atherosclerosis of the aorta was present in less than 20% (OR 3.1; 95% CI, 1.1-8.5, adjusted for age, years since menopause, smoking, and body mass index). The association remained after additional adjustment for diabetes, cholesterol level, systolic blood pressure, or alcohol use. No association was found for hormone use less than 1 year. CONCLUSION: Our results suggest that high-dose testosterone therapy may adversely affect atherosclerosis in postmenopausal women and indicate that androgen replacement in these women may not be harmless.", "entity": "Cholesterol", "aliases": "Cholesterol Epicholesterol", "definition": "The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.\n    ", "id": "MESH:D002784"}
{"mention": "alcohol", "mention_text": "OBJECTIVES: To study the long-term effects of androgen treatment on atherosclerosis in postmenopausal women. METHODS: In a population-based study in 513 naturally postmenopausal women aged 54-67 years, we studied the association between self-reported intramuscularly administered high-dose estrogen-testosterone therapy (estradiol- and testosterone esters) and aortic atherosclerosis. Aortic atherosclerosis was diagnosed by radiographic detection of calcified deposits in the abdominal aorta, which have been shown to reflect intima atherosclerosis. Hormone therapy users were compared with never users. RESULTS: Intramuscular hormone therapy use for 1 year or longer was reported by 25 women. In almost half of these women severe atherosclerosis of the aorta was present (n=11), while in women without hormone use severe atherosclerosis of the aorta was present in less than 20% (OR 3.1; 95% CI, 1.1-8.5, adjusted for age, years since menopause, smoking, and body mass index). The association remained after additional adjustment for diabetes, cholesterol level, systolic blood pressure, or alcohol use. No association was found for hormone use less than 1 year. CONCLUSION: Our results suggest that high-dose testosterone therapy may adversely affect atherosclerosis in postmenopausal women and indicate that androgen replacement in these women may not be harmless.", "entity": "Ethanol", "aliases": "Absolute Alcohol Ethyl Grain Ethanol", "definition": "A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.\n    ", "id": "MESH:D000431"}
{"mention": "Sirolimus", "mention_text": "Sirolimus-associated proteinuria and renal dysfunction.", "entity": "Sirolimus", "aliases": "AY 22 989 22-989 22989 I 2190A I-2190A I2190A Rapamune Rapamycin Sirolimus Wyeth Brand of", "definition": "A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.\n    ", "id": "MESH:D020123"}
{"mention": "proteinuria", "mention_text": "Sirolimus-associated proteinuria and renal dysfunction.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "renal dysfunction", "mention_text": "Sirolimus-associated proteinuria and renal dysfunction.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "Sirolimus", "mention_text": "Sirolimus is a novel immunosuppressant with potent antiproliferative actions through its ability to inhibit the raptor-containing mammalian target of rapamycin protein kinase. Sirolimus represents a major therapeutic advance in the prevention of acute renal allograft rejection and chronic allograft nephropathy. Its role in the therapy of glomerulonephritis, autoimmunity, cystic renal diseases and renal cancer is under investigation. Because sirolimus does not share the vasomotor renal adverse effects exhibited by calcineurin inhibitors, it has been designated a 'non-nephrotoxic drug'. However, clinical reports suggest that, under some circumstances, sirolimus is associated with proteinuria and acute renal dysfunction. A common risk factor appears to be presence of pre-existing chronic renal damage. The mechanisms of sirolimus-associated proteinuria are multifactorial and may be due to an increase in glomerular capillary pressure following calcineurin inhibitor withdrawal. It has also been suggested that sirolimus directly causes increased glomerular permeability/injury, but evidence for this mechanism is currently inconclusive. The acute renal dysfunction associated with sirolimus (such as in delayed graft function) may be due to suppression of compensatory renal cell proliferation and survival/repair processes. Although these adverse effects occur in some patients, their occurrence could be minimised by knowledge of the molecular effects of sirolimus on the kidney, the use of sirolimus in appropriate patient populations, close monitoring of proteinuria and renal function, use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers if proteinuria occurs and withdrawal if needed. Further long-term analysis of renal allograft studies using sirolimus as de novo immunosuppression along with clinical and laboratory studies will refine these issues in the future.", "entity": "Sirolimus", "aliases": "AY 22 989 22-989 22989 I 2190A I-2190A I2190A Rapamune Rapamycin Sirolimus Wyeth Brand of", "definition": "A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.\n    ", "id": "MESH:D020123"}
{"mention": "rapamycin", "mention_text": "Sirolimus is a novel immunosuppressant with potent antiproliferative actions through its ability to inhibit the raptor-containing mammalian target of rapamycin protein kinase. Sirolimus represents a major therapeutic advance in the prevention of acute renal allograft rejection and chronic allograft nephropathy. Its role in the therapy of glomerulonephritis, autoimmunity, cystic renal diseases and renal cancer is under investigation. Because sirolimus does not share the vasomotor renal adverse effects exhibited by calcineurin inhibitors, it has been designated a 'non-nephrotoxic drug'. However, clinical reports suggest that, under some circumstances, sirolimus is associated with proteinuria and acute renal dysfunction. A common risk factor appears to be presence of pre-existing chronic renal damage. The mechanisms of sirolimus-associated proteinuria are multifactorial and may be due to an increase in glomerular capillary pressure following calcineurin inhibitor withdrawal. It has also been suggested that sirolimus directly causes increased glomerular permeability/injury, but evidence for this mechanism is currently inconclusive. The acute renal dysfunction associated with sirolimus (such as in delayed graft function) may be due to suppression of compensatory renal cell proliferation and survival/repair processes. Although these adverse effects occur in some patients, their occurrence could be minimised by knowledge of the molecular effects of sirolimus on the kidney, the use of sirolimus in appropriate patient populations, close monitoring of proteinuria and renal function, use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers if proteinuria occurs and withdrawal if needed. Further long-term analysis of renal allograft studies using sirolimus as de novo immunosuppression along with clinical and laboratory studies will refine these issues in the future.", "entity": "Sirolimus", "aliases": "AY 22 989 22-989 22989 I 2190A I-2190A I2190A Rapamune Rapamycin Sirolimus Wyeth Brand of", "definition": "A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.\n    ", "id": "MESH:D020123"}
{"mention": "nephropathy", "mention_text": "Sirolimus is a novel immunosuppressant with potent antiproliferative actions through its ability to inhibit the raptor-containing mammalian target of rapamycin protein kinase. Sirolimus represents a major therapeutic advance in the prevention of acute renal allograft rejection and chronic allograft nephropathy. Its role in the therapy of glomerulonephritis, autoimmunity, cystic renal diseases and renal cancer is under investigation. Because sirolimus does not share the vasomotor renal adverse effects exhibited by calcineurin inhibitors, it has been designated a 'non-nephrotoxic drug'. However, clinical reports suggest that, under some circumstances, sirolimus is associated with proteinuria and acute renal dysfunction. A common risk factor appears to be presence of pre-existing chronic renal damage. The mechanisms of sirolimus-associated proteinuria are multifactorial and may be due to an increase in glomerular capillary pressure following calcineurin inhibitor withdrawal. It has also been suggested that sirolimus directly causes increased glomerular permeability/injury, but evidence for this mechanism is currently inconclusive. The acute renal dysfunction associated with sirolimus (such as in delayed graft function) may be due to suppression of compensatory renal cell proliferation and survival/repair processes. Although these adverse effects occur in some patients, their occurrence could be minimised by knowledge of the molecular effects of sirolimus on the kidney, the use of sirolimus in appropriate patient populations, close monitoring of proteinuria and renal function, use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers if proteinuria occurs and withdrawal if needed. Further long-term analysis of renal allograft studies using sirolimus as de novo immunosuppression along with clinical and laboratory studies will refine these issues in the future.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "glomerulonephritis", "mention_text": "Sirolimus is a novel immunosuppressant with potent antiproliferative actions through its ability to inhibit the raptor-containing mammalian target of rapamycin protein kinase. Sirolimus represents a major therapeutic advance in the prevention of acute renal allograft rejection and chronic allograft nephropathy. Its role in the therapy of glomerulonephritis, autoimmunity, cystic renal diseases and renal cancer is under investigation. Because sirolimus does not share the vasomotor renal adverse effects exhibited by calcineurin inhibitors, it has been designated a 'non-nephrotoxic drug'. However, clinical reports suggest that, under some circumstances, sirolimus is associated with proteinuria and acute renal dysfunction. A common risk factor appears to be presence of pre-existing chronic renal damage. The mechanisms of sirolimus-associated proteinuria are multifactorial and may be due to an increase in glomerular capillary pressure following calcineurin inhibitor withdrawal. It has also been suggested that sirolimus directly causes increased glomerular permeability/injury, but evidence for this mechanism is currently inconclusive. The acute renal dysfunction associated with sirolimus (such as in delayed graft function) may be due to suppression of compensatory renal cell proliferation and survival/repair processes. Although these adverse effects occur in some patients, their occurrence could be minimised by knowledge of the molecular effects of sirolimus on the kidney, the use of sirolimus in appropriate patient populations, close monitoring of proteinuria and renal function, use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers if proteinuria occurs and withdrawal if needed. Further long-term analysis of renal allograft studies using sirolimus as de novo immunosuppression along with clinical and laboratory studies will refine these issues in the future.", "entity": "Glomerulonephritis", "aliases": "Bright Disease Glomerulonephritides Glomerulonephritis", "definition": "Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.\n    ", "id": "MESH:D005921"}
{"mention": "autoimmunity", "mention_text": "Sirolimus is a novel immunosuppressant with potent antiproliferative actions through its ability to inhibit the raptor-containing mammalian target of rapamycin protein kinase. Sirolimus represents a major therapeutic advance in the prevention of acute renal allograft rejection and chronic allograft nephropathy. Its role in the therapy of glomerulonephritis, autoimmunity, cystic renal diseases and renal cancer is under investigation. Because sirolimus does not share the vasomotor renal adverse effects exhibited by calcineurin inhibitors, it has been designated a 'non-nephrotoxic drug'. However, clinical reports suggest that, under some circumstances, sirolimus is associated with proteinuria and acute renal dysfunction. A common risk factor appears to be presence of pre-existing chronic renal damage. The mechanisms of sirolimus-associated proteinuria are multifactorial and may be due to an increase in glomerular capillary pressure following calcineurin inhibitor withdrawal. It has also been suggested that sirolimus directly causes increased glomerular permeability/injury, but evidence for this mechanism is currently inconclusive. The acute renal dysfunction associated with sirolimus (such as in delayed graft function) may be due to suppression of compensatory renal cell proliferation and survival/repair processes. Although these adverse effects occur in some patients, their occurrence could be minimised by knowledge of the molecular effects of sirolimus on the kidney, the use of sirolimus in appropriate patient populations, close monitoring of proteinuria and renal function, use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers if proteinuria occurs and withdrawal if needed. Further long-term analysis of renal allograft studies using sirolimus as de novo immunosuppression along with clinical and laboratory studies will refine these issues in the future.", "entity": "Autoimmune Diseases", "aliases": "Autoimmune Disease Diseases", "definition": "Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.\n    ", "id": "MESH:D001327"}
{"mention": "cystic renal diseases", "mention_text": "Sirolimus is a novel immunosuppressant with potent antiproliferative actions through its ability to inhibit the raptor-containing mammalian target of rapamycin protein kinase. Sirolimus represents a major therapeutic advance in the prevention of acute renal allograft rejection and chronic allograft nephropathy. Its role in the therapy of glomerulonephritis, autoimmunity, cystic renal diseases and renal cancer is under investigation. Because sirolimus does not share the vasomotor renal adverse effects exhibited by calcineurin inhibitors, it has been designated a 'non-nephrotoxic drug'. However, clinical reports suggest that, under some circumstances, sirolimus is associated with proteinuria and acute renal dysfunction. A common risk factor appears to be presence of pre-existing chronic renal damage. The mechanisms of sirolimus-associated proteinuria are multifactorial and may be due to an increase in glomerular capillary pressure following calcineurin inhibitor withdrawal. It has also been suggested that sirolimus directly causes increased glomerular permeability/injury, but evidence for this mechanism is currently inconclusive. The acute renal dysfunction associated with sirolimus (such as in delayed graft function) may be due to suppression of compensatory renal cell proliferation and survival/repair processes. Although these adverse effects occur in some patients, their occurrence could be minimised by knowledge of the molecular effects of sirolimus on the kidney, the use of sirolimus in appropriate patient populations, close monitoring of proteinuria and renal function, use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers if proteinuria occurs and withdrawal if needed. Further long-term analysis of renal allograft studies using sirolimus as de novo immunosuppression along with clinical and laboratory studies will refine these issues in the future.", "entity": "Kidney Diseases, Cystic", "aliases": "Cystic Kidney Disease Diseases Kidneys Renal", "definition": "A heterogeneous group of hereditary and acquired disorders in which the KIDNEY contains one or more CYSTS unilaterally or bilaterally (KIDNEY, CYSTIC).\n    ", "id": "MESH:D052177"}
{"mention": "renal cancer", "mention_text": "Sirolimus is a novel immunosuppressant with potent antiproliferative actions through its ability to inhibit the raptor-containing mammalian target of rapamycin protein kinase. Sirolimus represents a major therapeutic advance in the prevention of acute renal allograft rejection and chronic allograft nephropathy. Its role in the therapy of glomerulonephritis, autoimmunity, cystic renal diseases and renal cancer is under investigation. Because sirolimus does not share the vasomotor renal adverse effects exhibited by calcineurin inhibitors, it has been designated a 'non-nephrotoxic drug'. However, clinical reports suggest that, under some circumstances, sirolimus is associated with proteinuria and acute renal dysfunction. A common risk factor appears to be presence of pre-existing chronic renal damage. The mechanisms of sirolimus-associated proteinuria are multifactorial and may be due to an increase in glomerular capillary pressure following calcineurin inhibitor withdrawal. It has also been suggested that sirolimus directly causes increased glomerular permeability/injury, but evidence for this mechanism is currently inconclusive. The acute renal dysfunction associated with sirolimus (such as in delayed graft function) may be due to suppression of compensatory renal cell proliferation and survival/repair processes. Although these adverse effects occur in some patients, their occurrence could be minimised by knowledge of the molecular effects of sirolimus on the kidney, the use of sirolimus in appropriate patient populations, close monitoring of proteinuria and renal function, use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers if proteinuria occurs and withdrawal if needed. Further long-term analysis of renal allograft studies using sirolimus as de novo immunosuppression along with clinical and laboratory studies will refine these issues in the future.", "entity": "Kidney Neoplasms", "aliases": "Cancer of Kidney the Renal Cancers Neoplasm Neoplasms", "definition": "Tumors or cancers of the KIDNEY.\n    ", "id": "MESH:D007680"}
{"mention": "sirolimus", "mention_text": "Sirolimus is a novel immunosuppressant with potent antiproliferative actions through its ability to inhibit the raptor-containing mammalian target of rapamycin protein kinase. Sirolimus represents a major therapeutic advance in the prevention of acute renal allograft rejection and chronic allograft nephropathy. Its role in the therapy of glomerulonephritis, autoimmunity, cystic renal diseases and renal cancer is under investigation. Because sirolimus does not share the vasomotor renal adverse effects exhibited by calcineurin inhibitors, it has been designated a 'non-nephrotoxic drug'. However, clinical reports suggest that, under some circumstances, sirolimus is associated with proteinuria and acute renal dysfunction. A common risk factor appears to be presence of pre-existing chronic renal damage. The mechanisms of sirolimus-associated proteinuria are multifactorial and may be due to an increase in glomerular capillary pressure following calcineurin inhibitor withdrawal. It has also been suggested that sirolimus directly causes increased glomerular permeability/injury, but evidence for this mechanism is currently inconclusive. The acute renal dysfunction associated with sirolimus (such as in delayed graft function) may be due to suppression of compensatory renal cell proliferation and survival/repair processes. Although these adverse effects occur in some patients, their occurrence could be minimised by knowledge of the molecular effects of sirolimus on the kidney, the use of sirolimus in appropriate patient populations, close monitoring of proteinuria and renal function, use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers if proteinuria occurs and withdrawal if needed. Further long-term analysis of renal allograft studies using sirolimus as de novo immunosuppression along with clinical and laboratory studies will refine these issues in the future.", "entity": "Sirolimus", "aliases": "AY 22 989 22-989 22989 I 2190A I-2190A I2190A Rapamune Rapamycin Sirolimus Wyeth Brand of", "definition": "A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.\n    ", "id": "MESH:D020123"}
{"mention": "nephrotoxic", "mention_text": "Sirolimus is a novel immunosuppressant with potent antiproliferative actions through its ability to inhibit the raptor-containing mammalian target of rapamycin protein kinase. Sirolimus represents a major therapeutic advance in the prevention of acute renal allograft rejection and chronic allograft nephropathy. Its role in the therapy of glomerulonephritis, autoimmunity, cystic renal diseases and renal cancer is under investigation. Because sirolimus does not share the vasomotor renal adverse effects exhibited by calcineurin inhibitors, it has been designated a 'non-nephrotoxic drug'. However, clinical reports suggest that, under some circumstances, sirolimus is associated with proteinuria and acute renal dysfunction. A common risk factor appears to be presence of pre-existing chronic renal damage. The mechanisms of sirolimus-associated proteinuria are multifactorial and may be due to an increase in glomerular capillary pressure following calcineurin inhibitor withdrawal. It has also been suggested that sirolimus directly causes increased glomerular permeability/injury, but evidence for this mechanism is currently inconclusive. The acute renal dysfunction associated with sirolimus (such as in delayed graft function) may be due to suppression of compensatory renal cell proliferation and survival/repair processes. Although these adverse effects occur in some patients, their occurrence could be minimised by knowledge of the molecular effects of sirolimus on the kidney, the use of sirolimus in appropriate patient populations, close monitoring of proteinuria and renal function, use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers if proteinuria occurs and withdrawal if needed. Further long-term analysis of renal allograft studies using sirolimus as de novo immunosuppression along with clinical and laboratory studies will refine these issues in the future.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "proteinuria", "mention_text": "Sirolimus is a novel immunosuppressant with potent antiproliferative actions through its ability to inhibit the raptor-containing mammalian target of rapamycin protein kinase. Sirolimus represents a major therapeutic advance in the prevention of acute renal allograft rejection and chronic allograft nephropathy. Its role in the therapy of glomerulonephritis, autoimmunity, cystic renal diseases and renal cancer is under investigation. Because sirolimus does not share the vasomotor renal adverse effects exhibited by calcineurin inhibitors, it has been designated a 'non-nephrotoxic drug'. However, clinical reports suggest that, under some circumstances, sirolimus is associated with proteinuria and acute renal dysfunction. A common risk factor appears to be presence of pre-existing chronic renal damage. The mechanisms of sirolimus-associated proteinuria are multifactorial and may be due to an increase in glomerular capillary pressure following calcineurin inhibitor withdrawal. It has also been suggested that sirolimus directly causes increased glomerular permeability/injury, but evidence for this mechanism is currently inconclusive. The acute renal dysfunction associated with sirolimus (such as in delayed graft function) may be due to suppression of compensatory renal cell proliferation and survival/repair processes. Although these adverse effects occur in some patients, their occurrence could be minimised by knowledge of the molecular effects of sirolimus on the kidney, the use of sirolimus in appropriate patient populations, close monitoring of proteinuria and renal function, use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers if proteinuria occurs and withdrawal if needed. Further long-term analysis of renal allograft studies using sirolimus as de novo immunosuppression along with clinical and laboratory studies will refine these issues in the future.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "acute renal dysfunction", "mention_text": "Sirolimus is a novel immunosuppressant with potent antiproliferative actions through its ability to inhibit the raptor-containing mammalian target of rapamycin protein kinase. Sirolimus represents a major therapeutic advance in the prevention of acute renal allograft rejection and chronic allograft nephropathy. Its role in the therapy of glomerulonephritis, autoimmunity, cystic renal diseases and renal cancer is under investigation. Because sirolimus does not share the vasomotor renal adverse effects exhibited by calcineurin inhibitors, it has been designated a 'non-nephrotoxic drug'. However, clinical reports suggest that, under some circumstances, sirolimus is associated with proteinuria and acute renal dysfunction. A common risk factor appears to be presence of pre-existing chronic renal damage. The mechanisms of sirolimus-associated proteinuria are multifactorial and may be due to an increase in glomerular capillary pressure following calcineurin inhibitor withdrawal. It has also been suggested that sirolimus directly causes increased glomerular permeability/injury, but evidence for this mechanism is currently inconclusive. The acute renal dysfunction associated with sirolimus (such as in delayed graft function) may be due to suppression of compensatory renal cell proliferation and survival/repair processes. Although these adverse effects occur in some patients, their occurrence could be minimised by knowledge of the molecular effects of sirolimus on the kidney, the use of sirolimus in appropriate patient populations, close monitoring of proteinuria and renal function, use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers if proteinuria occurs and withdrawal if needed. Further long-term analysis of renal allograft studies using sirolimus as de novo immunosuppression along with clinical and laboratory studies will refine these issues in the future.", "entity": "Acute Kidney Injury", "aliases": "Acute Kidney Failure Failures Injuries Injury Insufficiencies Insufficiency Renal", "definition": "Abrupt reduction in kidney function. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions.\n    ", "id": "MESH:D058186"}
{"mention": "chronic renal damage", "mention_text": "Sirolimus is a novel immunosuppressant with potent antiproliferative actions through its ability to inhibit the raptor-containing mammalian target of rapamycin protein kinase. Sirolimus represents a major therapeutic advance in the prevention of acute renal allograft rejection and chronic allograft nephropathy. Its role in the therapy of glomerulonephritis, autoimmunity, cystic renal diseases and renal cancer is under investigation. Because sirolimus does not share the vasomotor renal adverse effects exhibited by calcineurin inhibitors, it has been designated a 'non-nephrotoxic drug'. However, clinical reports suggest that, under some circumstances, sirolimus is associated with proteinuria and acute renal dysfunction. A common risk factor appears to be presence of pre-existing chronic renal damage. The mechanisms of sirolimus-associated proteinuria are multifactorial and may be due to an increase in glomerular capillary pressure following calcineurin inhibitor withdrawal. It has also been suggested that sirolimus directly causes increased glomerular permeability/injury, but evidence for this mechanism is currently inconclusive. The acute renal dysfunction associated with sirolimus (such as in delayed graft function) may be due to suppression of compensatory renal cell proliferation and survival/repair processes. Although these adverse effects occur in some patients, their occurrence could be minimised by knowledge of the molecular effects of sirolimus on the kidney, the use of sirolimus in appropriate patient populations, close monitoring of proteinuria and renal function, use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers if proteinuria occurs and withdrawal if needed. Further long-term analysis of renal allograft studies using sirolimus as de novo immunosuppression along with clinical and laboratory studies will refine these issues in the future.", "entity": "Renal Insufficiency, Chronic", "aliases": "Chronic Kidney Disease Diseases Insufficiencies Insufficiency Renal", "definition": "Conditions in which the KIDNEYS perform below the normal level for more than three months. Chronic kidney insufficiency is classified by five stages according to the decline in GLOMERULAR FILTRATION RATE and the degree of kidney damage (as measured by the level of PROTEINURIA). The most severe form is the end-stage renal disease (CHRONIC KIDNEY FAILURE). (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002)\n    ", "id": "MESH:D051436"}
{"mention": "angiotensin", "mention_text": "Sirolimus is a novel immunosuppressant with potent antiproliferative actions through its ability to inhibit the raptor-containing mammalian target of rapamycin protein kinase. Sirolimus represents a major therapeutic advance in the prevention of acute renal allograft rejection and chronic allograft nephropathy. Its role in the therapy of glomerulonephritis, autoimmunity, cystic renal diseases and renal cancer is under investigation. Because sirolimus does not share the vasomotor renal adverse effects exhibited by calcineurin inhibitors, it has been designated a 'non-nephrotoxic drug'. However, clinical reports suggest that, under some circumstances, sirolimus is associated with proteinuria and acute renal dysfunction. A common risk factor appears to be presence of pre-existing chronic renal damage. The mechanisms of sirolimus-associated proteinuria are multifactorial and may be due to an increase in glomerular capillary pressure following calcineurin inhibitor withdrawal. It has also been suggested that sirolimus directly causes increased glomerular permeability/injury, but evidence for this mechanism is currently inconclusive. The acute renal dysfunction associated with sirolimus (such as in delayed graft function) may be due to suppression of compensatory renal cell proliferation and survival/repair processes. Although these adverse effects occur in some patients, their occurrence could be minimised by knowledge of the molecular effects of sirolimus on the kidney, the use of sirolimus in appropriate patient populations, close monitoring of proteinuria and renal function, use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers if proteinuria occurs and withdrawal if needed. Further long-term analysis of renal allograft studies using sirolimus as de novo immunosuppression along with clinical and laboratory studies will refine these issues in the future.", "entity": "Angiotensins", "aliases": "Angiotensin Angiotensins", "definition": "Oligopeptides which are important in the regulation of blood pressure (VASOCONSTRICTION) and fluid homeostasis via the RENIN-ANGIOTENSIN SYSTEM. These include angiotensins derived naturally from precursor ANGIOTENSINOGEN, and those synthesized.\n    ", "id": "MESH:D000809"}
{"mention": "angiotensin II", "mention_text": "Sirolimus is a novel immunosuppressant with potent antiproliferative actions through its ability to inhibit the raptor-containing mammalian target of rapamycin protein kinase. Sirolimus represents a major therapeutic advance in the prevention of acute renal allograft rejection and chronic allograft nephropathy. Its role in the therapy of glomerulonephritis, autoimmunity, cystic renal diseases and renal cancer is under investigation. Because sirolimus does not share the vasomotor renal adverse effects exhibited by calcineurin inhibitors, it has been designated a 'non-nephrotoxic drug'. However, clinical reports suggest that, under some circumstances, sirolimus is associated with proteinuria and acute renal dysfunction. A common risk factor appears to be presence of pre-existing chronic renal damage. The mechanisms of sirolimus-associated proteinuria are multifactorial and may be due to an increase in glomerular capillary pressure following calcineurin inhibitor withdrawal. It has also been suggested that sirolimus directly causes increased glomerular permeability/injury, but evidence for this mechanism is currently inconclusive. The acute renal dysfunction associated with sirolimus (such as in delayed graft function) may be due to suppression of compensatory renal cell proliferation and survival/repair processes. Although these adverse effects occur in some patients, their occurrence could be minimised by knowledge of the molecular effects of sirolimus on the kidney, the use of sirolimus in appropriate patient populations, close monitoring of proteinuria and renal function, use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers if proteinuria occurs and withdrawal if needed. Further long-term analysis of renal allograft studies using sirolimus as de novo immunosuppression along with clinical and laboratory studies will refine these issues in the future.", "entity": "Angiotensin II", "aliases": "5 L Isoleucine Angiotensin II 5-L-Isoleucine ANG-(1-8)Octapeptide Ile(5)- Isoleucine(5)- Val(5)- Valine(5)- Angiotensin-(1-8) Octapeptide Isoleucine(5)-Angiotensin Isoleucyl(5)-Angiotensin Valyl(5)-Angiotensin", "definition": "An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.\n    ", "id": "MESH:D000804"}
{"mention": "myopathy", "mention_text": "Progressive myopathy with up-regulation of MHC-I associated with statin therapy.", "entity": "Muscular Diseases", "aliases": "Muscle Disorder Disorders Muscular Disease Diseases Myopathic Condition Conditions Myopathies Myopathy", "definition": "Acquired, familial, and congenital disorders of SKELETAL MUSCLE and SMOOTH MUSCLE.\n    ", "id": "MESH:D009135"}
{"mention": "statin", "mention_text": "Progressive myopathy with up-regulation of MHC-I associated with statin therapy.", "entity": "Simvastatin", "aliases": "MK 733 MK-733 MK733 Simvastatin Synvinolin Zocor", "definition": "A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL CHOLESTEROL.\n    ", "id": "MESH:D019821"}
{"mention": "Statins", "mention_text": "Statins can cause a necrotizing myopathy and hyperCKaemia which is reversible on cessation of the drug. What is less well known is a phenomenon whereby statins may induce a myopathy, which persists or may progress after stopping the drug. We investigated the muscle pathology in 8 such cases. All had myofibre necrosis but only 3 had an inflammatory infiltrate. In all cases there was diffuse or multifocal up-regulation of MHC-I expression even in non-necrotic fibres. Progressive improvement occurred in 7 cases after commencement of prednisolone and methotrexate, and in one case spontaneously. These observations suggest that statins may initiate an immune-mediated myopathy that persists after withdrawal of the drug and responds to immunosuppressive therapy. The mechanism of this myopathy is uncertain but may involve the induction by statins of an endoplasmic reticulum stress response with associated up-regulation of MHC-I expression and antigen presentation by muscle fibres.", "entity": "Simvastatin", "aliases": "MK 733 MK-733 MK733 Simvastatin Synvinolin Zocor", "definition": "A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL CHOLESTEROL.\n    ", "id": "MESH:D019821"}
{"mention": "myopathy", "mention_text": "Statins can cause a necrotizing myopathy and hyperCKaemia which is reversible on cessation of the drug. What is less well known is a phenomenon whereby statins may induce a myopathy, which persists or may progress after stopping the drug. We investigated the muscle pathology in 8 such cases. All had myofibre necrosis but only 3 had an inflammatory infiltrate. In all cases there was diffuse or multifocal up-regulation of MHC-I expression even in non-necrotic fibres. Progressive improvement occurred in 7 cases after commencement of prednisolone and methotrexate, and in one case spontaneously. These observations suggest that statins may initiate an immune-mediated myopathy that persists after withdrawal of the drug and responds to immunosuppressive therapy. The mechanism of this myopathy is uncertain but may involve the induction by statins of an endoplasmic reticulum stress response with associated up-regulation of MHC-I expression and antigen presentation by muscle fibres.", "entity": "Muscular Diseases", "aliases": "Muscle Disorder Disorders Muscular Disease Diseases Myopathic Condition Conditions Myopathies Myopathy", "definition": "Acquired, familial, and congenital disorders of SKELETAL MUSCLE and SMOOTH MUSCLE.\n    ", "id": "MESH:D009135"}
{"mention": "statins", "mention_text": "Statins can cause a necrotizing myopathy and hyperCKaemia which is reversible on cessation of the drug. What is less well known is a phenomenon whereby statins may induce a myopathy, which persists or may progress after stopping the drug. We investigated the muscle pathology in 8 such cases. All had myofibre necrosis but only 3 had an inflammatory infiltrate. In all cases there was diffuse or multifocal up-regulation of MHC-I expression even in non-necrotic fibres. Progressive improvement occurred in 7 cases after commencement of prednisolone and methotrexate, and in one case spontaneously. These observations suggest that statins may initiate an immune-mediated myopathy that persists after withdrawal of the drug and responds to immunosuppressive therapy. The mechanism of this myopathy is uncertain but may involve the induction by statins of an endoplasmic reticulum stress response with associated up-regulation of MHC-I expression and antigen presentation by muscle fibres.", "entity": "Simvastatin", "aliases": "MK 733 MK-733 MK733 Simvastatin Synvinolin Zocor", "definition": "A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL CHOLESTEROL.\n    ", "id": "MESH:D019821"}
{"mention": "necrosis", "mention_text": "Statins can cause a necrotizing myopathy and hyperCKaemia which is reversible on cessation of the drug. What is less well known is a phenomenon whereby statins may induce a myopathy, which persists or may progress after stopping the drug. We investigated the muscle pathology in 8 such cases. All had myofibre necrosis but only 3 had an inflammatory infiltrate. In all cases there was diffuse or multifocal up-regulation of MHC-I expression even in non-necrotic fibres. Progressive improvement occurred in 7 cases after commencement of prednisolone and methotrexate, and in one case spontaneously. These observations suggest that statins may initiate an immune-mediated myopathy that persists after withdrawal of the drug and responds to immunosuppressive therapy. The mechanism of this myopathy is uncertain but may involve the induction by statins of an endoplasmic reticulum stress response with associated up-regulation of MHC-I expression and antigen presentation by muscle fibres.", "entity": "Necrosis", "aliases": "Necroses Necrosis", "definition": "The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. Distinguish it from APOPTOSIS which is a normal, regulated cellular process.\n    ", "id": "MESH:D009336"}
{"mention": "necrotic", "mention_text": "Statins can cause a necrotizing myopathy and hyperCKaemia which is reversible on cessation of the drug. What is less well known is a phenomenon whereby statins may induce a myopathy, which persists or may progress after stopping the drug. We investigated the muscle pathology in 8 such cases. All had myofibre necrosis but only 3 had an inflammatory infiltrate. In all cases there was diffuse or multifocal up-regulation of MHC-I expression even in non-necrotic fibres. Progressive improvement occurred in 7 cases after commencement of prednisolone and methotrexate, and in one case spontaneously. These observations suggest that statins may initiate an immune-mediated myopathy that persists after withdrawal of the drug and responds to immunosuppressive therapy. The mechanism of this myopathy is uncertain but may involve the induction by statins of an endoplasmic reticulum stress response with associated up-regulation of MHC-I expression and antigen presentation by muscle fibres.", "entity": "Necrosis", "aliases": "Necroses Necrosis", "definition": "The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. Distinguish it from APOPTOSIS which is a normal, regulated cellular process.\n    ", "id": "MESH:D009336"}
{"mention": "prednisolone", "mention_text": "Statins can cause a necrotizing myopathy and hyperCKaemia which is reversible on cessation of the drug. What is less well known is a phenomenon whereby statins may induce a myopathy, which persists or may progress after stopping the drug. We investigated the muscle pathology in 8 such cases. All had myofibre necrosis but only 3 had an inflammatory infiltrate. In all cases there was diffuse or multifocal up-regulation of MHC-I expression even in non-necrotic fibres. Progressive improvement occurred in 7 cases after commencement of prednisolone and methotrexate, and in one case spontaneously. These observations suggest that statins may initiate an immune-mediated myopathy that persists after withdrawal of the drug and responds to immunosuppressive therapy. The mechanism of this myopathy is uncertain but may involve the induction by statins of an endoplasmic reticulum stress response with associated up-regulation of MHC-I expression and antigen presentation by muscle fibres.", "entity": "Prednisolone", "aliases": "Di Adreson F Di-Adreson-F DiAdresonF Predate Prednisolone Predonine", "definition": "A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states.\n    ", "id": "MESH:D011239"}
{"mention": "methotrexate", "mention_text": "Statins can cause a necrotizing myopathy and hyperCKaemia which is reversible on cessation of the drug. What is less well known is a phenomenon whereby statins may induce a myopathy, which persists or may progress after stopping the drug. We investigated the muscle pathology in 8 such cases. All had myofibre necrosis but only 3 had an inflammatory infiltrate. In all cases there was diffuse or multifocal up-regulation of MHC-I expression even in non-necrotic fibres. Progressive improvement occurred in 7 cases after commencement of prednisolone and methotrexate, and in one case spontaneously. These observations suggest that statins may initiate an immune-mediated myopathy that persists after withdrawal of the drug and responds to immunosuppressive therapy. The mechanism of this myopathy is uncertain but may involve the induction by statins of an endoplasmic reticulum stress response with associated up-regulation of MHC-I expression and antigen presentation by muscle fibres.", "entity": "Methotrexate", "aliases": "Amethopterin Dicesium Salt Methotrexate Hydrate Sodium (D)-Isomer (DL)-Isomer Disodium Mexate", "definition": "An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.\n    ", "id": "MESH:D008727"}
{"mention": "cyclic nucleotide", "mention_text": "Direct inhibition of cardiac hyperpolarization-activated cyclic nucleotide-gated pacemaker channels by clonidine.", "entity": "Nucleotides, Cyclic", "aliases": "Cyclic Nucleotides", "definition": "", "id": "MESH:D009712"}
{"mention": "clonidine", "mention_text": "Direct inhibition of cardiac hyperpolarization-activated cyclic nucleotide-gated pacemaker channels by clonidine.", "entity": "Clonidine", "aliases": "Boehringer Ingelheim Brand of Clonidine Hydrochloride Catapres Catapresan Catapressan Chlophazolin Clofelin Clofenil Dihydrochloride Monohydrobromide Monohydrochloride Clopheline Dixarit Gemiton Hemiton Isoglaucon Klofelin Klofenil M 5041T M-5041T M5041T ST 155 ST-155 ST155", "definition": "An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.\n    ", "id": "MESH:D003000"}
{"mention": "cardiovascular disease", "mention_text": "BACKGROUND: Inhibition of cardiac sympathetic tone represents an important strategy for treatment of cardiovascular disease, including arrhythmia, coronary heart disease, and chronic heart failure. Activation of presynaptic alpha2-adrenoceptors is the most widely accepted mechanism of action of the antisympathetic drug clonidine; however, other target proteins have been postulated to contribute to the in vivo actions of clonidine. METHODS AND RESULTS: To test whether clonidine elicits pharmacological effects independent of alpha2-adrenoceptors, we have generated mice with a targeted deletion of all 3 alpha2-adrenoceptor subtypes (alpha2ABC-/-). Alpha2ABC-/- mice were completely unresponsive to the analgesic and hypnotic effects of clonidine; however, clonidine significantly lowered heart rate in alpha2ABC-/- mice by up to 150 bpm. Clonidine-induced bradycardia in conscious alpha2ABC-/- mice was 32.3% (10 microg/kg) and 26.6% (100 microg/kg) of the effect in wild-type mice. A similar bradycardic effect of clonidine was observed in isolated spontaneously beating right atria from alpha2ABC-knockout and wild-type mice. Clonidine inhibited the native pacemaker current (I(f)) in isolated sinoatrial node pacemaker cells and the I(f)-generating hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 and HCN4 channels in transfected HEK293 cells. As a consequence of blocking I(f), clonidine reduced the slope of the diastolic depolarization and the frequency of pacemaker potentials in sinoatrial node cells from wild-type and alpha2ABC-knockout mice. CONCLUSIONS: Direct inhibition of cardiac HCN pacemaker channels contributes to the bradycardic effects of clonidine gene-targeted mice in vivo, and thus, clonidine-like drugs represent novel structures for future HCN channel inhibitors.", "entity": "Cardiovascular Diseases", "aliases": "Cardiovascular Disease Diseases", "definition": "Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.\n    ", "id": "MESH:D002318"}
{"mention": "arrhythmia", "mention_text": "BACKGROUND: Inhibition of cardiac sympathetic tone represents an important strategy for treatment of cardiovascular disease, including arrhythmia, coronary heart disease, and chronic heart failure. Activation of presynaptic alpha2-adrenoceptors is the most widely accepted mechanism of action of the antisympathetic drug clonidine; however, other target proteins have been postulated to contribute to the in vivo actions of clonidine. METHODS AND RESULTS: To test whether clonidine elicits pharmacological effects independent of alpha2-adrenoceptors, we have generated mice with a targeted deletion of all 3 alpha2-adrenoceptor subtypes (alpha2ABC-/-). Alpha2ABC-/- mice were completely unresponsive to the analgesic and hypnotic effects of clonidine; however, clonidine significantly lowered heart rate in alpha2ABC-/- mice by up to 150 bpm. Clonidine-induced bradycardia in conscious alpha2ABC-/- mice was 32.3% (10 microg/kg) and 26.6% (100 microg/kg) of the effect in wild-type mice. A similar bradycardic effect of clonidine was observed in isolated spontaneously beating right atria from alpha2ABC-knockout and wild-type mice. Clonidine inhibited the native pacemaker current (I(f)) in isolated sinoatrial node pacemaker cells and the I(f)-generating hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 and HCN4 channels in transfected HEK293 cells. As a consequence of blocking I(f), clonidine reduced the slope of the diastolic depolarization and the frequency of pacemaker potentials in sinoatrial node cells from wild-type and alpha2ABC-knockout mice. CONCLUSIONS: Direct inhibition of cardiac HCN pacemaker channels contributes to the bradycardic effects of clonidine gene-targeted mice in vivo, and thus, clonidine-like drugs represent novel structures for future HCN channel inhibitors.", "entity": "Arrhythmias, Cardiac", "aliases": "Arrhythmia Cardiac Arrhythmias Arrythmia Dysrhythmia", "definition": "Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.\n    ", "id": "MESH:D001145"}
{"mention": "coronary heart disease", "mention_text": "BACKGROUND: Inhibition of cardiac sympathetic tone represents an important strategy for treatment of cardiovascular disease, including arrhythmia, coronary heart disease, and chronic heart failure. Activation of presynaptic alpha2-adrenoceptors is the most widely accepted mechanism of action of the antisympathetic drug clonidine; however, other target proteins have been postulated to contribute to the in vivo actions of clonidine. METHODS AND RESULTS: To test whether clonidine elicits pharmacological effects independent of alpha2-adrenoceptors, we have generated mice with a targeted deletion of all 3 alpha2-adrenoceptor subtypes (alpha2ABC-/-). Alpha2ABC-/- mice were completely unresponsive to the analgesic and hypnotic effects of clonidine; however, clonidine significantly lowered heart rate in alpha2ABC-/- mice by up to 150 bpm. Clonidine-induced bradycardia in conscious alpha2ABC-/- mice was 32.3% (10 microg/kg) and 26.6% (100 microg/kg) of the effect in wild-type mice. A similar bradycardic effect of clonidine was observed in isolated spontaneously beating right atria from alpha2ABC-knockout and wild-type mice. Clonidine inhibited the native pacemaker current (I(f)) in isolated sinoatrial node pacemaker cells and the I(f)-generating hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 and HCN4 channels in transfected HEK293 cells. As a consequence of blocking I(f), clonidine reduced the slope of the diastolic depolarization and the frequency of pacemaker potentials in sinoatrial node cells from wild-type and alpha2ABC-knockout mice. CONCLUSIONS: Direct inhibition of cardiac HCN pacemaker channels contributes to the bradycardic effects of clonidine gene-targeted mice in vivo, and thus, clonidine-like drugs represent novel structures for future HCN channel inhibitors.", "entity": "Coronary Disease", "aliases": "Coronary Disease Diseases Heart", "definition": "An imbalance between myocardial functional requirements and the capacity of the CORONARY VESSELS to supply sufficient blood flow. It is a form of MYOCARDIAL ISCHEMIA (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels.\n    ", "id": "MESH:D003327"}
{"mention": "heart failure", "mention_text": "BACKGROUND: Inhibition of cardiac sympathetic tone represents an important strategy for treatment of cardiovascular disease, including arrhythmia, coronary heart disease, and chronic heart failure. Activation of presynaptic alpha2-adrenoceptors is the most widely accepted mechanism of action of the antisympathetic drug clonidine; however, other target proteins have been postulated to contribute to the in vivo actions of clonidine. METHODS AND RESULTS: To test whether clonidine elicits pharmacological effects independent of alpha2-adrenoceptors, we have generated mice with a targeted deletion of all 3 alpha2-adrenoceptor subtypes (alpha2ABC-/-). Alpha2ABC-/- mice were completely unresponsive to the analgesic and hypnotic effects of clonidine; however, clonidine significantly lowered heart rate in alpha2ABC-/- mice by up to 150 bpm. Clonidine-induced bradycardia in conscious alpha2ABC-/- mice was 32.3% (10 microg/kg) and 26.6% (100 microg/kg) of the effect in wild-type mice. A similar bradycardic effect of clonidine was observed in isolated spontaneously beating right atria from alpha2ABC-knockout and wild-type mice. Clonidine inhibited the native pacemaker current (I(f)) in isolated sinoatrial node pacemaker cells and the I(f)-generating hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 and HCN4 channels in transfected HEK293 cells. As a consequence of blocking I(f), clonidine reduced the slope of the diastolic depolarization and the frequency of pacemaker potentials in sinoatrial node cells from wild-type and alpha2ABC-knockout mice. CONCLUSIONS: Direct inhibition of cardiac HCN pacemaker channels contributes to the bradycardic effects of clonidine gene-targeted mice in vivo, and thus, clonidine-like drugs represent novel structures for future HCN channel inhibitors.", "entity": "Heart Failure", "aliases": "Cardiac Failure Congestive Heart Decompensation Left Sided Left-Sided Right Right-Sided Myocardial", "definition": "A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.\n    ", "id": "MESH:D006333"}
{"mention": "clonidine", "mention_text": "BACKGROUND: Inhibition of cardiac sympathetic tone represents an important strategy for treatment of cardiovascular disease, including arrhythmia, coronary heart disease, and chronic heart failure. Activation of presynaptic alpha2-adrenoceptors is the most widely accepted mechanism of action of the antisympathetic drug clonidine; however, other target proteins have been postulated to contribute to the in vivo actions of clonidine. METHODS AND RESULTS: To test whether clonidine elicits pharmacological effects independent of alpha2-adrenoceptors, we have generated mice with a targeted deletion of all 3 alpha2-adrenoceptor subtypes (alpha2ABC-/-). Alpha2ABC-/- mice were completely unresponsive to the analgesic and hypnotic effects of clonidine; however, clonidine significantly lowered heart rate in alpha2ABC-/- mice by up to 150 bpm. Clonidine-induced bradycardia in conscious alpha2ABC-/- mice was 32.3% (10 microg/kg) and 26.6% (100 microg/kg) of the effect in wild-type mice. A similar bradycardic effect of clonidine was observed in isolated spontaneously beating right atria from alpha2ABC-knockout and wild-type mice. Clonidine inhibited the native pacemaker current (I(f)) in isolated sinoatrial node pacemaker cells and the I(f)-generating hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 and HCN4 channels in transfected HEK293 cells. As a consequence of blocking I(f), clonidine reduced the slope of the diastolic depolarization and the frequency of pacemaker potentials in sinoatrial node cells from wild-type and alpha2ABC-knockout mice. CONCLUSIONS: Direct inhibition of cardiac HCN pacemaker channels contributes to the bradycardic effects of clonidine gene-targeted mice in vivo, and thus, clonidine-like drugs represent novel structures for future HCN channel inhibitors.", "entity": "Clonidine", "aliases": "Boehringer Ingelheim Brand of Clonidine Hydrochloride Catapres Catapresan Catapressan Chlophazolin Clofelin Clofenil Dihydrochloride Monohydrobromide Monohydrochloride Clopheline Dixarit Gemiton Hemiton Isoglaucon Klofelin Klofenil M 5041T M-5041T M5041T ST 155 ST-155 ST155", "definition": "An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.\n    ", "id": "MESH:D003000"}
{"mention": "Clonidine", "mention_text": "BACKGROUND: Inhibition of cardiac sympathetic tone represents an important strategy for treatment of cardiovascular disease, including arrhythmia, coronary heart disease, and chronic heart failure. Activation of presynaptic alpha2-adrenoceptors is the most widely accepted mechanism of action of the antisympathetic drug clonidine; however, other target proteins have been postulated to contribute to the in vivo actions of clonidine. METHODS AND RESULTS: To test whether clonidine elicits pharmacological effects independent of alpha2-adrenoceptors, we have generated mice with a targeted deletion of all 3 alpha2-adrenoceptor subtypes (alpha2ABC-/-). Alpha2ABC-/- mice were completely unresponsive to the analgesic and hypnotic effects of clonidine; however, clonidine significantly lowered heart rate in alpha2ABC-/- mice by up to 150 bpm. Clonidine-induced bradycardia in conscious alpha2ABC-/- mice was 32.3% (10 microg/kg) and 26.6% (100 microg/kg) of the effect in wild-type mice. A similar bradycardic effect of clonidine was observed in isolated spontaneously beating right atria from alpha2ABC-knockout and wild-type mice. Clonidine inhibited the native pacemaker current (I(f)) in isolated sinoatrial node pacemaker cells and the I(f)-generating hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 and HCN4 channels in transfected HEK293 cells. As a consequence of blocking I(f), clonidine reduced the slope of the diastolic depolarization and the frequency of pacemaker potentials in sinoatrial node cells from wild-type and alpha2ABC-knockout mice. CONCLUSIONS: Direct inhibition of cardiac HCN pacemaker channels contributes to the bradycardic effects of clonidine gene-targeted mice in vivo, and thus, clonidine-like drugs represent novel structures for future HCN channel inhibitors.", "entity": "Clonidine", "aliases": "Boehringer Ingelheim Brand of Clonidine Hydrochloride Catapres Catapresan Catapressan Chlophazolin Clofelin Clofenil Dihydrochloride Monohydrobromide Monohydrochloride Clopheline Dixarit Gemiton Hemiton Isoglaucon Klofelin Klofenil M 5041T M-5041T M5041T ST 155 ST-155 ST155", "definition": "An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.\n    ", "id": "MESH:D003000"}
{"mention": "bradycardia", "mention_text": "BACKGROUND: Inhibition of cardiac sympathetic tone represents an important strategy for treatment of cardiovascular disease, including arrhythmia, coronary heart disease, and chronic heart failure. Activation of presynaptic alpha2-adrenoceptors is the most widely accepted mechanism of action of the antisympathetic drug clonidine; however, other target proteins have been postulated to contribute to the in vivo actions of clonidine. METHODS AND RESULTS: To test whether clonidine elicits pharmacological effects independent of alpha2-adrenoceptors, we have generated mice with a targeted deletion of all 3 alpha2-adrenoceptor subtypes (alpha2ABC-/-). Alpha2ABC-/- mice were completely unresponsive to the analgesic and hypnotic effects of clonidine; however, clonidine significantly lowered heart rate in alpha2ABC-/- mice by up to 150 bpm. Clonidine-induced bradycardia in conscious alpha2ABC-/- mice was 32.3% (10 microg/kg) and 26.6% (100 microg/kg) of the effect in wild-type mice. A similar bradycardic effect of clonidine was observed in isolated spontaneously beating right atria from alpha2ABC-knockout and wild-type mice. Clonidine inhibited the native pacemaker current (I(f)) in isolated sinoatrial node pacemaker cells and the I(f)-generating hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 and HCN4 channels in transfected HEK293 cells. As a consequence of blocking I(f), clonidine reduced the slope of the diastolic depolarization and the frequency of pacemaker potentials in sinoatrial node cells from wild-type and alpha2ABC-knockout mice. CONCLUSIONS: Direct inhibition of cardiac HCN pacemaker channels contributes to the bradycardic effects of clonidine gene-targeted mice in vivo, and thus, clonidine-like drugs represent novel structures for future HCN channel inhibitors.", "entity": "Bradycardia", "aliases": "Bradyarrhythmia Bradyarrhythmias Bradycardia Bradycardias", "definition": "Cardiac arrhythmias that are characterized by excessively slow HEART RATE, usually below 50 beats per minute in human adults. They can be classified broadly into SINOATRIAL NODE dysfunction and ATRIOVENTRICULAR BLOCK.\n    ", "id": "MESH:D001919"}
{"mention": "cyclic nucleotide", "mention_text": "BACKGROUND: Inhibition of cardiac sympathetic tone represents an important strategy for treatment of cardiovascular disease, including arrhythmia, coronary heart disease, and chronic heart failure. Activation of presynaptic alpha2-adrenoceptors is the most widely accepted mechanism of action of the antisympathetic drug clonidine; however, other target proteins have been postulated to contribute to the in vivo actions of clonidine. METHODS AND RESULTS: To test whether clonidine elicits pharmacological effects independent of alpha2-adrenoceptors, we have generated mice with a targeted deletion of all 3 alpha2-adrenoceptor subtypes (alpha2ABC-/-). Alpha2ABC-/- mice were completely unresponsive to the analgesic and hypnotic effects of clonidine; however, clonidine significantly lowered heart rate in alpha2ABC-/- mice by up to 150 bpm. Clonidine-induced bradycardia in conscious alpha2ABC-/- mice was 32.3% (10 microg/kg) and 26.6% (100 microg/kg) of the effect in wild-type mice. A similar bradycardic effect of clonidine was observed in isolated spontaneously beating right atria from alpha2ABC-knockout and wild-type mice. Clonidine inhibited the native pacemaker current (I(f)) in isolated sinoatrial node pacemaker cells and the I(f)-generating hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 and HCN4 channels in transfected HEK293 cells. As a consequence of blocking I(f), clonidine reduced the slope of the diastolic depolarization and the frequency of pacemaker potentials in sinoatrial node cells from wild-type and alpha2ABC-knockout mice. CONCLUSIONS: Direct inhibition of cardiac HCN pacemaker channels contributes to the bradycardic effects of clonidine gene-targeted mice in vivo, and thus, clonidine-like drugs represent novel structures for future HCN channel inhibitors.", "entity": "Nucleotides, Cyclic", "aliases": "Cyclic Nucleotides", "definition": "", "id": "MESH:D009712"}
{"mention": "smoking", "mention_text": "Influence of smoking on developing cochlea. Does smoking during pregnancy affect the amplitudes of transient evoked otoacoustic emissions in newborns?", "entity": "Smoke", "aliases": "Smoke Smokes", "definition": "", "id": "MESH:D012906"}
{"mention": "smoking", "mention_text": "OBJECTIVE: Maternal tobacco smoking has negative effects on fetal growth. The influence of smoking during pregnancy on the developing cochlea has not been estimated, although smoking has been positively associated with hearing loss in adults. The objective of this study was to determine the effects of maternal smoking on transient evoked otoacoustic emissions (TEOAEs) of healthy neonates. METHODS: This study was undertaken as part of neonatal screening for hearing impairment and involved both ears of 200 newborns. Newborns whose mothers reported smoking during pregnancy (n=200 ears) were compared to a control group of newborns (n=200 ears), whose mothers were non-smokers. Exposure to tobacco was characterized as low (<5 cigarettes per day, n=88 ears), moderate (5< or =cigarettes per day<10, n=76) or high (> or =10 cigarettes per day, n=36). RESULTS: In exposed neonates, TEOAEs mean response (across frequency) and mean amplitude at 4000Hz was significantly lower than in non-exposed neonates. Comparisons between exposed newborns' subgroups revealed no significant differences. However, by comparing each subgroup to control group, we found statistically significant decreases of TEOAEs amplitudes at 4000Hz for all three groups. Mean TEOAEs responses of highly exposed newborns were also significantly lower in comparison to our control group. CONCLUSION: In utero, exposure to tobacco smoking seems to have a small impact on outer hair cells. These effects seem to be equally true for all exposed newborns, regardless of the degree of exposure. Further studies are needed in order to establish a potential negative effect of maternal smoking on the neonate's hearing acuity.", "entity": "Smoke", "aliases": "Smoke Smokes", "definition": "", "id": "MESH:D012906"}
{"mention": "hearing loss", "mention_text": "OBJECTIVE: Maternal tobacco smoking has negative effects on fetal growth. The influence of smoking during pregnancy on the developing cochlea has not been estimated, although smoking has been positively associated with hearing loss in adults. The objective of this study was to determine the effects of maternal smoking on transient evoked otoacoustic emissions (TEOAEs) of healthy neonates. METHODS: This study was undertaken as part of neonatal screening for hearing impairment and involved both ears of 200 newborns. Newborns whose mothers reported smoking during pregnancy (n=200 ears) were compared to a control group of newborns (n=200 ears), whose mothers were non-smokers. Exposure to tobacco was characterized as low (<5 cigarettes per day, n=88 ears), moderate (5< or =cigarettes per day<10, n=76) or high (> or =10 cigarettes per day, n=36). RESULTS: In exposed neonates, TEOAEs mean response (across frequency) and mean amplitude at 4000Hz was significantly lower than in non-exposed neonates. Comparisons between exposed newborns' subgroups revealed no significant differences. However, by comparing each subgroup to control group, we found statistically significant decreases of TEOAEs amplitudes at 4000Hz for all three groups. Mean TEOAEs responses of highly exposed newborns were also significantly lower in comparison to our control group. CONCLUSION: In utero, exposure to tobacco smoking seems to have a small impact on outer hair cells. These effects seem to be equally true for all exposed newborns, regardless of the degree of exposure. Further studies are needed in order to establish a potential negative effect of maternal smoking on the neonate's hearing acuity.", "entity": "Hearing Loss", "aliases": "Hearing Impairment Loss Hypoacuses Hypoacusis", "definition": "A general term for the complete or partial loss of the ability to hear from one or both ears.\n    ", "id": "MESH:D034381"}
{"mention": "hearing impairment", "mention_text": "OBJECTIVE: Maternal tobacco smoking has negative effects on fetal growth. The influence of smoking during pregnancy on the developing cochlea has not been estimated, although smoking has been positively associated with hearing loss in adults. The objective of this study was to determine the effects of maternal smoking on transient evoked otoacoustic emissions (TEOAEs) of healthy neonates. METHODS: This study was undertaken as part of neonatal screening for hearing impairment and involved both ears of 200 newborns. Newborns whose mothers reported smoking during pregnancy (n=200 ears) were compared to a control group of newborns (n=200 ears), whose mothers were non-smokers. Exposure to tobacco was characterized as low (<5 cigarettes per day, n=88 ears), moderate (5< or =cigarettes per day<10, n=76) or high (> or =10 cigarettes per day, n=36). RESULTS: In exposed neonates, TEOAEs mean response (across frequency) and mean amplitude at 4000Hz was significantly lower than in non-exposed neonates. Comparisons between exposed newborns' subgroups revealed no significant differences. However, by comparing each subgroup to control group, we found statistically significant decreases of TEOAEs amplitudes at 4000Hz for all three groups. Mean TEOAEs responses of highly exposed newborns were also significantly lower in comparison to our control group. CONCLUSION: In utero, exposure to tobacco smoking seems to have a small impact on outer hair cells. These effects seem to be equally true for all exposed newborns, regardless of the degree of exposure. Further studies are needed in order to establish a potential negative effect of maternal smoking on the neonate's hearing acuity.", "entity": "Hearing Loss", "aliases": "Hearing Impairment Loss Hypoacuses Hypoacusis", "definition": "A general term for the complete or partial loss of the ability to hear from one or both ears.\n    ", "id": "MESH:D034381"}
{"mention": "Neuroinflammation", "mention_text": "Neuroinflammation and behavioral abnormalities after neonatal terbutaline treatment in rats: implications for autism.", "entity": "Neurogenic Inflammation", "aliases": "Inflammation Neurogenic Inflammations", "definition": "Inflammation caused by an injurious stimulus of peripheral neurons and resulting in release of neuropeptides which affect vascular permeability and help initiate proinflammatory and immune reactions at the site of injury.\n    ", "id": "MESH:D020078"}
{"mention": "behavioral abnormalities", "mention_text": "Neuroinflammation and behavioral abnormalities after neonatal terbutaline treatment in rats: implications for autism.", "entity": "Mental Disorders", "aliases": "Behavior Disorders Diagnosis Psychiatric Disorder Mental", "definition": "Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.\n    ", "id": "MESH:D001523"}
{"mention": "terbutaline", "mention_text": "Neuroinflammation and behavioral abnormalities after neonatal terbutaline treatment in rats: implications for autism.", "entity": "Terbutaline", "aliases": "Aliud Brand of Terbutaline Sulfate Alpharma Arubendol Asthmoprotect AstraZeneca Azupharma Brethaire Brethine Bricanyl SA Butaliret Butalitab Contimit Dermapharm Estedi Fatol Hexal Hoechst KWD 2019 KWD-2019 KWD2019 Kendrick Lagap Lindopharm Monovent Novartis Stadapharm Taziken Tedipulmo Terbasmin Terbul Terbutalin AL Stada ratiopharm Terbutalin-ratiopharm Terbuturmant ct Arzneimittel ct-Arzneimittel pharma-stern terbutalin von", "definition": "A selective beta-2 adrenergic agonist used as a bronchodilator and tocolytic.\n    ", "id": "MESH:D013726"}
{"mention": "autism", "mention_text": "Neuroinflammation and behavioral abnormalities after neonatal terbutaline treatment in rats: implications for autism.", "entity": "Autistic Disorder", "aliases": "Autism Early Infantile Autisms Autistic Disorder Disorders Kanner Syndrome Kanner's Kanners", "definition": "A disorder beginning in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual. (DSM-IV)\n    ", "id": "MESH:D001321"}
{"mention": "Autism", "mention_text": "Autism is a neurodevelopmental disorder presenting before 3 years of age with deficits in communication and social skills and repetitive behaviors. In addition to genetic influences, recent studies suggest that prenatal drug or chemical exposures are risk factors for autism. Terbutaline, a beta2-adrenoceptor agonist used to arrest preterm labor, has been associated with increased concordance for autism in dizygotic twins. We studied the effects of terbutaline on microglial activation in different brain regions and behavioral outcomes in developing rats. Newborn rats were given terbutaline (10 mg/kg) daily on postnatal days (PN) 2 to 5 or PN 11 to 14 and examined 24 h after the last dose and at PN 30. Immunohistochemical studies showed that administration of terbutaline on PN 2 to 5 produced a robust increase in microglial activation on PN 30 in the cerebral cortex, as well as in cerebellar and cerebrocortical white matter. None of these effects occurred in animals given terbutaline on PN 11 to 14. In behavioral tests, animals treated with terbutaline on PN 2 to 5 showed consistent patterns of hyper-reactivity to novelty and aversive stimuli when assessed in a novel open field, as well as in the acoustic startle response test. Our findings indicate that beta2-adrenoceptor overstimulation during an early critical period results in microglial activation associated with innate neuroinflammatory pathways and behavioral abnormalities, similar to those described in autism. This study provides a useful animal model for understanding the neuropathological processes underlying autism spectrum disorders.", "entity": "Autistic Disorder", "aliases": "Autism Early Infantile Autisms Autistic Disorder Disorders Kanner Syndrome Kanner's Kanners", "definition": "A disorder beginning in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual. (DSM-IV)\n    ", "id": "MESH:D001321"}
{"mention": "neurodevelopmental disorder", "mention_text": "Autism is a neurodevelopmental disorder presenting before 3 years of age with deficits in communication and social skills and repetitive behaviors. In addition to genetic influences, recent studies suggest that prenatal drug or chemical exposures are risk factors for autism. Terbutaline, a beta2-adrenoceptor agonist used to arrest preterm labor, has been associated with increased concordance for autism in dizygotic twins. We studied the effects of terbutaline on microglial activation in different brain regions and behavioral outcomes in developing rats. Newborn rats were given terbutaline (10 mg/kg) daily on postnatal days (PN) 2 to 5 or PN 11 to 14 and examined 24 h after the last dose and at PN 30. Immunohistochemical studies showed that administration of terbutaline on PN 2 to 5 produced a robust increase in microglial activation on PN 30 in the cerebral cortex, as well as in cerebellar and cerebrocortical white matter. None of these effects occurred in animals given terbutaline on PN 11 to 14. In behavioral tests, animals treated with terbutaline on PN 2 to 5 showed consistent patterns of hyper-reactivity to novelty and aversive stimuli when assessed in a novel open field, as well as in the acoustic startle response test. Our findings indicate that beta2-adrenoceptor overstimulation during an early critical period results in microglial activation associated with innate neuroinflammatory pathways and behavioral abnormalities, similar to those described in autism. This study provides a useful animal model for understanding the neuropathological processes underlying autism spectrum disorders.", "entity": "Developmental Disabilities", "aliases": "Child Development Deviation Deviations Disorder Disorders Specific Developmental Delay Disabilities Disability", "definition": "Disorders in which there is a delay in development based on that expected for a given age level or stage of development. These impairments or disabilities originate before age 18, may be expected to continue indefinitely, and constitute a substantial impairment. Biological and nonbiological factors are involved in these disorders. (From American Psychiatric Glossary, 6th ed)\n    ", "id": "MESH:D002658"}
{"mention": "deficits in communication and social skills", "mention_text": "Autism is a neurodevelopmental disorder presenting before 3 years of age with deficits in communication and social skills and repetitive behaviors. In addition to genetic influences, recent studies suggest that prenatal drug or chemical exposures are risk factors for autism. Terbutaline, a beta2-adrenoceptor agonist used to arrest preterm labor, has been associated with increased concordance for autism in dizygotic twins. We studied the effects of terbutaline on microglial activation in different brain regions and behavioral outcomes in developing rats. Newborn rats were given terbutaline (10 mg/kg) daily on postnatal days (PN) 2 to 5 or PN 11 to 14 and examined 24 h after the last dose and at PN 30. Immunohistochemical studies showed that administration of terbutaline on PN 2 to 5 produced a robust increase in microglial activation on PN 30 in the cerebral cortex, as well as in cerebellar and cerebrocortical white matter. None of these effects occurred in animals given terbutaline on PN 11 to 14. In behavioral tests, animals treated with terbutaline on PN 2 to 5 showed consistent patterns of hyper-reactivity to novelty and aversive stimuli when assessed in a novel open field, as well as in the acoustic startle response test. Our findings indicate that beta2-adrenoceptor overstimulation during an early critical period results in microglial activation associated with innate neuroinflammatory pathways and behavioral abnormalities, similar to those described in autism. This study provides a useful animal model for understanding the neuropathological processes underlying autism spectrum disorders.", "entity": "Communication Disorders", "aliases": "Acquired Communication Disorder Disorders Childhood Disabilities Disability Developmental Neurogenic Communicative Dysfunction Dysfunctions", "definition": "Disorders of verbal and nonverbal communication caused by receptive or expressive LANGUAGE DISORDERS, cognitive dysfunction (e.g., MENTAL RETARDATION), psychiatric conditions, and HEARING DISORDERS.\n    ", "id": "MESH:D003147"}
{"mention": "repetitive behaviors", "mention_text": "Autism is a neurodevelopmental disorder presenting before 3 years of age with deficits in communication and social skills and repetitive behaviors. In addition to genetic influences, recent studies suggest that prenatal drug or chemical exposures are risk factors for autism. Terbutaline, a beta2-adrenoceptor agonist used to arrest preterm labor, has been associated with increased concordance for autism in dizygotic twins. We studied the effects of terbutaline on microglial activation in different brain regions and behavioral outcomes in developing rats. Newborn rats were given terbutaline (10 mg/kg) daily on postnatal days (PN) 2 to 5 or PN 11 to 14 and examined 24 h after the last dose and at PN 30. Immunohistochemical studies showed that administration of terbutaline on PN 2 to 5 produced a robust increase in microglial activation on PN 30 in the cerebral cortex, as well as in cerebellar and cerebrocortical white matter. None of these effects occurred in animals given terbutaline on PN 11 to 14. In behavioral tests, animals treated with terbutaline on PN 2 to 5 showed consistent patterns of hyper-reactivity to novelty and aversive stimuli when assessed in a novel open field, as well as in the acoustic startle response test. Our findings indicate that beta2-adrenoceptor overstimulation during an early critical period results in microglial activation associated with innate neuroinflammatory pathways and behavioral abnormalities, similar to those described in autism. This study provides a useful animal model for understanding the neuropathological processes underlying autism spectrum disorders.", "entity": "Mental Disorders", "aliases": "Behavior Disorders Diagnosis Psychiatric Disorder Mental", "definition": "Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.\n    ", "id": "MESH:D001523"}
{"mention": "autism", "mention_text": "Autism is a neurodevelopmental disorder presenting before 3 years of age with deficits in communication and social skills and repetitive behaviors. In addition to genetic influences, recent studies suggest that prenatal drug or chemical exposures are risk factors for autism. Terbutaline, a beta2-adrenoceptor agonist used to arrest preterm labor, has been associated with increased concordance for autism in dizygotic twins. We studied the effects of terbutaline on microglial activation in different brain regions and behavioral outcomes in developing rats. Newborn rats were given terbutaline (10 mg/kg) daily on postnatal days (PN) 2 to 5 or PN 11 to 14 and examined 24 h after the last dose and at PN 30. Immunohistochemical studies showed that administration of terbutaline on PN 2 to 5 produced a robust increase in microglial activation on PN 30 in the cerebral cortex, as well as in cerebellar and cerebrocortical white matter. None of these effects occurred in animals given terbutaline on PN 11 to 14. In behavioral tests, animals treated with terbutaline on PN 2 to 5 showed consistent patterns of hyper-reactivity to novelty and aversive stimuli when assessed in a novel open field, as well as in the acoustic startle response test. Our findings indicate that beta2-adrenoceptor overstimulation during an early critical period results in microglial activation associated with innate neuroinflammatory pathways and behavioral abnormalities, similar to those described in autism. This study provides a useful animal model for understanding the neuropathological processes underlying autism spectrum disorders.", "entity": "Autistic Disorder", "aliases": "Autism Early Infantile Autisms Autistic Disorder Disorders Kanner Syndrome Kanner's Kanners", "definition": "A disorder beginning in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual. (DSM-IV)\n    ", "id": "MESH:D001321"}
{"mention": "Terbutaline", "mention_text": "Autism is a neurodevelopmental disorder presenting before 3 years of age with deficits in communication and social skills and repetitive behaviors. In addition to genetic influences, recent studies suggest that prenatal drug or chemical exposures are risk factors for autism. Terbutaline, a beta2-adrenoceptor agonist used to arrest preterm labor, has been associated with increased concordance for autism in dizygotic twins. We studied the effects of terbutaline on microglial activation in different brain regions and behavioral outcomes in developing rats. Newborn rats were given terbutaline (10 mg/kg) daily on postnatal days (PN) 2 to 5 or PN 11 to 14 and examined 24 h after the last dose and at PN 30. Immunohistochemical studies showed that administration of terbutaline on PN 2 to 5 produced a robust increase in microglial activation on PN 30 in the cerebral cortex, as well as in cerebellar and cerebrocortical white matter. None of these effects occurred in animals given terbutaline on PN 11 to 14. In behavioral tests, animals treated with terbutaline on PN 2 to 5 showed consistent patterns of hyper-reactivity to novelty and aversive stimuli when assessed in a novel open field, as well as in the acoustic startle response test. Our findings indicate that beta2-adrenoceptor overstimulation during an early critical period results in microglial activation associated with innate neuroinflammatory pathways and behavioral abnormalities, similar to those described in autism. This study provides a useful animal model for understanding the neuropathological processes underlying autism spectrum disorders.", "entity": "Terbutaline", "aliases": "Aliud Brand of Terbutaline Sulfate Alpharma Arubendol Asthmoprotect AstraZeneca Azupharma Brethaire Brethine Bricanyl SA Butaliret Butalitab Contimit Dermapharm Estedi Fatol Hexal Hoechst KWD 2019 KWD-2019 KWD2019 Kendrick Lagap Lindopharm Monovent Novartis Stadapharm Taziken Tedipulmo Terbasmin Terbul Terbutalin AL Stada ratiopharm Terbutalin-ratiopharm Terbuturmant ct Arzneimittel ct-Arzneimittel pharma-stern terbutalin von", "definition": "A selective beta-2 adrenergic agonist used as a bronchodilator and tocolytic.\n    ", "id": "MESH:D013726"}
{"mention": "preterm labor", "mention_text": "Autism is a neurodevelopmental disorder presenting before 3 years of age with deficits in communication and social skills and repetitive behaviors. In addition to genetic influences, recent studies suggest that prenatal drug or chemical exposures are risk factors for autism. Terbutaline, a beta2-adrenoceptor agonist used to arrest preterm labor, has been associated with increased concordance for autism in dizygotic twins. We studied the effects of terbutaline on microglial activation in different brain regions and behavioral outcomes in developing rats. Newborn rats were given terbutaline (10 mg/kg) daily on postnatal days (PN) 2 to 5 or PN 11 to 14 and examined 24 h after the last dose and at PN 30. Immunohistochemical studies showed that administration of terbutaline on PN 2 to 5 produced a robust increase in microglial activation on PN 30 in the cerebral cortex, as well as in cerebellar and cerebrocortical white matter. None of these effects occurred in animals given terbutaline on PN 11 to 14. In behavioral tests, animals treated with terbutaline on PN 2 to 5 showed consistent patterns of hyper-reactivity to novelty and aversive stimuli when assessed in a novel open field, as well as in the acoustic startle response test. Our findings indicate that beta2-adrenoceptor overstimulation during an early critical period results in microglial activation associated with innate neuroinflammatory pathways and behavioral abnormalities, similar to those described in autism. This study provides a useful animal model for understanding the neuropathological processes underlying autism spectrum disorders.", "entity": "Obstetric Labor, Premature", "aliases": "Labor Premature Obstetric Preterm", "definition": "Onset of OBSTETRIC LABOR before term (TERM BIRTH) but usually after the FETUS has become viable. In humans, it occurs sometime during the 29th through 38th week of PREGNANCY. TOCOLYSIS inhibits premature labor and can prevent the BIRTH of premature infants (INFANT, PREMATURE).\n    ", "id": "MESH:D007752"}
{"mention": "terbutaline", "mention_text": "Autism is a neurodevelopmental disorder presenting before 3 years of age with deficits in communication and social skills and repetitive behaviors. In addition to genetic influences, recent studies suggest that prenatal drug or chemical exposures are risk factors for autism. Terbutaline, a beta2-adrenoceptor agonist used to arrest preterm labor, has been associated with increased concordance for autism in dizygotic twins. We studied the effects of terbutaline on microglial activation in different brain regions and behavioral outcomes in developing rats. Newborn rats were given terbutaline (10 mg/kg) daily on postnatal days (PN) 2 to 5 or PN 11 to 14 and examined 24 h after the last dose and at PN 30. Immunohistochemical studies showed that administration of terbutaline on PN 2 to 5 produced a robust increase in microglial activation on PN 30 in the cerebral cortex, as well as in cerebellar and cerebrocortical white matter. None of these effects occurred in animals given terbutaline on PN 11 to 14. In behavioral tests, animals treated with terbutaline on PN 2 to 5 showed consistent patterns of hyper-reactivity to novelty and aversive stimuli when assessed in a novel open field, as well as in the acoustic startle response test. Our findings indicate that beta2-adrenoceptor overstimulation during an early critical period results in microglial activation associated with innate neuroinflammatory pathways and behavioral abnormalities, similar to those described in autism. This study provides a useful animal model for understanding the neuropathological processes underlying autism spectrum disorders.", "entity": "Terbutaline", "aliases": "Aliud Brand of Terbutaline Sulfate Alpharma Arubendol Asthmoprotect AstraZeneca Azupharma Brethaire Brethine Bricanyl SA Butaliret Butalitab Contimit Dermapharm Estedi Fatol Hexal Hoechst KWD 2019 KWD-2019 KWD2019 Kendrick Lagap Lindopharm Monovent Novartis Stadapharm Taziken Tedipulmo Terbasmin Terbul Terbutalin AL Stada ratiopharm Terbutalin-ratiopharm Terbuturmant ct Arzneimittel ct-Arzneimittel pharma-stern terbutalin von", "definition": "A selective beta-2 adrenergic agonist used as a bronchodilator and tocolytic.\n    ", "id": "MESH:D013726"}
{"mention": "behavioral abnormalities", "mention_text": "Autism is a neurodevelopmental disorder presenting before 3 years of age with deficits in communication and social skills and repetitive behaviors. In addition to genetic influences, recent studies suggest that prenatal drug or chemical exposures are risk factors for autism. Terbutaline, a beta2-adrenoceptor agonist used to arrest preterm labor, has been associated with increased concordance for autism in dizygotic twins. We studied the effects of terbutaline on microglial activation in different brain regions and behavioral outcomes in developing rats. Newborn rats were given terbutaline (10 mg/kg) daily on postnatal days (PN) 2 to 5 or PN 11 to 14 and examined 24 h after the last dose and at PN 30. Immunohistochemical studies showed that administration of terbutaline on PN 2 to 5 produced a robust increase in microglial activation on PN 30 in the cerebral cortex, as well as in cerebellar and cerebrocortical white matter. None of these effects occurred in animals given terbutaline on PN 11 to 14. In behavioral tests, animals treated with terbutaline on PN 2 to 5 showed consistent patterns of hyper-reactivity to novelty and aversive stimuli when assessed in a novel open field, as well as in the acoustic startle response test. Our findings indicate that beta2-adrenoceptor overstimulation during an early critical period results in microglial activation associated with innate neuroinflammatory pathways and behavioral abnormalities, similar to those described in autism. This study provides a useful animal model for understanding the neuropathological processes underlying autism spectrum disorders.", "entity": "Mental Disorders", "aliases": "Behavior Disorders Diagnosis Psychiatric Disorder Mental", "definition": "Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.\n    ", "id": "MESH:D001523"}
{"mention": "autism spectrum disorders", "mention_text": "Autism is a neurodevelopmental disorder presenting before 3 years of age with deficits in communication and social skills and repetitive behaviors. In addition to genetic influences, recent studies suggest that prenatal drug or chemical exposures are risk factors for autism. Terbutaline, a beta2-adrenoceptor agonist used to arrest preterm labor, has been associated with increased concordance for autism in dizygotic twins. We studied the effects of terbutaline on microglial activation in different brain regions and behavioral outcomes in developing rats. Newborn rats were given terbutaline (10 mg/kg) daily on postnatal days (PN) 2 to 5 or PN 11 to 14 and examined 24 h after the last dose and at PN 30. Immunohistochemical studies showed that administration of terbutaline on PN 2 to 5 produced a robust increase in microglial activation on PN 30 in the cerebral cortex, as well as in cerebellar and cerebrocortical white matter. None of these effects occurred in animals given terbutaline on PN 11 to 14. In behavioral tests, animals treated with terbutaline on PN 2 to 5 showed consistent patterns of hyper-reactivity to novelty and aversive stimuli when assessed in a novel open field, as well as in the acoustic startle response test. Our findings indicate that beta2-adrenoceptor overstimulation during an early critical period results in microglial activation associated with innate neuroinflammatory pathways and behavioral abnormalities, similar to those described in autism. This study provides a useful animal model for understanding the neuropathological processes underlying autism spectrum disorders.", "entity": "Child Development Disorders, Pervasive", "aliases": "Autism Spectrum Disorder Disorders Child Development Pervasive", "definition": "Severe distortions in the development of many basic psychological functions that are not normal for any stage in development. These distortions are manifested in sustained social impairment, speech abnormalities, and peculiar motor movements.\n    ", "id": "MESH:D002659"}
{"mention": "myocarditis", "mention_text": "Acute myocarditis associated with clozapine.", "entity": "Myocarditis", "aliases": "Carditis Myocarditides Myocarditis", "definition": "Inflammatory processes of the muscular walls of the heart (MYOCARDIUM) which result in injury to the cardiac muscle cells (MYOCYTES, CARDIAC). Manifestations range from subclinical to sudden death (DEATH, SUDDEN). Myocarditis in association with cardiac dysfunction is classified as inflammatory CARDIOMYOPATHY usually caused by INFECTION, autoimmune diseases, or responses to toxic substances. Myocarditis is also a common cause of DILATED CARDIOMYOPATHY and other cardiomyopathies.\n    ", "id": "MESH:D009205"}
{"mention": "clozapine", "mention_text": "Acute myocarditis associated with clozapine.", "entity": "Clozapine", "aliases": "Clozapine Clozaril Leponex", "definition": "A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.\n    ", "id": "MESH:D003024"}
{"mention": "myocarditis", "mention_text": "OBJECTIVE: A case of acute myocarditis associated with the commencement of clozapine is described, highlighting the onset, course and possible contributing factors. There is an urgent need to raise awareness about this potentially fatal complication of clozapine use. RESULTS: A 20-year-old male with schizophrenia developed a sudden onset of myocarditis after commencement of clozapine. The patient recovered with intensive medical support. The symptoms occurred around 2 weeks after starting clozapine in an inpatient setting. Possible contributing factors may have been concomitant antidepressant use and unaccustomed physical activity. CONCLUSIONS: Myocarditis is an increasingly recognized complication associated with the use of clozapine. It can be fatal if not recognized and treated early. Considering that clozapine remains the gold standard in treatment of resistant psychosis, there is an urgent need to raise awareness among medical and paramedical staff involved in the care of these patients. There are also implications for recommendations and regulations regarding the use of clozapine.", "entity": "Myocarditis", "aliases": "Carditis Myocarditides Myocarditis", "definition": "Inflammatory processes of the muscular walls of the heart (MYOCARDIUM) which result in injury to the cardiac muscle cells (MYOCYTES, CARDIAC). Manifestations range from subclinical to sudden death (DEATH, SUDDEN). Myocarditis in association with cardiac dysfunction is classified as inflammatory CARDIOMYOPATHY usually caused by INFECTION, autoimmune diseases, or responses to toxic substances. Myocarditis is also a common cause of DILATED CARDIOMYOPATHY and other cardiomyopathies.\n    ", "id": "MESH:D009205"}
{"mention": "clozapine", "mention_text": "OBJECTIVE: A case of acute myocarditis associated with the commencement of clozapine is described, highlighting the onset, course and possible contributing factors. There is an urgent need to raise awareness about this potentially fatal complication of clozapine use. RESULTS: A 20-year-old male with schizophrenia developed a sudden onset of myocarditis after commencement of clozapine. The patient recovered with intensive medical support. The symptoms occurred around 2 weeks after starting clozapine in an inpatient setting. Possible contributing factors may have been concomitant antidepressant use and unaccustomed physical activity. CONCLUSIONS: Myocarditis is an increasingly recognized complication associated with the use of clozapine. It can be fatal if not recognized and treated early. Considering that clozapine remains the gold standard in treatment of resistant psychosis, there is an urgent need to raise awareness among medical and paramedical staff involved in the care of these patients. There are also implications for recommendations and regulations regarding the use of clozapine.", "entity": "Clozapine", "aliases": "Clozapine Clozaril Leponex", "definition": "A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.\n    ", "id": "MESH:D003024"}
{"mention": "schizophrenia", "mention_text": "OBJECTIVE: A case of acute myocarditis associated with the commencement of clozapine is described, highlighting the onset, course and possible contributing factors. There is an urgent need to raise awareness about this potentially fatal complication of clozapine use. RESULTS: A 20-year-old male with schizophrenia developed a sudden onset of myocarditis after commencement of clozapine. The patient recovered with intensive medical support. The symptoms occurred around 2 weeks after starting clozapine in an inpatient setting. Possible contributing factors may have been concomitant antidepressant use and unaccustomed physical activity. CONCLUSIONS: Myocarditis is an increasingly recognized complication associated with the use of clozapine. It can be fatal if not recognized and treated early. Considering that clozapine remains the gold standard in treatment of resistant psychosis, there is an urgent need to raise awareness among medical and paramedical staff involved in the care of these patients. There are also implications for recommendations and regulations regarding the use of clozapine.", "entity": "Schizophrenia", "aliases": "Dementia Praecox Disorder Schizophrenic Disorders Schizophrenia Schizophrenias", "definition": "A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior.\n    ", "id": "MESH:D012559"}
{"mention": "antidepressant", "mention_text": "OBJECTIVE: A case of acute myocarditis associated with the commencement of clozapine is described, highlighting the onset, course and possible contributing factors. There is an urgent need to raise awareness about this potentially fatal complication of clozapine use. RESULTS: A 20-year-old male with schizophrenia developed a sudden onset of myocarditis after commencement of clozapine. The patient recovered with intensive medical support. The symptoms occurred around 2 weeks after starting clozapine in an inpatient setting. Possible contributing factors may have been concomitant antidepressant use and unaccustomed physical activity. CONCLUSIONS: Myocarditis is an increasingly recognized complication associated with the use of clozapine. It can be fatal if not recognized and treated early. Considering that clozapine remains the gold standard in treatment of resistant psychosis, there is an urgent need to raise awareness among medical and paramedical staff involved in the care of these patients. There are also implications for recommendations and regulations regarding the use of clozapine.", "entity": "Antidepressive Agents", "aliases": "Agents Antidepressive Antidepressant Drugs Antidepressants Thymoanaleptics Thymoleptics", "definition": "Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.\n    ", "id": "MESH:D000928"}
{"mention": "Myocarditis", "mention_text": "OBJECTIVE: A case of acute myocarditis associated with the commencement of clozapine is described, highlighting the onset, course and possible contributing factors. There is an urgent need to raise awareness about this potentially fatal complication of clozapine use. RESULTS: A 20-year-old male with schizophrenia developed a sudden onset of myocarditis after commencement of clozapine. The patient recovered with intensive medical support. The symptoms occurred around 2 weeks after starting clozapine in an inpatient setting. Possible contributing factors may have been concomitant antidepressant use and unaccustomed physical activity. CONCLUSIONS: Myocarditis is an increasingly recognized complication associated with the use of clozapine. It can be fatal if not recognized and treated early. Considering that clozapine remains the gold standard in treatment of resistant psychosis, there is an urgent need to raise awareness among medical and paramedical staff involved in the care of these patients. There are also implications for recommendations and regulations regarding the use of clozapine.", "entity": "Myocarditis", "aliases": "Carditis Myocarditides Myocarditis", "definition": "Inflammatory processes of the muscular walls of the heart (MYOCARDIUM) which result in injury to the cardiac muscle cells (MYOCYTES, CARDIAC). Manifestations range from subclinical to sudden death (DEATH, SUDDEN). Myocarditis in association with cardiac dysfunction is classified as inflammatory CARDIOMYOPATHY usually caused by INFECTION, autoimmune diseases, or responses to toxic substances. Myocarditis is also a common cause of DILATED CARDIOMYOPATHY and other cardiomyopathies.\n    ", "id": "MESH:D009205"}
{"mention": "psychosis", "mention_text": "OBJECTIVE: A case of acute myocarditis associated with the commencement of clozapine is described, highlighting the onset, course and possible contributing factors. There is an urgent need to raise awareness about this potentially fatal complication of clozapine use. RESULTS: A 20-year-old male with schizophrenia developed a sudden onset of myocarditis after commencement of clozapine. The patient recovered with intensive medical support. The symptoms occurred around 2 weeks after starting clozapine in an inpatient setting. Possible contributing factors may have been concomitant antidepressant use and unaccustomed physical activity. CONCLUSIONS: Myocarditis is an increasingly recognized complication associated with the use of clozapine. It can be fatal if not recognized and treated early. Considering that clozapine remains the gold standard in treatment of resistant psychosis, there is an urgent need to raise awareness among medical and paramedical staff involved in the care of these patients. There are also implications for recommendations and regulations regarding the use of clozapine.", "entity": "Psychotic Disorders", "aliases": "Brief Reactive Psychoses Psychosis Disorder Psychotic Schizoaffective Schizophreniform Disorders", "definition": "Disorders in which there is a loss of ego boundaries or a gross impairment in reality testing with delusions or prominent hallucinations. (From DSM-IV, 1994)\n    ", "id": "MESH:D011618"}
{"mention": "Encephalopathy", "mention_text": "Encephalopathy induced by levetiracetam added to valproate.", "entity": "Brain Diseases", "aliases": "Brain Disease Diseases Disorder Disorders CNS Intracranial Central Nervous System Encephalon", "definition": "Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.\n    ", "id": "MESH:D001927"}
{"mention": "levetiracetam", "mention_text": "Encephalopathy induced by levetiracetam added to valproate.", "entity": "etiracetam", "aliases": "Keppra UCB 6474 Brand of Levetiracetam UCB-6474 alpha-ethyl-2-oxo-1-pyrrolidineacetamide etiracetam R-isomer S-isomer levetiracetam ucb L059 L060 ucb-L059 ucb-L060", "definition": "", "id": "MESH:C026098"}
{"mention": "valproate", "mention_text": "Encephalopathy induced by levetiracetam added to valproate.", "entity": "Valproic Acid", "aliases": "2 Propylpentanoic Acid 2-Propylpentanoic Acetate Dipropyl Propylisopropylacetic Valproic Calcium Valproate Convulsofin Depakene Depakine Depakote Divalproex Sodium Ergenyl Magnesium Semisodium Salt (2:1) Vupral", "definition": "A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.\n    ", "id": "MESH:D014635"}
{"mention": "levetiracetam", "mention_text": "BACKGROUND: We report on the manifestation of a levetiracetam (LEV)-induced encephalopathy. FINDINGS: A 28-year-old man suffering from idiopathic epilepsy with generalized seizures was treated with LEV (3000 mg) added to valproate (VPA) (2000 mg). Frequency of generalized tonic-clonic seizures increased from one per 6 months to two per month. Neuropsychological testing showed impaired word fluency, psychomotor speed and working memory. The interictal electroencephalogram (EEG) showed a generalized slowing to 5 per second theta rhythms with bilateral generalized high-amplitude discharges. OUTCOME: Following discontinuation of LEV, EEG and neuropsychological findings improved and seizure frequency decreased.", "entity": "etiracetam", "aliases": "Keppra UCB 6474 Brand of Levetiracetam UCB-6474 alpha-ethyl-2-oxo-1-pyrrolidineacetamide etiracetam R-isomer S-isomer levetiracetam ucb L059 L060 ucb-L059 ucb-L060", "definition": "", "id": "MESH:C026098"}
{"mention": "LEV", "mention_text": "BACKGROUND: We report on the manifestation of a levetiracetam (LEV)-induced encephalopathy. FINDINGS: A 28-year-old man suffering from idiopathic epilepsy with generalized seizures was treated with LEV (3000 mg) added to valproate (VPA) (2000 mg). Frequency of generalized tonic-clonic seizures increased from one per 6 months to two per month. Neuropsychological testing showed impaired word fluency, psychomotor speed and working memory. The interictal electroencephalogram (EEG) showed a generalized slowing to 5 per second theta rhythms with bilateral generalized high-amplitude discharges. OUTCOME: Following discontinuation of LEV, EEG and neuropsychological findings improved and seizure frequency decreased.", "entity": "etiracetam", "aliases": "Keppra UCB 6474 Brand of Levetiracetam UCB-6474 alpha-ethyl-2-oxo-1-pyrrolidineacetamide etiracetam R-isomer S-isomer levetiracetam ucb L059 L060 ucb-L059 ucb-L060", "definition": "", "id": "MESH:C026098"}
{"mention": "encephalopathy", "mention_text": "BACKGROUND: We report on the manifestation of a levetiracetam (LEV)-induced encephalopathy. FINDINGS: A 28-year-old man suffering from idiopathic epilepsy with generalized seizures was treated with LEV (3000 mg) added to valproate (VPA) (2000 mg). Frequency of generalized tonic-clonic seizures increased from one per 6 months to two per month. Neuropsychological testing showed impaired word fluency, psychomotor speed and working memory. The interictal electroencephalogram (EEG) showed a generalized slowing to 5 per second theta rhythms with bilateral generalized high-amplitude discharges. OUTCOME: Following discontinuation of LEV, EEG and neuropsychological findings improved and seizure frequency decreased.", "entity": "Brain Diseases", "aliases": "Brain Disease Diseases Disorder Disorders CNS Intracranial Central Nervous System Encephalon", "definition": "Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.\n    ", "id": "MESH:D001927"}
{"mention": "idiopathic epilepsy", "mention_text": "BACKGROUND: We report on the manifestation of a levetiracetam (LEV)-induced encephalopathy. FINDINGS: A 28-year-old man suffering from idiopathic epilepsy with generalized seizures was treated with LEV (3000 mg) added to valproate (VPA) (2000 mg). Frequency of generalized tonic-clonic seizures increased from one per 6 months to two per month. Neuropsychological testing showed impaired word fluency, psychomotor speed and working memory. The interictal electroencephalogram (EEG) showed a generalized slowing to 5 per second theta rhythms with bilateral generalized high-amplitude discharges. OUTCOME: Following discontinuation of LEV, EEG and neuropsychological findings improved and seizure frequency decreased.", "entity": "Epilepsy, Idiopathic Generalized", "aliases": "Epilepsy Idiopathic Generalized", "definition": "", "id": "MESH:C562694"}
{"mention": "seizures", "mention_text": "BACKGROUND: We report on the manifestation of a levetiracetam (LEV)-induced encephalopathy. FINDINGS: A 28-year-old man suffering from idiopathic epilepsy with generalized seizures was treated with LEV (3000 mg) added to valproate (VPA) (2000 mg). Frequency of generalized tonic-clonic seizures increased from one per 6 months to two per month. Neuropsychological testing showed impaired word fluency, psychomotor speed and working memory. The interictal electroencephalogram (EEG) showed a generalized slowing to 5 per second theta rhythms with bilateral generalized high-amplitude discharges. OUTCOME: Following discontinuation of LEV, EEG and neuropsychological findings improved and seizure frequency decreased.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "valproate", "mention_text": "BACKGROUND: We report on the manifestation of a levetiracetam (LEV)-induced encephalopathy. FINDINGS: A 28-year-old man suffering from idiopathic epilepsy with generalized seizures was treated with LEV (3000 mg) added to valproate (VPA) (2000 mg). Frequency of generalized tonic-clonic seizures increased from one per 6 months to two per month. Neuropsychological testing showed impaired word fluency, psychomotor speed and working memory. The interictal electroencephalogram (EEG) showed a generalized slowing to 5 per second theta rhythms with bilateral generalized high-amplitude discharges. OUTCOME: Following discontinuation of LEV, EEG and neuropsychological findings improved and seizure frequency decreased.", "entity": "Valproic Acid", "aliases": "2 Propylpentanoic Acid 2-Propylpentanoic Acetate Dipropyl Propylisopropylacetic Valproic Calcium Valproate Convulsofin Depakene Depakine Depakote Divalproex Sodium Ergenyl Magnesium Semisodium Salt (2:1) Vupral", "definition": "A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.\n    ", "id": "MESH:D014635"}
{"mention": "VPA", "mention_text": "BACKGROUND: We report on the manifestation of a levetiracetam (LEV)-induced encephalopathy. FINDINGS: A 28-year-old man suffering from idiopathic epilepsy with generalized seizures was treated with LEV (3000 mg) added to valproate (VPA) (2000 mg). Frequency of generalized tonic-clonic seizures increased from one per 6 months to two per month. Neuropsychological testing showed impaired word fluency, psychomotor speed and working memory. The interictal electroencephalogram (EEG) showed a generalized slowing to 5 per second theta rhythms with bilateral generalized high-amplitude discharges. OUTCOME: Following discontinuation of LEV, EEG and neuropsychological findings improved and seizure frequency decreased.", "entity": "Valproic Acid", "aliases": "2 Propylpentanoic Acid 2-Propylpentanoic Acetate Dipropyl Propylisopropylacetic Valproic Calcium Valproate Convulsofin Depakene Depakine Depakote Divalproex Sodium Ergenyl Magnesium Semisodium Salt (2:1) Vupral", "definition": "A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.\n    ", "id": "MESH:D014635"}
{"mention": "tonic-clonic seizures", "mention_text": "BACKGROUND: We report on the manifestation of a levetiracetam (LEV)-induced encephalopathy. FINDINGS: A 28-year-old man suffering from idiopathic epilepsy with generalized seizures was treated with LEV (3000 mg) added to valproate (VPA) (2000 mg). Frequency of generalized tonic-clonic seizures increased from one per 6 months to two per month. Neuropsychological testing showed impaired word fluency, psychomotor speed and working memory. The interictal electroencephalogram (EEG) showed a generalized slowing to 5 per second theta rhythms with bilateral generalized high-amplitude discharges. OUTCOME: Following discontinuation of LEV, EEG and neuropsychological findings improved and seizure frequency decreased.", "entity": "Epilepsy, Tonic-Clonic", "aliases": "Convulsion Disorder Tonic-Clonic Disorders Syndrome Syndromes Grand Mal Tonic Clonic Convulsions Cryptogenic Epilepsy Epilepsies Seizure Familial Symptomatic Major Motor", "definition": "A generalized seizure disorder characterized by recurrent major motor seizures. The initial brief tonic phase is marked by trunk flexion followed by diffuse extension of the trunk and extremities. The clonic phase features rhythmic flexor contractions of the trunk and limbs, pupillary dilation, elevations of blood pressure and pulse, urinary incontinence, and tongue biting. This is followed by a profound state of depressed consciousness (post-ictal state) which gradually improves over minutes to hours. The disorder may be cryptogenic, familial, or symptomatic (caused by an identified disease process). (From Adams et al., Principles of Neurology, 6th ed, p329)\n    ", "id": "MESH:D004830"}
{"mention": "impaired word fluency, psychomotor speed and working memory", "mention_text": "BACKGROUND: We report on the manifestation of a levetiracetam (LEV)-induced encephalopathy. FINDINGS: A 28-year-old man suffering from idiopathic epilepsy with generalized seizures was treated with LEV (3000 mg) added to valproate (VPA) (2000 mg). Frequency of generalized tonic-clonic seizures increased from one per 6 months to two per month. Neuropsychological testing showed impaired word fluency, psychomotor speed and working memory. The interictal electroencephalogram (EEG) showed a generalized slowing to 5 per second theta rhythms with bilateral generalized high-amplitude discharges. OUTCOME: Following discontinuation of LEV, EEG and neuropsychological findings improved and seizure frequency decreased.", "entity": "Memory Disorders", "aliases": "Age Related Memory Disorders Age-Related Disorder Cognitive Retention Deficit Deficits Semantic Spatial Loss Losses", "definition": "Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions.\n    ", "id": "MESH:D008569"}
{"mention": "seizure", "mention_text": "BACKGROUND: We report on the manifestation of a levetiracetam (LEV)-induced encephalopathy. FINDINGS: A 28-year-old man suffering from idiopathic epilepsy with generalized seizures was treated with LEV (3000 mg) added to valproate (VPA) (2000 mg). Frequency of generalized tonic-clonic seizures increased from one per 6 months to two per month. Neuropsychological testing showed impaired word fluency, psychomotor speed and working memory. The interictal electroencephalogram (EEG) showed a generalized slowing to 5 per second theta rhythms with bilateral generalized high-amplitude discharges. OUTCOME: Following discontinuation of LEV, EEG and neuropsychological findings improved and seizure frequency decreased.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "Norepinephrine", "mention_text": "Norepinephrine signaling through beta-adrenergic receptors is critical for expression of cocaine-induced anxiety.", "entity": "Norepinephrine", "aliases": "Abbott Brand of Levophed Bitartrate Arterenol Aventis Norepinephrine Hydrochloride Noradrenaline Levarterenol Levonor Levonorepinephrine Noradrénaline tartrate renaudin Norepinephrin d-Tartrate (1:1) (+)-Isomer (+,-)-Isomer l-Tartrate Monohydrate (1:2) Renaudin", "definition": "Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.\n    ", "id": "MESH:D009638"}
{"mention": "cocaine", "mention_text": "Norepinephrine signaling through beta-adrenergic receptors is critical for expression of cocaine-induced anxiety.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "anxiety", "mention_text": "Norepinephrine signaling through beta-adrenergic receptors is critical for expression of cocaine-induced anxiety.", "entity": "Anxiety Disorders", "aliases": "Anxiety Disorder Disorders Neuroses State Neurotic States", "definition": "Persistent and disabling ANXIETY.\n    ", "id": "MESH:D001008"}
{"mention": "Cocaine", "mention_text": "BACKGROUND: Cocaine is a widely abused psychostimulant that has both rewarding and aversive properties. While the mechanisms underlying cocaine's rewarding effects have been studied extensively, less attention has been paid to the unpleasant behavioral states induced by cocaine, such as anxiety. METHODS: In this study, we evaluated the performance of dopamine beta-hydroxylase knockout (Dbh -/-) mice, which lack norepinephrine (NE), in the elevated plus maze (EPM) to examine the contribution of noradrenergic signaling to cocaine-induced anxiety. RESULTS: We found that cocaine dose-dependently increased anxiety-like behavior in control (Dbh +/-) mice, as measured by a decrease in open arm exploration. The Dbh -/- mice had normal baseline performance in the EPM but were completely resistant to the anxiogenic effects of cocaine. Cocaine-induced anxiety was also attenuated in Dbh +/- mice following administration of disulfiram, a dopamine beta-hydroxylase (DBH) inhibitor. In experiments using specific adrenergic antagonists, we found that pretreatment with the beta-adrenergic receptor antagonist propranolol blocked cocaine-induced anxiety-like behavior in Dbh +/- and wild-type C57BL6/J mice, while the alpha(1) antagonist prazosin and the alpha(2) antagonist yohimbine had no effect. CONCLUSIONS: These results indicate that noradrenergic signaling via beta-adrenergic receptors is required for cocaine-induced anxiety in mice.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "cocaine", "mention_text": "BACKGROUND: Cocaine is a widely abused psychostimulant that has both rewarding and aversive properties. While the mechanisms underlying cocaine's rewarding effects have been studied extensively, less attention has been paid to the unpleasant behavioral states induced by cocaine, such as anxiety. METHODS: In this study, we evaluated the performance of dopamine beta-hydroxylase knockout (Dbh -/-) mice, which lack norepinephrine (NE), in the elevated plus maze (EPM) to examine the contribution of noradrenergic signaling to cocaine-induced anxiety. RESULTS: We found that cocaine dose-dependently increased anxiety-like behavior in control (Dbh +/-) mice, as measured by a decrease in open arm exploration. The Dbh -/- mice had normal baseline performance in the EPM but were completely resistant to the anxiogenic effects of cocaine. Cocaine-induced anxiety was also attenuated in Dbh +/- mice following administration of disulfiram, a dopamine beta-hydroxylase (DBH) inhibitor. In experiments using specific adrenergic antagonists, we found that pretreatment with the beta-adrenergic receptor antagonist propranolol blocked cocaine-induced anxiety-like behavior in Dbh +/- and wild-type C57BL6/J mice, while the alpha(1) antagonist prazosin and the alpha(2) antagonist yohimbine had no effect. CONCLUSIONS: These results indicate that noradrenergic signaling via beta-adrenergic receptors is required for cocaine-induced anxiety in mice.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "anxiety", "mention_text": "BACKGROUND: Cocaine is a widely abused psychostimulant that has both rewarding and aversive properties. While the mechanisms underlying cocaine's rewarding effects have been studied extensively, less attention has been paid to the unpleasant behavioral states induced by cocaine, such as anxiety. METHODS: In this study, we evaluated the performance of dopamine beta-hydroxylase knockout (Dbh -/-) mice, which lack norepinephrine (NE), in the elevated plus maze (EPM) to examine the contribution of noradrenergic signaling to cocaine-induced anxiety. RESULTS: We found that cocaine dose-dependently increased anxiety-like behavior in control (Dbh +/-) mice, as measured by a decrease in open arm exploration. The Dbh -/- mice had normal baseline performance in the EPM but were completely resistant to the anxiogenic effects of cocaine. Cocaine-induced anxiety was also attenuated in Dbh +/- mice following administration of disulfiram, a dopamine beta-hydroxylase (DBH) inhibitor. In experiments using specific adrenergic antagonists, we found that pretreatment with the beta-adrenergic receptor antagonist propranolol blocked cocaine-induced anxiety-like behavior in Dbh +/- and wild-type C57BL6/J mice, while the alpha(1) antagonist prazosin and the alpha(2) antagonist yohimbine had no effect. CONCLUSIONS: These results indicate that noradrenergic signaling via beta-adrenergic receptors is required for cocaine-induced anxiety in mice.", "entity": "Anxiety Disorders", "aliases": "Anxiety Disorder Disorders Neuroses State Neurotic States", "definition": "Persistent and disabling ANXIETY.\n    ", "id": "MESH:D001008"}
{"mention": "dopamine", "mention_text": "BACKGROUND: Cocaine is a widely abused psychostimulant that has both rewarding and aversive properties. While the mechanisms underlying cocaine's rewarding effects have been studied extensively, less attention has been paid to the unpleasant behavioral states induced by cocaine, such as anxiety. METHODS: In this study, we evaluated the performance of dopamine beta-hydroxylase knockout (Dbh -/-) mice, which lack norepinephrine (NE), in the elevated plus maze (EPM) to examine the contribution of noradrenergic signaling to cocaine-induced anxiety. RESULTS: We found that cocaine dose-dependently increased anxiety-like behavior in control (Dbh +/-) mice, as measured by a decrease in open arm exploration. The Dbh -/- mice had normal baseline performance in the EPM but were completely resistant to the anxiogenic effects of cocaine. Cocaine-induced anxiety was also attenuated in Dbh +/- mice following administration of disulfiram, a dopamine beta-hydroxylase (DBH) inhibitor. In experiments using specific adrenergic antagonists, we found that pretreatment with the beta-adrenergic receptor antagonist propranolol blocked cocaine-induced anxiety-like behavior in Dbh +/- and wild-type C57BL6/J mice, while the alpha(1) antagonist prazosin and the alpha(2) antagonist yohimbine had no effect. CONCLUSIONS: These results indicate that noradrenergic signaling via beta-adrenergic receptors is required for cocaine-induced anxiety in mice.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "norepinephrine", "mention_text": "BACKGROUND: Cocaine is a widely abused psychostimulant that has both rewarding and aversive properties. While the mechanisms underlying cocaine's rewarding effects have been studied extensively, less attention has been paid to the unpleasant behavioral states induced by cocaine, such as anxiety. METHODS: In this study, we evaluated the performance of dopamine beta-hydroxylase knockout (Dbh -/-) mice, which lack norepinephrine (NE), in the elevated plus maze (EPM) to examine the contribution of noradrenergic signaling to cocaine-induced anxiety. RESULTS: We found that cocaine dose-dependently increased anxiety-like behavior in control (Dbh +/-) mice, as measured by a decrease in open arm exploration. The Dbh -/- mice had normal baseline performance in the EPM but were completely resistant to the anxiogenic effects of cocaine. Cocaine-induced anxiety was also attenuated in Dbh +/- mice following administration of disulfiram, a dopamine beta-hydroxylase (DBH) inhibitor. In experiments using specific adrenergic antagonists, we found that pretreatment with the beta-adrenergic receptor antagonist propranolol blocked cocaine-induced anxiety-like behavior in Dbh +/- and wild-type C57BL6/J mice, while the alpha(1) antagonist prazosin and the alpha(2) antagonist yohimbine had no effect. CONCLUSIONS: These results indicate that noradrenergic signaling via beta-adrenergic receptors is required for cocaine-induced anxiety in mice.", "entity": "Norepinephrine", "aliases": "Abbott Brand of Levophed Bitartrate Arterenol Aventis Norepinephrine Hydrochloride Noradrenaline Levarterenol Levonor Levonorepinephrine Noradrénaline tartrate renaudin Norepinephrin d-Tartrate (1:1) (+)-Isomer (+,-)-Isomer l-Tartrate Monohydrate (1:2) Renaudin", "definition": "Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.\n    ", "id": "MESH:D009638"}
{"mention": "NE", "mention_text": "BACKGROUND: Cocaine is a widely abused psychostimulant that has both rewarding and aversive properties. While the mechanisms underlying cocaine's rewarding effects have been studied extensively, less attention has been paid to the unpleasant behavioral states induced by cocaine, such as anxiety. METHODS: In this study, we evaluated the performance of dopamine beta-hydroxylase knockout (Dbh -/-) mice, which lack norepinephrine (NE), in the elevated plus maze (EPM) to examine the contribution of noradrenergic signaling to cocaine-induced anxiety. RESULTS: We found that cocaine dose-dependently increased anxiety-like behavior in control (Dbh +/-) mice, as measured by a decrease in open arm exploration. The Dbh -/- mice had normal baseline performance in the EPM but were completely resistant to the anxiogenic effects of cocaine. Cocaine-induced anxiety was also attenuated in Dbh +/- mice following administration of disulfiram, a dopamine beta-hydroxylase (DBH) inhibitor. In experiments using specific adrenergic antagonists, we found that pretreatment with the beta-adrenergic receptor antagonist propranolol blocked cocaine-induced anxiety-like behavior in Dbh +/- and wild-type C57BL6/J mice, while the alpha(1) antagonist prazosin and the alpha(2) antagonist yohimbine had no effect. CONCLUSIONS: These results indicate that noradrenergic signaling via beta-adrenergic receptors is required for cocaine-induced anxiety in mice.", "entity": "Norepinephrine", "aliases": "Abbott Brand of Levophed Bitartrate Arterenol Aventis Norepinephrine Hydrochloride Noradrenaline Levarterenol Levonor Levonorepinephrine Noradrénaline tartrate renaudin Norepinephrin d-Tartrate (1:1) (+)-Isomer (+,-)-Isomer l-Tartrate Monohydrate (1:2) Renaudin", "definition": "Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.\n    ", "id": "MESH:D009638"}
{"mention": "disulfiram", "mention_text": "BACKGROUND: Cocaine is a widely abused psychostimulant that has both rewarding and aversive properties. While the mechanisms underlying cocaine's rewarding effects have been studied extensively, less attention has been paid to the unpleasant behavioral states induced by cocaine, such as anxiety. METHODS: In this study, we evaluated the performance of dopamine beta-hydroxylase knockout (Dbh -/-) mice, which lack norepinephrine (NE), in the elevated plus maze (EPM) to examine the contribution of noradrenergic signaling to cocaine-induced anxiety. RESULTS: We found that cocaine dose-dependently increased anxiety-like behavior in control (Dbh +/-) mice, as measured by a decrease in open arm exploration. The Dbh -/- mice had normal baseline performance in the EPM but were completely resistant to the anxiogenic effects of cocaine. Cocaine-induced anxiety was also attenuated in Dbh +/- mice following administration of disulfiram, a dopamine beta-hydroxylase (DBH) inhibitor. In experiments using specific adrenergic antagonists, we found that pretreatment with the beta-adrenergic receptor antagonist propranolol blocked cocaine-induced anxiety-like behavior in Dbh +/- and wild-type C57BL6/J mice, while the alpha(1) antagonist prazosin and the alpha(2) antagonist yohimbine had no effect. CONCLUSIONS: These results indicate that noradrenergic signaling via beta-adrenergic receptors is required for cocaine-induced anxiety in mice.", "entity": "Disulfiram", "aliases": "Alcophobin Allphar Brand of Disulfiram Altana Pharma Antabus Antabuse Anticol Bis(diethylthiocarbamoyl) Disulfide Bohm Dicupral Tetraethylthiuram Dumex Esperal Odyssey Orphan Sanofi Synthelabo Tetraethylthioperoxydicarbonic Diamide ((H2N)C(S))2S2 Teturam", "definition": "A carbamate derivative used as an alcohol deterrent. It is a relatively nontoxic substance when administered alone, but markedly alters the intermediary metabolism of alcohol. When alcohol is ingested after administration of disulfiram, blood acetaldehyde concentrations are increased, followed by flushing, systemic vasodilation, respiratory difficulties, nausea, hypotension, and other symptoms (acetaldehyde syndrome). It acts by inhibiting aldehyde dehydrogenase.\n    ", "id": "MESH:D004221"}
{"mention": "propranolol", "mention_text": "BACKGROUND: Cocaine is a widely abused psychostimulant that has both rewarding and aversive properties. While the mechanisms underlying cocaine's rewarding effects have been studied extensively, less attention has been paid to the unpleasant behavioral states induced by cocaine, such as anxiety. METHODS: In this study, we evaluated the performance of dopamine beta-hydroxylase knockout (Dbh -/-) mice, which lack norepinephrine (NE), in the elevated plus maze (EPM) to examine the contribution of noradrenergic signaling to cocaine-induced anxiety. RESULTS: We found that cocaine dose-dependently increased anxiety-like behavior in control (Dbh +/-) mice, as measured by a decrease in open arm exploration. The Dbh -/- mice had normal baseline performance in the EPM but were completely resistant to the anxiogenic effects of cocaine. Cocaine-induced anxiety was also attenuated in Dbh +/- mice following administration of disulfiram, a dopamine beta-hydroxylase (DBH) inhibitor. In experiments using specific adrenergic antagonists, we found that pretreatment with the beta-adrenergic receptor antagonist propranolol blocked cocaine-induced anxiety-like behavior in Dbh +/- and wild-type C57BL6/J mice, while the alpha(1) antagonist prazosin and the alpha(2) antagonist yohimbine had no effect. CONCLUSIONS: These results indicate that noradrenergic signaling via beta-adrenergic receptors is required for cocaine-induced anxiety in mice.", "entity": "Propranolol", "aliases": "AY 20694 AY-20694 AY20694 Anaprilin Anapriline Avlocardyl Betadren Dexpropranolol Dociton Hydrochloride Propranolol Inderal Obsidan Obzidan Propanolol Rexigen", "definition": "A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.\n    ", "id": "MESH:D011433"}
{"mention": "prazosin", "mention_text": "BACKGROUND: Cocaine is a widely abused psychostimulant that has both rewarding and aversive properties. While the mechanisms underlying cocaine's rewarding effects have been studied extensively, less attention has been paid to the unpleasant behavioral states induced by cocaine, such as anxiety. METHODS: In this study, we evaluated the performance of dopamine beta-hydroxylase knockout (Dbh -/-) mice, which lack norepinephrine (NE), in the elevated plus maze (EPM) to examine the contribution of noradrenergic signaling to cocaine-induced anxiety. RESULTS: We found that cocaine dose-dependently increased anxiety-like behavior in control (Dbh +/-) mice, as measured by a decrease in open arm exploration. The Dbh -/- mice had normal baseline performance in the EPM but were completely resistant to the anxiogenic effects of cocaine. Cocaine-induced anxiety was also attenuated in Dbh +/- mice following administration of disulfiram, a dopamine beta-hydroxylase (DBH) inhibitor. In experiments using specific adrenergic antagonists, we found that pretreatment with the beta-adrenergic receptor antagonist propranolol blocked cocaine-induced anxiety-like behavior in Dbh +/- and wild-type C57BL6/J mice, while the alpha(1) antagonist prazosin and the alpha(2) antagonist yohimbine had no effect. CONCLUSIONS: These results indicate that noradrenergic signaling via beta-adrenergic receptors is required for cocaine-induced anxiety in mice.", "entity": "Prazosin", "aliases": "Douglas Brand of Prazosin Hydrochloride Furazosin HCL Minipress Pfizer Pratsiol", "definition": "A selective adrenergic alpha-1 antagonist used in the treatment of HEART FAILURE; HYPERTENSION; PHEOCHROMOCYTOMA; RAYNAUD DISEASE; PROSTATIC HYPERTROPHY; and URINARY RETENTION.\n    ", "id": "MESH:D011224"}
{"mention": "yohimbine", "mention_text": "BACKGROUND: Cocaine is a widely abused psychostimulant that has both rewarding and aversive properties. While the mechanisms underlying cocaine's rewarding effects have been studied extensively, less attention has been paid to the unpleasant behavioral states induced by cocaine, such as anxiety. METHODS: In this study, we evaluated the performance of dopamine beta-hydroxylase knockout (Dbh -/-) mice, which lack norepinephrine (NE), in the elevated plus maze (EPM) to examine the contribution of noradrenergic signaling to cocaine-induced anxiety. RESULTS: We found that cocaine dose-dependently increased anxiety-like behavior in control (Dbh +/-) mice, as measured by a decrease in open arm exploration. The Dbh -/- mice had normal baseline performance in the EPM but were completely resistant to the anxiogenic effects of cocaine. Cocaine-induced anxiety was also attenuated in Dbh +/- mice following administration of disulfiram, a dopamine beta-hydroxylase (DBH) inhibitor. In experiments using specific adrenergic antagonists, we found that pretreatment with the beta-adrenergic receptor antagonist propranolol blocked cocaine-induced anxiety-like behavior in Dbh +/- and wild-type C57BL6/J mice, while the alpha(1) antagonist prazosin and the alpha(2) antagonist yohimbine had no effect. CONCLUSIONS: These results indicate that noradrenergic signaling via beta-adrenergic receptors is required for cocaine-induced anxiety in mice.", "entity": "Yohimbine", "aliases": "Aphrodine Hydrochloride Aphrodyne Aventis Brand of Yohimbine Corynanthine Tartrate Glenwood Kramer Palisades Pluriviron Rauhimbine Rauwolscine Solvay Star StegroPharm Yocon Yohimbin Spiegel Houdé Yohimex", "definition": "A plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of ERECTILE DYSFUNCTION.\n    ", "id": "MESH:D015016"}
{"mention": "Clonidine", "mention_text": "Clonidine for attention-deficit/hyperactivity disorder: II. ECG changes and adverse events analysis.", "entity": "Clonidine", "aliases": "Boehringer Ingelheim Brand of Clonidine Hydrochloride Catapres Catapresan Catapressan Chlophazolin Clofelin Clofenil Dihydrochloride Monohydrobromide Monohydrochloride Clopheline Dixarit Gemiton Hemiton Isoglaucon Klofelin Klofenil M 5041T M-5041T M5041T ST 155 ST-155 ST155", "definition": "An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.\n    ", "id": "MESH:D003000"}
{"mention": "attention-deficit/hyperactivity disorder", "mention_text": "Clonidine for attention-deficit/hyperactivity disorder: II. ECG changes and adverse events analysis.", "entity": "Attention Deficit Disorder with Hyperactivity", "aliases": "Attention Deficit Disorder with Hyperactivity Disorders Deficit-Hyperactivity Brain Dysfunction Minimal Hyperkinetic Syndrome Syndromes", "definition": "A behavior disorder originating in childhood in which the essential features are signs of developmentally inappropriate inattention, impulsivity, and hyperactivity. Although most individuals have symptoms of both inattention and hyperactivity-impulsivity, one or the other pattern may be predominant. The disorder is more frequent in males than females. Onset is in childhood. Symptoms often attenuate during late adolescence although a minority experience the full complement of symptoms into mid-adulthood. (From DSM-IV)\n    ", "id": "MESH:D001289"}
{"mention": "clonidine", "mention_text": "OBJECTIVE: To examine the safety and tolerability of clonidine used alone or with methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: In a 16-week multicenter, double-blind trial, 122 children with ADHD were randomly assigned to clonidine (n = 31), methylphenidate (n = 29), clonidine and methylphenidate (n = 32), or placebo (n = 30). Doses were flexibly titrated up to 0.6 mg/day for clonidine and 60 mg/day for methylphenidate (both with divided dosing). Groups were compared regarding adverse events and changes from baseline to week 16 in electrocardiograms and vital signs. RESULTS: There were more incidents of bradycardia in subjects treated with clonidine compared with those not treated with clonidine (17.5% versus 3.4%; p =.02), but no other significant group differences regarding electrocardiogram and other cardiovascular outcomes. There were no suggestions of interactions between clonidine and methylphenidate regarding cardiovascular outcomes. Moderate or severe adverse events were more common in subjects on clonidine (79.4% versus 49.2%; p =.0006) but not associated with higher rates of early study withdrawal. Drowsiness was common on clonidine, but generally resolved by 6 to 8 weeks. CONCLUSIONS: Clonidine, used alone or with methylphenidate, appears safe and well tolerated in childhood ADHD. Physicians prescribing clonidine should monitor for bradycardia and advise patients about the high likelihood of initial drowsiness.", "entity": "Clonidine", "aliases": "Boehringer Ingelheim Brand of Clonidine Hydrochloride Catapres Catapresan Catapressan Chlophazolin Clofelin Clofenil Dihydrochloride Monohydrobromide Monohydrochloride Clopheline Dixarit Gemiton Hemiton Isoglaucon Klofelin Klofenil M 5041T M-5041T M5041T ST 155 ST-155 ST155", "definition": "An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.\n    ", "id": "MESH:D003000"}
{"mention": "methylphenidate", "mention_text": "OBJECTIVE: To examine the safety and tolerability of clonidine used alone or with methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: In a 16-week multicenter, double-blind trial, 122 children with ADHD were randomly assigned to clonidine (n = 31), methylphenidate (n = 29), clonidine and methylphenidate (n = 32), or placebo (n = 30). Doses were flexibly titrated up to 0.6 mg/day for clonidine and 60 mg/day for methylphenidate (both with divided dosing). Groups were compared regarding adverse events and changes from baseline to week 16 in electrocardiograms and vital signs. RESULTS: There were more incidents of bradycardia in subjects treated with clonidine compared with those not treated with clonidine (17.5% versus 3.4%; p =.02), but no other significant group differences regarding electrocardiogram and other cardiovascular outcomes. There were no suggestions of interactions between clonidine and methylphenidate regarding cardiovascular outcomes. Moderate or severe adverse events were more common in subjects on clonidine (79.4% versus 49.2%; p =.0006) but not associated with higher rates of early study withdrawal. Drowsiness was common on clonidine, but generally resolved by 6 to 8 weeks. CONCLUSIONS: Clonidine, used alone or with methylphenidate, appears safe and well tolerated in childhood ADHD. Physicians prescribing clonidine should monitor for bradycardia and advise patients about the high likelihood of initial drowsiness.", "entity": "Methylphenidate", "aliases": "Celltech Brand of Methylphenidate Hydrochloride Centedrin Cephalon Concerta Daytrana Equasym Mallinckrodt Metadate Methylin Novartis 1 2 Phenidylate Ritalin SR Ritalin-SR Ritaline Tsentedrin", "definition": "A central nervous system stimulant used most commonly in the treatment of ATTENTION DEFICIT DISORDER in children and for NARCOLEPSY. Its mechanisms appear to be similar to those of DEXTROAMPHETAMINE. The d-isomer of this drug is referred to as DEXMETHYLPHENIDATE.\n    ", "id": "MESH:D008774"}
{"mention": "attention-deficit/hyperactivity disorder", "mention_text": "OBJECTIVE: To examine the safety and tolerability of clonidine used alone or with methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: In a 16-week multicenter, double-blind trial, 122 children with ADHD were randomly assigned to clonidine (n = 31), methylphenidate (n = 29), clonidine and methylphenidate (n = 32), or placebo (n = 30). Doses were flexibly titrated up to 0.6 mg/day for clonidine and 60 mg/day for methylphenidate (both with divided dosing). Groups were compared regarding adverse events and changes from baseline to week 16 in electrocardiograms and vital signs. RESULTS: There were more incidents of bradycardia in subjects treated with clonidine compared with those not treated with clonidine (17.5% versus 3.4%; p =.02), but no other significant group differences regarding electrocardiogram and other cardiovascular outcomes. There were no suggestions of interactions between clonidine and methylphenidate regarding cardiovascular outcomes. Moderate or severe adverse events were more common in subjects on clonidine (79.4% versus 49.2%; p =.0006) but not associated with higher rates of early study withdrawal. Drowsiness was common on clonidine, but generally resolved by 6 to 8 weeks. CONCLUSIONS: Clonidine, used alone or with methylphenidate, appears safe and well tolerated in childhood ADHD. Physicians prescribing clonidine should monitor for bradycardia and advise patients about the high likelihood of initial drowsiness.", "entity": "Attention Deficit Disorder with Hyperactivity", "aliases": "Attention Deficit Disorder with Hyperactivity Disorders Deficit-Hyperactivity Brain Dysfunction Minimal Hyperkinetic Syndrome Syndromes", "definition": "A behavior disorder originating in childhood in which the essential features are signs of developmentally inappropriate inattention, impulsivity, and hyperactivity. Although most individuals have symptoms of both inattention and hyperactivity-impulsivity, one or the other pattern may be predominant. The disorder is more frequent in males than females. Onset is in childhood. Symptoms often attenuate during late adolescence although a minority experience the full complement of symptoms into mid-adulthood. (From DSM-IV)\n    ", "id": "MESH:D001289"}
{"mention": "ADHD", "mention_text": "OBJECTIVE: To examine the safety and tolerability of clonidine used alone or with methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: In a 16-week multicenter, double-blind trial, 122 children with ADHD were randomly assigned to clonidine (n = 31), methylphenidate (n = 29), clonidine and methylphenidate (n = 32), or placebo (n = 30). Doses were flexibly titrated up to 0.6 mg/day for clonidine and 60 mg/day for methylphenidate (both with divided dosing). Groups were compared regarding adverse events and changes from baseline to week 16 in electrocardiograms and vital signs. RESULTS: There were more incidents of bradycardia in subjects treated with clonidine compared with those not treated with clonidine (17.5% versus 3.4%; p =.02), but no other significant group differences regarding electrocardiogram and other cardiovascular outcomes. There were no suggestions of interactions between clonidine and methylphenidate regarding cardiovascular outcomes. Moderate or severe adverse events were more common in subjects on clonidine (79.4% versus 49.2%; p =.0006) but not associated with higher rates of early study withdrawal. Drowsiness was common on clonidine, but generally resolved by 6 to 8 weeks. CONCLUSIONS: Clonidine, used alone or with methylphenidate, appears safe and well tolerated in childhood ADHD. Physicians prescribing clonidine should monitor for bradycardia and advise patients about the high likelihood of initial drowsiness.", "entity": "Attention Deficit Disorder with Hyperactivity", "aliases": "Attention Deficit Disorder with Hyperactivity Disorders Deficit-Hyperactivity Brain Dysfunction Minimal Hyperkinetic Syndrome Syndromes", "definition": "A behavior disorder originating in childhood in which the essential features are signs of developmentally inappropriate inattention, impulsivity, and hyperactivity. Although most individuals have symptoms of both inattention and hyperactivity-impulsivity, one or the other pattern may be predominant. The disorder is more frequent in males than females. Onset is in childhood. Symptoms often attenuate during late adolescence although a minority experience the full complement of symptoms into mid-adulthood. (From DSM-IV)\n    ", "id": "MESH:D001289"}
{"mention": "bradycardia", "mention_text": "OBJECTIVE: To examine the safety and tolerability of clonidine used alone or with methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: In a 16-week multicenter, double-blind trial, 122 children with ADHD were randomly assigned to clonidine (n = 31), methylphenidate (n = 29), clonidine and methylphenidate (n = 32), or placebo (n = 30). Doses were flexibly titrated up to 0.6 mg/day for clonidine and 60 mg/day for methylphenidate (both with divided dosing). Groups were compared regarding adverse events and changes from baseline to week 16 in electrocardiograms and vital signs. RESULTS: There were more incidents of bradycardia in subjects treated with clonidine compared with those not treated with clonidine (17.5% versus 3.4%; p =.02), but no other significant group differences regarding electrocardiogram and other cardiovascular outcomes. There were no suggestions of interactions between clonidine and methylphenidate regarding cardiovascular outcomes. Moderate or severe adverse events were more common in subjects on clonidine (79.4% versus 49.2%; p =.0006) but not associated with higher rates of early study withdrawal. Drowsiness was common on clonidine, but generally resolved by 6 to 8 weeks. CONCLUSIONS: Clonidine, used alone or with methylphenidate, appears safe and well tolerated in childhood ADHD. Physicians prescribing clonidine should monitor for bradycardia and advise patients about the high likelihood of initial drowsiness.", "entity": "Bradycardia", "aliases": "Bradyarrhythmia Bradyarrhythmias Bradycardia Bradycardias", "definition": "Cardiac arrhythmias that are characterized by excessively slow HEART RATE, usually below 50 beats per minute in human adults. They can be classified broadly into SINOATRIAL NODE dysfunction and ATRIOVENTRICULAR BLOCK.\n    ", "id": "MESH:D001919"}
{"mention": "Drowsiness", "mention_text": "OBJECTIVE: To examine the safety and tolerability of clonidine used alone or with methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: In a 16-week multicenter, double-blind trial, 122 children with ADHD were randomly assigned to clonidine (n = 31), methylphenidate (n = 29), clonidine and methylphenidate (n = 32), or placebo (n = 30). Doses were flexibly titrated up to 0.6 mg/day for clonidine and 60 mg/day for methylphenidate (both with divided dosing). Groups were compared regarding adverse events and changes from baseline to week 16 in electrocardiograms and vital signs. RESULTS: There were more incidents of bradycardia in subjects treated with clonidine compared with those not treated with clonidine (17.5% versus 3.4%; p =.02), but no other significant group differences regarding electrocardiogram and other cardiovascular outcomes. There were no suggestions of interactions between clonidine and methylphenidate regarding cardiovascular outcomes. Moderate or severe adverse events were more common in subjects on clonidine (79.4% versus 49.2%; p =.0006) but not associated with higher rates of early study withdrawal. Drowsiness was common on clonidine, but generally resolved by 6 to 8 weeks. CONCLUSIONS: Clonidine, used alone or with methylphenidate, appears safe and well tolerated in childhood ADHD. Physicians prescribing clonidine should monitor for bradycardia and advise patients about the high likelihood of initial drowsiness.", "entity": "Disorders of Excessive Somnolence", "aliases": "DOES (Disorders of Excessive Somnolence) DOESs Disorders Somnolence Disorder Hypersomnia Recurrent Hypersomnias Hypersomnolence Primary Secondary", "definition": "Disorders characterized by hypersomnolence during normal waking hours that may impair cognitive functioning. Subtypes include primary hypersomnia disorders (e.g., IDIOPATHIC HYPERSOMNOLENCE; NARCOLEPSY; and KLEINE-LEVIN SYNDROME) and secondary hypersomnia disorders where excessive somnolence can be attributed to a known cause (e.g., drug affect, MENTAL DISORDERS, and SLEEP APNEA SYNDROME). (From J Neurol Sci 1998 Jan 8;153(2):192-202; Thorpy, Principles and Practice of Sleep Medicine, 2nd ed, p320)\n    ", "id": "MESH:D006970"}
{"mention": "Clonidine", "mention_text": "OBJECTIVE: To examine the safety and tolerability of clonidine used alone or with methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: In a 16-week multicenter, double-blind trial, 122 children with ADHD were randomly assigned to clonidine (n = 31), methylphenidate (n = 29), clonidine and methylphenidate (n = 32), or placebo (n = 30). Doses were flexibly titrated up to 0.6 mg/day for clonidine and 60 mg/day for methylphenidate (both with divided dosing). Groups were compared regarding adverse events and changes from baseline to week 16 in electrocardiograms and vital signs. RESULTS: There were more incidents of bradycardia in subjects treated with clonidine compared with those not treated with clonidine (17.5% versus 3.4%; p =.02), but no other significant group differences regarding electrocardiogram and other cardiovascular outcomes. There were no suggestions of interactions between clonidine and methylphenidate regarding cardiovascular outcomes. Moderate or severe adverse events were more common in subjects on clonidine (79.4% versus 49.2%; p =.0006) but not associated with higher rates of early study withdrawal. Drowsiness was common on clonidine, but generally resolved by 6 to 8 weeks. CONCLUSIONS: Clonidine, used alone or with methylphenidate, appears safe and well tolerated in childhood ADHD. Physicians prescribing clonidine should monitor for bradycardia and advise patients about the high likelihood of initial drowsiness.", "entity": "Clonidine", "aliases": "Boehringer Ingelheim Brand of Clonidine Hydrochloride Catapres Catapresan Catapressan Chlophazolin Clofelin Clofenil Dihydrochloride Monohydrobromide Monohydrochloride Clopheline Dixarit Gemiton Hemiton Isoglaucon Klofelin Klofenil M 5041T M-5041T M5041T ST 155 ST-155 ST155", "definition": "An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.\n    ", "id": "MESH:D003000"}
{"mention": "drowsiness", "mention_text": "OBJECTIVE: To examine the safety and tolerability of clonidine used alone or with methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: In a 16-week multicenter, double-blind trial, 122 children with ADHD were randomly assigned to clonidine (n = 31), methylphenidate (n = 29), clonidine and methylphenidate (n = 32), or placebo (n = 30). Doses were flexibly titrated up to 0.6 mg/day for clonidine and 60 mg/day for methylphenidate (both with divided dosing). Groups were compared regarding adverse events and changes from baseline to week 16 in electrocardiograms and vital signs. RESULTS: There were more incidents of bradycardia in subjects treated with clonidine compared with those not treated with clonidine (17.5% versus 3.4%; p =.02), but no other significant group differences regarding electrocardiogram and other cardiovascular outcomes. There were no suggestions of interactions between clonidine and methylphenidate regarding cardiovascular outcomes. Moderate or severe adverse events were more common in subjects on clonidine (79.4% versus 49.2%; p =.0006) but not associated with higher rates of early study withdrawal. Drowsiness was common on clonidine, but generally resolved by 6 to 8 weeks. CONCLUSIONS: Clonidine, used alone or with methylphenidate, appears safe and well tolerated in childhood ADHD. Physicians prescribing clonidine should monitor for bradycardia and advise patients about the high likelihood of initial drowsiness.", "entity": "Disorders of Excessive Somnolence", "aliases": "DOES (Disorders of Excessive Somnolence) DOESs Disorders Somnolence Disorder Hypersomnia Recurrent Hypersomnias Hypersomnolence Primary Secondary", "definition": "Disorders characterized by hypersomnolence during normal waking hours that may impair cognitive functioning. Subtypes include primary hypersomnia disorders (e.g., IDIOPATHIC HYPERSOMNOLENCE; NARCOLEPSY; and KLEINE-LEVIN SYNDROME) and secondary hypersomnia disorders where excessive somnolence can be attributed to a known cause (e.g., drug affect, MENTAL DISORDERS, and SLEEP APNEA SYNDROME). (From J Neurol Sci 1998 Jan 8;153(2):192-202; Thorpy, Principles and Practice of Sleep Medicine, 2nd ed, p320)\n    ", "id": "MESH:D006970"}
{"mention": "Thalidomide", "mention_text": "Thalidomide has limited single-agent activity in relapsed or refractory indolent non-Hodgkin lymphomas: a phase II trial of the Cancer and Leukemia Group B.", "entity": "Thalidomide", "aliases": "Celgene Brand of Thalidomide Sedoval Thalomid", "definition": "A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.\n    ", "id": "MESH:D013792"}
{"mention": "non-Hodgkin lymphomas", "mention_text": "Thalidomide has limited single-agent activity in relapsed or refractory indolent non-Hodgkin lymphomas: a phase II trial of the Cancer and Leukemia Group B.", "entity": "Lymphoma, Non-Hodgkin", "aliases": "Diffuse Lymphoma Lymphomas Mixed Cell Small and Large Mixed-Cell Cleaved Cleaved-Cell Undifferentiated High-Grade Intermediate-Grade Low-Grade Lymphatic Sarcoma Sarcomas Lymphocytic-Histiocytic Atypical Lymphoid High Grade Intermediate Low Lymphocytic Histiocytic Non Hodgkin Hodgkin's Hodgkins Non-Hodgkin Non-Hodgkin's Familial Non-Hodgkins Nonhodgkin Nonhodgkin's Nonhodgkins Pleomorphic Non-Cleaved-Cell Noncleaved Noncleaved-Cell Lymphosarcoma Lymphosarcomas Reticulosarcoma Reticulosarcomas Ret", "definition": "Any of a group of malignant tumors of lymphoid tissue that differ from HODGKIN DISEASE, being more heterogeneous with respect to malignant cell lineage, clinical course, prognosis, and therapy. The only common feature among these tumors is the absence of giant REED-STERNBERG CELLS, a characteristic of Hodgkin's disease.\n    ", "id": "MESH:D008228"}
{"mention": "Cancer", "mention_text": "Thalidomide has limited single-agent activity in relapsed or refractory indolent non-Hodgkin lymphomas: a phase II trial of the Cancer and Leukemia Group B.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "Leukemia", "mention_text": "Thalidomide has limited single-agent activity in relapsed or refractory indolent non-Hodgkin lymphomas: a phase II trial of the Cancer and Leukemia Group B.", "entity": "Leukemia", "aliases": "Leucocythaemia Leucocythaemias Leucocythemia Leucocythemias Leukemia Leukemias", "definition": "A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006)\n    ", "id": "MESH:D007938"}
{"mention": "Thalidomide", "mention_text": "Thalidomide is an immunomodulatory agent with demonstrated activity in multiple myeloma, mantle cell lymphoma and lymphoplasmacytic lymphoma. Its activity is believed to be due modulation of the tumour milieu, including downregulation of angiogenesis and inflammatory cytokines. Between July 2001 and April 2004, 24 patients with relapsed/refractory indolent lymphomas received thalidomide 200 mg daily with escalation by 100 mg daily every 1-2 weeks as tolerated, up to a maximum of 800 mg daily. Patients had received a median of 2 (range, 1-4) prior regimens. Of 24 evaluable patients, two achieved a complete remission and one achieved a partial remission for an overall response rate of 12.5% (95% confidence interval: 2.6-32.4%). Eleven patients progressed during therapy. Grade 3-4 adverse effects included myelosuppression, fatigue, somnolence/depressed mood, neuropathy and dyspnea. Of concern was the occurrence of four thromboembolic events. Our results failed to demonstrate an important response rate to single agent thalidomide in indolent lymphomas and contrast with the higher activity level reported with the second generation immunomodulatory agent, lenalidomide.", "entity": "Thalidomide", "aliases": "Celgene Brand of Thalidomide Sedoval Thalomid", "definition": "A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.\n    ", "id": "MESH:D013792"}
{"mention": "multiple myeloma", "mention_text": "Thalidomide is an immunomodulatory agent with demonstrated activity in multiple myeloma, mantle cell lymphoma and lymphoplasmacytic lymphoma. Its activity is believed to be due modulation of the tumour milieu, including downregulation of angiogenesis and inflammatory cytokines. Between July 2001 and April 2004, 24 patients with relapsed/refractory indolent lymphomas received thalidomide 200 mg daily with escalation by 100 mg daily every 1-2 weeks as tolerated, up to a maximum of 800 mg daily. Patients had received a median of 2 (range, 1-4) prior regimens. Of 24 evaluable patients, two achieved a complete remission and one achieved a partial remission for an overall response rate of 12.5% (95% confidence interval: 2.6-32.4%). Eleven patients progressed during therapy. Grade 3-4 adverse effects included myelosuppression, fatigue, somnolence/depressed mood, neuropathy and dyspnea. Of concern was the occurrence of four thromboembolic events. Our results failed to demonstrate an important response rate to single agent thalidomide in indolent lymphomas and contrast with the higher activity level reported with the second generation immunomodulatory agent, lenalidomide.", "entity": "Multiple Myeloma", "aliases": "Cell Myeloma Plasma Myelomas Disease Kahler Multiple Plasma-Cell Myeloma-Multiple Myeloma-Multiples Myelomatoses Myelomatosis", "definition": "A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY.\n    ", "id": "MESH:D009101"}
{"mention": "mantle cell lymphoma", "mention_text": "Thalidomide is an immunomodulatory agent with demonstrated activity in multiple myeloma, mantle cell lymphoma and lymphoplasmacytic lymphoma. Its activity is believed to be due modulation of the tumour milieu, including downregulation of angiogenesis and inflammatory cytokines. Between July 2001 and April 2004, 24 patients with relapsed/refractory indolent lymphomas received thalidomide 200 mg daily with escalation by 100 mg daily every 1-2 weeks as tolerated, up to a maximum of 800 mg daily. Patients had received a median of 2 (range, 1-4) prior regimens. Of 24 evaluable patients, two achieved a complete remission and one achieved a partial remission for an overall response rate of 12.5% (95% confidence interval: 2.6-32.4%). Eleven patients progressed during therapy. Grade 3-4 adverse effects included myelosuppression, fatigue, somnolence/depressed mood, neuropathy and dyspnea. Of concern was the occurrence of four thromboembolic events. Our results failed to demonstrate an important response rate to single agent thalidomide in indolent lymphomas and contrast with the higher activity level reported with the second generation immunomodulatory agent, lenalidomide.", "entity": "Lymphoma, Mantle-Cell", "aliases": "Centrocytic Small-Cell Lymphoma Lymphomas Diffuse Lymphocytic Poorly Differentiated Poorly-Differentiated Small Cell Intermediate Mantle Mantle-Cell Mantle-Zone Zone", "definition": "A form of non-Hodgkin lymphoma having a usually diffuse pattern with both small and medium lymphocytes and small cleaved cells. It accounts for about 5% of adult non-Hodgkin lymphomas in the United States and Europe. The majority of mantle-cell lymphomas are associated with a t(11;14) translocation resulting in overexpression of the CYCLIN D1 gene (GENES, BCL-1).\n    ", "id": "MESH:D020522"}
{"mention": "lymphoplasmacytic lymphoma", "mention_text": "Thalidomide is an immunomodulatory agent with demonstrated activity in multiple myeloma, mantle cell lymphoma and lymphoplasmacytic lymphoma. Its activity is believed to be due modulation of the tumour milieu, including downregulation of angiogenesis and inflammatory cytokines. Between July 2001 and April 2004, 24 patients with relapsed/refractory indolent lymphomas received thalidomide 200 mg daily with escalation by 100 mg daily every 1-2 weeks as tolerated, up to a maximum of 800 mg daily. Patients had received a median of 2 (range, 1-4) prior regimens. Of 24 evaluable patients, two achieved a complete remission and one achieved a partial remission for an overall response rate of 12.5% (95% confidence interval: 2.6-32.4%). Eleven patients progressed during therapy. Grade 3-4 adverse effects included myelosuppression, fatigue, somnolence/depressed mood, neuropathy and dyspnea. Of concern was the occurrence of four thromboembolic events. Our results failed to demonstrate an important response rate to single agent thalidomide in indolent lymphomas and contrast with the higher activity level reported with the second generation immunomodulatory agent, lenalidomide.", "entity": "Lymphoma", "aliases": "Germinoblastic Sarcoma Sarcomas Germinoblastoma Germinoblastomas Lymphoma Malignant Lymphomas Reticulolymphosarcoma Reticulolymphosarcomas", "definition": "A general term for various neoplastic diseases of the lymphoid tissue.\n    ", "id": "MESH:D008223"}
{"mention": "tumour", "mention_text": "Thalidomide is an immunomodulatory agent with demonstrated activity in multiple myeloma, mantle cell lymphoma and lymphoplasmacytic lymphoma. Its activity is believed to be due modulation of the tumour milieu, including downregulation of angiogenesis and inflammatory cytokines. Between July 2001 and April 2004, 24 patients with relapsed/refractory indolent lymphomas received thalidomide 200 mg daily with escalation by 100 mg daily every 1-2 weeks as tolerated, up to a maximum of 800 mg daily. Patients had received a median of 2 (range, 1-4) prior regimens. Of 24 evaluable patients, two achieved a complete remission and one achieved a partial remission for an overall response rate of 12.5% (95% confidence interval: 2.6-32.4%). Eleven patients progressed during therapy. Grade 3-4 adverse effects included myelosuppression, fatigue, somnolence/depressed mood, neuropathy and dyspnea. Of concern was the occurrence of four thromboembolic events. Our results failed to demonstrate an important response rate to single agent thalidomide in indolent lymphomas and contrast with the higher activity level reported with the second generation immunomodulatory agent, lenalidomide.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "lymphomas", "mention_text": "Thalidomide is an immunomodulatory agent with demonstrated activity in multiple myeloma, mantle cell lymphoma and lymphoplasmacytic lymphoma. Its activity is believed to be due modulation of the tumour milieu, including downregulation of angiogenesis and inflammatory cytokines. Between July 2001 and April 2004, 24 patients with relapsed/refractory indolent lymphomas received thalidomide 200 mg daily with escalation by 100 mg daily every 1-2 weeks as tolerated, up to a maximum of 800 mg daily. Patients had received a median of 2 (range, 1-4) prior regimens. Of 24 evaluable patients, two achieved a complete remission and one achieved a partial remission for an overall response rate of 12.5% (95% confidence interval: 2.6-32.4%). Eleven patients progressed during therapy. Grade 3-4 adverse effects included myelosuppression, fatigue, somnolence/depressed mood, neuropathy and dyspnea. Of concern was the occurrence of four thromboembolic events. Our results failed to demonstrate an important response rate to single agent thalidomide in indolent lymphomas and contrast with the higher activity level reported with the second generation immunomodulatory agent, lenalidomide.", "entity": "Lymphoma", "aliases": "Germinoblastic Sarcoma Sarcomas Germinoblastoma Germinoblastomas Lymphoma Malignant Lymphomas Reticulolymphosarcoma Reticulolymphosarcomas", "definition": "A general term for various neoplastic diseases of the lymphoid tissue.\n    ", "id": "MESH:D008223"}
{"mention": "thalidomide", "mention_text": "Thalidomide is an immunomodulatory agent with demonstrated activity in multiple myeloma, mantle cell lymphoma and lymphoplasmacytic lymphoma. Its activity is believed to be due modulation of the tumour milieu, including downregulation of angiogenesis and inflammatory cytokines. Between July 2001 and April 2004, 24 patients with relapsed/refractory indolent lymphomas received thalidomide 200 mg daily with escalation by 100 mg daily every 1-2 weeks as tolerated, up to a maximum of 800 mg daily. Patients had received a median of 2 (range, 1-4) prior regimens. Of 24 evaluable patients, two achieved a complete remission and one achieved a partial remission for an overall response rate of 12.5% (95% confidence interval: 2.6-32.4%). Eleven patients progressed during therapy. Grade 3-4 adverse effects included myelosuppression, fatigue, somnolence/depressed mood, neuropathy and dyspnea. Of concern was the occurrence of four thromboembolic events. Our results failed to demonstrate an important response rate to single agent thalidomide in indolent lymphomas and contrast with the higher activity level reported with the second generation immunomodulatory agent, lenalidomide.", "entity": "Thalidomide", "aliases": "Celgene Brand of Thalidomide Sedoval Thalomid", "definition": "A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.\n    ", "id": "MESH:D013792"}
{"mention": "myelosuppression", "mention_text": "Thalidomide is an immunomodulatory agent with demonstrated activity in multiple myeloma, mantle cell lymphoma and lymphoplasmacytic lymphoma. Its activity is believed to be due modulation of the tumour milieu, including downregulation of angiogenesis and inflammatory cytokines. Between July 2001 and April 2004, 24 patients with relapsed/refractory indolent lymphomas received thalidomide 200 mg daily with escalation by 100 mg daily every 1-2 weeks as tolerated, up to a maximum of 800 mg daily. Patients had received a median of 2 (range, 1-4) prior regimens. Of 24 evaluable patients, two achieved a complete remission and one achieved a partial remission for an overall response rate of 12.5% (95% confidence interval: 2.6-32.4%). Eleven patients progressed during therapy. Grade 3-4 adverse effects included myelosuppression, fatigue, somnolence/depressed mood, neuropathy and dyspnea. Of concern was the occurrence of four thromboembolic events. Our results failed to demonstrate an important response rate to single agent thalidomide in indolent lymphomas and contrast with the higher activity level reported with the second generation immunomodulatory agent, lenalidomide.", "entity": "Bone Marrow Diseases", "aliases": "Bone Marrow Disease Diseases", "definition": "", "id": "MESH:D001855"}
{"mention": "fatigue", "mention_text": "Thalidomide is an immunomodulatory agent with demonstrated activity in multiple myeloma, mantle cell lymphoma and lymphoplasmacytic lymphoma. Its activity is believed to be due modulation of the tumour milieu, including downregulation of angiogenesis and inflammatory cytokines. Between July 2001 and April 2004, 24 patients with relapsed/refractory indolent lymphomas received thalidomide 200 mg daily with escalation by 100 mg daily every 1-2 weeks as tolerated, up to a maximum of 800 mg daily. Patients had received a median of 2 (range, 1-4) prior regimens. Of 24 evaluable patients, two achieved a complete remission and one achieved a partial remission for an overall response rate of 12.5% (95% confidence interval: 2.6-32.4%). Eleven patients progressed during therapy. Grade 3-4 adverse effects included myelosuppression, fatigue, somnolence/depressed mood, neuropathy and dyspnea. Of concern was the occurrence of four thromboembolic events. Our results failed to demonstrate an important response rate to single agent thalidomide in indolent lymphomas and contrast with the higher activity level reported with the second generation immunomodulatory agent, lenalidomide.", "entity": "Fatigue", "aliases": "Fatigue Lassitude", "definition": "The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.\n    ", "id": "MESH:D005221"}
{"mention": "somnolence", "mention_text": "Thalidomide is an immunomodulatory agent with demonstrated activity in multiple myeloma, mantle cell lymphoma and lymphoplasmacytic lymphoma. Its activity is believed to be due modulation of the tumour milieu, including downregulation of angiogenesis and inflammatory cytokines. Between July 2001 and April 2004, 24 patients with relapsed/refractory indolent lymphomas received thalidomide 200 mg daily with escalation by 100 mg daily every 1-2 weeks as tolerated, up to a maximum of 800 mg daily. Patients had received a median of 2 (range, 1-4) prior regimens. Of 24 evaluable patients, two achieved a complete remission and one achieved a partial remission for an overall response rate of 12.5% (95% confidence interval: 2.6-32.4%). Eleven patients progressed during therapy. Grade 3-4 adverse effects included myelosuppression, fatigue, somnolence/depressed mood, neuropathy and dyspnea. Of concern was the occurrence of four thromboembolic events. Our results failed to demonstrate an important response rate to single agent thalidomide in indolent lymphomas and contrast with the higher activity level reported with the second generation immunomodulatory agent, lenalidomide.", "entity": "Disorders of Excessive Somnolence", "aliases": "DOES (Disorders of Excessive Somnolence) DOESs Disorders Somnolence Disorder Hypersomnia Recurrent Hypersomnias Hypersomnolence Primary Secondary", "definition": "Disorders characterized by hypersomnolence during normal waking hours that may impair cognitive functioning. Subtypes include primary hypersomnia disorders (e.g., IDIOPATHIC HYPERSOMNOLENCE; NARCOLEPSY; and KLEINE-LEVIN SYNDROME) and secondary hypersomnia disorders where excessive somnolence can be attributed to a known cause (e.g., drug affect, MENTAL DISORDERS, and SLEEP APNEA SYNDROME). (From J Neurol Sci 1998 Jan 8;153(2):192-202; Thorpy, Principles and Practice of Sleep Medicine, 2nd ed, p320)\n    ", "id": "MESH:D006970"}
{"mention": "depressed mood", "mention_text": "Thalidomide is an immunomodulatory agent with demonstrated activity in multiple myeloma, mantle cell lymphoma and lymphoplasmacytic lymphoma. Its activity is believed to be due modulation of the tumour milieu, including downregulation of angiogenesis and inflammatory cytokines. Between July 2001 and April 2004, 24 patients with relapsed/refractory indolent lymphomas received thalidomide 200 mg daily with escalation by 100 mg daily every 1-2 weeks as tolerated, up to a maximum of 800 mg daily. Patients had received a median of 2 (range, 1-4) prior regimens. Of 24 evaluable patients, two achieved a complete remission and one achieved a partial remission for an overall response rate of 12.5% (95% confidence interval: 2.6-32.4%). Eleven patients progressed during therapy. Grade 3-4 adverse effects included myelosuppression, fatigue, somnolence/depressed mood, neuropathy and dyspnea. Of concern was the occurrence of four thromboembolic events. Our results failed to demonstrate an important response rate to single agent thalidomide in indolent lymphomas and contrast with the higher activity level reported with the second generation immunomodulatory agent, lenalidomide.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "neuropathy", "mention_text": "Thalidomide is an immunomodulatory agent with demonstrated activity in multiple myeloma, mantle cell lymphoma and lymphoplasmacytic lymphoma. Its activity is believed to be due modulation of the tumour milieu, including downregulation of angiogenesis and inflammatory cytokines. Between July 2001 and April 2004, 24 patients with relapsed/refractory indolent lymphomas received thalidomide 200 mg daily with escalation by 100 mg daily every 1-2 weeks as tolerated, up to a maximum of 800 mg daily. Patients had received a median of 2 (range, 1-4) prior regimens. Of 24 evaluable patients, two achieved a complete remission and one achieved a partial remission for an overall response rate of 12.5% (95% confidence interval: 2.6-32.4%). Eleven patients progressed during therapy. Grade 3-4 adverse effects included myelosuppression, fatigue, somnolence/depressed mood, neuropathy and dyspnea. Of concern was the occurrence of four thromboembolic events. Our results failed to demonstrate an important response rate to single agent thalidomide in indolent lymphomas and contrast with the higher activity level reported with the second generation immunomodulatory agent, lenalidomide.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "dyspnea", "mention_text": "Thalidomide is an immunomodulatory agent with demonstrated activity in multiple myeloma, mantle cell lymphoma and lymphoplasmacytic lymphoma. Its activity is believed to be due modulation of the tumour milieu, including downregulation of angiogenesis and inflammatory cytokines. Between July 2001 and April 2004, 24 patients with relapsed/refractory indolent lymphomas received thalidomide 200 mg daily with escalation by 100 mg daily every 1-2 weeks as tolerated, up to a maximum of 800 mg daily. Patients had received a median of 2 (range, 1-4) prior regimens. Of 24 evaluable patients, two achieved a complete remission and one achieved a partial remission for an overall response rate of 12.5% (95% confidence interval: 2.6-32.4%). Eleven patients progressed during therapy. Grade 3-4 adverse effects included myelosuppression, fatigue, somnolence/depressed mood, neuropathy and dyspnea. Of concern was the occurrence of four thromboembolic events. Our results failed to demonstrate an important response rate to single agent thalidomide in indolent lymphomas and contrast with the higher activity level reported with the second generation immunomodulatory agent, lenalidomide.", "entity": "Dyspnea", "aliases": "Breath Shortness Shortnesses Breathlessness Breathlessnesses Dyspnea Dyspneas of", "definition": "Difficult or labored breathing.\n    ", "id": "MESH:D004417"}
{"mention": "thromboembolic", "mention_text": "Thalidomide is an immunomodulatory agent with demonstrated activity in multiple myeloma, mantle cell lymphoma and lymphoplasmacytic lymphoma. Its activity is believed to be due modulation of the tumour milieu, including downregulation of angiogenesis and inflammatory cytokines. Between July 2001 and April 2004, 24 patients with relapsed/refractory indolent lymphomas received thalidomide 200 mg daily with escalation by 100 mg daily every 1-2 weeks as tolerated, up to a maximum of 800 mg daily. Patients had received a median of 2 (range, 1-4) prior regimens. Of 24 evaluable patients, two achieved a complete remission and one achieved a partial remission for an overall response rate of 12.5% (95% confidence interval: 2.6-32.4%). Eleven patients progressed during therapy. Grade 3-4 adverse effects included myelosuppression, fatigue, somnolence/depressed mood, neuropathy and dyspnea. Of concern was the occurrence of four thromboembolic events. Our results failed to demonstrate an important response rate to single agent thalidomide in indolent lymphomas and contrast with the higher activity level reported with the second generation immunomodulatory agent, lenalidomide.", "entity": "Thromboembolism", "aliases": "Thromboembolism Thromboembolisms", "definition": "Obstruction of a blood vessel (embolism) by a blood clot (THROMBUS) in the blood stream.\n    ", "id": "MESH:D013923"}
{"mention": "lenalidomide", "mention_text": "Thalidomide is an immunomodulatory agent with demonstrated activity in multiple myeloma, mantle cell lymphoma and lymphoplasmacytic lymphoma. Its activity is believed to be due modulation of the tumour milieu, including downregulation of angiogenesis and inflammatory cytokines. Between July 2001 and April 2004, 24 patients with relapsed/refractory indolent lymphomas received thalidomide 200 mg daily with escalation by 100 mg daily every 1-2 weeks as tolerated, up to a maximum of 800 mg daily. Patients had received a median of 2 (range, 1-4) prior regimens. Of 24 evaluable patients, two achieved a complete remission and one achieved a partial remission for an overall response rate of 12.5% (95% confidence interval: 2.6-32.4%). Eleven patients progressed during therapy. Grade 3-4 adverse effects included myelosuppression, fatigue, somnolence/depressed mood, neuropathy and dyspnea. Of concern was the occurrence of four thromboembolic events. Our results failed to demonstrate an important response rate to single agent thalidomide in indolent lymphomas and contrast with the higher activity level reported with the second generation immunomodulatory agent, lenalidomide.", "entity": "lenalidomide", "aliases": "2,6-Piperidinedione 3-(4-amino-1,3-dihydro-1-oxo-2H- isoindol-2-yl)- 3-(4-Amino-1-oxoisoindolin-2-yl)piperidine-2,6-dione CC 5013 CC-5013 CC5013 Celgene brand of lenalidomide IMiD3 cpd Revimid Revlimid", "definition": "", "id": "MESH:C467567"}
{"mention": "epinephrine", "mention_text": "Intracavernous epinephrine: a minimally invasive treatment for priapism in the emergency department.", "entity": "Epinephrine", "aliases": "4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-benzenediol Acetate Epinephrine Adrenaline Acid Tartrate Bitartrate Hydrochloride Allergan Brand of Epifrin Hydrogen Epitrate Lyophrin Medihaler-Epi", "definition": "The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.\n    ", "id": "MESH:D004837"}
{"mention": "priapism", "mention_text": "Intracavernous epinephrine: a minimally invasive treatment for priapism in the emergency department.", "entity": "Priapism", "aliases": "Priapism Priapisms", "definition": "A prolonged painful erection that may lasts hours and is not associated with sexual activity. It is seen in patients with SICKLE CELL ANEMIA, advanced malignancy, spinal trauma; and certain drug treatments.\n    ", "id": "MESH:D011317"}
{"mention": "Priapism", "mention_text": "Priapism is the prolonged erection of the penis in the absence of sexual arousal. A 45-year-old man, an admitted frequent cocaine user, presented to the Emergency Department (ED) on two separate occasions with a history of priapism after cocaine use. The management options in the ED, as exemplified by four individual case reports, in particular the use of a minimally invasive method of intracorporal epinephrine instillation, are discussed.", "entity": "Priapism", "aliases": "Priapism Priapisms", "definition": "A prolonged painful erection that may lasts hours and is not associated with sexual activity. It is seen in patients with SICKLE CELL ANEMIA, advanced malignancy, spinal trauma; and certain drug treatments.\n    ", "id": "MESH:D011317"}
{"mention": "cocaine", "mention_text": "Priapism is the prolonged erection of the penis in the absence of sexual arousal. A 45-year-old man, an admitted frequent cocaine user, presented to the Emergency Department (ED) on two separate occasions with a history of priapism after cocaine use. The management options in the ED, as exemplified by four individual case reports, in particular the use of a minimally invasive method of intracorporal epinephrine instillation, are discussed.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "priapism", "mention_text": "Priapism is the prolonged erection of the penis in the absence of sexual arousal. A 45-year-old man, an admitted frequent cocaine user, presented to the Emergency Department (ED) on two separate occasions with a history of priapism after cocaine use. The management options in the ED, as exemplified by four individual case reports, in particular the use of a minimally invasive method of intracorporal epinephrine instillation, are discussed.", "entity": "Priapism", "aliases": "Priapism Priapisms", "definition": "A prolonged painful erection that may lasts hours and is not associated with sexual activity. It is seen in patients with SICKLE CELL ANEMIA, advanced malignancy, spinal trauma; and certain drug treatments.\n    ", "id": "MESH:D011317"}
{"mention": "epinephrine", "mention_text": "Priapism is the prolonged erection of the penis in the absence of sexual arousal. A 45-year-old man, an admitted frequent cocaine user, presented to the Emergency Department (ED) on two separate occasions with a history of priapism after cocaine use. The management options in the ED, as exemplified by four individual case reports, in particular the use of a minimally invasive method of intracorporal epinephrine instillation, are discussed.", "entity": "Epinephrine", "aliases": "4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-benzenediol Acetate Epinephrine Adrenaline Acid Tartrate Bitartrate Hydrochloride Allergan Brand of Epifrin Hydrogen Epitrate Lyophrin Medihaler-Epi", "definition": "The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.\n    ", "id": "MESH:D004837"}
{"mention": "green tea", "mention_text": "Effect of green tea and vitamin E combination in isoproterenol induced myocardial infarction in rats.", "entity": "Plant Extracts", "aliases": "Extracts Plant", "definition": "Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.\n    ", "id": "MESH:D010936"}
{"mention": "vitamin E", "mention_text": "Effect of green tea and vitamin E combination in isoproterenol induced myocardial infarction in rats.", "entity": "Vitamin E", "aliases": "Vitamin E", "definition": "A generic descriptor for all TOCOPHEROLS and TOCOTRIENOLS that exhibit ALPHA-TOCOPHEROL activity. By virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus, these compounds exhibit varying degree of antioxidant activity, depending on the site and number of methyl groups and the type of ISOPRENOIDS.\n    ", "id": "MESH:D014810"}
{"mention": "isoproterenol", "mention_text": "Effect of green tea and vitamin E combination in isoproterenol induced myocardial infarction in rats.", "entity": "Isoproterenol", "aliases": "4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol Euspiran Hydrochloride Isoproterenol Isadrin Isadrine Isoprenaline Isopropyl Noradrenaline Isopropylarterenol Isopropylnoradrenaline Isopropylnorepinephrine Sulfate Isuprel Izadrin Norisodrine Novodrin", "definition": "Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.\n    ", "id": "MESH:D007545"}
{"mention": "myocardial infarction", "mention_text": "Effect of green tea and vitamin E combination in isoproterenol induced myocardial infarction in rats.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "green tea", "mention_text": "The present study was aimed to investigate the combined effects of green tea and vitamin E on heart weight, body weight, serum marker enzymes, lipid peroxidation, endogenous antioxidants and membrane bound ATPases in isoproterenol (ISO)-induced myocardial infarction in rats. Adult male albino rats, treated with ISO (200 mg/kg, s.c.) for 2 days at an interval of 24 h caused a significant (P<0.05) elevation of heart weight, serum marker enzymes, lipid peroxidation and Ca+2 ATPase level whereas there was a significant (P<0.05) decrease in body weight, endogenous antioxidants, Na+/ K+ ATPase and Mg+2 ATPase levels. Administration of green tea (100 mg/kg/day, p.o.) and vitamin E (100 mg/kg/day, p.o.) together for 30 consecutive days and challenged with ISO on the day 29th and 30th, showed a significant (P<0.05) decrease in heart weight, serum marker enzymes, lipid peroxidation, Ca+2 ATPase and a significant increase in the body weight, endogenous antioxidants, Na+/K+ ATPase and Mg+2 ATPase when compared with ISO treated group and green tea or vitamin E alone treated groups. These findings indicate the synergistic protective effect of green tea and vitamin E during ISO induced myocardial infarction in rats.", "entity": "Plant Extracts", "aliases": "Extracts Plant", "definition": "Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.\n    ", "id": "MESH:D010936"}
{"mention": "vitamin E", "mention_text": "The present study was aimed to investigate the combined effects of green tea and vitamin E on heart weight, body weight, serum marker enzymes, lipid peroxidation, endogenous antioxidants and membrane bound ATPases in isoproterenol (ISO)-induced myocardial infarction in rats. Adult male albino rats, treated with ISO (200 mg/kg, s.c.) for 2 days at an interval of 24 h caused a significant (P<0.05) elevation of heart weight, serum marker enzymes, lipid peroxidation and Ca+2 ATPase level whereas there was a significant (P<0.05) decrease in body weight, endogenous antioxidants, Na+/ K+ ATPase and Mg+2 ATPase levels. Administration of green tea (100 mg/kg/day, p.o.) and vitamin E (100 mg/kg/day, p.o.) together for 30 consecutive days and challenged with ISO on the day 29th and 30th, showed a significant (P<0.05) decrease in heart weight, serum marker enzymes, lipid peroxidation, Ca+2 ATPase and a significant increase in the body weight, endogenous antioxidants, Na+/K+ ATPase and Mg+2 ATPase when compared with ISO treated group and green tea or vitamin E alone treated groups. These findings indicate the synergistic protective effect of green tea and vitamin E during ISO induced myocardial infarction in rats.", "entity": "Vitamin E", "aliases": "Vitamin E", "definition": "A generic descriptor for all TOCOPHEROLS and TOCOTRIENOLS that exhibit ALPHA-TOCOPHEROL activity. By virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus, these compounds exhibit varying degree of antioxidant activity, depending on the site and number of methyl groups and the type of ISOPRENOIDS.\n    ", "id": "MESH:D014810"}
{"mention": "isoproterenol", "mention_text": "The present study was aimed to investigate the combined effects of green tea and vitamin E on heart weight, body weight, serum marker enzymes, lipid peroxidation, endogenous antioxidants and membrane bound ATPases in isoproterenol (ISO)-induced myocardial infarction in rats. Adult male albino rats, treated with ISO (200 mg/kg, s.c.) for 2 days at an interval of 24 h caused a significant (P<0.05) elevation of heart weight, serum marker enzymes, lipid peroxidation and Ca+2 ATPase level whereas there was a significant (P<0.05) decrease in body weight, endogenous antioxidants, Na+/ K+ ATPase and Mg+2 ATPase levels. Administration of green tea (100 mg/kg/day, p.o.) and vitamin E (100 mg/kg/day, p.o.) together for 30 consecutive days and challenged with ISO on the day 29th and 30th, showed a significant (P<0.05) decrease in heart weight, serum marker enzymes, lipid peroxidation, Ca+2 ATPase and a significant increase in the body weight, endogenous antioxidants, Na+/K+ ATPase and Mg+2 ATPase when compared with ISO treated group and green tea or vitamin E alone treated groups. These findings indicate the synergistic protective effect of green tea and vitamin E during ISO induced myocardial infarction in rats.", "entity": "Isoproterenol", "aliases": "4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol Euspiran Hydrochloride Isoproterenol Isadrin Isadrine Isoprenaline Isopropyl Noradrenaline Isopropylarterenol Isopropylnoradrenaline Isopropylnorepinephrine Sulfate Isuprel Izadrin Norisodrine Novodrin", "definition": "Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.\n    ", "id": "MESH:D007545"}
{"mention": "ISO", "mention_text": "The present study was aimed to investigate the combined effects of green tea and vitamin E on heart weight, body weight, serum marker enzymes, lipid peroxidation, endogenous antioxidants and membrane bound ATPases in isoproterenol (ISO)-induced myocardial infarction in rats. Adult male albino rats, treated with ISO (200 mg/kg, s.c.) for 2 days at an interval of 24 h caused a significant (P<0.05) elevation of heart weight, serum marker enzymes, lipid peroxidation and Ca+2 ATPase level whereas there was a significant (P<0.05) decrease in body weight, endogenous antioxidants, Na+/ K+ ATPase and Mg+2 ATPase levels. Administration of green tea (100 mg/kg/day, p.o.) and vitamin E (100 mg/kg/day, p.o.) together for 30 consecutive days and challenged with ISO on the day 29th and 30th, showed a significant (P<0.05) decrease in heart weight, serum marker enzymes, lipid peroxidation, Ca+2 ATPase and a significant increase in the body weight, endogenous antioxidants, Na+/K+ ATPase and Mg+2 ATPase when compared with ISO treated group and green tea or vitamin E alone treated groups. These findings indicate the synergistic protective effect of green tea and vitamin E during ISO induced myocardial infarction in rats.", "entity": "Isoproterenol", "aliases": "4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol Euspiran Hydrochloride Isoproterenol Isadrin Isadrine Isoprenaline Isopropyl Noradrenaline Isopropylarterenol Isopropylnoradrenaline Isopropylnorepinephrine Sulfate Isuprel Izadrin Norisodrine Novodrin", "definition": "Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.\n    ", "id": "MESH:D007545"}
{"mention": "myocardial infarction", "mention_text": "The present study was aimed to investigate the combined effects of green tea and vitamin E on heart weight, body weight, serum marker enzymes, lipid peroxidation, endogenous antioxidants and membrane bound ATPases in isoproterenol (ISO)-induced myocardial infarction in rats. Adult male albino rats, treated with ISO (200 mg/kg, s.c.) for 2 days at an interval of 24 h caused a significant (P<0.05) elevation of heart weight, serum marker enzymes, lipid peroxidation and Ca+2 ATPase level whereas there was a significant (P<0.05) decrease in body weight, endogenous antioxidants, Na+/ K+ ATPase and Mg+2 ATPase levels. Administration of green tea (100 mg/kg/day, p.o.) and vitamin E (100 mg/kg/day, p.o.) together for 30 consecutive days and challenged with ISO on the day 29th and 30th, showed a significant (P<0.05) decrease in heart weight, serum marker enzymes, lipid peroxidation, Ca+2 ATPase and a significant increase in the body weight, endogenous antioxidants, Na+/K+ ATPase and Mg+2 ATPase when compared with ISO treated group and green tea or vitamin E alone treated groups. These findings indicate the synergistic protective effect of green tea and vitamin E during ISO induced myocardial infarction in rats.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "Ca", "mention_text": "The present study was aimed to investigate the combined effects of green tea and vitamin E on heart weight, body weight, serum marker enzymes, lipid peroxidation, endogenous antioxidants and membrane bound ATPases in isoproterenol (ISO)-induced myocardial infarction in rats. Adult male albino rats, treated with ISO (200 mg/kg, s.c.) for 2 days at an interval of 24 h caused a significant (P<0.05) elevation of heart weight, serum marker enzymes, lipid peroxidation and Ca+2 ATPase level whereas there was a significant (P<0.05) decrease in body weight, endogenous antioxidants, Na+/ K+ ATPase and Mg+2 ATPase levels. Administration of green tea (100 mg/kg/day, p.o.) and vitamin E (100 mg/kg/day, p.o.) together for 30 consecutive days and challenged with ISO on the day 29th and 30th, showed a significant (P<0.05) decrease in heart weight, serum marker enzymes, lipid peroxidation, Ca+2 ATPase and a significant increase in the body weight, endogenous antioxidants, Na+/K+ ATPase and Mg+2 ATPase when compared with ISO treated group and green tea or vitamin E alone treated groups. These findings indicate the synergistic protective effect of green tea and vitamin E during ISO induced myocardial infarction in rats.", "entity": "Calcium", "aliases": "Blood Coagulation Factor IV Calcium", "definition": "A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.\n    ", "id": "MESH:D002118"}
{"mention": "Na", "mention_text": "The present study was aimed to investigate the combined effects of green tea and vitamin E on heart weight, body weight, serum marker enzymes, lipid peroxidation, endogenous antioxidants and membrane bound ATPases in isoproterenol (ISO)-induced myocardial infarction in rats. Adult male albino rats, treated with ISO (200 mg/kg, s.c.) for 2 days at an interval of 24 h caused a significant (P<0.05) elevation of heart weight, serum marker enzymes, lipid peroxidation and Ca+2 ATPase level whereas there was a significant (P<0.05) decrease in body weight, endogenous antioxidants, Na+/ K+ ATPase and Mg+2 ATPase levels. Administration of green tea (100 mg/kg/day, p.o.) and vitamin E (100 mg/kg/day, p.o.) together for 30 consecutive days and challenged with ISO on the day 29th and 30th, showed a significant (P<0.05) decrease in heart weight, serum marker enzymes, lipid peroxidation, Ca+2 ATPase and a significant increase in the body weight, endogenous antioxidants, Na+/K+ ATPase and Mg+2 ATPase when compared with ISO treated group and green tea or vitamin E alone treated groups. These findings indicate the synergistic protective effect of green tea and vitamin E during ISO induced myocardial infarction in rats.", "entity": "Sodium", "aliases": "Ion Level Sodium", "definition": "A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.\n    ", "id": "MESH:D012964"}
{"mention": "K", "mention_text": "The present study was aimed to investigate the combined effects of green tea and vitamin E on heart weight, body weight, serum marker enzymes, lipid peroxidation, endogenous antioxidants and membrane bound ATPases in isoproterenol (ISO)-induced myocardial infarction in rats. Adult male albino rats, treated with ISO (200 mg/kg, s.c.) for 2 days at an interval of 24 h caused a significant (P<0.05) elevation of heart weight, serum marker enzymes, lipid peroxidation and Ca+2 ATPase level whereas there was a significant (P<0.05) decrease in body weight, endogenous antioxidants, Na+/ K+ ATPase and Mg+2 ATPase levels. Administration of green tea (100 mg/kg/day, p.o.) and vitamin E (100 mg/kg/day, p.o.) together for 30 consecutive days and challenged with ISO on the day 29th and 30th, showed a significant (P<0.05) decrease in heart weight, serum marker enzymes, lipid peroxidation, Ca+2 ATPase and a significant increase in the body weight, endogenous antioxidants, Na+/K+ ATPase and Mg+2 ATPase when compared with ISO treated group and green tea or vitamin E alone treated groups. These findings indicate the synergistic protective effect of green tea and vitamin E during ISO induced myocardial infarction in rats.", "entity": "Potassium", "aliases": "Potassium", "definition": "An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.\n    ", "id": "MESH:D011188"}
{"mention": "Mg", "mention_text": "The present study was aimed to investigate the combined effects of green tea and vitamin E on heart weight, body weight, serum marker enzymes, lipid peroxidation, endogenous antioxidants and membrane bound ATPases in isoproterenol (ISO)-induced myocardial infarction in rats. Adult male albino rats, treated with ISO (200 mg/kg, s.c.) for 2 days at an interval of 24 h caused a significant (P<0.05) elevation of heart weight, serum marker enzymes, lipid peroxidation and Ca+2 ATPase level whereas there was a significant (P<0.05) decrease in body weight, endogenous antioxidants, Na+/ K+ ATPase and Mg+2 ATPase levels. Administration of green tea (100 mg/kg/day, p.o.) and vitamin E (100 mg/kg/day, p.o.) together for 30 consecutive days and challenged with ISO on the day 29th and 30th, showed a significant (P<0.05) decrease in heart weight, serum marker enzymes, lipid peroxidation, Ca+2 ATPase and a significant increase in the body weight, endogenous antioxidants, Na+/K+ ATPase and Mg+2 ATPase when compared with ISO treated group and green tea or vitamin E alone treated groups. These findings indicate the synergistic protective effect of green tea and vitamin E during ISO induced myocardial infarction in rats.", "entity": "Magnesium", "aliases": "Magnesium", "definition": "A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.\n    ", "id": "MESH:D008274"}
{"mention": "ocular myasthenia", "mention_text": "Development of ocular myasthenia during pegylated interferon and ribavirin treatment for chronic hepatitis C.", "entity": "Myasthenia Gravis", "aliases": "Generalized Myasthenia Gravis Ocular", "definition": "A disorder of neuromuscular transmission characterized by weakness of cranial and skeletal muscles. Autoantibodies directed against acetylcholine receptors damage the motor endplate portion of the NEUROMUSCULAR JUNCTION, impairing the transmission of impulses to skeletal muscles. Clinical manifestations may include diplopia, ptosis, and weakness of facial, bulbar, respiratory, and proximal limb muscles. The disease may remain limited to the ocular muscles. THYMOMA is commonly associated with this condition. (Adams et al., Principles of Neurology, 6th ed, p1459)\n    ", "id": "MESH:D009157"}
{"mention": "pegylated interferon", "mention_text": "Development of ocular myasthenia during pegylated interferon and ribavirin treatment for chronic hepatitis C.", "entity": "peginterferon alfa-2b", "aliases": "PEG INF alfa-2b alpha-2b PEG-IFNalpha-2b PEG-Intron Pegintron ViraferonPeg peg-proline-INFalpha-2b peg-proline-interferon peginterferon pegylated interferon polyethylene glycol-interferon", "definition": "", "id": "MESH:C417083"}
{"mention": "ribavirin", "mention_text": "Development of ocular myasthenia during pegylated interferon and ribavirin treatment for chronic hepatitis C.", "entity": "Ribavirin", "aliases": "Dermatech Brand of Ribavirin Essex Grossman ICN 1229 ICN-1229 ICN1229 Merck Pfizer Rebetol Ribamide Ribamidil Ribamidyl Ribasphere Ribovirin Three Rivers Pharmaceuticals Tribavirin Vilona Viramide Virazide Virazole", "definition": "A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses.\n    ", "id": "MESH:D012254"}
{"mention": "chronic hepatitis C", "mention_text": "Development of ocular myasthenia during pegylated interferon and ribavirin treatment for chronic hepatitis C.", "entity": "Hepatitis C, Chronic", "aliases": "Chronic Hepatitis C", "definition": "INFLAMMATION of the LIVER in humans that is caused by HEPATITIS C VIRUS lasting six months or more. Chronic hepatitis C can lead to LIVER CIRRHOSIS.\n    ", "id": "MESH:D019698"}
{"mention": "diplopia", "mention_text": "A 63-year-old male experienced sudden diplopia after 9 weeks of administration of pegylated interferon (IFN) alpha-2b and ribavirin for chronic hepatitis C (CHC). Ophthalmologic examinations showed ptosis on the right upper lid and restricted right eye movement without any other neurological signs. A brain imaging study and repetitive nerve stimulation test indicated no abnormality. The acetylcholine receptor antibody titer and response to acetylcholinesterase inhibitors were negative, and the results of thyroid function tests were normal. The patient's ophthalmological symptoms improved rapidly 3 weeks after discontinuation of pegylated IFN alpha-2b and ribavirin. The ocular myasthenia associated with combination therapy of pegylated IFN alpha-2b and ribavirin for CHC is very rarely reported; therefore, we present this case with a review of the various eye complications of IFN therapy.", "entity": "Diplopia", "aliases": "Cortical Diplopia Diplopias Horizontal Intermittent Monocular Refractive Unilateral Vertical Double Vision Polyopsia Polyopsias", "definition": "A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include REFRACTIVE ERRORS; STRABISMUS; OCULOMOTOR NERVE DISEASES; TROCHLEAR NERVE DISEASES; ABDUCENS NERVE DISEASES; and diseases of the BRAIN STEM and OCCIPITAL LOBE.\n    ", "id": "MESH:D004172"}
{"mention": "pegylated interferon (IFN) alpha-2b", "mention_text": "A 63-year-old male experienced sudden diplopia after 9 weeks of administration of pegylated interferon (IFN) alpha-2b and ribavirin for chronic hepatitis C (CHC). Ophthalmologic examinations showed ptosis on the right upper lid and restricted right eye movement without any other neurological signs. A brain imaging study and repetitive nerve stimulation test indicated no abnormality. The acetylcholine receptor antibody titer and response to acetylcholinesterase inhibitors were negative, and the results of thyroid function tests were normal. The patient's ophthalmological symptoms improved rapidly 3 weeks after discontinuation of pegylated IFN alpha-2b and ribavirin. The ocular myasthenia associated with combination therapy of pegylated IFN alpha-2b and ribavirin for CHC is very rarely reported; therefore, we present this case with a review of the various eye complications of IFN therapy.", "entity": "peginterferon alfa-2b", "aliases": "PEG INF alfa-2b alpha-2b PEG-IFNalpha-2b PEG-Intron Pegintron ViraferonPeg peg-proline-INFalpha-2b peg-proline-interferon peginterferon pegylated interferon polyethylene glycol-interferon", "definition": "", "id": "MESH:C417083"}
{"mention": "ribavirin", "mention_text": "A 63-year-old male experienced sudden diplopia after 9 weeks of administration of pegylated interferon (IFN) alpha-2b and ribavirin for chronic hepatitis C (CHC). Ophthalmologic examinations showed ptosis on the right upper lid and restricted right eye movement without any other neurological signs. A brain imaging study and repetitive nerve stimulation test indicated no abnormality. The acetylcholine receptor antibody titer and response to acetylcholinesterase inhibitors were negative, and the results of thyroid function tests were normal. The patient's ophthalmological symptoms improved rapidly 3 weeks after discontinuation of pegylated IFN alpha-2b and ribavirin. The ocular myasthenia associated with combination therapy of pegylated IFN alpha-2b and ribavirin for CHC is very rarely reported; therefore, we present this case with a review of the various eye complications of IFN therapy.", "entity": "Ribavirin", "aliases": "Dermatech Brand of Ribavirin Essex Grossman ICN 1229 ICN-1229 ICN1229 Merck Pfizer Rebetol Ribamide Ribamidil Ribamidyl Ribasphere Ribovirin Three Rivers Pharmaceuticals Tribavirin Vilona Viramide Virazide Virazole", "definition": "A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses.\n    ", "id": "MESH:D012254"}
{"mention": "chronic hepatitis C", "mention_text": "A 63-year-old male experienced sudden diplopia after 9 weeks of administration of pegylated interferon (IFN) alpha-2b and ribavirin for chronic hepatitis C (CHC). Ophthalmologic examinations showed ptosis on the right upper lid and restricted right eye movement without any other neurological signs. A brain imaging study and repetitive nerve stimulation test indicated no abnormality. The acetylcholine receptor antibody titer and response to acetylcholinesterase inhibitors were negative, and the results of thyroid function tests were normal. The patient's ophthalmological symptoms improved rapidly 3 weeks after discontinuation of pegylated IFN alpha-2b and ribavirin. The ocular myasthenia associated with combination therapy of pegylated IFN alpha-2b and ribavirin for CHC is very rarely reported; therefore, we present this case with a review of the various eye complications of IFN therapy.", "entity": "Hepatitis C, Chronic", "aliases": "Chronic Hepatitis C", "definition": "INFLAMMATION of the LIVER in humans that is caused by HEPATITIS C VIRUS lasting six months or more. Chronic hepatitis C can lead to LIVER CIRRHOSIS.\n    ", "id": "MESH:D019698"}
{"mention": "CHC", "mention_text": "A 63-year-old male experienced sudden diplopia after 9 weeks of administration of pegylated interferon (IFN) alpha-2b and ribavirin for chronic hepatitis C (CHC). Ophthalmologic examinations showed ptosis on the right upper lid and restricted right eye movement without any other neurological signs. A brain imaging study and repetitive nerve stimulation test indicated no abnormality. The acetylcholine receptor antibody titer and response to acetylcholinesterase inhibitors were negative, and the results of thyroid function tests were normal. The patient's ophthalmological symptoms improved rapidly 3 weeks after discontinuation of pegylated IFN alpha-2b and ribavirin. The ocular myasthenia associated with combination therapy of pegylated IFN alpha-2b and ribavirin for CHC is very rarely reported; therefore, we present this case with a review of the various eye complications of IFN therapy.", "entity": "Hepatitis C, Chronic", "aliases": "Chronic Hepatitis C", "definition": "INFLAMMATION of the LIVER in humans that is caused by HEPATITIS C VIRUS lasting six months or more. Chronic hepatitis C can lead to LIVER CIRRHOSIS.\n    ", "id": "MESH:D019698"}
{"mention": "ptosis on the right upper lid", "mention_text": "A 63-year-old male experienced sudden diplopia after 9 weeks of administration of pegylated interferon (IFN) alpha-2b and ribavirin for chronic hepatitis C (CHC). Ophthalmologic examinations showed ptosis on the right upper lid and restricted right eye movement without any other neurological signs. A brain imaging study and repetitive nerve stimulation test indicated no abnormality. The acetylcholine receptor antibody titer and response to acetylcholinesterase inhibitors were negative, and the results of thyroid function tests were normal. The patient's ophthalmological symptoms improved rapidly 3 weeks after discontinuation of pegylated IFN alpha-2b and ribavirin. The ocular myasthenia associated with combination therapy of pegylated IFN alpha-2b and ribavirin for CHC is very rarely reported; therefore, we present this case with a review of the various eye complications of IFN therapy.", "entity": "Blepharoptosis", "aliases": "Blepharoptoses Blepharoptosis Eyelid Ptoses Ptosis", "definition": "Drooping of the upper lid due to deficient development or paralysis of the levator palpebrae muscle.\n    ", "id": "MESH:D001763"}
{"mention": "restricted right eye movement", "mention_text": "A 63-year-old male experienced sudden diplopia after 9 weeks of administration of pegylated interferon (IFN) alpha-2b and ribavirin for chronic hepatitis C (CHC). Ophthalmologic examinations showed ptosis on the right upper lid and restricted right eye movement without any other neurological signs. A brain imaging study and repetitive nerve stimulation test indicated no abnormality. The acetylcholine receptor antibody titer and response to acetylcholinesterase inhibitors were negative, and the results of thyroid function tests were normal. The patient's ophthalmological symptoms improved rapidly 3 weeks after discontinuation of pegylated IFN alpha-2b and ribavirin. The ocular myasthenia associated with combination therapy of pegylated IFN alpha-2b and ribavirin for CHC is very rarely reported; therefore, we present this case with a review of the various eye complications of IFN therapy.", "entity": "Ocular Motility Disorders", "aliases": "Brown Tendon Sheath Syndrome Brown's Conjugate Gaze Spasm Spasms Convergence Excess Excesses Insufficiencies Insufficiency Cyclophoria Cyclophorias Deficiencies Smooth Pursuit Deficiency Deviation Skew Deviations Dyskinesia Paroxysmal Ocular Dyskinesias Eye Motility Disorder Disorders Movement Internuclear Ophthalmoplegia Ophthalmoplegias Torticollis Opsoclonus Parinaud Parinaud's Parinauds Pseudoophthalmoplegia Pseudoophthalmoplegias of", "definition": "Disorders that feature impairment of eye movements as a primary manifestation of disease. These conditions may be divided into infranuclear, nuclear, and supranuclear disorders. Diseases of the eye muscles or oculomotor cranial nerves (III, IV, and VI) are considered infranuclear. Nuclear disorders are caused by disease of the oculomotor, trochlear, or abducens nuclei in the BRAIN STEM. Supranuclear disorders are produced by dysfunction of higher order sensory and motor systems that control eye movements, including neural networks in the CEREBRAL CORTEX; BASAL GANGLIA; CEREBELLUM; and BRAIN STEM. Ocular torticollis refers to a head tilt that is caused by an ocular misalignment. Opsoclonus refers to rapid, conjugate oscillations of the eyes in multiple directions, which may occur as a parainfectious or paraneoplastic condition (e.g., OPSOCLONUS-MYOCLONUS SYNDROME). (Adams et al., Principles of Neurology, 6th ed, p240)\n    ", "id": "MESH:D015835"}
{"mention": "acetylcholine", "mention_text": "A 63-year-old male experienced sudden diplopia after 9 weeks of administration of pegylated interferon (IFN) alpha-2b and ribavirin for chronic hepatitis C (CHC). Ophthalmologic examinations showed ptosis on the right upper lid and restricted right eye movement without any other neurological signs. A brain imaging study and repetitive nerve stimulation test indicated no abnormality. The acetylcholine receptor antibody titer and response to acetylcholinesterase inhibitors were negative, and the results of thyroid function tests were normal. The patient's ophthalmological symptoms improved rapidly 3 weeks after discontinuation of pegylated IFN alpha-2b and ribavirin. The ocular myasthenia associated with combination therapy of pegylated IFN alpha-2b and ribavirin for CHC is very rarely reported; therefore, we present this case with a review of the various eye complications of IFN therapy.", "entity": "Acetylcholine", "aliases": "2-(Acetyloxy)-N,N,N-trimethylethanaminium Acetilcolina Cusi Acetylcholine Bromide Chloride Fluoride Hydroxide Iodide L Tartrate L-Tartrate Perchlorate Picrate (1:1) Sulfate Alcon Brand of Bournonville Bromoacetylcholine Chloroacetylcholine Ciba Vision Iolab Miochol", "definition": "A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.\n    ", "id": "MESH:D000109"}
{"mention": "pegylated IFN alpha-2b", "mention_text": "A 63-year-old male experienced sudden diplopia after 9 weeks of administration of pegylated interferon (IFN) alpha-2b and ribavirin for chronic hepatitis C (CHC). Ophthalmologic examinations showed ptosis on the right upper lid and restricted right eye movement without any other neurological signs. A brain imaging study and repetitive nerve stimulation test indicated no abnormality. The acetylcholine receptor antibody titer and response to acetylcholinesterase inhibitors were negative, and the results of thyroid function tests were normal. The patient's ophthalmological symptoms improved rapidly 3 weeks after discontinuation of pegylated IFN alpha-2b and ribavirin. The ocular myasthenia associated with combination therapy of pegylated IFN alpha-2b and ribavirin for CHC is very rarely reported; therefore, we present this case with a review of the various eye complications of IFN therapy.", "entity": "peginterferon alfa-2b", "aliases": "PEG INF alfa-2b alpha-2b PEG-IFNalpha-2b PEG-Intron Pegintron ViraferonPeg peg-proline-INFalpha-2b peg-proline-interferon peginterferon pegylated interferon polyethylene glycol-interferon", "definition": "", "id": "MESH:C417083"}
{"mention": "ocular myasthenia", "mention_text": "A 63-year-old male experienced sudden diplopia after 9 weeks of administration of pegylated interferon (IFN) alpha-2b and ribavirin for chronic hepatitis C (CHC). Ophthalmologic examinations showed ptosis on the right upper lid and restricted right eye movement without any other neurological signs. A brain imaging study and repetitive nerve stimulation test indicated no abnormality. The acetylcholine receptor antibody titer and response to acetylcholinesterase inhibitors were negative, and the results of thyroid function tests were normal. The patient's ophthalmological symptoms improved rapidly 3 weeks after discontinuation of pegylated IFN alpha-2b and ribavirin. The ocular myasthenia associated with combination therapy of pegylated IFN alpha-2b and ribavirin for CHC is very rarely reported; therefore, we present this case with a review of the various eye complications of IFN therapy.", "entity": "Myasthenia Gravis", "aliases": "Generalized Myasthenia Gravis Ocular", "definition": "A disorder of neuromuscular transmission characterized by weakness of cranial and skeletal muscles. Autoantibodies directed against acetylcholine receptors damage the motor endplate portion of the NEUROMUSCULAR JUNCTION, impairing the transmission of impulses to skeletal muscles. Clinical manifestations may include diplopia, ptosis, and weakness of facial, bulbar, respiratory, and proximal limb muscles. The disease may remain limited to the ocular muscles. THYMOMA is commonly associated with this condition. (Adams et al., Principles of Neurology, 6th ed, p1459)\n    ", "id": "MESH:D009157"}
{"mention": "IFN", "mention_text": "A 63-year-old male experienced sudden diplopia after 9 weeks of administration of pegylated interferon (IFN) alpha-2b and ribavirin for chronic hepatitis C (CHC). Ophthalmologic examinations showed ptosis on the right upper lid and restricted right eye movement without any other neurological signs. A brain imaging study and repetitive nerve stimulation test indicated no abnormality. The acetylcholine receptor antibody titer and response to acetylcholinesterase inhibitors were negative, and the results of thyroid function tests were normal. The patient's ophthalmological symptoms improved rapidly 3 weeks after discontinuation of pegylated IFN alpha-2b and ribavirin. The ocular myasthenia associated with combination therapy of pegylated IFN alpha-2b and ribavirin for CHC is very rarely reported; therefore, we present this case with a review of the various eye complications of IFN therapy.", "entity": "peginterferon alfa-2b", "aliases": "PEG INF alfa-2b alpha-2b PEG-IFNalpha-2b PEG-Intron Pegintron ViraferonPeg peg-proline-INFalpha-2b peg-proline-interferon peginterferon pegylated interferon polyethylene glycol-interferon", "definition": "", "id": "MESH:C417083"}
{"mention": "glycine", "mention_text": "The glycine transporter-1 inhibitor SSR103800 displays a selective and specific antipsychotic-like profile in normal and transgenic mice.", "entity": "Glycine", "aliases": "Acid Aminoacetic Calcium Salt Glycine Cobalt Copper Carbonate (1:1) Monosodium (2:1) Monolithium Monopotassium Hydrochloride Phosphate Sulfate (3:1) Monoammonium Monopotasssium Sodium Hydrogen", "definition": "A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter.\n    ", "id": "MESH:D005998"}
{"mention": "Schizophrenia", "mention_text": "Schizophrenia has been initially associated with dysfunction in dopamine neurotransmission. However, the observation that antagonists of the glutamate N-methyl-D-aspartate (NMDA) receptor produce schizophrenic-like symptoms in humans has led to the idea of a dysfunctioning of the glutamatergic system via its NMDA receptor. As a result, there is a growing interest in the development of pharmacological agents with potential antipsychotic properties that enhance the activity of the glutamatergic system via a modulation of the NMDA receptor. Among them are glycine transporter-1 (GlyT1) inhibitors such as SSR103800, which indirectly enhance NMDA receptor function by increasing the glycine (a co-agonist for the NMDA receptor) levels in the synapse. This study aimed at investigating the potential antipsychotic-like properties of SSR103800, with a particular focus on models of hyperactivity, involving either drug challenge (ie, amphetamine and MK-801) or transgenic mice (ie, NMDA Nr1(neo-/-) and DAT(-/-)). Results showed that SSR103800 (10-30 mg/kg p.o.) blocked hyperactivity induced by the non-competitive NMDA receptor antagonist, MK-801 and partially reversed spontaneous hyperactivity of NMDA Nr1(neo-/-) mice. In contrast, SSR103800 failed to affect hyperactivity induced by amphetamine or naturally observed in dopamine transporter (DAT(-/-)) knockout mice (10-30 mg/kg p.o.). Importantly, both classical (haloperidol) and atypical (olanzapine, clozapine and aripiprazole) antipsychotics were effective in all these models of hyperactivity. However, unlike these latter, SSR103800 did not produce catalepsy (retention on the bar test) up to 30 mg/kg p.o. Together these findings show that the GlyT1 inhibitor, SSR103800, produces antipsychotic-like effects, which differ from those observed with compounds primarily targeting the dopaminergic system, and has a reduced side-effect potential as compared with these latter drugs.", "entity": "Schizophrenia", "aliases": "Dementia Praecox Disorder Schizophrenic Disorders Schizophrenia Schizophrenias", "definition": "A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior.\n    ", "id": "MESH:D012559"}
{"mention": "dopamine", "mention_text": "Schizophrenia has been initially associated with dysfunction in dopamine neurotransmission. However, the observation that antagonists of the glutamate N-methyl-D-aspartate (NMDA) receptor produce schizophrenic-like symptoms in humans has led to the idea of a dysfunctioning of the glutamatergic system via its NMDA receptor. As a result, there is a growing interest in the development of pharmacological agents with potential antipsychotic properties that enhance the activity of the glutamatergic system via a modulation of the NMDA receptor. Among them are glycine transporter-1 (GlyT1) inhibitors such as SSR103800, which indirectly enhance NMDA receptor function by increasing the glycine (a co-agonist for the NMDA receptor) levels in the synapse. This study aimed at investigating the potential antipsychotic-like properties of SSR103800, with a particular focus on models of hyperactivity, involving either drug challenge (ie, amphetamine and MK-801) or transgenic mice (ie, NMDA Nr1(neo-/-) and DAT(-/-)). Results showed that SSR103800 (10-30 mg/kg p.o.) blocked hyperactivity induced by the non-competitive NMDA receptor antagonist, MK-801 and partially reversed spontaneous hyperactivity of NMDA Nr1(neo-/-) mice. In contrast, SSR103800 failed to affect hyperactivity induced by amphetamine or naturally observed in dopamine transporter (DAT(-/-)) knockout mice (10-30 mg/kg p.o.). Importantly, both classical (haloperidol) and atypical (olanzapine, clozapine and aripiprazole) antipsychotics were effective in all these models of hyperactivity. However, unlike these latter, SSR103800 did not produce catalepsy (retention on the bar test) up to 30 mg/kg p.o. Together these findings show that the GlyT1 inhibitor, SSR103800, produces antipsychotic-like effects, which differ from those observed with compounds primarily targeting the dopaminergic system, and has a reduced side-effect potential as compared with these latter drugs.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "glutamate", "mention_text": "Schizophrenia has been initially associated with dysfunction in dopamine neurotransmission. However, the observation that antagonists of the glutamate N-methyl-D-aspartate (NMDA) receptor produce schizophrenic-like symptoms in humans has led to the idea of a dysfunctioning of the glutamatergic system via its NMDA receptor. As a result, there is a growing interest in the development of pharmacological agents with potential antipsychotic properties that enhance the activity of the glutamatergic system via a modulation of the NMDA receptor. Among them are glycine transporter-1 (GlyT1) inhibitors such as SSR103800, which indirectly enhance NMDA receptor function by increasing the glycine (a co-agonist for the NMDA receptor) levels in the synapse. This study aimed at investigating the potential antipsychotic-like properties of SSR103800, with a particular focus on models of hyperactivity, involving either drug challenge (ie, amphetamine and MK-801) or transgenic mice (ie, NMDA Nr1(neo-/-) and DAT(-/-)). Results showed that SSR103800 (10-30 mg/kg p.o.) blocked hyperactivity induced by the non-competitive NMDA receptor antagonist, MK-801 and partially reversed spontaneous hyperactivity of NMDA Nr1(neo-/-) mice. In contrast, SSR103800 failed to affect hyperactivity induced by amphetamine or naturally observed in dopamine transporter (DAT(-/-)) knockout mice (10-30 mg/kg p.o.). Importantly, both classical (haloperidol) and atypical (olanzapine, clozapine and aripiprazole) antipsychotics were effective in all these models of hyperactivity. However, unlike these latter, SSR103800 did not produce catalepsy (retention on the bar test) up to 30 mg/kg p.o. Together these findings show that the GlyT1 inhibitor, SSR103800, produces antipsychotic-like effects, which differ from those observed with compounds primarily targeting the dopaminergic system, and has a reduced side-effect potential as compared with these latter drugs.", "entity": "Glutamic Acid", "aliases": "Aluminum L Glutamate L-Glutamate D D-Glutamate Potassium Glutamic Acid (D)-Isomer L-Glutamic", "definition": "A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.\n    ", "id": "MESH:D018698"}
{"mention": "N-methyl-D-aspartate", "mention_text": "Schizophrenia has been initially associated with dysfunction in dopamine neurotransmission. However, the observation that antagonists of the glutamate N-methyl-D-aspartate (NMDA) receptor produce schizophrenic-like symptoms in humans has led to the idea of a dysfunctioning of the glutamatergic system via its NMDA receptor. As a result, there is a growing interest in the development of pharmacological agents with potential antipsychotic properties that enhance the activity of the glutamatergic system via a modulation of the NMDA receptor. Among them are glycine transporter-1 (GlyT1) inhibitors such as SSR103800, which indirectly enhance NMDA receptor function by increasing the glycine (a co-agonist for the NMDA receptor) levels in the synapse. This study aimed at investigating the potential antipsychotic-like properties of SSR103800, with a particular focus on models of hyperactivity, involving either drug challenge (ie, amphetamine and MK-801) or transgenic mice (ie, NMDA Nr1(neo-/-) and DAT(-/-)). Results showed that SSR103800 (10-30 mg/kg p.o.) blocked hyperactivity induced by the non-competitive NMDA receptor antagonist, MK-801 and partially reversed spontaneous hyperactivity of NMDA Nr1(neo-/-) mice. In contrast, SSR103800 failed to affect hyperactivity induced by amphetamine or naturally observed in dopamine transporter (DAT(-/-)) knockout mice (10-30 mg/kg p.o.). Importantly, both classical (haloperidol) and atypical (olanzapine, clozapine and aripiprazole) antipsychotics were effective in all these models of hyperactivity. However, unlike these latter, SSR103800 did not produce catalepsy (retention on the bar test) up to 30 mg/kg p.o. Together these findings show that the GlyT1 inhibitor, SSR103800, produces antipsychotic-like effects, which differ from those observed with compounds primarily targeting the dopaminergic system, and has a reduced side-effect potential as compared with these latter drugs.", "entity": "N-Methylaspartate", "aliases": "Acid N-Methyl-D-aspartic N Methyl D aspartate aspartic Methylaspartate N-Methyl-D-aspartate N-Methylaspartate NMDA", "definition": "An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).\n    ", "id": "MESH:D016202"}
{"mention": "NMDA", "mention_text": "Schizophrenia has been initially associated with dysfunction in dopamine neurotransmission. However, the observation that antagonists of the glutamate N-methyl-D-aspartate (NMDA) receptor produce schizophrenic-like symptoms in humans has led to the idea of a dysfunctioning of the glutamatergic system via its NMDA receptor. As a result, there is a growing interest in the development of pharmacological agents with potential antipsychotic properties that enhance the activity of the glutamatergic system via a modulation of the NMDA receptor. Among them are glycine transporter-1 (GlyT1) inhibitors such as SSR103800, which indirectly enhance NMDA receptor function by increasing the glycine (a co-agonist for the NMDA receptor) levels in the synapse. This study aimed at investigating the potential antipsychotic-like properties of SSR103800, with a particular focus on models of hyperactivity, involving either drug challenge (ie, amphetamine and MK-801) or transgenic mice (ie, NMDA Nr1(neo-/-) and DAT(-/-)). Results showed that SSR103800 (10-30 mg/kg p.o.) blocked hyperactivity induced by the non-competitive NMDA receptor antagonist, MK-801 and partially reversed spontaneous hyperactivity of NMDA Nr1(neo-/-) mice. In contrast, SSR103800 failed to affect hyperactivity induced by amphetamine or naturally observed in dopamine transporter (DAT(-/-)) knockout mice (10-30 mg/kg p.o.). Importantly, both classical (haloperidol) and atypical (olanzapine, clozapine and aripiprazole) antipsychotics were effective in all these models of hyperactivity. However, unlike these latter, SSR103800 did not produce catalepsy (retention on the bar test) up to 30 mg/kg p.o. Together these findings show that the GlyT1 inhibitor, SSR103800, produces antipsychotic-like effects, which differ from those observed with compounds primarily targeting the dopaminergic system, and has a reduced side-effect potential as compared with these latter drugs.", "entity": "N-Methylaspartate", "aliases": "Acid N-Methyl-D-aspartic N Methyl D aspartate aspartic Methylaspartate N-Methyl-D-aspartate N-Methylaspartate NMDA", "definition": "An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).\n    ", "id": "MESH:D016202"}
{"mention": "schizophrenic", "mention_text": "Schizophrenia has been initially associated with dysfunction in dopamine neurotransmission. However, the observation that antagonists of the glutamate N-methyl-D-aspartate (NMDA) receptor produce schizophrenic-like symptoms in humans has led to the idea of a dysfunctioning of the glutamatergic system via its NMDA receptor. As a result, there is a growing interest in the development of pharmacological agents with potential antipsychotic properties that enhance the activity of the glutamatergic system via a modulation of the NMDA receptor. Among them are glycine transporter-1 (GlyT1) inhibitors such as SSR103800, which indirectly enhance NMDA receptor function by increasing the glycine (a co-agonist for the NMDA receptor) levels in the synapse. This study aimed at investigating the potential antipsychotic-like properties of SSR103800, with a particular focus on models of hyperactivity, involving either drug challenge (ie, amphetamine and MK-801) or transgenic mice (ie, NMDA Nr1(neo-/-) and DAT(-/-)). Results showed that SSR103800 (10-30 mg/kg p.o.) blocked hyperactivity induced by the non-competitive NMDA receptor antagonist, MK-801 and partially reversed spontaneous hyperactivity of NMDA Nr1(neo-/-) mice. In contrast, SSR103800 failed to affect hyperactivity induced by amphetamine or naturally observed in dopamine transporter (DAT(-/-)) knockout mice (10-30 mg/kg p.o.). Importantly, both classical (haloperidol) and atypical (olanzapine, clozapine and aripiprazole) antipsychotics were effective in all these models of hyperactivity. However, unlike these latter, SSR103800 did not produce catalepsy (retention on the bar test) up to 30 mg/kg p.o. Together these findings show that the GlyT1 inhibitor, SSR103800, produces antipsychotic-like effects, which differ from those observed with compounds primarily targeting the dopaminergic system, and has a reduced side-effect potential as compared with these latter drugs.", "entity": "Schizophrenia", "aliases": "Dementia Praecox Disorder Schizophrenic Disorders Schizophrenia Schizophrenias", "definition": "A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior.\n    ", "id": "MESH:D012559"}
{"mention": "glycine", "mention_text": "Schizophrenia has been initially associated with dysfunction in dopamine neurotransmission. However, the observation that antagonists of the glutamate N-methyl-D-aspartate (NMDA) receptor produce schizophrenic-like symptoms in humans has led to the idea of a dysfunctioning of the glutamatergic system via its NMDA receptor. As a result, there is a growing interest in the development of pharmacological agents with potential antipsychotic properties that enhance the activity of the glutamatergic system via a modulation of the NMDA receptor. Among them are glycine transporter-1 (GlyT1) inhibitors such as SSR103800, which indirectly enhance NMDA receptor function by increasing the glycine (a co-agonist for the NMDA receptor) levels in the synapse. This study aimed at investigating the potential antipsychotic-like properties of SSR103800, with a particular focus on models of hyperactivity, involving either drug challenge (ie, amphetamine and MK-801) or transgenic mice (ie, NMDA Nr1(neo-/-) and DAT(-/-)). Results showed that SSR103800 (10-30 mg/kg p.o.) blocked hyperactivity induced by the non-competitive NMDA receptor antagonist, MK-801 and partially reversed spontaneous hyperactivity of NMDA Nr1(neo-/-) mice. In contrast, SSR103800 failed to affect hyperactivity induced by amphetamine or naturally observed in dopamine transporter (DAT(-/-)) knockout mice (10-30 mg/kg p.o.). Importantly, both classical (haloperidol) and atypical (olanzapine, clozapine and aripiprazole) antipsychotics were effective in all these models of hyperactivity. However, unlike these latter, SSR103800 did not produce catalepsy (retention on the bar test) up to 30 mg/kg p.o. Together these findings show that the GlyT1 inhibitor, SSR103800, produces antipsychotic-like effects, which differ from those observed with compounds primarily targeting the dopaminergic system, and has a reduced side-effect potential as compared with these latter drugs.", "entity": "Glycine", "aliases": "Acid Aminoacetic Calcium Salt Glycine Cobalt Copper Carbonate (1:1) Monosodium (2:1) Monolithium Monopotassium Hydrochloride Phosphate Sulfate (3:1) Monoammonium Monopotasssium Sodium Hydrogen", "definition": "A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter.\n    ", "id": "MESH:D005998"}
{"mention": "hyperactivity", "mention_text": "Schizophrenia has been initially associated with dysfunction in dopamine neurotransmission. However, the observation that antagonists of the glutamate N-methyl-D-aspartate (NMDA) receptor produce schizophrenic-like symptoms in humans has led to the idea of a dysfunctioning of the glutamatergic system via its NMDA receptor. As a result, there is a growing interest in the development of pharmacological agents with potential antipsychotic properties that enhance the activity of the glutamatergic system via a modulation of the NMDA receptor. Among them are glycine transporter-1 (GlyT1) inhibitors such as SSR103800, which indirectly enhance NMDA receptor function by increasing the glycine (a co-agonist for the NMDA receptor) levels in the synapse. This study aimed at investigating the potential antipsychotic-like properties of SSR103800, with a particular focus on models of hyperactivity, involving either drug challenge (ie, amphetamine and MK-801) or transgenic mice (ie, NMDA Nr1(neo-/-) and DAT(-/-)). Results showed that SSR103800 (10-30 mg/kg p.o.) blocked hyperactivity induced by the non-competitive NMDA receptor antagonist, MK-801 and partially reversed spontaneous hyperactivity of NMDA Nr1(neo-/-) mice. In contrast, SSR103800 failed to affect hyperactivity induced by amphetamine or naturally observed in dopamine transporter (DAT(-/-)) knockout mice (10-30 mg/kg p.o.). Importantly, both classical (haloperidol) and atypical (olanzapine, clozapine and aripiprazole) antipsychotics were effective in all these models of hyperactivity. However, unlike these latter, SSR103800 did not produce catalepsy (retention on the bar test) up to 30 mg/kg p.o. Together these findings show that the GlyT1 inhibitor, SSR103800, produces antipsychotic-like effects, which differ from those observed with compounds primarily targeting the dopaminergic system, and has a reduced side-effect potential as compared with these latter drugs.", "entity": "Hyperkinesis", "aliases": "Generalized Hyperkinesia Hyperkinesias Hyperactivity Motor Hyperkinesis Hyperkinetic Movement Movements", "definition": "Excessive movement of muscles of the body as a whole, which may be associated with organic or psychological disorders.\n    ", "id": "MESH:D006948"}
{"mention": "amphetamine", "mention_text": "Schizophrenia has been initially associated with dysfunction in dopamine neurotransmission. However, the observation that antagonists of the glutamate N-methyl-D-aspartate (NMDA) receptor produce schizophrenic-like symptoms in humans has led to the idea of a dysfunctioning of the glutamatergic system via its NMDA receptor. As a result, there is a growing interest in the development of pharmacological agents with potential antipsychotic properties that enhance the activity of the glutamatergic system via a modulation of the NMDA receptor. Among them are glycine transporter-1 (GlyT1) inhibitors such as SSR103800, which indirectly enhance NMDA receptor function by increasing the glycine (a co-agonist for the NMDA receptor) levels in the synapse. This study aimed at investigating the potential antipsychotic-like properties of SSR103800, with a particular focus on models of hyperactivity, involving either drug challenge (ie, amphetamine and MK-801) or transgenic mice (ie, NMDA Nr1(neo-/-) and DAT(-/-)). Results showed that SSR103800 (10-30 mg/kg p.o.) blocked hyperactivity induced by the non-competitive NMDA receptor antagonist, MK-801 and partially reversed spontaneous hyperactivity of NMDA Nr1(neo-/-) mice. In contrast, SSR103800 failed to affect hyperactivity induced by amphetamine or naturally observed in dopamine transporter (DAT(-/-)) knockout mice (10-30 mg/kg p.o.). Importantly, both classical (haloperidol) and atypical (olanzapine, clozapine and aripiprazole) antipsychotics were effective in all these models of hyperactivity. However, unlike these latter, SSR103800 did not produce catalepsy (retention on the bar test) up to 30 mg/kg p.o. Together these findings show that the GlyT1 inhibitor, SSR103800, produces antipsychotic-like effects, which differ from those observed with compounds primarily targeting the dopaminergic system, and has a reduced side-effect potential as compared with these latter drugs.", "entity": "Amphetamine", "aliases": "Amfetamine Amphetamine Sulfate (2:1) Centramina Desoxynorephedrin Fenamine Levoamphetamine Miquel Brand of Mydrial Phenamine Phenopromin Thyramine l l-Amphetamine levo levo-Amphetamine", "definition": "A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE.\n    ", "id": "MESH:D000661"}
{"mention": "MK-801", "mention_text": "Schizophrenia has been initially associated with dysfunction in dopamine neurotransmission. However, the observation that antagonists of the glutamate N-methyl-D-aspartate (NMDA) receptor produce schizophrenic-like symptoms in humans has led to the idea of a dysfunctioning of the glutamatergic system via its NMDA receptor. As a result, there is a growing interest in the development of pharmacological agents with potential antipsychotic properties that enhance the activity of the glutamatergic system via a modulation of the NMDA receptor. Among them are glycine transporter-1 (GlyT1) inhibitors such as SSR103800, which indirectly enhance NMDA receptor function by increasing the glycine (a co-agonist for the NMDA receptor) levels in the synapse. This study aimed at investigating the potential antipsychotic-like properties of SSR103800, with a particular focus on models of hyperactivity, involving either drug challenge (ie, amphetamine and MK-801) or transgenic mice (ie, NMDA Nr1(neo-/-) and DAT(-/-)). Results showed that SSR103800 (10-30 mg/kg p.o.) blocked hyperactivity induced by the non-competitive NMDA receptor antagonist, MK-801 and partially reversed spontaneous hyperactivity of NMDA Nr1(neo-/-) mice. In contrast, SSR103800 failed to affect hyperactivity induced by amphetamine or naturally observed in dopamine transporter (DAT(-/-)) knockout mice (10-30 mg/kg p.o.). Importantly, both classical (haloperidol) and atypical (olanzapine, clozapine and aripiprazole) antipsychotics were effective in all these models of hyperactivity. However, unlike these latter, SSR103800 did not produce catalepsy (retention on the bar test) up to 30 mg/kg p.o. Together these findings show that the GlyT1 inhibitor, SSR103800, produces antipsychotic-like effects, which differ from those observed with compounds primarily targeting the dopaminergic system, and has a reduced side-effect potential as compared with these latter drugs.", "entity": "Dizocilpine Maleate", "aliases": "Dizocilpine Maleate MK 801 MK-801 MK801", "definition": "A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects.\n    ", "id": "MESH:D016291"}
{"mention": "haloperidol", "mention_text": "Schizophrenia has been initially associated with dysfunction in dopamine neurotransmission. However, the observation that antagonists of the glutamate N-methyl-D-aspartate (NMDA) receptor produce schizophrenic-like symptoms in humans has led to the idea of a dysfunctioning of the glutamatergic system via its NMDA receptor. As a result, there is a growing interest in the development of pharmacological agents with potential antipsychotic properties that enhance the activity of the glutamatergic system via a modulation of the NMDA receptor. Among them are glycine transporter-1 (GlyT1) inhibitors such as SSR103800, which indirectly enhance NMDA receptor function by increasing the glycine (a co-agonist for the NMDA receptor) levels in the synapse. This study aimed at investigating the potential antipsychotic-like properties of SSR103800, with a particular focus on models of hyperactivity, involving either drug challenge (ie, amphetamine and MK-801) or transgenic mice (ie, NMDA Nr1(neo-/-) and DAT(-/-)). Results showed that SSR103800 (10-30 mg/kg p.o.) blocked hyperactivity induced by the non-competitive NMDA receptor antagonist, MK-801 and partially reversed spontaneous hyperactivity of NMDA Nr1(neo-/-) mice. In contrast, SSR103800 failed to affect hyperactivity induced by amphetamine or naturally observed in dopamine transporter (DAT(-/-)) knockout mice (10-30 mg/kg p.o.). Importantly, both classical (haloperidol) and atypical (olanzapine, clozapine and aripiprazole) antipsychotics were effective in all these models of hyperactivity. However, unlike these latter, SSR103800 did not produce catalepsy (retention on the bar test) up to 30 mg/kg p.o. Together these findings show that the GlyT1 inhibitor, SSR103800, produces antipsychotic-like effects, which differ from those observed with compounds primarily targeting the dopaminergic system, and has a reduced side-effect potential as compared with these latter drugs.", "entity": "Haloperidol", "aliases": "Haldol Haloperidol", "definition": "A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)\n    ", "id": "MESH:D006220"}
{"mention": "olanzapine", "mention_text": "Schizophrenia has been initially associated with dysfunction in dopamine neurotransmission. However, the observation that antagonists of the glutamate N-methyl-D-aspartate (NMDA) receptor produce schizophrenic-like symptoms in humans has led to the idea of a dysfunctioning of the glutamatergic system via its NMDA receptor. As a result, there is a growing interest in the development of pharmacological agents with potential antipsychotic properties that enhance the activity of the glutamatergic system via a modulation of the NMDA receptor. Among them are glycine transporter-1 (GlyT1) inhibitors such as SSR103800, which indirectly enhance NMDA receptor function by increasing the glycine (a co-agonist for the NMDA receptor) levels in the synapse. This study aimed at investigating the potential antipsychotic-like properties of SSR103800, with a particular focus on models of hyperactivity, involving either drug challenge (ie, amphetamine and MK-801) or transgenic mice (ie, NMDA Nr1(neo-/-) and DAT(-/-)). Results showed that SSR103800 (10-30 mg/kg p.o.) blocked hyperactivity induced by the non-competitive NMDA receptor antagonist, MK-801 and partially reversed spontaneous hyperactivity of NMDA Nr1(neo-/-) mice. In contrast, SSR103800 failed to affect hyperactivity induced by amphetamine or naturally observed in dopamine transporter (DAT(-/-)) knockout mice (10-30 mg/kg p.o.). Importantly, both classical (haloperidol) and atypical (olanzapine, clozapine and aripiprazole) antipsychotics were effective in all these models of hyperactivity. However, unlike these latter, SSR103800 did not produce catalepsy (retention on the bar test) up to 30 mg/kg p.o. Together these findings show that the GlyT1 inhibitor, SSR103800, produces antipsychotic-like effects, which differ from those observed with compounds primarily targeting the dopaminergic system, and has a reduced side-effect potential as compared with these latter drugs.", "entity": "olanzapine", "aliases": "2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno(2,3-b)(1,5)benzodiazepine LY 170053 LY-170052 Zyprexa olanzapine pamoate", "definition": "", "id": "MESH:C076029"}
{"mention": "clozapine", "mention_text": "Schizophrenia has been initially associated with dysfunction in dopamine neurotransmission. However, the observation that antagonists of the glutamate N-methyl-D-aspartate (NMDA) receptor produce schizophrenic-like symptoms in humans has led to the idea of a dysfunctioning of the glutamatergic system via its NMDA receptor. As a result, there is a growing interest in the development of pharmacological agents with potential antipsychotic properties that enhance the activity of the glutamatergic system via a modulation of the NMDA receptor. Among them are glycine transporter-1 (GlyT1) inhibitors such as SSR103800, which indirectly enhance NMDA receptor function by increasing the glycine (a co-agonist for the NMDA receptor) levels in the synapse. This study aimed at investigating the potential antipsychotic-like properties of SSR103800, with a particular focus on models of hyperactivity, involving either drug challenge (ie, amphetamine and MK-801) or transgenic mice (ie, NMDA Nr1(neo-/-) and DAT(-/-)). Results showed that SSR103800 (10-30 mg/kg p.o.) blocked hyperactivity induced by the non-competitive NMDA receptor antagonist, MK-801 and partially reversed spontaneous hyperactivity of NMDA Nr1(neo-/-) mice. In contrast, SSR103800 failed to affect hyperactivity induced by amphetamine or naturally observed in dopamine transporter (DAT(-/-)) knockout mice (10-30 mg/kg p.o.). Importantly, both classical (haloperidol) and atypical (olanzapine, clozapine and aripiprazole) antipsychotics were effective in all these models of hyperactivity. However, unlike these latter, SSR103800 did not produce catalepsy (retention on the bar test) up to 30 mg/kg p.o. Together these findings show that the GlyT1 inhibitor, SSR103800, produces antipsychotic-like effects, which differ from those observed with compounds primarily targeting the dopaminergic system, and has a reduced side-effect potential as compared with these latter drugs.", "entity": "Clozapine", "aliases": "Clozapine Clozaril Leponex", "definition": "A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.\n    ", "id": "MESH:D003024"}
{"mention": "aripiprazole", "mention_text": "Schizophrenia has been initially associated with dysfunction in dopamine neurotransmission. However, the observation that antagonists of the glutamate N-methyl-D-aspartate (NMDA) receptor produce schizophrenic-like symptoms in humans has led to the idea of a dysfunctioning of the glutamatergic system via its NMDA receptor. As a result, there is a growing interest in the development of pharmacological agents with potential antipsychotic properties that enhance the activity of the glutamatergic system via a modulation of the NMDA receptor. Among them are glycine transporter-1 (GlyT1) inhibitors such as SSR103800, which indirectly enhance NMDA receptor function by increasing the glycine (a co-agonist for the NMDA receptor) levels in the synapse. This study aimed at investigating the potential antipsychotic-like properties of SSR103800, with a particular focus on models of hyperactivity, involving either drug challenge (ie, amphetamine and MK-801) or transgenic mice (ie, NMDA Nr1(neo-/-) and DAT(-/-)). Results showed that SSR103800 (10-30 mg/kg p.o.) blocked hyperactivity induced by the non-competitive NMDA receptor antagonist, MK-801 and partially reversed spontaneous hyperactivity of NMDA Nr1(neo-/-) mice. In contrast, SSR103800 failed to affect hyperactivity induced by amphetamine or naturally observed in dopamine transporter (DAT(-/-)) knockout mice (10-30 mg/kg p.o.). Importantly, both classical (haloperidol) and atypical (olanzapine, clozapine and aripiprazole) antipsychotics were effective in all these models of hyperactivity. However, unlike these latter, SSR103800 did not produce catalepsy (retention on the bar test) up to 30 mg/kg p.o. Together these findings show that the GlyT1 inhibitor, SSR103800, produces antipsychotic-like effects, which differ from those observed with compounds primarily targeting the dopaminergic system, and has a reduced side-effect potential as compared with these latter drugs.", "entity": "aripiprazole", "aliases": "7-(4-(4-(2,3-dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone Abilify OPC 14597 OPC-14597 aripiprazole", "definition": "", "id": "MESH:C094645"}
{"mention": "catalepsy", "mention_text": "Schizophrenia has been initially associated with dysfunction in dopamine neurotransmission. However, the observation that antagonists of the glutamate N-methyl-D-aspartate (NMDA) receptor produce schizophrenic-like symptoms in humans has led to the idea of a dysfunctioning of the glutamatergic system via its NMDA receptor. As a result, there is a growing interest in the development of pharmacological agents with potential antipsychotic properties that enhance the activity of the glutamatergic system via a modulation of the NMDA receptor. Among them are glycine transporter-1 (GlyT1) inhibitors such as SSR103800, which indirectly enhance NMDA receptor function by increasing the glycine (a co-agonist for the NMDA receptor) levels in the synapse. This study aimed at investigating the potential antipsychotic-like properties of SSR103800, with a particular focus on models of hyperactivity, involving either drug challenge (ie, amphetamine and MK-801) or transgenic mice (ie, NMDA Nr1(neo-/-) and DAT(-/-)). Results showed that SSR103800 (10-30 mg/kg p.o.) blocked hyperactivity induced by the non-competitive NMDA receptor antagonist, MK-801 and partially reversed spontaneous hyperactivity of NMDA Nr1(neo-/-) mice. In contrast, SSR103800 failed to affect hyperactivity induced by amphetamine or naturally observed in dopamine transporter (DAT(-/-)) knockout mice (10-30 mg/kg p.o.). Importantly, both classical (haloperidol) and atypical (olanzapine, clozapine and aripiprazole) antipsychotics were effective in all these models of hyperactivity. However, unlike these latter, SSR103800 did not produce catalepsy (retention on the bar test) up to 30 mg/kg p.o. Together these findings show that the GlyT1 inhibitor, SSR103800, produces antipsychotic-like effects, which differ from those observed with compounds primarily targeting the dopaminergic system, and has a reduced side-effect potential as compared with these latter drugs.", "entity": "Catalepsy", "aliases": "Anochlesia Anochlesias Catalepsies Catalepsy Cerea Flexibilitas Flexibilities Waxy Flexibility", "definition": "A condition characterized by inactivity, decreased responsiveness to stimuli, and a tendency to maintain an immobile posture. The limbs tend to remain in whatever position they are placed (waxy flexibility). Catalepsy may be associated with PSYCHOTIC DISORDERS (e.g., SCHIZOPHRENIA, CATATONIC), nervous system drug toxicity, and other conditions.\n    ", "id": "MESH:D002375"}
{"mention": "Phenylephrine", "mention_text": "Phenylephrine but not ephedrine reduces frontal lobe oxygenation following anesthesia-induced hypotension.", "entity": "Phenylephrine", "aliases": "(R)-3-Hydroxy-alpha-((methylamino)methyl)benzenemethanol Metaoxedrin Metasympatol Mezaton Neo Synephrine Neo-Synephrine Neosynephrine Phenylephrine Hydrochloride Tannate", "definition": "An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.\n    ", "id": "MESH:D010656"}
{"mention": "ephedrine", "mention_text": "Phenylephrine but not ephedrine reduces frontal lobe oxygenation following anesthesia-induced hypotension.", "entity": "Ephedrine", "aliases": "Ephedrine Erythro Isomer Hydrochloride Renaudin Sulfate of Brand Sal Phedrine Sal-Phedrine SalPhedrine Wendt", "definition": "A phenethylamine found in EPHEDRA SINICA. PSEUDOEPHEDRINE is an isomer. It is an alpha- and beta-adrenergic agonist that may also enhance release of norepinephrine. It has been used for asthma, heart failure, rhinitis, and urinary incontinence, and for its central nervous system stimulatory effects in the treatment of narcolepsy and depression. It has become less extensively used with the advent of more selective agonists.\n    ", "id": "MESH:D004809"}
{"mention": "reduces frontal lobe oxygenation", "mention_text": "Phenylephrine but not ephedrine reduces frontal lobe oxygenation following anesthesia-induced hypotension.", "entity": "Hypoxia, Brain", "aliases": "Anoxia Brain Cerebral Anoxic Damage Encephalopathies Encephalopathy Hypoxic Hypoxia", "definition": "A reduction in brain oxygen supply due to ANOXEMIA (a reduced amount of oxygen being carried in the blood by HEMOGLOBIN), or to a restriction of the blood supply to the brain, or both. Severe hypoxia is referred to as anoxia, and is a relatively common cause of injury to the central nervous system. Prolonged brain anoxia may lead to BRAIN DEATH or a PERSISTENT VEGETATIVE STATE. Histologically, this condition is characterized by neuronal loss which is most prominent in the HIPPOCAMPUS; GLOBUS PALLIDUS; CEREBELLUM; and inferior olives.\n    ", "id": "MESH:D002534"}
{"mention": "hypotension", "mention_text": "Phenylephrine but not ephedrine reduces frontal lobe oxygenation following anesthesia-induced hypotension.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "hypotension", "mention_text": "BACKGROUND: Vasopressor agents are used to correct anesthesia-induced hypotension. We describe the effect of phenylephrine and ephedrine on frontal lobe oxygenation (S(c)O(2)) following anesthesia-induced hypotension. METHODS: Following induction of anesthesia by fentanyl (0.15 mg kg(-1)) and propofol (2.0 mg kg(-1)), 13 patients received phenylephrine (0.1 mg iv) and 12 patients received ephedrine (10 mg iv) to restore mean arterial pressure (MAP). Heart rate (HR), MAP, stroke volume (SV), cardiac output (CO), and frontal lobe oxygenation (S(c)O(2)) were registered. RESULTS: Induction of anesthesia was followed by a decrease in MAP, HR, SV, and CO concomitant with an elevation in S(c)O(2). After administration of phenylephrine, MAP increased (51 +/- 12 to 81 +/- 13 mmHg; P < 0.001; mean +/- SD). However, a 14% (from 70 +/- 8% to 60 +/- 7%) reduction in S(c)O(2) (P < 0.05) followed with no change in CO (3.7 +/- 1.1 to 3.4 +/- 0.9 l min(-1)). The administration of ephedrine led to a similar increase in MAP (53 +/- 9 to 79 +/- 8 mmHg; P < 0.001), restored CO (3.2 +/- 1.2 to 5.0 +/- 1.3 l min(-1)), and preserved S(c)O(2). CONCLUSIONS: The utilization of phenylephrine to correct hypotension induced by anesthesia has a negative impact on S(c)O(2) while ephedrine maintains frontal lobe oxygenation potentially related to an increase in CO.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "phenylephrine", "mention_text": "BACKGROUND: Vasopressor agents are used to correct anesthesia-induced hypotension. We describe the effect of phenylephrine and ephedrine on frontal lobe oxygenation (S(c)O(2)) following anesthesia-induced hypotension. METHODS: Following induction of anesthesia by fentanyl (0.15 mg kg(-1)) and propofol (2.0 mg kg(-1)), 13 patients received phenylephrine (0.1 mg iv) and 12 patients received ephedrine (10 mg iv) to restore mean arterial pressure (MAP). Heart rate (HR), MAP, stroke volume (SV), cardiac output (CO), and frontal lobe oxygenation (S(c)O(2)) were registered. RESULTS: Induction of anesthesia was followed by a decrease in MAP, HR, SV, and CO concomitant with an elevation in S(c)O(2). After administration of phenylephrine, MAP increased (51 +/- 12 to 81 +/- 13 mmHg; P < 0.001; mean +/- SD). However, a 14% (from 70 +/- 8% to 60 +/- 7%) reduction in S(c)O(2) (P < 0.05) followed with no change in CO (3.7 +/- 1.1 to 3.4 +/- 0.9 l min(-1)). The administration of ephedrine led to a similar increase in MAP (53 +/- 9 to 79 +/- 8 mmHg; P < 0.001), restored CO (3.2 +/- 1.2 to 5.0 +/- 1.3 l min(-1)), and preserved S(c)O(2). CONCLUSIONS: The utilization of phenylephrine to correct hypotension induced by anesthesia has a negative impact on S(c)O(2) while ephedrine maintains frontal lobe oxygenation potentially related to an increase in CO.", "entity": "Phenylephrine", "aliases": "(R)-3-Hydroxy-alpha-((methylamino)methyl)benzenemethanol Metaoxedrin Metasympatol Mezaton Neo Synephrine Neo-Synephrine Neosynephrine Phenylephrine Hydrochloride Tannate", "definition": "An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.\n    ", "id": "MESH:D010656"}
{"mention": "ephedrine", "mention_text": "BACKGROUND: Vasopressor agents are used to correct anesthesia-induced hypotension. We describe the effect of phenylephrine and ephedrine on frontal lobe oxygenation (S(c)O(2)) following anesthesia-induced hypotension. METHODS: Following induction of anesthesia by fentanyl (0.15 mg kg(-1)) and propofol (2.0 mg kg(-1)), 13 patients received phenylephrine (0.1 mg iv) and 12 patients received ephedrine (10 mg iv) to restore mean arterial pressure (MAP). Heart rate (HR), MAP, stroke volume (SV), cardiac output (CO), and frontal lobe oxygenation (S(c)O(2)) were registered. RESULTS: Induction of anesthesia was followed by a decrease in MAP, HR, SV, and CO concomitant with an elevation in S(c)O(2). After administration of phenylephrine, MAP increased (51 +/- 12 to 81 +/- 13 mmHg; P < 0.001; mean +/- SD). However, a 14% (from 70 +/- 8% to 60 +/- 7%) reduction in S(c)O(2) (P < 0.05) followed with no change in CO (3.7 +/- 1.1 to 3.4 +/- 0.9 l min(-1)). The administration of ephedrine led to a similar increase in MAP (53 +/- 9 to 79 +/- 8 mmHg; P < 0.001), restored CO (3.2 +/- 1.2 to 5.0 +/- 1.3 l min(-1)), and preserved S(c)O(2). CONCLUSIONS: The utilization of phenylephrine to correct hypotension induced by anesthesia has a negative impact on S(c)O(2) while ephedrine maintains frontal lobe oxygenation potentially related to an increase in CO.", "entity": "Ephedrine", "aliases": "Ephedrine Erythro Isomer Hydrochloride Renaudin Sulfate of Brand Sal Phedrine Sal-Phedrine SalPhedrine Wendt", "definition": "A phenethylamine found in EPHEDRA SINICA. PSEUDOEPHEDRINE is an isomer. It is an alpha- and beta-adrenergic agonist that may also enhance release of norepinephrine. It has been used for asthma, heart failure, rhinitis, and urinary incontinence, and for its central nervous system stimulatory effects in the treatment of narcolepsy and depression. It has become less extensively used with the advent of more selective agonists.\n    ", "id": "MESH:D004809"}
{"mention": "fentanyl", "mention_text": "BACKGROUND: Vasopressor agents are used to correct anesthesia-induced hypotension. We describe the effect of phenylephrine and ephedrine on frontal lobe oxygenation (S(c)O(2)) following anesthesia-induced hypotension. METHODS: Following induction of anesthesia by fentanyl (0.15 mg kg(-1)) and propofol (2.0 mg kg(-1)), 13 patients received phenylephrine (0.1 mg iv) and 12 patients received ephedrine (10 mg iv) to restore mean arterial pressure (MAP). Heart rate (HR), MAP, stroke volume (SV), cardiac output (CO), and frontal lobe oxygenation (S(c)O(2)) were registered. RESULTS: Induction of anesthesia was followed by a decrease in MAP, HR, SV, and CO concomitant with an elevation in S(c)O(2). After administration of phenylephrine, MAP increased (51 +/- 12 to 81 +/- 13 mmHg; P < 0.001; mean +/- SD). However, a 14% (from 70 +/- 8% to 60 +/- 7%) reduction in S(c)O(2) (P < 0.05) followed with no change in CO (3.7 +/- 1.1 to 3.4 +/- 0.9 l min(-1)). The administration of ephedrine led to a similar increase in MAP (53 +/- 9 to 79 +/- 8 mmHg; P < 0.001), restored CO (3.2 +/- 1.2 to 5.0 +/- 1.3 l min(-1)), and preserved S(c)O(2). CONCLUSIONS: The utilization of phenylephrine to correct hypotension induced by anesthesia has a negative impact on S(c)O(2) while ephedrine maintains frontal lobe oxygenation potentially related to an increase in CO.", "entity": "Fentanyl", "aliases": "Cephalon Brand of Fentanyl Buccal OraVescent Duragesic Durogesic Fentanest Citrate Fentora Janssen Pharmaceutica Phentanyl R 4263 R-4263 R4263 Sublimaze Transmucosal Oral", "definition": "A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1078)\n    ", "id": "MESH:D005283"}
{"mention": "propofol", "mention_text": "BACKGROUND: Vasopressor agents are used to correct anesthesia-induced hypotension. We describe the effect of phenylephrine and ephedrine on frontal lobe oxygenation (S(c)O(2)) following anesthesia-induced hypotension. METHODS: Following induction of anesthesia by fentanyl (0.15 mg kg(-1)) and propofol (2.0 mg kg(-1)), 13 patients received phenylephrine (0.1 mg iv) and 12 patients received ephedrine (10 mg iv) to restore mean arterial pressure (MAP). Heart rate (HR), MAP, stroke volume (SV), cardiac output (CO), and frontal lobe oxygenation (S(c)O(2)) were registered. RESULTS: Induction of anesthesia was followed by a decrease in MAP, HR, SV, and CO concomitant with an elevation in S(c)O(2). After administration of phenylephrine, MAP increased (51 +/- 12 to 81 +/- 13 mmHg; P < 0.001; mean +/- SD). However, a 14% (from 70 +/- 8% to 60 +/- 7%) reduction in S(c)O(2) (P < 0.05) followed with no change in CO (3.7 +/- 1.1 to 3.4 +/- 0.9 l min(-1)). The administration of ephedrine led to a similar increase in MAP (53 +/- 9 to 79 +/- 8 mmHg; P < 0.001), restored CO (3.2 +/- 1.2 to 5.0 +/- 1.3 l min(-1)), and preserved S(c)O(2). CONCLUSIONS: The utilization of phenylephrine to correct hypotension induced by anesthesia has a negative impact on S(c)O(2) while ephedrine maintains frontal lobe oxygenation potentially related to an increase in CO.", "entity": "Propofol", "aliases": "2,6 Diisopropylphenol 2,6-Bis(1-methylethyl)phenol 2,6-Diisopropylphenol Abbott Brand of Propofol Alpha Aquafol Astra AstraZeneca Braun Curamed Diprivan Disoprivan Disoprofol Fresenius Kabi Fresofol ICI 35,868 35868 ICI-35,868 ICI-35868 ICI35,868 ICI35868 Ivofol Juste Parnell Pisa MCT Rovi Propofol-Lipuro Recofol Schering Zeneca", "definition": "An intravenous anesthetic agent which has the advantage of a very rapid onset after infusion or bolus injection plus a very short recovery period of a couple of minutes. (From Smith and Reynard, Textbook of Pharmacology, 1992, 1st ed, p206). Propofol has been used as ANTICONVULSANTS and ANTIEMETICS.\n    ", "id": "MESH:D015742"}
{"mention": "stroke", "mention_text": "BACKGROUND: Vasopressor agents are used to correct anesthesia-induced hypotension. We describe the effect of phenylephrine and ephedrine on frontal lobe oxygenation (S(c)O(2)) following anesthesia-induced hypotension. METHODS: Following induction of anesthesia by fentanyl (0.15 mg kg(-1)) and propofol (2.0 mg kg(-1)), 13 patients received phenylephrine (0.1 mg iv) and 12 patients received ephedrine (10 mg iv) to restore mean arterial pressure (MAP). Heart rate (HR), MAP, stroke volume (SV), cardiac output (CO), and frontal lobe oxygenation (S(c)O(2)) were registered. RESULTS: Induction of anesthesia was followed by a decrease in MAP, HR, SV, and CO concomitant with an elevation in S(c)O(2). After administration of phenylephrine, MAP increased (51 +/- 12 to 81 +/- 13 mmHg; P < 0.001; mean +/- SD). However, a 14% (from 70 +/- 8% to 60 +/- 7%) reduction in S(c)O(2) (P < 0.05) followed with no change in CO (3.7 +/- 1.1 to 3.4 +/- 0.9 l min(-1)). The administration of ephedrine led to a similar increase in MAP (53 +/- 9 to 79 +/- 8 mmHg; P < 0.001), restored CO (3.2 +/- 1.2 to 5.0 +/- 1.3 l min(-1)), and preserved S(c)O(2). CONCLUSIONS: The utilization of phenylephrine to correct hypotension induced by anesthesia has a negative impact on S(c)O(2) while ephedrine maintains frontal lobe oxygenation potentially related to an increase in CO.", "entity": "Stroke", "aliases": "Acute Cerebrovascular Accident Accidents Stroke Strokes Apoplexy Brain Vascular CVA (Cerebrovascular Accident) CVAs Cerebral", "definition": "A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)\n    ", "id": "MESH:D020521"}
{"mention": "a decrease in MAP", "mention_text": "BACKGROUND: Vasopressor agents are used to correct anesthesia-induced hypotension. We describe the effect of phenylephrine and ephedrine on frontal lobe oxygenation (S(c)O(2)) following anesthesia-induced hypotension. METHODS: Following induction of anesthesia by fentanyl (0.15 mg kg(-1)) and propofol (2.0 mg kg(-1)), 13 patients received phenylephrine (0.1 mg iv) and 12 patients received ephedrine (10 mg iv) to restore mean arterial pressure (MAP). Heart rate (HR), MAP, stroke volume (SV), cardiac output (CO), and frontal lobe oxygenation (S(c)O(2)) were registered. RESULTS: Induction of anesthesia was followed by a decrease in MAP, HR, SV, and CO concomitant with an elevation in S(c)O(2). After administration of phenylephrine, MAP increased (51 +/- 12 to 81 +/- 13 mmHg; P < 0.001; mean +/- SD). However, a 14% (from 70 +/- 8% to 60 +/- 7%) reduction in S(c)O(2) (P < 0.05) followed with no change in CO (3.7 +/- 1.1 to 3.4 +/- 0.9 l min(-1)). The administration of ephedrine led to a similar increase in MAP (53 +/- 9 to 79 +/- 8 mmHg; P < 0.001), restored CO (3.2 +/- 1.2 to 5.0 +/- 1.3 l min(-1)), and preserved S(c)O(2). CONCLUSIONS: The utilization of phenylephrine to correct hypotension induced by anesthesia has a negative impact on S(c)O(2) while ephedrine maintains frontal lobe oxygenation potentially related to an increase in CO.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "obsessive-compulsive-like behaviors", "mention_text": "A novel, multiple symptom model of obsessive-compulsive-like behaviors in animals.", "entity": "Obsessive-Compulsive Disorder", "aliases": "Anankastic Personalities Personality Disorder Obsessive-Compulsive Disorders Neuroses Neurosis Obsessive Compulsive", "definition": "An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which the individual does not derive pleasure although it may provide a release from tension.\n    ", "id": "MESH:D009771"}
{"mention": "obsessive-compulsive disorder", "mention_text": "BACKGROUND: Current animal models of obsessive-compulsive disorder (OCD) typically involve acute, drug-induced symptom provocation or a genetic association with stereotypies or anxiety. None of these current models demonstrate multiple OCD-like behaviors. METHODS: Neonatal rats were treated with the tricyclic antidepressant clomipramine or vehicle between days 9 and 16 twice daily and behaviorally tested in adulthood. RESULTS: Clomipramine exposure in immature rats produced significant behavioral and biochemical changes that include enhanced anxiety (elevated plus maze and marble burying), behavioral inflexibility (perseveration in the spontaneous alternation task and impaired reversal learning), working memory impairment (e.g., win-shift paradigm), hoarding, and corticostriatal dysfunction. Dopamine D2 receptors were elevated in the striatum, whereas serotonin 2C, but not serotonin 1A, receptors were elevated in the orbital frontal cortex. CONCLUSIONS: This is the first demonstration of multiple symptoms consistent with an OCD-like profile in animals. Moreover, these behaviors are accompanied by biochemical changes in brain regions previously identified as relevant to OCD. This novel model of OCD demonstrates that drug exposure during a sensitive period can program disease-like systems permanently, which could have implications for current and future therapeutic strategies for this and other psychiatric disorders.", "entity": "Obsessive-Compulsive Disorder", "aliases": "Anankastic Personalities Personality Disorder Obsessive-Compulsive Disorders Neuroses Neurosis Obsessive Compulsive", "definition": "An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which the individual does not derive pleasure although it may provide a release from tension.\n    ", "id": "MESH:D009771"}
{"mention": "OCD", "mention_text": "BACKGROUND: Current animal models of obsessive-compulsive disorder (OCD) typically involve acute, drug-induced symptom provocation or a genetic association with stereotypies or anxiety. None of these current models demonstrate multiple OCD-like behaviors. METHODS: Neonatal rats were treated with the tricyclic antidepressant clomipramine or vehicle between days 9 and 16 twice daily and behaviorally tested in adulthood. RESULTS: Clomipramine exposure in immature rats produced significant behavioral and biochemical changes that include enhanced anxiety (elevated plus maze and marble burying), behavioral inflexibility (perseveration in the spontaneous alternation task and impaired reversal learning), working memory impairment (e.g., win-shift paradigm), hoarding, and corticostriatal dysfunction. Dopamine D2 receptors were elevated in the striatum, whereas serotonin 2C, but not serotonin 1A, receptors were elevated in the orbital frontal cortex. CONCLUSIONS: This is the first demonstration of multiple symptoms consistent with an OCD-like profile in animals. Moreover, these behaviors are accompanied by biochemical changes in brain regions previously identified as relevant to OCD. This novel model of OCD demonstrates that drug exposure during a sensitive period can program disease-like systems permanently, which could have implications for current and future therapeutic strategies for this and other psychiatric disorders.", "entity": "Obsessive-Compulsive Disorder", "aliases": "Anankastic Personalities Personality Disorder Obsessive-Compulsive Disorders Neuroses Neurosis Obsessive Compulsive", "definition": "An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which the individual does not derive pleasure although it may provide a release from tension.\n    ", "id": "MESH:D009771"}
{"mention": "anxiety", "mention_text": "BACKGROUND: Current animal models of obsessive-compulsive disorder (OCD) typically involve acute, drug-induced symptom provocation or a genetic association with stereotypies or anxiety. None of these current models demonstrate multiple OCD-like behaviors. METHODS: Neonatal rats were treated with the tricyclic antidepressant clomipramine or vehicle between days 9 and 16 twice daily and behaviorally tested in adulthood. RESULTS: Clomipramine exposure in immature rats produced significant behavioral and biochemical changes that include enhanced anxiety (elevated plus maze and marble burying), behavioral inflexibility (perseveration in the spontaneous alternation task and impaired reversal learning), working memory impairment (e.g., win-shift paradigm), hoarding, and corticostriatal dysfunction. Dopamine D2 receptors were elevated in the striatum, whereas serotonin 2C, but not serotonin 1A, receptors were elevated in the orbital frontal cortex. CONCLUSIONS: This is the first demonstration of multiple symptoms consistent with an OCD-like profile in animals. Moreover, these behaviors are accompanied by biochemical changes in brain regions previously identified as relevant to OCD. This novel model of OCD demonstrates that drug exposure during a sensitive period can program disease-like systems permanently, which could have implications for current and future therapeutic strategies for this and other psychiatric disorders.", "entity": "Anxiety Disorders", "aliases": "Anxiety Disorder Disorders Neuroses State Neurotic States", "definition": "Persistent and disabling ANXIETY.\n    ", "id": "MESH:D001008"}
{"mention": "antidepressant", "mention_text": "BACKGROUND: Current animal models of obsessive-compulsive disorder (OCD) typically involve acute, drug-induced symptom provocation or a genetic association with stereotypies or anxiety. None of these current models demonstrate multiple OCD-like behaviors. METHODS: Neonatal rats were treated with the tricyclic antidepressant clomipramine or vehicle between days 9 and 16 twice daily and behaviorally tested in adulthood. RESULTS: Clomipramine exposure in immature rats produced significant behavioral and biochemical changes that include enhanced anxiety (elevated plus maze and marble burying), behavioral inflexibility (perseveration in the spontaneous alternation task and impaired reversal learning), working memory impairment (e.g., win-shift paradigm), hoarding, and corticostriatal dysfunction. Dopamine D2 receptors were elevated in the striatum, whereas serotonin 2C, but not serotonin 1A, receptors were elevated in the orbital frontal cortex. CONCLUSIONS: This is the first demonstration of multiple symptoms consistent with an OCD-like profile in animals. Moreover, these behaviors are accompanied by biochemical changes in brain regions previously identified as relevant to OCD. This novel model of OCD demonstrates that drug exposure during a sensitive period can program disease-like systems permanently, which could have implications for current and future therapeutic strategies for this and other psychiatric disorders.", "entity": "Antidepressive Agents", "aliases": "Agents Antidepressive Antidepressant Drugs Antidepressants Thymoanaleptics Thymoleptics", "definition": "Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.\n    ", "id": "MESH:D000928"}
{"mention": "clomipramine", "mention_text": "BACKGROUND: Current animal models of obsessive-compulsive disorder (OCD) typically involve acute, drug-induced symptom provocation or a genetic association with stereotypies or anxiety. None of these current models demonstrate multiple OCD-like behaviors. METHODS: Neonatal rats were treated with the tricyclic antidepressant clomipramine or vehicle between days 9 and 16 twice daily and behaviorally tested in adulthood. RESULTS: Clomipramine exposure in immature rats produced significant behavioral and biochemical changes that include enhanced anxiety (elevated plus maze and marble burying), behavioral inflexibility (perseveration in the spontaneous alternation task and impaired reversal learning), working memory impairment (e.g., win-shift paradigm), hoarding, and corticostriatal dysfunction. Dopamine D2 receptors were elevated in the striatum, whereas serotonin 2C, but not serotonin 1A, receptors were elevated in the orbital frontal cortex. CONCLUSIONS: This is the first demonstration of multiple symptoms consistent with an OCD-like profile in animals. Moreover, these behaviors are accompanied by biochemical changes in brain regions previously identified as relevant to OCD. This novel model of OCD demonstrates that drug exposure during a sensitive period can program disease-like systems permanently, which could have implications for current and future therapeutic strategies for this and other psychiatric disorders.", "entity": "Clomipramine", "aliases": "Anafranil Chlomipramine Chlorimipramine Clomipramine Hydrochloride Maleate (1:1) Monohydrochloride Hydiphen", "definition": "A tricyclic antidepressant similar to IMIPRAMINE that selectively inhibits the uptake of serotonin in the brain. It is readily absorbed from the gastrointestinal tract and demethylated in the liver to form its primary active metabolite, desmethylclomipramine.\n    ", "id": "MESH:D002997"}
{"mention": "Clomipramine", "mention_text": "BACKGROUND: Current animal models of obsessive-compulsive disorder (OCD) typically involve acute, drug-induced symptom provocation or a genetic association with stereotypies or anxiety. None of these current models demonstrate multiple OCD-like behaviors. METHODS: Neonatal rats were treated with the tricyclic antidepressant clomipramine or vehicle between days 9 and 16 twice daily and behaviorally tested in adulthood. RESULTS: Clomipramine exposure in immature rats produced significant behavioral and biochemical changes that include enhanced anxiety (elevated plus maze and marble burying), behavioral inflexibility (perseveration in the spontaneous alternation task and impaired reversal learning), working memory impairment (e.g., win-shift paradigm), hoarding, and corticostriatal dysfunction. Dopamine D2 receptors were elevated in the striatum, whereas serotonin 2C, but not serotonin 1A, receptors were elevated in the orbital frontal cortex. CONCLUSIONS: This is the first demonstration of multiple symptoms consistent with an OCD-like profile in animals. Moreover, these behaviors are accompanied by biochemical changes in brain regions previously identified as relevant to OCD. This novel model of OCD demonstrates that drug exposure during a sensitive period can program disease-like systems permanently, which could have implications for current and future therapeutic strategies for this and other psychiatric disorders.", "entity": "Clomipramine", "aliases": "Anafranil Chlomipramine Chlorimipramine Clomipramine Hydrochloride Maleate (1:1) Monohydrochloride Hydiphen", "definition": "A tricyclic antidepressant similar to IMIPRAMINE that selectively inhibits the uptake of serotonin in the brain. It is readily absorbed from the gastrointestinal tract and demethylated in the liver to form its primary active metabolite, desmethylclomipramine.\n    ", "id": "MESH:D002997"}
{"mention": "memory impairment", "mention_text": "BACKGROUND: Current animal models of obsessive-compulsive disorder (OCD) typically involve acute, drug-induced symptom provocation or a genetic association with stereotypies or anxiety. None of these current models demonstrate multiple OCD-like behaviors. METHODS: Neonatal rats were treated with the tricyclic antidepressant clomipramine or vehicle between days 9 and 16 twice daily and behaviorally tested in adulthood. RESULTS: Clomipramine exposure in immature rats produced significant behavioral and biochemical changes that include enhanced anxiety (elevated plus maze and marble burying), behavioral inflexibility (perseveration in the spontaneous alternation task and impaired reversal learning), working memory impairment (e.g., win-shift paradigm), hoarding, and corticostriatal dysfunction. Dopamine D2 receptors were elevated in the striatum, whereas serotonin 2C, but not serotonin 1A, receptors were elevated in the orbital frontal cortex. CONCLUSIONS: This is the first demonstration of multiple symptoms consistent with an OCD-like profile in animals. Moreover, these behaviors are accompanied by biochemical changes in brain regions previously identified as relevant to OCD. This novel model of OCD demonstrates that drug exposure during a sensitive period can program disease-like systems permanently, which could have implications for current and future therapeutic strategies for this and other psychiatric disorders.", "entity": "Memory Disorders", "aliases": "Age Related Memory Disorders Age-Related Disorder Cognitive Retention Deficit Deficits Semantic Spatial Loss Losses", "definition": "Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions.\n    ", "id": "MESH:D008569"}
{"mention": "hoarding", "mention_text": "BACKGROUND: Current animal models of obsessive-compulsive disorder (OCD) typically involve acute, drug-induced symptom provocation or a genetic association with stereotypies or anxiety. None of these current models demonstrate multiple OCD-like behaviors. METHODS: Neonatal rats were treated with the tricyclic antidepressant clomipramine or vehicle between days 9 and 16 twice daily and behaviorally tested in adulthood. RESULTS: Clomipramine exposure in immature rats produced significant behavioral and biochemical changes that include enhanced anxiety (elevated plus maze and marble burying), behavioral inflexibility (perseveration in the spontaneous alternation task and impaired reversal learning), working memory impairment (e.g., win-shift paradigm), hoarding, and corticostriatal dysfunction. Dopamine D2 receptors were elevated in the striatum, whereas serotonin 2C, but not serotonin 1A, receptors were elevated in the orbital frontal cortex. CONCLUSIONS: This is the first demonstration of multiple symptoms consistent with an OCD-like profile in animals. Moreover, these behaviors are accompanied by biochemical changes in brain regions previously identified as relevant to OCD. This novel model of OCD demonstrates that drug exposure during a sensitive period can program disease-like systems permanently, which could have implications for current and future therapeutic strategies for this and other psychiatric disorders.", "entity": "Obsessive Hoarding", "aliases": "Hoarding Obsessive Hoardings", "definition": "Persistent difficulty discarding or parting with possessions, regardless of the value of these possessions. Epidemiological studies suggest that hoarding occurs in 2-5% of the population and can lead to substantial distress and disability, as well as serious public health consequences.\n    ", "id": "MESH:D060845"}
{"mention": "Dopamine", "mention_text": "BACKGROUND: Current animal models of obsessive-compulsive disorder (OCD) typically involve acute, drug-induced symptom provocation or a genetic association with stereotypies or anxiety. None of these current models demonstrate multiple OCD-like behaviors. METHODS: Neonatal rats were treated with the tricyclic antidepressant clomipramine or vehicle between days 9 and 16 twice daily and behaviorally tested in adulthood. RESULTS: Clomipramine exposure in immature rats produced significant behavioral and biochemical changes that include enhanced anxiety (elevated plus maze and marble burying), behavioral inflexibility (perseveration in the spontaneous alternation task and impaired reversal learning), working memory impairment (e.g., win-shift paradigm), hoarding, and corticostriatal dysfunction. Dopamine D2 receptors were elevated in the striatum, whereas serotonin 2C, but not serotonin 1A, receptors were elevated in the orbital frontal cortex. CONCLUSIONS: This is the first demonstration of multiple symptoms consistent with an OCD-like profile in animals. Moreover, these behaviors are accompanied by biochemical changes in brain regions previously identified as relevant to OCD. This novel model of OCD demonstrates that drug exposure during a sensitive period can program disease-like systems permanently, which could have implications for current and future therapeutic strategies for this and other psychiatric disorders.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "serotonin", "mention_text": "BACKGROUND: Current animal models of obsessive-compulsive disorder (OCD) typically involve acute, drug-induced symptom provocation or a genetic association with stereotypies or anxiety. None of these current models demonstrate multiple OCD-like behaviors. METHODS: Neonatal rats were treated with the tricyclic antidepressant clomipramine or vehicle between days 9 and 16 twice daily and behaviorally tested in adulthood. RESULTS: Clomipramine exposure in immature rats produced significant behavioral and biochemical changes that include enhanced anxiety (elevated plus maze and marble burying), behavioral inflexibility (perseveration in the spontaneous alternation task and impaired reversal learning), working memory impairment (e.g., win-shift paradigm), hoarding, and corticostriatal dysfunction. Dopamine D2 receptors were elevated in the striatum, whereas serotonin 2C, but not serotonin 1A, receptors were elevated in the orbital frontal cortex. CONCLUSIONS: This is the first demonstration of multiple symptoms consistent with an OCD-like profile in animals. Moreover, these behaviors are accompanied by biochemical changes in brain regions previously identified as relevant to OCD. This novel model of OCD demonstrates that drug exposure during a sensitive period can program disease-like systems permanently, which could have implications for current and future therapeutic strategies for this and other psychiatric disorders.", "entity": "Serotonin", "aliases": "3-(2-Aminoethyl)-1H-indol-5-ol 5 Hydroxytryptamine 5-HT 5-Hydroxytryptamine Enteramine Hippophaine Serotonin", "definition": "A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.\n    ", "id": "MESH:D012701"}
{"mention": "psychiatric disorders", "mention_text": "BACKGROUND: Current animal models of obsessive-compulsive disorder (OCD) typically involve acute, drug-induced symptom provocation or a genetic association with stereotypies or anxiety. None of these current models demonstrate multiple OCD-like behaviors. METHODS: Neonatal rats were treated with the tricyclic antidepressant clomipramine or vehicle between days 9 and 16 twice daily and behaviorally tested in adulthood. RESULTS: Clomipramine exposure in immature rats produced significant behavioral and biochemical changes that include enhanced anxiety (elevated plus maze and marble burying), behavioral inflexibility (perseveration in the spontaneous alternation task and impaired reversal learning), working memory impairment (e.g., win-shift paradigm), hoarding, and corticostriatal dysfunction. Dopamine D2 receptors were elevated in the striatum, whereas serotonin 2C, but not serotonin 1A, receptors were elevated in the orbital frontal cortex. CONCLUSIONS: This is the first demonstration of multiple symptoms consistent with an OCD-like profile in animals. Moreover, these behaviors are accompanied by biochemical changes in brain regions previously identified as relevant to OCD. This novel model of OCD demonstrates that drug exposure during a sensitive period can program disease-like systems permanently, which could have implications for current and future therapeutic strategies for this and other psychiatric disorders.", "entity": "Mental Disorders", "aliases": "Behavior Disorders Diagnosis Psychiatric Disorder Mental", "definition": "Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.\n    ", "id": "MESH:D001523"}
{"mention": "hemolytic uremic syndrome", "mention_text": "Late recovery of renal function in a woman with the hemolytic uremic syndrome.", "entity": "Hemolytic-Uremic Syndrome", "aliases": "Gasser Syndrome Gasser's Gassers Hemolytic Uremic Hemolytic-Uremic", "definition": "A syndrome that is associated with microvascular diseases of the KIDNEY, such as RENAL CORTICAL NECROSIS. It is characterized by hemolytic anemia (ANEMIA, HEMOLYTIC); THROMBOCYTOPENIA; and ACUTE RENAL FAILURE.\n    ", "id": "MESH:D006463"}
{"mention": "hemolytic uremic syndrome", "mention_text": "A case is reported of the hemolytic uremic syndrome (HUS) in a woman taking oral contraceptives. She was treated with heparin, dipyridamole and hemodialysis; and after more than three months, her urinary output rose above 500 ml; and six months after the onset of anuria, dialysis treatment was stopped. This case emphasizes the possibility that HUS in adults is not invariably irreversible and that, despite prolonged oliguria, recovery of renal function can be obtained. Therefore, in adult patients affected by HUS, dialysis should not be discontinued prematurely; moreover, bilateral nephrectomy, for treatment of severe hypertension and microangiopathic hemolytic anemia, should be performed with caution.", "entity": "Hemolytic-Uremic Syndrome", "aliases": "Gasser Syndrome Gasser's Gassers Hemolytic Uremic Hemolytic-Uremic", "definition": "A syndrome that is associated with microvascular diseases of the KIDNEY, such as RENAL CORTICAL NECROSIS. It is characterized by hemolytic anemia (ANEMIA, HEMOLYTIC); THROMBOCYTOPENIA; and ACUTE RENAL FAILURE.\n    ", "id": "MESH:D006463"}
{"mention": "HUS", "mention_text": "A case is reported of the hemolytic uremic syndrome (HUS) in a woman taking oral contraceptives. She was treated with heparin, dipyridamole and hemodialysis; and after more than three months, her urinary output rose above 500 ml; and six months after the onset of anuria, dialysis treatment was stopped. This case emphasizes the possibility that HUS in adults is not invariably irreversible and that, despite prolonged oliguria, recovery of renal function can be obtained. Therefore, in adult patients affected by HUS, dialysis should not be discontinued prematurely; moreover, bilateral nephrectomy, for treatment of severe hypertension and microangiopathic hemolytic anemia, should be performed with caution.", "entity": "Hemolytic-Uremic Syndrome", "aliases": "Gasser Syndrome Gasser's Gassers Hemolytic Uremic Hemolytic-Uremic", "definition": "A syndrome that is associated with microvascular diseases of the KIDNEY, such as RENAL CORTICAL NECROSIS. It is characterized by hemolytic anemia (ANEMIA, HEMOLYTIC); THROMBOCYTOPENIA; and ACUTE RENAL FAILURE.\n    ", "id": "MESH:D006463"}
{"mention": "oral contraceptives", "mention_text": "A case is reported of the hemolytic uremic syndrome (HUS) in a woman taking oral contraceptives. She was treated with heparin, dipyridamole and hemodialysis; and after more than three months, her urinary output rose above 500 ml; and six months after the onset of anuria, dialysis treatment was stopped. This case emphasizes the possibility that HUS in adults is not invariably irreversible and that, despite prolonged oliguria, recovery of renal function can be obtained. Therefore, in adult patients affected by HUS, dialysis should not be discontinued prematurely; moreover, bilateral nephrectomy, for treatment of severe hypertension and microangiopathic hemolytic anemia, should be performed with caution.", "entity": "Contraceptives, Oral", "aliases": "Contraceptives Low-Dose Oral Phasic Low Dose", "definition": "Compounds, usually hormonal, taken orally in order to block ovulation and prevent the occurrence of pregnancy. The hormones are generally estrogen or progesterone or both.\n    ", "id": "MESH:D003276"}
{"mention": "heparin", "mention_text": "A case is reported of the hemolytic uremic syndrome (HUS) in a woman taking oral contraceptives. She was treated with heparin, dipyridamole and hemodialysis; and after more than three months, her urinary output rose above 500 ml; and six months after the onset of anuria, dialysis treatment was stopped. This case emphasizes the possibility that HUS in adults is not invariably irreversible and that, despite prolonged oliguria, recovery of renal function can be obtained. Therefore, in adult patients affected by HUS, dialysis should not be discontinued prematurely; moreover, bilateral nephrectomy, for treatment of severe hypertension and microangiopathic hemolytic anemia, should be performed with caution.", "entity": "Heparin", "aliases": "Heparin Sodium Unfractionated Heparinic Acid Liquaemin alpha alpha-Heparin", "definition": "A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.\n    ", "id": "MESH:D006493"}
{"mention": "dipyridamole", "mention_text": "A case is reported of the hemolytic uremic syndrome (HUS) in a woman taking oral contraceptives. She was treated with heparin, dipyridamole and hemodialysis; and after more than three months, her urinary output rose above 500 ml; and six months after the onset of anuria, dialysis treatment was stopped. This case emphasizes the possibility that HUS in adults is not invariably irreversible and that, despite prolonged oliguria, recovery of renal function can be obtained. Therefore, in adult patients affected by HUS, dialysis should not be discontinued prematurely; moreover, bilateral nephrectomy, for treatment of severe hypertension and microangiopathic hemolytic anemia, should be performed with caution.", "entity": "Dipyridamole", "aliases": "Antistenocardin Apo-Dipyridamole Apotex Brand of Dipyridamole Ashbourne Belmac Berlin Chemie Berlin-Chemie Boehringer Ingelheim Cerebrovase Cléridium Curantil Curantyl Dipyramidole IPRAD Kurantil Miosen Novo-Dipiradol Novopharm Persantin Persantine", "definition": "A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752)\n    ", "id": "MESH:D004176"}
{"mention": "anuria", "mention_text": "A case is reported of the hemolytic uremic syndrome (HUS) in a woman taking oral contraceptives. She was treated with heparin, dipyridamole and hemodialysis; and after more than three months, her urinary output rose above 500 ml; and six months after the onset of anuria, dialysis treatment was stopped. This case emphasizes the possibility that HUS in adults is not invariably irreversible and that, despite prolonged oliguria, recovery of renal function can be obtained. Therefore, in adult patients affected by HUS, dialysis should not be discontinued prematurely; moreover, bilateral nephrectomy, for treatment of severe hypertension and microangiopathic hemolytic anemia, should be performed with caution.", "entity": "Anuria", "aliases": "Anuria Anurias", "definition": "Absence of urine formation. It is usually associated with complete bilateral ureteral (URETER) obstruction, complete lower urinary tract obstruction, or unilateral ureteral obstruction when a solitary kidney is present.\n    ", "id": "MESH:D001002"}
{"mention": "oliguria", "mention_text": "A case is reported of the hemolytic uremic syndrome (HUS) in a woman taking oral contraceptives. She was treated with heparin, dipyridamole and hemodialysis; and after more than three months, her urinary output rose above 500 ml; and six months after the onset of anuria, dialysis treatment was stopped. This case emphasizes the possibility that HUS in adults is not invariably irreversible and that, despite prolonged oliguria, recovery of renal function can be obtained. Therefore, in adult patients affected by HUS, dialysis should not be discontinued prematurely; moreover, bilateral nephrectomy, for treatment of severe hypertension and microangiopathic hemolytic anemia, should be performed with caution.", "entity": "Oliguria", "aliases": "Oliguria Oligurias", "definition": "Decreased URINE output that is below the normal range. Oliguria can be defined as urine output of less than or equal to 0.5 or 1 ml/kg/hr depending on the age.\n    ", "id": "MESH:D009846"}
{"mention": "hypertension", "mention_text": "A case is reported of the hemolytic uremic syndrome (HUS) in a woman taking oral contraceptives. She was treated with heparin, dipyridamole and hemodialysis; and after more than three months, her urinary output rose above 500 ml; and six months after the onset of anuria, dialysis treatment was stopped. This case emphasizes the possibility that HUS in adults is not invariably irreversible and that, despite prolonged oliguria, recovery of renal function can be obtained. Therefore, in adult patients affected by HUS, dialysis should not be discontinued prematurely; moreover, bilateral nephrectomy, for treatment of severe hypertension and microangiopathic hemolytic anemia, should be performed with caution.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "microangiopathic hemolytic anemia", "mention_text": "A case is reported of the hemolytic uremic syndrome (HUS) in a woman taking oral contraceptives. She was treated with heparin, dipyridamole and hemodialysis; and after more than three months, her urinary output rose above 500 ml; and six months after the onset of anuria, dialysis treatment was stopped. This case emphasizes the possibility that HUS in adults is not invariably irreversible and that, despite prolonged oliguria, recovery of renal function can be obtained. Therefore, in adult patients affected by HUS, dialysis should not be discontinued prematurely; moreover, bilateral nephrectomy, for treatment of severe hypertension and microangiopathic hemolytic anemia, should be performed with caution.", "entity": "Anemia, Hemolytic", "aliases": "Acquired Hemolytic Anemia Microangiopathic", "definition": "A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES).\n    ", "id": "MESH:D000743"}
{"mention": "acetylsalicylic acid", "mention_text": "Effects of acetylsalicylic acid, dipyridamole, and hydrocortisone on epinephrine-induced myocardial injury in dogs.", "entity": "Aspirin", "aliases": "2-(Acetyloxy)benzoic Acid Acetylsalicylic Acetysal Acylpyrin Aloxiprimum Aspirin Colfarit Dispril Easprin Ecotrin Endosprin Magnecyl Micristin Polopirin Polopiryna Solprin Solupsan Zorprin", "definition": "The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)\n    ", "id": "MESH:D001241"}
{"mention": "dipyridamole", "mention_text": "Effects of acetylsalicylic acid, dipyridamole, and hydrocortisone on epinephrine-induced myocardial injury in dogs.", "entity": "Dipyridamole", "aliases": "Antistenocardin Apo-Dipyridamole Apotex Brand of Dipyridamole Ashbourne Belmac Berlin Chemie Berlin-Chemie Boehringer Ingelheim Cerebrovase Cléridium Curantil Curantyl Dipyramidole IPRAD Kurantil Miosen Novo-Dipiradol Novopharm Persantin Persantine", "definition": "A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752)\n    ", "id": "MESH:D004176"}
{"mention": "hydrocortisone", "mention_text": "Effects of acetylsalicylic acid, dipyridamole, and hydrocortisone on epinephrine-induced myocardial injury in dogs.", "entity": "Hydrocortisone", "aliases": "11 Epicortisol 11-Epicortisol Cortifair Cortisol Cortril Hydrocortisone (11 alpha)-Isomer (9 beta,10 alpha,11", "definition": "The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.\n    ", "id": "MESH:D006854"}
{"mention": "epinephrine", "mention_text": "Effects of acetylsalicylic acid, dipyridamole, and hydrocortisone on epinephrine-induced myocardial injury in dogs.", "entity": "Epinephrine", "aliases": "4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-benzenediol Acetate Epinephrine Adrenaline Acid Tartrate Bitartrate Hydrochloride Allergan Brand of Epifrin Hydrogen Epitrate Lyophrin Medihaler-Epi", "definition": "The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.\n    ", "id": "MESH:D004837"}
{"mention": "myocardial injury", "mention_text": "Effects of acetylsalicylic acid, dipyridamole, and hydrocortisone on epinephrine-induced myocardial injury in dogs.", "entity": "Cardiomyopathies", "aliases": "Cardiomyopathies Primary Secondary Cardiomyopathy Disease Myocardial Diseases Myocardiopathies Myocardiopathy", "definition": "A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).\n    ", "id": "MESH:D009202"}
{"mention": "myocardial injury", "mention_text": "A reproducible model for producing diffuse myocardial injury (epinephrine infusion) has been developed to study the cardioprotective effects of agents or maneuvers which might alter the evolution of acute myocardial infarction. Infusions of epinephrine (4 mug per kilogram per minute for 6 hours) increased radiocalcium uptakes into intact myocardium and each of its subcellular components with the mitochondrial fraction showing the most consistent changes when compared to saline-infused control animals (4,957 vs. 827 counts per minute per gram of dried tissue or fraction). Myocardial concentrations of calcium also increased significantly (12.0 vs. 5.0 mg.per 100 Gm. of fat-free dry weight). Infusions of calcium chloride sufficient to raise serum calcium concentrations 2 mEq. per liter failed to increase calcium influx into the myocardial cell. Mitochondrial radiocalcium uptakes were significantly decreased in animals pretreated with acetylsalicylic acid or dipyridamole or when hydrocortisone was added to the epinephrine infusion (2,682,2,803, and 3,424 counts per minute per gram of dried fraction, respectively). Myocardial calcium concentrations also were decreased (11.2, 8.3, and 8.9 mg. per 100 Gm. of fat-free dry weight, respectively) in the three treatment groups, being significantly decreased only in the last two. Evidence of microscopic damage was graded as less severe in the three treatment groups. Acetylsalicylic acid, dipyridamole, and hydrocortisone all appear to have cardioprotective effects when tested in this model.", "entity": "Cardiomyopathies", "aliases": "Cardiomyopathies Primary Secondary Cardiomyopathy Disease Myocardial Diseases Myocardiopathies Myocardiopathy", "definition": "A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).\n    ", "id": "MESH:D009202"}
{"mention": "epinephrine", "mention_text": "A reproducible model for producing diffuse myocardial injury (epinephrine infusion) has been developed to study the cardioprotective effects of agents or maneuvers which might alter the evolution of acute myocardial infarction. Infusions of epinephrine (4 mug per kilogram per minute for 6 hours) increased radiocalcium uptakes into intact myocardium and each of its subcellular components with the mitochondrial fraction showing the most consistent changes when compared to saline-infused control animals (4,957 vs. 827 counts per minute per gram of dried tissue or fraction). Myocardial concentrations of calcium also increased significantly (12.0 vs. 5.0 mg.per 100 Gm. of fat-free dry weight). Infusions of calcium chloride sufficient to raise serum calcium concentrations 2 mEq. per liter failed to increase calcium influx into the myocardial cell. Mitochondrial radiocalcium uptakes were significantly decreased in animals pretreated with acetylsalicylic acid or dipyridamole or when hydrocortisone was added to the epinephrine infusion (2,682,2,803, and 3,424 counts per minute per gram of dried fraction, respectively). Myocardial calcium concentrations also were decreased (11.2, 8.3, and 8.9 mg. per 100 Gm. of fat-free dry weight, respectively) in the three treatment groups, being significantly decreased only in the last two. Evidence of microscopic damage was graded as less severe in the three treatment groups. Acetylsalicylic acid, dipyridamole, and hydrocortisone all appear to have cardioprotective effects when tested in this model.", "entity": "Epinephrine", "aliases": "4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-benzenediol Acetate Epinephrine Adrenaline Acid Tartrate Bitartrate Hydrochloride Allergan Brand of Epifrin Hydrogen Epitrate Lyophrin Medihaler-Epi", "definition": "The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.\n    ", "id": "MESH:D004837"}
{"mention": "myocardial infarction", "mention_text": "A reproducible model for producing diffuse myocardial injury (epinephrine infusion) has been developed to study the cardioprotective effects of agents or maneuvers which might alter the evolution of acute myocardial infarction. Infusions of epinephrine (4 mug per kilogram per minute for 6 hours) increased radiocalcium uptakes into intact myocardium and each of its subcellular components with the mitochondrial fraction showing the most consistent changes when compared to saline-infused control animals (4,957 vs. 827 counts per minute per gram of dried tissue or fraction). Myocardial concentrations of calcium also increased significantly (12.0 vs. 5.0 mg.per 100 Gm. of fat-free dry weight). Infusions of calcium chloride sufficient to raise serum calcium concentrations 2 mEq. per liter failed to increase calcium influx into the myocardial cell. Mitochondrial radiocalcium uptakes were significantly decreased in animals pretreated with acetylsalicylic acid or dipyridamole or when hydrocortisone was added to the epinephrine infusion (2,682,2,803, and 3,424 counts per minute per gram of dried fraction, respectively). Myocardial calcium concentrations also were decreased (11.2, 8.3, and 8.9 mg. per 100 Gm. of fat-free dry weight, respectively) in the three treatment groups, being significantly decreased only in the last two. Evidence of microscopic damage was graded as less severe in the three treatment groups. Acetylsalicylic acid, dipyridamole, and hydrocortisone all appear to have cardioprotective effects when tested in this model.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "radiocalcium", "mention_text": "A reproducible model for producing diffuse myocardial injury (epinephrine infusion) has been developed to study the cardioprotective effects of agents or maneuvers which might alter the evolution of acute myocardial infarction. Infusions of epinephrine (4 mug per kilogram per minute for 6 hours) increased radiocalcium uptakes into intact myocardium and each of its subcellular components with the mitochondrial fraction showing the most consistent changes when compared to saline-infused control animals (4,957 vs. 827 counts per minute per gram of dried tissue or fraction). Myocardial concentrations of calcium also increased significantly (12.0 vs. 5.0 mg.per 100 Gm. of fat-free dry weight). Infusions of calcium chloride sufficient to raise serum calcium concentrations 2 mEq. per liter failed to increase calcium influx into the myocardial cell. Mitochondrial radiocalcium uptakes were significantly decreased in animals pretreated with acetylsalicylic acid or dipyridamole or when hydrocortisone was added to the epinephrine infusion (2,682,2,803, and 3,424 counts per minute per gram of dried fraction, respectively). Myocardial calcium concentrations also were decreased (11.2, 8.3, and 8.9 mg. per 100 Gm. of fat-free dry weight, respectively) in the three treatment groups, being significantly decreased only in the last two. Evidence of microscopic damage was graded as less severe in the three treatment groups. Acetylsalicylic acid, dipyridamole, and hydrocortisone all appear to have cardioprotective effects when tested in this model.", "entity": "Calcium Radioisotopes", "aliases": "Calcium Radioisotopes", "definition": "Unstable isotopes of calcium that decay or disintegrate emitting radiation. Ca atoms with atomic weights 39, 41, 45, 47, 49, and 50 are radioactive calcium isotopes.\n    ", "id": "MESH:D002132"}
{"mention": "calcium", "mention_text": "A reproducible model for producing diffuse myocardial injury (epinephrine infusion) has been developed to study the cardioprotective effects of agents or maneuvers which might alter the evolution of acute myocardial infarction. Infusions of epinephrine (4 mug per kilogram per minute for 6 hours) increased radiocalcium uptakes into intact myocardium and each of its subcellular components with the mitochondrial fraction showing the most consistent changes when compared to saline-infused control animals (4,957 vs. 827 counts per minute per gram of dried tissue or fraction). Myocardial concentrations of calcium also increased significantly (12.0 vs. 5.0 mg.per 100 Gm. of fat-free dry weight). Infusions of calcium chloride sufficient to raise serum calcium concentrations 2 mEq. per liter failed to increase calcium influx into the myocardial cell. Mitochondrial radiocalcium uptakes were significantly decreased in animals pretreated with acetylsalicylic acid or dipyridamole or when hydrocortisone was added to the epinephrine infusion (2,682,2,803, and 3,424 counts per minute per gram of dried fraction, respectively). Myocardial calcium concentrations also were decreased (11.2, 8.3, and 8.9 mg. per 100 Gm. of fat-free dry weight, respectively) in the three treatment groups, being significantly decreased only in the last two. Evidence of microscopic damage was graded as less severe in the three treatment groups. Acetylsalicylic acid, dipyridamole, and hydrocortisone all appear to have cardioprotective effects when tested in this model.", "entity": "Calcium", "aliases": "Blood Coagulation Factor IV Calcium", "definition": "A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.\n    ", "id": "MESH:D002118"}
{"mention": "calcium chloride", "mention_text": "A reproducible model for producing diffuse myocardial injury (epinephrine infusion) has been developed to study the cardioprotective effects of agents or maneuvers which might alter the evolution of acute myocardial infarction. Infusions of epinephrine (4 mug per kilogram per minute for 6 hours) increased radiocalcium uptakes into intact myocardium and each of its subcellular components with the mitochondrial fraction showing the most consistent changes when compared to saline-infused control animals (4,957 vs. 827 counts per minute per gram of dried tissue or fraction). Myocardial concentrations of calcium also increased significantly (12.0 vs. 5.0 mg.per 100 Gm. of fat-free dry weight). Infusions of calcium chloride sufficient to raise serum calcium concentrations 2 mEq. per liter failed to increase calcium influx into the myocardial cell. Mitochondrial radiocalcium uptakes were significantly decreased in animals pretreated with acetylsalicylic acid or dipyridamole or when hydrocortisone was added to the epinephrine infusion (2,682,2,803, and 3,424 counts per minute per gram of dried fraction, respectively). Myocardial calcium concentrations also were decreased (11.2, 8.3, and 8.9 mg. per 100 Gm. of fat-free dry weight, respectively) in the three treatment groups, being significantly decreased only in the last two. Evidence of microscopic damage was graded as less severe in the three treatment groups. Acetylsalicylic acid, dipyridamole, and hydrocortisone all appear to have cardioprotective effects when tested in this model.", "entity": "Calcium Chloride", "aliases": "Calcium Chloride Dihydrate Anhydrous", "definition": "A salt used to replenish calcium levels, as an acid-producing diuretic, and as an antidote for magnesium poisoning.\n    ", "id": "MESH:D002122"}
{"mention": "acetylsalicylic acid", "mention_text": "A reproducible model for producing diffuse myocardial injury (epinephrine infusion) has been developed to study the cardioprotective effects of agents or maneuvers which might alter the evolution of acute myocardial infarction. Infusions of epinephrine (4 mug per kilogram per minute for 6 hours) increased radiocalcium uptakes into intact myocardium and each of its subcellular components with the mitochondrial fraction showing the most consistent changes when compared to saline-infused control animals (4,957 vs. 827 counts per minute per gram of dried tissue or fraction). Myocardial concentrations of calcium also increased significantly (12.0 vs. 5.0 mg.per 100 Gm. of fat-free dry weight). Infusions of calcium chloride sufficient to raise serum calcium concentrations 2 mEq. per liter failed to increase calcium influx into the myocardial cell. Mitochondrial radiocalcium uptakes were significantly decreased in animals pretreated with acetylsalicylic acid or dipyridamole or when hydrocortisone was added to the epinephrine infusion (2,682,2,803, and 3,424 counts per minute per gram of dried fraction, respectively). Myocardial calcium concentrations also were decreased (11.2, 8.3, and 8.9 mg. per 100 Gm. of fat-free dry weight, respectively) in the three treatment groups, being significantly decreased only in the last two. Evidence of microscopic damage was graded as less severe in the three treatment groups. Acetylsalicylic acid, dipyridamole, and hydrocortisone all appear to have cardioprotective effects when tested in this model.", "entity": "Aspirin", "aliases": "2-(Acetyloxy)benzoic Acid Acetylsalicylic Acetysal Acylpyrin Aloxiprimum Aspirin Colfarit Dispril Easprin Ecotrin Endosprin Magnecyl Micristin Polopirin Polopiryna Solprin Solupsan Zorprin", "definition": "The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)\n    ", "id": "MESH:D001241"}
{"mention": "dipyridamole", "mention_text": "A reproducible model for producing diffuse myocardial injury (epinephrine infusion) has been developed to study the cardioprotective effects of agents or maneuvers which might alter the evolution of acute myocardial infarction. Infusions of epinephrine (4 mug per kilogram per minute for 6 hours) increased radiocalcium uptakes into intact myocardium and each of its subcellular components with the mitochondrial fraction showing the most consistent changes when compared to saline-infused control animals (4,957 vs. 827 counts per minute per gram of dried tissue or fraction). Myocardial concentrations of calcium also increased significantly (12.0 vs. 5.0 mg.per 100 Gm. of fat-free dry weight). Infusions of calcium chloride sufficient to raise serum calcium concentrations 2 mEq. per liter failed to increase calcium influx into the myocardial cell. Mitochondrial radiocalcium uptakes were significantly decreased in animals pretreated with acetylsalicylic acid or dipyridamole or when hydrocortisone was added to the epinephrine infusion (2,682,2,803, and 3,424 counts per minute per gram of dried fraction, respectively). Myocardial calcium concentrations also were decreased (11.2, 8.3, and 8.9 mg. per 100 Gm. of fat-free dry weight, respectively) in the three treatment groups, being significantly decreased only in the last two. Evidence of microscopic damage was graded as less severe in the three treatment groups. Acetylsalicylic acid, dipyridamole, and hydrocortisone all appear to have cardioprotective effects when tested in this model.", "entity": "Dipyridamole", "aliases": "Antistenocardin Apo-Dipyridamole Apotex Brand of Dipyridamole Ashbourne Belmac Berlin Chemie Berlin-Chemie Boehringer Ingelheim Cerebrovase Cléridium Curantil Curantyl Dipyramidole IPRAD Kurantil Miosen Novo-Dipiradol Novopharm Persantin Persantine", "definition": "A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752)\n    ", "id": "MESH:D004176"}
{"mention": "hydrocortisone", "mention_text": "A reproducible model for producing diffuse myocardial injury (epinephrine infusion) has been developed to study the cardioprotective effects of agents or maneuvers which might alter the evolution of acute myocardial infarction. Infusions of epinephrine (4 mug per kilogram per minute for 6 hours) increased radiocalcium uptakes into intact myocardium and each of its subcellular components with the mitochondrial fraction showing the most consistent changes when compared to saline-infused control animals (4,957 vs. 827 counts per minute per gram of dried tissue or fraction). Myocardial concentrations of calcium also increased significantly (12.0 vs. 5.0 mg.per 100 Gm. of fat-free dry weight). Infusions of calcium chloride sufficient to raise serum calcium concentrations 2 mEq. per liter failed to increase calcium influx into the myocardial cell. Mitochondrial radiocalcium uptakes were significantly decreased in animals pretreated with acetylsalicylic acid or dipyridamole or when hydrocortisone was added to the epinephrine infusion (2,682,2,803, and 3,424 counts per minute per gram of dried fraction, respectively). Myocardial calcium concentrations also were decreased (11.2, 8.3, and 8.9 mg. per 100 Gm. of fat-free dry weight, respectively) in the three treatment groups, being significantly decreased only in the last two. Evidence of microscopic damage was graded as less severe in the three treatment groups. Acetylsalicylic acid, dipyridamole, and hydrocortisone all appear to have cardioprotective effects when tested in this model.", "entity": "Hydrocortisone", "aliases": "11 Epicortisol 11-Epicortisol Cortifair Cortisol Cortril Hydrocortisone (11 alpha)-Isomer (9 beta,10 alpha,11", "definition": "The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.\n    ", "id": "MESH:D006854"}
{"mention": "Acetylsalicylic acid", "mention_text": "A reproducible model for producing diffuse myocardial injury (epinephrine infusion) has been developed to study the cardioprotective effects of agents or maneuvers which might alter the evolution of acute myocardial infarction. Infusions of epinephrine (4 mug per kilogram per minute for 6 hours) increased radiocalcium uptakes into intact myocardium and each of its subcellular components with the mitochondrial fraction showing the most consistent changes when compared to saline-infused control animals (4,957 vs. 827 counts per minute per gram of dried tissue or fraction). Myocardial concentrations of calcium also increased significantly (12.0 vs. 5.0 mg.per 100 Gm. of fat-free dry weight). Infusions of calcium chloride sufficient to raise serum calcium concentrations 2 mEq. per liter failed to increase calcium influx into the myocardial cell. Mitochondrial radiocalcium uptakes were significantly decreased in animals pretreated with acetylsalicylic acid or dipyridamole or when hydrocortisone was added to the epinephrine infusion (2,682,2,803, and 3,424 counts per minute per gram of dried fraction, respectively). Myocardial calcium concentrations also were decreased (11.2, 8.3, and 8.9 mg. per 100 Gm. of fat-free dry weight, respectively) in the three treatment groups, being significantly decreased only in the last two. Evidence of microscopic damage was graded as less severe in the three treatment groups. Acetylsalicylic acid, dipyridamole, and hydrocortisone all appear to have cardioprotective effects when tested in this model.", "entity": "Aspirin", "aliases": "2-(Acetyloxy)benzoic Acid Acetylsalicylic Acetysal Acylpyrin Aloxiprimum Aspirin Colfarit Dispril Easprin Ecotrin Endosprin Magnecyl Micristin Polopirin Polopiryna Solprin Solupsan Zorprin", "definition": "The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)\n    ", "id": "MESH:D001241"}
{"mention": "depressive", "mention_text": "Changes in depressive status associated with topical beta-blockers.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "Depression", "mention_text": "Depression and sexual dysfunction have been related to side effects of topical beta-blockers. We performed a preliminary study in order to determine any difference between a non selective beta-blocker (timolol) and a selective beta-blocker (betaxolol) regarding CNS side effects. Eight glaucomatous patients chronically treated with timolol 0.5%/12h, suffering from depression diagnosed through DMS-III-R criteria, were included in the study. During the six-month follow up, depression was quantified through the Beck and Zung-Conde scales every two months. In a double blind cross-over study with control group, the patients under timolol treatment presented higher depression values measured through the Beck and the Zung-Conde scales (p < 0.001 vs control). These results suggest that betaxolol could be less of a depression-inducer than timolol in predisposed patients.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "sexual dysfunction", "mention_text": "Depression and sexual dysfunction have been related to side effects of topical beta-blockers. We performed a preliminary study in order to determine any difference between a non selective beta-blocker (timolol) and a selective beta-blocker (betaxolol) regarding CNS side effects. Eight glaucomatous patients chronically treated with timolol 0.5%/12h, suffering from depression diagnosed through DMS-III-R criteria, were included in the study. During the six-month follow up, depression was quantified through the Beck and Zung-Conde scales every two months. In a double blind cross-over study with control group, the patients under timolol treatment presented higher depression values measured through the Beck and the Zung-Conde scales (p < 0.001 vs control). These results suggest that betaxolol could be less of a depression-inducer than timolol in predisposed patients.", "entity": "Sexual Dysfunction, Physiological", "aliases": "Physiological Sexual Disorder Disorders Dysfunction Dysfunctions Sex", "definition": "Physiological disturbances in normal sexual performance in either the male or the female.\n    ", "id": "MESH:D012735"}
{"mention": "timolol", "mention_text": "Depression and sexual dysfunction have been related to side effects of topical beta-blockers. We performed a preliminary study in order to determine any difference between a non selective beta-blocker (timolol) and a selective beta-blocker (betaxolol) regarding CNS side effects. Eight glaucomatous patients chronically treated with timolol 0.5%/12h, suffering from depression diagnosed through DMS-III-R criteria, were included in the study. During the six-month follow up, depression was quantified through the Beck and Zung-Conde scales every two months. In a double blind cross-over study with control group, the patients under timolol treatment presented higher depression values measured through the Beck and the Zung-Conde scales (p < 0.001 vs control). These results suggest that betaxolol could be less of a depression-inducer than timolol in predisposed patients.", "entity": "Timolol", "aliases": "(S)-1-((1,1-Dimethylethyl)amino)-3-((4-(4-morpholinyl)-1,2,5-thiadazol-3-yl)oxy)-2-propanol Blocadren Hemihydrate Timolol L 714,465 L-714,465 L714,465 MK 950 MK-950 MK950 Optimol Timacar Maleate (1:1) Salt Timoptic Timoptol", "definition": "A beta-adrenergic antagonist similar in action to PROPRANOLOL. The levo-isomer is the more active. Timolol has been proposed as an antihypertensive, antiarrhythmic, antiangina, and antiglaucoma agent. It is also used in the treatment of MIGRAINE DISORDERS and tremor.\n    ", "id": "MESH:D013999"}
{"mention": "betaxolol", "mention_text": "Depression and sexual dysfunction have been related to side effects of topical beta-blockers. We performed a preliminary study in order to determine any difference between a non selective beta-blocker (timolol) and a selective beta-blocker (betaxolol) regarding CNS side effects. Eight glaucomatous patients chronically treated with timolol 0.5%/12h, suffering from depression diagnosed through DMS-III-R criteria, were included in the study. During the six-month follow up, depression was quantified through the Beck and Zung-Conde scales every two months. In a double blind cross-over study with control group, the patients under timolol treatment presented higher depression values measured through the Beck and the Zung-Conde scales (p < 0.001 vs control). These results suggest that betaxolol could be less of a depression-inducer than timolol in predisposed patients.", "entity": "Betaxolol", "aliases": "ALO 1401 02 ALO-1401-02 ALO140102 Alcon Brand of Betaxolol Hydrochloride Allphar Betoptic Betoptima Boots Kerlon Kerlone Lorex Oxodal SL 75212 SL-75212 SL75212 Schwarz Searle Synthelabo Synthélabo", "definition": "A cardioselective beta-1-adrenergic antagonist with no partial agonist activity.\n    ", "id": "MESH:D015784"}
{"mention": "glaucomatous", "mention_text": "Depression and sexual dysfunction have been related to side effects of topical beta-blockers. We performed a preliminary study in order to determine any difference between a non selective beta-blocker (timolol) and a selective beta-blocker (betaxolol) regarding CNS side effects. Eight glaucomatous patients chronically treated with timolol 0.5%/12h, suffering from depression diagnosed through DMS-III-R criteria, were included in the study. During the six-month follow up, depression was quantified through the Beck and Zung-Conde scales every two months. In a double blind cross-over study with control group, the patients under timolol treatment presented higher depression values measured through the Beck and the Zung-Conde scales (p < 0.001 vs control). These results suggest that betaxolol could be less of a depression-inducer than timolol in predisposed patients.", "entity": "Glaucoma", "aliases": "Glaucoma Glaucomas", "definition": "An ocular disease, occurring in many forms, having as its primary characteristics an unstable or a sustained increase in the intraocular pressure which the eye cannot withstand without damage to its structure or impairment of its function. The consequences of the increased pressure may be manifested in a variety of symptoms, depending upon type and severity, such as excavation of the optic disk, hardness of the eyeball, corneal anesthesia, reduced visual acuity, seeing of colored halos around lights, disturbed dark adaptation, visual field defects, and headaches. (Dictionary of Visual Science, 4th ed)\n    ", "id": "MESH:D005901"}
{"mention": "depression", "mention_text": "Depression and sexual dysfunction have been related to side effects of topical beta-blockers. We performed a preliminary study in order to determine any difference between a non selective beta-blocker (timolol) and a selective beta-blocker (betaxolol) regarding CNS side effects. Eight glaucomatous patients chronically treated with timolol 0.5%/12h, suffering from depression diagnosed through DMS-III-R criteria, were included in the study. During the six-month follow up, depression was quantified through the Beck and Zung-Conde scales every two months. In a double blind cross-over study with control group, the patients under timolol treatment presented higher depression values measured through the Beck and the Zung-Conde scales (p < 0.001 vs control). These results suggest that betaxolol could be less of a depression-inducer than timolol in predisposed patients.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "ifosfamide", "mention_text": "Long-term follow-up of ifosfamide renal toxicity in children treated for malignant mesenchymal tumors: an International Society of Pediatric Oncology report.", "entity": "Ifosfamide", "aliases": "Asta Z 4942 Holoxan Ifosfamide Iphosphamide Iso Endoxan Iso-Endoxan Isofosfamide Isophosphamide NSC 109,724 109724 NSC-109,724 NSC-109724 NSC109,724 NSC109724", "definition": "Positional isomer of CYCLOPHOSPHAMIDE which is active as an alkylating agent and an immunosuppressive agent.\n    ", "id": "MESH:D007069"}
{"mention": "renal toxicity", "mention_text": "Long-term follow-up of ifosfamide renal toxicity in children treated for malignant mesenchymal tumors: an International Society of Pediatric Oncology report.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "malignant mesenchymal tumors", "mention_text": "Long-term follow-up of ifosfamide renal toxicity in children treated for malignant mesenchymal tumors: an International Society of Pediatric Oncology report.", "entity": "Malignant mesenchymal tumor", "aliases": "Malignant mesenchymal tumor mesenchymoma", "definition": "", "id": "MESH:C535700"}
{"mention": "malignant mesenchymal tumors", "mention_text": "The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g/m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty-eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi's syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g/m2 of ifosfamide, a younger age (less than 2 1/2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children.", "entity": "Malignant mesenchymal tumor", "aliases": "Malignant mesenchymal tumor mesenchymoma", "definition": "", "id": "MESH:C535700"}
{"mention": "ifosfamide", "mention_text": "The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g/m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty-eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi's syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g/m2 of ifosfamide, a younger age (less than 2 1/2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children.", "entity": "Ifosfamide", "aliases": "Asta Z 4942 Holoxan Ifosfamide Iphosphamide Iso Endoxan Iso-Endoxan Isofosfamide Isophosphamide NSC 109,724 109724 NSC-109,724 NSC-109724 NSC109,724 NSC109724", "definition": "Positional isomer of CYCLOPHOSPHAMIDE which is active as an alkylating agent and an immunosuppressive agent.\n    ", "id": "MESH:D007069"}
{"mention": "Malignant Mesenchymal Tumor", "mention_text": "The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g/m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty-eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi's syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g/m2 of ifosfamide, a younger age (less than 2 1/2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children.", "entity": "Malignant mesenchymal tumor", "aliases": "Malignant mesenchymal tumor mesenchymoma", "definition": "", "id": "MESH:C535700"}
{"mention": "ifosfamide, vincristine, and dactinomycin", "mention_text": "The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g/m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty-eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi's syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g/m2 of ifosfamide, a younger age (less than 2 1/2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children.", "entity": "IVA protocol", "aliases": "IVA protocol", "definition": "", "id": "MESH:C064227"}
{"mention": "IVA", "mention_text": "The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g/m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty-eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi's syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g/m2 of ifosfamide, a younger age (less than 2 1/2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children.", "entity": "IVA protocol", "aliases": "IVA protocol", "definition": "", "id": "MESH:C064227"}
{"mention": "cisplatin", "mention_text": "The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g/m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty-eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi's syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g/m2 of ifosfamide, a younger age (less than 2 1/2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children.", "entity": "Cisplatin", "aliases": "Biocisplatinum Cisplatin Diamminodichloride Platinum Dichlorodiammineplatinum NSC-119875 Platidiam Platino Platinol cis Diamminedichloroplatinum cis-Diamminedichloroplatinum cis-Diamminedichloroplatinum(II) cis-Dichlorodiammineplatinum(II) cis-Platinum", "definition": "An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.\n    ", "id": "MESH:D002945"}
{"mention": "tumor", "mention_text": "The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g/m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty-eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi's syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g/m2 of ifosfamide, a younger age (less than 2 1/2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "glucosuria", "mention_text": "The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g/m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty-eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi's syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g/m2 of ifosfamide, a younger age (less than 2 1/2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children.", "entity": "Glycosuria, Renal", "aliases": "Glycosuria Renal Glucosuria", "definition": "An autosomal inherited disorder due to defective reabsorption of GLUCOSE by the PROXIMAL RENAL TUBULES. The urinary loss of glucose can reach beyond 50 g/day. It is attributed to the mutations in the SODIUM-GLUCOSE TRANSPORTER 2 encoded by the SLC5A2 gene.\n    ", "id": "MESH:D006030"}
{"mention": "proteinuria", "mention_text": "The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g/m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty-eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi's syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g/m2 of ifosfamide, a younger age (less than 2 1/2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "aminoaciduria", "mention_text": "The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g/m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty-eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi's syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g/m2 of ifosfamide, a younger age (less than 2 1/2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children.", "entity": "Renal Aminoacidurias", "aliases": "Aminoaciduria Renal Aminoacidurias", "definition": "A group of inherited kidney disorders characterized by the abnormally elevated levels of AMINO ACIDS in URINE. Genetic mutations of transport proteins result in the defective reabsorption of free amino acids at the PROXIMAL RENAL TUBULES. Renal aminoaciduria are classified by the specific amino acid or acids involved.\n    ", "id": "MESH:D000608"}
{"mention": "creatinine", "mention_text": "The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g/m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty-eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi's syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g/m2 of ifosfamide, a younger age (less than 2 1/2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children.", "entity": "Creatinine", "aliases": "Creatinine Sulfate Salt Krebiozen", "definition": "", "id": "MESH:D003404"}
{"mention": "phosphate", "mention_text": "The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g/m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty-eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi's syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g/m2 of ifosfamide, a younger age (less than 2 1/2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children.", "entity": "Phosphates", "aliases": "Inorganic Phosphates Orthophosphate", "definition": "Inorganic salts of phosphoric acid.\n    ", "id": "MESH:D010710"}
{"mention": "renal abnormalities", "mention_text": "The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g/m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty-eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi's syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g/m2 of ifosfamide, a younger age (less than 2 1/2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "toxicity", "mention_text": "The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g/m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty-eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi's syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g/m2 of ifosfamide, a younger age (less than 2 1/2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "Fanconi's syndrome", "mention_text": "The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g/m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty-eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi's syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g/m2 of ifosfamide, a younger age (less than 2 1/2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children.", "entity": "Fanconi Syndrome", "aliases": "Adult Fanconi Syndrome Bickel De Toni-Debre-Fanconi Diabete Pseudo-Phlorizin Diabetes Renotubular with Intestinal Malabsorption and Galactose Intolerance without Cystinosis Renal Type Glycogenosis Fanconi-Bickel Syndromes Glycogen Storage Disease XI Hepatic Amino Aciduria Glucosuria Nephropathy Hepatorenal Idiopathic Lignac Lignac-Fanconi Luder Sheldon Luder-Sheldon Neonatal Primary Proximal Tubular Dysfunction Pseudo Phlorizin", "definition": "A hereditary or acquired form of generalized dysfunction of the PROXIMAL KIDNEY TUBULE without primary involvement of the KIDNEY GLOMERULUS. It is usually characterized by the tubular wasting of nutrients and salts (GLUCOSE; AMINO ACIDS; PHOSPHATES; and BICARBONATES) resulting in HYPOKALEMIA; ACIDOSIS; HYPERCALCIURIA; and PROTEINURIA.\n    ", "id": "MESH:D005198"}
{"mention": "TDFS", "mention_text": "The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g/m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty-eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi's syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g/m2 of ifosfamide, a younger age (less than 2 1/2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children.", "entity": "Fanconi Syndrome", "aliases": "Adult Fanconi Syndrome Bickel De Toni-Debre-Fanconi Diabete Pseudo-Phlorizin Diabetes Renotubular with Intestinal Malabsorption and Galactose Intolerance without Cystinosis Renal Type Glycogenosis Fanconi-Bickel Syndromes Glycogen Storage Disease XI Hepatic Amino Aciduria Glucosuria Nephropathy Hepatorenal Idiopathic Lignac Lignac-Fanconi Luder Sheldon Luder-Sheldon Neonatal Primary Proximal Tubular Dysfunction Pseudo Phlorizin", "definition": "A hereditary or acquired form of generalized dysfunction of the PROXIMAL KIDNEY TUBULE without primary involvement of the KIDNEY GLOMERULUS. It is usually characterized by the tubular wasting of nutrients and salts (GLUCOSE; AMINO ACIDS; PHOSPHATES; and BICARBONATES) resulting in HYPOKALEMIA; ACIDOSIS; HYPERCALCIURIA; and PROTEINURIA.\n    ", "id": "MESH:D005198"}
{"mention": "mesenchymal tumors", "mention_text": "The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g/m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty-eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi's syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g/m2 of ifosfamide, a younger age (less than 2 1/2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children.", "entity": "Malignant mesenchymal tumor", "aliases": "Malignant mesenchymal tumor mesenchymoma", "definition": "", "id": "MESH:C535700"}
{"mention": "dopamine", "mention_text": "Evidence for an involvement of D1 and D2 dopamine receptors in mediating nicotine-induced hyperactivity in rats.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "nicotine", "mention_text": "Evidence for an involvement of D1 and D2 dopamine receptors in mediating nicotine-induced hyperactivity in rats.", "entity": "Nicotine", "aliases": "Bitartrate Nicotine Tartrate", "definition": "Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.\n    ", "id": "MESH:D009538"}
{"mention": "hyperactivity", "mention_text": "Evidence for an involvement of D1 and D2 dopamine receptors in mediating nicotine-induced hyperactivity in rats.", "entity": "Hyperkinesis", "aliases": "Generalized Hyperkinesia Hyperkinesias Hyperactivity Motor Hyperkinesis Hyperkinetic Movement Movements", "definition": "Excessive movement of muscles of the body as a whole, which may be associated with organic or psychological disorders.\n    ", "id": "MESH:D006948"}
{"mention": "nicotine", "mention_text": "Previous studies have suggested that repeated exposure of rats to the drug or to the experimental environment is necessary to observe nicotine-induced locomotor stimulation. In the present study the role of habituation to the experimental environment on the stimulant effect of nicotine in rats was examined. In addition, the role of dopamine receptors in mediating nicotine-induced locomotor stimulation was investigated by examining the effects of selective D1 and D2 dopamine receptor antagonists on activity induced by nicotine. Locomotor activity was assessed in male Sprague-Dawley rats tested in photocell cages. Nicotine (1.0 mg/kg) caused a significant increase in locomotor activity in rats that were habituated to the test environment, but had only a weak and delayed stimulant action in rats that were unfamiliar with the test environment. The stimulant action of nicotine was blocked by the central nicotinic antagonist mecamylamine but not by the peripheral nicotinic blocker hexamethonium, indicating that the response is probably mediated by central nicotinic receptors. Nicotine-induced hyperactivity was blocked by the selective D1 antagonist SCH 23390, the selective D2 antagonist raclopride and the D1/D2 antagonist fluphenazine. Pretreatment with the D2 agonist PHNO enhanced nicotine-induced hyperactivity, whereas the D1 agonist SKF 38393 had no effect. The results indicate that acute nicotine injection induces a pronounced hyperactivity in rats habituated to the test environment. The effect appears to be mediated by central nicotine receptors, possibly located on dopaminergic neurons, and also requires the activation of both D1 and D2 dopamine receptors.", "entity": "Nicotine", "aliases": "Bitartrate Nicotine Tartrate", "definition": "Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.\n    ", "id": "MESH:D009538"}
{"mention": "dopamine", "mention_text": "Previous studies have suggested that repeated exposure of rats to the drug or to the experimental environment is necessary to observe nicotine-induced locomotor stimulation. In the present study the role of habituation to the experimental environment on the stimulant effect of nicotine in rats was examined. In addition, the role of dopamine receptors in mediating nicotine-induced locomotor stimulation was investigated by examining the effects of selective D1 and D2 dopamine receptor antagonists on activity induced by nicotine. Locomotor activity was assessed in male Sprague-Dawley rats tested in photocell cages. Nicotine (1.0 mg/kg) caused a significant increase in locomotor activity in rats that were habituated to the test environment, but had only a weak and delayed stimulant action in rats that were unfamiliar with the test environment. The stimulant action of nicotine was blocked by the central nicotinic antagonist mecamylamine but not by the peripheral nicotinic blocker hexamethonium, indicating that the response is probably mediated by central nicotinic receptors. Nicotine-induced hyperactivity was blocked by the selective D1 antagonist SCH 23390, the selective D2 antagonist raclopride and the D1/D2 antagonist fluphenazine. Pretreatment with the D2 agonist PHNO enhanced nicotine-induced hyperactivity, whereas the D1 agonist SKF 38393 had no effect. The results indicate that acute nicotine injection induces a pronounced hyperactivity in rats habituated to the test environment. The effect appears to be mediated by central nicotine receptors, possibly located on dopaminergic neurons, and also requires the activation of both D1 and D2 dopamine receptors.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "Nicotine", "mention_text": "Previous studies have suggested that repeated exposure of rats to the drug or to the experimental environment is necessary to observe nicotine-induced locomotor stimulation. In the present study the role of habituation to the experimental environment on the stimulant effect of nicotine in rats was examined. In addition, the role of dopamine receptors in mediating nicotine-induced locomotor stimulation was investigated by examining the effects of selective D1 and D2 dopamine receptor antagonists on activity induced by nicotine. Locomotor activity was assessed in male Sprague-Dawley rats tested in photocell cages. Nicotine (1.0 mg/kg) caused a significant increase in locomotor activity in rats that were habituated to the test environment, but had only a weak and delayed stimulant action in rats that were unfamiliar with the test environment. The stimulant action of nicotine was blocked by the central nicotinic antagonist mecamylamine but not by the peripheral nicotinic blocker hexamethonium, indicating that the response is probably mediated by central nicotinic receptors. Nicotine-induced hyperactivity was blocked by the selective D1 antagonist SCH 23390, the selective D2 antagonist raclopride and the D1/D2 antagonist fluphenazine. Pretreatment with the D2 agonist PHNO enhanced nicotine-induced hyperactivity, whereas the D1 agonist SKF 38393 had no effect. The results indicate that acute nicotine injection induces a pronounced hyperactivity in rats habituated to the test environment. The effect appears to be mediated by central nicotine receptors, possibly located on dopaminergic neurons, and also requires the activation of both D1 and D2 dopamine receptors.", "entity": "Nicotine", "aliases": "Bitartrate Nicotine Tartrate", "definition": "Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.\n    ", "id": "MESH:D009538"}
{"mention": "increase in locomotor activity", "mention_text": "Previous studies have suggested that repeated exposure of rats to the drug or to the experimental environment is necessary to observe nicotine-induced locomotor stimulation. In the present study the role of habituation to the experimental environment on the stimulant effect of nicotine in rats was examined. In addition, the role of dopamine receptors in mediating nicotine-induced locomotor stimulation was investigated by examining the effects of selective D1 and D2 dopamine receptor antagonists on activity induced by nicotine. Locomotor activity was assessed in male Sprague-Dawley rats tested in photocell cages. Nicotine (1.0 mg/kg) caused a significant increase in locomotor activity in rats that were habituated to the test environment, but had only a weak and delayed stimulant action in rats that were unfamiliar with the test environment. The stimulant action of nicotine was blocked by the central nicotinic antagonist mecamylamine but not by the peripheral nicotinic blocker hexamethonium, indicating that the response is probably mediated by central nicotinic receptors. Nicotine-induced hyperactivity was blocked by the selective D1 antagonist SCH 23390, the selective D2 antagonist raclopride and the D1/D2 antagonist fluphenazine. Pretreatment with the D2 agonist PHNO enhanced nicotine-induced hyperactivity, whereas the D1 agonist SKF 38393 had no effect. The results indicate that acute nicotine injection induces a pronounced hyperactivity in rats habituated to the test environment. The effect appears to be mediated by central nicotine receptors, possibly located on dopaminergic neurons, and also requires the activation of both D1 and D2 dopamine receptors.", "entity": "Hyperkinesis", "aliases": "Generalized Hyperkinesia Hyperkinesias Hyperactivity Motor Hyperkinesis Hyperkinetic Movement Movements", "definition": "Excessive movement of muscles of the body as a whole, which may be associated with organic or psychological disorders.\n    ", "id": "MESH:D006948"}
{"mention": "mecamylamine", "mention_text": "Previous studies have suggested that repeated exposure of rats to the drug or to the experimental environment is necessary to observe nicotine-induced locomotor stimulation. In the present study the role of habituation to the experimental environment on the stimulant effect of nicotine in rats was examined. In addition, the role of dopamine receptors in mediating nicotine-induced locomotor stimulation was investigated by examining the effects of selective D1 and D2 dopamine receptor antagonists on activity induced by nicotine. Locomotor activity was assessed in male Sprague-Dawley rats tested in photocell cages. Nicotine (1.0 mg/kg) caused a significant increase in locomotor activity in rats that were habituated to the test environment, but had only a weak and delayed stimulant action in rats that were unfamiliar with the test environment. The stimulant action of nicotine was blocked by the central nicotinic antagonist mecamylamine but not by the peripheral nicotinic blocker hexamethonium, indicating that the response is probably mediated by central nicotinic receptors. Nicotine-induced hyperactivity was blocked by the selective D1 antagonist SCH 23390, the selective D2 antagonist raclopride and the D1/D2 antagonist fluphenazine. Pretreatment with the D2 agonist PHNO enhanced nicotine-induced hyperactivity, whereas the D1 agonist SKF 38393 had no effect. The results indicate that acute nicotine injection induces a pronounced hyperactivity in rats habituated to the test environment. The effect appears to be mediated by central nicotine receptors, possibly located on dopaminergic neurons, and also requires the activation of both D1 and D2 dopamine receptors.", "entity": "Mecamylamine", "aliases": "Mecamylamine", "definition": "A nicotinic antagonist that is well absorbed from the gastrointestinal tract and crosses the blood-brain barrier. Mecamylamine has been used as a ganglionic blocker in treating hypertension, but, like most ganglionic blockers, is more often used now as a research tool.\n    ", "id": "MESH:D008464"}
{"mention": "hexamethonium", "mention_text": "Previous studies have suggested that repeated exposure of rats to the drug or to the experimental environment is necessary to observe nicotine-induced locomotor stimulation. In the present study the role of habituation to the experimental environment on the stimulant effect of nicotine in rats was examined. In addition, the role of dopamine receptors in mediating nicotine-induced locomotor stimulation was investigated by examining the effects of selective D1 and D2 dopamine receptor antagonists on activity induced by nicotine. Locomotor activity was assessed in male Sprague-Dawley rats tested in photocell cages. Nicotine (1.0 mg/kg) caused a significant increase in locomotor activity in rats that were habituated to the test environment, but had only a weak and delayed stimulant action in rats that were unfamiliar with the test environment. The stimulant action of nicotine was blocked by the central nicotinic antagonist mecamylamine but not by the peripheral nicotinic blocker hexamethonium, indicating that the response is probably mediated by central nicotinic receptors. Nicotine-induced hyperactivity was blocked by the selective D1 antagonist SCH 23390, the selective D2 antagonist raclopride and the D1/D2 antagonist fluphenazine. Pretreatment with the D2 agonist PHNO enhanced nicotine-induced hyperactivity, whereas the D1 agonist SKF 38393 had no effect. The results indicate that acute nicotine injection induces a pronounced hyperactivity in rats habituated to the test environment. The effect appears to be mediated by central nicotine receptors, possibly located on dopaminergic neurons, and also requires the activation of both D1 and D2 dopamine receptors.", "entity": "Hexamethonium", "aliases": "Bitartrate Hexamethonium Bromide Chloride Depressin Dibromide Dihydrate Dichloride Dihydroxide Diiodide Dimethylsulfate Diperchlorate Iodide Monotartrate Hexonium", "definition": "A nicotinic cholinergic antagonist often referred to as the prototypical ganglionic blocker. It is poorly absorbed from the gastrointestinal tract and does not cross the blood-brain barrier. It has been used for a variety of therapeutic purposes including hypertension but, like the other ganglionic blockers, it has been replaced by more specific drugs for most purposes, although it is widely used a research tool.\n    ", "id": "MESH:D018738"}
{"mention": "hyperactivity", "mention_text": "Previous studies have suggested that repeated exposure of rats to the drug or to the experimental environment is necessary to observe nicotine-induced locomotor stimulation. In the present study the role of habituation to the experimental environment on the stimulant effect of nicotine in rats was examined. In addition, the role of dopamine receptors in mediating nicotine-induced locomotor stimulation was investigated by examining the effects of selective D1 and D2 dopamine receptor antagonists on activity induced by nicotine. Locomotor activity was assessed in male Sprague-Dawley rats tested in photocell cages. Nicotine (1.0 mg/kg) caused a significant increase in locomotor activity in rats that were habituated to the test environment, but had only a weak and delayed stimulant action in rats that were unfamiliar with the test environment. The stimulant action of nicotine was blocked by the central nicotinic antagonist mecamylamine but not by the peripheral nicotinic blocker hexamethonium, indicating that the response is probably mediated by central nicotinic receptors. Nicotine-induced hyperactivity was blocked by the selective D1 antagonist SCH 23390, the selective D2 antagonist raclopride and the D1/D2 antagonist fluphenazine. Pretreatment with the D2 agonist PHNO enhanced nicotine-induced hyperactivity, whereas the D1 agonist SKF 38393 had no effect. The results indicate that acute nicotine injection induces a pronounced hyperactivity in rats habituated to the test environment. The effect appears to be mediated by central nicotine receptors, possibly located on dopaminergic neurons, and also requires the activation of both D1 and D2 dopamine receptors.", "entity": "Hyperkinesis", "aliases": "Generalized Hyperkinesia Hyperkinesias Hyperactivity Motor Hyperkinesis Hyperkinetic Movement Movements", "definition": "Excessive movement of muscles of the body as a whole, which may be associated with organic or psychological disorders.\n    ", "id": "MESH:D006948"}
{"mention": "SCH 23390", "mention_text": "Previous studies have suggested that repeated exposure of rats to the drug or to the experimental environment is necessary to observe nicotine-induced locomotor stimulation. In the present study the role of habituation to the experimental environment on the stimulant effect of nicotine in rats was examined. In addition, the role of dopamine receptors in mediating nicotine-induced locomotor stimulation was investigated by examining the effects of selective D1 and D2 dopamine receptor antagonists on activity induced by nicotine. Locomotor activity was assessed in male Sprague-Dawley rats tested in photocell cages. Nicotine (1.0 mg/kg) caused a significant increase in locomotor activity in rats that were habituated to the test environment, but had only a weak and delayed stimulant action in rats that were unfamiliar with the test environment. The stimulant action of nicotine was blocked by the central nicotinic antagonist mecamylamine but not by the peripheral nicotinic blocker hexamethonium, indicating that the response is probably mediated by central nicotinic receptors. Nicotine-induced hyperactivity was blocked by the selective D1 antagonist SCH 23390, the selective D2 antagonist raclopride and the D1/D2 antagonist fluphenazine. Pretreatment with the D2 agonist PHNO enhanced nicotine-induced hyperactivity, whereas the D1 agonist SKF 38393 had no effect. The results indicate that acute nicotine injection induces a pronounced hyperactivity in rats habituated to the test environment. The effect appears to be mediated by central nicotine receptors, possibly located on dopaminergic neurons, and also requires the activation of both D1 and D2 dopamine receptors.", "entity": "SCH 23390", "aliases": "7-chloro-3-methyl-1-phenyl-1,2,4,5-tetrahydro-3-benzazepin-8-ol R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3- benzazepine-7-ol SCH 23390 SCH-23390 SCH23390", "definition": "", "id": "MESH:C534628"}
{"mention": "raclopride", "mention_text": "Previous studies have suggested that repeated exposure of rats to the drug or to the experimental environment is necessary to observe nicotine-induced locomotor stimulation. In the present study the role of habituation to the experimental environment on the stimulant effect of nicotine in rats was examined. In addition, the role of dopamine receptors in mediating nicotine-induced locomotor stimulation was investigated by examining the effects of selective D1 and D2 dopamine receptor antagonists on activity induced by nicotine. Locomotor activity was assessed in male Sprague-Dawley rats tested in photocell cages. Nicotine (1.0 mg/kg) caused a significant increase in locomotor activity in rats that were habituated to the test environment, but had only a weak and delayed stimulant action in rats that were unfamiliar with the test environment. The stimulant action of nicotine was blocked by the central nicotinic antagonist mecamylamine but not by the peripheral nicotinic blocker hexamethonium, indicating that the response is probably mediated by central nicotinic receptors. Nicotine-induced hyperactivity was blocked by the selective D1 antagonist SCH 23390, the selective D2 antagonist raclopride and the D1/D2 antagonist fluphenazine. Pretreatment with the D2 agonist PHNO enhanced nicotine-induced hyperactivity, whereas the D1 agonist SKF 38393 had no effect. The results indicate that acute nicotine injection induces a pronounced hyperactivity in rats habituated to the test environment. The effect appears to be mediated by central nicotine receptors, possibly located on dopaminergic neurons, and also requires the activation of both D1 and D2 dopamine receptors.", "entity": "Raclopride", "aliases": "C11 Raclopride FLA 870 FLA-870 FLA870 FLB 472 FLB-472 FLB472", "definition": "A substituted benzamide that has antipsychotic properties. It is a dopamine D2 receptor (see RECEPTORS, DOPAMINE D2) antagonist.\n    ", "id": "MESH:D020891"}
{"mention": "fluphenazine", "mention_text": "Previous studies have suggested that repeated exposure of rats to the drug or to the experimental environment is necessary to observe nicotine-induced locomotor stimulation. In the present study the role of habituation to the experimental environment on the stimulant effect of nicotine in rats was examined. In addition, the role of dopamine receptors in mediating nicotine-induced locomotor stimulation was investigated by examining the effects of selective D1 and D2 dopamine receptor antagonists on activity induced by nicotine. Locomotor activity was assessed in male Sprague-Dawley rats tested in photocell cages. Nicotine (1.0 mg/kg) caused a significant increase in locomotor activity in rats that were habituated to the test environment, but had only a weak and delayed stimulant action in rats that were unfamiliar with the test environment. The stimulant action of nicotine was blocked by the central nicotinic antagonist mecamylamine but not by the peripheral nicotinic blocker hexamethonium, indicating that the response is probably mediated by central nicotinic receptors. Nicotine-induced hyperactivity was blocked by the selective D1 antagonist SCH 23390, the selective D2 antagonist raclopride and the D1/D2 antagonist fluphenazine. Pretreatment with the D2 agonist PHNO enhanced nicotine-induced hyperactivity, whereas the D1 agonist SKF 38393 had no effect. The results indicate that acute nicotine injection induces a pronounced hyperactivity in rats habituated to the test environment. The effect appears to be mediated by central nicotine receptors, possibly located on dopaminergic neurons, and also requires the activation of both D1 and D2 dopamine receptors.", "entity": "Fluphenazine", "aliases": "Flufenazin Fluphenazine Hydrochloride Lyogen Prolixin", "definition": "A phenothiazine used in the treatment of PSYCHOSES. Its properties and uses are generally similar to those of CHLORPROMAZINE.\n    ", "id": "MESH:D005476"}
{"mention": "SKF 38393", "mention_text": "Previous studies have suggested that repeated exposure of rats to the drug or to the experimental environment is necessary to observe nicotine-induced locomotor stimulation. In the present study the role of habituation to the experimental environment on the stimulant effect of nicotine in rats was examined. In addition, the role of dopamine receptors in mediating nicotine-induced locomotor stimulation was investigated by examining the effects of selective D1 and D2 dopamine receptor antagonists on activity induced by nicotine. Locomotor activity was assessed in male Sprague-Dawley rats tested in photocell cages. Nicotine (1.0 mg/kg) caused a significant increase in locomotor activity in rats that were habituated to the test environment, but had only a weak and delayed stimulant action in rats that were unfamiliar with the test environment. The stimulant action of nicotine was blocked by the central nicotinic antagonist mecamylamine but not by the peripheral nicotinic blocker hexamethonium, indicating that the response is probably mediated by central nicotinic receptors. Nicotine-induced hyperactivity was blocked by the selective D1 antagonist SCH 23390, the selective D2 antagonist raclopride and the D1/D2 antagonist fluphenazine. Pretreatment with the D2 agonist PHNO enhanced nicotine-induced hyperactivity, whereas the D1 agonist SKF 38393 had no effect. The results indicate that acute nicotine injection induces a pronounced hyperactivity in rats habituated to the test environment. The effect appears to be mediated by central nicotine receptors, possibly located on dopaminergic neurons, and also requires the activation of both D1 and D2 dopamine receptors.", "entity": "2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine", "aliases": "1H-3-Benzazepine-7,8-diol 2,3,4,5-tetrahydro-1-phenyl- 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine R-SK&F 38393 RSK&F SK&F SK&F-38393 SK&F38393 SKF A 38393-A 38393A SKF-38393 SKF38393", "definition": "A selective D1 dopamine receptor agonist used primarily as a research tool.\n    ", "id": "MESH:D015647"}
{"mention": "mefloquine", "mention_text": "Neuropsychiatric side effects after the use of mefloquine.", "entity": "Mefloquine", "aliases": "Hoffmann La Roche Brand of Mefloquine Hydrochloride Hoffmann-La Lariam Mephloquine Ro 21 5998 001 Ro-21-5998-001 Ro215998001 WR 142,490 177,602 WR-142,490 WR-177,602 WR142,490 WR177,602", "definition": "A phospholipid-interacting antimalarial drug (ANTIMALARIALS). It is very effective against PLASMODIUM FALCIPARUM with very few side effects.\n    ", "id": "MESH:D015767"}
{"mention": "mefloquine", "mention_text": "This study describes neuropsychiatric side effects in patients after treatment with mefloquine. Reactions consisted mainly of seizures, acute psychoses, anxiety neurosis, and major disturbances of sleep-wake rhythm. Side effects occurred after both therapeutic and prophylactic intake and were graded from moderate to severe. In a risk analysis of neuropsychiatric side effects in Germany, it is estimated that one of 8,000 mefloquine users suffers from such reactions. The incidence calculation revealed that one of 215 therapeutic users had reactions, compared with one of 13,000 in the prophylaxis group, making the risk of neuropsychiatric reactions after mefloquine treatment 60 times higher than after prophylaxis. Therefore, certain limitations for malaria prophylaxis and treatment with mefloquine are recommended.", "entity": "Mefloquine", "aliases": "Hoffmann La Roche Brand of Mefloquine Hydrochloride Hoffmann-La Lariam Mephloquine Ro 21 5998 001 Ro-21-5998-001 Ro215998001 WR 142,490 177,602 WR-142,490 WR-177,602 WR142,490 WR177,602", "definition": "A phospholipid-interacting antimalarial drug (ANTIMALARIALS). It is very effective against PLASMODIUM FALCIPARUM with very few side effects.\n    ", "id": "MESH:D015767"}
{"mention": "seizures", "mention_text": "This study describes neuropsychiatric side effects in patients after treatment with mefloquine. Reactions consisted mainly of seizures, acute psychoses, anxiety neurosis, and major disturbances of sleep-wake rhythm. Side effects occurred after both therapeutic and prophylactic intake and were graded from moderate to severe. In a risk analysis of neuropsychiatric side effects in Germany, it is estimated that one of 8,000 mefloquine users suffers from such reactions. The incidence calculation revealed that one of 215 therapeutic users had reactions, compared with one of 13,000 in the prophylaxis group, making the risk of neuropsychiatric reactions after mefloquine treatment 60 times higher than after prophylaxis. Therefore, certain limitations for malaria prophylaxis and treatment with mefloquine are recommended.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "psychoses", "mention_text": "This study describes neuropsychiatric side effects in patients after treatment with mefloquine. Reactions consisted mainly of seizures, acute psychoses, anxiety neurosis, and major disturbances of sleep-wake rhythm. Side effects occurred after both therapeutic and prophylactic intake and were graded from moderate to severe. In a risk analysis of neuropsychiatric side effects in Germany, it is estimated that one of 8,000 mefloquine users suffers from such reactions. The incidence calculation revealed that one of 215 therapeutic users had reactions, compared with one of 13,000 in the prophylaxis group, making the risk of neuropsychiatric reactions after mefloquine treatment 60 times higher than after prophylaxis. Therefore, certain limitations for malaria prophylaxis and treatment with mefloquine are recommended.", "entity": "Psychoses, Substance-Induced", "aliases": "Drug Psychoses Substance Induced Substance-Induced Toxic", "definition": "Psychotic organic mental disorders resulting from the toxic effect of drugs and chemicals or other harmful substance.\n    ", "id": "MESH:D011605"}
{"mention": "anxiety neurosis", "mention_text": "This study describes neuropsychiatric side effects in patients after treatment with mefloquine. Reactions consisted mainly of seizures, acute psychoses, anxiety neurosis, and major disturbances of sleep-wake rhythm. Side effects occurred after both therapeutic and prophylactic intake and were graded from moderate to severe. In a risk analysis of neuropsychiatric side effects in Germany, it is estimated that one of 8,000 mefloquine users suffers from such reactions. The incidence calculation revealed that one of 215 therapeutic users had reactions, compared with one of 13,000 in the prophylaxis group, making the risk of neuropsychiatric reactions after mefloquine treatment 60 times higher than after prophylaxis. Therefore, certain limitations for malaria prophylaxis and treatment with mefloquine are recommended.", "entity": "Anxiety Disorders", "aliases": "Anxiety Disorder Disorders Neuroses State Neurotic States", "definition": "Persistent and disabling ANXIETY.\n    ", "id": "MESH:D001008"}
{"mention": "disturbances of sleep-wake rhythm", "mention_text": "This study describes neuropsychiatric side effects in patients after treatment with mefloquine. Reactions consisted mainly of seizures, acute psychoses, anxiety neurosis, and major disturbances of sleep-wake rhythm. Side effects occurred after both therapeutic and prophylactic intake and were graded from moderate to severe. In a risk analysis of neuropsychiatric side effects in Germany, it is estimated that one of 8,000 mefloquine users suffers from such reactions. The incidence calculation revealed that one of 215 therapeutic users had reactions, compared with one of 13,000 in the prophylaxis group, making the risk of neuropsychiatric reactions after mefloquine treatment 60 times higher than after prophylaxis. Therefore, certain limitations for malaria prophylaxis and treatment with mefloquine are recommended.", "entity": "Sleep Disorders", "aliases": "Long Sleeper Syndrome Syndromes Neurogenic Tachypnea Sleep-Related Tachypneas Phenotype Short Sleep Phenotypes Disorders Related Subwakefullness", "definition": "Conditions characterized by disturbances of usual sleep patterns or behaviors. Sleep disorders may be divided into three major categories: DYSSOMNIAS (i.e. disorders characterized by insomnia or hypersomnia), PARASOMNIAS (abnormal sleep behaviors), and sleep disorders secondary to medical or psychiatric disorders. (From Thorpy, Sleep Disorders Medicine, 1994, p187)\n    ", "id": "MESH:D012893"}
{"mention": "malaria", "mention_text": "This study describes neuropsychiatric side effects in patients after treatment with mefloquine. Reactions consisted mainly of seizures, acute psychoses, anxiety neurosis, and major disturbances of sleep-wake rhythm. Side effects occurred after both therapeutic and prophylactic intake and were graded from moderate to severe. In a risk analysis of neuropsychiatric side effects in Germany, it is estimated that one of 8,000 mefloquine users suffers from such reactions. The incidence calculation revealed that one of 215 therapeutic users had reactions, compared with one of 13,000 in the prophylaxis group, making the risk of neuropsychiatric reactions after mefloquine treatment 60 times higher than after prophylaxis. Therefore, certain limitations for malaria prophylaxis and treatment with mefloquine are recommended.", "entity": "Malaria", "aliases": "Fever Marsh Remittent Infection Plasmodium Infections Malaria Paludism", "definition": "A protozoan disease caused in humans by four species of the PLASMODIUM genus: PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; PLASMODIUM OVALE; and PLASMODIUM MALARIAE; and transmitted by the bite of an infected female mosquito of the genus ANOPHELES. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high FEVER; SWEATING; shaking CHILLS; and ANEMIA. Malaria in ANIMALS is caused by other species of plasmodia.\n    ", "id": "MESH:D008288"}
{"mention": "pain", "mention_text": "Reduction in injection pain using buffered lidocaine as a local anesthetic before cardiac catheterization.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "lidocaine", "mention_text": "Reduction in injection pain using buffered lidocaine as a local anesthetic before cardiac catheterization.", "entity": "Lidocaine", "aliases": "2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide 2-2EtN-2MePhAcN Astrazeneca Brand of Lidocaine Dalcaine Jenapharm Lidocanine Hydrochloride Carbonate (2:1) Hydrocarbonate Monoacetate Monohydrochloride Monohydrate Sulfate (1:1) Lignocaine Novocol Octocaine Strathmann Xylesthesin Xylocaine Xylocitin Xyloneural", "definition": "A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.\n    ", "id": "MESH:D008012"}
{"mention": "pain", "mention_text": "Previous reports have suggested that pain associated with the injection of lidocaine is related to the acidic pH of the solution. To determine if the addition of a buffering solution to adjust the pH of lidocaine into the physiologic range would reduce pain during injection, we performed a blinded randomized study in patients undergoing cardiac catheterization. Twenty patients were asked to quantify the severity of pain after receiving standard lidocaine in one femoral area and buffered lidocaine in the opposite femoral area. The mean pain score for buffered lidocaine was significantly lower than the mean score for standard lidocaine (2.7 +/- 1.9 vs. 3.8 +/- 2.2, P = 0.03). The pH adjustment of standard lidocaine can be accomplished easily in the catheterization laboratory before injection and results in a reduction of the pain occurring during the infiltration of tissues.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "lidocaine", "mention_text": "Previous reports have suggested that pain associated with the injection of lidocaine is related to the acidic pH of the solution. To determine if the addition of a buffering solution to adjust the pH of lidocaine into the physiologic range would reduce pain during injection, we performed a blinded randomized study in patients undergoing cardiac catheterization. Twenty patients were asked to quantify the severity of pain after receiving standard lidocaine in one femoral area and buffered lidocaine in the opposite femoral area. The mean pain score for buffered lidocaine was significantly lower than the mean score for standard lidocaine (2.7 +/- 1.9 vs. 3.8 +/- 2.2, P = 0.03). The pH adjustment of standard lidocaine can be accomplished easily in the catheterization laboratory before injection and results in a reduction of the pain occurring during the infiltration of tissues.", "entity": "Lidocaine", "aliases": "2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide 2-2EtN-2MePhAcN Astrazeneca Brand of Lidocaine Dalcaine Jenapharm Lidocanine Hydrochloride Carbonate (2:1) Hydrocarbonate Monoacetate Monohydrochloride Monohydrate Sulfate (1:1) Lignocaine Novocol Octocaine Strathmann Xylesthesin Xylocaine Xylocitin Xyloneural", "definition": "A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.\n    ", "id": "MESH:D008012"}
{"mention": "mazindol", "mention_text": "Randomized, double-blind trial of mazindol in Duchenne dystrophy.", "entity": "Mazindol", "aliases": "AN-448 AN448 Diestet Mazanor Mazindol Medix Brand Novartis Searle Wyeth Mazindole of Sanjorex Sanorex Solucaps Teronac Teronak", "definition": "Tricyclic anorexigenic agent unrelated to and less toxic than AMPHETAMINE, but with some similar side effects. It inhibits uptake of catecholamines and blocks the binding of cocaine to the dopamine uptake transporter.\n    ", "id": "MESH:D008454"}
{"mention": "Duchenne dystrophy", "mention_text": "Randomized, double-blind trial of mazindol in Duchenne dystrophy.", "entity": "Muscular Dystrophy, Duchenne", "aliases": "Becker Muscular Dystrophy Becker's Cardiomyopathy Dilated 3B X-Linked Childhood Pseudohypertrophic Duchenne Type Progressive and Duchenne-Becker Duchenne-Type Types", "definition": "An X-linked recessive muscle disease caused by an inability to synthesize DYSTROPHIN, which is involved with maintaining the integrity of the sarcolemma. Muscle fibers undergo a process that features degeneration and regeneration. Clinical manifestations include proximal weakness in the first few years of life, pseudohypertrophy, cardiomyopathy (see MYOCARDIAL DISEASES), and an increased incidence of impaired mentation. Becker muscular dystrophy is a closely related condition featuring a later onset of disease (usually adolescence) and a slowly progressive course. (Adams et al., Principles of Neurology, 6th ed, p1415)\n    ", "id": "MESH:D020388"}
{"mention": "weakness", "mention_text": "There is evidence that growth hormone may be related to the progression of weakness in Duchenne dystrophy. We conducted a 12-month controlled trial of mazindol, a putative growth hormone secretion inhibitor, in 83 boys with Duchenne dystrophy. Muscle strength, contractures, functional ability and pulmonary function were tested at baseline, and 6 and 12 months after treatment with mazindol (3 mg/d) or placebo. The study was designed to have a power of greater than 0.90 to detect a slowing to 25% of the expected rate of progression of weakness at P less than 0.05. Mazindol did not benefit strength at any point in the study. Side effects attributable to mazindol included decreased appetite (36%), dry mouth (10%), behavioral change (22%), and gastrointestinal symptoms (18%); mazindol dosage was reduced in 43% of patients. The effect of mazindol on GH secretion was estimated indirectly by comparing the postabsorptive IGF-I levels obtained following 3, 6, 9, and 12 months in the mazindol treated to those in the placebo groups. Although mazindol-treated patients gained less weight and height than placebo-treated patients, no significant effect on IGF-I levels was observed. Mazindol doses not slow the progression of weakness in Duchenne dystrophy.", "entity": "Muscle Weakness", "aliases": "Muscle Weakness Weaknesses Muscular", "definition": "A vague complaint of debility, fatigue, or exhaustion attributable to weakness of various muscles. The weakness can be characterized as subacute or chronic, often progressive, and is a manifestation of many muscle and neuromuscular diseases. (From Wyngaarden et al., Cecil Textbook of Medicine, 19th ed, p2251)\n    ", "id": "MESH:D018908"}
{"mention": "Duchenne dystrophy", "mention_text": "There is evidence that growth hormone may be related to the progression of weakness in Duchenne dystrophy. We conducted a 12-month controlled trial of mazindol, a putative growth hormone secretion inhibitor, in 83 boys with Duchenne dystrophy. Muscle strength, contractures, functional ability and pulmonary function were tested at baseline, and 6 and 12 months after treatment with mazindol (3 mg/d) or placebo. The study was designed to have a power of greater than 0.90 to detect a slowing to 25% of the expected rate of progression of weakness at P less than 0.05. Mazindol did not benefit strength at any point in the study. Side effects attributable to mazindol included decreased appetite (36%), dry mouth (10%), behavioral change (22%), and gastrointestinal symptoms (18%); mazindol dosage was reduced in 43% of patients. The effect of mazindol on GH secretion was estimated indirectly by comparing the postabsorptive IGF-I levels obtained following 3, 6, 9, and 12 months in the mazindol treated to those in the placebo groups. Although mazindol-treated patients gained less weight and height than placebo-treated patients, no significant effect on IGF-I levels was observed. Mazindol doses not slow the progression of weakness in Duchenne dystrophy.", "entity": "Muscular Dystrophy, Duchenne", "aliases": "Becker Muscular Dystrophy Becker's Cardiomyopathy Dilated 3B X-Linked Childhood Pseudohypertrophic Duchenne Type Progressive and Duchenne-Becker Duchenne-Type Types", "definition": "An X-linked recessive muscle disease caused by an inability to synthesize DYSTROPHIN, which is involved with maintaining the integrity of the sarcolemma. Muscle fibers undergo a process that features degeneration and regeneration. Clinical manifestations include proximal weakness in the first few years of life, pseudohypertrophy, cardiomyopathy (see MYOCARDIAL DISEASES), and an increased incidence of impaired mentation. Becker muscular dystrophy is a closely related condition featuring a later onset of disease (usually adolescence) and a slowly progressive course. (Adams et al., Principles of Neurology, 6th ed, p1415)\n    ", "id": "MESH:D020388"}
{"mention": "mazindol", "mention_text": "There is evidence that growth hormone may be related to the progression of weakness in Duchenne dystrophy. We conducted a 12-month controlled trial of mazindol, a putative growth hormone secretion inhibitor, in 83 boys with Duchenne dystrophy. Muscle strength, contractures, functional ability and pulmonary function were tested at baseline, and 6 and 12 months after treatment with mazindol (3 mg/d) or placebo. The study was designed to have a power of greater than 0.90 to detect a slowing to 25% of the expected rate of progression of weakness at P less than 0.05. Mazindol did not benefit strength at any point in the study. Side effects attributable to mazindol included decreased appetite (36%), dry mouth (10%), behavioral change (22%), and gastrointestinal symptoms (18%); mazindol dosage was reduced in 43% of patients. The effect of mazindol on GH secretion was estimated indirectly by comparing the postabsorptive IGF-I levels obtained following 3, 6, 9, and 12 months in the mazindol treated to those in the placebo groups. Although mazindol-treated patients gained less weight and height than placebo-treated patients, no significant effect on IGF-I levels was observed. Mazindol doses not slow the progression of weakness in Duchenne dystrophy.", "entity": "Mazindol", "aliases": "AN-448 AN448 Diestet Mazanor Mazindol Medix Brand Novartis Searle Wyeth Mazindole of Sanjorex Sanorex Solucaps Teronac Teronak", "definition": "Tricyclic anorexigenic agent unrelated to and less toxic than AMPHETAMINE, but with some similar side effects. It inhibits uptake of catecholamines and blocks the binding of cocaine to the dopamine uptake transporter.\n    ", "id": "MESH:D008454"}
{"mention": "Mazindol", "mention_text": "There is evidence that growth hormone may be related to the progression of weakness in Duchenne dystrophy. We conducted a 12-month controlled trial of mazindol, a putative growth hormone secretion inhibitor, in 83 boys with Duchenne dystrophy. Muscle strength, contractures, functional ability and pulmonary function were tested at baseline, and 6 and 12 months after treatment with mazindol (3 mg/d) or placebo. The study was designed to have a power of greater than 0.90 to detect a slowing to 25% of the expected rate of progression of weakness at P less than 0.05. Mazindol did not benefit strength at any point in the study. Side effects attributable to mazindol included decreased appetite (36%), dry mouth (10%), behavioral change (22%), and gastrointestinal symptoms (18%); mazindol dosage was reduced in 43% of patients. The effect of mazindol on GH secretion was estimated indirectly by comparing the postabsorptive IGF-I levels obtained following 3, 6, 9, and 12 months in the mazindol treated to those in the placebo groups. Although mazindol-treated patients gained less weight and height than placebo-treated patients, no significant effect on IGF-I levels was observed. Mazindol doses not slow the progression of weakness in Duchenne dystrophy.", "entity": "Mazindol", "aliases": "AN-448 AN448 Diestet Mazanor Mazindol Medix Brand Novartis Searle Wyeth Mazindole of Sanjorex Sanorex Solucaps Teronac Teronak", "definition": "Tricyclic anorexigenic agent unrelated to and less toxic than AMPHETAMINE, but with some similar side effects. It inhibits uptake of catecholamines and blocks the binding of cocaine to the dopamine uptake transporter.\n    ", "id": "MESH:D008454"}
{"mention": "decreased appetite", "mention_text": "There is evidence that growth hormone may be related to the progression of weakness in Duchenne dystrophy. We conducted a 12-month controlled trial of mazindol, a putative growth hormone secretion inhibitor, in 83 boys with Duchenne dystrophy. Muscle strength, contractures, functional ability and pulmonary function were tested at baseline, and 6 and 12 months after treatment with mazindol (3 mg/d) or placebo. The study was designed to have a power of greater than 0.90 to detect a slowing to 25% of the expected rate of progression of weakness at P less than 0.05. Mazindol did not benefit strength at any point in the study. Side effects attributable to mazindol included decreased appetite (36%), dry mouth (10%), behavioral change (22%), and gastrointestinal symptoms (18%); mazindol dosage was reduced in 43% of patients. The effect of mazindol on GH secretion was estimated indirectly by comparing the postabsorptive IGF-I levels obtained following 3, 6, 9, and 12 months in the mazindol treated to those in the placebo groups. Although mazindol-treated patients gained less weight and height than placebo-treated patients, no significant effect on IGF-I levels was observed. Mazindol doses not slow the progression of weakness in Duchenne dystrophy.", "entity": "Eating Disorders", "aliases": "Appetite Disorder Disorders Eating", "definition": "A group of disorders characterized by physiological and psychological disturbances in appetite or food intake.\n    ", "id": "MESH:D001068"}
{"mention": "dry mouth", "mention_text": "There is evidence that growth hormone may be related to the progression of weakness in Duchenne dystrophy. We conducted a 12-month controlled trial of mazindol, a putative growth hormone secretion inhibitor, in 83 boys with Duchenne dystrophy. Muscle strength, contractures, functional ability and pulmonary function were tested at baseline, and 6 and 12 months after treatment with mazindol (3 mg/d) or placebo. The study was designed to have a power of greater than 0.90 to detect a slowing to 25% of the expected rate of progression of weakness at P less than 0.05. Mazindol did not benefit strength at any point in the study. Side effects attributable to mazindol included decreased appetite (36%), dry mouth (10%), behavioral change (22%), and gastrointestinal symptoms (18%); mazindol dosage was reduced in 43% of patients. The effect of mazindol on GH secretion was estimated indirectly by comparing the postabsorptive IGF-I levels obtained following 3, 6, 9, and 12 months in the mazindol treated to those in the placebo groups. Although mazindol-treated patients gained less weight and height than placebo-treated patients, no significant effect on IGF-I levels was observed. Mazindol doses not slow the progression of weakness in Duchenne dystrophy.", "entity": "Xerostomia", "aliases": "Asialia Asialias Dryness Mouth Hyposalivation Hyposalivations Xerostomia Xerostomias", "definition": "Decreased salivary flow.\n    ", "id": "MESH:D014987"}
{"mention": "gastrointestinal symptoms", "mention_text": "There is evidence that growth hormone may be related to the progression of weakness in Duchenne dystrophy. We conducted a 12-month controlled trial of mazindol, a putative growth hormone secretion inhibitor, in 83 boys with Duchenne dystrophy. Muscle strength, contractures, functional ability and pulmonary function were tested at baseline, and 6 and 12 months after treatment with mazindol (3 mg/d) or placebo. The study was designed to have a power of greater than 0.90 to detect a slowing to 25% of the expected rate of progression of weakness at P less than 0.05. Mazindol did not benefit strength at any point in the study. Side effects attributable to mazindol included decreased appetite (36%), dry mouth (10%), behavioral change (22%), and gastrointestinal symptoms (18%); mazindol dosage was reduced in 43% of patients. The effect of mazindol on GH secretion was estimated indirectly by comparing the postabsorptive IGF-I levels obtained following 3, 6, 9, and 12 months in the mazindol treated to those in the placebo groups. Although mazindol-treated patients gained less weight and height than placebo-treated patients, no significant effect on IGF-I levels was observed. Mazindol doses not slow the progression of weakness in Duchenne dystrophy.", "entity": "Signs and Symptoms, Digestive", "aliases": "Signs and Symptoms Digestive", "definition": "Digestive system manifestations of diseases of the gastrointestinal system or of other organs.\n    ", "id": "MESH:D012817"}
{"mention": "Pentoxifylline", "mention_text": "Pentoxifylline (Trental) does not inhibit dipyridamole-induced coronary hyperemia: implications for dipyridamole-thallium-201 myocardial imaging.", "entity": "Pentoxifylline", "aliases": "Agapurin BL 191 BL-191 BL191 Oxpentifylline Pentoxifylline Pentoxil Torental Trental", "definition": "A METHYLXANTHINE derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production.\n    ", "id": "MESH:D010431"}
{"mention": "Trental", "mention_text": "Pentoxifylline (Trental) does not inhibit dipyridamole-induced coronary hyperemia: implications for dipyridamole-thallium-201 myocardial imaging.", "entity": "Pentoxifylline", "aliases": "Agapurin BL 191 BL-191 BL191 Oxpentifylline Pentoxifylline Pentoxil Torental Trental", "definition": "A METHYLXANTHINE derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production.\n    ", "id": "MESH:D010431"}
{"mention": "dipyridamole", "mention_text": "Pentoxifylline (Trental) does not inhibit dipyridamole-induced coronary hyperemia: implications for dipyridamole-thallium-201 myocardial imaging.", "entity": "Dipyridamole", "aliases": "Antistenocardin Apo-Dipyridamole Apotex Brand of Dipyridamole Ashbourne Belmac Berlin Chemie Berlin-Chemie Boehringer Ingelheim Cerebrovase Cléridium Curantil Curantyl Dipyramidole IPRAD Kurantil Miosen Novo-Dipiradol Novopharm Persantin Persantine", "definition": "A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752)\n    ", "id": "MESH:D004176"}
{"mention": "hyperemia", "mention_text": "Pentoxifylline (Trental) does not inhibit dipyridamole-induced coronary hyperemia: implications for dipyridamole-thallium-201 myocardial imaging.", "entity": "Hyperemia", "aliases": "Active Hyperemia Arterial Congestion Venous Engorgement Passive Reactive Hyperemias", "definition": "The presence of an increased amount of blood in a body part or an organ leading to congestion or engorgement of blood vessels. Hyperemia can be due to increase of blood flow into the area (active or arterial), or due to obstruction of outflow of blood from the area (passive or venous).\n    ", "id": "MESH:D006940"}
{"mention": "thallium", "mention_text": "Pentoxifylline (Trental) does not inhibit dipyridamole-induced coronary hyperemia: implications for dipyridamole-thallium-201 myocardial imaging.", "entity": "Thallium", "aliases": "Thallium", "definition": "A heavy, bluish white metal, atomic number 81, atomic weight [204.382; 204.385], symbol Tl.\n    ", "id": "MESH:D013793"}
{"mention": "Dipyridamole", "mention_text": "Dipyridamole-thallium-201 imaging is often performed in patients unable to exercise because of peripheral vascular disease. Many of these patients are taking pentoxifylline (Trental), a methylxanthine derivative which may improve intermittent claudication. Whether pentoxifylline inhibits dipyridamole-induced coronary hyperemia like other methylxanthines such as theophylline and should be stopped prior to dipyridamole-thallium-201 imaging is unknown. Therefore, we studied the hyperemic response to dipyridamole in seven open-chest anesthetized dogs after pretreatment with either pentoxifylline (0, 7.5, or 15 mg/kg i.v.) or theophylline (3 mg/kg i.v.). Baseline circumflex coronary blood flows did not differ significantly among treatment groups. Dipyridamole significantly increased coronary blood flow before and after 7.5 or 15 mm/kg i.v. pentoxifylline (p less than 0.002). Neither dose of pentoxifylline significantly decreased the dipyridamole-induced hyperemia, while peak coronary blood flow was significantly lower after theophylline (p less than 0.01). We conclude that pentoxyifylline does not inhibit dipyridamole-induced coronary hyperemia even at high doses.", "entity": "Dipyridamole", "aliases": "Antistenocardin Apo-Dipyridamole Apotex Brand of Dipyridamole Ashbourne Belmac Berlin Chemie Berlin-Chemie Boehringer Ingelheim Cerebrovase Cléridium Curantil Curantyl Dipyramidole IPRAD Kurantil Miosen Novo-Dipiradol Novopharm Persantin Persantine", "definition": "A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752)\n    ", "id": "MESH:D004176"}
{"mention": "thallium", "mention_text": "Dipyridamole-thallium-201 imaging is often performed in patients unable to exercise because of peripheral vascular disease. Many of these patients are taking pentoxifylline (Trental), a methylxanthine derivative which may improve intermittent claudication. Whether pentoxifylline inhibits dipyridamole-induced coronary hyperemia like other methylxanthines such as theophylline and should be stopped prior to dipyridamole-thallium-201 imaging is unknown. Therefore, we studied the hyperemic response to dipyridamole in seven open-chest anesthetized dogs after pretreatment with either pentoxifylline (0, 7.5, or 15 mg/kg i.v.) or theophylline (3 mg/kg i.v.). Baseline circumflex coronary blood flows did not differ significantly among treatment groups. Dipyridamole significantly increased coronary blood flow before and after 7.5 or 15 mm/kg i.v. pentoxifylline (p less than 0.002). Neither dose of pentoxifylline significantly decreased the dipyridamole-induced hyperemia, while peak coronary blood flow was significantly lower after theophylline (p less than 0.01). We conclude that pentoxyifylline does not inhibit dipyridamole-induced coronary hyperemia even at high doses.", "entity": "Thallium", "aliases": "Thallium", "definition": "A heavy, bluish white metal, atomic number 81, atomic weight [204.382; 204.385], symbol Tl.\n    ", "id": "MESH:D013793"}
{"mention": "peripheral vascular disease", "mention_text": "Dipyridamole-thallium-201 imaging is often performed in patients unable to exercise because of peripheral vascular disease. Many of these patients are taking pentoxifylline (Trental), a methylxanthine derivative which may improve intermittent claudication. Whether pentoxifylline inhibits dipyridamole-induced coronary hyperemia like other methylxanthines such as theophylline and should be stopped prior to dipyridamole-thallium-201 imaging is unknown. Therefore, we studied the hyperemic response to dipyridamole in seven open-chest anesthetized dogs after pretreatment with either pentoxifylline (0, 7.5, or 15 mg/kg i.v.) or theophylline (3 mg/kg i.v.). Baseline circumflex coronary blood flows did not differ significantly among treatment groups. Dipyridamole significantly increased coronary blood flow before and after 7.5 or 15 mm/kg i.v. pentoxifylline (p less than 0.002). Neither dose of pentoxifylline significantly decreased the dipyridamole-induced hyperemia, while peak coronary blood flow was significantly lower after theophylline (p less than 0.01). We conclude that pentoxyifylline does not inhibit dipyridamole-induced coronary hyperemia even at high doses.", "entity": "Peripheral Vascular Diseases", "aliases": "Angiopathies Peripheral Angiopathy Disease Vascular Diseases", "definition": "Pathological processes involving any one of the BLOOD VESSELS in the vasculature outside the HEART.\n    ", "id": "MESH:D016491"}
{"mention": "pentoxifylline", "mention_text": "Dipyridamole-thallium-201 imaging is often performed in patients unable to exercise because of peripheral vascular disease. Many of these patients are taking pentoxifylline (Trental), a methylxanthine derivative which may improve intermittent claudication. Whether pentoxifylline inhibits dipyridamole-induced coronary hyperemia like other methylxanthines such as theophylline and should be stopped prior to dipyridamole-thallium-201 imaging is unknown. Therefore, we studied the hyperemic response to dipyridamole in seven open-chest anesthetized dogs after pretreatment with either pentoxifylline (0, 7.5, or 15 mg/kg i.v.) or theophylline (3 mg/kg i.v.). Baseline circumflex coronary blood flows did not differ significantly among treatment groups. Dipyridamole significantly increased coronary blood flow before and after 7.5 or 15 mm/kg i.v. pentoxifylline (p less than 0.002). Neither dose of pentoxifylline significantly decreased the dipyridamole-induced hyperemia, while peak coronary blood flow was significantly lower after theophylline (p less than 0.01). We conclude that pentoxyifylline does not inhibit dipyridamole-induced coronary hyperemia even at high doses.", "entity": "Pentoxifylline", "aliases": "Agapurin BL 191 BL-191 BL191 Oxpentifylline Pentoxifylline Pentoxil Torental Trental", "definition": "A METHYLXANTHINE derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production.\n    ", "id": "MESH:D010431"}
{"mention": "Trental", "mention_text": "Dipyridamole-thallium-201 imaging is often performed in patients unable to exercise because of peripheral vascular disease. Many of these patients are taking pentoxifylline (Trental), a methylxanthine derivative which may improve intermittent claudication. Whether pentoxifylline inhibits dipyridamole-induced coronary hyperemia like other methylxanthines such as theophylline and should be stopped prior to dipyridamole-thallium-201 imaging is unknown. Therefore, we studied the hyperemic response to dipyridamole in seven open-chest anesthetized dogs after pretreatment with either pentoxifylline (0, 7.5, or 15 mg/kg i.v.) or theophylline (3 mg/kg i.v.). Baseline circumflex coronary blood flows did not differ significantly among treatment groups. Dipyridamole significantly increased coronary blood flow before and after 7.5 or 15 mm/kg i.v. pentoxifylline (p less than 0.002). Neither dose of pentoxifylline significantly decreased the dipyridamole-induced hyperemia, while peak coronary blood flow was significantly lower after theophylline (p less than 0.01). We conclude that pentoxyifylline does not inhibit dipyridamole-induced coronary hyperemia even at high doses.", "entity": "Pentoxifylline", "aliases": "Agapurin BL 191 BL-191 BL191 Oxpentifylline Pentoxifylline Pentoxil Torental Trental", "definition": "A METHYLXANTHINE derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production.\n    ", "id": "MESH:D010431"}
{"mention": "methylxanthine", "mention_text": "Dipyridamole-thallium-201 imaging is often performed in patients unable to exercise because of peripheral vascular disease. Many of these patients are taking pentoxifylline (Trental), a methylxanthine derivative which may improve intermittent claudication. Whether pentoxifylline inhibits dipyridamole-induced coronary hyperemia like other methylxanthines such as theophylline and should be stopped prior to dipyridamole-thallium-201 imaging is unknown. Therefore, we studied the hyperemic response to dipyridamole in seven open-chest anesthetized dogs after pretreatment with either pentoxifylline (0, 7.5, or 15 mg/kg i.v.) or theophylline (3 mg/kg i.v.). Baseline circumflex coronary blood flows did not differ significantly among treatment groups. Dipyridamole significantly increased coronary blood flow before and after 7.5 or 15 mm/kg i.v. pentoxifylline (p less than 0.002). Neither dose of pentoxifylline significantly decreased the dipyridamole-induced hyperemia, while peak coronary blood flow was significantly lower after theophylline (p less than 0.01). We conclude that pentoxyifylline does not inhibit dipyridamole-induced coronary hyperemia even at high doses.", "entity": "methylxanthine", "aliases": "methylxanthine", "definition": "", "id": "MESH:C008514"}
{"mention": "intermittent claudication", "mention_text": "Dipyridamole-thallium-201 imaging is often performed in patients unable to exercise because of peripheral vascular disease. Many of these patients are taking pentoxifylline (Trental), a methylxanthine derivative which may improve intermittent claudication. Whether pentoxifylline inhibits dipyridamole-induced coronary hyperemia like other methylxanthines such as theophylline and should be stopped prior to dipyridamole-thallium-201 imaging is unknown. Therefore, we studied the hyperemic response to dipyridamole in seven open-chest anesthetized dogs after pretreatment with either pentoxifylline (0, 7.5, or 15 mg/kg i.v.) or theophylline (3 mg/kg i.v.). Baseline circumflex coronary blood flows did not differ significantly among treatment groups. Dipyridamole significantly increased coronary blood flow before and after 7.5 or 15 mm/kg i.v. pentoxifylline (p less than 0.002). Neither dose of pentoxifylline significantly decreased the dipyridamole-induced hyperemia, while peak coronary blood flow was significantly lower after theophylline (p less than 0.01). We conclude that pentoxyifylline does not inhibit dipyridamole-induced coronary hyperemia even at high doses.", "entity": "Intermittent Claudication", "aliases": "Claudication Intermittent", "definition": "A symptom complex characterized by pain and weakness in SKELETAL MUSCLE group associated with exercise, such as leg pain and weakness brought on by walking. Such muscle limpness disappears after a brief rest and is often relates to arterial STENOSIS; muscle ISCHEMIA; and accumulation of LACTATE.\n    ", "id": "MESH:D007383"}
{"mention": "dipyridamole", "mention_text": "Dipyridamole-thallium-201 imaging is often performed in patients unable to exercise because of peripheral vascular disease. Many of these patients are taking pentoxifylline (Trental), a methylxanthine derivative which may improve intermittent claudication. Whether pentoxifylline inhibits dipyridamole-induced coronary hyperemia like other methylxanthines such as theophylline and should be stopped prior to dipyridamole-thallium-201 imaging is unknown. Therefore, we studied the hyperemic response to dipyridamole in seven open-chest anesthetized dogs after pretreatment with either pentoxifylline (0, 7.5, or 15 mg/kg i.v.) or theophylline (3 mg/kg i.v.). Baseline circumflex coronary blood flows did not differ significantly among treatment groups. Dipyridamole significantly increased coronary blood flow before and after 7.5 or 15 mm/kg i.v. pentoxifylline (p less than 0.002). Neither dose of pentoxifylline significantly decreased the dipyridamole-induced hyperemia, while peak coronary blood flow was significantly lower after theophylline (p less than 0.01). We conclude that pentoxyifylline does not inhibit dipyridamole-induced coronary hyperemia even at high doses.", "entity": "Dipyridamole", "aliases": "Antistenocardin Apo-Dipyridamole Apotex Brand of Dipyridamole Ashbourne Belmac Berlin Chemie Berlin-Chemie Boehringer Ingelheim Cerebrovase Cléridium Curantil Curantyl Dipyramidole IPRAD Kurantil Miosen Novo-Dipiradol Novopharm Persantin Persantine", "definition": "A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752)\n    ", "id": "MESH:D004176"}
{"mention": "hyperemia", "mention_text": "Dipyridamole-thallium-201 imaging is often performed in patients unable to exercise because of peripheral vascular disease. Many of these patients are taking pentoxifylline (Trental), a methylxanthine derivative which may improve intermittent claudication. Whether pentoxifylline inhibits dipyridamole-induced coronary hyperemia like other methylxanthines such as theophylline and should be stopped prior to dipyridamole-thallium-201 imaging is unknown. Therefore, we studied the hyperemic response to dipyridamole in seven open-chest anesthetized dogs after pretreatment with either pentoxifylline (0, 7.5, or 15 mg/kg i.v.) or theophylline (3 mg/kg i.v.). Baseline circumflex coronary blood flows did not differ significantly among treatment groups. Dipyridamole significantly increased coronary blood flow before and after 7.5 or 15 mm/kg i.v. pentoxifylline (p less than 0.002). Neither dose of pentoxifylline significantly decreased the dipyridamole-induced hyperemia, while peak coronary blood flow was significantly lower after theophylline (p less than 0.01). We conclude that pentoxyifylline does not inhibit dipyridamole-induced coronary hyperemia even at high doses.", "entity": "Hyperemia", "aliases": "Active Hyperemia Arterial Congestion Venous Engorgement Passive Reactive Hyperemias", "definition": "The presence of an increased amount of blood in a body part or an organ leading to congestion or engorgement of blood vessels. Hyperemia can be due to increase of blood flow into the area (active or arterial), or due to obstruction of outflow of blood from the area (passive or venous).\n    ", "id": "MESH:D006940"}
{"mention": "methylxanthines", "mention_text": "Dipyridamole-thallium-201 imaging is often performed in patients unable to exercise because of peripheral vascular disease. Many of these patients are taking pentoxifylline (Trental), a methylxanthine derivative which may improve intermittent claudication. Whether pentoxifylline inhibits dipyridamole-induced coronary hyperemia like other methylxanthines such as theophylline and should be stopped prior to dipyridamole-thallium-201 imaging is unknown. Therefore, we studied the hyperemic response to dipyridamole in seven open-chest anesthetized dogs after pretreatment with either pentoxifylline (0, 7.5, or 15 mg/kg i.v.) or theophylline (3 mg/kg i.v.). Baseline circumflex coronary blood flows did not differ significantly among treatment groups. Dipyridamole significantly increased coronary blood flow before and after 7.5 or 15 mm/kg i.v. pentoxifylline (p less than 0.002). Neither dose of pentoxifylline significantly decreased the dipyridamole-induced hyperemia, while peak coronary blood flow was significantly lower after theophylline (p less than 0.01). We conclude that pentoxyifylline does not inhibit dipyridamole-induced coronary hyperemia even at high doses.", "entity": "methylxanthine", "aliases": "methylxanthine", "definition": "", "id": "MESH:C008514"}
{"mention": "theophylline", "mention_text": "Dipyridamole-thallium-201 imaging is often performed in patients unable to exercise because of peripheral vascular disease. Many of these patients are taking pentoxifylline (Trental), a methylxanthine derivative which may improve intermittent claudication. Whether pentoxifylline inhibits dipyridamole-induced coronary hyperemia like other methylxanthines such as theophylline and should be stopped prior to dipyridamole-thallium-201 imaging is unknown. Therefore, we studied the hyperemic response to dipyridamole in seven open-chest anesthetized dogs after pretreatment with either pentoxifylline (0, 7.5, or 15 mg/kg i.v.) or theophylline (3 mg/kg i.v.). Baseline circumflex coronary blood flows did not differ significantly among treatment groups. Dipyridamole significantly increased coronary blood flow before and after 7.5 or 15 mm/kg i.v. pentoxifylline (p less than 0.002). Neither dose of pentoxifylline significantly decreased the dipyridamole-induced hyperemia, while peak coronary blood flow was significantly lower after theophylline (p less than 0.01). We conclude that pentoxyifylline does not inhibit dipyridamole-induced coronary hyperemia even at high doses.", "entity": "Theophylline", "aliases": "1,3 Dimethylxanthine 1,3-Dimethylxanthine 3,7-Dihydro-1,3-dimethyl-1H-purine-2,6-dione Accurbron Aerobin Aerolate Afonilum Retard Anhydrous Theophylline Aquaphyllin Armophylline Bronchoparat Bronkodyl Constant T Constant-T ConstantT Elixophyllin Euphylong Fameasan Brand of Sodium Glycinate Fujisawa Glycine Theophyllinate Lodrane Monospan Mundipharma Nuelin S.A. Quibron SR T-SR TSR Slo Phyllin Slo-Phyllin SloPhyllin Somophyllin Somophyllin-T SomophyllinT Sustaire Synophylate Theo 24 Dur Theo-24 T", "definition": "A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLATE CYCLASE and cyclic AMP.\n    ", "id": "MESH:D013806"}
{"mention": "pentoxyifylline", "mention_text": "Dipyridamole-thallium-201 imaging is often performed in patients unable to exercise because of peripheral vascular disease. Many of these patients are taking pentoxifylline (Trental), a methylxanthine derivative which may improve intermittent claudication. Whether pentoxifylline inhibits dipyridamole-induced coronary hyperemia like other methylxanthines such as theophylline and should be stopped prior to dipyridamole-thallium-201 imaging is unknown. Therefore, we studied the hyperemic response to dipyridamole in seven open-chest anesthetized dogs after pretreatment with either pentoxifylline (0, 7.5, or 15 mg/kg i.v.) or theophylline (3 mg/kg i.v.). Baseline circumflex coronary blood flows did not differ significantly among treatment groups. Dipyridamole significantly increased coronary blood flow before and after 7.5 or 15 mm/kg i.v. pentoxifylline (p less than 0.002). Neither dose of pentoxifylline significantly decreased the dipyridamole-induced hyperemia, while peak coronary blood flow was significantly lower after theophylline (p less than 0.01). We conclude that pentoxyifylline does not inhibit dipyridamole-induced coronary hyperemia even at high doses.", "entity": "Pentoxifylline", "aliases": "Agapurin BL 191 BL-191 BL191 Oxpentifylline Pentoxifylline Pentoxil Torental Trental", "definition": "A METHYLXANTHINE derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production.\n    ", "id": "MESH:D010431"}
{"mention": "death", "mention_text": "Cause of death among patients with Parkinson's disease: a rare mortality due to cerebral haemorrhage.", "entity": "Death", "aliases": "Cardiac Death Determination of Near-Death Experience", "definition": "Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.\n    ", "id": "MESH:D003643"}
{"mention": "Parkinson's disease", "mention_text": "Cause of death among patients with Parkinson's disease: a rare mortality due to cerebral haemorrhage.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "cerebral haemorrhage", "mention_text": "Cause of death among patients with Parkinson's disease: a rare mortality due to cerebral haemorrhage.", "entity": "Cerebral Hemorrhage", "aliases": "Brain Hemorrhage Cerebral Hemorrhages Parenchymal Cerebrum Intracerebral", "definition": "Bleeding into one or both CEREBRAL HEMISPHERES including the BASAL GANGLIA and the CEREBRAL CORTEX. It is often associated with HYPERTENSION and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D002543"}
{"mention": "death", "mention_text": "Causes of death, with special reference to cerebral haemorrhage, among 240 patients with pathologically verified Parkinson's disease were investigated using the Annuals of the Pathological Autopsy Cases in Japan from 1981 to 1985. The leading causes of death were pneumonia and bronchitis (44.1%), malignant neoplasms (11.6%), heart diseases (4.1%), cerebral infarction (3.7%) and septicaemia (3.3%). Cerebral haemorrhage was the 11th most frequent cause of death, accounting for only 0.8% of deaths among the patients, whereas it was the 5th most common cause of death among the Japanese general population in 1985. The low incidence of cerebral haemorrhage as a cause of death in patients with Parkinson's disease may reflect the hypotensive effect of levodopa and a hypotensive mechanism due to reduced noradrenaline levels in the parkinsonian brain.", "entity": "Death", "aliases": "Cardiac Death Determination of Near-Death Experience", "definition": "Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.\n    ", "id": "MESH:D003643"}
{"mention": "cerebral haemorrhage", "mention_text": "Causes of death, with special reference to cerebral haemorrhage, among 240 patients with pathologically verified Parkinson's disease were investigated using the Annuals of the Pathological Autopsy Cases in Japan from 1981 to 1985. The leading causes of death were pneumonia and bronchitis (44.1%), malignant neoplasms (11.6%), heart diseases (4.1%), cerebral infarction (3.7%) and septicaemia (3.3%). Cerebral haemorrhage was the 11th most frequent cause of death, accounting for only 0.8% of deaths among the patients, whereas it was the 5th most common cause of death among the Japanese general population in 1985. The low incidence of cerebral haemorrhage as a cause of death in patients with Parkinson's disease may reflect the hypotensive effect of levodopa and a hypotensive mechanism due to reduced noradrenaline levels in the parkinsonian brain.", "entity": "Cerebral Hemorrhage", "aliases": "Brain Hemorrhage Cerebral Hemorrhages Parenchymal Cerebrum Intracerebral", "definition": "Bleeding into one or both CEREBRAL HEMISPHERES including the BASAL GANGLIA and the CEREBRAL CORTEX. It is often associated with HYPERTENSION and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D002543"}
{"mention": "Parkinson's disease", "mention_text": "Causes of death, with special reference to cerebral haemorrhage, among 240 patients with pathologically verified Parkinson's disease were investigated using the Annuals of the Pathological Autopsy Cases in Japan from 1981 to 1985. The leading causes of death were pneumonia and bronchitis (44.1%), malignant neoplasms (11.6%), heart diseases (4.1%), cerebral infarction (3.7%) and septicaemia (3.3%). Cerebral haemorrhage was the 11th most frequent cause of death, accounting for only 0.8% of deaths among the patients, whereas it was the 5th most common cause of death among the Japanese general population in 1985. The low incidence of cerebral haemorrhage as a cause of death in patients with Parkinson's disease may reflect the hypotensive effect of levodopa and a hypotensive mechanism due to reduced noradrenaline levels in the parkinsonian brain.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "pneumonia", "mention_text": "Causes of death, with special reference to cerebral haemorrhage, among 240 patients with pathologically verified Parkinson's disease were investigated using the Annuals of the Pathological Autopsy Cases in Japan from 1981 to 1985. The leading causes of death were pneumonia and bronchitis (44.1%), malignant neoplasms (11.6%), heart diseases (4.1%), cerebral infarction (3.7%) and septicaemia (3.3%). Cerebral haemorrhage was the 11th most frequent cause of death, accounting for only 0.8% of deaths among the patients, whereas it was the 5th most common cause of death among the Japanese general population in 1985. The low incidence of cerebral haemorrhage as a cause of death in patients with Parkinson's disease may reflect the hypotensive effect of levodopa and a hypotensive mechanism due to reduced noradrenaline levels in the parkinsonian brain.", "entity": "Pneumonia", "aliases": "Experimental Lung Inflammation Inflammations Pulmonary Lobar Pneumonia Pneumonias Pneumonitides Pneumonitis", "definition": "Inflammation of any part, segment or lobe, of the lung parenchyma.\n    ", "id": "MESH:D011014"}
{"mention": "bronchitis", "mention_text": "Causes of death, with special reference to cerebral haemorrhage, among 240 patients with pathologically verified Parkinson's disease were investigated using the Annuals of the Pathological Autopsy Cases in Japan from 1981 to 1985. The leading causes of death were pneumonia and bronchitis (44.1%), malignant neoplasms (11.6%), heart diseases (4.1%), cerebral infarction (3.7%) and septicaemia (3.3%). Cerebral haemorrhage was the 11th most frequent cause of death, accounting for only 0.8% of deaths among the patients, whereas it was the 5th most common cause of death among the Japanese general population in 1985. The low incidence of cerebral haemorrhage as a cause of death in patients with Parkinson's disease may reflect the hypotensive effect of levodopa and a hypotensive mechanism due to reduced noradrenaline levels in the parkinsonian brain.", "entity": "Bronchitis", "aliases": "Bronchitides Bronchitis", "definition": "Inflammation of the large airways in the lung including any part of the BRONCHI, from the PRIMARY BRONCHI to the TERTIARY BRONCHI.\n    ", "id": "MESH:D001991"}
{"mention": "neoplasms", "mention_text": "Causes of death, with special reference to cerebral haemorrhage, among 240 patients with pathologically verified Parkinson's disease were investigated using the Annuals of the Pathological Autopsy Cases in Japan from 1981 to 1985. The leading causes of death were pneumonia and bronchitis (44.1%), malignant neoplasms (11.6%), heart diseases (4.1%), cerebral infarction (3.7%) and septicaemia (3.3%). Cerebral haemorrhage was the 11th most frequent cause of death, accounting for only 0.8% of deaths among the patients, whereas it was the 5th most common cause of death among the Japanese general population in 1985. The low incidence of cerebral haemorrhage as a cause of death in patients with Parkinson's disease may reflect the hypotensive effect of levodopa and a hypotensive mechanism due to reduced noradrenaline levels in the parkinsonian brain.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "heart diseases", "mention_text": "Causes of death, with special reference to cerebral haemorrhage, among 240 patients with pathologically verified Parkinson's disease were investigated using the Annuals of the Pathological Autopsy Cases in Japan from 1981 to 1985. The leading causes of death were pneumonia and bronchitis (44.1%), malignant neoplasms (11.6%), heart diseases (4.1%), cerebral infarction (3.7%) and septicaemia (3.3%). Cerebral haemorrhage was the 11th most frequent cause of death, accounting for only 0.8% of deaths among the patients, whereas it was the 5th most common cause of death among the Japanese general population in 1985. The low incidence of cerebral haemorrhage as a cause of death in patients with Parkinson's disease may reflect the hypotensive effect of levodopa and a hypotensive mechanism due to reduced noradrenaline levels in the parkinsonian brain.", "entity": "Heart Diseases", "aliases": "Cardiac Disease Diseases Heart", "definition": "Pathological conditions involving the HEART including its structural and functional abnormalities.\n    ", "id": "MESH:D006331"}
{"mention": "cerebral infarction", "mention_text": "Causes of death, with special reference to cerebral haemorrhage, among 240 patients with pathologically verified Parkinson's disease were investigated using the Annuals of the Pathological Autopsy Cases in Japan from 1981 to 1985. The leading causes of death were pneumonia and bronchitis (44.1%), malignant neoplasms (11.6%), heart diseases (4.1%), cerebral infarction (3.7%) and septicaemia (3.3%). Cerebral haemorrhage was the 11th most frequent cause of death, accounting for only 0.8% of deaths among the patients, whereas it was the 5th most common cause of death among the Japanese general population in 1985. The low incidence of cerebral haemorrhage as a cause of death in patients with Parkinson's disease may reflect the hypotensive effect of levodopa and a hypotensive mechanism due to reduced noradrenaline levels in the parkinsonian brain.", "entity": "Cerebral Infarction", "aliases": "Anterior Choroidal Artery Infarction Cerebral Left Hemisphere Right Infarctions Subcortical Posterior", "definition": "The formation of an area of NECROSIS in the CEREBRUM caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., INFARCTION, ANTERIOR CEREBRAL ARTERY), and etiology (e.g., embolic infarction).\n    ", "id": "MESH:D002544"}
{"mention": "septicaemia", "mention_text": "Causes of death, with special reference to cerebral haemorrhage, among 240 patients with pathologically verified Parkinson's disease were investigated using the Annuals of the Pathological Autopsy Cases in Japan from 1981 to 1985. The leading causes of death were pneumonia and bronchitis (44.1%), malignant neoplasms (11.6%), heart diseases (4.1%), cerebral infarction (3.7%) and septicaemia (3.3%). Cerebral haemorrhage was the 11th most frequent cause of death, accounting for only 0.8% of deaths among the patients, whereas it was the 5th most common cause of death among the Japanese general population in 1985. The low incidence of cerebral haemorrhage as a cause of death in patients with Parkinson's disease may reflect the hypotensive effect of levodopa and a hypotensive mechanism due to reduced noradrenaline levels in the parkinsonian brain.", "entity": "Sepsis", "aliases": "Blood Poisoning Poisonings Pyaemia Pyaemias Pyemia Pyemias Pyohemia Pyohemias Sepsis Severe Septicemia Septicemias", "definition": "Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by HYPOTENSION despite adequate fluid infusion, it is called SEPTIC SHOCK.\n    ", "id": "MESH:D018805"}
{"mention": "Cerebral haemorrhage", "mention_text": "Causes of death, with special reference to cerebral haemorrhage, among 240 patients with pathologically verified Parkinson's disease were investigated using the Annuals of the Pathological Autopsy Cases in Japan from 1981 to 1985. The leading causes of death were pneumonia and bronchitis (44.1%), malignant neoplasms (11.6%), heart diseases (4.1%), cerebral infarction (3.7%) and septicaemia (3.3%). Cerebral haemorrhage was the 11th most frequent cause of death, accounting for only 0.8% of deaths among the patients, whereas it was the 5th most common cause of death among the Japanese general population in 1985. The low incidence of cerebral haemorrhage as a cause of death in patients with Parkinson's disease may reflect the hypotensive effect of levodopa and a hypotensive mechanism due to reduced noradrenaline levels in the parkinsonian brain.", "entity": "Cerebral Hemorrhage", "aliases": "Brain Hemorrhage Cerebral Hemorrhages Parenchymal Cerebrum Intracerebral", "definition": "Bleeding into one or both CEREBRAL HEMISPHERES including the BASAL GANGLIA and the CEREBRAL CORTEX. It is often associated with HYPERTENSION and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D002543"}
{"mention": "deaths", "mention_text": "Causes of death, with special reference to cerebral haemorrhage, among 240 patients with pathologically verified Parkinson's disease were investigated using the Annuals of the Pathological Autopsy Cases in Japan from 1981 to 1985. The leading causes of death were pneumonia and bronchitis (44.1%), malignant neoplasms (11.6%), heart diseases (4.1%), cerebral infarction (3.7%) and septicaemia (3.3%). Cerebral haemorrhage was the 11th most frequent cause of death, accounting for only 0.8% of deaths among the patients, whereas it was the 5th most common cause of death among the Japanese general population in 1985. The low incidence of cerebral haemorrhage as a cause of death in patients with Parkinson's disease may reflect the hypotensive effect of levodopa and a hypotensive mechanism due to reduced noradrenaline levels in the parkinsonian brain.", "entity": "Death", "aliases": "Cardiac Death Determination of Near-Death Experience", "definition": "Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.\n    ", "id": "MESH:D003643"}
{"mention": "hypotensive", "mention_text": "Causes of death, with special reference to cerebral haemorrhage, among 240 patients with pathologically verified Parkinson's disease were investigated using the Annuals of the Pathological Autopsy Cases in Japan from 1981 to 1985. The leading causes of death were pneumonia and bronchitis (44.1%), malignant neoplasms (11.6%), heart diseases (4.1%), cerebral infarction (3.7%) and septicaemia (3.3%). Cerebral haemorrhage was the 11th most frequent cause of death, accounting for only 0.8% of deaths among the patients, whereas it was the 5th most common cause of death among the Japanese general population in 1985. The low incidence of cerebral haemorrhage as a cause of death in patients with Parkinson's disease may reflect the hypotensive effect of levodopa and a hypotensive mechanism due to reduced noradrenaline levels in the parkinsonian brain.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "levodopa", "mention_text": "Causes of death, with special reference to cerebral haemorrhage, among 240 patients with pathologically verified Parkinson's disease were investigated using the Annuals of the Pathological Autopsy Cases in Japan from 1981 to 1985. The leading causes of death were pneumonia and bronchitis (44.1%), malignant neoplasms (11.6%), heart diseases (4.1%), cerebral infarction (3.7%) and septicaemia (3.3%). Cerebral haemorrhage was the 11th most frequent cause of death, accounting for only 0.8% of deaths among the patients, whereas it was the 5th most common cause of death among the Japanese general population in 1985. The low incidence of cerebral haemorrhage as a cause of death in patients with Parkinson's disease may reflect the hypotensive effect of levodopa and a hypotensive mechanism due to reduced noradrenaline levels in the parkinsonian brain.", "entity": "Levodopa", "aliases": "3 Hydroxy L tyrosine 3-Hydroxy-L-tyrosine Dopaflex Dopar 3,4 Dihydroxyphenylalanine Dopa L-3,4-Dihydroxyphenylalanine L-Dopa Larodopa Levodopa Levopa Medphano Brand of Roberts Roche", "definition": "The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.\n    ", "id": "MESH:D007980"}
{"mention": "noradrenaline", "mention_text": "Causes of death, with special reference to cerebral haemorrhage, among 240 patients with pathologically verified Parkinson's disease were investigated using the Annuals of the Pathological Autopsy Cases in Japan from 1981 to 1985. The leading causes of death were pneumonia and bronchitis (44.1%), malignant neoplasms (11.6%), heart diseases (4.1%), cerebral infarction (3.7%) and septicaemia (3.3%). Cerebral haemorrhage was the 11th most frequent cause of death, accounting for only 0.8% of deaths among the patients, whereas it was the 5th most common cause of death among the Japanese general population in 1985. The low incidence of cerebral haemorrhage as a cause of death in patients with Parkinson's disease may reflect the hypotensive effect of levodopa and a hypotensive mechanism due to reduced noradrenaline levels in the parkinsonian brain.", "entity": "Norepinephrine", "aliases": "Abbott Brand of Levophed Bitartrate Arterenol Aventis Norepinephrine Hydrochloride Noradrenaline Levarterenol Levonor Levonorepinephrine Noradrénaline tartrate renaudin Norepinephrin d-Tartrate (1:1) (+)-Isomer (+,-)-Isomer l-Tartrate Monohydrate (1:2) Renaudin", "definition": "Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.\n    ", "id": "MESH:D009638"}
{"mention": "parkinsonian", "mention_text": "Causes of death, with special reference to cerebral haemorrhage, among 240 patients with pathologically verified Parkinson's disease were investigated using the Annuals of the Pathological Autopsy Cases in Japan from 1981 to 1985. The leading causes of death were pneumonia and bronchitis (44.1%), malignant neoplasms (11.6%), heart diseases (4.1%), cerebral infarction (3.7%) and septicaemia (3.3%). Cerebral haemorrhage was the 11th most frequent cause of death, accounting for only 0.8% of deaths among the patients, whereas it was the 5th most common cause of death among the Japanese general population in 1985. The low incidence of cerebral haemorrhage as a cause of death in patients with Parkinson's disease may reflect the hypotensive effect of levodopa and a hypotensive mechanism due to reduced noradrenaline levels in the parkinsonian brain.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "ribavirin", "mention_text": "Tolerance and antiviral effect of ribavirin in patients with Argentine hemorrhagic fever.", "entity": "Ribavirin", "aliases": "Dermatech Brand of Ribavirin Essex Grossman ICN 1229 ICN-1229 ICN1229 Merck Pfizer Rebetol Ribamide Ribamidil Ribamidyl Ribasphere Ribovirin Three Rivers Pharmaceuticals Tribavirin Vilona Viramide Virazide Virazole", "definition": "A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses.\n    ", "id": "MESH:D012254"}
{"mention": "Argentine hemorrhagic fever", "mention_text": "Tolerance and antiviral effect of ribavirin in patients with Argentine hemorrhagic fever.", "entity": "Hemorrhagic Fever, American", "aliases": "American Hemorrhagic Fever Argentinian Bolivian", "definition": "Diseases caused by American hemorrhagic fever viruses (ARENAVIRUSES, NEW WORLD).\n    ", "id": "MESH:D006478"}
{"mention": "ribavirin", "mention_text": "Tolerance and antiviral effect of ribavirin was studied in 6 patients with Argentine hemorrhagic fever (AHF) of more than 8 days of evolution. Administration of ribavirin resulted in a neutralization of viremia and a drop of endogenous interferon titers. The average time of death was delayed. A reversible anemia was the only adverse effect observed. From these results, we conclude that ribavirin has an antiviral effect in advanced cases of AHF, and that anemia, the only secondary reaction observed, can be easily managed. The possible beneficial effect of ribavirin during the initial days of AHF is discussed.", "entity": "Ribavirin", "aliases": "Dermatech Brand of Ribavirin Essex Grossman ICN 1229 ICN-1229 ICN1229 Merck Pfizer Rebetol Ribamide Ribamidil Ribamidyl Ribasphere Ribovirin Three Rivers Pharmaceuticals Tribavirin Vilona Viramide Virazide Virazole", "definition": "A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses.\n    ", "id": "MESH:D012254"}
{"mention": "Argentine hemorrhagic fever", "mention_text": "Tolerance and antiviral effect of ribavirin was studied in 6 patients with Argentine hemorrhagic fever (AHF) of more than 8 days of evolution. Administration of ribavirin resulted in a neutralization of viremia and a drop of endogenous interferon titers. The average time of death was delayed. A reversible anemia was the only adverse effect observed. From these results, we conclude that ribavirin has an antiviral effect in advanced cases of AHF, and that anemia, the only secondary reaction observed, can be easily managed. The possible beneficial effect of ribavirin during the initial days of AHF is discussed.", "entity": "Hemorrhagic Fever, American", "aliases": "American Hemorrhagic Fever Argentinian Bolivian", "definition": "Diseases caused by American hemorrhagic fever viruses (ARENAVIRUSES, NEW WORLD).\n    ", "id": "MESH:D006478"}
{"mention": "AHF", "mention_text": "Tolerance and antiviral effect of ribavirin was studied in 6 patients with Argentine hemorrhagic fever (AHF) of more than 8 days of evolution. Administration of ribavirin resulted in a neutralization of viremia and a drop of endogenous interferon titers. The average time of death was delayed. A reversible anemia was the only adverse effect observed. From these results, we conclude that ribavirin has an antiviral effect in advanced cases of AHF, and that anemia, the only secondary reaction observed, can be easily managed. The possible beneficial effect of ribavirin during the initial days of AHF is discussed.", "entity": "Hemorrhagic Fever, American", "aliases": "American Hemorrhagic Fever Argentinian Bolivian", "definition": "Diseases caused by American hemorrhagic fever viruses (ARENAVIRUSES, NEW WORLD).\n    ", "id": "MESH:D006478"}
{"mention": "viremia", "mention_text": "Tolerance and antiviral effect of ribavirin was studied in 6 patients with Argentine hemorrhagic fever (AHF) of more than 8 days of evolution. Administration of ribavirin resulted in a neutralization of viremia and a drop of endogenous interferon titers. The average time of death was delayed. A reversible anemia was the only adverse effect observed. From these results, we conclude that ribavirin has an antiviral effect in advanced cases of AHF, and that anemia, the only secondary reaction observed, can be easily managed. The possible beneficial effect of ribavirin during the initial days of AHF is discussed.", "entity": "Viremia", "aliases": "Viremia Viremias", "definition": "The presence of viruses in the blood.\n    ", "id": "MESH:D014766"}
{"mention": "death", "mention_text": "Tolerance and antiviral effect of ribavirin was studied in 6 patients with Argentine hemorrhagic fever (AHF) of more than 8 days of evolution. Administration of ribavirin resulted in a neutralization of viremia and a drop of endogenous interferon titers. The average time of death was delayed. A reversible anemia was the only adverse effect observed. From these results, we conclude that ribavirin has an antiviral effect in advanced cases of AHF, and that anemia, the only secondary reaction observed, can be easily managed. The possible beneficial effect of ribavirin during the initial days of AHF is discussed.", "entity": "Death", "aliases": "Cardiac Death Determination of Near-Death Experience", "definition": "Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.\n    ", "id": "MESH:D003643"}
{"mention": "anemia", "mention_text": "Tolerance and antiviral effect of ribavirin was studied in 6 patients with Argentine hemorrhagic fever (AHF) of more than 8 days of evolution. Administration of ribavirin resulted in a neutralization of viremia and a drop of endogenous interferon titers. The average time of death was delayed. A reversible anemia was the only adverse effect observed. From these results, we conclude that ribavirin has an antiviral effect in advanced cases of AHF, and that anemia, the only secondary reaction observed, can be easily managed. The possible beneficial effect of ribavirin during the initial days of AHF is discussed.", "entity": "Anemia", "aliases": "Anemia Anemias", "definition": "A reduction in the number of circulating ERYTHROCYTES or in the quantity of HEMOGLOBIN.\n    ", "id": "MESH:D000740"}
{"mention": "Dipyridamole", "mention_text": "Dipyridamole-induced myocardial ischemia.", "entity": "Dipyridamole", "aliases": "Antistenocardin Apo-Dipyridamole Apotex Brand of Dipyridamole Ashbourne Belmac Berlin Chemie Berlin-Chemie Boehringer Ingelheim Cerebrovase Cléridium Curantil Curantyl Dipyramidole IPRAD Kurantil Miosen Novo-Dipiradol Novopharm Persantin Persantine", "definition": "A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752)\n    ", "id": "MESH:D004176"}
{"mention": "myocardial ischemia", "mention_text": "Dipyridamole-induced myocardial ischemia.", "entity": "Myocardial Ischemia", "aliases": "Disease Ischemic Heart Diseases Ischemia Myocardial Ischemias", "definition": "A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).\n    ", "id": "MESH:D017202"}
{"mention": "Angina", "mention_text": "Angina and ischemic electrocardiographic changes occurred after administration of oral dipyridamole in four patients awaiting urgent myocardial revascularization procedures. To our knowledge, this has not previously been reported as a side effect of preoperative dipyridamole therapy, although dipyridamole-induced myocardial ischemia has been demonstrated to occur in animals and humans with coronary artery disease. Epicardial coronary collateral vessels were demonstrated in all four patients; a coronary \"steal\" phenomenon may be the mechanism of the dipyridamole-induced ischemia observed.", "entity": "Angina Pectoris", "aliases": "Angina Pectoris Angor Stenocardia Stenocardias", "definition": "The symptom of paroxysmal pain consequent to MYOCARDIAL ISCHEMIA usually of distinctive character, location and radiation. It is thought to be provoked by a transient stressful situation during which the oxygen requirements of the MYOCARDIUM exceed that supplied by the CORONARY CIRCULATION.\n    ", "id": "MESH:D000787"}
{"mention": "dipyridamole", "mention_text": "Angina and ischemic electrocardiographic changes occurred after administration of oral dipyridamole in four patients awaiting urgent myocardial revascularization procedures. To our knowledge, this has not previously been reported as a side effect of preoperative dipyridamole therapy, although dipyridamole-induced myocardial ischemia has been demonstrated to occur in animals and humans with coronary artery disease. Epicardial coronary collateral vessels were demonstrated in all four patients; a coronary \"steal\" phenomenon may be the mechanism of the dipyridamole-induced ischemia observed.", "entity": "Dipyridamole", "aliases": "Antistenocardin Apo-Dipyridamole Apotex Brand of Dipyridamole Ashbourne Belmac Berlin Chemie Berlin-Chemie Boehringer Ingelheim Cerebrovase Cléridium Curantil Curantyl Dipyramidole IPRAD Kurantil Miosen Novo-Dipiradol Novopharm Persantin Persantine", "definition": "A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752)\n    ", "id": "MESH:D004176"}
{"mention": "myocardial ischemia", "mention_text": "Angina and ischemic electrocardiographic changes occurred after administration of oral dipyridamole in four patients awaiting urgent myocardial revascularization procedures. To our knowledge, this has not previously been reported as a side effect of preoperative dipyridamole therapy, although dipyridamole-induced myocardial ischemia has been demonstrated to occur in animals and humans with coronary artery disease. Epicardial coronary collateral vessels were demonstrated in all four patients; a coronary \"steal\" phenomenon may be the mechanism of the dipyridamole-induced ischemia observed.", "entity": "Myocardial Ischemia", "aliases": "Disease Ischemic Heart Diseases Ischemia Myocardial Ischemias", "definition": "A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).\n    ", "id": "MESH:D017202"}
{"mention": "coronary artery disease", "mention_text": "Angina and ischemic electrocardiographic changes occurred after administration of oral dipyridamole in four patients awaiting urgent myocardial revascularization procedures. To our knowledge, this has not previously been reported as a side effect of preoperative dipyridamole therapy, although dipyridamole-induced myocardial ischemia has been demonstrated to occur in animals and humans with coronary artery disease. Epicardial coronary collateral vessels were demonstrated in all four patients; a coronary \"steal\" phenomenon may be the mechanism of the dipyridamole-induced ischemia observed.", "entity": "Coronary Artery Disease", "aliases": "Arterioscleroses Coronary Arteriosclerosis Artery Disease Diseases Atheroscleroses Atherosclerosis", "definition": "Pathological processes of CORONARY ARTERIES that may derive from a congenital abnormality, atherosclerotic, or non-atherosclerotic cause.\n    ", "id": "MESH:D003324"}
{"mention": "ischemia", "mention_text": "Angina and ischemic electrocardiographic changes occurred after administration of oral dipyridamole in four patients awaiting urgent myocardial revascularization procedures. To our knowledge, this has not previously been reported as a side effect of preoperative dipyridamole therapy, although dipyridamole-induced myocardial ischemia has been demonstrated to occur in animals and humans with coronary artery disease. Epicardial coronary collateral vessels were demonstrated in all four patients; a coronary \"steal\" phenomenon may be the mechanism of the dipyridamole-induced ischemia observed.", "entity": "Ischemia", "aliases": "Ischemia Ischemias", "definition": "A hypoperfusion of the BLOOD through an organ or tissue caused by a PATHOLOGIC CONSTRICTION or obstruction of its BLOOD VESSELS, or an absence of BLOOD CIRCULATION.\n    ", "id": "MESH:D007511"}
{"mention": "Nitroprusside", "mention_text": "Nitroprusside-induced hypotension evokes ACTH secretion which is primarily mediated by enhanced secretion of immunoreactive corticotropin-releasing factor (irCRF) into the hypophysial-portal circulation. Portal plasma concentrations of neither arginine vasopressin nor oxytocin are significantly altered in this paradigm. Application of a delayed feedback signal, in the form of a 2-h systemic corticosterone infusion in urethane-anesthetized rats with pharmacological blockade of glucocorticoid synthesis, is without effect on the resting secretion of arginine vasopressin and oxytocin at any corticosterone feedback dose tested. Resting irCRF levels are suppressed only at the highest corticosterone infusion rate, which resulted in systemic corticosterone levels of 40 micrograms/dl. Suppression of irCRF secretion in response to nitroprusside-induced hypotension is observed and occurs at a plasma corticosterone level between 8-12 micrograms/dl. These studies provide further evidence for a strong central component of the delayed feedback process which is mediated by modulation of irCRF release.", "entity": "Nitroprusside", "aliases": "Abbott Brand of Sodium Nitroprusside Bayer Cyanonitrosylferrate Disodium Salt Faulding Fides Ecopharma Ketostix Naniprus Nipride Nipruton Nitriate Nitroferricyanide Nitropress Nitroprussiat Dihydrate Roche SERB", "definition": "A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.\n    ", "id": "MESH:D009599"}
{"mention": "hypotension", "mention_text": "Nitroprusside-induced hypotension evokes ACTH secretion which is primarily mediated by enhanced secretion of immunoreactive corticotropin-releasing factor (irCRF) into the hypophysial-portal circulation. Portal plasma concentrations of neither arginine vasopressin nor oxytocin are significantly altered in this paradigm. Application of a delayed feedback signal, in the form of a 2-h systemic corticosterone infusion in urethane-anesthetized rats with pharmacological blockade of glucocorticoid synthesis, is without effect on the resting secretion of arginine vasopressin and oxytocin at any corticosterone feedback dose tested. Resting irCRF levels are suppressed only at the highest corticosterone infusion rate, which resulted in systemic corticosterone levels of 40 micrograms/dl. Suppression of irCRF secretion in response to nitroprusside-induced hypotension is observed and occurs at a plasma corticosterone level between 8-12 micrograms/dl. These studies provide further evidence for a strong central component of the delayed feedback process which is mediated by modulation of irCRF release.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "arginine vasopressin", "mention_text": "Nitroprusside-induced hypotension evokes ACTH secretion which is primarily mediated by enhanced secretion of immunoreactive corticotropin-releasing factor (irCRF) into the hypophysial-portal circulation. Portal plasma concentrations of neither arginine vasopressin nor oxytocin are significantly altered in this paradigm. Application of a delayed feedback signal, in the form of a 2-h systemic corticosterone infusion in urethane-anesthetized rats with pharmacological blockade of glucocorticoid synthesis, is without effect on the resting secretion of arginine vasopressin and oxytocin at any corticosterone feedback dose tested. Resting irCRF levels are suppressed only at the highest corticosterone infusion rate, which resulted in systemic corticosterone levels of 40 micrograms/dl. Suppression of irCRF secretion in response to nitroprusside-induced hypotension is observed and occurs at a plasma corticosterone level between 8-12 micrograms/dl. These studies provide further evidence for a strong central component of the delayed feedback process which is mediated by modulation of irCRF release.", "entity": "Arginine Vasopressin", "aliases": "Arg Vasopressin Arg-Vasopressin Arginine Argipressin Tannate", "definition": "The predominant form of mammalian antidiuretic hormone. It is a nonapeptide containing an ARGININE at residue 8 and two disulfide-linked cysteines at residues of 1 and 6. Arg-vasopressin is used to treat DIABETES INSIPIDUS or to improve vasomotor tone and BLOOD PRESSURE.\n    ", "id": "MESH:D001127"}
{"mention": "oxytocin", "mention_text": "Nitroprusside-induced hypotension evokes ACTH secretion which is primarily mediated by enhanced secretion of immunoreactive corticotropin-releasing factor (irCRF) into the hypophysial-portal circulation. Portal plasma concentrations of neither arginine vasopressin nor oxytocin are significantly altered in this paradigm. Application of a delayed feedback signal, in the form of a 2-h systemic corticosterone infusion in urethane-anesthetized rats with pharmacological blockade of glucocorticoid synthesis, is without effect on the resting secretion of arginine vasopressin and oxytocin at any corticosterone feedback dose tested. Resting irCRF levels are suppressed only at the highest corticosterone infusion rate, which resulted in systemic corticosterone levels of 40 micrograms/dl. Suppression of irCRF secretion in response to nitroprusside-induced hypotension is observed and occurs at a plasma corticosterone level between 8-12 micrograms/dl. These studies provide further evidence for a strong central component of the delayed feedback process which is mediated by modulation of irCRF release.", "entity": "Oxytocin", "aliases": "Ocytocin Oxytocin Pitocin Syntocinon", "definition": "A nonapeptide hormone released from the neurohypophysis (PITUITARY GLAND, POSTERIOR). It differs from VASOPRESSIN by two amino acids at residues 3 and 8. Oxytocin acts on SMOOTH MUSCLE CELLS, such as causing UTERINE CONTRACTIONS and MILK EJECTION.\n    ", "id": "MESH:D010121"}
{"mention": "corticosterone", "mention_text": "Nitroprusside-induced hypotension evokes ACTH secretion which is primarily mediated by enhanced secretion of immunoreactive corticotropin-releasing factor (irCRF) into the hypophysial-portal circulation. Portal plasma concentrations of neither arginine vasopressin nor oxytocin are significantly altered in this paradigm. Application of a delayed feedback signal, in the form of a 2-h systemic corticosterone infusion in urethane-anesthetized rats with pharmacological blockade of glucocorticoid synthesis, is without effect on the resting secretion of arginine vasopressin and oxytocin at any corticosterone feedback dose tested. Resting irCRF levels are suppressed only at the highest corticosterone infusion rate, which resulted in systemic corticosterone levels of 40 micrograms/dl. Suppression of irCRF secretion in response to nitroprusside-induced hypotension is observed and occurs at a plasma corticosterone level between 8-12 micrograms/dl. These studies provide further evidence for a strong central component of the delayed feedback process which is mediated by modulation of irCRF release.", "entity": "Corticosterone", "aliases": "Corticosterone", "definition": "An adrenocortical steroid that has modest but significant activities as a mineralocorticoid and a glucocorticoid. (From Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1437)\n    ", "id": "MESH:D003345"}
{"mention": "urethane", "mention_text": "Nitroprusside-induced hypotension evokes ACTH secretion which is primarily mediated by enhanced secretion of immunoreactive corticotropin-releasing factor (irCRF) into the hypophysial-portal circulation. Portal plasma concentrations of neither arginine vasopressin nor oxytocin are significantly altered in this paradigm. Application of a delayed feedback signal, in the form of a 2-h systemic corticosterone infusion in urethane-anesthetized rats with pharmacological blockade of glucocorticoid synthesis, is without effect on the resting secretion of arginine vasopressin and oxytocin at any corticosterone feedback dose tested. Resting irCRF levels are suppressed only at the highest corticosterone infusion rate, which resulted in systemic corticosterone levels of 40 micrograms/dl. Suppression of irCRF secretion in response to nitroprusside-induced hypotension is observed and occurs at a plasma corticosterone level between 8-12 micrograms/dl. These studies provide further evidence for a strong central component of the delayed feedback process which is mediated by modulation of irCRF release.", "entity": "Urethane", "aliases": "Carbamate Ethyl Urethan Urethane", "definition": "Antineoplastic agent that is also used as a veterinary anesthetic. It has also been used as an intermediate in organic synthesis. Urethane is suspected to be a carcinogen.\n    ", "id": "MESH:D014520"}
{"mention": "nitroprusside", "mention_text": "Nitroprusside-induced hypotension evokes ACTH secretion which is primarily mediated by enhanced secretion of immunoreactive corticotropin-releasing factor (irCRF) into the hypophysial-portal circulation. Portal plasma concentrations of neither arginine vasopressin nor oxytocin are significantly altered in this paradigm. Application of a delayed feedback signal, in the form of a 2-h systemic corticosterone infusion in urethane-anesthetized rats with pharmacological blockade of glucocorticoid synthesis, is without effect on the resting secretion of arginine vasopressin and oxytocin at any corticosterone feedback dose tested. Resting irCRF levels are suppressed only at the highest corticosterone infusion rate, which resulted in systemic corticosterone levels of 40 micrograms/dl. Suppression of irCRF secretion in response to nitroprusside-induced hypotension is observed and occurs at a plasma corticosterone level between 8-12 micrograms/dl. These studies provide further evidence for a strong central component of the delayed feedback process which is mediated by modulation of irCRF release.", "entity": "Nitroprusside", "aliases": "Abbott Brand of Sodium Nitroprusside Bayer Cyanonitrosylferrate Disodium Salt Faulding Fides Ecopharma Ketostix Naniprus Nipride Nipruton Nitriate Nitroferricyanide Nitropress Nitroprussiat Dihydrate Roche SERB", "definition": "A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.\n    ", "id": "MESH:D009599"}
{"mention": "catalepsy", "mention_text": "Noradrenergic involvement in catalepsy induced by delta 9-tetrahydrocannabinol.", "entity": "Catalepsy", "aliases": "Anochlesia Anochlesias Catalepsies Catalepsy Cerea Flexibilitas Flexibilities Waxy Flexibility", "definition": "A condition characterized by inactivity, decreased responsiveness to stimuli, and a tendency to maintain an immobile posture. The limbs tend to remain in whatever position they are placed (waxy flexibility). Catalepsy may be associated with PSYCHOTIC DISORDERS (e.g., SCHIZOPHRENIA, CATATONIC), nervous system drug toxicity, and other conditions.\n    ", "id": "MESH:D002375"}
{"mention": "delta 9-tetrahydrocannabinol", "mention_text": "Noradrenergic involvement in catalepsy induced by delta 9-tetrahydrocannabinol.", "entity": "Dronabinol", "aliases": "9 ene Tetrahydrocannabinol 9-ene-Tetrahydrocannabinol Dronabinol Marinol Solvay Brand of THC (6a-trans)-Isomer (6aR-cis)-Isomer (6aS-cis)-Isomer Trans Isomer Trans-(+-)-Isomer Trans-Isomer delta(1)-THC delta(1)-Tetrahydrocannabinol delta(9)-THC delta(9)-Tetrahydrocannabinol", "definition": "A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound.\n    ", "id": "MESH:D013759"}
{"mention": "delta 9-tetrahydrocannabinol", "mention_text": "In order to elucidate the role of the catecholaminergic system in the cataleptogenic effect of delta 9-tetrahydrocannabinol (THC), the effect of pretreatment with 6-hydroxydopamine (6-OHDA) or with desipramine and 6-OHDA and lesions of the locus coeruleus were investigated in rats. The cataleptogenic effect of THC was significantly reduced in rats treated with 6-OHDA and in rats with lesions of the locus coeruleus but not in rats treated with desipramine and 6-OHDA, as compared with control rats. On the contrary, the cataleptogenic effect of haloperidol was significantly reduced in rats treated with desipramine and 6-OHDA but not in rats treated with 6-OHDA or in rats with lesions of the locus coeruleus. These results indicate that noradrenergic neurons have an important role in the manifestation of catalepsy induced by THC, whereas dopaminergic neurons are important in catalepsy induced by haloperidol.", "entity": "Dronabinol", "aliases": "9 ene Tetrahydrocannabinol 9-ene-Tetrahydrocannabinol Dronabinol Marinol Solvay Brand of THC (6a-trans)-Isomer (6aR-cis)-Isomer (6aS-cis)-Isomer Trans Isomer Trans-(+-)-Isomer Trans-Isomer delta(1)-THC delta(1)-Tetrahydrocannabinol delta(9)-THC delta(9)-Tetrahydrocannabinol", "definition": "A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound.\n    ", "id": "MESH:D013759"}
{"mention": "THC", "mention_text": "In order to elucidate the role of the catecholaminergic system in the cataleptogenic effect of delta 9-tetrahydrocannabinol (THC), the effect of pretreatment with 6-hydroxydopamine (6-OHDA) or with desipramine and 6-OHDA and lesions of the locus coeruleus were investigated in rats. The cataleptogenic effect of THC was significantly reduced in rats treated with 6-OHDA and in rats with lesions of the locus coeruleus but not in rats treated with desipramine and 6-OHDA, as compared with control rats. On the contrary, the cataleptogenic effect of haloperidol was significantly reduced in rats treated with desipramine and 6-OHDA but not in rats treated with 6-OHDA or in rats with lesions of the locus coeruleus. These results indicate that noradrenergic neurons have an important role in the manifestation of catalepsy induced by THC, whereas dopaminergic neurons are important in catalepsy induced by haloperidol.", "entity": "Dronabinol", "aliases": "9 ene Tetrahydrocannabinol 9-ene-Tetrahydrocannabinol Dronabinol Marinol Solvay Brand of THC (6a-trans)-Isomer (6aR-cis)-Isomer (6aS-cis)-Isomer Trans Isomer Trans-(+-)-Isomer Trans-Isomer delta(1)-THC delta(1)-Tetrahydrocannabinol delta(9)-THC delta(9)-Tetrahydrocannabinol", "definition": "A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound.\n    ", "id": "MESH:D013759"}
{"mention": "6-hydroxydopamine", "mention_text": "In order to elucidate the role of the catecholaminergic system in the cataleptogenic effect of delta 9-tetrahydrocannabinol (THC), the effect of pretreatment with 6-hydroxydopamine (6-OHDA) or with desipramine and 6-OHDA and lesions of the locus coeruleus were investigated in rats. The cataleptogenic effect of THC was significantly reduced in rats treated with 6-OHDA and in rats with lesions of the locus coeruleus but not in rats treated with desipramine and 6-OHDA, as compared with control rats. On the contrary, the cataleptogenic effect of haloperidol was significantly reduced in rats treated with desipramine and 6-OHDA but not in rats treated with 6-OHDA or in rats with lesions of the locus coeruleus. These results indicate that noradrenergic neurons have an important role in the manifestation of catalepsy induced by THC, whereas dopaminergic neurons are important in catalepsy induced by haloperidol.", "entity": "Oxidopamine", "aliases": "6 Hydroxydopamine 6-Hydroxydopamine 6-OHDA Hydrobromide Oxidopamine Hydrochloride", "definition": "A neurotransmitter analogue that depletes noradrenergic stores in nerve endings and induces a reduction of dopamine levels in the brain. Its mechanism of action is related to the production of cytolytic free-radicals.\n    ", "id": "MESH:D016627"}
{"mention": "6-OHDA", "mention_text": "In order to elucidate the role of the catecholaminergic system in the cataleptogenic effect of delta 9-tetrahydrocannabinol (THC), the effect of pretreatment with 6-hydroxydopamine (6-OHDA) or with desipramine and 6-OHDA and lesions of the locus coeruleus were investigated in rats. The cataleptogenic effect of THC was significantly reduced in rats treated with 6-OHDA and in rats with lesions of the locus coeruleus but not in rats treated with desipramine and 6-OHDA, as compared with control rats. On the contrary, the cataleptogenic effect of haloperidol was significantly reduced in rats treated with desipramine and 6-OHDA but not in rats treated with 6-OHDA or in rats with lesions of the locus coeruleus. These results indicate that noradrenergic neurons have an important role in the manifestation of catalepsy induced by THC, whereas dopaminergic neurons are important in catalepsy induced by haloperidol.", "entity": "Oxidopamine", "aliases": "6 Hydroxydopamine 6-Hydroxydopamine 6-OHDA Hydrobromide Oxidopamine Hydrochloride", "definition": "A neurotransmitter analogue that depletes noradrenergic stores in nerve endings and induces a reduction of dopamine levels in the brain. Its mechanism of action is related to the production of cytolytic free-radicals.\n    ", "id": "MESH:D016627"}
{"mention": "desipramine", "mention_text": "In order to elucidate the role of the catecholaminergic system in the cataleptogenic effect of delta 9-tetrahydrocannabinol (THC), the effect of pretreatment with 6-hydroxydopamine (6-OHDA) or with desipramine and 6-OHDA and lesions of the locus coeruleus were investigated in rats. The cataleptogenic effect of THC was significantly reduced in rats treated with 6-OHDA and in rats with lesions of the locus coeruleus but not in rats treated with desipramine and 6-OHDA, as compared with control rats. On the contrary, the cataleptogenic effect of haloperidol was significantly reduced in rats treated with desipramine and 6-OHDA but not in rats treated with 6-OHDA or in rats with lesions of the locus coeruleus. These results indicate that noradrenergic neurons have an important role in the manifestation of catalepsy induced by THC, whereas dopaminergic neurons are important in catalepsy induced by haloperidol.", "entity": "Desipramine", "aliases": "Apo-Desipramine Apotex Brand of Desipramine Hydrochloride Aventis Behring Demethylimipramine Desmethylimipramine Norpramin Novartis Novo-Desipramine Novopharm Nu Pharm Nu-Desipramine Nu-Pharm PMS-Desipramine Pertofran Pertofrane Pertrofran Petylyl Pharmascience Ratiopharm Rhône Poulenc Rorer Rhône-Poulenc Temmler ratio-Desipramine", "definition": "A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholinergic activity, through its affinity to muscarinic receptors.\n    ", "id": "MESH:D003891"}
{"mention": "haloperidol", "mention_text": "In order to elucidate the role of the catecholaminergic system in the cataleptogenic effect of delta 9-tetrahydrocannabinol (THC), the effect of pretreatment with 6-hydroxydopamine (6-OHDA) or with desipramine and 6-OHDA and lesions of the locus coeruleus were investigated in rats. The cataleptogenic effect of THC was significantly reduced in rats treated with 6-OHDA and in rats with lesions of the locus coeruleus but not in rats treated with desipramine and 6-OHDA, as compared with control rats. On the contrary, the cataleptogenic effect of haloperidol was significantly reduced in rats treated with desipramine and 6-OHDA but not in rats treated with 6-OHDA or in rats with lesions of the locus coeruleus. These results indicate that noradrenergic neurons have an important role in the manifestation of catalepsy induced by THC, whereas dopaminergic neurons are important in catalepsy induced by haloperidol.", "entity": "Haloperidol", "aliases": "Haldol Haloperidol", "definition": "A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)\n    ", "id": "MESH:D006220"}
{"mention": "catalepsy", "mention_text": "In order to elucidate the role of the catecholaminergic system in the cataleptogenic effect of delta 9-tetrahydrocannabinol (THC), the effect of pretreatment with 6-hydroxydopamine (6-OHDA) or with desipramine and 6-OHDA and lesions of the locus coeruleus were investigated in rats. The cataleptogenic effect of THC was significantly reduced in rats treated with 6-OHDA and in rats with lesions of the locus coeruleus but not in rats treated with desipramine and 6-OHDA, as compared with control rats. On the contrary, the cataleptogenic effect of haloperidol was significantly reduced in rats treated with desipramine and 6-OHDA but not in rats treated with 6-OHDA or in rats with lesions of the locus coeruleus. These results indicate that noradrenergic neurons have an important role in the manifestation of catalepsy induced by THC, whereas dopaminergic neurons are important in catalepsy induced by haloperidol.", "entity": "Catalepsy", "aliases": "Anochlesia Anochlesias Catalepsies Catalepsy Cerea Flexibilitas Flexibilities Waxy Flexibility", "definition": "A condition characterized by inactivity, decreased responsiveness to stimuli, and a tendency to maintain an immobile posture. The limbs tend to remain in whatever position they are placed (waxy flexibility). Catalepsy may be associated with PSYCHOTIC DISORDERS (e.g., SCHIZOPHRENIA, CATATONIC), nervous system drug toxicity, and other conditions.\n    ", "id": "MESH:D002375"}
{"mention": "alfentanil", "mention_text": "Intracranial pressure increases during alfentanil-induced rigidity.", "entity": "Alfentanil", "aliases": "Alfenta Alfentanil Hydrochloride Alfentanyl Esteve Brand of Fanaxal ICI Janssen Limifen R 39209 R-39209 R39209 Rapifen", "definition": "A short-acting opioid anesthetic and analgesic derivative of FENTANYL. It produces an early peak analgesic effect and fast recovery of consciousness. Alfentanil is effective as an anesthetic during surgery, for supplementation of analgesia during surgical procedures, and as an analgesic for critically ill patients.\n    ", "id": "MESH:D015760"}
{"mention": "rigidity", "mention_text": "Intracranial pressure increases during alfentanil-induced rigidity.", "entity": "Muscle Rigidity", "aliases": "Catatonic Rigidity Cogwheel Rigidities Extensor Extrapyramidal Gegenhalten Gegenhaltens Muscle Muscular Nuchal", "definition": "Continuous involuntary sustained muscle contraction which is often a manifestation of BASAL GANGLIA DISEASES. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from MUSCLE SPASTICITY. (From Adams et al., Principles of Neurology, 6th ed, p73)\n    ", "id": "MESH:D009127"}
{"mention": "alfentanil", "mention_text": "Intracranial pressure (ICP) was measured during alfentanil-induced rigidity in rats. Ten rats had arterial, central venous (CVP), and subdural cannulae inserted under halothane anesthesia. The animals were mechanically ventilated to achieve normocarbia (PCO2 = 42 +/- 1 mmHg, mean +/- SE). Following instrumentation, halothane was discontinued and alfentanil (125 mu/kg) administered iv during emergence from halothane anesthesia. In the five rats that developed somatic rigidity, ICP and CVP increased significantly above baseline (delta ICP 7.5 +/- 1.0 mmHg, delta CVP 5.9 +/- 1.3 mmHg). These variables returned to baseline when rigidity was abolished with metocurine. In five rats that did not become rigid, ICP and CVP did not change following alfentanil. These observations suggest that rigidity should be prevented when alfentanil, and, presumably, other opiates, are used in the anesthetic management of patients with ICP problems.", "entity": "Alfentanil", "aliases": "Alfenta Alfentanil Hydrochloride Alfentanyl Esteve Brand of Fanaxal ICI Janssen Limifen R 39209 R-39209 R39209 Rapifen", "definition": "A short-acting opioid anesthetic and analgesic derivative of FENTANYL. It produces an early peak analgesic effect and fast recovery of consciousness. Alfentanil is effective as an anesthetic during surgery, for supplementation of analgesia during surgical procedures, and as an analgesic for critically ill patients.\n    ", "id": "MESH:D015760"}
{"mention": "rigidity", "mention_text": "Intracranial pressure (ICP) was measured during alfentanil-induced rigidity in rats. Ten rats had arterial, central venous (CVP), and subdural cannulae inserted under halothane anesthesia. The animals were mechanically ventilated to achieve normocarbia (PCO2 = 42 +/- 1 mmHg, mean +/- SE). Following instrumentation, halothane was discontinued and alfentanil (125 mu/kg) administered iv during emergence from halothane anesthesia. In the five rats that developed somatic rigidity, ICP and CVP increased significantly above baseline (delta ICP 7.5 +/- 1.0 mmHg, delta CVP 5.9 +/- 1.3 mmHg). These variables returned to baseline when rigidity was abolished with metocurine. In five rats that did not become rigid, ICP and CVP did not change following alfentanil. These observations suggest that rigidity should be prevented when alfentanil, and, presumably, other opiates, are used in the anesthetic management of patients with ICP problems.", "entity": "Muscle Rigidity", "aliases": "Catatonic Rigidity Cogwheel Rigidities Extensor Extrapyramidal Gegenhalten Gegenhaltens Muscle Muscular Nuchal", "definition": "Continuous involuntary sustained muscle contraction which is often a manifestation of BASAL GANGLIA DISEASES. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from MUSCLE SPASTICITY. (From Adams et al., Principles of Neurology, 6th ed, p73)\n    ", "id": "MESH:D009127"}
{"mention": "halothane", "mention_text": "Intracranial pressure (ICP) was measured during alfentanil-induced rigidity in rats. Ten rats had arterial, central venous (CVP), and subdural cannulae inserted under halothane anesthesia. The animals were mechanically ventilated to achieve normocarbia (PCO2 = 42 +/- 1 mmHg, mean +/- SE). Following instrumentation, halothane was discontinued and alfentanil (125 mu/kg) administered iv during emergence from halothane anesthesia. In the five rats that developed somatic rigidity, ICP and CVP increased significantly above baseline (delta ICP 7.5 +/- 1.0 mmHg, delta CVP 5.9 +/- 1.3 mmHg). These variables returned to baseline when rigidity was abolished with metocurine. In five rats that did not become rigid, ICP and CVP did not change following alfentanil. These observations suggest that rigidity should be prevented when alfentanil, and, presumably, other opiates, are used in the anesthetic management of patients with ICP problems.", "entity": "Halothane", "aliases": "1,1,1-Trifluoro-2-Chloro-2-Bromoethane Fluothane Ftorotan Halothane Narcotan", "definition": "A nonflammable, halogenated, hydrocarbon anesthetic that provides relatively rapid induction with little or no excitement. Analgesia may not be adequate. NITROUS OXIDE is often given concomitantly. Because halothane may not produce sufficient muscle relaxation, supplemental neuromuscular blocking agents may be required. (From AMA Drug Evaluations Annual, 1994, p178)\n    ", "id": "MESH:D006221"}
{"mention": "somatic rigidity", "mention_text": "Intracranial pressure (ICP) was measured during alfentanil-induced rigidity in rats. Ten rats had arterial, central venous (CVP), and subdural cannulae inserted under halothane anesthesia. The animals were mechanically ventilated to achieve normocarbia (PCO2 = 42 +/- 1 mmHg, mean +/- SE). Following instrumentation, halothane was discontinued and alfentanil (125 mu/kg) administered iv during emergence from halothane anesthesia. In the five rats that developed somatic rigidity, ICP and CVP increased significantly above baseline (delta ICP 7.5 +/- 1.0 mmHg, delta CVP 5.9 +/- 1.3 mmHg). These variables returned to baseline when rigidity was abolished with metocurine. In five rats that did not become rigid, ICP and CVP did not change following alfentanil. These observations suggest that rigidity should be prevented when alfentanil, and, presumably, other opiates, are used in the anesthetic management of patients with ICP problems.", "entity": "Muscle Rigidity", "aliases": "Catatonic Rigidity Cogwheel Rigidities Extensor Extrapyramidal Gegenhalten Gegenhaltens Muscle Muscular Nuchal", "definition": "Continuous involuntary sustained muscle contraction which is often a manifestation of BASAL GANGLIA DISEASES. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from MUSCLE SPASTICITY. (From Adams et al., Principles of Neurology, 6th ed, p73)\n    ", "id": "MESH:D009127"}
{"mention": "metocurine", "mention_text": "Intracranial pressure (ICP) was measured during alfentanil-induced rigidity in rats. Ten rats had arterial, central venous (CVP), and subdural cannulae inserted under halothane anesthesia. The animals were mechanically ventilated to achieve normocarbia (PCO2 = 42 +/- 1 mmHg, mean +/- SE). Following instrumentation, halothane was discontinued and alfentanil (125 mu/kg) administered iv during emergence from halothane anesthesia. In the five rats that developed somatic rigidity, ICP and CVP increased significantly above baseline (delta ICP 7.5 +/- 1.0 mmHg, delta CVP 5.9 +/- 1.3 mmHg). These variables returned to baseline when rigidity was abolished with metocurine. In five rats that did not become rigid, ICP and CVP did not change following alfentanil. These observations suggest that rigidity should be prevented when alfentanil, and, presumably, other opiates, are used in the anesthetic management of patients with ICP problems.", "entity": "metocurine", "aliases": "DMCDM Metubine dimethyl dl-curine dimethochloride dimethyl-L-curine dimethoiodide dimethylchondrocurarine dimethylcurarine dimethylcurine metocurine dichloride dichloride(1alpha)-isomer (1'alpha)-isomer (1beta)-(+-)-isomer dihydroxide diiodide (1beta)-isomer iodide", "definition": "", "id": "MESH:C032943"}
{"mention": "cis-platin", "mention_text": "Adverse cardiac effects during induction chemotherapy treatment with cis-platin and 5-fluorouracil.", "entity": "Cisplatin", "aliases": "Biocisplatinum Cisplatin Diamminodichloride Platinum Dichlorodiammineplatinum NSC-119875 Platidiam Platino Platinol cis Diamminedichloroplatinum cis-Diamminedichloroplatinum cis-Diamminedichloroplatinum(II) cis-Dichlorodiammineplatinum(II) cis-Platinum", "definition": "An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.\n    ", "id": "MESH:D002945"}
{"mention": "5-fluorouracil", "mention_text": "Adverse cardiac effects during induction chemotherapy treatment with cis-platin and 5-fluorouracil.", "entity": "Fluorouracil", "aliases": "5 FU Lederle medac Fluorouracil biosyn HU Hexal 5-FU 5-Fluorouracil 5-Fluorouracil-biosyn 5-HU 5FU Adrucil Allergan Brand of CSP Carac Dakota Fluorouracile Dermatech Dermik Efudex Efudix Ferrer Fluoro Uracile ICN Fluoro-Uracile Fluoroplex GRY Mononitrate Monopotassium Salt Monosodium Potassium Teva Fluorouracil-GRY Fluorouracilo Far Fluoruracil Fluracedyl Flurodex Gry Haemato fu Haemato-fu Neocorp Neofluor Onkofluor Onkoworks Pharmachemie Ribofluor Riemser Roche ribosepharm", "definition": "A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.\n    ", "id": "MESH:D005472"}
{"mention": "head and neck carcinoma", "mention_text": "Survival for patients with advanced head and neck carcinoma and esophageal carcinoma is poor with radiotherapy and/or surgery. Obviously, there is a need for effective chemotherapy. In the present study, cis-platin (80-120 mg/m2BSA) and 5-FU (1000 mg/m2BSA daily as a continuous infusion during 5 days) were given to 76 patients before radiotherapy and surgery. The aim of the study was to clarify the incidence and severity of adverse cardiac effects to this treatment. Before treatment all patients had a cardiac evaluation and during treatment serial ECG recordings were performed. In the pre-treatment evaluation, signs of cardiovascular disease were found in 33 patients (43%). During treatment, adverse cardiac effects were observed in 14 patients (18%). The mean age of these patients was the same as for the entire group, 64 years. The incidence of cardiotoxicity was not higher in patients with signs of cardiovascular disease than in those without in the pre-treatment evaluation. The most common signs of cardiotoxicity were chest pain, ST-T wave changes and atrial fibrillation. This was followed by ventricular fibrillation in one patient and sudden death in another. It is concluded that patients on 5-FU treatment should be under close supervision and that the treatment should be discontinued if chest pain or tachyarrhythmia is observed.", "entity": "Head and Neck Neoplasms", "aliases": "Cancer of Head and Neck the Neoplasms Neoplasm UADT Upper Aerodigestive Tract", "definition": "Soft tissue tumors or cancer arising from the mucosal surfaces of the LIP; oral cavity; PHARYNX; LARYNX; and cervical esophagus. Other sites included are the NOSE and PARANASAL SINUSES; SALIVARY GLANDS; THYROID GLAND and PARATHYROID GLANDS; and MELANOMA and non-melanoma skin cancers of the head and neck. (from Holland et al., Cancer Medicine, 4th ed, p1651)\n    ", "id": "MESH:D006258"}
{"mention": "esophageal carcinoma", "mention_text": "Survival for patients with advanced head and neck carcinoma and esophageal carcinoma is poor with radiotherapy and/or surgery. Obviously, there is a need for effective chemotherapy. In the present study, cis-platin (80-120 mg/m2BSA) and 5-FU (1000 mg/m2BSA daily as a continuous infusion during 5 days) were given to 76 patients before radiotherapy and surgery. The aim of the study was to clarify the incidence and severity of adverse cardiac effects to this treatment. Before treatment all patients had a cardiac evaluation and during treatment serial ECG recordings were performed. In the pre-treatment evaluation, signs of cardiovascular disease were found in 33 patients (43%). During treatment, adverse cardiac effects were observed in 14 patients (18%). The mean age of these patients was the same as for the entire group, 64 years. The incidence of cardiotoxicity was not higher in patients with signs of cardiovascular disease than in those without in the pre-treatment evaluation. The most common signs of cardiotoxicity were chest pain, ST-T wave changes and atrial fibrillation. This was followed by ventricular fibrillation in one patient and sudden death in another. It is concluded that patients on 5-FU treatment should be under close supervision and that the treatment should be discontinued if chest pain or tachyarrhythmia is observed.", "entity": "Esophageal Neoplasms", "aliases": "Cancer of Esophagus the Esophageal Cancers Neoplasm Neoplasms", "definition": "Tumors or cancer of the ESOPHAGUS.\n    ", "id": "MESH:D004938"}
{"mention": "cis-platin", "mention_text": "Survival for patients with advanced head and neck carcinoma and esophageal carcinoma is poor with radiotherapy and/or surgery. Obviously, there is a need for effective chemotherapy. In the present study, cis-platin (80-120 mg/m2BSA) and 5-FU (1000 mg/m2BSA daily as a continuous infusion during 5 days) were given to 76 patients before radiotherapy and surgery. The aim of the study was to clarify the incidence and severity of adverse cardiac effects to this treatment. Before treatment all patients had a cardiac evaluation and during treatment serial ECG recordings were performed. In the pre-treatment evaluation, signs of cardiovascular disease were found in 33 patients (43%). During treatment, adverse cardiac effects were observed in 14 patients (18%). The mean age of these patients was the same as for the entire group, 64 years. The incidence of cardiotoxicity was not higher in patients with signs of cardiovascular disease than in those without in the pre-treatment evaluation. The most common signs of cardiotoxicity were chest pain, ST-T wave changes and atrial fibrillation. This was followed by ventricular fibrillation in one patient and sudden death in another. It is concluded that patients on 5-FU treatment should be under close supervision and that the treatment should be discontinued if chest pain or tachyarrhythmia is observed.", "entity": "Cisplatin", "aliases": "Biocisplatinum Cisplatin Diamminodichloride Platinum Dichlorodiammineplatinum NSC-119875 Platidiam Platino Platinol cis Diamminedichloroplatinum cis-Diamminedichloroplatinum cis-Diamminedichloroplatinum(II) cis-Dichlorodiammineplatinum(II) cis-Platinum", "definition": "An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.\n    ", "id": "MESH:D002945"}
{"mention": "5-FU", "mention_text": "Survival for patients with advanced head and neck carcinoma and esophageal carcinoma is poor with radiotherapy and/or surgery. Obviously, there is a need for effective chemotherapy. In the present study, cis-platin (80-120 mg/m2BSA) and 5-FU (1000 mg/m2BSA daily as a continuous infusion during 5 days) were given to 76 patients before radiotherapy and surgery. The aim of the study was to clarify the incidence and severity of adverse cardiac effects to this treatment. Before treatment all patients had a cardiac evaluation and during treatment serial ECG recordings were performed. In the pre-treatment evaluation, signs of cardiovascular disease were found in 33 patients (43%). During treatment, adverse cardiac effects were observed in 14 patients (18%). The mean age of these patients was the same as for the entire group, 64 years. The incidence of cardiotoxicity was not higher in patients with signs of cardiovascular disease than in those without in the pre-treatment evaluation. The most common signs of cardiotoxicity were chest pain, ST-T wave changes and atrial fibrillation. This was followed by ventricular fibrillation in one patient and sudden death in another. It is concluded that patients on 5-FU treatment should be under close supervision and that the treatment should be discontinued if chest pain or tachyarrhythmia is observed.", "entity": "Fluorouracil", "aliases": "5 FU Lederle medac Fluorouracil biosyn HU Hexal 5-FU 5-Fluorouracil 5-Fluorouracil-biosyn 5-HU 5FU Adrucil Allergan Brand of CSP Carac Dakota Fluorouracile Dermatech Dermik Efudex Efudix Ferrer Fluoro Uracile ICN Fluoro-Uracile Fluoroplex GRY Mononitrate Monopotassium Salt Monosodium Potassium Teva Fluorouracil-GRY Fluorouracilo Far Fluoruracil Fluracedyl Flurodex Gry Haemato fu Haemato-fu Neocorp Neofluor Onkofluor Onkoworks Pharmachemie Ribofluor Riemser Roche ribosepharm", "definition": "A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.\n    ", "id": "MESH:D005472"}
{"mention": "cardiovascular disease", "mention_text": "Survival for patients with advanced head and neck carcinoma and esophageal carcinoma is poor with radiotherapy and/or surgery. Obviously, there is a need for effective chemotherapy. In the present study, cis-platin (80-120 mg/m2BSA) and 5-FU (1000 mg/m2BSA daily as a continuous infusion during 5 days) were given to 76 patients before radiotherapy and surgery. The aim of the study was to clarify the incidence and severity of adverse cardiac effects to this treatment. Before treatment all patients had a cardiac evaluation and during treatment serial ECG recordings were performed. In the pre-treatment evaluation, signs of cardiovascular disease were found in 33 patients (43%). During treatment, adverse cardiac effects were observed in 14 patients (18%). The mean age of these patients was the same as for the entire group, 64 years. The incidence of cardiotoxicity was not higher in patients with signs of cardiovascular disease than in those without in the pre-treatment evaluation. The most common signs of cardiotoxicity were chest pain, ST-T wave changes and atrial fibrillation. This was followed by ventricular fibrillation in one patient and sudden death in another. It is concluded that patients on 5-FU treatment should be under close supervision and that the treatment should be discontinued if chest pain or tachyarrhythmia is observed.", "entity": "Cardiovascular Diseases", "aliases": "Cardiovascular Disease Diseases", "definition": "Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.\n    ", "id": "MESH:D002318"}
{"mention": "cardiotoxicity", "mention_text": "Survival for patients with advanced head and neck carcinoma and esophageal carcinoma is poor with radiotherapy and/or surgery. Obviously, there is a need for effective chemotherapy. In the present study, cis-platin (80-120 mg/m2BSA) and 5-FU (1000 mg/m2BSA daily as a continuous infusion during 5 days) were given to 76 patients before radiotherapy and surgery. The aim of the study was to clarify the incidence and severity of adverse cardiac effects to this treatment. Before treatment all patients had a cardiac evaluation and during treatment serial ECG recordings were performed. In the pre-treatment evaluation, signs of cardiovascular disease were found in 33 patients (43%). During treatment, adverse cardiac effects were observed in 14 patients (18%). The mean age of these patients was the same as for the entire group, 64 years. The incidence of cardiotoxicity was not higher in patients with signs of cardiovascular disease than in those without in the pre-treatment evaluation. The most common signs of cardiotoxicity were chest pain, ST-T wave changes and atrial fibrillation. This was followed by ventricular fibrillation in one patient and sudden death in another. It is concluded that patients on 5-FU treatment should be under close supervision and that the treatment should be discontinued if chest pain or tachyarrhythmia is observed.", "entity": "Cardiotoxicity", "aliases": "Cardiac Toxicities Toxicity Cardiotoxicities Cardiotoxicity", "definition": "Damage to the heart or its function secondary to exposure to toxic substances such as drugs used in CHEMOTHERAPY; IMMUNOTHERAPY; or RADIATION.\n    ", "id": "MESH:D066126"}
{"mention": "chest pain", "mention_text": "Survival for patients with advanced head and neck carcinoma and esophageal carcinoma is poor with radiotherapy and/or surgery. Obviously, there is a need for effective chemotherapy. In the present study, cis-platin (80-120 mg/m2BSA) and 5-FU (1000 mg/m2BSA daily as a continuous infusion during 5 days) were given to 76 patients before radiotherapy and surgery. The aim of the study was to clarify the incidence and severity of adverse cardiac effects to this treatment. Before treatment all patients had a cardiac evaluation and during treatment serial ECG recordings were performed. In the pre-treatment evaluation, signs of cardiovascular disease were found in 33 patients (43%). During treatment, adverse cardiac effects were observed in 14 patients (18%). The mean age of these patients was the same as for the entire group, 64 years. The incidence of cardiotoxicity was not higher in patients with signs of cardiovascular disease than in those without in the pre-treatment evaluation. The most common signs of cardiotoxicity were chest pain, ST-T wave changes and atrial fibrillation. This was followed by ventricular fibrillation in one patient and sudden death in another. It is concluded that patients on 5-FU treatment should be under close supervision and that the treatment should be discontinued if chest pain or tachyarrhythmia is observed.", "entity": "Chest Pain", "aliases": "Chest Pain Pains", "definition": "Pressure, burning, or numbness in the chest.\n    ", "id": "MESH:D002637"}
{"mention": "atrial fibrillation", "mention_text": "Survival for patients with advanced head and neck carcinoma and esophageal carcinoma is poor with radiotherapy and/or surgery. Obviously, there is a need for effective chemotherapy. In the present study, cis-platin (80-120 mg/m2BSA) and 5-FU (1000 mg/m2BSA daily as a continuous infusion during 5 days) were given to 76 patients before radiotherapy and surgery. The aim of the study was to clarify the incidence and severity of adverse cardiac effects to this treatment. Before treatment all patients had a cardiac evaluation and during treatment serial ECG recordings were performed. In the pre-treatment evaluation, signs of cardiovascular disease were found in 33 patients (43%). During treatment, adverse cardiac effects were observed in 14 patients (18%). The mean age of these patients was the same as for the entire group, 64 years. The incidence of cardiotoxicity was not higher in patients with signs of cardiovascular disease than in those without in the pre-treatment evaluation. The most common signs of cardiotoxicity were chest pain, ST-T wave changes and atrial fibrillation. This was followed by ventricular fibrillation in one patient and sudden death in another. It is concluded that patients on 5-FU treatment should be under close supervision and that the treatment should be discontinued if chest pain or tachyarrhythmia is observed.", "entity": "Atrial Fibrillation", "aliases": "Atrial Fibrillation Fibrillations Auricular Familial", "definition": "Abnormal cardiac rhythm that is characterized by rapid, uncoordinated firing of electrical impulses in the upper chambers of the heart (HEART ATRIA). In such case, blood cannot be effectively pumped into the lower chambers of the heart (HEART VENTRICLES). It is caused by abnormal impulse generation.\n    ", "id": "MESH:D001281"}
{"mention": "ventricular fibrillation", "mention_text": "Survival for patients with advanced head and neck carcinoma and esophageal carcinoma is poor with radiotherapy and/or surgery. Obviously, there is a need for effective chemotherapy. In the present study, cis-platin (80-120 mg/m2BSA) and 5-FU (1000 mg/m2BSA daily as a continuous infusion during 5 days) were given to 76 patients before radiotherapy and surgery. The aim of the study was to clarify the incidence and severity of adverse cardiac effects to this treatment. Before treatment all patients had a cardiac evaluation and during treatment serial ECG recordings were performed. In the pre-treatment evaluation, signs of cardiovascular disease were found in 33 patients (43%). During treatment, adverse cardiac effects were observed in 14 patients (18%). The mean age of these patients was the same as for the entire group, 64 years. The incidence of cardiotoxicity was not higher in patients with signs of cardiovascular disease than in those without in the pre-treatment evaluation. The most common signs of cardiotoxicity were chest pain, ST-T wave changes and atrial fibrillation. This was followed by ventricular fibrillation in one patient and sudden death in another. It is concluded that patients on 5-FU treatment should be under close supervision and that the treatment should be discontinued if chest pain or tachyarrhythmia is observed.", "entity": "Ventricular Fibrillation", "aliases": "Fibrillation Ventricular Fibrillations", "definition": "A potentially lethal cardiac arrhythmia that is characterized by uncoordinated extremely rapid firing of electrical impulses (400-600/min) in HEART VENTRICLES. Such asynchronous ventricular quivering or fibrillation prevents any effective cardiac output and results in unconsciousness (SYNCOPE). It is one of the major electrocardiographic patterns seen with CARDIAC ARREST.\n    ", "id": "MESH:D014693"}
{"mention": "sudden death", "mention_text": "Survival for patients with advanced head and neck carcinoma and esophageal carcinoma is poor with radiotherapy and/or surgery. Obviously, there is a need for effective chemotherapy. In the present study, cis-platin (80-120 mg/m2BSA) and 5-FU (1000 mg/m2BSA daily as a continuous infusion during 5 days) were given to 76 patients before radiotherapy and surgery. The aim of the study was to clarify the incidence and severity of adverse cardiac effects to this treatment. Before treatment all patients had a cardiac evaluation and during treatment serial ECG recordings were performed. In the pre-treatment evaluation, signs of cardiovascular disease were found in 33 patients (43%). During treatment, adverse cardiac effects were observed in 14 patients (18%). The mean age of these patients was the same as for the entire group, 64 years. The incidence of cardiotoxicity was not higher in patients with signs of cardiovascular disease than in those without in the pre-treatment evaluation. The most common signs of cardiotoxicity were chest pain, ST-T wave changes and atrial fibrillation. This was followed by ventricular fibrillation in one patient and sudden death in another. It is concluded that patients on 5-FU treatment should be under close supervision and that the treatment should be discontinued if chest pain or tachyarrhythmia is observed.", "entity": "Death, Sudden", "aliases": "Death Sudden", "definition": "The abrupt cessation of all vital bodily functions, manifested by the permanent loss of total cerebral, respiratory, and cardiovascular functions.\n    ", "id": "MESH:D003645"}
{"mention": "tachyarrhythmia", "mention_text": "Survival for patients with advanced head and neck carcinoma and esophageal carcinoma is poor with radiotherapy and/or surgery. Obviously, there is a need for effective chemotherapy. In the present study, cis-platin (80-120 mg/m2BSA) and 5-FU (1000 mg/m2BSA daily as a continuous infusion during 5 days) were given to 76 patients before radiotherapy and surgery. The aim of the study was to clarify the incidence and severity of adverse cardiac effects to this treatment. Before treatment all patients had a cardiac evaluation and during treatment serial ECG recordings were performed. In the pre-treatment evaluation, signs of cardiovascular disease were found in 33 patients (43%). During treatment, adverse cardiac effects were observed in 14 patients (18%). The mean age of these patients was the same as for the entire group, 64 years. The incidence of cardiotoxicity was not higher in patients with signs of cardiovascular disease than in those without in the pre-treatment evaluation. The most common signs of cardiotoxicity were chest pain, ST-T wave changes and atrial fibrillation. This was followed by ventricular fibrillation in one patient and sudden death in another. It is concluded that patients on 5-FU treatment should be under close supervision and that the treatment should be discontinued if chest pain or tachyarrhythmia is observed.", "entity": "Tachycardia", "aliases": "Tachyarrhythmia Tachyarrhythmias Tachycardia Tachycardias", "definition": "Abnormally rapid heartbeat, usually with a HEART RATE above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia.\n    ", "id": "MESH:D013610"}
{"mention": "Verapamil", "mention_text": "Verapamil-induced carbamazepine neurotoxicity. A report of two cases.", "entity": "Verapamil", "aliases": "Calan Cordilox Dexverapamil Falicard Finoptin Hydrochloride Verapamil Iproveratril Isoptin Isoptine Izoptin Lekoptin Sandoz Brand of", "definition": "A calcium channel blocker that is a class IV anti-arrhythmia agent.\n    ", "id": "MESH:D014700"}
{"mention": "carbamazepine", "mention_text": "Verapamil-induced carbamazepine neurotoxicity. A report of two cases.", "entity": "Carbamazepine", "aliases": "Amizepine Carbamazepine Acetate Anhydrous Dihydrate Hydrochloride L-Tartrate (4:1) Phosphate Sulfate (2:1) Carbazepin Epitol Finlepsin Neurotol Tegretol", "definition": "An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of PHENYTOIN; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar.\n    ", "id": "MESH:D002220"}
{"mention": "neurotoxicity", "mention_text": "Verapamil-induced carbamazepine neurotoxicity. A report of two cases.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "carbamazepine", "mention_text": "Two patients with signs of carbamazepine neurotoxicity after combined treatment with verapamil showed complete recovery after discontinuation of the calcium entry blocker. Use of verapamil in combination with carbamazepine should either be avoided or prescribed only with appropriate adjustment of the carbamazepine dose (usually reduction of the carbamazepine dose by one half).", "entity": "Carbamazepine", "aliases": "Amizepine Carbamazepine Acetate Anhydrous Dihydrate Hydrochloride L-Tartrate (4:1) Phosphate Sulfate (2:1) Carbazepin Epitol Finlepsin Neurotol Tegretol", "definition": "An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of PHENYTOIN; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar.\n    ", "id": "MESH:D002220"}
{"mention": "neurotoxicity", "mention_text": "Two patients with signs of carbamazepine neurotoxicity after combined treatment with verapamil showed complete recovery after discontinuation of the calcium entry blocker. Use of verapamil in combination with carbamazepine should either be avoided or prescribed only with appropriate adjustment of the carbamazepine dose (usually reduction of the carbamazepine dose by one half).", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "verapamil", "mention_text": "Two patients with signs of carbamazepine neurotoxicity after combined treatment with verapamil showed complete recovery after discontinuation of the calcium entry blocker. Use of verapamil in combination with carbamazepine should either be avoided or prescribed only with appropriate adjustment of the carbamazepine dose (usually reduction of the carbamazepine dose by one half).", "entity": "Verapamil", "aliases": "Calan Cordilox Dexverapamil Falicard Finoptin Hydrochloride Verapamil Iproveratril Isoptin Isoptine Izoptin Lekoptin Sandoz Brand of", "definition": "A calcium channel blocker that is a class IV anti-arrhythmia agent.\n    ", "id": "MESH:D014700"}
{"mention": "calcium", "mention_text": "Two patients with signs of carbamazepine neurotoxicity after combined treatment with verapamil showed complete recovery after discontinuation of the calcium entry blocker. Use of verapamil in combination with carbamazepine should either be avoided or prescribed only with appropriate adjustment of the carbamazepine dose (usually reduction of the carbamazepine dose by one half).", "entity": "Calcium", "aliases": "Blood Coagulation Factor IV Calcium", "definition": "A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.\n    ", "id": "MESH:D002118"}
{"mention": "auditory neurotoxicity", "mention_text": "Serial studies of auditory neurotoxicity in patients receiving deferoxamine therapy.", "entity": "Hearing Disorders", "aliases": "Distorted Hearing Dysacusis Disorder Disorders Paracousis Paracusis", "definition": "Conditions that impair the transmission of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways.\n    ", "id": "MESH:D006311"}
{"mention": "deferoxamine", "mention_text": "Serial studies of auditory neurotoxicity in patients receiving deferoxamine therapy.", "entity": "Deferoxamine", "aliases": "B Deferoxamine Desferrioxamine Mesilate Mesylate Methanesulfonate Deferoximine Deferrioxamine Desferal Desferioximine Desferroxamine", "definition": "Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form.\n    ", "id": "MESH:D003676"}
{"mention": "auditory neurotoxicity", "mention_text": "Visual and auditory neurotoxicity was previously documented in 42 of 89 patients with transfusion-dependent anemia who were receiving iron chelation therapy with daily subcutaneous deferoxamine. Twenty-two patients in the affected group had abnormal audiograms with deficits mostly in the high frequency range of 4,000 to 8,000 Hz and in the hearing threshold levels of 30 to 100 decibels. When deferoxamine therapy was discontinued and serial studies were performed, audiograms in seven cases reverted to normal or near normal within two to three weeks, and nine of 13 patients with symptoms became asymptomatic. Audiograms from 15 patients remained abnormal and four patients required hearing aids because of permanent disability. Since 18 of the 22 patients were initially receiving deferoxamine doses in excess of the commonly recommended 50 mg/kg per dose, therapy was restarted with lower doses, usually 50 mg/kg per dose or less depending on the degree of auditory abnormality, and with the exception of two cases no further toxicity was demonstrated. Auditory deterioration and improvement, demonstrated serially in individual patients receiving and not receiving deferoxamine, respectively, provided convincing evidence for a cause-and-effect relation between deferoxamine administration and ototoxicity. Based on these data, a plan of management was developed that allows effective yet safe administration of deferoxamine. A dose of 50 mg/kg is recommended in those without audiogram abnormalities. With mild toxicity, a reduction to 30 or 40 mg/kg per dose should result in a reversal of the abnormal results to normal within four weeks. Moderate abnormalities require a reduction of deferoxamine to 25 mg/kg per dose with careful monitoring. In those with symptoms of hearing loss, the drug should be stopped for four weeks, and when the audiogram is stable or improved, therapy should be restarted at 10 to 25 mg/kg per dose. Serial audiograms should be performed every six months in those without problems and more frequently in young patients with normal serum ferritin values and in those with auditory dysfunction.", "entity": "Hearing Disorders", "aliases": "Distorted Hearing Dysacusis Disorder Disorders Paracousis Paracusis", "definition": "Conditions that impair the transmission of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways.\n    ", "id": "MESH:D006311"}
{"mention": "anemia", "mention_text": "Visual and auditory neurotoxicity was previously documented in 42 of 89 patients with transfusion-dependent anemia who were receiving iron chelation therapy with daily subcutaneous deferoxamine. Twenty-two patients in the affected group had abnormal audiograms with deficits mostly in the high frequency range of 4,000 to 8,000 Hz and in the hearing threshold levels of 30 to 100 decibels. When deferoxamine therapy was discontinued and serial studies were performed, audiograms in seven cases reverted to normal or near normal within two to three weeks, and nine of 13 patients with symptoms became asymptomatic. Audiograms from 15 patients remained abnormal and four patients required hearing aids because of permanent disability. Since 18 of the 22 patients were initially receiving deferoxamine doses in excess of the commonly recommended 50 mg/kg per dose, therapy was restarted with lower doses, usually 50 mg/kg per dose or less depending on the degree of auditory abnormality, and with the exception of two cases no further toxicity was demonstrated. Auditory deterioration and improvement, demonstrated serially in individual patients receiving and not receiving deferoxamine, respectively, provided convincing evidence for a cause-and-effect relation between deferoxamine administration and ototoxicity. Based on these data, a plan of management was developed that allows effective yet safe administration of deferoxamine. A dose of 50 mg/kg is recommended in those without audiogram abnormalities. With mild toxicity, a reduction to 30 or 40 mg/kg per dose should result in a reversal of the abnormal results to normal within four weeks. Moderate abnormalities require a reduction of deferoxamine to 25 mg/kg per dose with careful monitoring. In those with symptoms of hearing loss, the drug should be stopped for four weeks, and when the audiogram is stable or improved, therapy should be restarted at 10 to 25 mg/kg per dose. Serial audiograms should be performed every six months in those without problems and more frequently in young patients with normal serum ferritin values and in those with auditory dysfunction.", "entity": "Anemia", "aliases": "Anemia Anemias", "definition": "A reduction in the number of circulating ERYTHROCYTES or in the quantity of HEMOGLOBIN.\n    ", "id": "MESH:D000740"}
{"mention": "iron", "mention_text": "Visual and auditory neurotoxicity was previously documented in 42 of 89 patients with transfusion-dependent anemia who were receiving iron chelation therapy with daily subcutaneous deferoxamine. Twenty-two patients in the affected group had abnormal audiograms with deficits mostly in the high frequency range of 4,000 to 8,000 Hz and in the hearing threshold levels of 30 to 100 decibels. When deferoxamine therapy was discontinued and serial studies were performed, audiograms in seven cases reverted to normal or near normal within two to three weeks, and nine of 13 patients with symptoms became asymptomatic. Audiograms from 15 patients remained abnormal and four patients required hearing aids because of permanent disability. Since 18 of the 22 patients were initially receiving deferoxamine doses in excess of the commonly recommended 50 mg/kg per dose, therapy was restarted with lower doses, usually 50 mg/kg per dose or less depending on the degree of auditory abnormality, and with the exception of two cases no further toxicity was demonstrated. Auditory deterioration and improvement, demonstrated serially in individual patients receiving and not receiving deferoxamine, respectively, provided convincing evidence for a cause-and-effect relation between deferoxamine administration and ototoxicity. Based on these data, a plan of management was developed that allows effective yet safe administration of deferoxamine. A dose of 50 mg/kg is recommended in those without audiogram abnormalities. With mild toxicity, a reduction to 30 or 40 mg/kg per dose should result in a reversal of the abnormal results to normal within four weeks. Moderate abnormalities require a reduction of deferoxamine to 25 mg/kg per dose with careful monitoring. In those with symptoms of hearing loss, the drug should be stopped for four weeks, and when the audiogram is stable or improved, therapy should be restarted at 10 to 25 mg/kg per dose. Serial audiograms should be performed every six months in those without problems and more frequently in young patients with normal serum ferritin values and in those with auditory dysfunction.", "entity": "Iron", "aliases": "Iron", "definition": "A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN.\n    ", "id": "MESH:D007501"}
{"mention": "deferoxamine", "mention_text": "Visual and auditory neurotoxicity was previously documented in 42 of 89 patients with transfusion-dependent anemia who were receiving iron chelation therapy with daily subcutaneous deferoxamine. Twenty-two patients in the affected group had abnormal audiograms with deficits mostly in the high frequency range of 4,000 to 8,000 Hz and in the hearing threshold levels of 30 to 100 decibels. When deferoxamine therapy was discontinued and serial studies were performed, audiograms in seven cases reverted to normal or near normal within two to three weeks, and nine of 13 patients with symptoms became asymptomatic. Audiograms from 15 patients remained abnormal and four patients required hearing aids because of permanent disability. Since 18 of the 22 patients were initially receiving deferoxamine doses in excess of the commonly recommended 50 mg/kg per dose, therapy was restarted with lower doses, usually 50 mg/kg per dose or less depending on the degree of auditory abnormality, and with the exception of two cases no further toxicity was demonstrated. Auditory deterioration and improvement, demonstrated serially in individual patients receiving and not receiving deferoxamine, respectively, provided convincing evidence for a cause-and-effect relation between deferoxamine administration and ototoxicity. Based on these data, a plan of management was developed that allows effective yet safe administration of deferoxamine. A dose of 50 mg/kg is recommended in those without audiogram abnormalities. With mild toxicity, a reduction to 30 or 40 mg/kg per dose should result in a reversal of the abnormal results to normal within four weeks. Moderate abnormalities require a reduction of deferoxamine to 25 mg/kg per dose with careful monitoring. In those with symptoms of hearing loss, the drug should be stopped for four weeks, and when the audiogram is stable or improved, therapy should be restarted at 10 to 25 mg/kg per dose. Serial audiograms should be performed every six months in those without problems and more frequently in young patients with normal serum ferritin values and in those with auditory dysfunction.", "entity": "Deferoxamine", "aliases": "B Deferoxamine Desferrioxamine Mesilate Mesylate Methanesulfonate Deferoximine Deferrioxamine Desferal Desferioximine Desferroxamine", "definition": "Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form.\n    ", "id": "MESH:D003676"}
{"mention": "abnormal audiograms with deficits mostly in the high frequency range of 4,000 to 8,000 Hz", "mention_text": "Visual and auditory neurotoxicity was previously documented in 42 of 89 patients with transfusion-dependent anemia who were receiving iron chelation therapy with daily subcutaneous deferoxamine. Twenty-two patients in the affected group had abnormal audiograms with deficits mostly in the high frequency range of 4,000 to 8,000 Hz and in the hearing threshold levels of 30 to 100 decibels. When deferoxamine therapy was discontinued and serial studies were performed, audiograms in seven cases reverted to normal or near normal within two to three weeks, and nine of 13 patients with symptoms became asymptomatic. Audiograms from 15 patients remained abnormal and four patients required hearing aids because of permanent disability. Since 18 of the 22 patients were initially receiving deferoxamine doses in excess of the commonly recommended 50 mg/kg per dose, therapy was restarted with lower doses, usually 50 mg/kg per dose or less depending on the degree of auditory abnormality, and with the exception of two cases no further toxicity was demonstrated. Auditory deterioration and improvement, demonstrated serially in individual patients receiving and not receiving deferoxamine, respectively, provided convincing evidence for a cause-and-effect relation between deferoxamine administration and ototoxicity. Based on these data, a plan of management was developed that allows effective yet safe administration of deferoxamine. A dose of 50 mg/kg is recommended in those without audiogram abnormalities. With mild toxicity, a reduction to 30 or 40 mg/kg per dose should result in a reversal of the abnormal results to normal within four weeks. Moderate abnormalities require a reduction of deferoxamine to 25 mg/kg per dose with careful monitoring. In those with symptoms of hearing loss, the drug should be stopped for four weeks, and when the audiogram is stable or improved, therapy should be restarted at 10 to 25 mg/kg per dose. Serial audiograms should be performed every six months in those without problems and more frequently in young patients with normal serum ferritin values and in those with auditory dysfunction.", "entity": "Hearing Loss, High-Frequency", "aliases": "Hearing Loss High Frequency High-Frequency", "definition": "Hearing loss in frequencies above 1000 hertz.\n    ", "id": "MESH:D006316"}
{"mention": "permanent disability", "mention_text": "Visual and auditory neurotoxicity was previously documented in 42 of 89 patients with transfusion-dependent anemia who were receiving iron chelation therapy with daily subcutaneous deferoxamine. Twenty-two patients in the affected group had abnormal audiograms with deficits mostly in the high frequency range of 4,000 to 8,000 Hz and in the hearing threshold levels of 30 to 100 decibels. When deferoxamine therapy was discontinued and serial studies were performed, audiograms in seven cases reverted to normal or near normal within two to three weeks, and nine of 13 patients with symptoms became asymptomatic. Audiograms from 15 patients remained abnormal and four patients required hearing aids because of permanent disability. Since 18 of the 22 patients were initially receiving deferoxamine doses in excess of the commonly recommended 50 mg/kg per dose, therapy was restarted with lower doses, usually 50 mg/kg per dose or less depending on the degree of auditory abnormality, and with the exception of two cases no further toxicity was demonstrated. Auditory deterioration and improvement, demonstrated serially in individual patients receiving and not receiving deferoxamine, respectively, provided convincing evidence for a cause-and-effect relation between deferoxamine administration and ototoxicity. Based on these data, a plan of management was developed that allows effective yet safe administration of deferoxamine. A dose of 50 mg/kg is recommended in those without audiogram abnormalities. With mild toxicity, a reduction to 30 or 40 mg/kg per dose should result in a reversal of the abnormal results to normal within four weeks. Moderate abnormalities require a reduction of deferoxamine to 25 mg/kg per dose with careful monitoring. In those with symptoms of hearing loss, the drug should be stopped for four weeks, and when the audiogram is stable or improved, therapy should be restarted at 10 to 25 mg/kg per dose. Serial audiograms should be performed every six months in those without problems and more frequently in young patients with normal serum ferritin values and in those with auditory dysfunction.", "entity": "Deafness", "aliases": "Acquired Deafness Bilateral Complete Hearing Loss Deaf Mutism Deaf-Mutism Prelingual Extreme", "definition": "A general term for the complete loss of the ability to hear from both ears.\n    ", "id": "MESH:D003638"}
{"mention": "auditory abnormality", "mention_text": "Visual and auditory neurotoxicity was previously documented in 42 of 89 patients with transfusion-dependent anemia who were receiving iron chelation therapy with daily subcutaneous deferoxamine. Twenty-two patients in the affected group had abnormal audiograms with deficits mostly in the high frequency range of 4,000 to 8,000 Hz and in the hearing threshold levels of 30 to 100 decibels. When deferoxamine therapy was discontinued and serial studies were performed, audiograms in seven cases reverted to normal or near normal within two to three weeks, and nine of 13 patients with symptoms became asymptomatic. Audiograms from 15 patients remained abnormal and four patients required hearing aids because of permanent disability. Since 18 of the 22 patients were initially receiving deferoxamine doses in excess of the commonly recommended 50 mg/kg per dose, therapy was restarted with lower doses, usually 50 mg/kg per dose or less depending on the degree of auditory abnormality, and with the exception of two cases no further toxicity was demonstrated. Auditory deterioration and improvement, demonstrated serially in individual patients receiving and not receiving deferoxamine, respectively, provided convincing evidence for a cause-and-effect relation between deferoxamine administration and ototoxicity. Based on these data, a plan of management was developed that allows effective yet safe administration of deferoxamine. A dose of 50 mg/kg is recommended in those without audiogram abnormalities. With mild toxicity, a reduction to 30 or 40 mg/kg per dose should result in a reversal of the abnormal results to normal within four weeks. Moderate abnormalities require a reduction of deferoxamine to 25 mg/kg per dose with careful monitoring. In those with symptoms of hearing loss, the drug should be stopped for four weeks, and when the audiogram is stable or improved, therapy should be restarted at 10 to 25 mg/kg per dose. Serial audiograms should be performed every six months in those without problems and more frequently in young patients with normal serum ferritin values and in those with auditory dysfunction.", "entity": "Hearing Disorders", "aliases": "Distorted Hearing Dysacusis Disorder Disorders Paracousis Paracusis", "definition": "Conditions that impair the transmission of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways.\n    ", "id": "MESH:D006311"}
{"mention": "toxicity", "mention_text": "Visual and auditory neurotoxicity was previously documented in 42 of 89 patients with transfusion-dependent anemia who were receiving iron chelation therapy with daily subcutaneous deferoxamine. Twenty-two patients in the affected group had abnormal audiograms with deficits mostly in the high frequency range of 4,000 to 8,000 Hz and in the hearing threshold levels of 30 to 100 decibels. When deferoxamine therapy was discontinued and serial studies were performed, audiograms in seven cases reverted to normal or near normal within two to three weeks, and nine of 13 patients with symptoms became asymptomatic. Audiograms from 15 patients remained abnormal and four patients required hearing aids because of permanent disability. Since 18 of the 22 patients were initially receiving deferoxamine doses in excess of the commonly recommended 50 mg/kg per dose, therapy was restarted with lower doses, usually 50 mg/kg per dose or less depending on the degree of auditory abnormality, and with the exception of two cases no further toxicity was demonstrated. Auditory deterioration and improvement, demonstrated serially in individual patients receiving and not receiving deferoxamine, respectively, provided convincing evidence for a cause-and-effect relation between deferoxamine administration and ototoxicity. Based on these data, a plan of management was developed that allows effective yet safe administration of deferoxamine. A dose of 50 mg/kg is recommended in those without audiogram abnormalities. With mild toxicity, a reduction to 30 or 40 mg/kg per dose should result in a reversal of the abnormal results to normal within four weeks. Moderate abnormalities require a reduction of deferoxamine to 25 mg/kg per dose with careful monitoring. In those with symptoms of hearing loss, the drug should be stopped for four weeks, and when the audiogram is stable or improved, therapy should be restarted at 10 to 25 mg/kg per dose. Serial audiograms should be performed every six months in those without problems and more frequently in young patients with normal serum ferritin values and in those with auditory dysfunction.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "ototoxicity", "mention_text": "Visual and auditory neurotoxicity was previously documented in 42 of 89 patients with transfusion-dependent anemia who were receiving iron chelation therapy with daily subcutaneous deferoxamine. Twenty-two patients in the affected group had abnormal audiograms with deficits mostly in the high frequency range of 4,000 to 8,000 Hz and in the hearing threshold levels of 30 to 100 decibels. When deferoxamine therapy was discontinued and serial studies were performed, audiograms in seven cases reverted to normal or near normal within two to three weeks, and nine of 13 patients with symptoms became asymptomatic. Audiograms from 15 patients remained abnormal and four patients required hearing aids because of permanent disability. Since 18 of the 22 patients were initially receiving deferoxamine doses in excess of the commonly recommended 50 mg/kg per dose, therapy was restarted with lower doses, usually 50 mg/kg per dose or less depending on the degree of auditory abnormality, and with the exception of two cases no further toxicity was demonstrated. Auditory deterioration and improvement, demonstrated serially in individual patients receiving and not receiving deferoxamine, respectively, provided convincing evidence for a cause-and-effect relation between deferoxamine administration and ototoxicity. Based on these data, a plan of management was developed that allows effective yet safe administration of deferoxamine. A dose of 50 mg/kg is recommended in those without audiogram abnormalities. With mild toxicity, a reduction to 30 or 40 mg/kg per dose should result in a reversal of the abnormal results to normal within four weeks. Moderate abnormalities require a reduction of deferoxamine to 25 mg/kg per dose with careful monitoring. In those with symptoms of hearing loss, the drug should be stopped for four weeks, and when the audiogram is stable or improved, therapy should be restarted at 10 to 25 mg/kg per dose. Serial audiograms should be performed every six months in those without problems and more frequently in young patients with normal serum ferritin values and in those with auditory dysfunction.", "entity": "Hearing Disorders", "aliases": "Distorted Hearing Dysacusis Disorder Disorders Paracousis Paracusis", "definition": "Conditions that impair the transmission of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways.\n    ", "id": "MESH:D006311"}
{"mention": "hearing loss", "mention_text": "Visual and auditory neurotoxicity was previously documented in 42 of 89 patients with transfusion-dependent anemia who were receiving iron chelation therapy with daily subcutaneous deferoxamine. Twenty-two patients in the affected group had abnormal audiograms with deficits mostly in the high frequency range of 4,000 to 8,000 Hz and in the hearing threshold levels of 30 to 100 decibels. When deferoxamine therapy was discontinued and serial studies were performed, audiograms in seven cases reverted to normal or near normal within two to three weeks, and nine of 13 patients with symptoms became asymptomatic. Audiograms from 15 patients remained abnormal and four patients required hearing aids because of permanent disability. Since 18 of the 22 patients were initially receiving deferoxamine doses in excess of the commonly recommended 50 mg/kg per dose, therapy was restarted with lower doses, usually 50 mg/kg per dose or less depending on the degree of auditory abnormality, and with the exception of two cases no further toxicity was demonstrated. Auditory deterioration and improvement, demonstrated serially in individual patients receiving and not receiving deferoxamine, respectively, provided convincing evidence for a cause-and-effect relation between deferoxamine administration and ototoxicity. Based on these data, a plan of management was developed that allows effective yet safe administration of deferoxamine. A dose of 50 mg/kg is recommended in those without audiogram abnormalities. With mild toxicity, a reduction to 30 or 40 mg/kg per dose should result in a reversal of the abnormal results to normal within four weeks. Moderate abnormalities require a reduction of deferoxamine to 25 mg/kg per dose with careful monitoring. In those with symptoms of hearing loss, the drug should be stopped for four weeks, and when the audiogram is stable or improved, therapy should be restarted at 10 to 25 mg/kg per dose. Serial audiograms should be performed every six months in those without problems and more frequently in young patients with normal serum ferritin values and in those with auditory dysfunction.", "entity": "Hearing Loss", "aliases": "Hearing Impairment Loss Hypoacuses Hypoacusis", "definition": "A general term for the complete or partial loss of the ability to hear from one or both ears.\n    ", "id": "MESH:D034381"}
{"mention": "auditory dysfunction", "mention_text": "Visual and auditory neurotoxicity was previously documented in 42 of 89 patients with transfusion-dependent anemia who were receiving iron chelation therapy with daily subcutaneous deferoxamine. Twenty-two patients in the affected group had abnormal audiograms with deficits mostly in the high frequency range of 4,000 to 8,000 Hz and in the hearing threshold levels of 30 to 100 decibels. When deferoxamine therapy was discontinued and serial studies were performed, audiograms in seven cases reverted to normal or near normal within two to three weeks, and nine of 13 patients with symptoms became asymptomatic. Audiograms from 15 patients remained abnormal and four patients required hearing aids because of permanent disability. Since 18 of the 22 patients were initially receiving deferoxamine doses in excess of the commonly recommended 50 mg/kg per dose, therapy was restarted with lower doses, usually 50 mg/kg per dose or less depending on the degree of auditory abnormality, and with the exception of two cases no further toxicity was demonstrated. Auditory deterioration and improvement, demonstrated serially in individual patients receiving and not receiving deferoxamine, respectively, provided convincing evidence for a cause-and-effect relation between deferoxamine administration and ototoxicity. Based on these data, a plan of management was developed that allows effective yet safe administration of deferoxamine. A dose of 50 mg/kg is recommended in those without audiogram abnormalities. With mild toxicity, a reduction to 30 or 40 mg/kg per dose should result in a reversal of the abnormal results to normal within four weeks. Moderate abnormalities require a reduction of deferoxamine to 25 mg/kg per dose with careful monitoring. In those with symptoms of hearing loss, the drug should be stopped for four weeks, and when the audiogram is stable or improved, therapy should be restarted at 10 to 25 mg/kg per dose. Serial audiograms should be performed every six months in those without problems and more frequently in young patients with normal serum ferritin values and in those with auditory dysfunction.", "entity": "Hearing Disorders", "aliases": "Distorted Hearing Dysacusis Disorder Disorders Paracousis Paracusis", "definition": "Conditions that impair the transmission of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways.\n    ", "id": "MESH:D006311"}
{"mention": "Flurbiprofen", "mention_text": "Flurbiprofen in the treatment of juvenile rheumatoid arthritis.", "entity": "Flurbiprofen", "aliases": "2-Fluoro-alpha-methyl-(1,1'-biphenyl)-4-acetic Acid Abbott Brand of Flurbiprofen Allergan Sodium Ansaid Apo Apo-Flurbiprofen Apotex BTS 18322 BTS-18322 BTS18322 Cantabria Cebutid Crookes Dobrofen E 7869 E-7869 E7869 Flubiprofen Flugalin Pfizer Fluriproben Froben SR Klosterfrau Knoll Neo Artrol Novo Flurprofen Novo-Flurprofen Novopharm Nu Pharm Nu-Flurbiprofen Nu-Pharm Ocufen Ocuflur Pharm-Allergan Ratiopharm Recordati Shire Strefen ratio ratio-Flurbiprofen", "definition": "An anti-inflammatory analgesic and antipyretic of the phenylalkynoic acid series. It has been shown to reduce bone resorption in periodontal disease by inhibiting CARBONIC ANHYDRASE.\n    ", "id": "MESH:D005480"}
{"mention": "juvenile rheumatoid arthritis", "mention_text": "Flurbiprofen in the treatment of juvenile rheumatoid arthritis.", "entity": "Arthritis, Juvenile", "aliases": "Arthritis Juvenile Chronic Enthesitis-Related Idiopathic Psoriatic Rheumatoid Systemic Enthesitis Related Oligoarthritis Onset Still Disease Stills Juvenile-Onset Still's Polyarthritis Factor Negative Positive", "definition": "Arthritis of children, with onset before 16 years of age. The terms juvenile rheumatoid arthritis (JRA) and juvenile idiopathic arthritis (JIA) refer to classification systems for chronic arthritis in children. Only one subtype of juvenile arthritis (polyarticular-onset, rheumatoid factor-positive) clinically resembles adult rheumatoid arthritis and is considered its childhood equivalent.\n    ", "id": "MESH:D001171"}
{"mention": "juvenile rheumatoid arthritis", "mention_text": "Thirty-four patients with juvenile rheumatoid arthritis, who were treated with flurbiprofen at a maximum dose of 4 mg/kg/day, had statistically significant decreases from baseline in 6 arthritis indices after 12 weeks of treatment. Improvements were seen in the number of tender joints, the severity of swelling and tenderness, the time of walk 50 feet, the duration of morning stiffness and the circumference of the left knee. The most frequently observed side effect was fecal occult blood (25% of patients); however, there was no other evidence of gastrointestinal (GI) bleeding in these patients. One patient was prematurely discontinued from the study for severe headache and abdominal pain. Most side effects were mild and related to the GI tract.", "entity": "Arthritis, Juvenile", "aliases": "Arthritis Juvenile Chronic Enthesitis-Related Idiopathic Psoriatic Rheumatoid Systemic Enthesitis Related Oligoarthritis Onset Still Disease Stills Juvenile-Onset Still's Polyarthritis Factor Negative Positive", "definition": "Arthritis of children, with onset before 16 years of age. The terms juvenile rheumatoid arthritis (JRA) and juvenile idiopathic arthritis (JIA) refer to classification systems for chronic arthritis in children. Only one subtype of juvenile arthritis (polyarticular-onset, rheumatoid factor-positive) clinically resembles adult rheumatoid arthritis and is considered its childhood equivalent.\n    ", "id": "MESH:D001171"}
{"mention": "flurbiprofen", "mention_text": "Thirty-four patients with juvenile rheumatoid arthritis, who were treated with flurbiprofen at a maximum dose of 4 mg/kg/day, had statistically significant decreases from baseline in 6 arthritis indices after 12 weeks of treatment. Improvements were seen in the number of tender joints, the severity of swelling and tenderness, the time of walk 50 feet, the duration of morning stiffness and the circumference of the left knee. The most frequently observed side effect was fecal occult blood (25% of patients); however, there was no other evidence of gastrointestinal (GI) bleeding in these patients. One patient was prematurely discontinued from the study for severe headache and abdominal pain. Most side effects were mild and related to the GI tract.", "entity": "Flurbiprofen", "aliases": "2-Fluoro-alpha-methyl-(1,1'-biphenyl)-4-acetic Acid Abbott Brand of Flurbiprofen Allergan Sodium Ansaid Apo Apo-Flurbiprofen Apotex BTS 18322 BTS-18322 BTS18322 Cantabria Cebutid Crookes Dobrofen E 7869 E-7869 E7869 Flubiprofen Flugalin Pfizer Fluriproben Froben SR Klosterfrau Knoll Neo Artrol Novo Flurprofen Novo-Flurprofen Novopharm Nu Pharm Nu-Flurbiprofen Nu-Pharm Ocufen Ocuflur Pharm-Allergan Ratiopharm Recordati Shire Strefen ratio ratio-Flurbiprofen", "definition": "An anti-inflammatory analgesic and antipyretic of the phenylalkynoic acid series. It has been shown to reduce bone resorption in periodontal disease by inhibiting CARBONIC ANHYDRASE.\n    ", "id": "MESH:D005480"}
{"mention": "arthritis", "mention_text": "Thirty-four patients with juvenile rheumatoid arthritis, who were treated with flurbiprofen at a maximum dose of 4 mg/kg/day, had statistically significant decreases from baseline in 6 arthritis indices after 12 weeks of treatment. Improvements were seen in the number of tender joints, the severity of swelling and tenderness, the time of walk 50 feet, the duration of morning stiffness and the circumference of the left knee. The most frequently observed side effect was fecal occult blood (25% of patients); however, there was no other evidence of gastrointestinal (GI) bleeding in these patients. One patient was prematurely discontinued from the study for severe headache and abdominal pain. Most side effects were mild and related to the GI tract.", "entity": "Arthritis", "aliases": "Arthritides Arthritis Polyarthritides Polyarthritis", "definition": "", "id": "MESH:D001168"}
{"mention": "swelling", "mention_text": "Thirty-four patients with juvenile rheumatoid arthritis, who were treated with flurbiprofen at a maximum dose of 4 mg/kg/day, had statistically significant decreases from baseline in 6 arthritis indices after 12 weeks of treatment. Improvements were seen in the number of tender joints, the severity of swelling and tenderness, the time of walk 50 feet, the duration of morning stiffness and the circumference of the left knee. The most frequently observed side effect was fecal occult blood (25% of patients); however, there was no other evidence of gastrointestinal (GI) bleeding in these patients. One patient was prematurely discontinued from the study for severe headache and abdominal pain. Most side effects were mild and related to the GI tract.", "entity": "Edema", "aliases": "Anasarca Dropsy Edema Hydrops", "definition": "Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE.\n    ", "id": "MESH:D004487"}
{"mention": "gastrointestinal (GI) bleeding", "mention_text": "Thirty-four patients with juvenile rheumatoid arthritis, who were treated with flurbiprofen at a maximum dose of 4 mg/kg/day, had statistically significant decreases from baseline in 6 arthritis indices after 12 weeks of treatment. Improvements were seen in the number of tender joints, the severity of swelling and tenderness, the time of walk 50 feet, the duration of morning stiffness and the circumference of the left knee. The most frequently observed side effect was fecal occult blood (25% of patients); however, there was no other evidence of gastrointestinal (GI) bleeding in these patients. One patient was prematurely discontinued from the study for severe headache and abdominal pain. Most side effects were mild and related to the GI tract.", "entity": "Gastrointestinal Hemorrhage", "aliases": "Gastrointestinal Hemorrhage Hemorrhages Hematochezia Hematochezias", "definition": "Bleeding in any segment of the GASTROINTESTINAL TRACT from ESOPHAGUS to RECTUM.\n    ", "id": "MESH:D006471"}
{"mention": "headache", "mention_text": "Thirty-four patients with juvenile rheumatoid arthritis, who were treated with flurbiprofen at a maximum dose of 4 mg/kg/day, had statistically significant decreases from baseline in 6 arthritis indices after 12 weeks of treatment. Improvements were seen in the number of tender joints, the severity of swelling and tenderness, the time of walk 50 feet, the duration of morning stiffness and the circumference of the left knee. The most frequently observed side effect was fecal occult blood (25% of patients); however, there was no other evidence of gastrointestinal (GI) bleeding in these patients. One patient was prematurely discontinued from the study for severe headache and abdominal pain. Most side effects were mild and related to the GI tract.", "entity": "Headache", "aliases": "Bilateral Headache Headaches Cephalalgia Cephalalgias Cephalgia Cephalgias Cephalodynia Cephalodynias Cranial Pain Pains Generalized Head Ocular Orthostatic Periorbital Retro-Ocular Sharp Throbbing Unilateral Vertex Hemicrania Retro", "definition": "The symptom of PAIN in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of HEADACHE DISORDERS.\n    ", "id": "MESH:D006261"}
{"mention": "abdominal pain", "mention_text": "Thirty-four patients with juvenile rheumatoid arthritis, who were treated with flurbiprofen at a maximum dose of 4 mg/kg/day, had statistically significant decreases from baseline in 6 arthritis indices after 12 weeks of treatment. Improvements were seen in the number of tender joints, the severity of swelling and tenderness, the time of walk 50 feet, the duration of morning stiffness and the circumference of the left knee. The most frequently observed side effect was fecal occult blood (25% of patients); however, there was no other evidence of gastrointestinal (GI) bleeding in these patients. One patient was prematurely discontinued from the study for severe headache and abdominal pain. Most side effects were mild and related to the GI tract.", "entity": "Abdominal Pain", "aliases": "Abdominal Pain Pains", "definition": "Sensation of discomfort, distress, or agony in the abdominal region; generally associated with functional disorders, tissue injuries, or diseases.\n    ", "id": "MESH:D015746"}
{"mention": "neurotoxic", "mention_text": "The correlation between neurotoxic esterase inhibition and mipafox-induced neuropathic damage in rats.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "mipafox", "mention_text": "The correlation between neurotoxic esterase inhibition and mipafox-induced neuropathic damage in rats.", "entity": "mipafox", "aliases": "N,N'-di-isopropylphosphorodiamidic fluoride N,N'-diisopropylphosphorodiamidic mipafox", "definition": "", "id": "MESH:C005238"}
{"mention": "neuropathic damage", "mention_text": "The correlation between neurotoxic esterase inhibition and mipafox-induced neuropathic damage in rats.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "neuropathic damage", "mention_text": "The correlation between neuropathic damage and inhibition of neurotoxic esterase or neuropathy target enzyme (NTE) was examined in rats acutely exposed to Mipafox (N, N'-diisopropylphosphorodiamidofluoridate), a neurotoxic organophosphate. Brain and spinal cord NTE activities were measured in Long-Evans male rats 1 hr post-exposure to various dosages of Mipafox (ip, 1-15 mg/kg). These data were correlated with histologically scored cervical cord damage in a separate group of similarly dosed rats sampled 14-21 days post-exposure. Those dosages (greater than or equal to 10 mg/kg) that inhibited mean NTE activity in the spinal cord greater than or equal to 73% and brain greater than or equal to 67% of control values produced severe (greater than or equal to 3) cervical cord pathology in 85% of the rats. In contrast, dosages of Mipafox (less than or equal to 5 mg/kg) which inhibited mean NTE activity in spinal cord less than or equal to 61% and brain less than or equal to 60% produced this degree of cord damage in only 9% of the animals. These data indicate that a critical percentage of NTE inhibition in brain and spinal cord sampled shortly after Mipafox exposure can predict neuropathic damage in rats several weeks later.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "neurotoxic", "mention_text": "The correlation between neuropathic damage and inhibition of neurotoxic esterase or neuropathy target enzyme (NTE) was examined in rats acutely exposed to Mipafox (N, N'-diisopropylphosphorodiamidofluoridate), a neurotoxic organophosphate. Brain and spinal cord NTE activities were measured in Long-Evans male rats 1 hr post-exposure to various dosages of Mipafox (ip, 1-15 mg/kg). These data were correlated with histologically scored cervical cord damage in a separate group of similarly dosed rats sampled 14-21 days post-exposure. Those dosages (greater than or equal to 10 mg/kg) that inhibited mean NTE activity in the spinal cord greater than or equal to 73% and brain greater than or equal to 67% of control values produced severe (greater than or equal to 3) cervical cord pathology in 85% of the rats. In contrast, dosages of Mipafox (less than or equal to 5 mg/kg) which inhibited mean NTE activity in spinal cord less than or equal to 61% and brain less than or equal to 60% produced this degree of cord damage in only 9% of the animals. These data indicate that a critical percentage of NTE inhibition in brain and spinal cord sampled shortly after Mipafox exposure can predict neuropathic damage in rats several weeks later.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "neuropathy", "mention_text": "The correlation between neuropathic damage and inhibition of neurotoxic esterase or neuropathy target enzyme (NTE) was examined in rats acutely exposed to Mipafox (N, N'-diisopropylphosphorodiamidofluoridate), a neurotoxic organophosphate. Brain and spinal cord NTE activities were measured in Long-Evans male rats 1 hr post-exposure to various dosages of Mipafox (ip, 1-15 mg/kg). These data were correlated with histologically scored cervical cord damage in a separate group of similarly dosed rats sampled 14-21 days post-exposure. Those dosages (greater than or equal to 10 mg/kg) that inhibited mean NTE activity in the spinal cord greater than or equal to 73% and brain greater than or equal to 67% of control values produced severe (greater than or equal to 3) cervical cord pathology in 85% of the rats. In contrast, dosages of Mipafox (less than or equal to 5 mg/kg) which inhibited mean NTE activity in spinal cord less than or equal to 61% and brain less than or equal to 60% produced this degree of cord damage in only 9% of the animals. These data indicate that a critical percentage of NTE inhibition in brain and spinal cord sampled shortly after Mipafox exposure can predict neuropathic damage in rats several weeks later.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "Mipafox", "mention_text": "The correlation between neuropathic damage and inhibition of neurotoxic esterase or neuropathy target enzyme (NTE) was examined in rats acutely exposed to Mipafox (N, N'-diisopropylphosphorodiamidofluoridate), a neurotoxic organophosphate. Brain and spinal cord NTE activities were measured in Long-Evans male rats 1 hr post-exposure to various dosages of Mipafox (ip, 1-15 mg/kg). These data were correlated with histologically scored cervical cord damage in a separate group of similarly dosed rats sampled 14-21 days post-exposure. Those dosages (greater than or equal to 10 mg/kg) that inhibited mean NTE activity in the spinal cord greater than or equal to 73% and brain greater than or equal to 67% of control values produced severe (greater than or equal to 3) cervical cord pathology in 85% of the rats. In contrast, dosages of Mipafox (less than or equal to 5 mg/kg) which inhibited mean NTE activity in spinal cord less than or equal to 61% and brain less than or equal to 60% produced this degree of cord damage in only 9% of the animals. These data indicate that a critical percentage of NTE inhibition in brain and spinal cord sampled shortly after Mipafox exposure can predict neuropathic damage in rats several weeks later.", "entity": "mipafox", "aliases": "N,N'-di-isopropylphosphorodiamidic fluoride N,N'-diisopropylphosphorodiamidic mipafox", "definition": "", "id": "MESH:C005238"}
{"mention": "N, N'-diisopropylphosphorodiamidofluoridate", "mention_text": "The correlation between neuropathic damage and inhibition of neurotoxic esterase or neuropathy target enzyme (NTE) was examined in rats acutely exposed to Mipafox (N, N'-diisopropylphosphorodiamidofluoridate), a neurotoxic organophosphate. Brain and spinal cord NTE activities were measured in Long-Evans male rats 1 hr post-exposure to various dosages of Mipafox (ip, 1-15 mg/kg). These data were correlated with histologically scored cervical cord damage in a separate group of similarly dosed rats sampled 14-21 days post-exposure. Those dosages (greater than or equal to 10 mg/kg) that inhibited mean NTE activity in the spinal cord greater than or equal to 73% and brain greater than or equal to 67% of control values produced severe (greater than or equal to 3) cervical cord pathology in 85% of the rats. In contrast, dosages of Mipafox (less than or equal to 5 mg/kg) which inhibited mean NTE activity in spinal cord less than or equal to 61% and brain less than or equal to 60% produced this degree of cord damage in only 9% of the animals. These data indicate that a critical percentage of NTE inhibition in brain and spinal cord sampled shortly after Mipafox exposure can predict neuropathic damage in rats several weeks later.", "entity": "mipafox", "aliases": "N,N'-di-isopropylphosphorodiamidic fluoride N,N'-diisopropylphosphorodiamidic mipafox", "definition": "", "id": "MESH:C005238"}
{"mention": "organophosphate", "mention_text": "The correlation between neuropathic damage and inhibition of neurotoxic esterase or neuropathy target enzyme (NTE) was examined in rats acutely exposed to Mipafox (N, N'-diisopropylphosphorodiamidofluoridate), a neurotoxic organophosphate. Brain and spinal cord NTE activities were measured in Long-Evans male rats 1 hr post-exposure to various dosages of Mipafox (ip, 1-15 mg/kg). These data were correlated with histologically scored cervical cord damage in a separate group of similarly dosed rats sampled 14-21 days post-exposure. Those dosages (greater than or equal to 10 mg/kg) that inhibited mean NTE activity in the spinal cord greater than or equal to 73% and brain greater than or equal to 67% of control values produced severe (greater than or equal to 3) cervical cord pathology in 85% of the rats. In contrast, dosages of Mipafox (less than or equal to 5 mg/kg) which inhibited mean NTE activity in spinal cord less than or equal to 61% and brain less than or equal to 60% produced this degree of cord damage in only 9% of the animals. These data indicate that a critical percentage of NTE inhibition in brain and spinal cord sampled shortly after Mipafox exposure can predict neuropathic damage in rats several weeks later.", "entity": "Organophosphates", "aliases": "Acid Esters Phosphoric Organic Phosphates Organophosphates Organopyrophosphates", "definition": "Carbon-containing phosphoric acid derivatives. Included under this heading are compounds that have CARBON atoms bound to one or more OXYGEN atoms of the P(=O)(O)3 structure. Note that several specific classes of endogenous phosphorus-containing compounds such as NUCLEOTIDES; PHOSPHOLIPIDS; and PHOSPHOPROTEINS are listed elsewhere.\n    ", "id": "MESH:D010755"}
{"mention": "cord damage", "mention_text": "The correlation between neuropathic damage and inhibition of neurotoxic esterase or neuropathy target enzyme (NTE) was examined in rats acutely exposed to Mipafox (N, N'-diisopropylphosphorodiamidofluoridate), a neurotoxic organophosphate. Brain and spinal cord NTE activities were measured in Long-Evans male rats 1 hr post-exposure to various dosages of Mipafox (ip, 1-15 mg/kg). These data were correlated with histologically scored cervical cord damage in a separate group of similarly dosed rats sampled 14-21 days post-exposure. Those dosages (greater than or equal to 10 mg/kg) that inhibited mean NTE activity in the spinal cord greater than or equal to 73% and brain greater than or equal to 67% of control values produced severe (greater than or equal to 3) cervical cord pathology in 85% of the rats. In contrast, dosages of Mipafox (less than or equal to 5 mg/kg) which inhibited mean NTE activity in spinal cord less than or equal to 61% and brain less than or equal to 60% produced this degree of cord damage in only 9% of the animals. These data indicate that a critical percentage of NTE inhibition in brain and spinal cord sampled shortly after Mipafox exposure can predict neuropathic damage in rats several weeks later.", "entity": "Spinal Cord Diseases", "aliases": "Myelopathies Myelopathy Spinal Cord Disease Diseases Disorder Disorders", "definition": "Pathologic conditions which feature SPINAL CORD damage or dysfunction, including disorders involving the meninges and perimeningeal spaces surrounding the spinal cord. Traumatic injuries, vascular diseases, infections, and inflammatory/autoimmune processes may affect the spinal cord.\n    ", "id": "MESH:D013118"}
{"mention": "Cerebral infarction", "mention_text": "Cerebral infarction with a single oral dose of phenylpropanolamine.", "entity": "Cerebral Infarction", "aliases": "Anterior Choroidal Artery Infarction Cerebral Left Hemisphere Right Infarctions Subcortical Posterior", "definition": "The formation of an area of NECROSIS in the CEREBRUM caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., INFARCTION, ANTERIOR CEREBRAL ARTERY), and etiology (e.g., embolic infarction).\n    ", "id": "MESH:D002544"}
{"mention": "phenylpropanolamine", "mention_text": "Cerebral infarction with a single oral dose of phenylpropanolamine.", "entity": "Phenylpropanolamine", "aliases": "Dexatrim Hydrochloride Phenylpropanolamine Norephedrine Prolamine Propagest", "definition": "A sympathomimetic that acts mainly by causing release of NOREPINEPHRINE but also has direct agonist activity at some adrenergic receptors. It is most commonly used as a nasal vasoconstrictor and an appetite depressant.\n    ", "id": "MESH:D010665"}
{"mention": "Phenylpropanolamine", "mention_text": "Phenylpropanolamine (PPA), a synthetic sympathomimetic that is structurally similar to amphetamine, is available over the counter in anorectics, nasal congestants, and cold preparations. Its prolonged use or overuse has been associated with seizures, intracerebral hemorrhage, neuropsychiatric symptoms, and nonhemorrhagic cerebral infarction. We report the case of a young woman who suffered a cerebral infarction after taking a single oral dose of PPA.", "entity": "Phenylpropanolamine", "aliases": "Dexatrim Hydrochloride Phenylpropanolamine Norephedrine Prolamine Propagest", "definition": "A sympathomimetic that acts mainly by causing release of NOREPINEPHRINE but also has direct agonist activity at some adrenergic receptors. It is most commonly used as a nasal vasoconstrictor and an appetite depressant.\n    ", "id": "MESH:D010665"}
{"mention": "PPA", "mention_text": "Phenylpropanolamine (PPA), a synthetic sympathomimetic that is structurally similar to amphetamine, is available over the counter in anorectics, nasal congestants, and cold preparations. Its prolonged use or overuse has been associated with seizures, intracerebral hemorrhage, neuropsychiatric symptoms, and nonhemorrhagic cerebral infarction. We report the case of a young woman who suffered a cerebral infarction after taking a single oral dose of PPA.", "entity": "Phenylpropanolamine", "aliases": "Dexatrim Hydrochloride Phenylpropanolamine Norephedrine Prolamine Propagest", "definition": "A sympathomimetic that acts mainly by causing release of NOREPINEPHRINE but also has direct agonist activity at some adrenergic receptors. It is most commonly used as a nasal vasoconstrictor and an appetite depressant.\n    ", "id": "MESH:D010665"}
{"mention": "amphetamine", "mention_text": "Phenylpropanolamine (PPA), a synthetic sympathomimetic that is structurally similar to amphetamine, is available over the counter in anorectics, nasal congestants, and cold preparations. Its prolonged use or overuse has been associated with seizures, intracerebral hemorrhage, neuropsychiatric symptoms, and nonhemorrhagic cerebral infarction. We report the case of a young woman who suffered a cerebral infarction after taking a single oral dose of PPA.", "entity": "Amphetamine", "aliases": "Amfetamine Amphetamine Sulfate (2:1) Centramina Desoxynorephedrin Fenamine Levoamphetamine Miquel Brand of Mydrial Phenamine Phenopromin Thyramine l l-Amphetamine levo levo-Amphetamine", "definition": "A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE.\n    ", "id": "MESH:D000661"}
{"mention": "seizures", "mention_text": "Phenylpropanolamine (PPA), a synthetic sympathomimetic that is structurally similar to amphetamine, is available over the counter in anorectics, nasal congestants, and cold preparations. Its prolonged use or overuse has been associated with seizures, intracerebral hemorrhage, neuropsychiatric symptoms, and nonhemorrhagic cerebral infarction. We report the case of a young woman who suffered a cerebral infarction after taking a single oral dose of PPA.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "intracerebral hemorrhage", "mention_text": "Phenylpropanolamine (PPA), a synthetic sympathomimetic that is structurally similar to amphetamine, is available over the counter in anorectics, nasal congestants, and cold preparations. Its prolonged use or overuse has been associated with seizures, intracerebral hemorrhage, neuropsychiatric symptoms, and nonhemorrhagic cerebral infarction. We report the case of a young woman who suffered a cerebral infarction after taking a single oral dose of PPA.", "entity": "Cerebral Hemorrhage", "aliases": "Brain Hemorrhage Cerebral Hemorrhages Parenchymal Cerebrum Intracerebral", "definition": "Bleeding into one or both CEREBRAL HEMISPHERES including the BASAL GANGLIA and the CEREBRAL CORTEX. It is often associated with HYPERTENSION and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D002543"}
{"mention": "neuropsychiatric symptoms", "mention_text": "Phenylpropanolamine (PPA), a synthetic sympathomimetic that is structurally similar to amphetamine, is available over the counter in anorectics, nasal congestants, and cold preparations. Its prolonged use or overuse has been associated with seizures, intracerebral hemorrhage, neuropsychiatric symptoms, and nonhemorrhagic cerebral infarction. We report the case of a young woman who suffered a cerebral infarction after taking a single oral dose of PPA.", "entity": "Mental Disorders", "aliases": "Behavior Disorders Diagnosis Psychiatric Disorder Mental", "definition": "Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.\n    ", "id": "MESH:D001523"}
{"mention": "cerebral infarction", "mention_text": "Phenylpropanolamine (PPA), a synthetic sympathomimetic that is structurally similar to amphetamine, is available over the counter in anorectics, nasal congestants, and cold preparations. Its prolonged use or overuse has been associated with seizures, intracerebral hemorrhage, neuropsychiatric symptoms, and nonhemorrhagic cerebral infarction. We report the case of a young woman who suffered a cerebral infarction after taking a single oral dose of PPA.", "entity": "Cerebral Infarction", "aliases": "Anterior Choroidal Artery Infarction Cerebral Left Hemisphere Right Infarctions Subcortical Posterior", "definition": "The formation of an area of NECROSIS in the CEREBRUM caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., INFARCTION, ANTERIOR CEREBRAL ARTERY), and etiology (e.g., embolic infarction).\n    ", "id": "MESH:D002544"}
{"mention": "psoriasis", "mention_text": "Treatment of psoriasis with azathioprine.", "entity": "Psoriasis", "aliases": "Palmoplantaris Pustulosis Psoriases Psoriasis Pustular of Palms and Soles Palmaris et Plantaris", "definition": "A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis.\n    ", "id": "MESH:D011565"}
{"mention": "azathioprine", "mention_text": "Treatment of psoriasis with azathioprine.", "entity": "Azathioprine", "aliases": "Azathioprine Sodium Salt Sulfate Azothioprine Immuran Imuran Imurel", "definition": "An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance has been listed as a known carcinogen. (Merck Index, 11th ed)\n    ", "id": "MESH:D001379"}
{"mention": "Azathioprine", "mention_text": "Azathioprine treatment benefited 19 (66%) out of 29 patients suffering from severe psoriasis. Haematological complications were not troublesome and results of biochemical liver function tests remained normal. Minimal cholestasis was seen in two cases and portal fibrosis of a reversible degree in eight. Liver biopsies should be undertaken at regular intervals if azathioprine therapy is continued so that structural liver damage may be detected at an early and reversible stage.", "entity": "Azathioprine", "aliases": "Azathioprine Sodium Salt Sulfate Azothioprine Immuran Imuran Imurel", "definition": "An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance has been listed as a known carcinogen. (Merck Index, 11th ed)\n    ", "id": "MESH:D001379"}
{"mention": "psoriasis", "mention_text": "Azathioprine treatment benefited 19 (66%) out of 29 patients suffering from severe psoriasis. Haematological complications were not troublesome and results of biochemical liver function tests remained normal. Minimal cholestasis was seen in two cases and portal fibrosis of a reversible degree in eight. Liver biopsies should be undertaken at regular intervals if azathioprine therapy is continued so that structural liver damage may be detected at an early and reversible stage.", "entity": "Psoriasis", "aliases": "Palmoplantaris Pustulosis Psoriases Psoriasis Pustular of Palms and Soles Palmaris et Plantaris", "definition": "A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis.\n    ", "id": "MESH:D011565"}
{"mention": "cholestasis", "mention_text": "Azathioprine treatment benefited 19 (66%) out of 29 patients suffering from severe psoriasis. Haematological complications were not troublesome and results of biochemical liver function tests remained normal. Minimal cholestasis was seen in two cases and portal fibrosis of a reversible degree in eight. Liver biopsies should be undertaken at regular intervals if azathioprine therapy is continued so that structural liver damage may be detected at an early and reversible stage.", "entity": "Cholestasis", "aliases": "Bile Duct Obstruction Obstructions Biliary Stases Stasis Cholestases Cholestasis", "definition": "Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).\n    ", "id": "MESH:D002779"}
{"mention": "fibrosis", "mention_text": "Azathioprine treatment benefited 19 (66%) out of 29 patients suffering from severe psoriasis. Haematological complications were not troublesome and results of biochemical liver function tests remained normal. Minimal cholestasis was seen in two cases and portal fibrosis of a reversible degree in eight. Liver biopsies should be undertaken at regular intervals if azathioprine therapy is continued so that structural liver damage may be detected at an early and reversible stage.", "entity": "Fibrosis", "aliases": "Cirrhosis Fibroses Fibrosis", "definition": "Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.\n    ", "id": "MESH:D005355"}
{"mention": "azathioprine", "mention_text": "Azathioprine treatment benefited 19 (66%) out of 29 patients suffering from severe psoriasis. Haematological complications were not troublesome and results of biochemical liver function tests remained normal. Minimal cholestasis was seen in two cases and portal fibrosis of a reversible degree in eight. Liver biopsies should be undertaken at regular intervals if azathioprine therapy is continued so that structural liver damage may be detected at an early and reversible stage.", "entity": "Azathioprine", "aliases": "Azathioprine Sodium Salt Sulfate Azothioprine Immuran Imuran Imurel", "definition": "An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance has been listed as a known carcinogen. (Merck Index, 11th ed)\n    ", "id": "MESH:D001379"}
{"mention": "liver damage", "mention_text": "Azathioprine treatment benefited 19 (66%) out of 29 patients suffering from severe psoriasis. Haematological complications were not troublesome and results of biochemical liver function tests remained normal. Minimal cholestasis was seen in two cases and portal fibrosis of a reversible degree in eight. Liver biopsies should be undertaken at regular intervals if azathioprine therapy is continued so that structural liver damage may be detected at an early and reversible stage.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "lithium", "mention_text": "Maternal lithium and neonatal Ebstein's anomaly: evaluation with cross-sectional echocardiography.", "entity": "Lithium", "aliases": "Lithium", "definition": "An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.\n    ", "id": "MESH:D008094"}
{"mention": "Ebstein's anomaly", "mention_text": "Maternal lithium and neonatal Ebstein's anomaly: evaluation with cross-sectional echocardiography.", "entity": "Ebstein Anomaly", "aliases": "Anomaly Ebstein Ebstein's Malformation Familial Ebsteins", "definition": "A congenital heart defect characterized by downward or apical displacement of the TRICUSPID VALVE, usually with the septal and posterior leaflets being attached to the wall of the RIGHT VENTRICLE. It is characterized by a huge RIGHT ATRIUM and a small and less effective right ventricle.\n    ", "id": "MESH:D004437"}
{"mention": "lithium", "mention_text": "Cross-sectional echocardiography was used to evaluate two neonates whose mothers ingested lithium during pregnancy. In one infant, Ebstein's anomaly of the tricuspid valve was identified. In the other infant cross-sectional echocardiography provided reassurance that the infant did not have Ebstein's anomaly. Cross-sectional echocardiographic screening of newborns exposed to lithium during gestation can provide highly accurate, noninvasive assessment of the presence or absence of lithium-induced cardiac malformations.", "entity": "Lithium", "aliases": "Lithium", "definition": "An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.\n    ", "id": "MESH:D008094"}
{"mention": "Ebstein's anomaly", "mention_text": "Cross-sectional echocardiography was used to evaluate two neonates whose mothers ingested lithium during pregnancy. In one infant, Ebstein's anomaly of the tricuspid valve was identified. In the other infant cross-sectional echocardiography provided reassurance that the infant did not have Ebstein's anomaly. Cross-sectional echocardiographic screening of newborns exposed to lithium during gestation can provide highly accurate, noninvasive assessment of the presence or absence of lithium-induced cardiac malformations.", "entity": "Ebstein Anomaly", "aliases": "Anomaly Ebstein Ebstein's Malformation Familial Ebsteins", "definition": "A congenital heart defect characterized by downward or apical displacement of the TRICUSPID VALVE, usually with the septal and posterior leaflets being attached to the wall of the RIGHT VENTRICLE. It is characterized by a huge RIGHT ATRIUM and a small and less effective right ventricle.\n    ", "id": "MESH:D004437"}
{"mention": "cardiac malformations", "mention_text": "Cross-sectional echocardiography was used to evaluate two neonates whose mothers ingested lithium during pregnancy. In one infant, Ebstein's anomaly of the tricuspid valve was identified. In the other infant cross-sectional echocardiography provided reassurance that the infant did not have Ebstein's anomaly. Cross-sectional echocardiographic screening of newborns exposed to lithium during gestation can provide highly accurate, noninvasive assessment of the presence or absence of lithium-induced cardiac malformations.", "entity": "Heart Diseases", "aliases": "Cardiac Disease Diseases Heart", "definition": "Pathological conditions involving the HEART including its structural and functional abnormalities.\n    ", "id": "MESH:D006331"}
{"mention": "myocardial infarction", "mention_text": "Effects of training on the extent of experimental myocardial infarction in aging rats.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "isoproterenol", "mention_text": "The effects of exercise on the severity of isoproterenol-induced myocardial infarction were studied in female albino rats of 20,40,60 and 80 weeks of age. The rats were trained to swim for a specific duration and for a particular period. The occurrence of infarcts were confirmed by histological methods. Elevations in the serum GOT and GPT were maximum in the sedentary-isoproterenols and minimum in the exercise-controls. These changes in the serum transaminases were associated with corresponding depletions in the cardiac GOT and GPT. However, age was seen to interfere with the responses exhibited by the young and old rats. Studies dealing with myocardial infarction are more informative when dealt with age.", "entity": "Isoproterenol", "aliases": "4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol Euspiran Hydrochloride Isoproterenol Isadrin Isadrine Isoprenaline Isopropyl Noradrenaline Isopropylarterenol Isopropylnoradrenaline Isopropylnorepinephrine Sulfate Isuprel Izadrin Norisodrine Novodrin", "definition": "Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.\n    ", "id": "MESH:D007545"}
{"mention": "myocardial infarction", "mention_text": "The effects of exercise on the severity of isoproterenol-induced myocardial infarction were studied in female albino rats of 20,40,60 and 80 weeks of age. The rats were trained to swim for a specific duration and for a particular period. The occurrence of infarcts were confirmed by histological methods. Elevations in the serum GOT and GPT were maximum in the sedentary-isoproterenols and minimum in the exercise-controls. These changes in the serum transaminases were associated with corresponding depletions in the cardiac GOT and GPT. However, age was seen to interfere with the responses exhibited by the young and old rats. Studies dealing with myocardial infarction are more informative when dealt with age.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "infarcts", "mention_text": "The effects of exercise on the severity of isoproterenol-induced myocardial infarction were studied in female albino rats of 20,40,60 and 80 weeks of age. The rats were trained to swim for a specific duration and for a particular period. The occurrence of infarcts were confirmed by histological methods. Elevations in the serum GOT and GPT were maximum in the sedentary-isoproterenols and minimum in the exercise-controls. These changes in the serum transaminases were associated with corresponding depletions in the cardiac GOT and GPT. However, age was seen to interfere with the responses exhibited by the young and old rats. Studies dealing with myocardial infarction are more informative when dealt with age.", "entity": "Infarction", "aliases": "Infarction Infarctions", "definition": "Formation of an infarct, which is NECROSIS in tissue due to local ISCHEMIA resulting from obstruction of BLOOD CIRCULATION, most commonly by a THROMBUS or EMBOLUS.\n    ", "id": "MESH:D007238"}
{"mention": "isoproterenols", "mention_text": "The effects of exercise on the severity of isoproterenol-induced myocardial infarction were studied in female albino rats of 20,40,60 and 80 weeks of age. The rats were trained to swim for a specific duration and for a particular period. The occurrence of infarcts were confirmed by histological methods. Elevations in the serum GOT and GPT were maximum in the sedentary-isoproterenols and minimum in the exercise-controls. These changes in the serum transaminases were associated with corresponding depletions in the cardiac GOT and GPT. However, age was seen to interfere with the responses exhibited by the young and old rats. Studies dealing with myocardial infarction are more informative when dealt with age.", "entity": "Isoproterenol", "aliases": "4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol Euspiran Hydrochloride Isoproterenol Isadrin Isadrine Isoprenaline Isopropyl Noradrenaline Isopropylarterenol Isopropylnoradrenaline Isopropylnorepinephrine Sulfate Isuprel Izadrin Norisodrine Novodrin", "definition": "Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.\n    ", "id": "MESH:D007545"}
{"mention": "polyethylene glycol 400", "mention_text": "Effect of polyethylene glycol 400 on adriamycin toxicity in mice.", "entity": "Polyethylene Glycols", "aliases": "1000 PEG 3350 4000 Polyethylene Glycol 6000 Carbowax 400 600 Carbowax-400 Carbowax400 2000 Glycols Lauromacrogol Lauromacrogols Macrogol 300 Macrogols Miralax Miralaxs Oxide Oxides 8000 PEG-400 PEO PEO-400 Peg Polyethyleneoxide Polyethyleneoxides Polyox FRA Polyoxyethylene Polyoxyethylenes Tritons Vigilon", "definition": "Polymers of ETHYLENE OXIDE and water, and their ethers. They vary in consistency from liquid to solid depending on the molecular weight indicated by a number following the name. They are used as SURFACTANTS, dispersing agents, solvents, ointment and suppository bases, vehicles, and tablet excipients. Some specific groups are NONOXYNOLS, OCTOXYNOLS, and POLOXAMERS.\n    ", "id": "MESH:D011092"}
{"mention": "adriamycin", "mention_text": "Effect of polyethylene glycol 400 on adriamycin toxicity in mice.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "toxicity", "mention_text": "Effect of polyethylene glycol 400 on adriamycin toxicity in mice.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "polyethylene glycol 400", "mention_text": "The effect of a widely used organic solvent, polyethylene glycol 400 (PEG 400), on the toxic action of an acute or chronic treatment with adriamycin (ADR) was evaluated in mice. PEG 400 impressively decreased both acute high-dose and chronic low-dose-ADR-associated lethality. Light microscopic analysis showed a significant protection against ADR-induced cardiac morphological alterations. Such treatment did not diminish the ADR antitumor activity in L1210 leukemia and in Ehrlich ascites tumor.", "entity": "Polyethylene Glycols", "aliases": "1000 PEG 3350 4000 Polyethylene Glycol 6000 Carbowax 400 600 Carbowax-400 Carbowax400 2000 Glycols Lauromacrogol Lauromacrogols Macrogol 300 Macrogols Miralax Miralaxs Oxide Oxides 8000 PEG-400 PEO PEO-400 Peg Polyethyleneoxide Polyethyleneoxides Polyox FRA Polyoxyethylene Polyoxyethylenes Tritons Vigilon", "definition": "Polymers of ETHYLENE OXIDE and water, and their ethers. They vary in consistency from liquid to solid depending on the molecular weight indicated by a number following the name. They are used as SURFACTANTS, dispersing agents, solvents, ointment and suppository bases, vehicles, and tablet excipients. Some specific groups are NONOXYNOLS, OCTOXYNOLS, and POLOXAMERS.\n    ", "id": "MESH:D011092"}
{"mention": "PEG 400", "mention_text": "The effect of a widely used organic solvent, polyethylene glycol 400 (PEG 400), on the toxic action of an acute or chronic treatment with adriamycin (ADR) was evaluated in mice. PEG 400 impressively decreased both acute high-dose and chronic low-dose-ADR-associated lethality. Light microscopic analysis showed a significant protection against ADR-induced cardiac morphological alterations. Such treatment did not diminish the ADR antitumor activity in L1210 leukemia and in Ehrlich ascites tumor.", "entity": "Polyethylene Glycols", "aliases": "1000 PEG 3350 4000 Polyethylene Glycol 6000 Carbowax 400 600 Carbowax-400 Carbowax400 2000 Glycols Lauromacrogol Lauromacrogols Macrogol 300 Macrogols Miralax Miralaxs Oxide Oxides 8000 PEG-400 PEO PEO-400 Peg Polyethyleneoxide Polyethyleneoxides Polyox FRA Polyoxyethylene Polyoxyethylenes Tritons Vigilon", "definition": "Polymers of ETHYLENE OXIDE and water, and their ethers. They vary in consistency from liquid to solid depending on the molecular weight indicated by a number following the name. They are used as SURFACTANTS, dispersing agents, solvents, ointment and suppository bases, vehicles, and tablet excipients. Some specific groups are NONOXYNOLS, OCTOXYNOLS, and POLOXAMERS.\n    ", "id": "MESH:D011092"}
{"mention": "adriamycin", "mention_text": "The effect of a widely used organic solvent, polyethylene glycol 400 (PEG 400), on the toxic action of an acute or chronic treatment with adriamycin (ADR) was evaluated in mice. PEG 400 impressively decreased both acute high-dose and chronic low-dose-ADR-associated lethality. Light microscopic analysis showed a significant protection against ADR-induced cardiac morphological alterations. Such treatment did not diminish the ADR antitumor activity in L1210 leukemia and in Ehrlich ascites tumor.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "ADR", "mention_text": "The effect of a widely used organic solvent, polyethylene glycol 400 (PEG 400), on the toxic action of an acute or chronic treatment with adriamycin (ADR) was evaluated in mice. PEG 400 impressively decreased both acute high-dose and chronic low-dose-ADR-associated lethality. Light microscopic analysis showed a significant protection against ADR-induced cardiac morphological alterations. Such treatment did not diminish the ADR antitumor activity in L1210 leukemia and in Ehrlich ascites tumor.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "cardiac morphological alterations", "mention_text": "The effect of a widely used organic solvent, polyethylene glycol 400 (PEG 400), on the toxic action of an acute or chronic treatment with adriamycin (ADR) was evaluated in mice. PEG 400 impressively decreased both acute high-dose and chronic low-dose-ADR-associated lethality. Light microscopic analysis showed a significant protection against ADR-induced cardiac morphological alterations. Such treatment did not diminish the ADR antitumor activity in L1210 leukemia and in Ehrlich ascites tumor.", "entity": "Cardiomyopathies", "aliases": "Cardiomyopathies Primary Secondary Cardiomyopathy Disease Myocardial Diseases Myocardiopathies Myocardiopathy", "definition": "A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).\n    ", "id": "MESH:D009202"}
{"mention": "L1210 leukemia", "mention_text": "The effect of a widely used organic solvent, polyethylene glycol 400 (PEG 400), on the toxic action of an acute or chronic treatment with adriamycin (ADR) was evaluated in mice. PEG 400 impressively decreased both acute high-dose and chronic low-dose-ADR-associated lethality. Light microscopic analysis showed a significant protection against ADR-induced cardiac morphological alterations. Such treatment did not diminish the ADR antitumor activity in L1210 leukemia and in Ehrlich ascites tumor.", "entity": "Leukemia L1210", "aliases": "L 1210 Leukemia L1210", "definition": "", "id": "MESH:D007939"}
{"mention": "Ehrlich ascites tumor", "mention_text": "The effect of a widely used organic solvent, polyethylene glycol 400 (PEG 400), on the toxic action of an acute or chronic treatment with adriamycin (ADR) was evaluated in mice. PEG 400 impressively decreased both acute high-dose and chronic low-dose-ADR-associated lethality. Light microscopic analysis showed a significant protection against ADR-induced cardiac morphological alterations. Such treatment did not diminish the ADR antitumor activity in L1210 leukemia and in Ehrlich ascites tumor.", "entity": "Carcinoma, Ehrlich Tumor", "aliases": "Ascites Tumor Ehrlich Carcinoma", "definition": "A transplantable, poorly differentiated malignant tumor which appeared originally as a spontaneous breast carcinoma in a mouse. It grows in both solid and ascitic forms.\n    ", "id": "MESH:D002286"}
{"mention": "BCNU", "mention_text": "Intra-arterial BCNU chemotherapy for treatment of malignant gliomas of the central nervous system.", "entity": "Carmustine", "aliases": "1,3-Bis(2-Chloroethyl)-1-Nitrosourea BCNU BiCNU Carmustine FIVB N,N'-Bis(2-Chloroethyl)-N-Nitrosourea Nitrumon", "definition": "A cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other malignant neoplasms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p462) This substance may reasonably be anticipated to be a carcinogen according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed)\n    ", "id": "MESH:D002330"}
{"mention": "malignant gliomas", "mention_text": "Intra-arterial BCNU chemotherapy for treatment of malignant gliomas of the central nervous system.", "entity": "Glioma", "aliases": "Glial Cell Tumor Tumors Glioma Malignant Mixed Gliomas", "definition": "Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)\n    ", "id": "MESH:D005910"}
{"mention": "BCNU", "mention_text": "Because of the rapid systemic clearance of BCNU (1,3-bis-(2-chloroethyl)-1-nitrosourea), intra-arterial administration should provide a substantial advantage over intravenous administration for the treatment of malignant gliomas. Thirty-six patients were treated with BCNU every 6 to 8 weeks, either by transfemoral catheterization of the internal carotid or vertebral artery or through a fully implantable intracarotid drug delivery system, beginning with a dose of 200 mg/sq m body surface area. Twelve patients with Grade III or IV astrocytomas were treated after partial resection of the tumor without prior radiation therapy. After two to seven cycles of chemotherapy, nine patients showed a decrease in tumor size and surrounding edema on contrast-enhanced computerized tomography scans. In the nine responders, median duration of chemotherapy response from the time of operation was 25 weeks (range 12 to more than 91 weeks). The median duration of survival in the 12 patients was 54 weeks (range 21 to more than 156 weeks), with an 18-month survival rate of 42%. Twenty-four patients with recurrent Grade I to IV astrocytomas, whose resection and irradiation therapy had failed, received two to eight courses of intra-arterial BCNU therapy. Seventeen of these had a response or were stable for a median of 20 weeks (range 6 to more than 66 weeks). The catheterization procedure is safe, with no immediate complication in 111 infusions of BCNU. A delayed complication in nine patients has been unilateral loss of vision secondary to a retinal vasculitis. The frequency of visual loss decreased after the concentration of the ethanol diluent was lowered.", "entity": "Carmustine", "aliases": "1,3-Bis(2-Chloroethyl)-1-Nitrosourea BCNU BiCNU Carmustine FIVB N,N'-Bis(2-Chloroethyl)-N-Nitrosourea Nitrumon", "definition": "A cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other malignant neoplasms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p462) This substance may reasonably be anticipated to be a carcinogen according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed)\n    ", "id": "MESH:D002330"}
{"mention": "1,3-bis-(2-chloroethyl)-1-nitrosourea", "mention_text": "Because of the rapid systemic clearance of BCNU (1,3-bis-(2-chloroethyl)-1-nitrosourea), intra-arterial administration should provide a substantial advantage over intravenous administration for the treatment of malignant gliomas. Thirty-six patients were treated with BCNU every 6 to 8 weeks, either by transfemoral catheterization of the internal carotid or vertebral artery or through a fully implantable intracarotid drug delivery system, beginning with a dose of 200 mg/sq m body surface area. Twelve patients with Grade III or IV astrocytomas were treated after partial resection of the tumor without prior radiation therapy. After two to seven cycles of chemotherapy, nine patients showed a decrease in tumor size and surrounding edema on contrast-enhanced computerized tomography scans. In the nine responders, median duration of chemotherapy response from the time of operation was 25 weeks (range 12 to more than 91 weeks). The median duration of survival in the 12 patients was 54 weeks (range 21 to more than 156 weeks), with an 18-month survival rate of 42%. Twenty-four patients with recurrent Grade I to IV astrocytomas, whose resection and irradiation therapy had failed, received two to eight courses of intra-arterial BCNU therapy. Seventeen of these had a response or were stable for a median of 20 weeks (range 6 to more than 66 weeks). The catheterization procedure is safe, with no immediate complication in 111 infusions of BCNU. A delayed complication in nine patients has been unilateral loss of vision secondary to a retinal vasculitis. The frequency of visual loss decreased after the concentration of the ethanol diluent was lowered.", "entity": "Carmustine", "aliases": "1,3-Bis(2-Chloroethyl)-1-Nitrosourea BCNU BiCNU Carmustine FIVB N,N'-Bis(2-Chloroethyl)-N-Nitrosourea Nitrumon", "definition": "A cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other malignant neoplasms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p462) This substance may reasonably be anticipated to be a carcinogen according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed)\n    ", "id": "MESH:D002330"}
{"mention": "malignant gliomas", "mention_text": "Because of the rapid systemic clearance of BCNU (1,3-bis-(2-chloroethyl)-1-nitrosourea), intra-arterial administration should provide a substantial advantage over intravenous administration for the treatment of malignant gliomas. Thirty-six patients were treated with BCNU every 6 to 8 weeks, either by transfemoral catheterization of the internal carotid or vertebral artery or through a fully implantable intracarotid drug delivery system, beginning with a dose of 200 mg/sq m body surface area. Twelve patients with Grade III or IV astrocytomas were treated after partial resection of the tumor without prior radiation therapy. After two to seven cycles of chemotherapy, nine patients showed a decrease in tumor size and surrounding edema on contrast-enhanced computerized tomography scans. In the nine responders, median duration of chemotherapy response from the time of operation was 25 weeks (range 12 to more than 91 weeks). The median duration of survival in the 12 patients was 54 weeks (range 21 to more than 156 weeks), with an 18-month survival rate of 42%. Twenty-four patients with recurrent Grade I to IV astrocytomas, whose resection and irradiation therapy had failed, received two to eight courses of intra-arterial BCNU therapy. Seventeen of these had a response or were stable for a median of 20 weeks (range 6 to more than 66 weeks). The catheterization procedure is safe, with no immediate complication in 111 infusions of BCNU. A delayed complication in nine patients has been unilateral loss of vision secondary to a retinal vasculitis. The frequency of visual loss decreased after the concentration of the ethanol diluent was lowered.", "entity": "Glioma", "aliases": "Glial Cell Tumor Tumors Glioma Malignant Mixed Gliomas", "definition": "Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)\n    ", "id": "MESH:D005910"}
{"mention": "astrocytomas", "mention_text": "Because of the rapid systemic clearance of BCNU (1,3-bis-(2-chloroethyl)-1-nitrosourea), intra-arterial administration should provide a substantial advantage over intravenous administration for the treatment of malignant gliomas. Thirty-six patients were treated with BCNU every 6 to 8 weeks, either by transfemoral catheterization of the internal carotid or vertebral artery or through a fully implantable intracarotid drug delivery system, beginning with a dose of 200 mg/sq m body surface area. Twelve patients with Grade III or IV astrocytomas were treated after partial resection of the tumor without prior radiation therapy. After two to seven cycles of chemotherapy, nine patients showed a decrease in tumor size and surrounding edema on contrast-enhanced computerized tomography scans. In the nine responders, median duration of chemotherapy response from the time of operation was 25 weeks (range 12 to more than 91 weeks). The median duration of survival in the 12 patients was 54 weeks (range 21 to more than 156 weeks), with an 18-month survival rate of 42%. Twenty-four patients with recurrent Grade I to IV astrocytomas, whose resection and irradiation therapy had failed, received two to eight courses of intra-arterial BCNU therapy. Seventeen of these had a response or were stable for a median of 20 weeks (range 6 to more than 66 weeks). The catheterization procedure is safe, with no immediate complication in 111 infusions of BCNU. A delayed complication in nine patients has been unilateral loss of vision secondary to a retinal vasculitis. The frequency of visual loss decreased after the concentration of the ethanol diluent was lowered.", "entity": "Astrocytoma", "aliases": "Anaplastic Astrocytoma Astrocytomas Astrocytic Glioma Gliomas Cerebral Childhood Fibrillary Gemistocytic Grade I II III Intracranial Juvenile Pilocytic Protoplasmic Subependymal Giant Cell Astroglioma Astrogliomas Mixed Oligoastrocytoma Oligoastrocytomas", "definition": "Neoplasms of the brain and spinal cord derived from glial cells which vary from histologically benign forms to highly anaplastic and malignant tumors. Fibrillary astrocytomas are the most common type and may be classified in order of increasing malignancy (grades I through IV). In the first two decades of life, astrocytomas tend to originate in the cerebellar hemispheres; in adults, they most frequently arise in the cerebrum and frequently undergo malignant transformation. (From Devita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2013-7; Holland et al., Cancer Medicine, 3d ed, p1082)\n    ", "id": "MESH:D001254"}
{"mention": "tumor", "mention_text": "Because of the rapid systemic clearance of BCNU (1,3-bis-(2-chloroethyl)-1-nitrosourea), intra-arterial administration should provide a substantial advantage over intravenous administration for the treatment of malignant gliomas. Thirty-six patients were treated with BCNU every 6 to 8 weeks, either by transfemoral catheterization of the internal carotid or vertebral artery or through a fully implantable intracarotid drug delivery system, beginning with a dose of 200 mg/sq m body surface area. Twelve patients with Grade III or IV astrocytomas were treated after partial resection of the tumor without prior radiation therapy. After two to seven cycles of chemotherapy, nine patients showed a decrease in tumor size and surrounding edema on contrast-enhanced computerized tomography scans. In the nine responders, median duration of chemotherapy response from the time of operation was 25 weeks (range 12 to more than 91 weeks). The median duration of survival in the 12 patients was 54 weeks (range 21 to more than 156 weeks), with an 18-month survival rate of 42%. Twenty-four patients with recurrent Grade I to IV astrocytomas, whose resection and irradiation therapy had failed, received two to eight courses of intra-arterial BCNU therapy. Seventeen of these had a response or were stable for a median of 20 weeks (range 6 to more than 66 weeks). The catheterization procedure is safe, with no immediate complication in 111 infusions of BCNU. A delayed complication in nine patients has been unilateral loss of vision secondary to a retinal vasculitis. The frequency of visual loss decreased after the concentration of the ethanol diluent was lowered.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "edema", "mention_text": "Because of the rapid systemic clearance of BCNU (1,3-bis-(2-chloroethyl)-1-nitrosourea), intra-arterial administration should provide a substantial advantage over intravenous administration for the treatment of malignant gliomas. Thirty-six patients were treated with BCNU every 6 to 8 weeks, either by transfemoral catheterization of the internal carotid or vertebral artery or through a fully implantable intracarotid drug delivery system, beginning with a dose of 200 mg/sq m body surface area. Twelve patients with Grade III or IV astrocytomas were treated after partial resection of the tumor without prior radiation therapy. After two to seven cycles of chemotherapy, nine patients showed a decrease in tumor size and surrounding edema on contrast-enhanced computerized tomography scans. In the nine responders, median duration of chemotherapy response from the time of operation was 25 weeks (range 12 to more than 91 weeks). The median duration of survival in the 12 patients was 54 weeks (range 21 to more than 156 weeks), with an 18-month survival rate of 42%. Twenty-four patients with recurrent Grade I to IV astrocytomas, whose resection and irradiation therapy had failed, received two to eight courses of intra-arterial BCNU therapy. Seventeen of these had a response or were stable for a median of 20 weeks (range 6 to more than 66 weeks). The catheterization procedure is safe, with no immediate complication in 111 infusions of BCNU. A delayed complication in nine patients has been unilateral loss of vision secondary to a retinal vasculitis. The frequency of visual loss decreased after the concentration of the ethanol diluent was lowered.", "entity": "Edema", "aliases": "Anasarca Dropsy Edema Hydrops", "definition": "Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE.\n    ", "id": "MESH:D004487"}
{"mention": "loss of vision", "mention_text": "Because of the rapid systemic clearance of BCNU (1,3-bis-(2-chloroethyl)-1-nitrosourea), intra-arterial administration should provide a substantial advantage over intravenous administration for the treatment of malignant gliomas. Thirty-six patients were treated with BCNU every 6 to 8 weeks, either by transfemoral catheterization of the internal carotid or vertebral artery or through a fully implantable intracarotid drug delivery system, beginning with a dose of 200 mg/sq m body surface area. Twelve patients with Grade III or IV astrocytomas were treated after partial resection of the tumor without prior radiation therapy. After two to seven cycles of chemotherapy, nine patients showed a decrease in tumor size and surrounding edema on contrast-enhanced computerized tomography scans. In the nine responders, median duration of chemotherapy response from the time of operation was 25 weeks (range 12 to more than 91 weeks). The median duration of survival in the 12 patients was 54 weeks (range 21 to more than 156 weeks), with an 18-month survival rate of 42%. Twenty-four patients with recurrent Grade I to IV astrocytomas, whose resection and irradiation therapy had failed, received two to eight courses of intra-arterial BCNU therapy. Seventeen of these had a response or were stable for a median of 20 weeks (range 6 to more than 66 weeks). The catheterization procedure is safe, with no immediate complication in 111 infusions of BCNU. A delayed complication in nine patients has been unilateral loss of vision secondary to a retinal vasculitis. The frequency of visual loss decreased after the concentration of the ethanol diluent was lowered.", "entity": "Vision Disorders", "aliases": "Blindness Day Disabilities Vision Disability Disorder Visual Disorders Hemeralopia Hemeralopias Impairment Impairments Macropsia Macropsias Metamorphopsia Metamorphopsias Micropsia Micropsias", "definition": "Visual impairments limiting one or more of the basic functions of the eye: visual acuity, dark adaptation, color vision, or peripheral vision. These may result from EYE DISEASES; OPTIC NERVE DISEASES; VISUAL PATHWAY diseases; OCCIPITAL LOBE diseases; OCULAR MOTILITY DISORDERS; and other conditions (From Newell, Ophthalmology: Principles and Concepts, 7th ed, p132).\n    ", "id": "MESH:D014786"}
{"mention": "retinal vasculitis", "mention_text": "Because of the rapid systemic clearance of BCNU (1,3-bis-(2-chloroethyl)-1-nitrosourea), intra-arterial administration should provide a substantial advantage over intravenous administration for the treatment of malignant gliomas. Thirty-six patients were treated with BCNU every 6 to 8 weeks, either by transfemoral catheterization of the internal carotid or vertebral artery or through a fully implantable intracarotid drug delivery system, beginning with a dose of 200 mg/sq m body surface area. Twelve patients with Grade III or IV astrocytomas were treated after partial resection of the tumor without prior radiation therapy. After two to seven cycles of chemotherapy, nine patients showed a decrease in tumor size and surrounding edema on contrast-enhanced computerized tomography scans. In the nine responders, median duration of chemotherapy response from the time of operation was 25 weeks (range 12 to more than 91 weeks). The median duration of survival in the 12 patients was 54 weeks (range 21 to more than 156 weeks), with an 18-month survival rate of 42%. Twenty-four patients with recurrent Grade I to IV astrocytomas, whose resection and irradiation therapy had failed, received two to eight courses of intra-arterial BCNU therapy. Seventeen of these had a response or were stable for a median of 20 weeks (range 6 to more than 66 weeks). The catheterization procedure is safe, with no immediate complication in 111 infusions of BCNU. A delayed complication in nine patients has been unilateral loss of vision secondary to a retinal vasculitis. The frequency of visual loss decreased after the concentration of the ethanol diluent was lowered.", "entity": "Retinal Vasculitis", "aliases": "Retinal Vasculitis", "definition": "Inflammation of the retinal vasculature with various causes including infectious disease; LUPUS ERYTHEMATOSUS, SYSTEMIC; MULTIPLE SCLEROSIS; BEHCET SYNDROME; and CHORIORETINITIS.\n    ", "id": "MESH:D031300"}
{"mention": "visual loss", "mention_text": "Because of the rapid systemic clearance of BCNU (1,3-bis-(2-chloroethyl)-1-nitrosourea), intra-arterial administration should provide a substantial advantage over intravenous administration for the treatment of malignant gliomas. Thirty-six patients were treated with BCNU every 6 to 8 weeks, either by transfemoral catheterization of the internal carotid or vertebral artery or through a fully implantable intracarotid drug delivery system, beginning with a dose of 200 mg/sq m body surface area. Twelve patients with Grade III or IV astrocytomas were treated after partial resection of the tumor without prior radiation therapy. After two to seven cycles of chemotherapy, nine patients showed a decrease in tumor size and surrounding edema on contrast-enhanced computerized tomography scans. In the nine responders, median duration of chemotherapy response from the time of operation was 25 weeks (range 12 to more than 91 weeks). The median duration of survival in the 12 patients was 54 weeks (range 21 to more than 156 weeks), with an 18-month survival rate of 42%. Twenty-four patients with recurrent Grade I to IV astrocytomas, whose resection and irradiation therapy had failed, received two to eight courses of intra-arterial BCNU therapy. Seventeen of these had a response or were stable for a median of 20 weeks (range 6 to more than 66 weeks). The catheterization procedure is safe, with no immediate complication in 111 infusions of BCNU. A delayed complication in nine patients has been unilateral loss of vision secondary to a retinal vasculitis. The frequency of visual loss decreased after the concentration of the ethanol diluent was lowered.", "entity": "Vision Disorders", "aliases": "Blindness Day Disabilities Vision Disability Disorder Visual Disorders Hemeralopia Hemeralopias Impairment Impairments Macropsia Macropsias Metamorphopsia Metamorphopsias Micropsia Micropsias", "definition": "Visual impairments limiting one or more of the basic functions of the eye: visual acuity, dark adaptation, color vision, or peripheral vision. These may result from EYE DISEASES; OPTIC NERVE DISEASES; VISUAL PATHWAY diseases; OCCIPITAL LOBE diseases; OCULAR MOTILITY DISORDERS; and other conditions (From Newell, Ophthalmology: Principles and Concepts, 7th ed, p132).\n    ", "id": "MESH:D014786"}
{"mention": "ethanol", "mention_text": "Because of the rapid systemic clearance of BCNU (1,3-bis-(2-chloroethyl)-1-nitrosourea), intra-arterial administration should provide a substantial advantage over intravenous administration for the treatment of malignant gliomas. Thirty-six patients were treated with BCNU every 6 to 8 weeks, either by transfemoral catheterization of the internal carotid or vertebral artery or through a fully implantable intracarotid drug delivery system, beginning with a dose of 200 mg/sq m body surface area. Twelve patients with Grade III or IV astrocytomas were treated after partial resection of the tumor without prior radiation therapy. After two to seven cycles of chemotherapy, nine patients showed a decrease in tumor size and surrounding edema on contrast-enhanced computerized tomography scans. In the nine responders, median duration of chemotherapy response from the time of operation was 25 weeks (range 12 to more than 91 weeks). The median duration of survival in the 12 patients was 54 weeks (range 21 to more than 156 weeks), with an 18-month survival rate of 42%. Twenty-four patients with recurrent Grade I to IV astrocytomas, whose resection and irradiation therapy had failed, received two to eight courses of intra-arterial BCNU therapy. Seventeen of these had a response or were stable for a median of 20 weeks (range 6 to more than 66 weeks). The catheterization procedure is safe, with no immediate complication in 111 infusions of BCNU. A delayed complication in nine patients has been unilateral loss of vision secondary to a retinal vasculitis. The frequency of visual loss decreased after the concentration of the ethanol diluent was lowered.", "entity": "Ethanol", "aliases": "Absolute Alcohol Ethyl Grain Ethanol", "definition": "A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.\n    ", "id": "MESH:D000431"}
{"mention": "noradrenaline", "mention_text": "Blood pressure response to chronic low-dose intrarenal noradrenaline infusion in conscious rats.", "entity": "Norepinephrine", "aliases": "Abbott Brand of Levophed Bitartrate Arterenol Aventis Norepinephrine Hydrochloride Noradrenaline Levarterenol Levonor Levonorepinephrine Noradrénaline tartrate renaudin Norepinephrin d-Tartrate (1:1) (+)-Isomer (+,-)-Isomer l-Tartrate Monohydrate (1:2) Renaudin", "definition": "Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.\n    ", "id": "MESH:D009638"}
{"mention": "Sodium chloride", "mention_text": "Sodium chloride solution (0.9%) or noradrenaline in doses of 4, 12 and 36 micrograms h-1 kg-1 was infused for five consecutive days, either intrarenally (by a new technique) or intravenously into rats with one kidney removed. Intrarenal infusion of noradrenaline caused hypertension at doses which did not do so when infused intravenously. Intrarenal compared with intravenous infusion of noradrenaline caused higher plasma noradrenaline concentrations and a shift of the plasma noradrenaline concentration-blood pressure effect curve towards lower plasma noradrenaline levels. These results suggest that hypertension after chronic intrarenal noradrenaline infusion is produced by relatively higher levels of circulating noradrenaline and by triggering of an additional intrarenal pressor mechanism.", "entity": "Sodium Chloride", "aliases": "Saline Solution Sodium Chloride (22)Na (24)NaCl", "definition": "A ubiquitous sodium salt that is commonly used to season food.\n    ", "id": "MESH:D012965"}
{"mention": "noradrenaline", "mention_text": "Sodium chloride solution (0.9%) or noradrenaline in doses of 4, 12 and 36 micrograms h-1 kg-1 was infused for five consecutive days, either intrarenally (by a new technique) or intravenously into rats with one kidney removed. Intrarenal infusion of noradrenaline caused hypertension at doses which did not do so when infused intravenously. Intrarenal compared with intravenous infusion of noradrenaline caused higher plasma noradrenaline concentrations and a shift of the plasma noradrenaline concentration-blood pressure effect curve towards lower plasma noradrenaline levels. These results suggest that hypertension after chronic intrarenal noradrenaline infusion is produced by relatively higher levels of circulating noradrenaline and by triggering of an additional intrarenal pressor mechanism.", "entity": "Norepinephrine", "aliases": "Abbott Brand of Levophed Bitartrate Arterenol Aventis Norepinephrine Hydrochloride Noradrenaline Levarterenol Levonor Levonorepinephrine Noradrénaline tartrate renaudin Norepinephrin d-Tartrate (1:1) (+)-Isomer (+,-)-Isomer l-Tartrate Monohydrate (1:2) Renaudin", "definition": "Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.\n    ", "id": "MESH:D009638"}
{"mention": "hypertension", "mention_text": "Sodium chloride solution (0.9%) or noradrenaline in doses of 4, 12 and 36 micrograms h-1 kg-1 was infused for five consecutive days, either intrarenally (by a new technique) or intravenously into rats with one kidney removed. Intrarenal infusion of noradrenaline caused hypertension at doses which did not do so when infused intravenously. Intrarenal compared with intravenous infusion of noradrenaline caused higher plasma noradrenaline concentrations and a shift of the plasma noradrenaline concentration-blood pressure effect curve towards lower plasma noradrenaline levels. These results suggest that hypertension after chronic intrarenal noradrenaline infusion is produced by relatively higher levels of circulating noradrenaline and by triggering of an additional intrarenal pressor mechanism.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "cimetidine", "mention_text": "Age and renal clearance of cimetidine.", "entity": "Cimetidine", "aliases": "Altramet Biomet Biomet400 Cimetidine HCl Hydrochloride Eureceptor Histodil N-Cyano-N'-methyl-N''-(2-(((5-methyl-1H-imidazol-4-yl)methyl)thio)ethyl)guanidine SK&F 92334 SK&F-92334 SK&F92334 SKF SKF-92334 SKF92334 Tagamet", "definition": "A histamine congener, it competitively inhibits HISTAMINE binding to HISTAMINE H2 RECEPTORS. Cimetidine has a range of pharmacological actions. It inhibits GASTRIC ACID secretion, as well as PEPSIN and GASTRIN output.\n    ", "id": "MESH:D002927"}
{"mention": "cimetidine", "mention_text": "In 35 patients (ages 20 to 86 yr) receiving cimetidine therapeutically two serum samples and all urine formed in the interim were collected for analysis of cimetidine by high-pressure liquid chromatography and for creatinine. Cimetidine clearance decreased with age. The extrapolated 6-hr serum concentration of cimetidine per unit dose, after intravenous cimetidine, increased with age of the patients. The ratio of cimetidine clearance to creatinine clearance (Rc) averaged 4.8 +/- 2.0, indicating net tubular secretion for cimetidine. Rc seemed to be independent of age and decreased with increasing serum concentration of cimetidine, suggesting that secretion of cimetidine is a saturable process. There was only one case of dementia possibly due to cimetidine (with a drug level of 1.9 microgram/ml 6 hr after a dose) in a group of 13 patients without liver or kidney disease who had cimetidine levels above 1.25 microgram/ml. Thus, high cimetidine levels alone do not always induce dementia.", "entity": "Cimetidine", "aliases": "Altramet Biomet Biomet400 Cimetidine HCl Hydrochloride Eureceptor Histodil N-Cyano-N'-methyl-N''-(2-(((5-methyl-1H-imidazol-4-yl)methyl)thio)ethyl)guanidine SK&F 92334 SK&F-92334 SK&F92334 SKF SKF-92334 SKF92334 Tagamet", "definition": "A histamine congener, it competitively inhibits HISTAMINE binding to HISTAMINE H2 RECEPTORS. Cimetidine has a range of pharmacological actions. It inhibits GASTRIC ACID secretion, as well as PEPSIN and GASTRIN output.\n    ", "id": "MESH:D002927"}
{"mention": "creatinine", "mention_text": "In 35 patients (ages 20 to 86 yr) receiving cimetidine therapeutically two serum samples and all urine formed in the interim were collected for analysis of cimetidine by high-pressure liquid chromatography and for creatinine. Cimetidine clearance decreased with age. The extrapolated 6-hr serum concentration of cimetidine per unit dose, after intravenous cimetidine, increased with age of the patients. The ratio of cimetidine clearance to creatinine clearance (Rc) averaged 4.8 +/- 2.0, indicating net tubular secretion for cimetidine. Rc seemed to be independent of age and decreased with increasing serum concentration of cimetidine, suggesting that secretion of cimetidine is a saturable process. There was only one case of dementia possibly due to cimetidine (with a drug level of 1.9 microgram/ml 6 hr after a dose) in a group of 13 patients without liver or kidney disease who had cimetidine levels above 1.25 microgram/ml. Thus, high cimetidine levels alone do not always induce dementia.", "entity": "Creatinine", "aliases": "Creatinine Sulfate Salt Krebiozen", "definition": "", "id": "MESH:D003404"}
{"mention": "Cimetidine", "mention_text": "In 35 patients (ages 20 to 86 yr) receiving cimetidine therapeutically two serum samples and all urine formed in the interim were collected for analysis of cimetidine by high-pressure liquid chromatography and for creatinine. Cimetidine clearance decreased with age. The extrapolated 6-hr serum concentration of cimetidine per unit dose, after intravenous cimetidine, increased with age of the patients. The ratio of cimetidine clearance to creatinine clearance (Rc) averaged 4.8 +/- 2.0, indicating net tubular secretion for cimetidine. Rc seemed to be independent of age and decreased with increasing serum concentration of cimetidine, suggesting that secretion of cimetidine is a saturable process. There was only one case of dementia possibly due to cimetidine (with a drug level of 1.9 microgram/ml 6 hr after a dose) in a group of 13 patients without liver or kidney disease who had cimetidine levels above 1.25 microgram/ml. Thus, high cimetidine levels alone do not always induce dementia.", "entity": "Cimetidine", "aliases": "Altramet Biomet Biomet400 Cimetidine HCl Hydrochloride Eureceptor Histodil N-Cyano-N'-methyl-N''-(2-(((5-methyl-1H-imidazol-4-yl)methyl)thio)ethyl)guanidine SK&F 92334 SK&F-92334 SK&F92334 SKF SKF-92334 SKF92334 Tagamet", "definition": "A histamine congener, it competitively inhibits HISTAMINE binding to HISTAMINE H2 RECEPTORS. Cimetidine has a range of pharmacological actions. It inhibits GASTRIC ACID secretion, as well as PEPSIN and GASTRIN output.\n    ", "id": "MESH:D002927"}
{"mention": "dementia", "mention_text": "In 35 patients (ages 20 to 86 yr) receiving cimetidine therapeutically two serum samples and all urine formed in the interim were collected for analysis of cimetidine by high-pressure liquid chromatography and for creatinine. Cimetidine clearance decreased with age. The extrapolated 6-hr serum concentration of cimetidine per unit dose, after intravenous cimetidine, increased with age of the patients. The ratio of cimetidine clearance to creatinine clearance (Rc) averaged 4.8 +/- 2.0, indicating net tubular secretion for cimetidine. Rc seemed to be independent of age and decreased with increasing serum concentration of cimetidine, suggesting that secretion of cimetidine is a saturable process. There was only one case of dementia possibly due to cimetidine (with a drug level of 1.9 microgram/ml 6 hr after a dose) in a group of 13 patients without liver or kidney disease who had cimetidine levels above 1.25 microgram/ml. Thus, high cimetidine levels alone do not always induce dementia.", "entity": "Dementia", "aliases": "Amentia Amentias Dementia Familial Dementias Senile Paranoid", "definition": "An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness.\n    ", "id": "MESH:D003704"}
{"mention": "kidney disease", "mention_text": "In 35 patients (ages 20 to 86 yr) receiving cimetidine therapeutically two serum samples and all urine formed in the interim were collected for analysis of cimetidine by high-pressure liquid chromatography and for creatinine. Cimetidine clearance decreased with age. The extrapolated 6-hr serum concentration of cimetidine per unit dose, after intravenous cimetidine, increased with age of the patients. The ratio of cimetidine clearance to creatinine clearance (Rc) averaged 4.8 +/- 2.0, indicating net tubular secretion for cimetidine. Rc seemed to be independent of age and decreased with increasing serum concentration of cimetidine, suggesting that secretion of cimetidine is a saturable process. There was only one case of dementia possibly due to cimetidine (with a drug level of 1.9 microgram/ml 6 hr after a dose) in a group of 13 patients without liver or kidney disease who had cimetidine levels above 1.25 microgram/ml. Thus, high cimetidine levels alone do not always induce dementia.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "clear cell adenocarcinoma", "mention_text": "Development of clear cell adenocarcinoma in DES-exposed offspring under observation.", "entity": "Adenocarcinoma, Clear Cell", "aliases": "Adenocarcinoma Clear Cell Adenocarcinomas", "definition": "An adenocarcinoma characterized by the presence of varying combinations of clear and hobnail-shaped tumor cells. There are three predominant patterns described as tubulocystic, solid, and papillary. These tumors, usually located in the female reproductive organs, have been seen more frequently in young women since 1970 as a result of the association with intrauterine exposure to diethylstilbestrol. (From Holland et al., Cancer Medicine, 3d ed)\n    ", "id": "MESH:D018262"}
{"mention": "DES", "mention_text": "Development of clear cell adenocarcinoma in DES-exposed offspring under observation.", "entity": "Diethylstilbestrol", "aliases": "APS Brand of Diethylstilbestrol Agostilben Apstil Co Pharma Co-Pharma (Z)-Isomer Disodium Salt Distilbène Estrogen Stilbene Gerda Stilbestrol Tampovagan", "definition": "A synthetic nonsteroidal estrogen used in the treatment of menopausal and postmenopausal disorders. It was also used formerly as a growth promoter in animals. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), diethylstilbestrol has been listed as a known carcinogen. (Merck, 11th ed)\n    ", "id": "MESH:D004054"}
{"mention": "clear cell adenocarcinoma", "mention_text": "Two cases of clear cell adenocarcinoma of the vagina detected at follow-up in young women exposed in utero to diethylstilbestrol are reported. One patient, aged 23, had been followed for 2 years before carcinoma was diagnosed; the second patient, aged 22, had been seen on a regular basis for 5 years, 8 months. In both instances, suspicion of the presence of carcinoma was aroused by the palpation of a small nodule in the vaginal fornix. Hysterosalpingography was performed on both patients and, in 1 instance, an abnormal x-ray film was reflected by the gross appearance of the uterine cavity found in the surgical specimen.", "entity": "Adenocarcinoma, Clear Cell", "aliases": "Adenocarcinoma Clear Cell Adenocarcinomas", "definition": "An adenocarcinoma characterized by the presence of varying combinations of clear and hobnail-shaped tumor cells. There are three predominant patterns described as tubulocystic, solid, and papillary. These tumors, usually located in the female reproductive organs, have been seen more frequently in young women since 1970 as a result of the association with intrauterine exposure to diethylstilbestrol. (From Holland et al., Cancer Medicine, 3d ed)\n    ", "id": "MESH:D018262"}
{"mention": "adenocarcinoma of the vagina", "mention_text": "Two cases of clear cell adenocarcinoma of the vagina detected at follow-up in young women exposed in utero to diethylstilbestrol are reported. One patient, aged 23, had been followed for 2 years before carcinoma was diagnosed; the second patient, aged 22, had been seen on a regular basis for 5 years, 8 months. In both instances, suspicion of the presence of carcinoma was aroused by the palpation of a small nodule in the vaginal fornix. Hysterosalpingography was performed on both patients and, in 1 instance, an abnormal x-ray film was reflected by the gross appearance of the uterine cavity found in the surgical specimen.", "entity": "Vaginal Neoplasms", "aliases": "Cancer of Vagina the Vaginal Cancers Neoplasm Neoplasms", "definition": "Tumors or cancer of the VAGINA.\n    ", "id": "MESH:D014625"}
{"mention": "diethylstilbestrol", "mention_text": "Two cases of clear cell adenocarcinoma of the vagina detected at follow-up in young women exposed in utero to diethylstilbestrol are reported. One patient, aged 23, had been followed for 2 years before carcinoma was diagnosed; the second patient, aged 22, had been seen on a regular basis for 5 years, 8 months. In both instances, suspicion of the presence of carcinoma was aroused by the palpation of a small nodule in the vaginal fornix. Hysterosalpingography was performed on both patients and, in 1 instance, an abnormal x-ray film was reflected by the gross appearance of the uterine cavity found in the surgical specimen.", "entity": "Diethylstilbestrol", "aliases": "APS Brand of Diethylstilbestrol Agostilben Apstil Co Pharma Co-Pharma (Z)-Isomer Disodium Salt Distilbène Estrogen Stilbene Gerda Stilbestrol Tampovagan", "definition": "A synthetic nonsteroidal estrogen used in the treatment of menopausal and postmenopausal disorders. It was also used formerly as a growth promoter in animals. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), diethylstilbestrol has been listed as a known carcinogen. (Merck, 11th ed)\n    ", "id": "MESH:D004054"}
{"mention": "carcinoma", "mention_text": "Two cases of clear cell adenocarcinoma of the vagina detected at follow-up in young women exposed in utero to diethylstilbestrol are reported. One patient, aged 23, had been followed for 2 years before carcinoma was diagnosed; the second patient, aged 22, had been seen on a regular basis for 5 years, 8 months. In both instances, suspicion of the presence of carcinoma was aroused by the palpation of a small nodule in the vaginal fornix. Hysterosalpingography was performed on both patients and, in 1 instance, an abnormal x-ray film was reflected by the gross appearance of the uterine cavity found in the surgical specimen.", "entity": "Carcinoma", "aliases": "Anaplastic Carcinoma Carcinomas Spindle Cell Spindle-Cell Undifferentiated Carcinomatoses Carcinomatosis Epithelial Neoplasm Malignant Neoplasms Tumor Tumors Epithelioma Epitheliomas", "definition": "A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm but is often wrongly used as a synonym for \"cancer.\" (From Dorland, 27th ed)\n    ", "id": "MESH:D002277"}
{"mention": "Phenobarbitone", "mention_text": "Phenobarbitone-induced enlargement of the liver in the rat: its relationship to carbon tetrachloride-induced cirrhosis.", "entity": "Phenobarbital", "aliases": "Acid Phenylethylbarbituric Gardenal Hysteps Luminal Monosodium Salt Phenobarbital Phenemal Sodium Phenobarbitone Phenylbarbital", "definition": "A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.\n    ", "id": "MESH:D010634"}
{"mention": "enlargement of the liver", "mention_text": "Phenobarbitone-induced enlargement of the liver in the rat: its relationship to carbon tetrachloride-induced cirrhosis.", "entity": "Hepatomegaly", "aliases": "Enlarged Liver Hepatomegaly", "definition": "Enlargement of the liver.\n    ", "id": "MESH:D006529"}
{"mention": "carbon tetrachloride", "mention_text": "Phenobarbitone-induced enlargement of the liver in the rat: its relationship to carbon tetrachloride-induced cirrhosis.", "entity": "Carbon Tetrachloride", "aliases": "Carbon Tetrachloride Tetrachloromethane", "definition": "A solvent for oils, fats, lacquers, varnishes, rubber waxes, and resins, and a starting material in the manufacturing of organic compounds. Poisoning by inhalation, ingestion or skin absorption is possible and may be fatal. (Merck Index, 11th ed)\n    ", "id": "MESH:D002251"}
{"mention": "cirrhosis", "mention_text": "Phenobarbitone-induced enlargement of the liver in the rat: its relationship to carbon tetrachloride-induced cirrhosis.", "entity": "Fibrosis", "aliases": "Cirrhosis Fibroses Fibrosis", "definition": "Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.\n    ", "id": "MESH:D005355"}
{"mention": "cirrhosis of the liver", "mention_text": "The yield of severe cirrhosis of the liver (defined as a shrunken finely nodular liver with micronodular histology, ascites greater than 30 ml, plasma albumin less than 2.2 g/dl, splenomegaly 2-3 times normal, and testicular atrophy approximately half normal weight) after 12 doses of carbon tetrachloride given intragastrically in the phenobarbitone-primed rat was increased from 25% to 56% by giving the initial \"calibrating\" dose of carbon tetrachloride at the peak of the phenobarbitone-induced enlargement of the liver. At this point it was assumed that the cytochrome P450/CCl4 toxic state was both maximal and stable. The optimal rat size to begin phenobarbitone was determined as 100 g, and this size as a group had a mean maximum relative liver weight increase 47% greater than normal rats of the same body weight. The optimal time for the initial dose of carbon tetrachloride was after 14 days on phenobarbitone.", "entity": "Liver Cirrhosis", "aliases": "Cirrhoses Hepatic Liver Cirrhosis Fibroses Fibrosis", "definition": "Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules.\n    ", "id": "MESH:D008103"}
{"mention": "ascites", "mention_text": "The yield of severe cirrhosis of the liver (defined as a shrunken finely nodular liver with micronodular histology, ascites greater than 30 ml, plasma albumin less than 2.2 g/dl, splenomegaly 2-3 times normal, and testicular atrophy approximately half normal weight) after 12 doses of carbon tetrachloride given intragastrically in the phenobarbitone-primed rat was increased from 25% to 56% by giving the initial \"calibrating\" dose of carbon tetrachloride at the peak of the phenobarbitone-induced enlargement of the liver. At this point it was assumed that the cytochrome P450/CCl4 toxic state was both maximal and stable. The optimal rat size to begin phenobarbitone was determined as 100 g, and this size as a group had a mean maximum relative liver weight increase 47% greater than normal rats of the same body weight. The optimal time for the initial dose of carbon tetrachloride was after 14 days on phenobarbitone.", "entity": "Ascites", "aliases": "Ascites", "definition": "Accumulation or retention of free fluid within the peritoneal cavity.\n    ", "id": "MESH:D001201"}
{"mention": "splenomegaly", "mention_text": "The yield of severe cirrhosis of the liver (defined as a shrunken finely nodular liver with micronodular histology, ascites greater than 30 ml, plasma albumin less than 2.2 g/dl, splenomegaly 2-3 times normal, and testicular atrophy approximately half normal weight) after 12 doses of carbon tetrachloride given intragastrically in the phenobarbitone-primed rat was increased from 25% to 56% by giving the initial \"calibrating\" dose of carbon tetrachloride at the peak of the phenobarbitone-induced enlargement of the liver. At this point it was assumed that the cytochrome P450/CCl4 toxic state was both maximal and stable. The optimal rat size to begin phenobarbitone was determined as 100 g, and this size as a group had a mean maximum relative liver weight increase 47% greater than normal rats of the same body weight. The optimal time for the initial dose of carbon tetrachloride was after 14 days on phenobarbitone.", "entity": "Splenomegaly", "aliases": "Enlarged Spleen Splenomegaly", "definition": "Enlargement of the spleen.\n    ", "id": "MESH:D013163"}
{"mention": "atrophy", "mention_text": "The yield of severe cirrhosis of the liver (defined as a shrunken finely nodular liver with micronodular histology, ascites greater than 30 ml, plasma albumin less than 2.2 g/dl, splenomegaly 2-3 times normal, and testicular atrophy approximately half normal weight) after 12 doses of carbon tetrachloride given intragastrically in the phenobarbitone-primed rat was increased from 25% to 56% by giving the initial \"calibrating\" dose of carbon tetrachloride at the peak of the phenobarbitone-induced enlargement of the liver. At this point it was assumed that the cytochrome P450/CCl4 toxic state was both maximal and stable. The optimal rat size to begin phenobarbitone was determined as 100 g, and this size as a group had a mean maximum relative liver weight increase 47% greater than normal rats of the same body weight. The optimal time for the initial dose of carbon tetrachloride was after 14 days on phenobarbitone.", "entity": "Atrophy", "aliases": "Atrophies Atrophy", "definition": "Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes.\n    ", "id": "MESH:D001284"}
{"mention": "carbon tetrachloride", "mention_text": "The yield of severe cirrhosis of the liver (defined as a shrunken finely nodular liver with micronodular histology, ascites greater than 30 ml, plasma albumin less than 2.2 g/dl, splenomegaly 2-3 times normal, and testicular atrophy approximately half normal weight) after 12 doses of carbon tetrachloride given intragastrically in the phenobarbitone-primed rat was increased from 25% to 56% by giving the initial \"calibrating\" dose of carbon tetrachloride at the peak of the phenobarbitone-induced enlargement of the liver. At this point it was assumed that the cytochrome P450/CCl4 toxic state was both maximal and stable. The optimal rat size to begin phenobarbitone was determined as 100 g, and this size as a group had a mean maximum relative liver weight increase 47% greater than normal rats of the same body weight. The optimal time for the initial dose of carbon tetrachloride was after 14 days on phenobarbitone.", "entity": "Carbon Tetrachloride", "aliases": "Carbon Tetrachloride Tetrachloromethane", "definition": "A solvent for oils, fats, lacquers, varnishes, rubber waxes, and resins, and a starting material in the manufacturing of organic compounds. Poisoning by inhalation, ingestion or skin absorption is possible and may be fatal. (Merck Index, 11th ed)\n    ", "id": "MESH:D002251"}
{"mention": "phenobarbitone", "mention_text": "The yield of severe cirrhosis of the liver (defined as a shrunken finely nodular liver with micronodular histology, ascites greater than 30 ml, plasma albumin less than 2.2 g/dl, splenomegaly 2-3 times normal, and testicular atrophy approximately half normal weight) after 12 doses of carbon tetrachloride given intragastrically in the phenobarbitone-primed rat was increased from 25% to 56% by giving the initial \"calibrating\" dose of carbon tetrachloride at the peak of the phenobarbitone-induced enlargement of the liver. At this point it was assumed that the cytochrome P450/CCl4 toxic state was both maximal and stable. The optimal rat size to begin phenobarbitone was determined as 100 g, and this size as a group had a mean maximum relative liver weight increase 47% greater than normal rats of the same body weight. The optimal time for the initial dose of carbon tetrachloride was after 14 days on phenobarbitone.", "entity": "Phenobarbital", "aliases": "Acid Phenylethylbarbituric Gardenal Hysteps Luminal Monosodium Salt Phenobarbital Phenemal Sodium Phenobarbitone Phenylbarbital", "definition": "A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.\n    ", "id": "MESH:D010634"}
{"mention": "enlargement of the liver", "mention_text": "The yield of severe cirrhosis of the liver (defined as a shrunken finely nodular liver with micronodular histology, ascites greater than 30 ml, plasma albumin less than 2.2 g/dl, splenomegaly 2-3 times normal, and testicular atrophy approximately half normal weight) after 12 doses of carbon tetrachloride given intragastrically in the phenobarbitone-primed rat was increased from 25% to 56% by giving the initial \"calibrating\" dose of carbon tetrachloride at the peak of the phenobarbitone-induced enlargement of the liver. At this point it was assumed that the cytochrome P450/CCl4 toxic state was both maximal and stable. The optimal rat size to begin phenobarbitone was determined as 100 g, and this size as a group had a mean maximum relative liver weight increase 47% greater than normal rats of the same body weight. The optimal time for the initial dose of carbon tetrachloride was after 14 days on phenobarbitone.", "entity": "Hepatomegaly", "aliases": "Enlarged Liver Hepatomegaly", "definition": "Enlargement of the liver.\n    ", "id": "MESH:D006529"}
{"mention": "CCl4", "mention_text": "The yield of severe cirrhosis of the liver (defined as a shrunken finely nodular liver with micronodular histology, ascites greater than 30 ml, plasma albumin less than 2.2 g/dl, splenomegaly 2-3 times normal, and testicular atrophy approximately half normal weight) after 12 doses of carbon tetrachloride given intragastrically in the phenobarbitone-primed rat was increased from 25% to 56% by giving the initial \"calibrating\" dose of carbon tetrachloride at the peak of the phenobarbitone-induced enlargement of the liver. At this point it was assumed that the cytochrome P450/CCl4 toxic state was both maximal and stable. The optimal rat size to begin phenobarbitone was determined as 100 g, and this size as a group had a mean maximum relative liver weight increase 47% greater than normal rats of the same body weight. The optimal time for the initial dose of carbon tetrachloride was after 14 days on phenobarbitone.", "entity": "Carbon Tetrachloride", "aliases": "Carbon Tetrachloride Tetrachloromethane", "definition": "A solvent for oils, fats, lacquers, varnishes, rubber waxes, and resins, and a starting material in the manufacturing of organic compounds. Poisoning by inhalation, ingestion or skin absorption is possible and may be fatal. (Merck Index, 11th ed)\n    ", "id": "MESH:D002251"}
{"mention": "lithium", "mention_text": "Attenuation of the lithium-induced diabetes-insipidus-like syndrome by amiloride in rats.", "entity": "Lithium", "aliases": "Lithium", "definition": "An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.\n    ", "id": "MESH:D008094"}
{"mention": "diabetes-insipidus-like syndrome", "mention_text": "Attenuation of the lithium-induced diabetes-insipidus-like syndrome by amiloride in rats.", "entity": "Diabetes Insipidus", "aliases": "Diabetes Insipidus", "definition": "A disease that is characterized by frequent urination, excretion of large amounts of dilute URINE, and excessive THIRST. Etiologies of diabetes insipidus include deficiency of antidiuretic hormone (also known as ADH or VASOPRESSIN) secreted by the NEUROHYPOPHYSIS, impaired KIDNEY response to ADH, and impaired hypothalamic regulation of thirst.\n    ", "id": "MESH:D003919"}
{"mention": "amiloride", "mention_text": "Attenuation of the lithium-induced diabetes-insipidus-like syndrome by amiloride in rats.", "entity": "Amiloride", "aliases": "Alphapharm Brand of Amiloride Hydrochloride Amidal Amiduret Trom Amiloberag Anhydrous Amrad Berolina Cahill May Roberts Douglas Kaluril Merck Sharp & Dohme Midamor Midoride Modamide Trommsdorff", "definition": "A pyrazine compound inhibiting SODIUM reabsorption through SODIUM CHANNELS in renal EPITHELIAL CELLS. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with DIURETICS to spare POTASSIUM loss. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p705)\n    ", "id": "MESH:D000584"}
{"mention": "amiloride", "mention_text": "The effect of amiloride on lithium-induced polydipsia and polyuria and on the lithium concentration in the plasma, brain, kidney, thyroid and red blood cells was investigated in rats, chronically treated with LiCl. Amiloride reduced the drinking and urine volume of rats in an acute (6 or 12 h) and a subacute (3 days) experiment. 6 h after the administration of amiloride, a reduction was observed in the lithium content of the renal medulla but not in the other organs studied. At 12 h, all the tissues showed a slight increase in lithium levels. After 3 days of combined treatment, a marked elevation in plasma and tissue lithium levels accompanied a reduction in water intake. In all the experiments, the attenuation of the lithium-induced diabetes-insipidus-like syndrome by amiloride was accompanied by a reduction of the ratio between the lithium concentration in the renal medulla and its levels in the blood and an elevation in the plasma potassium level. It is concluded that acute amiloride administration to lithium-treated patients suffering from polydipsia and polyuria might relieve these patients but prolonged amiloride supplementation would result in elevated lithium levels and might be hazardous.", "entity": "Amiloride", "aliases": "Alphapharm Brand of Amiloride Hydrochloride Amidal Amiduret Trom Amiloberag Anhydrous Amrad Berolina Cahill May Roberts Douglas Kaluril Merck Sharp & Dohme Midamor Midoride Modamide Trommsdorff", "definition": "A pyrazine compound inhibiting SODIUM reabsorption through SODIUM CHANNELS in renal EPITHELIAL CELLS. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with DIURETICS to spare POTASSIUM loss. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p705)\n    ", "id": "MESH:D000584"}
{"mention": "lithium", "mention_text": "The effect of amiloride on lithium-induced polydipsia and polyuria and on the lithium concentration in the plasma, brain, kidney, thyroid and red blood cells was investigated in rats, chronically treated with LiCl. Amiloride reduced the drinking and urine volume of rats in an acute (6 or 12 h) and a subacute (3 days) experiment. 6 h after the administration of amiloride, a reduction was observed in the lithium content of the renal medulla but not in the other organs studied. At 12 h, all the tissues showed a slight increase in lithium levels. After 3 days of combined treatment, a marked elevation in plasma and tissue lithium levels accompanied a reduction in water intake. In all the experiments, the attenuation of the lithium-induced diabetes-insipidus-like syndrome by amiloride was accompanied by a reduction of the ratio between the lithium concentration in the renal medulla and its levels in the blood and an elevation in the plasma potassium level. It is concluded that acute amiloride administration to lithium-treated patients suffering from polydipsia and polyuria might relieve these patients but prolonged amiloride supplementation would result in elevated lithium levels and might be hazardous.", "entity": "Lithium", "aliases": "Lithium", "definition": "An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.\n    ", "id": "MESH:D008094"}
{"mention": "polydipsia", "mention_text": "The effect of amiloride on lithium-induced polydipsia and polyuria and on the lithium concentration in the plasma, brain, kidney, thyroid and red blood cells was investigated in rats, chronically treated with LiCl. Amiloride reduced the drinking and urine volume of rats in an acute (6 or 12 h) and a subacute (3 days) experiment. 6 h after the administration of amiloride, a reduction was observed in the lithium content of the renal medulla but not in the other organs studied. At 12 h, all the tissues showed a slight increase in lithium levels. After 3 days of combined treatment, a marked elevation in plasma and tissue lithium levels accompanied a reduction in water intake. In all the experiments, the attenuation of the lithium-induced diabetes-insipidus-like syndrome by amiloride was accompanied by a reduction of the ratio between the lithium concentration in the renal medulla and its levels in the blood and an elevation in the plasma potassium level. It is concluded that acute amiloride administration to lithium-treated patients suffering from polydipsia and polyuria might relieve these patients but prolonged amiloride supplementation would result in elevated lithium levels and might be hazardous.", "entity": "Polydipsia", "aliases": "Polydipsia Polydipsias", "definition": "Excessive thirst manifested by excessive fluid intake. It is characteristic of many diseases such as DIABETES MELLITUS; DIABETES INSIPIDUS; and NEPHROGENIC DIABETES INSIPIDUS. The condition may be psychogenic in origin.\n    ", "id": "MESH:D059606"}
{"mention": "polyuria", "mention_text": "The effect of amiloride on lithium-induced polydipsia and polyuria and on the lithium concentration in the plasma, brain, kidney, thyroid and red blood cells was investigated in rats, chronically treated with LiCl. Amiloride reduced the drinking and urine volume of rats in an acute (6 or 12 h) and a subacute (3 days) experiment. 6 h after the administration of amiloride, a reduction was observed in the lithium content of the renal medulla but not in the other organs studied. At 12 h, all the tissues showed a slight increase in lithium levels. After 3 days of combined treatment, a marked elevation in plasma and tissue lithium levels accompanied a reduction in water intake. In all the experiments, the attenuation of the lithium-induced diabetes-insipidus-like syndrome by amiloride was accompanied by a reduction of the ratio between the lithium concentration in the renal medulla and its levels in the blood and an elevation in the plasma potassium level. It is concluded that acute amiloride administration to lithium-treated patients suffering from polydipsia and polyuria might relieve these patients but prolonged amiloride supplementation would result in elevated lithium levels and might be hazardous.", "entity": "Polyuria", "aliases": "Polyuria Polyurias", "definition": "Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes (DIABETES MELLITUS; DIABETES INSIPIDUS).\n    ", "id": "MESH:D011141"}
{"mention": "LiCl", "mention_text": "The effect of amiloride on lithium-induced polydipsia and polyuria and on the lithium concentration in the plasma, brain, kidney, thyroid and red blood cells was investigated in rats, chronically treated with LiCl. Amiloride reduced the drinking and urine volume of rats in an acute (6 or 12 h) and a subacute (3 days) experiment. 6 h after the administration of amiloride, a reduction was observed in the lithium content of the renal medulla but not in the other organs studied. At 12 h, all the tissues showed a slight increase in lithium levels. After 3 days of combined treatment, a marked elevation in plasma and tissue lithium levels accompanied a reduction in water intake. In all the experiments, the attenuation of the lithium-induced diabetes-insipidus-like syndrome by amiloride was accompanied by a reduction of the ratio between the lithium concentration in the renal medulla and its levels in the blood and an elevation in the plasma potassium level. It is concluded that acute amiloride administration to lithium-treated patients suffering from polydipsia and polyuria might relieve these patients but prolonged amiloride supplementation would result in elevated lithium levels and might be hazardous.", "entity": "Lithium Chloride", "aliases": "Chloride Lithium", "definition": "A salt of lithium that has been used experimentally as an immunomodulator.\n    ", "id": "MESH:D018021"}
{"mention": "Amiloride", "mention_text": "The effect of amiloride on lithium-induced polydipsia and polyuria and on the lithium concentration in the plasma, brain, kidney, thyroid and red blood cells was investigated in rats, chronically treated with LiCl. Amiloride reduced the drinking and urine volume of rats in an acute (6 or 12 h) and a subacute (3 days) experiment. 6 h after the administration of amiloride, a reduction was observed in the lithium content of the renal medulla but not in the other organs studied. At 12 h, all the tissues showed a slight increase in lithium levels. After 3 days of combined treatment, a marked elevation in plasma and tissue lithium levels accompanied a reduction in water intake. In all the experiments, the attenuation of the lithium-induced diabetes-insipidus-like syndrome by amiloride was accompanied by a reduction of the ratio between the lithium concentration in the renal medulla and its levels in the blood and an elevation in the plasma potassium level. It is concluded that acute amiloride administration to lithium-treated patients suffering from polydipsia and polyuria might relieve these patients but prolonged amiloride supplementation would result in elevated lithium levels and might be hazardous.", "entity": "Amiloride", "aliases": "Alphapharm Brand of Amiloride Hydrochloride Amidal Amiduret Trom Amiloberag Anhydrous Amrad Berolina Cahill May Roberts Douglas Kaluril Merck Sharp & Dohme Midamor Midoride Modamide Trommsdorff", "definition": "A pyrazine compound inhibiting SODIUM reabsorption through SODIUM CHANNELS in renal EPITHELIAL CELLS. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with DIURETICS to spare POTASSIUM loss. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p705)\n    ", "id": "MESH:D000584"}
{"mention": "diabetes-insipidus-like syndrome", "mention_text": "The effect of amiloride on lithium-induced polydipsia and polyuria and on the lithium concentration in the plasma, brain, kidney, thyroid and red blood cells was investigated in rats, chronically treated with LiCl. Amiloride reduced the drinking and urine volume of rats in an acute (6 or 12 h) and a subacute (3 days) experiment. 6 h after the administration of amiloride, a reduction was observed in the lithium content of the renal medulla but not in the other organs studied. At 12 h, all the tissues showed a slight increase in lithium levels. After 3 days of combined treatment, a marked elevation in plasma and tissue lithium levels accompanied a reduction in water intake. In all the experiments, the attenuation of the lithium-induced diabetes-insipidus-like syndrome by amiloride was accompanied by a reduction of the ratio between the lithium concentration in the renal medulla and its levels in the blood and an elevation in the plasma potassium level. It is concluded that acute amiloride administration to lithium-treated patients suffering from polydipsia and polyuria might relieve these patients but prolonged amiloride supplementation would result in elevated lithium levels and might be hazardous.", "entity": "Diabetes Insipidus", "aliases": "Diabetes Insipidus", "definition": "A disease that is characterized by frequent urination, excretion of large amounts of dilute URINE, and excessive THIRST. Etiologies of diabetes insipidus include deficiency of antidiuretic hormone (also known as ADH or VASOPRESSIN) secreted by the NEUROHYPOPHYSIS, impaired KIDNEY response to ADH, and impaired hypothalamic regulation of thirst.\n    ", "id": "MESH:D003919"}
{"mention": "potassium", "mention_text": "The effect of amiloride on lithium-induced polydipsia and polyuria and on the lithium concentration in the plasma, brain, kidney, thyroid and red blood cells was investigated in rats, chronically treated with LiCl. Amiloride reduced the drinking and urine volume of rats in an acute (6 or 12 h) and a subacute (3 days) experiment. 6 h after the administration of amiloride, a reduction was observed in the lithium content of the renal medulla but not in the other organs studied. At 12 h, all the tissues showed a slight increase in lithium levels. After 3 days of combined treatment, a marked elevation in plasma and tissue lithium levels accompanied a reduction in water intake. In all the experiments, the attenuation of the lithium-induced diabetes-insipidus-like syndrome by amiloride was accompanied by a reduction of the ratio between the lithium concentration in the renal medulla and its levels in the blood and an elevation in the plasma potassium level. It is concluded that acute amiloride administration to lithium-treated patients suffering from polydipsia and polyuria might relieve these patients but prolonged amiloride supplementation would result in elevated lithium levels and might be hazardous.", "entity": "Potassium", "aliases": "Potassium", "definition": "An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.\n    ", "id": "MESH:D011188"}
{"mention": "alprazolam", "mention_text": "Safety and side-effects of alprazolam. Controlled study in agoraphobia with panic disorder.", "entity": "Alprazolam", "aliases": "Alphapharm Brand of Alprazolam Apotex Kenral Novopharm Nu-Pharm Orion Pfizer Temmler Alprazolan Alprox Apo Alpraz Apo-Alpraz ApoAlpraz Arzneimittelwerk Dresden Cassadan D-65MT D65MT Esparon Kalma Novo Alprazol Novo-Alprazol NovoAlprazol Nu Pharm Nu-Alpraz NuAlpraz Ralozam Tafil Trankimazin U-31,889 U31,889 Xanax", "definition": "A triazolobenzodiazepine compound with antianxiety and sedative-hypnotic actions, that is efficacious in the treatment of PANIC DISORDERS, with or without AGORAPHOBIA, and in generalized ANXIETY DISORDERS. (From AMA Drug Evaluations Annual, 1994, p238)\n    ", "id": "MESH:D000525"}
{"mention": "agoraphobia", "mention_text": "Safety and side-effects of alprazolam. Controlled study in agoraphobia with panic disorder.", "entity": "Agoraphobia", "aliases": "Agoraphobia Agoraphobias", "definition": "Obsessive, persistent, intense fear of open places.\n    ", "id": "MESH:D000379"}
{"mention": "panic disorder", "mention_text": "Safety and side-effects of alprazolam. Controlled study in agoraphobia with panic disorder.", "entity": "Panic Disorder", "aliases": "Attack Panic Attacks Disorder Disorders", "definition": "A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait.\n    ", "id": "MESH:D016584"}
{"mention": "benzodiazepines", "mention_text": "BACKGROUND: The widespread use of benzodiazepines has led to increasing recognition of their unwanted effects. The efficacy of alprazolam and placebo in panic disorder with agoraphobia, and the side-effect and adverse effect profiles of both drug groups were measured. METHOD: In London and Toronto 154 patients who met DSM-III criteria for panic disorder with agoraphobia were randomised to alprazolam or placebo. Subjects in each drug group also received either exposure or relaxation. Treatment was from weeks 0 to 8 and was then tapered from weeks 8 to 16. RESULTS: Mean alprazolam dose was 5 mg daily. Compared with placebo subjects, alprazolam patients developed more adverse reactions (21% v. 0%) of depression, enuresis, disinhibition and aggression; and more side-effects, particularly sedation, irritability, impaired memory, weight loss and ataxia. Side-effects tended to diminish during treatment but remained significant at week 8. Despite this, the drop-out rate was low. CONCLUSIONS: Alprazolam caused side-effects and adverse effects during treatment but many patients were willing to accept these.", "entity": "Benzodiazepines", "aliases": "Benzodiazepine Compounds Benzodiazepines", "definition": "A group of two-ring heterocyclic compounds consisting of a benzene ring fused to a diazepine ring.\n    ", "id": "MESH:D001569"}
{"mention": "alprazolam", "mention_text": "BACKGROUND: The widespread use of benzodiazepines has led to increasing recognition of their unwanted effects. The efficacy of alprazolam and placebo in panic disorder with agoraphobia, and the side-effect and adverse effect profiles of both drug groups were measured. METHOD: In London and Toronto 154 patients who met DSM-III criteria for panic disorder with agoraphobia were randomised to alprazolam or placebo. Subjects in each drug group also received either exposure or relaxation. Treatment was from weeks 0 to 8 and was then tapered from weeks 8 to 16. RESULTS: Mean alprazolam dose was 5 mg daily. Compared with placebo subjects, alprazolam patients developed more adverse reactions (21% v. 0%) of depression, enuresis, disinhibition and aggression; and more side-effects, particularly sedation, irritability, impaired memory, weight loss and ataxia. Side-effects tended to diminish during treatment but remained significant at week 8. Despite this, the drop-out rate was low. CONCLUSIONS: Alprazolam caused side-effects and adverse effects during treatment but many patients were willing to accept these.", "entity": "Alprazolam", "aliases": "Alphapharm Brand of Alprazolam Apotex Kenral Novopharm Nu-Pharm Orion Pfizer Temmler Alprazolan Alprox Apo Alpraz Apo-Alpraz ApoAlpraz Arzneimittelwerk Dresden Cassadan D-65MT D65MT Esparon Kalma Novo Alprazol Novo-Alprazol NovoAlprazol Nu Pharm Nu-Alpraz NuAlpraz Ralozam Tafil Trankimazin U-31,889 U31,889 Xanax", "definition": "A triazolobenzodiazepine compound with antianxiety and sedative-hypnotic actions, that is efficacious in the treatment of PANIC DISORDERS, with or without AGORAPHOBIA, and in generalized ANXIETY DISORDERS. (From AMA Drug Evaluations Annual, 1994, p238)\n    ", "id": "MESH:D000525"}
{"mention": "panic disorder", "mention_text": "BACKGROUND: The widespread use of benzodiazepines has led to increasing recognition of their unwanted effects. The efficacy of alprazolam and placebo in panic disorder with agoraphobia, and the side-effect and adverse effect profiles of both drug groups were measured. METHOD: In London and Toronto 154 patients who met DSM-III criteria for panic disorder with agoraphobia were randomised to alprazolam or placebo. Subjects in each drug group also received either exposure or relaxation. Treatment was from weeks 0 to 8 and was then tapered from weeks 8 to 16. RESULTS: Mean alprazolam dose was 5 mg daily. Compared with placebo subjects, alprazolam patients developed more adverse reactions (21% v. 0%) of depression, enuresis, disinhibition and aggression; and more side-effects, particularly sedation, irritability, impaired memory, weight loss and ataxia. Side-effects tended to diminish during treatment but remained significant at week 8. Despite this, the drop-out rate was low. CONCLUSIONS: Alprazolam caused side-effects and adverse effects during treatment but many patients were willing to accept these.", "entity": "Panic Disorder", "aliases": "Attack Panic Attacks Disorder Disorders", "definition": "A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait.\n    ", "id": "MESH:D016584"}
{"mention": "agoraphobia", "mention_text": "BACKGROUND: The widespread use of benzodiazepines has led to increasing recognition of their unwanted effects. The efficacy of alprazolam and placebo in panic disorder with agoraphobia, and the side-effect and adverse effect profiles of both drug groups were measured. METHOD: In London and Toronto 154 patients who met DSM-III criteria for panic disorder with agoraphobia were randomised to alprazolam or placebo. Subjects in each drug group also received either exposure or relaxation. Treatment was from weeks 0 to 8 and was then tapered from weeks 8 to 16. RESULTS: Mean alprazolam dose was 5 mg daily. Compared with placebo subjects, alprazolam patients developed more adverse reactions (21% v. 0%) of depression, enuresis, disinhibition and aggression; and more side-effects, particularly sedation, irritability, impaired memory, weight loss and ataxia. Side-effects tended to diminish during treatment but remained significant at week 8. Despite this, the drop-out rate was low. CONCLUSIONS: Alprazolam caused side-effects and adverse effects during treatment but many patients were willing to accept these.", "entity": "Agoraphobia", "aliases": "Agoraphobia Agoraphobias", "definition": "Obsessive, persistent, intense fear of open places.\n    ", "id": "MESH:D000379"}
{"mention": "depression", "mention_text": "BACKGROUND: The widespread use of benzodiazepines has led to increasing recognition of their unwanted effects. The efficacy of alprazolam and placebo in panic disorder with agoraphobia, and the side-effect and adverse effect profiles of both drug groups were measured. METHOD: In London and Toronto 154 patients who met DSM-III criteria for panic disorder with agoraphobia were randomised to alprazolam or placebo. Subjects in each drug group also received either exposure or relaxation. Treatment was from weeks 0 to 8 and was then tapered from weeks 8 to 16. RESULTS: Mean alprazolam dose was 5 mg daily. Compared with placebo subjects, alprazolam patients developed more adverse reactions (21% v. 0%) of depression, enuresis, disinhibition and aggression; and more side-effects, particularly sedation, irritability, impaired memory, weight loss and ataxia. Side-effects tended to diminish during treatment but remained significant at week 8. Despite this, the drop-out rate was low. CONCLUSIONS: Alprazolam caused side-effects and adverse effects during treatment but many patients were willing to accept these.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "enuresis", "mention_text": "BACKGROUND: The widespread use of benzodiazepines has led to increasing recognition of their unwanted effects. The efficacy of alprazolam and placebo in panic disorder with agoraphobia, and the side-effect and adverse effect profiles of both drug groups were measured. METHOD: In London and Toronto 154 patients who met DSM-III criteria for panic disorder with agoraphobia were randomised to alprazolam or placebo. Subjects in each drug group also received either exposure or relaxation. Treatment was from weeks 0 to 8 and was then tapered from weeks 8 to 16. RESULTS: Mean alprazolam dose was 5 mg daily. Compared with placebo subjects, alprazolam patients developed more adverse reactions (21% v. 0%) of depression, enuresis, disinhibition and aggression; and more side-effects, particularly sedation, irritability, impaired memory, weight loss and ataxia. Side-effects tended to diminish during treatment but remained significant at week 8. Despite this, the drop-out rate was low. CONCLUSIONS: Alprazolam caused side-effects and adverse effects during treatment but many patients were willing to accept these.", "entity": "Enuresis", "aliases": "Enuresis", "definition": "Involuntary discharge of URINE after expected age of completed development of urinary control. This can happen during the daytime (DIURNAL ENURESIS) while one is awake or during sleep (NOCTURNAL ENURESIS). Enuresis can be in children or in adults (as persistent primary enuresis and secondary adult-onset enuresis).\n    ", "id": "MESH:D004775"}
{"mention": "aggression", "mention_text": "BACKGROUND: The widespread use of benzodiazepines has led to increasing recognition of their unwanted effects. The efficacy of alprazolam and placebo in panic disorder with agoraphobia, and the side-effect and adverse effect profiles of both drug groups were measured. METHOD: In London and Toronto 154 patients who met DSM-III criteria for panic disorder with agoraphobia were randomised to alprazolam or placebo. Subjects in each drug group also received either exposure or relaxation. Treatment was from weeks 0 to 8 and was then tapered from weeks 8 to 16. RESULTS: Mean alprazolam dose was 5 mg daily. Compared with placebo subjects, alprazolam patients developed more adverse reactions (21% v. 0%) of depression, enuresis, disinhibition and aggression; and more side-effects, particularly sedation, irritability, impaired memory, weight loss and ataxia. Side-effects tended to diminish during treatment but remained significant at week 8. Despite this, the drop-out rate was low. CONCLUSIONS: Alprazolam caused side-effects and adverse effects during treatment but many patients were willing to accept these.", "entity": "Mental Disorders", "aliases": "Behavior Disorders Diagnosis Psychiatric Disorder Mental", "definition": "Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.\n    ", "id": "MESH:D001523"}
{"mention": "irritability", "mention_text": "BACKGROUND: The widespread use of benzodiazepines has led to increasing recognition of their unwanted effects. The efficacy of alprazolam and placebo in panic disorder with agoraphobia, and the side-effect and adverse effect profiles of both drug groups were measured. METHOD: In London and Toronto 154 patients who met DSM-III criteria for panic disorder with agoraphobia were randomised to alprazolam or placebo. Subjects in each drug group also received either exposure or relaxation. Treatment was from weeks 0 to 8 and was then tapered from weeks 8 to 16. RESULTS: Mean alprazolam dose was 5 mg daily. Compared with placebo subjects, alprazolam patients developed more adverse reactions (21% v. 0%) of depression, enuresis, disinhibition and aggression; and more side-effects, particularly sedation, irritability, impaired memory, weight loss and ataxia. Side-effects tended to diminish during treatment but remained significant at week 8. Despite this, the drop-out rate was low. CONCLUSIONS: Alprazolam caused side-effects and adverse effects during treatment but many patients were willing to accept these.", "entity": "Mental Disorders", "aliases": "Behavior Disorders Diagnosis Psychiatric Disorder Mental", "definition": "Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.\n    ", "id": "MESH:D001523"}
{"mention": "impaired memory", "mention_text": "BACKGROUND: The widespread use of benzodiazepines has led to increasing recognition of their unwanted effects. The efficacy of alprazolam and placebo in panic disorder with agoraphobia, and the side-effect and adverse effect profiles of both drug groups were measured. METHOD: In London and Toronto 154 patients who met DSM-III criteria for panic disorder with agoraphobia were randomised to alprazolam or placebo. Subjects in each drug group also received either exposure or relaxation. Treatment was from weeks 0 to 8 and was then tapered from weeks 8 to 16. RESULTS: Mean alprazolam dose was 5 mg daily. Compared with placebo subjects, alprazolam patients developed more adverse reactions (21% v. 0%) of depression, enuresis, disinhibition and aggression; and more side-effects, particularly sedation, irritability, impaired memory, weight loss and ataxia. Side-effects tended to diminish during treatment but remained significant at week 8. Despite this, the drop-out rate was low. CONCLUSIONS: Alprazolam caused side-effects and adverse effects during treatment but many patients were willing to accept these.", "entity": "Memory Disorders", "aliases": "Age Related Memory Disorders Age-Related Disorder Cognitive Retention Deficit Deficits Semantic Spatial Loss Losses", "definition": "Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions.\n    ", "id": "MESH:D008569"}
{"mention": "weight loss", "mention_text": "BACKGROUND: The widespread use of benzodiazepines has led to increasing recognition of their unwanted effects. The efficacy of alprazolam and placebo in panic disorder with agoraphobia, and the side-effect and adverse effect profiles of both drug groups were measured. METHOD: In London and Toronto 154 patients who met DSM-III criteria for panic disorder with agoraphobia were randomised to alprazolam or placebo. Subjects in each drug group also received either exposure or relaxation. Treatment was from weeks 0 to 8 and was then tapered from weeks 8 to 16. RESULTS: Mean alprazolam dose was 5 mg daily. Compared with placebo subjects, alprazolam patients developed more adverse reactions (21% v. 0%) of depression, enuresis, disinhibition and aggression; and more side-effects, particularly sedation, irritability, impaired memory, weight loss and ataxia. Side-effects tended to diminish during treatment but remained significant at week 8. Despite this, the drop-out rate was low. CONCLUSIONS: Alprazolam caused side-effects and adverse effects during treatment but many patients were willing to accept these.", "entity": "Weight Loss", "aliases": "Loss Weight Losses Reduction Reductions", "definition": "Decrease in existing BODY WEIGHT.\n    ", "id": "MESH:D015431"}
{"mention": "ataxia", "mention_text": "BACKGROUND: The widespread use of benzodiazepines has led to increasing recognition of their unwanted effects. The efficacy of alprazolam and placebo in panic disorder with agoraphobia, and the side-effect and adverse effect profiles of both drug groups were measured. METHOD: In London and Toronto 154 patients who met DSM-III criteria for panic disorder with agoraphobia were randomised to alprazolam or placebo. Subjects in each drug group also received either exposure or relaxation. Treatment was from weeks 0 to 8 and was then tapered from weeks 8 to 16. RESULTS: Mean alprazolam dose was 5 mg daily. Compared with placebo subjects, alprazolam patients developed more adverse reactions (21% v. 0%) of depression, enuresis, disinhibition and aggression; and more side-effects, particularly sedation, irritability, impaired memory, weight loss and ataxia. Side-effects tended to diminish during treatment but remained significant at week 8. Despite this, the drop-out rate was low. CONCLUSIONS: Alprazolam caused side-effects and adverse effects during treatment but many patients were willing to accept these.", "entity": "Ataxia", "aliases": "Appendicular Ataxia Ataxias Limb Motor Sensory Truncal Ataxy Coordination Impairment Impairments Lack Dyscoordination Dyssynergia Incoordination Incoordinations of Rubral Tremor Tremors", "definition": "Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or PERIPHERAL NERVE DISEASES. Motor ataxia may be associated with CEREBELLAR DISEASES; CEREBRAL CORTEX diseases; THALAMIC DISEASES; BASAL GANGLIA DISEASES; injury to the RED NUCLEUS; and other conditions.\n    ", "id": "MESH:D001259"}
{"mention": "Alprazolam", "mention_text": "BACKGROUND: The widespread use of benzodiazepines has led to increasing recognition of their unwanted effects. The efficacy of alprazolam and placebo in panic disorder with agoraphobia, and the side-effect and adverse effect profiles of both drug groups were measured. METHOD: In London and Toronto 154 patients who met DSM-III criteria for panic disorder with agoraphobia were randomised to alprazolam or placebo. Subjects in each drug group also received either exposure or relaxation. Treatment was from weeks 0 to 8 and was then tapered from weeks 8 to 16. RESULTS: Mean alprazolam dose was 5 mg daily. Compared with placebo subjects, alprazolam patients developed more adverse reactions (21% v. 0%) of depression, enuresis, disinhibition and aggression; and more side-effects, particularly sedation, irritability, impaired memory, weight loss and ataxia. Side-effects tended to diminish during treatment but remained significant at week 8. Despite this, the drop-out rate was low. CONCLUSIONS: Alprazolam caused side-effects and adverse effects during treatment but many patients were willing to accept these.", "entity": "Alprazolam", "aliases": "Alphapharm Brand of Alprazolam Apotex Kenral Novopharm Nu-Pharm Orion Pfizer Temmler Alprazolan Alprox Apo Alpraz Apo-Alpraz ApoAlpraz Arzneimittelwerk Dresden Cassadan D-65MT D65MT Esparon Kalma Novo Alprazol Novo-Alprazol NovoAlprazol Nu Pharm Nu-Alpraz NuAlpraz Ralozam Tafil Trankimazin U-31,889 U31,889 Xanax", "definition": "A triazolobenzodiazepine compound with antianxiety and sedative-hypnotic actions, that is efficacious in the treatment of PANIC DISORDERS, with or without AGORAPHOBIA, and in generalized ANXIETY DISORDERS. (From AMA Drug Evaluations Annual, 1994, p238)\n    ", "id": "MESH:D000525"}
{"mention": "Dup 753", "mention_text": "Dup 753 prevents the development of puromycin aminonucleoside-induced nephrosis.", "entity": "Losartan", "aliases": "2-Butyl-4-chloro-1-((2'-(1H-etrazol-5-yl) (1,1'-biphenyl)-4-yl)methyl)-1H-imidazole-5-methanol Cozaar DuP 753 DuP-753 DuP753 Losartan Monopotassium Salt Potassium MK 954 MK-954 MK954", "definition": "An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.\n    ", "id": "MESH:D019808"}
{"mention": "puromycin aminonucleoside", "mention_text": "Dup 753 prevents the development of puromycin aminonucleoside-induced nephrosis.", "entity": "Puromycin Aminonucleoside", "aliases": "3' Amino 3' deoxy N,N dimethyladenosine 3'-Amino-3'-deoxy-N,N-dimethyladenosine Aminonucleoside Puromycin", "definition": "PUROMYCIN derivative that lacks the methoxyphenylalanyl group on the amine of the sugar ring. It is an antibiotic with antineoplastic properties and can cause nephrosis.\n    ", "id": "MESH:D011692"}
{"mention": "nephrosis", "mention_text": "Dup 753 prevents the development of puromycin aminonucleoside-induced nephrosis.", "entity": "Nephrosis", "aliases": "Nephroses Nephrosis", "definition": "Pathological processes of the KIDNEY without inflammatory or neoplastic components. Nephrosis may be a primary disorder or secondary complication of other diseases. It is characterized by the NEPHROTIC SYNDROME indicating the presence of PROTEINURIA and HYPOALBUMINEMIA with accompanying EDEMA.\n    ", "id": "MESH:D009401"}
{"mention": "nephrotic syndromes", "mention_text": "The appearance of nephrotic syndromes such as proteinuria, hypoalbuminemia, hypercholesterolemia and increase in blood nitrogen urea, induced in rats by injection of puromycin aminonucleoside was markedly inhibited by oral administration of Dup 753 (losartan), a novel angiotensin II receptor antagonist, at a dose of 1 or 2 mg/kg per day. The results suggest a possible involvement of the renin-angiotensin system in the development of puromycin aminonucleoside-induced nephrosis.", "entity": "Nephrotic Syndrome", "aliases": "Nephrotic Syndrome Syndromes", "definition": "A condition characterized by severe PROTEINURIA, greater than 3.5 g/day in an average adult. The substantial loss of protein in the urine results in complications such as HYPOPROTEINEMIA; generalized EDEMA; HYPERTENSION; and HYPERLIPIDEMIAS. Diseases associated with nephrotic syndrome generally cause chronic kidney dysfunction.\n    ", "id": "MESH:D009404"}
{"mention": "proteinuria", "mention_text": "The appearance of nephrotic syndromes such as proteinuria, hypoalbuminemia, hypercholesterolemia and increase in blood nitrogen urea, induced in rats by injection of puromycin aminonucleoside was markedly inhibited by oral administration of Dup 753 (losartan), a novel angiotensin II receptor antagonist, at a dose of 1 or 2 mg/kg per day. The results suggest a possible involvement of the renin-angiotensin system in the development of puromycin aminonucleoside-induced nephrosis.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "hypoalbuminemia", "mention_text": "The appearance of nephrotic syndromes such as proteinuria, hypoalbuminemia, hypercholesterolemia and increase in blood nitrogen urea, induced in rats by injection of puromycin aminonucleoside was markedly inhibited by oral administration of Dup 753 (losartan), a novel angiotensin II receptor antagonist, at a dose of 1 or 2 mg/kg per day. The results suggest a possible involvement of the renin-angiotensin system in the development of puromycin aminonucleoside-induced nephrosis.", "entity": "Hypoalbuminemia", "aliases": "Hypoalbuminemia", "definition": "A condition in which albumin level in blood (SERUM ALBUMIN) is below the normal range. Hypoalbuminemia may be due to decreased hepatic albumin synthesis, increased albumin catabolism, altered albumin distribution, or albumin loss through the urine (ALBUMINURIA).\n    ", "id": "MESH:D034141"}
{"mention": "hypercholesterolemia", "mention_text": "The appearance of nephrotic syndromes such as proteinuria, hypoalbuminemia, hypercholesterolemia and increase in blood nitrogen urea, induced in rats by injection of puromycin aminonucleoside was markedly inhibited by oral administration of Dup 753 (losartan), a novel angiotensin II receptor antagonist, at a dose of 1 or 2 mg/kg per day. The results suggest a possible involvement of the renin-angiotensin system in the development of puromycin aminonucleoside-induced nephrosis.", "entity": "Hypercholesterolemia", "aliases": "Elevated Cholesterol Hypercholesteremia Hypercholesteremias Hypercholesterolemia Hypercholesterolemias", "definition": "A condition with abnormally high levels of CHOLESTEROL in the blood. It is defined as a cholesterol value exceeding the 95th percentile for the population.\n    ", "id": "MESH:D006937"}
{"mention": "blood nitrogen urea", "mention_text": "The appearance of nephrotic syndromes such as proteinuria, hypoalbuminemia, hypercholesterolemia and increase in blood nitrogen urea, induced in rats by injection of puromycin aminonucleoside was markedly inhibited by oral administration of Dup 753 (losartan), a novel angiotensin II receptor antagonist, at a dose of 1 or 2 mg/kg per day. The results suggest a possible involvement of the renin-angiotensin system in the development of puromycin aminonucleoside-induced nephrosis.", "entity": "Blood Urea Nitrogen", "aliases": "BUN Blood Urea Nitrogen", "definition": "The urea concentration of the blood stated in terms of nitrogen content. Serum (plasma) urea nitrogen is approximately 12% higher than blood urea nitrogen concentration because of the greater protein content of red blood cells. Increases in blood or serum urea nitrogen are referred to as azotemia and may have prerenal, renal, or postrenal causes. (From Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984)\n    ", "id": "MESH:D001806"}
{"mention": "puromycin aminonucleoside", "mention_text": "The appearance of nephrotic syndromes such as proteinuria, hypoalbuminemia, hypercholesterolemia and increase in blood nitrogen urea, induced in rats by injection of puromycin aminonucleoside was markedly inhibited by oral administration of Dup 753 (losartan), a novel angiotensin II receptor antagonist, at a dose of 1 or 2 mg/kg per day. The results suggest a possible involvement of the renin-angiotensin system in the development of puromycin aminonucleoside-induced nephrosis.", "entity": "Puromycin Aminonucleoside", "aliases": "3' Amino 3' deoxy N,N dimethyladenosine 3'-Amino-3'-deoxy-N,N-dimethyladenosine Aminonucleoside Puromycin", "definition": "PUROMYCIN derivative that lacks the methoxyphenylalanyl group on the amine of the sugar ring. It is an antibiotic with antineoplastic properties and can cause nephrosis.\n    ", "id": "MESH:D011692"}
{"mention": "Dup 753", "mention_text": "The appearance of nephrotic syndromes such as proteinuria, hypoalbuminemia, hypercholesterolemia and increase in blood nitrogen urea, induced in rats by injection of puromycin aminonucleoside was markedly inhibited by oral administration of Dup 753 (losartan), a novel angiotensin II receptor antagonist, at a dose of 1 or 2 mg/kg per day. The results suggest a possible involvement of the renin-angiotensin system in the development of puromycin aminonucleoside-induced nephrosis.", "entity": "Losartan", "aliases": "2-Butyl-4-chloro-1-((2'-(1H-etrazol-5-yl) (1,1'-biphenyl)-4-yl)methyl)-1H-imidazole-5-methanol Cozaar DuP 753 DuP-753 DuP753 Losartan Monopotassium Salt Potassium MK 954 MK-954 MK954", "definition": "An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.\n    ", "id": "MESH:D019808"}
{"mention": "losartan", "mention_text": "The appearance of nephrotic syndromes such as proteinuria, hypoalbuminemia, hypercholesterolemia and increase in blood nitrogen urea, induced in rats by injection of puromycin aminonucleoside was markedly inhibited by oral administration of Dup 753 (losartan), a novel angiotensin II receptor antagonist, at a dose of 1 or 2 mg/kg per day. The results suggest a possible involvement of the renin-angiotensin system in the development of puromycin aminonucleoside-induced nephrosis.", "entity": "Losartan", "aliases": "2-Butyl-4-chloro-1-((2'-(1H-etrazol-5-yl) (1,1'-biphenyl)-4-yl)methyl)-1H-imidazole-5-methanol Cozaar DuP 753 DuP-753 DuP753 Losartan Monopotassium Salt Potassium MK 954 MK-954 MK954", "definition": "An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.\n    ", "id": "MESH:D019808"}
{"mention": "angiotensin II", "mention_text": "The appearance of nephrotic syndromes such as proteinuria, hypoalbuminemia, hypercholesterolemia and increase in blood nitrogen urea, induced in rats by injection of puromycin aminonucleoside was markedly inhibited by oral administration of Dup 753 (losartan), a novel angiotensin II receptor antagonist, at a dose of 1 or 2 mg/kg per day. The results suggest a possible involvement of the renin-angiotensin system in the development of puromycin aminonucleoside-induced nephrosis.", "entity": "Angiotensin II", "aliases": "5 L Isoleucine Angiotensin II 5-L-Isoleucine ANG-(1-8)Octapeptide Ile(5)- Isoleucine(5)- Val(5)- Valine(5)- Angiotensin-(1-8) Octapeptide Isoleucine(5)-Angiotensin Isoleucyl(5)-Angiotensin Valyl(5)-Angiotensin", "definition": "An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.\n    ", "id": "MESH:D000804"}
{"mention": "angiotensin", "mention_text": "The appearance of nephrotic syndromes such as proteinuria, hypoalbuminemia, hypercholesterolemia and increase in blood nitrogen urea, induced in rats by injection of puromycin aminonucleoside was markedly inhibited by oral administration of Dup 753 (losartan), a novel angiotensin II receptor antagonist, at a dose of 1 or 2 mg/kg per day. The results suggest a possible involvement of the renin-angiotensin system in the development of puromycin aminonucleoside-induced nephrosis.", "entity": "Angiotensins", "aliases": "Angiotensin Angiotensins", "definition": "Oligopeptides which are important in the regulation of blood pressure (VASOCONSTRICTION) and fluid homeostasis via the RENIN-ANGIOTENSIN SYSTEM. These include angiotensins derived naturally from precursor ANGIOTENSINOGEN, and those synthesized.\n    ", "id": "MESH:D000809"}
{"mention": "nephrosis", "mention_text": "The appearance of nephrotic syndromes such as proteinuria, hypoalbuminemia, hypercholesterolemia and increase in blood nitrogen urea, induced in rats by injection of puromycin aminonucleoside was markedly inhibited by oral administration of Dup 753 (losartan), a novel angiotensin II receptor antagonist, at a dose of 1 or 2 mg/kg per day. The results suggest a possible involvement of the renin-angiotensin system in the development of puromycin aminonucleoside-induced nephrosis.", "entity": "Nephrosis", "aliases": "Nephroses Nephrosis", "definition": "Pathological processes of the KIDNEY without inflammatory or neoplastic components. Nephrosis may be a primary disorder or secondary complication of other diseases. It is characterized by the NEPHROTIC SYNDROME indicating the presence of PROTEINURIA and HYPOALBUMINEMIA with accompanying EDEMA.\n    ", "id": "MESH:D009401"}
{"mention": "Sodium bicarbonate", "mention_text": "Sodium bicarbonate alleviates penile pain induced by intracavernous injections for erectile dysfunction.", "entity": "Sodium Bicarbonate", "aliases": "Baking Soda Bicarbonate Sodium Carbonic Acid Monosodium Salt Hydrogen Carbonate", "definition": "A white, crystalline powder that is commonly used as a pH buffering agent, an electrolyte replenisher, systemic alkalizer and in topical cleansing solutions.\n    ", "id": "MESH:D017693"}
{"mention": "penile pain", "mention_text": "Sodium bicarbonate alleviates penile pain induced by intracavernous injections for erectile dysfunction.", "entity": "Dyspareunia", "aliases": "Dyspareunia", "definition": "Recurrent genital pain occurring during, before, or after SEXUAL INTERCOURSE in either the male or the female.\n    ", "id": "MESH:D004414"}
{"mention": "erectile dysfunction", "mention_text": "Sodium bicarbonate alleviates penile pain induced by intracavernous injections for erectile dysfunction.", "entity": "Erectile Dysfunction", "aliases": "Dysfunction Erectile Impotence Male Sexual", "definition": "The inability in the male to have a PENILE ERECTION due to psychological or organ dysfunction.\n    ", "id": "MESH:D007172"}
{"mention": "penile pain", "mention_text": "In an attempt to determine whether penile pain associated with intracorporeal injections could be due to the acidity of the medication, we performed a randomized study comparing the incidence of penile pain following intracorporeal injections with or without the addition of sodium bicarbonate to the intracorporeal medications. A total of 38 consecutive patients who presented to our clinic with impotence received 0.2 ml. of a combination of 3 drugs: 6 mg. papaverine, 100 micrograms. phentolamine and 10 micrograms. prostaglandin E1 with (pH 7.05) or without (pH 4.17) the addition of sodium bicarbonate (0.03 mEq.). Of the 19 patients without sodium bicarbonate added to the medication 11 (58%) complained of penile pain due to the medication, while only 1 of the 19 men (5%) who received sodium bicarbonate complained of penile pain. From these data we conclude that the penile pain following intracorporeal injections is most likely due to the acidity of the medication, which can be overcome by elevating the pH to a neutral level.", "entity": "Dyspareunia", "aliases": "Dyspareunia", "definition": "Recurrent genital pain occurring during, before, or after SEXUAL INTERCOURSE in either the male or the female.\n    ", "id": "MESH:D004414"}
{"mention": "sodium bicarbonate", "mention_text": "In an attempt to determine whether penile pain associated with intracorporeal injections could be due to the acidity of the medication, we performed a randomized study comparing the incidence of penile pain following intracorporeal injections with or without the addition of sodium bicarbonate to the intracorporeal medications. A total of 38 consecutive patients who presented to our clinic with impotence received 0.2 ml. of a combination of 3 drugs: 6 mg. papaverine, 100 micrograms. phentolamine and 10 micrograms. prostaglandin E1 with (pH 7.05) or without (pH 4.17) the addition of sodium bicarbonate (0.03 mEq.). Of the 19 patients without sodium bicarbonate added to the medication 11 (58%) complained of penile pain due to the medication, while only 1 of the 19 men (5%) who received sodium bicarbonate complained of penile pain. From these data we conclude that the penile pain following intracorporeal injections is most likely due to the acidity of the medication, which can be overcome by elevating the pH to a neutral level.", "entity": "Sodium Bicarbonate", "aliases": "Baking Soda Bicarbonate Sodium Carbonic Acid Monosodium Salt Hydrogen Carbonate", "definition": "A white, crystalline powder that is commonly used as a pH buffering agent, an electrolyte replenisher, systemic alkalizer and in topical cleansing solutions.\n    ", "id": "MESH:D017693"}
{"mention": "impotence", "mention_text": "In an attempt to determine whether penile pain associated with intracorporeal injections could be due to the acidity of the medication, we performed a randomized study comparing the incidence of penile pain following intracorporeal injections with or without the addition of sodium bicarbonate to the intracorporeal medications. A total of 38 consecutive patients who presented to our clinic with impotence received 0.2 ml. of a combination of 3 drugs: 6 mg. papaverine, 100 micrograms. phentolamine and 10 micrograms. prostaglandin E1 with (pH 7.05) or without (pH 4.17) the addition of sodium bicarbonate (0.03 mEq.). Of the 19 patients without sodium bicarbonate added to the medication 11 (58%) complained of penile pain due to the medication, while only 1 of the 19 men (5%) who received sodium bicarbonate complained of penile pain. From these data we conclude that the penile pain following intracorporeal injections is most likely due to the acidity of the medication, which can be overcome by elevating the pH to a neutral level.", "entity": "Erectile Dysfunction", "aliases": "Dysfunction Erectile Impotence Male Sexual", "definition": "The inability in the male to have a PENILE ERECTION due to psychological or organ dysfunction.\n    ", "id": "MESH:D007172"}
{"mention": "papaverine", "mention_text": "In an attempt to determine whether penile pain associated with intracorporeal injections could be due to the acidity of the medication, we performed a randomized study comparing the incidence of penile pain following intracorporeal injections with or without the addition of sodium bicarbonate to the intracorporeal medications. A total of 38 consecutive patients who presented to our clinic with impotence received 0.2 ml. of a combination of 3 drugs: 6 mg. papaverine, 100 micrograms. phentolamine and 10 micrograms. prostaglandin E1 with (pH 7.05) or without (pH 4.17) the addition of sodium bicarbonate (0.03 mEq.). Of the 19 patients without sodium bicarbonate added to the medication 11 (58%) complained of penile pain due to the medication, while only 1 of the 19 men (5%) who received sodium bicarbonate complained of penile pain. From these data we conclude that the penile pain following intracorporeal injections is most likely due to the acidity of the medication, which can be overcome by elevating the pH to a neutral level.", "entity": "Papaverine", "aliases": "Cerespan Hydrochloride Papaverine Pavabid Pavatym", "definition": "An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels.\n    ", "id": "MESH:D010208"}
{"mention": "phentolamine", "mention_text": "In an attempt to determine whether penile pain associated with intracorporeal injections could be due to the acidity of the medication, we performed a randomized study comparing the incidence of penile pain following intracorporeal injections with or without the addition of sodium bicarbonate to the intracorporeal medications. A total of 38 consecutive patients who presented to our clinic with impotence received 0.2 ml. of a combination of 3 drugs: 6 mg. papaverine, 100 micrograms. phentolamine and 10 micrograms. prostaglandin E1 with (pH 7.05) or without (pH 4.17) the addition of sodium bicarbonate (0.03 mEq.). Of the 19 patients without sodium bicarbonate added to the medication 11 (58%) complained of penile pain due to the medication, while only 1 of the 19 men (5%) who received sodium bicarbonate complained of penile pain. From these data we conclude that the penile pain following intracorporeal injections is most likely due to the acidity of the medication, which can be overcome by elevating the pH to a neutral level.", "entity": "Phentolamine", "aliases": "Alliance Brand of Phentolamine Mesylate Fentolamin Mesilate Methanesulfonate Mono-hydrochloride Novartis Paladin Mono hydrochloride Regitine Regityn Rogitine Schering-Plough Z-Max", "definition": "A nonselective alpha-adrenergic antagonist. It is used in the treatment of hypertension and hypertensive emergencies, pheochromocytoma, vasospasm of RAYNAUD DISEASE and frostbite, clonidine withdrawal syndrome, impotence, and peripheral vascular disease.\n    ", "id": "MESH:D010646"}
{"mention": "prostaglandin E1", "mention_text": "In an attempt to determine whether penile pain associated with intracorporeal injections could be due to the acidity of the medication, we performed a randomized study comparing the incidence of penile pain following intracorporeal injections with or without the addition of sodium bicarbonate to the intracorporeal medications. A total of 38 consecutive patients who presented to our clinic with impotence received 0.2 ml. of a combination of 3 drugs: 6 mg. papaverine, 100 micrograms. phentolamine and 10 micrograms. prostaglandin E1 with (pH 7.05) or without (pH 4.17) the addition of sodium bicarbonate (0.03 mEq.). Of the 19 patients without sodium bicarbonate added to the medication 11 (58%) complained of penile pain due to the medication, while only 1 of the 19 men (5%) who received sodium bicarbonate complained of penile pain. From these data we conclude that the penile pain following intracorporeal injections is most likely due to the acidity of the medication, which can be overcome by elevating the pH to a neutral level.", "entity": "Alprostadil", "aliases": "Abbott Brand of Alprostadil Allphar Astra AstraZeneca Caverject Edex Hoyer Janssen Lipo PGE1 Lipo-PGE1 Minprog Muse PGE1alpha Paladin Pharmacia 1 2 Prostaglandin E1 E1alpha Prostavasin Prostin VR Prostine Schwarz Pharma Sugiran Vasaprostan Viridal Vivus", "definition": "A potent vasodilator agent that increases peripheral blood flow.\n    ", "id": "MESH:D000527"}
{"mention": "octreotide", "mention_text": "Prospective study of the long-term effects of somatostatin analog (octreotide) on gallbladder function and gallstone formation in Chinese acromegalic patients.", "entity": "Octreotide", "aliases": "Compound 201 995 201-995 201995 Octreotide Acetate Salt SAN SM SMS Sandostatin Sandostatine Sandoz", "definition": "A potent, long-acting synthetic SOMATOSTATIN octapeptide analog that inhibits secretion of GROWTH HORMONE and is used to treat hormone-secreting tumors; DIABETES MELLITUS; HYPOTENSION, ORTHOSTATIC; HYPERINSULINISM; hypergastrinemia; and small bowel fistula.\n    ", "id": "MESH:D015282"}
{"mention": "gallstone", "mention_text": "Prospective study of the long-term effects of somatostatin analog (octreotide) on gallbladder function and gallstone formation in Chinese acromegalic patients.", "entity": "Gallstones", "aliases": "Biliary Calculi Common Bile Duct Gall Stones Gallstones Stone Gallstone", "definition": "Solid crystalline precipitates in the BILIARY TRACT, usually formed in the GALLBLADDER, resulting in the condition of CHOLELITHIASIS. Gallstones, derived from the BILE, consist mainly of calcium, cholesterol, or bilirubin.\n    ", "id": "MESH:D042882"}
{"mention": "acromegalic", "mention_text": "Prospective study of the long-term effects of somatostatin analog (octreotide) on gallbladder function and gallstone formation in Chinese acromegalic patients.", "entity": "Acromegaly", "aliases": "Acromegaly Hypersecretion Syndrome Somatotropin (Acromegaly) Syndromes Inappropriate GH Secretion Growth Hormone", "definition": "A condition caused by prolonged exposure to excessive HUMAN GROWTH HORMONE in adults. It is characterized by bony enlargement of the FACE; lower jaw (PROGNATHISM); hands; FEET; HEAD; and THORAX. The most common etiology is a GROWTH HORMONE-SECRETING PITUITARY ADENOMA. (From Joynt, Clinical Neurology, 1992, Ch36, pp79-80)\n    ", "id": "MESH:D000172"}
{"mention": "acromegaly", "mention_text": "This article reports the changes in gallbladder function examined by ultrasonography in 20 Chinese patients with active acromegaly treated with sc injection of the somatostatin analog octreotide in dosages of 300-1500 micrograms/day for a mean of 24.2 +/- 13.9 months. During treatment with octreotide, 17 patients developed sludge, 10 had gallstones, and 1 developed acute cholecystitis requiring surgery. In all of 7 patients examined acutely, gallbladder contractility was inhibited after a single 100-micrograms injection. In 8 patients followed for 24 weeks, gallbladder contractility remained depressed throughout therapy. After withdrawal of octreotide in 10 patients without gallstones, 8 patients assessed had return of normal gallbladder contractility within 1 month. In 8 of the remaining 10 patients who developed gallstones during treatment, gallbladder contractility normalized in 5 patients (3 of whom has disappearance of their stones within 3 weeks), and remained depressed in 3 (2 of whom had stones present at 6 months). Our results suggest that the suppression of gallbladder contractility is the cause of the successive formation of bile sludge, gallstones, and cholecystitis during octreotide therapy in Chinese acromegalic patients. It is therefore very important to follow the changes of gallbladder function during long-term octreotide therapy of acromegalic patients.", "entity": "Acromegaly", "aliases": "Acromegaly Hypersecretion Syndrome Somatotropin (Acromegaly) Syndromes Inappropriate GH Secretion Growth Hormone", "definition": "A condition caused by prolonged exposure to excessive HUMAN GROWTH HORMONE in adults. It is characterized by bony enlargement of the FACE; lower jaw (PROGNATHISM); hands; FEET; HEAD; and THORAX. The most common etiology is a GROWTH HORMONE-SECRETING PITUITARY ADENOMA. (From Joynt, Clinical Neurology, 1992, Ch36, pp79-80)\n    ", "id": "MESH:D000172"}
{"mention": "octreotide", "mention_text": "This article reports the changes in gallbladder function examined by ultrasonography in 20 Chinese patients with active acromegaly treated with sc injection of the somatostatin analog octreotide in dosages of 300-1500 micrograms/day for a mean of 24.2 +/- 13.9 months. During treatment with octreotide, 17 patients developed sludge, 10 had gallstones, and 1 developed acute cholecystitis requiring surgery. In all of 7 patients examined acutely, gallbladder contractility was inhibited after a single 100-micrograms injection. In 8 patients followed for 24 weeks, gallbladder contractility remained depressed throughout therapy. After withdrawal of octreotide in 10 patients without gallstones, 8 patients assessed had return of normal gallbladder contractility within 1 month. In 8 of the remaining 10 patients who developed gallstones during treatment, gallbladder contractility normalized in 5 patients (3 of whom has disappearance of their stones within 3 weeks), and remained depressed in 3 (2 of whom had stones present at 6 months). Our results suggest that the suppression of gallbladder contractility is the cause of the successive formation of bile sludge, gallstones, and cholecystitis during octreotide therapy in Chinese acromegalic patients. It is therefore very important to follow the changes of gallbladder function during long-term octreotide therapy of acromegalic patients.", "entity": "Octreotide", "aliases": "Compound 201 995 201-995 201995 Octreotide Acetate Salt SAN SM SMS Sandostatin Sandostatine Sandoz", "definition": "A potent, long-acting synthetic SOMATOSTATIN octapeptide analog that inhibits secretion of GROWTH HORMONE and is used to treat hormone-secreting tumors; DIABETES MELLITUS; HYPOTENSION, ORTHOSTATIC; HYPERINSULINISM; hypergastrinemia; and small bowel fistula.\n    ", "id": "MESH:D015282"}
{"mention": "gallstones", "mention_text": "This article reports the changes in gallbladder function examined by ultrasonography in 20 Chinese patients with active acromegaly treated with sc injection of the somatostatin analog octreotide in dosages of 300-1500 micrograms/day for a mean of 24.2 +/- 13.9 months. During treatment with octreotide, 17 patients developed sludge, 10 had gallstones, and 1 developed acute cholecystitis requiring surgery. In all of 7 patients examined acutely, gallbladder contractility was inhibited after a single 100-micrograms injection. In 8 patients followed for 24 weeks, gallbladder contractility remained depressed throughout therapy. After withdrawal of octreotide in 10 patients without gallstones, 8 patients assessed had return of normal gallbladder contractility within 1 month. In 8 of the remaining 10 patients who developed gallstones during treatment, gallbladder contractility normalized in 5 patients (3 of whom has disappearance of their stones within 3 weeks), and remained depressed in 3 (2 of whom had stones present at 6 months). Our results suggest that the suppression of gallbladder contractility is the cause of the successive formation of bile sludge, gallstones, and cholecystitis during octreotide therapy in Chinese acromegalic patients. It is therefore very important to follow the changes of gallbladder function during long-term octreotide therapy of acromegalic patients.", "entity": "Gallstones", "aliases": "Biliary Calculi Common Bile Duct Gall Stones Gallstones Stone Gallstone", "definition": "Solid crystalline precipitates in the BILIARY TRACT, usually formed in the GALLBLADDER, resulting in the condition of CHOLELITHIASIS. Gallstones, derived from the BILE, consist mainly of calcium, cholesterol, or bilirubin.\n    ", "id": "MESH:D042882"}
{"mention": "acute cholecystitis", "mention_text": "This article reports the changes in gallbladder function examined by ultrasonography in 20 Chinese patients with active acromegaly treated with sc injection of the somatostatin analog octreotide in dosages of 300-1500 micrograms/day for a mean of 24.2 +/- 13.9 months. During treatment with octreotide, 17 patients developed sludge, 10 had gallstones, and 1 developed acute cholecystitis requiring surgery. In all of 7 patients examined acutely, gallbladder contractility was inhibited after a single 100-micrograms injection. In 8 patients followed for 24 weeks, gallbladder contractility remained depressed throughout therapy. After withdrawal of octreotide in 10 patients without gallstones, 8 patients assessed had return of normal gallbladder contractility within 1 month. In 8 of the remaining 10 patients who developed gallstones during treatment, gallbladder contractility normalized in 5 patients (3 of whom has disappearance of their stones within 3 weeks), and remained depressed in 3 (2 of whom had stones present at 6 months). Our results suggest that the suppression of gallbladder contractility is the cause of the successive formation of bile sludge, gallstones, and cholecystitis during octreotide therapy in Chinese acromegalic patients. It is therefore very important to follow the changes of gallbladder function during long-term octreotide therapy of acromegalic patients.", "entity": "Cholecystitis, Acute", "aliases": "Acute Cholecystitis", "definition": "Acute inflammation of the GALLBLADDER wall. It is characterized by the presence of ABDOMINAL PAIN; FEVER; and LEUKOCYTOSIS. Gallstone obstruction of the CYSTIC DUCT is present in approximately 90% of the cases.\n    ", "id": "MESH:D041881"}
{"mention": "depressed", "mention_text": "This article reports the changes in gallbladder function examined by ultrasonography in 20 Chinese patients with active acromegaly treated with sc injection of the somatostatin analog octreotide in dosages of 300-1500 micrograms/day for a mean of 24.2 +/- 13.9 months. During treatment with octreotide, 17 patients developed sludge, 10 had gallstones, and 1 developed acute cholecystitis requiring surgery. In all of 7 patients examined acutely, gallbladder contractility was inhibited after a single 100-micrograms injection. In 8 patients followed for 24 weeks, gallbladder contractility remained depressed throughout therapy. After withdrawal of octreotide in 10 patients without gallstones, 8 patients assessed had return of normal gallbladder contractility within 1 month. In 8 of the remaining 10 patients who developed gallstones during treatment, gallbladder contractility normalized in 5 patients (3 of whom has disappearance of their stones within 3 weeks), and remained depressed in 3 (2 of whom had stones present at 6 months). Our results suggest that the suppression of gallbladder contractility is the cause of the successive formation of bile sludge, gallstones, and cholecystitis during octreotide therapy in Chinese acromegalic patients. It is therefore very important to follow the changes of gallbladder function during long-term octreotide therapy of acromegalic patients.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "cholecystitis", "mention_text": "This article reports the changes in gallbladder function examined by ultrasonography in 20 Chinese patients with active acromegaly treated with sc injection of the somatostatin analog octreotide in dosages of 300-1500 micrograms/day for a mean of 24.2 +/- 13.9 months. During treatment with octreotide, 17 patients developed sludge, 10 had gallstones, and 1 developed acute cholecystitis requiring surgery. In all of 7 patients examined acutely, gallbladder contractility was inhibited after a single 100-micrograms injection. In 8 patients followed for 24 weeks, gallbladder contractility remained depressed throughout therapy. After withdrawal of octreotide in 10 patients without gallstones, 8 patients assessed had return of normal gallbladder contractility within 1 month. In 8 of the remaining 10 patients who developed gallstones during treatment, gallbladder contractility normalized in 5 patients (3 of whom has disappearance of their stones within 3 weeks), and remained depressed in 3 (2 of whom had stones present at 6 months). Our results suggest that the suppression of gallbladder contractility is the cause of the successive formation of bile sludge, gallstones, and cholecystitis during octreotide therapy in Chinese acromegalic patients. It is therefore very important to follow the changes of gallbladder function during long-term octreotide therapy of acromegalic patients.", "entity": "Cholecystitis", "aliases": "Cholecystitis Empyema Gall Bladder Gallbladder Inflammation", "definition": "Inflammation of the GALLBLADDER; generally caused by impairment of BILE flow, GALLSTONES in the BILIARY TRACT, infections, or other diseases.\n    ", "id": "MESH:D002764"}
{"mention": "acromegalic", "mention_text": "This article reports the changes in gallbladder function examined by ultrasonography in 20 Chinese patients with active acromegaly treated with sc injection of the somatostatin analog octreotide in dosages of 300-1500 micrograms/day for a mean of 24.2 +/- 13.9 months. During treatment with octreotide, 17 patients developed sludge, 10 had gallstones, and 1 developed acute cholecystitis requiring surgery. In all of 7 patients examined acutely, gallbladder contractility was inhibited after a single 100-micrograms injection. In 8 patients followed for 24 weeks, gallbladder contractility remained depressed throughout therapy. After withdrawal of octreotide in 10 patients without gallstones, 8 patients assessed had return of normal gallbladder contractility within 1 month. In 8 of the remaining 10 patients who developed gallstones during treatment, gallbladder contractility normalized in 5 patients (3 of whom has disappearance of their stones within 3 weeks), and remained depressed in 3 (2 of whom had stones present at 6 months). Our results suggest that the suppression of gallbladder contractility is the cause of the successive formation of bile sludge, gallstones, and cholecystitis during octreotide therapy in Chinese acromegalic patients. It is therefore very important to follow the changes of gallbladder function during long-term octreotide therapy of acromegalic patients.", "entity": "Acromegaly", "aliases": "Acromegaly Hypersecretion Syndrome Somatotropin (Acromegaly) Syndromes Inappropriate GH Secretion Growth Hormone", "definition": "A condition caused by prolonged exposure to excessive HUMAN GROWTH HORMONE in adults. It is characterized by bony enlargement of the FACE; lower jaw (PROGNATHISM); hands; FEET; HEAD; and THORAX. The most common etiology is a GROWTH HORMONE-SECRETING PITUITARY ADENOMA. (From Joynt, Clinical Neurology, 1992, Ch36, pp79-80)\n    ", "id": "MESH:D000172"}
{"mention": "levodopa", "mention_text": "Improvement of levodopa-induced dyskinesia by propranolol in Parkinson's disease.", "entity": "Levodopa", "aliases": "3 Hydroxy L tyrosine 3-Hydroxy-L-tyrosine Dopaflex Dopar 3,4 Dihydroxyphenylalanine Dopa L-3,4-Dihydroxyphenylalanine L-Dopa Larodopa Levodopa Levopa Medphano Brand of Roberts Roche", "definition": "The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.\n    ", "id": "MESH:D007980"}
{"mention": "dyskinesia", "mention_text": "Improvement of levodopa-induced dyskinesia by propranolol in Parkinson's disease.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "propranolol", "mention_text": "Improvement of levodopa-induced dyskinesia by propranolol in Parkinson's disease.", "entity": "Propranolol", "aliases": "AY 20694 AY-20694 AY20694 Anaprilin Anapriline Avlocardyl Betadren Dexpropranolol Dociton Hydrochloride Propranolol Inderal Obsidan Obzidan Propanolol Rexigen", "definition": "A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.\n    ", "id": "MESH:D011433"}
{"mention": "Parkinson's disease", "mention_text": "Improvement of levodopa-induced dyskinesia by propranolol in Parkinson's disease.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "Parkinson's disease", "mention_text": "Seven patients suffering from Parkinson's disease (PD) with severely disabling dyskinesia received low-dose propranolol as an adjunct to the currently used medical treatment. There was a significant 40% improvement in the dyskinesia score without increase of parkinsonian motor disability. Ballistic and choreic dyskinesia were markedly ameliorated, whereas dystonia was not. This study suggests that administration of low doses of beta-blockers may improve levodopa-induced ballistic and choreic dyskinesia in PD.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "PD", "mention_text": "Seven patients suffering from Parkinson's disease (PD) with severely disabling dyskinesia received low-dose propranolol as an adjunct to the currently used medical treatment. There was a significant 40% improvement in the dyskinesia score without increase of parkinsonian motor disability. Ballistic and choreic dyskinesia were markedly ameliorated, whereas dystonia was not. This study suggests that administration of low doses of beta-blockers may improve levodopa-induced ballistic and choreic dyskinesia in PD.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "dyskinesia", "mention_text": "Seven patients suffering from Parkinson's disease (PD) with severely disabling dyskinesia received low-dose propranolol as an adjunct to the currently used medical treatment. There was a significant 40% improvement in the dyskinesia score without increase of parkinsonian motor disability. Ballistic and choreic dyskinesia were markedly ameliorated, whereas dystonia was not. This study suggests that administration of low doses of beta-blockers may improve levodopa-induced ballistic and choreic dyskinesia in PD.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "propranolol", "mention_text": "Seven patients suffering from Parkinson's disease (PD) with severely disabling dyskinesia received low-dose propranolol as an adjunct to the currently used medical treatment. There was a significant 40% improvement in the dyskinesia score without increase of parkinsonian motor disability. Ballistic and choreic dyskinesia were markedly ameliorated, whereas dystonia was not. This study suggests that administration of low doses of beta-blockers may improve levodopa-induced ballistic and choreic dyskinesia in PD.", "entity": "Propranolol", "aliases": "AY 20694 AY-20694 AY20694 Anaprilin Anapriline Avlocardyl Betadren Dexpropranolol Dociton Hydrochloride Propranolol Inderal Obsidan Obzidan Propanolol Rexigen", "definition": "A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.\n    ", "id": "MESH:D011433"}
{"mention": "parkinsonian", "mention_text": "Seven patients suffering from Parkinson's disease (PD) with severely disabling dyskinesia received low-dose propranolol as an adjunct to the currently used medical treatment. There was a significant 40% improvement in the dyskinesia score without increase of parkinsonian motor disability. Ballistic and choreic dyskinesia were markedly ameliorated, whereas dystonia was not. This study suggests that administration of low doses of beta-blockers may improve levodopa-induced ballistic and choreic dyskinesia in PD.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "motor disability", "mention_text": "Seven patients suffering from Parkinson's disease (PD) with severely disabling dyskinesia received low-dose propranolol as an adjunct to the currently used medical treatment. There was a significant 40% improvement in the dyskinesia score without increase of parkinsonian motor disability. Ballistic and choreic dyskinesia were markedly ameliorated, whereas dystonia was not. This study suggests that administration of low doses of beta-blockers may improve levodopa-induced ballistic and choreic dyskinesia in PD.", "entity": "Movement Disorders", "aliases": "Dyskinesia Syndrome Syndromes Lingual-Facial-Buccal Linguofacial Oral Oral-facial Orofacial Tardive Dyskinesias Dystonia Dystonias Etat Marbre Lingual Facial Buccal Movement Disorder Disorders facial Status Marmoratus", "definition": "Syndromes which feature DYSKINESIAS as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions.\n    ", "id": "MESH:D009069"}
{"mention": "dystonia", "mention_text": "Seven patients suffering from Parkinson's disease (PD) with severely disabling dyskinesia received low-dose propranolol as an adjunct to the currently used medical treatment. There was a significant 40% improvement in the dyskinesia score without increase of parkinsonian motor disability. Ballistic and choreic dyskinesia were markedly ameliorated, whereas dystonia was not. This study suggests that administration of low doses of beta-blockers may improve levodopa-induced ballistic and choreic dyskinesia in PD.", "entity": "Dystonia", "aliases": "Diurnal Dystonia Limb Muscle Paroxysmal", "definition": "An attitude or posture due to the co-contraction of agonists and antagonist muscles in one region of the body. It most often affects the large axial muscles of the trunk and limb girdles. Conditions which feature persistent or recurrent episodes of dystonia as a primary manifestation of disease are referred to as DYSTONIC DISORDERS. (Adams et al., Principles of Neurology, 6th ed, p77)\n    ", "id": "MESH:D004421"}
{"mention": "levodopa", "mention_text": "Seven patients suffering from Parkinson's disease (PD) with severely disabling dyskinesia received low-dose propranolol as an adjunct to the currently used medical treatment. There was a significant 40% improvement in the dyskinesia score without increase of parkinsonian motor disability. Ballistic and choreic dyskinesia were markedly ameliorated, whereas dystonia was not. This study suggests that administration of low doses of beta-blockers may improve levodopa-induced ballistic and choreic dyskinesia in PD.", "entity": "Levodopa", "aliases": "3 Hydroxy L tyrosine 3-Hydroxy-L-tyrosine Dopaflex Dopar 3,4 Dihydroxyphenylalanine Dopa L-3,4-Dihydroxyphenylalanine L-Dopa Larodopa Levodopa Levopa Medphano Brand of Roberts Roche", "definition": "The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.\n    ", "id": "MESH:D007980"}
{"mention": "encephalopathy", "mention_text": "Morphological features of encephalopathy after chronic administration of the antiepileptic drug valproate to rats. A transmission electron microscopic study of capillaries in the cerebellar cortex.", "entity": "Brain Diseases", "aliases": "Brain Disease Diseases Disorder Disorders CNS Intracranial Central Nervous System Encephalon", "definition": "Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.\n    ", "id": "MESH:D001927"}
{"mention": "valproate", "mention_text": "Morphological features of encephalopathy after chronic administration of the antiepileptic drug valproate to rats. A transmission electron microscopic study of capillaries in the cerebellar cortex.", "entity": "Valproic Acid", "aliases": "2 Propylpentanoic Acid 2-Propylpentanoic Acetate Dipropyl Propylisopropylacetic Valproic Calcium Valproate Convulsofin Depakene Depakine Depakote Divalproex Sodium Ergenyl Magnesium Semisodium Salt (2:1) Vupral", "definition": "A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.\n    ", "id": "MESH:D014635"}
{"mention": "sodium valproate", "mention_text": "Long-term intragastric application of the antiepileptic drug sodium valproate (Vupral \"Polfa\") at the effective dose of 200 mg/kg b. w. once daily to rats for 1, 3, 6, 9 and 12 months revealed neurological disorders indicating cerebellum damage (\"valproate encephalopathy\"). The first ultrastructural changes in structural elements of the blood-brain-barrier (BBB) in the cerebellar cortex were detectable after 3 months of the experiment. They became more severe in the later months of the experiment, and were most severe after 12 months, located mainly in the molecular layer of the cerebellar cortex. Lesions of the capillary included necrosis of endothelial cells. Organelles of these cells, in particular the mitochondria (increased number and size, distinct degeneration of their matrix and cristae) and Golgi apparatus were altered. Reduced size of capillary lumen and occlusion were caused by swollen endothelial cells which had luminal protrusions and swollen microvilli. Pressure on the vessel wall was produced by enlarged perivascular astrocytic processes. Fragments of necrotic endothelial cells were in the vascular lumens and in these there was loosening and breaking of tight cellular junctions. Damage to the vascular basement lamina was also observed. Damage to the capillary was accompanied by marked damage to neuroglial cells, mainly to perivascular processes of astrocytes. The proliferation of astrocytes (Bergmann's in particular) and occasionally of oligodendrocytes was found. Alterations in the structural elements of the BBB coexisted with marked lesions of neurons of the cerebellum (Purkinje cells are earliest). In electron micrographs both luminal and antiluminal sides of the BBB of the cerebellar cortex had similar lesions. The possible influence of the hepatic damage, mainly hyperammonemia, upon the development of valproate encephalopathy is discussed.", "entity": "Valproic Acid", "aliases": "2 Propylpentanoic Acid 2-Propylpentanoic Acetate Dipropyl Propylisopropylacetic Valproic Calcium Valproate Convulsofin Depakene Depakine Depakote Divalproex Sodium Ergenyl Magnesium Semisodium Salt (2:1) Vupral", "definition": "A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.\n    ", "id": "MESH:D014635"}
{"mention": "neurological disorders", "mention_text": "Long-term intragastric application of the antiepileptic drug sodium valproate (Vupral \"Polfa\") at the effective dose of 200 mg/kg b. w. once daily to rats for 1, 3, 6, 9 and 12 months revealed neurological disorders indicating cerebellum damage (\"valproate encephalopathy\"). The first ultrastructural changes in structural elements of the blood-brain-barrier (BBB) in the cerebellar cortex were detectable after 3 months of the experiment. They became more severe in the later months of the experiment, and were most severe after 12 months, located mainly in the molecular layer of the cerebellar cortex. Lesions of the capillary included necrosis of endothelial cells. Organelles of these cells, in particular the mitochondria (increased number and size, distinct degeneration of their matrix and cristae) and Golgi apparatus were altered. Reduced size of capillary lumen and occlusion were caused by swollen endothelial cells which had luminal protrusions and swollen microvilli. Pressure on the vessel wall was produced by enlarged perivascular astrocytic processes. Fragments of necrotic endothelial cells were in the vascular lumens and in these there was loosening and breaking of tight cellular junctions. Damage to the vascular basement lamina was also observed. Damage to the capillary was accompanied by marked damage to neuroglial cells, mainly to perivascular processes of astrocytes. The proliferation of astrocytes (Bergmann's in particular) and occasionally of oligodendrocytes was found. Alterations in the structural elements of the BBB coexisted with marked lesions of neurons of the cerebellum (Purkinje cells are earliest). In electron micrographs both luminal and antiluminal sides of the BBB of the cerebellar cortex had similar lesions. The possible influence of the hepatic damage, mainly hyperammonemia, upon the development of valproate encephalopathy is discussed.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "cerebellum damage", "mention_text": "Long-term intragastric application of the antiepileptic drug sodium valproate (Vupral \"Polfa\") at the effective dose of 200 mg/kg b. w. once daily to rats for 1, 3, 6, 9 and 12 months revealed neurological disorders indicating cerebellum damage (\"valproate encephalopathy\"). The first ultrastructural changes in structural elements of the blood-brain-barrier (BBB) in the cerebellar cortex were detectable after 3 months of the experiment. They became more severe in the later months of the experiment, and were most severe after 12 months, located mainly in the molecular layer of the cerebellar cortex. Lesions of the capillary included necrosis of endothelial cells. Organelles of these cells, in particular the mitochondria (increased number and size, distinct degeneration of their matrix and cristae) and Golgi apparatus were altered. Reduced size of capillary lumen and occlusion were caused by swollen endothelial cells which had luminal protrusions and swollen microvilli. Pressure on the vessel wall was produced by enlarged perivascular astrocytic processes. Fragments of necrotic endothelial cells were in the vascular lumens and in these there was loosening and breaking of tight cellular junctions. Damage to the vascular basement lamina was also observed. Damage to the capillary was accompanied by marked damage to neuroglial cells, mainly to perivascular processes of astrocytes. The proliferation of astrocytes (Bergmann's in particular) and occasionally of oligodendrocytes was found. Alterations in the structural elements of the BBB coexisted with marked lesions of neurons of the cerebellum (Purkinje cells are earliest). In electron micrographs both luminal and antiluminal sides of the BBB of the cerebellar cortex had similar lesions. The possible influence of the hepatic damage, mainly hyperammonemia, upon the development of valproate encephalopathy is discussed.", "entity": "Cerebellar Diseases", "aliases": "Cerebellar Disease Diseases Disorder Disorders Dysfunction Dysfunctions Syndrome Syndromes Cerebellum", "definition": "Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, GAIT ATAXIA, and MUSCLE HYPOTONIA.\n    ", "id": "MESH:D002526"}
{"mention": "valproate", "mention_text": "Long-term intragastric application of the antiepileptic drug sodium valproate (Vupral \"Polfa\") at the effective dose of 200 mg/kg b. w. once daily to rats for 1, 3, 6, 9 and 12 months revealed neurological disorders indicating cerebellum damage (\"valproate encephalopathy\"). The first ultrastructural changes in structural elements of the blood-brain-barrier (BBB) in the cerebellar cortex were detectable after 3 months of the experiment. They became more severe in the later months of the experiment, and were most severe after 12 months, located mainly in the molecular layer of the cerebellar cortex. Lesions of the capillary included necrosis of endothelial cells. Organelles of these cells, in particular the mitochondria (increased number and size, distinct degeneration of their matrix and cristae) and Golgi apparatus were altered. Reduced size of capillary lumen and occlusion were caused by swollen endothelial cells which had luminal protrusions and swollen microvilli. Pressure on the vessel wall was produced by enlarged perivascular astrocytic processes. Fragments of necrotic endothelial cells were in the vascular lumens and in these there was loosening and breaking of tight cellular junctions. Damage to the vascular basement lamina was also observed. Damage to the capillary was accompanied by marked damage to neuroglial cells, mainly to perivascular processes of astrocytes. The proliferation of astrocytes (Bergmann's in particular) and occasionally of oligodendrocytes was found. Alterations in the structural elements of the BBB coexisted with marked lesions of neurons of the cerebellum (Purkinje cells are earliest). In electron micrographs both luminal and antiluminal sides of the BBB of the cerebellar cortex had similar lesions. The possible influence of the hepatic damage, mainly hyperammonemia, upon the development of valproate encephalopathy is discussed.", "entity": "Valproic Acid", "aliases": "2 Propylpentanoic Acid 2-Propylpentanoic Acetate Dipropyl Propylisopropylacetic Valproic Calcium Valproate Convulsofin Depakene Depakine Depakote Divalproex Sodium Ergenyl Magnesium Semisodium Salt (2:1) Vupral", "definition": "A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.\n    ", "id": "MESH:D014635"}
{"mention": "encephalopathy", "mention_text": "Long-term intragastric application of the antiepileptic drug sodium valproate (Vupral \"Polfa\") at the effective dose of 200 mg/kg b. w. once daily to rats for 1, 3, 6, 9 and 12 months revealed neurological disorders indicating cerebellum damage (\"valproate encephalopathy\"). The first ultrastructural changes in structural elements of the blood-brain-barrier (BBB) in the cerebellar cortex were detectable after 3 months of the experiment. They became more severe in the later months of the experiment, and were most severe after 12 months, located mainly in the molecular layer of the cerebellar cortex. Lesions of the capillary included necrosis of endothelial cells. Organelles of these cells, in particular the mitochondria (increased number and size, distinct degeneration of their matrix and cristae) and Golgi apparatus were altered. Reduced size of capillary lumen and occlusion were caused by swollen endothelial cells which had luminal protrusions and swollen microvilli. Pressure on the vessel wall was produced by enlarged perivascular astrocytic processes. Fragments of necrotic endothelial cells were in the vascular lumens and in these there was loosening and breaking of tight cellular junctions. Damage to the vascular basement lamina was also observed. Damage to the capillary was accompanied by marked damage to neuroglial cells, mainly to perivascular processes of astrocytes. The proliferation of astrocytes (Bergmann's in particular) and occasionally of oligodendrocytes was found. Alterations in the structural elements of the BBB coexisted with marked lesions of neurons of the cerebellum (Purkinje cells are earliest). In electron micrographs both luminal and antiluminal sides of the BBB of the cerebellar cortex had similar lesions. The possible influence of the hepatic damage, mainly hyperammonemia, upon the development of valproate encephalopathy is discussed.", "entity": "Brain Diseases", "aliases": "Brain Disease Diseases Disorder Disorders CNS Intracranial Central Nervous System Encephalon", "definition": "Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.\n    ", "id": "MESH:D001927"}
{"mention": "necrosis", "mention_text": "Long-term intragastric application of the antiepileptic drug sodium valproate (Vupral \"Polfa\") at the effective dose of 200 mg/kg b. w. once daily to rats for 1, 3, 6, 9 and 12 months revealed neurological disorders indicating cerebellum damage (\"valproate encephalopathy\"). The first ultrastructural changes in structural elements of the blood-brain-barrier (BBB) in the cerebellar cortex were detectable after 3 months of the experiment. They became more severe in the later months of the experiment, and were most severe after 12 months, located mainly in the molecular layer of the cerebellar cortex. Lesions of the capillary included necrosis of endothelial cells. Organelles of these cells, in particular the mitochondria (increased number and size, distinct degeneration of their matrix and cristae) and Golgi apparatus were altered. Reduced size of capillary lumen and occlusion were caused by swollen endothelial cells which had luminal protrusions and swollen microvilli. Pressure on the vessel wall was produced by enlarged perivascular astrocytic processes. Fragments of necrotic endothelial cells were in the vascular lumens and in these there was loosening and breaking of tight cellular junctions. Damage to the vascular basement lamina was also observed. Damage to the capillary was accompanied by marked damage to neuroglial cells, mainly to perivascular processes of astrocytes. The proliferation of astrocytes (Bergmann's in particular) and occasionally of oligodendrocytes was found. Alterations in the structural elements of the BBB coexisted with marked lesions of neurons of the cerebellum (Purkinje cells are earliest). In electron micrographs both luminal and antiluminal sides of the BBB of the cerebellar cortex had similar lesions. The possible influence of the hepatic damage, mainly hyperammonemia, upon the development of valproate encephalopathy is discussed.", "entity": "Necrosis", "aliases": "Necroses Necrosis", "definition": "The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. Distinguish it from APOPTOSIS which is a normal, regulated cellular process.\n    ", "id": "MESH:D009336"}
{"mention": "luminal", "mention_text": "Long-term intragastric application of the antiepileptic drug sodium valproate (Vupral \"Polfa\") at the effective dose of 200 mg/kg b. w. once daily to rats for 1, 3, 6, 9 and 12 months revealed neurological disorders indicating cerebellum damage (\"valproate encephalopathy\"). The first ultrastructural changes in structural elements of the blood-brain-barrier (BBB) in the cerebellar cortex were detectable after 3 months of the experiment. They became more severe in the later months of the experiment, and were most severe after 12 months, located mainly in the molecular layer of the cerebellar cortex. Lesions of the capillary included necrosis of endothelial cells. Organelles of these cells, in particular the mitochondria (increased number and size, distinct degeneration of their matrix and cristae) and Golgi apparatus were altered. Reduced size of capillary lumen and occlusion were caused by swollen endothelial cells which had luminal protrusions and swollen microvilli. Pressure on the vessel wall was produced by enlarged perivascular astrocytic processes. Fragments of necrotic endothelial cells were in the vascular lumens and in these there was loosening and breaking of tight cellular junctions. Damage to the vascular basement lamina was also observed. Damage to the capillary was accompanied by marked damage to neuroglial cells, mainly to perivascular processes of astrocytes. The proliferation of astrocytes (Bergmann's in particular) and occasionally of oligodendrocytes was found. Alterations in the structural elements of the BBB coexisted with marked lesions of neurons of the cerebellum (Purkinje cells are earliest). In electron micrographs both luminal and antiluminal sides of the BBB of the cerebellar cortex had similar lesions. The possible influence of the hepatic damage, mainly hyperammonemia, upon the development of valproate encephalopathy is discussed.", "entity": "Phenobarbital", "aliases": "Acid Phenylethylbarbituric Gardenal Hysteps Luminal Monosodium Salt Phenobarbital Phenemal Sodium Phenobarbitone Phenylbarbital", "definition": "A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.\n    ", "id": "MESH:D010634"}
{"mention": "necrotic", "mention_text": "Long-term intragastric application of the antiepileptic drug sodium valproate (Vupral \"Polfa\") at the effective dose of 200 mg/kg b. w. once daily to rats for 1, 3, 6, 9 and 12 months revealed neurological disorders indicating cerebellum damage (\"valproate encephalopathy\"). The first ultrastructural changes in structural elements of the blood-brain-barrier (BBB) in the cerebellar cortex were detectable after 3 months of the experiment. They became more severe in the later months of the experiment, and were most severe after 12 months, located mainly in the molecular layer of the cerebellar cortex. Lesions of the capillary included necrosis of endothelial cells. Organelles of these cells, in particular the mitochondria (increased number and size, distinct degeneration of their matrix and cristae) and Golgi apparatus were altered. Reduced size of capillary lumen and occlusion were caused by swollen endothelial cells which had luminal protrusions and swollen microvilli. Pressure on the vessel wall was produced by enlarged perivascular astrocytic processes. Fragments of necrotic endothelial cells were in the vascular lumens and in these there was loosening and breaking of tight cellular junctions. Damage to the vascular basement lamina was also observed. Damage to the capillary was accompanied by marked damage to neuroglial cells, mainly to perivascular processes of astrocytes. The proliferation of astrocytes (Bergmann's in particular) and occasionally of oligodendrocytes was found. Alterations in the structural elements of the BBB coexisted with marked lesions of neurons of the cerebellum (Purkinje cells are earliest). In electron micrographs both luminal and antiluminal sides of the BBB of the cerebellar cortex had similar lesions. The possible influence of the hepatic damage, mainly hyperammonemia, upon the development of valproate encephalopathy is discussed.", "entity": "Necrosis", "aliases": "Necroses Necrosis", "definition": "The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. Distinguish it from APOPTOSIS which is a normal, regulated cellular process.\n    ", "id": "MESH:D009336"}
{"mention": "hepatic damage", "mention_text": "Long-term intragastric application of the antiepileptic drug sodium valproate (Vupral \"Polfa\") at the effective dose of 200 mg/kg b. w. once daily to rats for 1, 3, 6, 9 and 12 months revealed neurological disorders indicating cerebellum damage (\"valproate encephalopathy\"). The first ultrastructural changes in structural elements of the blood-brain-barrier (BBB) in the cerebellar cortex were detectable after 3 months of the experiment. They became more severe in the later months of the experiment, and were most severe after 12 months, located mainly in the molecular layer of the cerebellar cortex. Lesions of the capillary included necrosis of endothelial cells. Organelles of these cells, in particular the mitochondria (increased number and size, distinct degeneration of their matrix and cristae) and Golgi apparatus were altered. Reduced size of capillary lumen and occlusion were caused by swollen endothelial cells which had luminal protrusions and swollen microvilli. Pressure on the vessel wall was produced by enlarged perivascular astrocytic processes. Fragments of necrotic endothelial cells were in the vascular lumens and in these there was loosening and breaking of tight cellular junctions. Damage to the vascular basement lamina was also observed. Damage to the capillary was accompanied by marked damage to neuroglial cells, mainly to perivascular processes of astrocytes. The proliferation of astrocytes (Bergmann's in particular) and occasionally of oligodendrocytes was found. Alterations in the structural elements of the BBB coexisted with marked lesions of neurons of the cerebellum (Purkinje cells are earliest). In electron micrographs both luminal and antiluminal sides of the BBB of the cerebellar cortex had similar lesions. The possible influence of the hepatic damage, mainly hyperammonemia, upon the development of valproate encephalopathy is discussed.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "hyperammonemia", "mention_text": "Long-term intragastric application of the antiepileptic drug sodium valproate (Vupral \"Polfa\") at the effective dose of 200 mg/kg b. w. once daily to rats for 1, 3, 6, 9 and 12 months revealed neurological disorders indicating cerebellum damage (\"valproate encephalopathy\"). The first ultrastructural changes in structural elements of the blood-brain-barrier (BBB) in the cerebellar cortex were detectable after 3 months of the experiment. They became more severe in the later months of the experiment, and were most severe after 12 months, located mainly in the molecular layer of the cerebellar cortex. Lesions of the capillary included necrosis of endothelial cells. Organelles of these cells, in particular the mitochondria (increased number and size, distinct degeneration of their matrix and cristae) and Golgi apparatus were altered. Reduced size of capillary lumen and occlusion were caused by swollen endothelial cells which had luminal protrusions and swollen microvilli. Pressure on the vessel wall was produced by enlarged perivascular astrocytic processes. Fragments of necrotic endothelial cells were in the vascular lumens and in these there was loosening and breaking of tight cellular junctions. Damage to the vascular basement lamina was also observed. Damage to the capillary was accompanied by marked damage to neuroglial cells, mainly to perivascular processes of astrocytes. The proliferation of astrocytes (Bergmann's in particular) and occasionally of oligodendrocytes was found. Alterations in the structural elements of the BBB coexisted with marked lesions of neurons of the cerebellum (Purkinje cells are earliest). In electron micrographs both luminal and antiluminal sides of the BBB of the cerebellar cortex had similar lesions. The possible influence of the hepatic damage, mainly hyperammonemia, upon the development of valproate encephalopathy is discussed.", "entity": "Hyperammonemia", "aliases": "Hyperammonemia", "definition": "Elevated level of AMMONIA in the blood. It is a sign of defective CATABOLISM of AMINO ACIDS or ammonia to UREA.\n    ", "id": "MESH:D022124"}
{"mention": "toxicity", "mention_text": "Macula toxicity after intravitreal amikacin.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "amikacin", "mention_text": "Macula toxicity after intravitreal amikacin.", "entity": "Amikacin", "aliases": "A.M.K Amikacin Sulfate Amikacina Medical Normon Amikafur Amikalem Amikason's Amikayect Amikin Amiklin Amukin Apothecon Brand of BB K 8 K8 BB-K BB-K8 BBK BBK8 Biclin Biklin Bristol Myers Squibb Bristol-Myers Collins Cryopharma Fustery Galen Gamikal Grossmann Kanbine Lemery Mead Johnson Norman Oprad Pisa Rovi Son's Yectamid", "definition": "A broad-spectrum antibiotic derived from KANAMYCIN. It is reno- and oto-toxic like the other aminoglycoside antibiotics.\n    ", "id": "MESH:D000583"}
{"mention": "aminoglycosides", "mention_text": "BACKGROUND: Although intravitreal aminoglycosides have substantially improved visual prognosis in endophthalmitis, macular infarction may impair full visual recovery. METHODS: We present a case of presumed amikacin retinal toxicity following treatment with amikacin and vancomycin for alpha-haemolytic streptococcal endophthalmitis. RESULTS: Endophthalmitis resolved with improvement in visual acuity to 6/24 at three months. Fundus fluorescein angiography confirmed macular capillary closure and telangiectasis. CONCLUSIONS: Currently accepted intravitreal antibiotic regimens may cause retinal toxicity and macular ischaemia. Treatment strategies aimed at avoiding retinal toxicity are discussed.", "entity": "Aminoglycosides", "aliases": "Aminoglycosides", "definition": "Glycosylated compounds in which there is an amino substituent on the glycoside. Some of them are clinically important ANTIBIOTICS.\n    ", "id": "MESH:D000617"}
{"mention": "endophthalmitis", "mention_text": "BACKGROUND: Although intravitreal aminoglycosides have substantially improved visual prognosis in endophthalmitis, macular infarction may impair full visual recovery. METHODS: We present a case of presumed amikacin retinal toxicity following treatment with amikacin and vancomycin for alpha-haemolytic streptococcal endophthalmitis. RESULTS: Endophthalmitis resolved with improvement in visual acuity to 6/24 at three months. Fundus fluorescein angiography confirmed macular capillary closure and telangiectasis. CONCLUSIONS: Currently accepted intravitreal antibiotic regimens may cause retinal toxicity and macular ischaemia. Treatment strategies aimed at avoiding retinal toxicity are discussed.", "entity": "Endophthalmitis", "aliases": "Endophthalmitides Infectious Endophthalmitis Ophthalmia Ophthalmias", "definition": "Suppurative inflammation of the tissues of the internal structures of the eye frequently associated with an infection.\n    ", "id": "MESH:D009877"}
{"mention": "infarction", "mention_text": "BACKGROUND: Although intravitreal aminoglycosides have substantially improved visual prognosis in endophthalmitis, macular infarction may impair full visual recovery. METHODS: We present a case of presumed amikacin retinal toxicity following treatment with amikacin and vancomycin for alpha-haemolytic streptococcal endophthalmitis. RESULTS: Endophthalmitis resolved with improvement in visual acuity to 6/24 at three months. Fundus fluorescein angiography confirmed macular capillary closure and telangiectasis. CONCLUSIONS: Currently accepted intravitreal antibiotic regimens may cause retinal toxicity and macular ischaemia. Treatment strategies aimed at avoiding retinal toxicity are discussed.", "entity": "Infarction", "aliases": "Infarction Infarctions", "definition": "Formation of an infarct, which is NECROSIS in tissue due to local ISCHEMIA resulting from obstruction of BLOOD CIRCULATION, most commonly by a THROMBUS or EMBOLUS.\n    ", "id": "MESH:D007238"}
{"mention": "amikacin", "mention_text": "BACKGROUND: Although intravitreal aminoglycosides have substantially improved visual prognosis in endophthalmitis, macular infarction may impair full visual recovery. METHODS: We present a case of presumed amikacin retinal toxicity following treatment with amikacin and vancomycin for alpha-haemolytic streptococcal endophthalmitis. RESULTS: Endophthalmitis resolved with improvement in visual acuity to 6/24 at three months. Fundus fluorescein angiography confirmed macular capillary closure and telangiectasis. CONCLUSIONS: Currently accepted intravitreal antibiotic regimens may cause retinal toxicity and macular ischaemia. Treatment strategies aimed at avoiding retinal toxicity are discussed.", "entity": "Amikacin", "aliases": "A.M.K Amikacin Sulfate Amikacina Medical Normon Amikafur Amikalem Amikason's Amikayect Amikin Amiklin Amukin Apothecon Brand of BB K 8 K8 BB-K BB-K8 BBK BBK8 Biclin Biklin Bristol Myers Squibb Bristol-Myers Collins Cryopharma Fustery Galen Gamikal Grossmann Kanbine Lemery Mead Johnson Norman Oprad Pisa Rovi Son's Yectamid", "definition": "A broad-spectrum antibiotic derived from KANAMYCIN. It is reno- and oto-toxic like the other aminoglycoside antibiotics.\n    ", "id": "MESH:D000583"}
{"mention": "retinal toxicity", "mention_text": "BACKGROUND: Although intravitreal aminoglycosides have substantially improved visual prognosis in endophthalmitis, macular infarction may impair full visual recovery. METHODS: We present a case of presumed amikacin retinal toxicity following treatment with amikacin and vancomycin for alpha-haemolytic streptococcal endophthalmitis. RESULTS: Endophthalmitis resolved with improvement in visual acuity to 6/24 at three months. Fundus fluorescein angiography confirmed macular capillary closure and telangiectasis. CONCLUSIONS: Currently accepted intravitreal antibiotic regimens may cause retinal toxicity and macular ischaemia. Treatment strategies aimed at avoiding retinal toxicity are discussed.", "entity": "Retinal Diseases", "aliases": "Disease Retinal Diseases", "definition": "", "id": "MESH:D012164"}
{"mention": "vancomycin", "mention_text": "BACKGROUND: Although intravitreal aminoglycosides have substantially improved visual prognosis in endophthalmitis, macular infarction may impair full visual recovery. METHODS: We present a case of presumed amikacin retinal toxicity following treatment with amikacin and vancomycin for alpha-haemolytic streptococcal endophthalmitis. RESULTS: Endophthalmitis resolved with improvement in visual acuity to 6/24 at three months. Fundus fluorescein angiography confirmed macular capillary closure and telangiectasis. CONCLUSIONS: Currently accepted intravitreal antibiotic regimens may cause retinal toxicity and macular ischaemia. Treatment strategies aimed at avoiding retinal toxicity are discussed.", "entity": "Vancomycin", "aliases": "AB-Vancomycin Abbott Brand of Vancomycin Hydrochloride Azupharma Chiesi Combino Dakota Diatracin Dista Eli Lilly Hexal MIP Norman Sulfate VANCO-cell Vanco Vanco-saar Vancocin HCl Vancocine Vancomicina Phar Phosphate (1:2) Decahydrate Vancomycin-ratiopharm Vancomycine cell pharm curasan ratiopharm", "definition": "Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to RISTOCETIN that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear.\n    ", "id": "MESH:D014640"}
{"mention": "streptococcal endophthalmitis", "mention_text": "BACKGROUND: Although intravitreal aminoglycosides have substantially improved visual prognosis in endophthalmitis, macular infarction may impair full visual recovery. METHODS: We present a case of presumed amikacin retinal toxicity following treatment with amikacin and vancomycin for alpha-haemolytic streptococcal endophthalmitis. RESULTS: Endophthalmitis resolved with improvement in visual acuity to 6/24 at three months. Fundus fluorescein angiography confirmed macular capillary closure and telangiectasis. CONCLUSIONS: Currently accepted intravitreal antibiotic regimens may cause retinal toxicity and macular ischaemia. Treatment strategies aimed at avoiding retinal toxicity are discussed.", "entity": "Streptococcal Infections", "aliases": "Infection Streptococcal Infections", "definition": "Infections with bacteria of the genus STREPTOCOCCUS.\n    ", "id": "MESH:D013290"}
{"mention": "Endophthalmitis", "mention_text": "BACKGROUND: Although intravitreal aminoglycosides have substantially improved visual prognosis in endophthalmitis, macular infarction may impair full visual recovery. METHODS: We present a case of presumed amikacin retinal toxicity following treatment with amikacin and vancomycin for alpha-haemolytic streptococcal endophthalmitis. RESULTS: Endophthalmitis resolved with improvement in visual acuity to 6/24 at three months. Fundus fluorescein angiography confirmed macular capillary closure and telangiectasis. CONCLUSIONS: Currently accepted intravitreal antibiotic regimens may cause retinal toxicity and macular ischaemia. Treatment strategies aimed at avoiding retinal toxicity are discussed.", "entity": "Endophthalmitis", "aliases": "Endophthalmitides Infectious Endophthalmitis Ophthalmia Ophthalmias", "definition": "Suppurative inflammation of the tissues of the internal structures of the eye frequently associated with an infection.\n    ", "id": "MESH:D009877"}
{"mention": "fluorescein", "mention_text": "BACKGROUND: Although intravitreal aminoglycosides have substantially improved visual prognosis in endophthalmitis, macular infarction may impair full visual recovery. METHODS: We present a case of presumed amikacin retinal toxicity following treatment with amikacin and vancomycin for alpha-haemolytic streptococcal endophthalmitis. RESULTS: Endophthalmitis resolved with improvement in visual acuity to 6/24 at three months. Fundus fluorescein angiography confirmed macular capillary closure and telangiectasis. CONCLUSIONS: Currently accepted intravitreal antibiotic regimens may cause retinal toxicity and macular ischaemia. Treatment strategies aimed at avoiding retinal toxicity are discussed.", "entity": "Fluorescein", "aliases": "Alcon Brand of Fluorescein Sodium Allergan C.I. 45350 Cahill May Roberts Chauvin Colircusi Fluoresceina D & C Yellow No. 7 8 and D&C Diba Diofluor Dioptic Dipotassium Salt Disodium Fluor I Strip A.T. Fluor-I-Strip Monosodium Minims Fluoresceine Fluorescite Fluorescéine sodique Faure Fluorets Ful Glo Ful-Glo Funduscein Stains Novartis Optifluor Smith Nephew Sola Barnes Hind Sola-Barnes-Hind Uranine Wyeth", "definition": "A phthalic indicator dye that appears yellow-green in normal tear film and bright green in a more alkaline medium such as the aqueous humor, used as a diagnostic aid in corneal injuries and corneal trauma.\n    ", "id": "MESH:D019793"}
{"mention": "telangiectasis", "mention_text": "BACKGROUND: Although intravitreal aminoglycosides have substantially improved visual prognosis in endophthalmitis, macular infarction may impair full visual recovery. METHODS: We present a case of presumed amikacin retinal toxicity following treatment with amikacin and vancomycin for alpha-haemolytic streptococcal endophthalmitis. RESULTS: Endophthalmitis resolved with improvement in visual acuity to 6/24 at three months. Fundus fluorescein angiography confirmed macular capillary closure and telangiectasis. CONCLUSIONS: Currently accepted intravitreal antibiotic regimens may cause retinal toxicity and macular ischaemia. Treatment strategies aimed at avoiding retinal toxicity are discussed.", "entity": "Telangiectasis", "aliases": "Spider Vein Veins Telangiectases Telangiectasia Telangiectasias Telangiectasis", "definition": "Permanent dilation of preexisting blood vessels (CAPILLARIES; ARTERIOLES; VENULES) creating small focal red lesions, most commonly in the skin or mucous membranes. It is characterized by the prominence of skin blood vessels, such as vascular spiders.\n    ", "id": "MESH:D013684"}
{"mention": "ischaemia", "mention_text": "BACKGROUND: Although intravitreal aminoglycosides have substantially improved visual prognosis in endophthalmitis, macular infarction may impair full visual recovery. METHODS: We present a case of presumed amikacin retinal toxicity following treatment with amikacin and vancomycin for alpha-haemolytic streptococcal endophthalmitis. RESULTS: Endophthalmitis resolved with improvement in visual acuity to 6/24 at three months. Fundus fluorescein angiography confirmed macular capillary closure and telangiectasis. CONCLUSIONS: Currently accepted intravitreal antibiotic regimens may cause retinal toxicity and macular ischaemia. Treatment strategies aimed at avoiding retinal toxicity are discussed.", "entity": "Ischemia", "aliases": "Ischemia Ischemias", "definition": "A hypoperfusion of the BLOOD through an organ or tissue caused by a PATHOLOGIC CONSTRICTION or obstruction of its BLOOD VESSELS, or an absence of BLOOD CIRCULATION.\n    ", "id": "MESH:D007511"}
{"mention": "atrioventricular reentrant tachycardia", "mention_text": "Iatrogenically induced intractable atrioventricular reentrant tachycardia after verapamil and catheter ablation in a patient with Wolff-Parkinson-White syndrome and idiopathic dilated cardiomyopathy.", "entity": "Tachycardia, Atrioventricular Nodal Reentry", "aliases": "AV Nodal Reentrant Tachycardia Atrioventricular Reentry", "definition": "Abnormally rapid heartbeats caused by reentry of atrial impulse into the dual (fast and slow) pathways of ATRIOVENTRICULAR NODE. The common type involves a blocked atrial impulse in the slow pathway which reenters the fast pathway in a retrograde direction and simultaneously conducts to the atria and the ventricles leading to rapid HEART RATE of 150-250 beats per minute.\n    ", "id": "MESH:D013611"}
{"mention": "verapamil", "mention_text": "Iatrogenically induced intractable atrioventricular reentrant tachycardia after verapamil and catheter ablation in a patient with Wolff-Parkinson-White syndrome and idiopathic dilated cardiomyopathy.", "entity": "Verapamil", "aliases": "Calan Cordilox Dexverapamil Falicard Finoptin Hydrochloride Verapamil Iproveratril Isoptin Isoptine Izoptin Lekoptin Sandoz Brand of", "definition": "A calcium channel blocker that is a class IV anti-arrhythmia agent.\n    ", "id": "MESH:D014700"}
{"mention": "Wolff-Parkinson-White syndrome", "mention_text": "Iatrogenically induced intractable atrioventricular reentrant tachycardia after verapamil and catheter ablation in a patient with Wolff-Parkinson-White syndrome and idiopathic dilated cardiomyopathy.", "entity": "Wolff-Parkinson-White Syndrome", "aliases": "Anomalous Ventricular Excitation Syndrome Auriculoventricular Accessory Pathway False Bundle-Branch Block WPW Wolf-Parkinson-White Wolff-Parkinson-White Pre-Excitation with Arrhythmia Wolf Parkinson White Wolff", "definition": "A form of ventricular pre-excitation characterized by a short PR interval and a long QRS interval with a delta wave. In this syndrome, atrial impulses are abnormally conducted to the HEART VENTRICLES via an ACCESSORY CONDUCTING PATHWAY that is located between the wall of the right or left atria and the ventricles, also known as a BUNDLE OF KENT. The inherited form can be caused by mutation of PRKAG2 gene encoding a gamma-2 regulatory subunit of AMP-activated protein kinase.\n    ", "id": "MESH:D014927"}
{"mention": "idiopathic dilated cardiomyopathy", "mention_text": "Iatrogenically induced intractable atrioventricular reentrant tachycardia after verapamil and catheter ablation in a patient with Wolff-Parkinson-White syndrome and idiopathic dilated cardiomyopathy.", "entity": "Cardiomyopathy, Dilated", "aliases": "1A Dilated cardiomyopathy 1As Cardiomyopathies Congestive Familial Idiopathic Cardiomyopathy 1a Autosomal Recessive CMD1A LMNA With Conduction Defect 1 with Deffect1", "definition": "A form of CARDIAC MUSCLE disease that is characterized by ventricular dilation, VENTRICULAR DYSFUNCTION, and HEART FAILURE. Risk factors include SMOKING; ALCOHOL DRINKING; HYPERTENSION; INFECTION; PREGNANCY; and mutations in the LMNA gene encoding LAMIN TYPE A, a NUCLEAR LAMINA protein.\n    ", "id": "MESH:D002311"}
{"mention": "WPW syndrome", "mention_text": "In a patient with WPW syndrome and idiopathic dilated cardiomyopathy, intractable atrioventricular reentrant tachycardia (AVRT) was iatrogenically induced. QRS without preexcitation, caused by junctional escape beats after verapamil or unidirectional antegrade block of accessory pathway after catheter ablation, established frequent AVRT attack.", "entity": "Wolff-Parkinson-White Syndrome", "aliases": "Anomalous Ventricular Excitation Syndrome Auriculoventricular Accessory Pathway False Bundle-Branch Block WPW Wolf-Parkinson-White Wolff-Parkinson-White Pre-Excitation with Arrhythmia Wolf Parkinson White Wolff", "definition": "A form of ventricular pre-excitation characterized by a short PR interval and a long QRS interval with a delta wave. In this syndrome, atrial impulses are abnormally conducted to the HEART VENTRICLES via an ACCESSORY CONDUCTING PATHWAY that is located between the wall of the right or left atria and the ventricles, also known as a BUNDLE OF KENT. The inherited form can be caused by mutation of PRKAG2 gene encoding a gamma-2 regulatory subunit of AMP-activated protein kinase.\n    ", "id": "MESH:D014927"}
{"mention": "idiopathic dilated cardiomyopathy", "mention_text": "In a patient with WPW syndrome and idiopathic dilated cardiomyopathy, intractable atrioventricular reentrant tachycardia (AVRT) was iatrogenically induced. QRS without preexcitation, caused by junctional escape beats after verapamil or unidirectional antegrade block of accessory pathway after catheter ablation, established frequent AVRT attack.", "entity": "Cardiomyopathy, Dilated", "aliases": "1A Dilated cardiomyopathy 1As Cardiomyopathies Congestive Familial Idiopathic Cardiomyopathy 1a Autosomal Recessive CMD1A LMNA With Conduction Defect 1 with Deffect1", "definition": "A form of CARDIAC MUSCLE disease that is characterized by ventricular dilation, VENTRICULAR DYSFUNCTION, and HEART FAILURE. Risk factors include SMOKING; ALCOHOL DRINKING; HYPERTENSION; INFECTION; PREGNANCY; and mutations in the LMNA gene encoding LAMIN TYPE A, a NUCLEAR LAMINA protein.\n    ", "id": "MESH:D002311"}
{"mention": "atrioventricular reentrant tachycardia", "mention_text": "In a patient with WPW syndrome and idiopathic dilated cardiomyopathy, intractable atrioventricular reentrant tachycardia (AVRT) was iatrogenically induced. QRS without preexcitation, caused by junctional escape beats after verapamil or unidirectional antegrade block of accessory pathway after catheter ablation, established frequent AVRT attack.", "entity": "Tachycardia, Atrioventricular Nodal Reentry", "aliases": "AV Nodal Reentrant Tachycardia Atrioventricular Reentry", "definition": "Abnormally rapid heartbeats caused by reentry of atrial impulse into the dual (fast and slow) pathways of ATRIOVENTRICULAR NODE. The common type involves a blocked atrial impulse in the slow pathway which reenters the fast pathway in a retrograde direction and simultaneously conducts to the atria and the ventricles leading to rapid HEART RATE of 150-250 beats per minute.\n    ", "id": "MESH:D013611"}
{"mention": "AVRT", "mention_text": "In a patient with WPW syndrome and idiopathic dilated cardiomyopathy, intractable atrioventricular reentrant tachycardia (AVRT) was iatrogenically induced. QRS without preexcitation, caused by junctional escape beats after verapamil or unidirectional antegrade block of accessory pathway after catheter ablation, established frequent AVRT attack.", "entity": "Tachycardia, Atrioventricular Nodal Reentry", "aliases": "AV Nodal Reentrant Tachycardia Atrioventricular Reentry", "definition": "Abnormally rapid heartbeats caused by reentry of atrial impulse into the dual (fast and slow) pathways of ATRIOVENTRICULAR NODE. The common type involves a blocked atrial impulse in the slow pathway which reenters the fast pathway in a retrograde direction and simultaneously conducts to the atria and the ventricles leading to rapid HEART RATE of 150-250 beats per minute.\n    ", "id": "MESH:D013611"}
{"mention": "verapamil", "mention_text": "In a patient with WPW syndrome and idiopathic dilated cardiomyopathy, intractable atrioventricular reentrant tachycardia (AVRT) was iatrogenically induced. QRS without preexcitation, caused by junctional escape beats after verapamil or unidirectional antegrade block of accessory pathway after catheter ablation, established frequent AVRT attack.", "entity": "Verapamil", "aliases": "Calan Cordilox Dexverapamil Falicard Finoptin Hydrochloride Verapamil Iproveratril Isoptin Isoptine Izoptin Lekoptin Sandoz Brand of", "definition": "A calcium channel blocker that is a class IV anti-arrhythmia agent.\n    ", "id": "MESH:D014700"}
{"mention": "liver disease", "mention_text": "Epidemic of liver disease caused by hydrochlorofluorocarbons used as ozone-sparing substitutes of chlorofluorocarbons.", "entity": "Liver Diseases", "aliases": "Disease Liver Diseases Dysfunction Dysfunctions", "definition": "Pathological processes of the LIVER.\n    ", "id": "MESH:D008107"}
{"mention": "ozone", "mention_text": "Epidemic of liver disease caused by hydrochlorofluorocarbons used as ozone-sparing substitutes of chlorofluorocarbons.", "entity": "Ozone", "aliases": "Ground Level Ozone Low Tropospheric", "definition": "The unstable triatomic form of oxygen, O3. It is a powerful oxidant that is produced for various chemical and industrial uses. Its production is also catalyzed in the ATMOSPHERE by ULTRAVIOLET RAY irradiation of oxygen or other ozone precursors such as VOLATILE ORGANIC COMPOUNDS and NITROGEN OXIDES. About 90% of the ozone in the atmosphere exists in the stratosphere (STRATOSPHERIC OZONE).\n    ", "id": "MESH:D010126"}
{"mention": "chlorofluorocarbons", "mention_text": "Epidemic of liver disease caused by hydrochlorofluorocarbons used as ozone-sparing substitutes of chlorofluorocarbons.", "entity": "Chlorofluorocarbons", "aliases": "Chlorofluorocarbon Derivatives Chlorofluorocarbons Freon Freons", "definition": "A series of hydrocarbons containing both chlorine and fluorine. These have been used as refrigerants, blowing agents, cleaning fluids, solvents, and as fire extinguishing agents. They have been shown to cause stratospheric ozone depletion and have been banned for many uses.\n    ", "id": "MESH:D017402"}
{"mention": "ozone", "mention_text": "BACKGROUND: Hydrochlorofluorocarbons (HCFCs) are used increasingly in industry as substitutes for ozone-depleting chlorofluorocarbons (CFCs). Limited studies in animals indicate potential hepatotoxicity of some of these compounds. We investigated an epidemic of liver disease in nine industrial workers who had had repeated accidental exposure to a mixture of 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123) and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124). All nine exposed workers were affected to various degrees. Both compounds are metabolised in the same way as 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) to form reactive trifluoroacetyl halide intermediates, which have been implicated in the hepatotoxicity of halothane. We aimed to test whether HCFCs 123 and 124 can result in serious liver disease. METHODS: For one severely affected worker liver biopsy and immunohistochemical stainings for the presence of trifluoroacetyl protein adducts were done. The serum of six affected workers and five controls was tested for autoantibodies that react with human liver cytochrome-P450 2E1 (P450 2E1) and P58 protein disulphide isomerase isoform (P58). FINDINGS: The liver biopsy sample showed hepatocellular necrosis which was prominent in perivenular zone three and extended focally from portal tracts to portal tracts and centrilobular areas (bridging necrosis). Trifluoroacetyl-adducted proteins were detected in surviving hepatocytes. Autoantibodies against P450 2E1 or P58, previously associated with halothane hepatitis, were detected in the serum of five affected workers. INTERPRETATION: Repeated exposure of human beings to HCFCs 123 and 124 can result in serious liver injury in a large proportion of the exposed population. Although the exact mechanism of hepatotoxicity of these agents is not known, the results suggest that trifluoroacetyl-altered liver proteins are involved. In view of the potentially widespread use of these compounds, there is an urgent need to develop safer alternatives.", "entity": "Ozone", "aliases": "Ground Level Ozone Low Tropospheric", "definition": "The unstable triatomic form of oxygen, O3. It is a powerful oxidant that is produced for various chemical and industrial uses. Its production is also catalyzed in the ATMOSPHERE by ULTRAVIOLET RAY irradiation of oxygen or other ozone precursors such as VOLATILE ORGANIC COMPOUNDS and NITROGEN OXIDES. About 90% of the ozone in the atmosphere exists in the stratosphere (STRATOSPHERIC OZONE).\n    ", "id": "MESH:D010126"}
{"mention": "chlorofluorocarbons", "mention_text": "BACKGROUND: Hydrochlorofluorocarbons (HCFCs) are used increasingly in industry as substitutes for ozone-depleting chlorofluorocarbons (CFCs). Limited studies in animals indicate potential hepatotoxicity of some of these compounds. We investigated an epidemic of liver disease in nine industrial workers who had had repeated accidental exposure to a mixture of 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123) and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124). All nine exposed workers were affected to various degrees. Both compounds are metabolised in the same way as 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) to form reactive trifluoroacetyl halide intermediates, which have been implicated in the hepatotoxicity of halothane. We aimed to test whether HCFCs 123 and 124 can result in serious liver disease. METHODS: For one severely affected worker liver biopsy and immunohistochemical stainings for the presence of trifluoroacetyl protein adducts were done. The serum of six affected workers and five controls was tested for autoantibodies that react with human liver cytochrome-P450 2E1 (P450 2E1) and P58 protein disulphide isomerase isoform (P58). FINDINGS: The liver biopsy sample showed hepatocellular necrosis which was prominent in perivenular zone three and extended focally from portal tracts to portal tracts and centrilobular areas (bridging necrosis). Trifluoroacetyl-adducted proteins were detected in surviving hepatocytes. Autoantibodies against P450 2E1 or P58, previously associated with halothane hepatitis, were detected in the serum of five affected workers. INTERPRETATION: Repeated exposure of human beings to HCFCs 123 and 124 can result in serious liver injury in a large proportion of the exposed population. Although the exact mechanism of hepatotoxicity of these agents is not known, the results suggest that trifluoroacetyl-altered liver proteins are involved. In view of the potentially widespread use of these compounds, there is an urgent need to develop safer alternatives.", "entity": "Chlorofluorocarbons", "aliases": "Chlorofluorocarbon Derivatives Chlorofluorocarbons Freon Freons", "definition": "A series of hydrocarbons containing both chlorine and fluorine. These have been used as refrigerants, blowing agents, cleaning fluids, solvents, and as fire extinguishing agents. They have been shown to cause stratospheric ozone depletion and have been banned for many uses.\n    ", "id": "MESH:D017402"}
{"mention": "CFCs", "mention_text": "BACKGROUND: Hydrochlorofluorocarbons (HCFCs) are used increasingly in industry as substitutes for ozone-depleting chlorofluorocarbons (CFCs). Limited studies in animals indicate potential hepatotoxicity of some of these compounds. We investigated an epidemic of liver disease in nine industrial workers who had had repeated accidental exposure to a mixture of 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123) and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124). All nine exposed workers were affected to various degrees. Both compounds are metabolised in the same way as 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) to form reactive trifluoroacetyl halide intermediates, which have been implicated in the hepatotoxicity of halothane. We aimed to test whether HCFCs 123 and 124 can result in serious liver disease. METHODS: For one severely affected worker liver biopsy and immunohistochemical stainings for the presence of trifluoroacetyl protein adducts were done. The serum of six affected workers and five controls was tested for autoantibodies that react with human liver cytochrome-P450 2E1 (P450 2E1) and P58 protein disulphide isomerase isoform (P58). FINDINGS: The liver biopsy sample showed hepatocellular necrosis which was prominent in perivenular zone three and extended focally from portal tracts to portal tracts and centrilobular areas (bridging necrosis). Trifluoroacetyl-adducted proteins were detected in surviving hepatocytes. Autoantibodies against P450 2E1 or P58, previously associated with halothane hepatitis, were detected in the serum of five affected workers. INTERPRETATION: Repeated exposure of human beings to HCFCs 123 and 124 can result in serious liver injury in a large proportion of the exposed population. Although the exact mechanism of hepatotoxicity of these agents is not known, the results suggest that trifluoroacetyl-altered liver proteins are involved. In view of the potentially widespread use of these compounds, there is an urgent need to develop safer alternatives.", "entity": "Chlorofluorocarbons", "aliases": "Chlorofluorocarbon Derivatives Chlorofluorocarbons Freon Freons", "definition": "A series of hydrocarbons containing both chlorine and fluorine. These have been used as refrigerants, blowing agents, cleaning fluids, solvents, and as fire extinguishing agents. They have been shown to cause stratospheric ozone depletion and have been banned for many uses.\n    ", "id": "MESH:D017402"}
{"mention": "hepatotoxicity", "mention_text": "BACKGROUND: Hydrochlorofluorocarbons (HCFCs) are used increasingly in industry as substitutes for ozone-depleting chlorofluorocarbons (CFCs). Limited studies in animals indicate potential hepatotoxicity of some of these compounds. We investigated an epidemic of liver disease in nine industrial workers who had had repeated accidental exposure to a mixture of 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123) and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124). All nine exposed workers were affected to various degrees. Both compounds are metabolised in the same way as 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) to form reactive trifluoroacetyl halide intermediates, which have been implicated in the hepatotoxicity of halothane. We aimed to test whether HCFCs 123 and 124 can result in serious liver disease. METHODS: For one severely affected worker liver biopsy and immunohistochemical stainings for the presence of trifluoroacetyl protein adducts were done. The serum of six affected workers and five controls was tested for autoantibodies that react with human liver cytochrome-P450 2E1 (P450 2E1) and P58 protein disulphide isomerase isoform (P58). FINDINGS: The liver biopsy sample showed hepatocellular necrosis which was prominent in perivenular zone three and extended focally from portal tracts to portal tracts and centrilobular areas (bridging necrosis). Trifluoroacetyl-adducted proteins were detected in surviving hepatocytes. Autoantibodies against P450 2E1 or P58, previously associated with halothane hepatitis, were detected in the serum of five affected workers. INTERPRETATION: Repeated exposure of human beings to HCFCs 123 and 124 can result in serious liver injury in a large proportion of the exposed population. Although the exact mechanism of hepatotoxicity of these agents is not known, the results suggest that trifluoroacetyl-altered liver proteins are involved. In view of the potentially widespread use of these compounds, there is an urgent need to develop safer alternatives.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "liver disease", "mention_text": "BACKGROUND: Hydrochlorofluorocarbons (HCFCs) are used increasingly in industry as substitutes for ozone-depleting chlorofluorocarbons (CFCs). Limited studies in animals indicate potential hepatotoxicity of some of these compounds. We investigated an epidemic of liver disease in nine industrial workers who had had repeated accidental exposure to a mixture of 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123) and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124). All nine exposed workers were affected to various degrees. Both compounds are metabolised in the same way as 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) to form reactive trifluoroacetyl halide intermediates, which have been implicated in the hepatotoxicity of halothane. We aimed to test whether HCFCs 123 and 124 can result in serious liver disease. METHODS: For one severely affected worker liver biopsy and immunohistochemical stainings for the presence of trifluoroacetyl protein adducts were done. The serum of six affected workers and five controls was tested for autoantibodies that react with human liver cytochrome-P450 2E1 (P450 2E1) and P58 protein disulphide isomerase isoform (P58). FINDINGS: The liver biopsy sample showed hepatocellular necrosis which was prominent in perivenular zone three and extended focally from portal tracts to portal tracts and centrilobular areas (bridging necrosis). Trifluoroacetyl-adducted proteins were detected in surviving hepatocytes. Autoantibodies against P450 2E1 or P58, previously associated with halothane hepatitis, were detected in the serum of five affected workers. INTERPRETATION: Repeated exposure of human beings to HCFCs 123 and 124 can result in serious liver injury in a large proportion of the exposed population. Although the exact mechanism of hepatotoxicity of these agents is not known, the results suggest that trifluoroacetyl-altered liver proteins are involved. In view of the potentially widespread use of these compounds, there is an urgent need to develop safer alternatives.", "entity": "Liver Diseases", "aliases": "Disease Liver Diseases Dysfunction Dysfunctions", "definition": "Pathological processes of the LIVER.\n    ", "id": "MESH:D008107"}
{"mention": "1,1-dichloro-2,2,2-trifluoroethane", "mention_text": "BACKGROUND: Hydrochlorofluorocarbons (HCFCs) are used increasingly in industry as substitutes for ozone-depleting chlorofluorocarbons (CFCs). Limited studies in animals indicate potential hepatotoxicity of some of these compounds. We investigated an epidemic of liver disease in nine industrial workers who had had repeated accidental exposure to a mixture of 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123) and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124). All nine exposed workers were affected to various degrees. Both compounds are metabolised in the same way as 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) to form reactive trifluoroacetyl halide intermediates, which have been implicated in the hepatotoxicity of halothane. We aimed to test whether HCFCs 123 and 124 can result in serious liver disease. METHODS: For one severely affected worker liver biopsy and immunohistochemical stainings for the presence of trifluoroacetyl protein adducts were done. The serum of six affected workers and five controls was tested for autoantibodies that react with human liver cytochrome-P450 2E1 (P450 2E1) and P58 protein disulphide isomerase isoform (P58). FINDINGS: The liver biopsy sample showed hepatocellular necrosis which was prominent in perivenular zone three and extended focally from portal tracts to portal tracts and centrilobular areas (bridging necrosis). Trifluoroacetyl-adducted proteins were detected in surviving hepatocytes. Autoantibodies against P450 2E1 or P58, previously associated with halothane hepatitis, were detected in the serum of five affected workers. INTERPRETATION: Repeated exposure of human beings to HCFCs 123 and 124 can result in serious liver injury in a large proportion of the exposed population. Although the exact mechanism of hepatotoxicity of these agents is not known, the results suggest that trifluoroacetyl-altered liver proteins are involved. In view of the potentially widespread use of these compounds, there is an urgent need to develop safer alternatives.", "entity": "2,2-dichloro-1,1,1-trifluoroethane", "aliases": "1,1-dichloro-2,2,2-trifluoroethane 2,2-DCTFE 2,2-dichloro-1,1,1-trifluoroethane FC-123 Freon 123 Freon-123 HCFC HCFC-123", "definition": "", "id": "MESH:C067411"}
{"mention": "HCFC 123", "mention_text": "BACKGROUND: Hydrochlorofluorocarbons (HCFCs) are used increasingly in industry as substitutes for ozone-depleting chlorofluorocarbons (CFCs). Limited studies in animals indicate potential hepatotoxicity of some of these compounds. We investigated an epidemic of liver disease in nine industrial workers who had had repeated accidental exposure to a mixture of 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123) and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124). All nine exposed workers were affected to various degrees. Both compounds are metabolised in the same way as 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) to form reactive trifluoroacetyl halide intermediates, which have been implicated in the hepatotoxicity of halothane. We aimed to test whether HCFCs 123 and 124 can result in serious liver disease. METHODS: For one severely affected worker liver biopsy and immunohistochemical stainings for the presence of trifluoroacetyl protein adducts were done. The serum of six affected workers and five controls was tested for autoantibodies that react with human liver cytochrome-P450 2E1 (P450 2E1) and P58 protein disulphide isomerase isoform (P58). FINDINGS: The liver biopsy sample showed hepatocellular necrosis which was prominent in perivenular zone three and extended focally from portal tracts to portal tracts and centrilobular areas (bridging necrosis). Trifluoroacetyl-adducted proteins were detected in surviving hepatocytes. Autoantibodies against P450 2E1 or P58, previously associated with halothane hepatitis, were detected in the serum of five affected workers. INTERPRETATION: Repeated exposure of human beings to HCFCs 123 and 124 can result in serious liver injury in a large proportion of the exposed population. Although the exact mechanism of hepatotoxicity of these agents is not known, the results suggest that trifluoroacetyl-altered liver proteins are involved. In view of the potentially widespread use of these compounds, there is an urgent need to develop safer alternatives.", "entity": "2,2-dichloro-1,1,1-trifluoroethane", "aliases": "1,1-dichloro-2,2,2-trifluoroethane 2,2-DCTFE 2,2-dichloro-1,1,1-trifluoroethane FC-123 Freon 123 Freon-123 HCFC HCFC-123", "definition": "", "id": "MESH:C067411"}
{"mention": "1-chloro-1,2,2,2-tetrafluoroethane", "mention_text": "BACKGROUND: Hydrochlorofluorocarbons (HCFCs) are used increasingly in industry as substitutes for ozone-depleting chlorofluorocarbons (CFCs). Limited studies in animals indicate potential hepatotoxicity of some of these compounds. We investigated an epidemic of liver disease in nine industrial workers who had had repeated accidental exposure to a mixture of 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123) and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124). All nine exposed workers were affected to various degrees. Both compounds are metabolised in the same way as 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) to form reactive trifluoroacetyl halide intermediates, which have been implicated in the hepatotoxicity of halothane. We aimed to test whether HCFCs 123 and 124 can result in serious liver disease. METHODS: For one severely affected worker liver biopsy and immunohistochemical stainings for the presence of trifluoroacetyl protein adducts were done. The serum of six affected workers and five controls was tested for autoantibodies that react with human liver cytochrome-P450 2E1 (P450 2E1) and P58 protein disulphide isomerase isoform (P58). FINDINGS: The liver biopsy sample showed hepatocellular necrosis which was prominent in perivenular zone three and extended focally from portal tracts to portal tracts and centrilobular areas (bridging necrosis). Trifluoroacetyl-adducted proteins were detected in surviving hepatocytes. Autoantibodies against P450 2E1 or P58, previously associated with halothane hepatitis, were detected in the serum of five affected workers. INTERPRETATION: Repeated exposure of human beings to HCFCs 123 and 124 can result in serious liver injury in a large proportion of the exposed population. Although the exact mechanism of hepatotoxicity of these agents is not known, the results suggest that trifluoroacetyl-altered liver proteins are involved. In view of the potentially widespread use of these compounds, there is an urgent need to develop safer alternatives.", "entity": "1,1,1,2-tetrafluoro-2-chloroethane", "aliases": "1,1,1,2-tetrafluoro-2-chloroethane 2-chloro-1,1,1,2-tetrafuoroethane Freon 124 HCFC HCFC-124 R-124", "definition": "", "id": "MESH:C072959"}
{"mention": "HCFC 124", "mention_text": "BACKGROUND: Hydrochlorofluorocarbons (HCFCs) are used increasingly in industry as substitutes for ozone-depleting chlorofluorocarbons (CFCs). Limited studies in animals indicate potential hepatotoxicity of some of these compounds. We investigated an epidemic of liver disease in nine industrial workers who had had repeated accidental exposure to a mixture of 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123) and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124). All nine exposed workers were affected to various degrees. Both compounds are metabolised in the same way as 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) to form reactive trifluoroacetyl halide intermediates, which have been implicated in the hepatotoxicity of halothane. We aimed to test whether HCFCs 123 and 124 can result in serious liver disease. METHODS: For one severely affected worker liver biopsy and immunohistochemical stainings for the presence of trifluoroacetyl protein adducts were done. The serum of six affected workers and five controls was tested for autoantibodies that react with human liver cytochrome-P450 2E1 (P450 2E1) and P58 protein disulphide isomerase isoform (P58). FINDINGS: The liver biopsy sample showed hepatocellular necrosis which was prominent in perivenular zone three and extended focally from portal tracts to portal tracts and centrilobular areas (bridging necrosis). Trifluoroacetyl-adducted proteins were detected in surviving hepatocytes. Autoantibodies against P450 2E1 or P58, previously associated with halothane hepatitis, were detected in the serum of five affected workers. INTERPRETATION: Repeated exposure of human beings to HCFCs 123 and 124 can result in serious liver injury in a large proportion of the exposed population. Although the exact mechanism of hepatotoxicity of these agents is not known, the results suggest that trifluoroacetyl-altered liver proteins are involved. In view of the potentially widespread use of these compounds, there is an urgent need to develop safer alternatives.", "entity": "1,1,1,2-tetrafluoro-2-chloroethane", "aliases": "1,1,1,2-tetrafluoro-2-chloroethane 2-chloro-1,1,1,2-tetrafuoroethane Freon 124 HCFC HCFC-124 R-124", "definition": "", "id": "MESH:C072959"}
{"mention": "1-bromo-1-chloro-2,2,2-trifluoroethane", "mention_text": "BACKGROUND: Hydrochlorofluorocarbons (HCFCs) are used increasingly in industry as substitutes for ozone-depleting chlorofluorocarbons (CFCs). Limited studies in animals indicate potential hepatotoxicity of some of these compounds. We investigated an epidemic of liver disease in nine industrial workers who had had repeated accidental exposure to a mixture of 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123) and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124). All nine exposed workers were affected to various degrees. Both compounds are metabolised in the same way as 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) to form reactive trifluoroacetyl halide intermediates, which have been implicated in the hepatotoxicity of halothane. We aimed to test whether HCFCs 123 and 124 can result in serious liver disease. METHODS: For one severely affected worker liver biopsy and immunohistochemical stainings for the presence of trifluoroacetyl protein adducts were done. The serum of six affected workers and five controls was tested for autoantibodies that react with human liver cytochrome-P450 2E1 (P450 2E1) and P58 protein disulphide isomerase isoform (P58). FINDINGS: The liver biopsy sample showed hepatocellular necrosis which was prominent in perivenular zone three and extended focally from portal tracts to portal tracts and centrilobular areas (bridging necrosis). Trifluoroacetyl-adducted proteins were detected in surviving hepatocytes. Autoantibodies against P450 2E1 or P58, previously associated with halothane hepatitis, were detected in the serum of five affected workers. INTERPRETATION: Repeated exposure of human beings to HCFCs 123 and 124 can result in serious liver injury in a large proportion of the exposed population. Although the exact mechanism of hepatotoxicity of these agents is not known, the results suggest that trifluoroacetyl-altered liver proteins are involved. In view of the potentially widespread use of these compounds, there is an urgent need to develop safer alternatives.", "entity": "Halothane", "aliases": "1,1,1-Trifluoro-2-Chloro-2-Bromoethane Fluothane Ftorotan Halothane Narcotan", "definition": "A nonflammable, halogenated, hydrocarbon anesthetic that provides relatively rapid induction with little or no excitement. Analgesia may not be adequate. NITROUS OXIDE is often given concomitantly. Because halothane may not produce sufficient muscle relaxation, supplemental neuromuscular blocking agents may be required. (From AMA Drug Evaluations Annual, 1994, p178)\n    ", "id": "MESH:D006221"}
{"mention": "halothane", "mention_text": "BACKGROUND: Hydrochlorofluorocarbons (HCFCs) are used increasingly in industry as substitutes for ozone-depleting chlorofluorocarbons (CFCs). Limited studies in animals indicate potential hepatotoxicity of some of these compounds. We investigated an epidemic of liver disease in nine industrial workers who had had repeated accidental exposure to a mixture of 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123) and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124). All nine exposed workers were affected to various degrees. Both compounds are metabolised in the same way as 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) to form reactive trifluoroacetyl halide intermediates, which have been implicated in the hepatotoxicity of halothane. We aimed to test whether HCFCs 123 and 124 can result in serious liver disease. METHODS: For one severely affected worker liver biopsy and immunohistochemical stainings for the presence of trifluoroacetyl protein adducts were done. The serum of six affected workers and five controls was tested for autoantibodies that react with human liver cytochrome-P450 2E1 (P450 2E1) and P58 protein disulphide isomerase isoform (P58). FINDINGS: The liver biopsy sample showed hepatocellular necrosis which was prominent in perivenular zone three and extended focally from portal tracts to portal tracts and centrilobular areas (bridging necrosis). Trifluoroacetyl-adducted proteins were detected in surviving hepatocytes. Autoantibodies against P450 2E1 or P58, previously associated with halothane hepatitis, were detected in the serum of five affected workers. INTERPRETATION: Repeated exposure of human beings to HCFCs 123 and 124 can result in serious liver injury in a large proportion of the exposed population. Although the exact mechanism of hepatotoxicity of these agents is not known, the results suggest that trifluoroacetyl-altered liver proteins are involved. In view of the potentially widespread use of these compounds, there is an urgent need to develop safer alternatives.", "entity": "Halothane", "aliases": "1,1,1-Trifluoro-2-Chloro-2-Bromoethane Fluothane Ftorotan Halothane Narcotan", "definition": "A nonflammable, halogenated, hydrocarbon anesthetic that provides relatively rapid induction with little or no excitement. Analgesia may not be adequate. NITROUS OXIDE is often given concomitantly. Because halothane may not produce sufficient muscle relaxation, supplemental neuromuscular blocking agents may be required. (From AMA Drug Evaluations Annual, 1994, p178)\n    ", "id": "MESH:D006221"}
{"mention": "trifluoroacetyl", "mention_text": "BACKGROUND: Hydrochlorofluorocarbons (HCFCs) are used increasingly in industry as substitutes for ozone-depleting chlorofluorocarbons (CFCs). Limited studies in animals indicate potential hepatotoxicity of some of these compounds. We investigated an epidemic of liver disease in nine industrial workers who had had repeated accidental exposure to a mixture of 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123) and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124). All nine exposed workers were affected to various degrees. Both compounds are metabolised in the same way as 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) to form reactive trifluoroacetyl halide intermediates, which have been implicated in the hepatotoxicity of halothane. We aimed to test whether HCFCs 123 and 124 can result in serious liver disease. METHODS: For one severely affected worker liver biopsy and immunohistochemical stainings for the presence of trifluoroacetyl protein adducts were done. The serum of six affected workers and five controls was tested for autoantibodies that react with human liver cytochrome-P450 2E1 (P450 2E1) and P58 protein disulphide isomerase isoform (P58). FINDINGS: The liver biopsy sample showed hepatocellular necrosis which was prominent in perivenular zone three and extended focally from portal tracts to portal tracts and centrilobular areas (bridging necrosis). Trifluoroacetyl-adducted proteins were detected in surviving hepatocytes. Autoantibodies against P450 2E1 or P58, previously associated with halothane hepatitis, were detected in the serum of five affected workers. INTERPRETATION: Repeated exposure of human beings to HCFCs 123 and 124 can result in serious liver injury in a large proportion of the exposed population. Although the exact mechanism of hepatotoxicity of these agents is not known, the results suggest that trifluoroacetyl-altered liver proteins are involved. In view of the potentially widespread use of these compounds, there is an urgent need to develop safer alternatives.", "entity": "Trifluoroacetic Acid", "aliases": "Acid Trifluoroacetic Cesium Trifluoroacetate", "definition": "A very strong halogenated derivative of acetic acid. It is used in acid catalyzed reactions, especially those where an ester is cleaved in peptide synthesis.\n    ", "id": "MESH:D014269"}
{"mention": "HCFCs 123", "mention_text": "BACKGROUND: Hydrochlorofluorocarbons (HCFCs) are used increasingly in industry as substitutes for ozone-depleting chlorofluorocarbons (CFCs). Limited studies in animals indicate potential hepatotoxicity of some of these compounds. We investigated an epidemic of liver disease in nine industrial workers who had had repeated accidental exposure to a mixture of 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123) and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124). All nine exposed workers were affected to various degrees. Both compounds are metabolised in the same way as 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) to form reactive trifluoroacetyl halide intermediates, which have been implicated in the hepatotoxicity of halothane. We aimed to test whether HCFCs 123 and 124 can result in serious liver disease. METHODS: For one severely affected worker liver biopsy and immunohistochemical stainings for the presence of trifluoroacetyl protein adducts were done. The serum of six affected workers and five controls was tested for autoantibodies that react with human liver cytochrome-P450 2E1 (P450 2E1) and P58 protein disulphide isomerase isoform (P58). FINDINGS: The liver biopsy sample showed hepatocellular necrosis which was prominent in perivenular zone three and extended focally from portal tracts to portal tracts and centrilobular areas (bridging necrosis). Trifluoroacetyl-adducted proteins were detected in surviving hepatocytes. Autoantibodies against P450 2E1 or P58, previously associated with halothane hepatitis, were detected in the serum of five affected workers. INTERPRETATION: Repeated exposure of human beings to HCFCs 123 and 124 can result in serious liver injury in a large proportion of the exposed population. Although the exact mechanism of hepatotoxicity of these agents is not known, the results suggest that trifluoroacetyl-altered liver proteins are involved. In view of the potentially widespread use of these compounds, there is an urgent need to develop safer alternatives.", "entity": "2,2-dichloro-1,1,1-trifluoroethane", "aliases": "1,1-dichloro-2,2,2-trifluoroethane 2,2-DCTFE 2,2-dichloro-1,1,1-trifluoroethane FC-123 Freon 123 Freon-123 HCFC HCFC-123", "definition": "", "id": "MESH:C067411"}
{"mention": "necrosis", "mention_text": "BACKGROUND: Hydrochlorofluorocarbons (HCFCs) are used increasingly in industry as substitutes for ozone-depleting chlorofluorocarbons (CFCs). Limited studies in animals indicate potential hepatotoxicity of some of these compounds. We investigated an epidemic of liver disease in nine industrial workers who had had repeated accidental exposure to a mixture of 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123) and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124). All nine exposed workers were affected to various degrees. Both compounds are metabolised in the same way as 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) to form reactive trifluoroacetyl halide intermediates, which have been implicated in the hepatotoxicity of halothane. We aimed to test whether HCFCs 123 and 124 can result in serious liver disease. METHODS: For one severely affected worker liver biopsy and immunohistochemical stainings for the presence of trifluoroacetyl protein adducts were done. The serum of six affected workers and five controls was tested for autoantibodies that react with human liver cytochrome-P450 2E1 (P450 2E1) and P58 protein disulphide isomerase isoform (P58). FINDINGS: The liver biopsy sample showed hepatocellular necrosis which was prominent in perivenular zone three and extended focally from portal tracts to portal tracts and centrilobular areas (bridging necrosis). Trifluoroacetyl-adducted proteins were detected in surviving hepatocytes. Autoantibodies against P450 2E1 or P58, previously associated with halothane hepatitis, were detected in the serum of five affected workers. INTERPRETATION: Repeated exposure of human beings to HCFCs 123 and 124 can result in serious liver injury in a large proportion of the exposed population. Although the exact mechanism of hepatotoxicity of these agents is not known, the results suggest that trifluoroacetyl-altered liver proteins are involved. In view of the potentially widespread use of these compounds, there is an urgent need to develop safer alternatives.", "entity": "Necrosis", "aliases": "Necroses Necrosis", "definition": "The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. Distinguish it from APOPTOSIS which is a normal, regulated cellular process.\n    ", "id": "MESH:D009336"}
{"mention": "Trifluoroacetyl", "mention_text": "BACKGROUND: Hydrochlorofluorocarbons (HCFCs) are used increasingly in industry as substitutes for ozone-depleting chlorofluorocarbons (CFCs). Limited studies in animals indicate potential hepatotoxicity of some of these compounds. We investigated an epidemic of liver disease in nine industrial workers who had had repeated accidental exposure to a mixture of 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123) and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124). All nine exposed workers were affected to various degrees. Both compounds are metabolised in the same way as 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) to form reactive trifluoroacetyl halide intermediates, which have been implicated in the hepatotoxicity of halothane. We aimed to test whether HCFCs 123 and 124 can result in serious liver disease. METHODS: For one severely affected worker liver biopsy and immunohistochemical stainings for the presence of trifluoroacetyl protein adducts were done. The serum of six affected workers and five controls was tested for autoantibodies that react with human liver cytochrome-P450 2E1 (P450 2E1) and P58 protein disulphide isomerase isoform (P58). FINDINGS: The liver biopsy sample showed hepatocellular necrosis which was prominent in perivenular zone three and extended focally from portal tracts to portal tracts and centrilobular areas (bridging necrosis). Trifluoroacetyl-adducted proteins were detected in surviving hepatocytes. Autoantibodies against P450 2E1 or P58, previously associated with halothane hepatitis, were detected in the serum of five affected workers. INTERPRETATION: Repeated exposure of human beings to HCFCs 123 and 124 can result in serious liver injury in a large proportion of the exposed population. Although the exact mechanism of hepatotoxicity of these agents is not known, the results suggest that trifluoroacetyl-altered liver proteins are involved. In view of the potentially widespread use of these compounds, there is an urgent need to develop safer alternatives.", "entity": "Trifluoroacetic Acid", "aliases": "Acid Trifluoroacetic Cesium Trifluoroacetate", "definition": "A very strong halogenated derivative of acetic acid. It is used in acid catalyzed reactions, especially those where an ester is cleaved in peptide synthesis.\n    ", "id": "MESH:D014269"}
{"mention": "halothane hepatitis", "mention_text": "BACKGROUND: Hydrochlorofluorocarbons (HCFCs) are used increasingly in industry as substitutes for ozone-depleting chlorofluorocarbons (CFCs). Limited studies in animals indicate potential hepatotoxicity of some of these compounds. We investigated an epidemic of liver disease in nine industrial workers who had had repeated accidental exposure to a mixture of 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123) and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124). All nine exposed workers were affected to various degrees. Both compounds are metabolised in the same way as 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) to form reactive trifluoroacetyl halide intermediates, which have been implicated in the hepatotoxicity of halothane. We aimed to test whether HCFCs 123 and 124 can result in serious liver disease. METHODS: For one severely affected worker liver biopsy and immunohistochemical stainings for the presence of trifluoroacetyl protein adducts were done. The serum of six affected workers and five controls was tested for autoantibodies that react with human liver cytochrome-P450 2E1 (P450 2E1) and P58 protein disulphide isomerase isoform (P58). FINDINGS: The liver biopsy sample showed hepatocellular necrosis which was prominent in perivenular zone three and extended focally from portal tracts to portal tracts and centrilobular areas (bridging necrosis). Trifluoroacetyl-adducted proteins were detected in surviving hepatocytes. Autoantibodies against P450 2E1 or P58, previously associated with halothane hepatitis, were detected in the serum of five affected workers. INTERPRETATION: Repeated exposure of human beings to HCFCs 123 and 124 can result in serious liver injury in a large proportion of the exposed population. Although the exact mechanism of hepatotoxicity of these agents is not known, the results suggest that trifluoroacetyl-altered liver proteins are involved. In view of the potentially widespread use of these compounds, there is an urgent need to develop safer alternatives.", "entity": "Halothane Hepatitis", "aliases": "Halothane Hepatitis", "definition": "", "id": "MESH:C562477"}
{"mention": "liver injury", "mention_text": "BACKGROUND: Hydrochlorofluorocarbons (HCFCs) are used increasingly in industry as substitutes for ozone-depleting chlorofluorocarbons (CFCs). Limited studies in animals indicate potential hepatotoxicity of some of these compounds. We investigated an epidemic of liver disease in nine industrial workers who had had repeated accidental exposure to a mixture of 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123) and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124). All nine exposed workers were affected to various degrees. Both compounds are metabolised in the same way as 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) to form reactive trifluoroacetyl halide intermediates, which have been implicated in the hepatotoxicity of halothane. We aimed to test whether HCFCs 123 and 124 can result in serious liver disease. METHODS: For one severely affected worker liver biopsy and immunohistochemical stainings for the presence of trifluoroacetyl protein adducts were done. The serum of six affected workers and five controls was tested for autoantibodies that react with human liver cytochrome-P450 2E1 (P450 2E1) and P58 protein disulphide isomerase isoform (P58). FINDINGS: The liver biopsy sample showed hepatocellular necrosis which was prominent in perivenular zone three and extended focally from portal tracts to portal tracts and centrilobular areas (bridging necrosis). Trifluoroacetyl-adducted proteins were detected in surviving hepatocytes. Autoantibodies against P450 2E1 or P58, previously associated with halothane hepatitis, were detected in the serum of five affected workers. INTERPRETATION: Repeated exposure of human beings to HCFCs 123 and 124 can result in serious liver injury in a large proportion of the exposed population. Although the exact mechanism of hepatotoxicity of these agents is not known, the results suggest that trifluoroacetyl-altered liver proteins are involved. In view of the potentially widespread use of these compounds, there is an urgent need to develop safer alternatives.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "hearing loss", "mention_text": "The effect of different anaesthetic agents in hearing loss following spinal anaesthesia.", "entity": "Hearing Loss", "aliases": "Hearing Impairment Loss Hypoacuses Hypoacusis", "definition": "A general term for the complete or partial loss of the ability to hear from one or both ears.\n    ", "id": "MESH:D034381"}
{"mention": "hearing loss", "mention_text": "The cause of hearing loss after spinal anaesthesia is unknown. Up until now, the only factor studied has been the effect of the diameter of the spinal needle on post-operative sensorineural hearing loss. The aim of this study was to describe this hearing loss and to investigate other factors influencing the degree of hearing loss. Two groups of 22 similar patients were studied: one group received 6 mL prilocaine 2%; and the other received 3 mL bupivacaine 0.5%. Patients given prilocaine were more likely to develop hearing loss (10 out of 22) than those given bupivacaine (4 out of 22) (P < 0.05). The average hearing loss for speech frequencies was about 10 dB after prilocaine and 15 dB after bupivacaine. None of the patients complained of subjective hearing loss. Long-term follow-up of the patients was not possible.", "entity": "Hearing Loss", "aliases": "Hearing Impairment Loss Hypoacuses Hypoacusis", "definition": "A general term for the complete or partial loss of the ability to hear from one or both ears.\n    ", "id": "MESH:D034381"}
{"mention": "sensorineural hearing loss", "mention_text": "The cause of hearing loss after spinal anaesthesia is unknown. Up until now, the only factor studied has been the effect of the diameter of the spinal needle on post-operative sensorineural hearing loss. The aim of this study was to describe this hearing loss and to investigate other factors influencing the degree of hearing loss. Two groups of 22 similar patients were studied: one group received 6 mL prilocaine 2%; and the other received 3 mL bupivacaine 0.5%. Patients given prilocaine were more likely to develop hearing loss (10 out of 22) than those given bupivacaine (4 out of 22) (P < 0.05). The average hearing loss for speech frequencies was about 10 dB after prilocaine and 15 dB after bupivacaine. None of the patients complained of subjective hearing loss. Long-term follow-up of the patients was not possible.", "entity": "Hearing Loss, Sensorineural", "aliases": "Cochlear Hearing Loss Sensorineural", "definition": "Hearing loss resulting from damage to the COCHLEA and the sensorineural elements which lie internally beyond the oval and round windows. These elements include the AUDITORY NERVE and its connections in the BRAINSTEM.\n    ", "id": "MESH:D006319"}
{"mention": "prilocaine", "mention_text": "The cause of hearing loss after spinal anaesthesia is unknown. Up until now, the only factor studied has been the effect of the diameter of the spinal needle on post-operative sensorineural hearing loss. The aim of this study was to describe this hearing loss and to investigate other factors influencing the degree of hearing loss. Two groups of 22 similar patients were studied: one group received 6 mL prilocaine 2%; and the other received 3 mL bupivacaine 0.5%. Patients given prilocaine were more likely to develop hearing loss (10 out of 22) than those given bupivacaine (4 out of 22) (P < 0.05). The average hearing loss for speech frequencies was about 10 dB after prilocaine and 15 dB after bupivacaine. None of the patients complained of subjective hearing loss. Long-term follow-up of the patients was not possible.", "entity": "Prilocaine", "aliases": "Astra Brand of Prilocaine Hydrochloride AstraZeneca Citanest Octapressin Delvet Inibsa Parnell Propitocaine Xylonest", "definition": "A local anesthetic that is similar pharmacologically to LIDOCAINE. Currently, it is used most often for infiltration anesthesia in dentistry.\n    ", "id": "MESH:D011318"}
{"mention": "bupivacaine", "mention_text": "The cause of hearing loss after spinal anaesthesia is unknown. Up until now, the only factor studied has been the effect of the diameter of the spinal needle on post-operative sensorineural hearing loss. The aim of this study was to describe this hearing loss and to investigate other factors influencing the degree of hearing loss. Two groups of 22 similar patients were studied: one group received 6 mL prilocaine 2%; and the other received 3 mL bupivacaine 0.5%. Patients given prilocaine were more likely to develop hearing loss (10 out of 22) than those given bupivacaine (4 out of 22) (P < 0.05). The average hearing loss for speech frequencies was about 10 dB after prilocaine and 15 dB after bupivacaine. None of the patients complained of subjective hearing loss. Long-term follow-up of the patients was not possible.", "entity": "Bupivacaine", "aliases": "1-Butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide Abbott Brand of Bupivacaine Hydrochloride Anhydrous Astra AstraZeneca Aventis Braun Bupivacaina Bupivacain Janapharm RPR Bupivacain-RPR Carbonate Monohydrochloride Monohydrate Buvacaina Carbostesin Dolanaest Inibsa Jenapharm Marcain Marcaine Pisa Sensorcaine Strathmann Svedocain Sin Vasoconstr", "definition": "A widely used local anesthetic agent.\n    ", "id": "MESH:D002045"}
{"mention": "neurological deficit", "mention_text": "A transient neurological deficit following intrathecal injection of 1% hyperbaric bupivacaine for unilateral spinal anaesthesia.", "entity": "Neurologic Manifestations", "aliases": "Deficit Focal Neurologic Deficits Dysfunction Dysfunctions Finding Findings Manifestation Neurological Manifestations Sign Signs and Symptoms Symptom", "definition": "Clinical signs and symptoms caused by nervous system injury or dysfunction.\n    ", "id": "MESH:D009461"}
{"mention": "bupivacaine", "mention_text": "A transient neurological deficit following intrathecal injection of 1% hyperbaric bupivacaine for unilateral spinal anaesthesia.", "entity": "Bupivacaine", "aliases": "1-Butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide Abbott Brand of Bupivacaine Hydrochloride Anhydrous Astra AstraZeneca Aventis Braun Bupivacaina Bupivacain Janapharm RPR Bupivacain-RPR Carbonate Monohydrochloride Monohydrate Buvacaina Carbostesin Dolanaest Inibsa Jenapharm Marcain Marcaine Pisa Sensorcaine Strathmann Svedocain Sin Vasoconstr", "definition": "A widely used local anesthetic agent.\n    ", "id": "MESH:D002045"}
{"mention": "neurological deficit", "mention_text": "We describe a case of transient neurological deficit that occurred after unilateral spinal anaesthesia with 8 mg of 1% hyperbaric bupivacaine slowly injected through a 25-gauge pencil-point spinal needle. The surgery and anaesthesia were uneventful, but 3 days after surgery, the patient reported an area of hypoaesthesia over L3-L4 dermatomes of the leg which had been operated on (loss of pinprick sensation) without reduction in muscular strength. Sensation in this area returned to normal over the following 2 weeks. Prospective multicentre studies with a large population and a long follow-up should be performed in order to evaluate the incidence of this unusual side effect. However, we suggest that a low solution concentration should be preferred for unilateral spinal anaesthesia with a hyperbaric anaesthetic solution (if pencil-point needle and slow injection rate are employed), in order to minimize the risk of a localized high peak anaesthetic concentration, which might lead to a transient neurological deficit.", "entity": "Neurologic Manifestations", "aliases": "Deficit Focal Neurologic Deficits Dysfunction Dysfunctions Finding Findings Manifestation Neurological Manifestations Sign Signs and Symptoms Symptom", "definition": "Clinical signs and symptoms caused by nervous system injury or dysfunction.\n    ", "id": "MESH:D009461"}
{"mention": "bupivacaine", "mention_text": "We describe a case of transient neurological deficit that occurred after unilateral spinal anaesthesia with 8 mg of 1% hyperbaric bupivacaine slowly injected through a 25-gauge pencil-point spinal needle. The surgery and anaesthesia were uneventful, but 3 days after surgery, the patient reported an area of hypoaesthesia over L3-L4 dermatomes of the leg which had been operated on (loss of pinprick sensation) without reduction in muscular strength. Sensation in this area returned to normal over the following 2 weeks. Prospective multicentre studies with a large population and a long follow-up should be performed in order to evaluate the incidence of this unusual side effect. However, we suggest that a low solution concentration should be preferred for unilateral spinal anaesthesia with a hyperbaric anaesthetic solution (if pencil-point needle and slow injection rate are employed), in order to minimize the risk of a localized high peak anaesthetic concentration, which might lead to a transient neurological deficit.", "entity": "Bupivacaine", "aliases": "1-Butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide Abbott Brand of Bupivacaine Hydrochloride Anhydrous Astra AstraZeneca Aventis Braun Bupivacaina Bupivacain Janapharm RPR Bupivacain-RPR Carbonate Monohydrochloride Monohydrate Buvacaina Carbostesin Dolanaest Inibsa Jenapharm Marcain Marcaine Pisa Sensorcaine Strathmann Svedocain Sin Vasoconstr", "definition": "A widely used local anesthetic agent.\n    ", "id": "MESH:D002045"}
{"mention": "loss of pinprick sensation", "mention_text": "We describe a case of transient neurological deficit that occurred after unilateral spinal anaesthesia with 8 mg of 1% hyperbaric bupivacaine slowly injected through a 25-gauge pencil-point spinal needle. The surgery and anaesthesia were uneventful, but 3 days after surgery, the patient reported an area of hypoaesthesia over L3-L4 dermatomes of the leg which had been operated on (loss of pinprick sensation) without reduction in muscular strength. Sensation in this area returned to normal over the following 2 weeks. Prospective multicentre studies with a large population and a long follow-up should be performed in order to evaluate the incidence of this unusual side effect. However, we suggest that a low solution concentration should be preferred for unilateral spinal anaesthesia with a hyperbaric anaesthetic solution (if pencil-point needle and slow injection rate are employed), in order to minimize the risk of a localized high peak anaesthetic concentration, which might lead to a transient neurological deficit.", "entity": "Sensation Disorders", "aliases": "Sensation Disorder Disorders Senses Special Sensory", "definition": "Disorders of the special senses (i.e., VISION; HEARING; TASTE; and SMELL) or somatosensory system (i.e., afferent components of the PERIPHERAL NERVOUS SYSTEM).\n    ", "id": "MESH:D012678"}
{"mention": "Pethidine", "mention_text": "Pethidine-associated seizure in a healthy adolescent receiving pethidine for postoperative pain control.", "entity": "Meperidine", "aliases": "Demerol Dolantin Dolargan Dolcontral Dolin Dolosal Dolsin Isonipecain Lidol Lydol Meperidine Hydrochloride Operidine EPJ I EPJ-I Pethidine", "definition": "A narcotic analgesic that can be used for the relief of most types of moderate to severe pain, including postoperative pain and the pain of labor. Prolonged use may lead to dependence of the morphine type; withdrawal symptoms appear more rapidly than with morphine and are of shorter duration.\n    ", "id": "MESH:D008614"}
{"mention": "seizure", "mention_text": "Pethidine-associated seizure in a healthy adolescent receiving pethidine for postoperative pain control.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "pethidine", "mention_text": "Pethidine-associated seizure in a healthy adolescent receiving pethidine for postoperative pain control.", "entity": "Meperidine", "aliases": "Demerol Dolantin Dolargan Dolcontral Dolin Dolosal Dolsin Isonipecain Lidol Lydol Meperidine Hydrochloride Operidine EPJ I EPJ-I Pethidine", "definition": "A narcotic analgesic that can be used for the relief of most types of moderate to severe pain, including postoperative pain and the pain of labor. Prolonged use may lead to dependence of the morphine type; withdrawal symptoms appear more rapidly than with morphine and are of shorter duration.\n    ", "id": "MESH:D008614"}
{"mention": "postoperative pain", "mention_text": "Pethidine-associated seizure in a healthy adolescent receiving pethidine for postoperative pain control.", "entity": "Pain, Postoperative", "aliases": "Pain Postoperative Pains", "definition": "Pain during the period after surgery.\n    ", "id": "MESH:D010149"}
{"mention": "pethidine", "mention_text": "A healthy 17-year-old male received standard intermittent doses of pethidine via a patient-controlled analgesia (PCA) pump for management of postoperative pain control. Twenty-three h postoperatively he developed a brief self-limited seizure. Both plasma pethidine and norpethidine were elevated in the range associated with clinical manifestations of central nervous system excitation. No other risk factors for CNS toxicity were identified. This method allowed frequent self-dosing of pethidine at short time intervals and rapid accumulation of pethidine and norpethidine. The routine use of pethidine via PCA even for a brief postoperative analgesia should be reconsidered.", "entity": "Meperidine", "aliases": "Demerol Dolantin Dolargan Dolcontral Dolin Dolosal Dolsin Isonipecain Lidol Lydol Meperidine Hydrochloride Operidine EPJ I EPJ-I Pethidine", "definition": "A narcotic analgesic that can be used for the relief of most types of moderate to severe pain, including postoperative pain and the pain of labor. Prolonged use may lead to dependence of the morphine type; withdrawal symptoms appear more rapidly than with morphine and are of shorter duration.\n    ", "id": "MESH:D008614"}
{"mention": "postoperative pain", "mention_text": "A healthy 17-year-old male received standard intermittent doses of pethidine via a patient-controlled analgesia (PCA) pump for management of postoperative pain control. Twenty-three h postoperatively he developed a brief self-limited seizure. Both plasma pethidine and norpethidine were elevated in the range associated with clinical manifestations of central nervous system excitation. No other risk factors for CNS toxicity were identified. This method allowed frequent self-dosing of pethidine at short time intervals and rapid accumulation of pethidine and norpethidine. The routine use of pethidine via PCA even for a brief postoperative analgesia should be reconsidered.", "entity": "Pain, Postoperative", "aliases": "Pain Postoperative Pains", "definition": "Pain during the period after surgery.\n    ", "id": "MESH:D010149"}
{"mention": "seizure", "mention_text": "A healthy 17-year-old male received standard intermittent doses of pethidine via a patient-controlled analgesia (PCA) pump for management of postoperative pain control. Twenty-three h postoperatively he developed a brief self-limited seizure. Both plasma pethidine and norpethidine were elevated in the range associated with clinical manifestations of central nervous system excitation. No other risk factors for CNS toxicity were identified. This method allowed frequent self-dosing of pethidine at short time intervals and rapid accumulation of pethidine and norpethidine. The routine use of pethidine via PCA even for a brief postoperative analgesia should be reconsidered.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "norpethidine", "mention_text": "A healthy 17-year-old male received standard intermittent doses of pethidine via a patient-controlled analgesia (PCA) pump for management of postoperative pain control. Twenty-three h postoperatively he developed a brief self-limited seizure. Both plasma pethidine and norpethidine were elevated in the range associated with clinical manifestations of central nervous system excitation. No other risk factors for CNS toxicity were identified. This method allowed frequent self-dosing of pethidine at short time intervals and rapid accumulation of pethidine and norpethidine. The routine use of pethidine via PCA even for a brief postoperative analgesia should be reconsidered.", "entity": "normeperidine", "aliases": "normeperidine carbonate (2:1) hydrochloride 3H-labeled cpd norpethidine", "definition": "", "id": "MESH:C002752"}
{"mention": "toxicity", "mention_text": "A healthy 17-year-old male received standard intermittent doses of pethidine via a patient-controlled analgesia (PCA) pump for management of postoperative pain control. Twenty-three h postoperatively he developed a brief self-limited seizure. Both plasma pethidine and norpethidine were elevated in the range associated with clinical manifestations of central nervous system excitation. No other risk factors for CNS toxicity were identified. This method allowed frequent self-dosing of pethidine at short time intervals and rapid accumulation of pethidine and norpethidine. The routine use of pethidine via PCA even for a brief postoperative analgesia should be reconsidered.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "vanishing bile duct", "mention_text": "Drug-associated acute-onset vanishing bile duct and Stevens-Johnson syndromes in a child.", "entity": "Bile Duct Diseases", "aliases": "Bile Duct Disease Diseases", "definition": "Diseases in any part of the ductal system of the BILIARY TRACT from the smallest BILE CANALICULI to the largest COMMON BILE DUCT.\n    ", "id": "MESH:D001649"}
{"mention": "Stevens-Johnson syndromes", "mention_text": "Drug-associated acute-onset vanishing bile duct and Stevens-Johnson syndromes in a child.", "entity": "Stevens-Johnson Syndrome", "aliases": "Drug Induced Stevens Johnson Syndrome Drug-Induced Stevens-Johnson Syndromes Epidermal Necrolyses Toxic Necrolysis Lyell Lyell's Mycoplasma Mycoplasma-Induced Nonstaphylococcal Scalded Skin Spectrum", "definition": "Rare cutaneous eruption characterized by extensive KERATINOCYTE apoptosis resulting in skin detachment with mucosal involvement. It is often provoked by the use of drugs (e.g., antibiotics and anticonvulsants) or associated with PNEUMONIA, MYCOPLASMA. It is considered a continuum of Toxic Epidermal Necrolysis.\n    ", "id": "MESH:D013262"}
{"mention": "vanishing bile duct", "mention_text": "Acute vanishing bile duct syndrome is a rare but established cause of progressive cholestasis in adults, is most often drug or toxin related, and is of unknown pathogenesis. It has not been reported previously in children. Stevens-Johnson syndrome is a well-recognized immune complex-mediated hypersensitivity reaction that affects all age groups, is drug or infection induced, and has classic systemic, mucosal, and dermatologic manifestations. A previously healthy child who developed acute, severe, rapidly progressive vanishing bile duct syndrome shortly after Stevens-Johnson syndrome is described; this was temporally associated with ibuprofen use. Despite therapy with ursodeoxycholic acid, prednisone, and then tacrolimus, her cholestatic disease was unrelenting, with cirrhosis shown by biopsy 6 months after presentation. This case documents acute drug-related vanishing bile duct syndrome in the pediatric age group and suggests shared immune mechanisms in the pathogenesis of both Stevens-Johnson syndrome and vanishing bile duct syndrome.", "entity": "Bile Duct Diseases", "aliases": "Bile Duct Disease Diseases", "definition": "Diseases in any part of the ductal system of the BILIARY TRACT from the smallest BILE CANALICULI to the largest COMMON BILE DUCT.\n    ", "id": "MESH:D001649"}
{"mention": "cholestasis", "mention_text": "Acute vanishing bile duct syndrome is a rare but established cause of progressive cholestasis in adults, is most often drug or toxin related, and is of unknown pathogenesis. It has not been reported previously in children. Stevens-Johnson syndrome is a well-recognized immune complex-mediated hypersensitivity reaction that affects all age groups, is drug or infection induced, and has classic systemic, mucosal, and dermatologic manifestations. A previously healthy child who developed acute, severe, rapidly progressive vanishing bile duct syndrome shortly after Stevens-Johnson syndrome is described; this was temporally associated with ibuprofen use. Despite therapy with ursodeoxycholic acid, prednisone, and then tacrolimus, her cholestatic disease was unrelenting, with cirrhosis shown by biopsy 6 months after presentation. This case documents acute drug-related vanishing bile duct syndrome in the pediatric age group and suggests shared immune mechanisms in the pathogenesis of both Stevens-Johnson syndrome and vanishing bile duct syndrome.", "entity": "Cholestasis", "aliases": "Bile Duct Obstruction Obstructions Biliary Stases Stasis Cholestases Cholestasis", "definition": "Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).\n    ", "id": "MESH:D002779"}
{"mention": "Stevens-Johnson syndrome", "mention_text": "Acute vanishing bile duct syndrome is a rare but established cause of progressive cholestasis in adults, is most often drug or toxin related, and is of unknown pathogenesis. It has not been reported previously in children. Stevens-Johnson syndrome is a well-recognized immune complex-mediated hypersensitivity reaction that affects all age groups, is drug or infection induced, and has classic systemic, mucosal, and dermatologic manifestations. A previously healthy child who developed acute, severe, rapidly progressive vanishing bile duct syndrome shortly after Stevens-Johnson syndrome is described; this was temporally associated with ibuprofen use. Despite therapy with ursodeoxycholic acid, prednisone, and then tacrolimus, her cholestatic disease was unrelenting, with cirrhosis shown by biopsy 6 months after presentation. This case documents acute drug-related vanishing bile duct syndrome in the pediatric age group and suggests shared immune mechanisms in the pathogenesis of both Stevens-Johnson syndrome and vanishing bile duct syndrome.", "entity": "Stevens-Johnson Syndrome", "aliases": "Drug Induced Stevens Johnson Syndrome Drug-Induced Stevens-Johnson Syndromes Epidermal Necrolyses Toxic Necrolysis Lyell Lyell's Mycoplasma Mycoplasma-Induced Nonstaphylococcal Scalded Skin Spectrum", "definition": "Rare cutaneous eruption characterized by extensive KERATINOCYTE apoptosis resulting in skin detachment with mucosal involvement. It is often provoked by the use of drugs (e.g., antibiotics and anticonvulsants) or associated with PNEUMONIA, MYCOPLASMA. It is considered a continuum of Toxic Epidermal Necrolysis.\n    ", "id": "MESH:D013262"}
{"mention": "hypersensitivity", "mention_text": "Acute vanishing bile duct syndrome is a rare but established cause of progressive cholestasis in adults, is most often drug or toxin related, and is of unknown pathogenesis. It has not been reported previously in children. Stevens-Johnson syndrome is a well-recognized immune complex-mediated hypersensitivity reaction that affects all age groups, is drug or infection induced, and has classic systemic, mucosal, and dermatologic manifestations. A previously healthy child who developed acute, severe, rapidly progressive vanishing bile duct syndrome shortly after Stevens-Johnson syndrome is described; this was temporally associated with ibuprofen use. Despite therapy with ursodeoxycholic acid, prednisone, and then tacrolimus, her cholestatic disease was unrelenting, with cirrhosis shown by biopsy 6 months after presentation. This case documents acute drug-related vanishing bile duct syndrome in the pediatric age group and suggests shared immune mechanisms in the pathogenesis of both Stevens-Johnson syndrome and vanishing bile duct syndrome.", "entity": "Drug Hypersensitivity", "aliases": "Allergies Drug Allergy Hypersensitivities Hypersensitivity", "definition": "Immunologically mediated adverse reactions to medicinal substances used legally or illegally.\n    ", "id": "MESH:D004342"}
{"mention": "infection", "mention_text": "Acute vanishing bile duct syndrome is a rare but established cause of progressive cholestasis in adults, is most often drug or toxin related, and is of unknown pathogenesis. It has not been reported previously in children. Stevens-Johnson syndrome is a well-recognized immune complex-mediated hypersensitivity reaction that affects all age groups, is drug or infection induced, and has classic systemic, mucosal, and dermatologic manifestations. A previously healthy child who developed acute, severe, rapidly progressive vanishing bile duct syndrome shortly after Stevens-Johnson syndrome is described; this was temporally associated with ibuprofen use. Despite therapy with ursodeoxycholic acid, prednisone, and then tacrolimus, her cholestatic disease was unrelenting, with cirrhosis shown by biopsy 6 months after presentation. This case documents acute drug-related vanishing bile duct syndrome in the pediatric age group and suggests shared immune mechanisms in the pathogenesis of both Stevens-Johnson syndrome and vanishing bile duct syndrome.", "entity": "Infection", "aliases": "Infection Infections", "definition": "Invasion of the host organism by microorganisms that can cause pathological conditions or diseases.\n    ", "id": "MESH:D007239"}
{"mention": "vanishing bile duct syndrome", "mention_text": "Acute vanishing bile duct syndrome is a rare but established cause of progressive cholestasis in adults, is most often drug or toxin related, and is of unknown pathogenesis. It has not been reported previously in children. Stevens-Johnson syndrome is a well-recognized immune complex-mediated hypersensitivity reaction that affects all age groups, is drug or infection induced, and has classic systemic, mucosal, and dermatologic manifestations. A previously healthy child who developed acute, severe, rapidly progressive vanishing bile duct syndrome shortly after Stevens-Johnson syndrome is described; this was temporally associated with ibuprofen use. Despite therapy with ursodeoxycholic acid, prednisone, and then tacrolimus, her cholestatic disease was unrelenting, with cirrhosis shown by biopsy 6 months after presentation. This case documents acute drug-related vanishing bile duct syndrome in the pediatric age group and suggests shared immune mechanisms in the pathogenesis of both Stevens-Johnson syndrome and vanishing bile duct syndrome.", "entity": "Bile Duct Diseases", "aliases": "Bile Duct Disease Diseases", "definition": "Diseases in any part of the ductal system of the BILIARY TRACT from the smallest BILE CANALICULI to the largest COMMON BILE DUCT.\n    ", "id": "MESH:D001649"}
{"mention": "ibuprofen", "mention_text": "Acute vanishing bile duct syndrome is a rare but established cause of progressive cholestasis in adults, is most often drug or toxin related, and is of unknown pathogenesis. It has not been reported previously in children. Stevens-Johnson syndrome is a well-recognized immune complex-mediated hypersensitivity reaction that affects all age groups, is drug or infection induced, and has classic systemic, mucosal, and dermatologic manifestations. A previously healthy child who developed acute, severe, rapidly progressive vanishing bile duct syndrome shortly after Stevens-Johnson syndrome is described; this was temporally associated with ibuprofen use. Despite therapy with ursodeoxycholic acid, prednisone, and then tacrolimus, her cholestatic disease was unrelenting, with cirrhosis shown by biopsy 6 months after presentation. This case documents acute drug-related vanishing bile duct syndrome in the pediatric age group and suggests shared immune mechanisms in the pathogenesis of both Stevens-Johnson syndrome and vanishing bile duct syndrome.", "entity": "Ibuprofen", "aliases": "Aluminum Salt Ibuprofen Brufen Calcium I.V. Solution IP 82 IP-82 IP82 Ibumetin Zinc (+-)-Isomer (R)-Isomer (S)-Isomer Copper (2+) Magnesium Potassium Sodium Ibuprofen-Zinc Motrin Nuprin Rufen Salprofen Trauma Dolgit Gel Trauma-Dolgit TraumaDolgit alpha-Methyl-4-(2-methylpropyl)benzeneacetic Acid", "definition": "A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis.\n    ", "id": "MESH:D007052"}
{"mention": "ursodeoxycholic acid", "mention_text": "Acute vanishing bile duct syndrome is a rare but established cause of progressive cholestasis in adults, is most often drug or toxin related, and is of unknown pathogenesis. It has not been reported previously in children. Stevens-Johnson syndrome is a well-recognized immune complex-mediated hypersensitivity reaction that affects all age groups, is drug or infection induced, and has classic systemic, mucosal, and dermatologic manifestations. A previously healthy child who developed acute, severe, rapidly progressive vanishing bile duct syndrome shortly after Stevens-Johnson syndrome is described; this was temporally associated with ibuprofen use. Despite therapy with ursodeoxycholic acid, prednisone, and then tacrolimus, her cholestatic disease was unrelenting, with cirrhosis shown by biopsy 6 months after presentation. This case documents acute drug-related vanishing bile duct syndrome in the pediatric age group and suggests shared immune mechanisms in the pathogenesis of both Stevens-Johnson syndrome and vanishing bile duct syndrome.", "entity": "Ursodeoxycholic Acid", "aliases": "3 alpha,7 beta Dihydroxy 5 beta cholan 24 oic Acid beta-Dihydroxy-5 beta-cholan-24-oic Deoxyursocholic Ursacholic Ursodeoxycholic Antigen Brand of Aventis Axcan CP Cholit-Ursan Cholofalk Delursan Destolit Estedi Falk Farmasa Galen Heumann Niddapharm Norgine Orphan Provalis Sanofi Synthelabo Sodium Ursodeoxycholate Tramedico Urdox Urso Ursobilane Ursochol Ursodiol Ursofalk Ursogal Ursolite Ursolvan Vita Zambon", "definition": "An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.\n    ", "id": "MESH:D014580"}
{"mention": "prednisone", "mention_text": "Acute vanishing bile duct syndrome is a rare but established cause of progressive cholestasis in adults, is most often drug or toxin related, and is of unknown pathogenesis. It has not been reported previously in children. Stevens-Johnson syndrome is a well-recognized immune complex-mediated hypersensitivity reaction that affects all age groups, is drug or infection induced, and has classic systemic, mucosal, and dermatologic manifestations. A previously healthy child who developed acute, severe, rapidly progressive vanishing bile duct syndrome shortly after Stevens-Johnson syndrome is described; this was temporally associated with ibuprofen use. Despite therapy with ursodeoxycholic acid, prednisone, and then tacrolimus, her cholestatic disease was unrelenting, with cirrhosis shown by biopsy 6 months after presentation. This case documents acute drug-related vanishing bile duct syndrome in the pediatric age group and suggests shared immune mechanisms in the pathogenesis of both Stevens-Johnson syndrome and vanishing bile duct syndrome.", "entity": "Prednisone", "aliases": "Apo-Prednisone Apotex Brand of Prednisone Aventis Cortan Cortancyl Cutason Dacortin Decortin Decortisyl Dehydrocortisone Deltasone Diba Encorton Encortone Enkortolon Fawns & McAllan Ferring GALENpharma Halsey Drug Hexal Hoechst ICN Kortancyl Lichtenstein Liquid Pred Merck Merz Meticorten Orasone Panafcort Panasol Pharmacia Predni Tablinen Prednidib Predniment Prednison Galen acsis Pronisone Rectodelt Schering-Plough Seatrace Solvay Sone Sterapred Trommsdorff Ultracorten Winpred acis delta-Cortis", "definition": "A synthetic anti-inflammatory glucocorticoid derived from CORTISONE. It is biologically inert and converted to PREDNISOLONE in the liver.\n    ", "id": "MESH:D011241"}
{"mention": "tacrolimus", "mention_text": "Acute vanishing bile duct syndrome is a rare but established cause of progressive cholestasis in adults, is most often drug or toxin related, and is of unknown pathogenesis. It has not been reported previously in children. Stevens-Johnson syndrome is a well-recognized immune complex-mediated hypersensitivity reaction that affects all age groups, is drug or infection induced, and has classic systemic, mucosal, and dermatologic manifestations. A previously healthy child who developed acute, severe, rapidly progressive vanishing bile duct syndrome shortly after Stevens-Johnson syndrome is described; this was temporally associated with ibuprofen use. Despite therapy with ursodeoxycholic acid, prednisone, and then tacrolimus, her cholestatic disease was unrelenting, with cirrhosis shown by biopsy 6 months after presentation. This case documents acute drug-related vanishing bile duct syndrome in the pediatric age group and suggests shared immune mechanisms in the pathogenesis of both Stevens-Johnson syndrome and vanishing bile duct syndrome.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "cholestatic disease", "mention_text": "Acute vanishing bile duct syndrome is a rare but established cause of progressive cholestasis in adults, is most often drug or toxin related, and is of unknown pathogenesis. It has not been reported previously in children. Stevens-Johnson syndrome is a well-recognized immune complex-mediated hypersensitivity reaction that affects all age groups, is drug or infection induced, and has classic systemic, mucosal, and dermatologic manifestations. A previously healthy child who developed acute, severe, rapidly progressive vanishing bile duct syndrome shortly after Stevens-Johnson syndrome is described; this was temporally associated with ibuprofen use. Despite therapy with ursodeoxycholic acid, prednisone, and then tacrolimus, her cholestatic disease was unrelenting, with cirrhosis shown by biopsy 6 months after presentation. This case documents acute drug-related vanishing bile duct syndrome in the pediatric age group and suggests shared immune mechanisms in the pathogenesis of both Stevens-Johnson syndrome and vanishing bile duct syndrome.", "entity": "Cholestasis", "aliases": "Bile Duct Obstruction Obstructions Biliary Stases Stasis Cholestases Cholestasis", "definition": "Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).\n    ", "id": "MESH:D002779"}
{"mention": "cirrhosis", "mention_text": "Acute vanishing bile duct syndrome is a rare but established cause of progressive cholestasis in adults, is most often drug or toxin related, and is of unknown pathogenesis. It has not been reported previously in children. Stevens-Johnson syndrome is a well-recognized immune complex-mediated hypersensitivity reaction that affects all age groups, is drug or infection induced, and has classic systemic, mucosal, and dermatologic manifestations. A previously healthy child who developed acute, severe, rapidly progressive vanishing bile duct syndrome shortly after Stevens-Johnson syndrome is described; this was temporally associated with ibuprofen use. Despite therapy with ursodeoxycholic acid, prednisone, and then tacrolimus, her cholestatic disease was unrelenting, with cirrhosis shown by biopsy 6 months after presentation. This case documents acute drug-related vanishing bile duct syndrome in the pediatric age group and suggests shared immune mechanisms in the pathogenesis of both Stevens-Johnson syndrome and vanishing bile duct syndrome.", "entity": "Fibrosis", "aliases": "Cirrhosis Fibroses Fibrosis", "definition": "Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.\n    ", "id": "MESH:D005355"}
{"mention": "primary pulmonary hypertension", "mention_text": "High incidence of primary pulmonary hypertension associated with appetite suppressants in Belgium.", "entity": "Hypertension, Pulmonary", "aliases": "Hypertension Pulmonary", "definition": "Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES.\n    ", "id": "MESH:D006976"}
{"mention": "appetite suppressants", "mention_text": "High incidence of primary pulmonary hypertension associated with appetite suppressants in Belgium.", "entity": "Appetite Depressants", "aliases": "Agents Anorectic Anorectics Anorexic Drugs Anorexigenic Appetite Depressants Depressing Suppressant Suppressants Appetite-Depressing Appetite-Suppressant", "definition": "Agents that are used to suppress appetite.\n    ", "id": "MESH:D001067"}
{"mention": "Primary pulmonary hypertension", "mention_text": "Primary pulmonary hypertension is a rare, progressive and incurable disease, which has been associated with the intake of appetite suppressant drugs. The importance of this association was evaluated in Belgium while this country still had no restriction on the prescription of appetite suppressants. Thirty-five patients with primary pulmonary hypertension and 85 matched controls were recruited over 32 months (1992-1994) in Belgium. Exposure to appetite-suppressants was assessed on the basis of hospital records and standardized interview. Twenty-three of the patients had previously taken appetite suppressants, mainly fenfluramines, as compared with only 5 of the controls (66 versus 6%, p<0.0001). Five patients died before the interview, all of them had taken appetite suppressants. In 8 patients the diagnosis of primary pulmonary hypertension was uncertain, 5 of them had taken appetite suppressants. The patients who had been exposed to appetite suppressants tended to be on average more severely ill, and to have a shorter median delay between onset of symptoms and diagnosis. A policy of unrestricted prescription of appetite suppressants may lead to a high incidence of associated primary pulmonary hypertension. Intake of appetite suppressants may accelerate the progression of the disease.", "entity": "Hypertension, Pulmonary", "aliases": "Hypertension Pulmonary", "definition": "Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES.\n    ", "id": "MESH:D006976"}
{"mention": "appetite suppressant", "mention_text": "Primary pulmonary hypertension is a rare, progressive and incurable disease, which has been associated with the intake of appetite suppressant drugs. The importance of this association was evaluated in Belgium while this country still had no restriction on the prescription of appetite suppressants. Thirty-five patients with primary pulmonary hypertension and 85 matched controls were recruited over 32 months (1992-1994) in Belgium. Exposure to appetite-suppressants was assessed on the basis of hospital records and standardized interview. Twenty-three of the patients had previously taken appetite suppressants, mainly fenfluramines, as compared with only 5 of the controls (66 versus 6%, p<0.0001). Five patients died before the interview, all of them had taken appetite suppressants. In 8 patients the diagnosis of primary pulmonary hypertension was uncertain, 5 of them had taken appetite suppressants. The patients who had been exposed to appetite suppressants tended to be on average more severely ill, and to have a shorter median delay between onset of symptoms and diagnosis. A policy of unrestricted prescription of appetite suppressants may lead to a high incidence of associated primary pulmonary hypertension. Intake of appetite suppressants may accelerate the progression of the disease.", "entity": "Appetite Depressants", "aliases": "Agents Anorectic Anorectics Anorexic Drugs Anorexigenic Appetite Depressants Depressing Suppressant Suppressants Appetite-Depressing Appetite-Suppressant", "definition": "Agents that are used to suppress appetite.\n    ", "id": "MESH:D001067"}
{"mention": "appetite suppressants", "mention_text": "Primary pulmonary hypertension is a rare, progressive and incurable disease, which has been associated with the intake of appetite suppressant drugs. The importance of this association was evaluated in Belgium while this country still had no restriction on the prescription of appetite suppressants. Thirty-five patients with primary pulmonary hypertension and 85 matched controls were recruited over 32 months (1992-1994) in Belgium. Exposure to appetite-suppressants was assessed on the basis of hospital records and standardized interview. Twenty-three of the patients had previously taken appetite suppressants, mainly fenfluramines, as compared with only 5 of the controls (66 versus 6%, p<0.0001). Five patients died before the interview, all of them had taken appetite suppressants. In 8 patients the diagnosis of primary pulmonary hypertension was uncertain, 5 of them had taken appetite suppressants. The patients who had been exposed to appetite suppressants tended to be on average more severely ill, and to have a shorter median delay between onset of symptoms and diagnosis. A policy of unrestricted prescription of appetite suppressants may lead to a high incidence of associated primary pulmonary hypertension. Intake of appetite suppressants may accelerate the progression of the disease.", "entity": "Appetite Depressants", "aliases": "Agents Anorectic Anorectics Anorexic Drugs Anorexigenic Appetite Depressants Depressing Suppressant Suppressants Appetite-Depressing Appetite-Suppressant", "definition": "Agents that are used to suppress appetite.\n    ", "id": "MESH:D001067"}
{"mention": "primary pulmonary hypertension", "mention_text": "Primary pulmonary hypertension is a rare, progressive and incurable disease, which has been associated with the intake of appetite suppressant drugs. The importance of this association was evaluated in Belgium while this country still had no restriction on the prescription of appetite suppressants. Thirty-five patients with primary pulmonary hypertension and 85 matched controls were recruited over 32 months (1992-1994) in Belgium. Exposure to appetite-suppressants was assessed on the basis of hospital records and standardized interview. Twenty-three of the patients had previously taken appetite suppressants, mainly fenfluramines, as compared with only 5 of the controls (66 versus 6%, p<0.0001). Five patients died before the interview, all of them had taken appetite suppressants. In 8 patients the diagnosis of primary pulmonary hypertension was uncertain, 5 of them had taken appetite suppressants. The patients who had been exposed to appetite suppressants tended to be on average more severely ill, and to have a shorter median delay between onset of symptoms and diagnosis. A policy of unrestricted prescription of appetite suppressants may lead to a high incidence of associated primary pulmonary hypertension. Intake of appetite suppressants may accelerate the progression of the disease.", "entity": "Hypertension, Pulmonary", "aliases": "Hypertension Pulmonary", "definition": "Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES.\n    ", "id": "MESH:D006976"}
{"mention": "appetite-suppressants", "mention_text": "Primary pulmonary hypertension is a rare, progressive and incurable disease, which has been associated with the intake of appetite suppressant drugs. The importance of this association was evaluated in Belgium while this country still had no restriction on the prescription of appetite suppressants. Thirty-five patients with primary pulmonary hypertension and 85 matched controls were recruited over 32 months (1992-1994) in Belgium. Exposure to appetite-suppressants was assessed on the basis of hospital records and standardized interview. Twenty-three of the patients had previously taken appetite suppressants, mainly fenfluramines, as compared with only 5 of the controls (66 versus 6%, p<0.0001). Five patients died before the interview, all of them had taken appetite suppressants. In 8 patients the diagnosis of primary pulmonary hypertension was uncertain, 5 of them had taken appetite suppressants. The patients who had been exposed to appetite suppressants tended to be on average more severely ill, and to have a shorter median delay between onset of symptoms and diagnosis. A policy of unrestricted prescription of appetite suppressants may lead to a high incidence of associated primary pulmonary hypertension. Intake of appetite suppressants may accelerate the progression of the disease.", "entity": "Appetite Depressants", "aliases": "Agents Anorectic Anorectics Anorexic Drugs Anorexigenic Appetite Depressants Depressing Suppressant Suppressants Appetite-Depressing Appetite-Suppressant", "definition": "Agents that are used to suppress appetite.\n    ", "id": "MESH:D001067"}
{"mention": "fenfluramines", "mention_text": "Primary pulmonary hypertension is a rare, progressive and incurable disease, which has been associated with the intake of appetite suppressant drugs. The importance of this association was evaluated in Belgium while this country still had no restriction on the prescription of appetite suppressants. Thirty-five patients with primary pulmonary hypertension and 85 matched controls were recruited over 32 months (1992-1994) in Belgium. Exposure to appetite-suppressants was assessed on the basis of hospital records and standardized interview. Twenty-three of the patients had previously taken appetite suppressants, mainly fenfluramines, as compared with only 5 of the controls (66 versus 6%, p<0.0001). Five patients died before the interview, all of them had taken appetite suppressants. In 8 patients the diagnosis of primary pulmonary hypertension was uncertain, 5 of them had taken appetite suppressants. The patients who had been exposed to appetite suppressants tended to be on average more severely ill, and to have a shorter median delay between onset of symptoms and diagnosis. A policy of unrestricted prescription of appetite suppressants may lead to a high incidence of associated primary pulmonary hypertension. Intake of appetite suppressants may accelerate the progression of the disease.", "entity": "Fenfluramine", "aliases": "Fenfluramine Hydrochloride (+-)-Isomer R Isomer R-Isomer Isomeride Pondimin Robins Brand of", "definition": "A centrally active drug that apparently both blocks serotonin uptake and provokes transport-mediated serotonin release.\n    ", "id": "MESH:D005277"}
{"mention": "Choreoathetoid movements", "mention_text": "Choreoathetoid movements associated with rapid adjustment to methadone.", "entity": "Chorea", "aliases": "Benign Hereditary Chorea Choreas Disorder Disorders Syndrome Syndromes Chronic Progressive Rheumatic Senile Sydenham Sydenham's Choreatic Choreic Movement Movements Choreiform Dyskinesia Paroxysmal Dyskinesias Without Dementia St. Vitus Dance Vitus's Dances Vituss Sydenhams", "definition": "Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as CHOREATIC DISORDERS. Chorea is also a frequent manifestation of BASAL GANGLIA DISEASES.\n    ", "id": "MESH:D002819"}
{"mention": "methadone", "mention_text": "Choreoathetoid movements associated with rapid adjustment to methadone.", "entity": "Methadone", "aliases": "Amidone Biodone Biomet Brand of Methadone Hydrochloride Dolophine Esteve Generics GlaxoSmithKline Mallinckrodt Martindale Metadol Metasedin Methaddict Methadose Methex Pharmascience Phenadone Phymet Physeptone Pinadone Pinewood Rosemont Roxane Symoron Yamanouchi addiCare", "definition": "A synthetic opioid that is used as the hydrochloride. It is an opioid analgesic that is primarily a mu-opioid agonist. It has actions and uses similar to those of MORPHINE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1082-3)\n    ", "id": "MESH:D008691"}
{"mention": "Choreatiform", "mention_text": "Choreatiform hyperkinesias are known to be occasional movement abnormalities during intoxications with cocaine but not opiates. This is a case report of euphoria and choreoathetoid movements both transiently induced by rapid adjustment to the selective mu-opioid receptor agonist methadone in an inpatient previously abusing heroine and cocaine. In addition, minor EEG abnormalities occurred. Possible underlying neurobiological phenomena are discussed.", "entity": "Chorea", "aliases": "Benign Hereditary Chorea Choreas Disorder Disorders Syndrome Syndromes Chronic Progressive Rheumatic Senile Sydenham Sydenham's Choreatic Choreic Movement Movements Choreiform Dyskinesia Paroxysmal Dyskinesias Without Dementia St. Vitus Dance Vitus's Dances Vituss Sydenhams", "definition": "Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as CHOREATIC DISORDERS. Chorea is also a frequent manifestation of BASAL GANGLIA DISEASES.\n    ", "id": "MESH:D002819"}
{"mention": "hyperkinesias", "mention_text": "Choreatiform hyperkinesias are known to be occasional movement abnormalities during intoxications with cocaine but not opiates. This is a case report of euphoria and choreoathetoid movements both transiently induced by rapid adjustment to the selective mu-opioid receptor agonist methadone in an inpatient previously abusing heroine and cocaine. In addition, minor EEG abnormalities occurred. Possible underlying neurobiological phenomena are discussed.", "entity": "Hyperkinesis", "aliases": "Generalized Hyperkinesia Hyperkinesias Hyperactivity Motor Hyperkinesis Hyperkinetic Movement Movements", "definition": "Excessive movement of muscles of the body as a whole, which may be associated with organic or psychological disorders.\n    ", "id": "MESH:D006948"}
{"mention": "movement abnormalities", "mention_text": "Choreatiform hyperkinesias are known to be occasional movement abnormalities during intoxications with cocaine but not opiates. This is a case report of euphoria and choreoathetoid movements both transiently induced by rapid adjustment to the selective mu-opioid receptor agonist methadone in an inpatient previously abusing heroine and cocaine. In addition, minor EEG abnormalities occurred. Possible underlying neurobiological phenomena are discussed.", "entity": "Dyskinesias", "aliases": "Abnormal Movement Movements Asterixis Ballismus Dyskinesia Dyskinesias Hemiballism Hemiballismus Involuntary", "definition": "Abnormal involuntary movements which primarily affect the extremities, trunk, or jaw that occur as a manifestation of an underlying disease process. Conditions which feature recurrent or persistent episodes of dyskinesia as a primary manifestation of disease may be referred to as dyskinesia syndromes (see MOVEMENT DISORDERS). Dyskinesias are also a relatively common manifestation of BASAL GANGLIA DISEASES.\n    ", "id": "MESH:D020820"}
{"mention": "cocaine", "mention_text": "Choreatiform hyperkinesias are known to be occasional movement abnormalities during intoxications with cocaine but not opiates. This is a case report of euphoria and choreoathetoid movements both transiently induced by rapid adjustment to the selective mu-opioid receptor agonist methadone in an inpatient previously abusing heroine and cocaine. In addition, minor EEG abnormalities occurred. Possible underlying neurobiological phenomena are discussed.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "choreoathetoid movements", "mention_text": "Choreatiform hyperkinesias are known to be occasional movement abnormalities during intoxications with cocaine but not opiates. This is a case report of euphoria and choreoathetoid movements both transiently induced by rapid adjustment to the selective mu-opioid receptor agonist methadone in an inpatient previously abusing heroine and cocaine. In addition, minor EEG abnormalities occurred. Possible underlying neurobiological phenomena are discussed.", "entity": "Chorea", "aliases": "Benign Hereditary Chorea Choreas Disorder Disorders Syndrome Syndromes Chronic Progressive Rheumatic Senile Sydenham Sydenham's Choreatic Choreic Movement Movements Choreiform Dyskinesia Paroxysmal Dyskinesias Without Dementia St. Vitus Dance Vitus's Dances Vituss Sydenhams", "definition": "Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as CHOREATIC DISORDERS. Chorea is also a frequent manifestation of BASAL GANGLIA DISEASES.\n    ", "id": "MESH:D002819"}
{"mention": "methadone", "mention_text": "Choreatiform hyperkinesias are known to be occasional movement abnormalities during intoxications with cocaine but not opiates. This is a case report of euphoria and choreoathetoid movements both transiently induced by rapid adjustment to the selective mu-opioid receptor agonist methadone in an inpatient previously abusing heroine and cocaine. In addition, minor EEG abnormalities occurred. Possible underlying neurobiological phenomena are discussed.", "entity": "Methadone", "aliases": "Amidone Biodone Biomet Brand of Methadone Hydrochloride Dolophine Esteve Generics GlaxoSmithKline Mallinckrodt Martindale Metadol Metasedin Methaddict Methadose Methex Pharmascience Phenadone Phymet Physeptone Pinadone Pinewood Rosemont Roxane Symoron Yamanouchi addiCare", "definition": "A synthetic opioid that is used as the hydrochloride. It is an opioid analgesic that is primarily a mu-opioid agonist. It has actions and uses similar to those of MORPHINE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1082-3)\n    ", "id": "MESH:D008691"}
{"mention": "heroine", "mention_text": "Choreatiform hyperkinesias are known to be occasional movement abnormalities during intoxications with cocaine but not opiates. This is a case report of euphoria and choreoathetoid movements both transiently induced by rapid adjustment to the selective mu-opioid receptor agonist methadone in an inpatient previously abusing heroine and cocaine. In addition, minor EEG abnormalities occurred. Possible underlying neurobiological phenomena are discussed.", "entity": "Heroin", "aliases": "APS Brand of Heroin Hydrochloride Diacetylmorphine Diagesil Diamorf Diamorphine Evans Vaccines Min I Jet Morphine Sulphate Min-I-Jet", "definition": "A narcotic analgesic that may be habit-forming. It is a controlled substance (opium derivative) listed in the U.S. Code of Federal Regulations, Title 21 Parts 329.1, 1308.11 (1987). Sale is forbidden in the United States by Federal statute. (Merck Index, 11th ed)\n    ", "id": "MESH:D003932"}
{"mention": "Cocaine", "mention_text": "Cocaine-induced mood disorder: prevalence rates and psychiatric symptoms in an outpatient cocaine-dependent sample.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "mood disorder", "mention_text": "Cocaine-induced mood disorder: prevalence rates and psychiatric symptoms in an outpatient cocaine-dependent sample.", "entity": "Mood Disorders", "aliases": "Affective Disorder Disorders Mood", "definition": "Those disorders that have a disturbance in mood as their predominant feature.\n    ", "id": "MESH:D019964"}
{"mention": "psychiatric", "mention_text": "Cocaine-induced mood disorder: prevalence rates and psychiatric symptoms in an outpatient cocaine-dependent sample.", "entity": "Mental Disorders", "aliases": "Behavior Disorders Diagnosis Psychiatric Disorder Mental", "definition": "Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.\n    ", "id": "MESH:D001523"}
{"mention": "cocaine", "mention_text": "Cocaine-induced mood disorder: prevalence rates and psychiatric symptoms in an outpatient cocaine-dependent sample.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "mood disorders", "mention_text": "This paper attempts to examine and compare prevalence rates and symptom patterns of DSM substance-induced and other mood disorders. 243 cocaine-dependent outpatients with cocaine-induced mood disorder (CIMD), other mood disorders, or no mood disorder were compared on measures of psychiatric symptoms. The prevalence rate for CIMD was 12% at baseline. Introduction of the DSM-IV diagnosis of CIMD did not substantially affect rates of the other depressive disorders. Patients with CIMD had symptom severity levels between those of patients with and without a mood disorder. These findings suggest some validity for the new DSM-IV diagnosis of CIMD, but also suggest that it requires further specification and replication.", "entity": "Mood Disorders", "aliases": "Affective Disorder Disorders Mood", "definition": "Those disorders that have a disturbance in mood as their predominant feature.\n    ", "id": "MESH:D019964"}
{"mention": "cocaine", "mention_text": "This paper attempts to examine and compare prevalence rates and symptom patterns of DSM substance-induced and other mood disorders. 243 cocaine-dependent outpatients with cocaine-induced mood disorder (CIMD), other mood disorders, or no mood disorder were compared on measures of psychiatric symptoms. The prevalence rate for CIMD was 12% at baseline. Introduction of the DSM-IV diagnosis of CIMD did not substantially affect rates of the other depressive disorders. Patients with CIMD had symptom severity levels between those of patients with and without a mood disorder. These findings suggest some validity for the new DSM-IV diagnosis of CIMD, but also suggest that it requires further specification and replication.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "mood disorder", "mention_text": "This paper attempts to examine and compare prevalence rates and symptom patterns of DSM substance-induced and other mood disorders. 243 cocaine-dependent outpatients with cocaine-induced mood disorder (CIMD), other mood disorders, or no mood disorder were compared on measures of psychiatric symptoms. The prevalence rate for CIMD was 12% at baseline. Introduction of the DSM-IV diagnosis of CIMD did not substantially affect rates of the other depressive disorders. Patients with CIMD had symptom severity levels between those of patients with and without a mood disorder. These findings suggest some validity for the new DSM-IV diagnosis of CIMD, but also suggest that it requires further specification and replication.", "entity": "Mood Disorders", "aliases": "Affective Disorder Disorders Mood", "definition": "Those disorders that have a disturbance in mood as their predominant feature.\n    ", "id": "MESH:D019964"}
{"mention": "CIMD", "mention_text": "This paper attempts to examine and compare prevalence rates and symptom patterns of DSM substance-induced and other mood disorders. 243 cocaine-dependent outpatients with cocaine-induced mood disorder (CIMD), other mood disorders, or no mood disorder were compared on measures of psychiatric symptoms. The prevalence rate for CIMD was 12% at baseline. Introduction of the DSM-IV diagnosis of CIMD did not substantially affect rates of the other depressive disorders. Patients with CIMD had symptom severity levels between those of patients with and without a mood disorder. These findings suggest some validity for the new DSM-IV diagnosis of CIMD, but also suggest that it requires further specification and replication.", "entity": "Cocaine-Related Disorders", "aliases": "Abuse Cocaine Addiction Dependence Related Disorders Cocaine-Related Disorder Dependences", "definition": "Disorders related or resulting from use of cocaine.\n    ", "id": "MESH:D019970"}
{"mention": "psychiatric", "mention_text": "This paper attempts to examine and compare prevalence rates and symptom patterns of DSM substance-induced and other mood disorders. 243 cocaine-dependent outpatients with cocaine-induced mood disorder (CIMD), other mood disorders, or no mood disorder were compared on measures of psychiatric symptoms. The prevalence rate for CIMD was 12% at baseline. Introduction of the DSM-IV diagnosis of CIMD did not substantially affect rates of the other depressive disorders. Patients with CIMD had symptom severity levels between those of patients with and without a mood disorder. These findings suggest some validity for the new DSM-IV diagnosis of CIMD, but also suggest that it requires further specification and replication.", "entity": "Mental Disorders", "aliases": "Behavior Disorders Diagnosis Psychiatric Disorder Mental", "definition": "Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.\n    ", "id": "MESH:D001523"}
{"mention": "depressive disorders", "mention_text": "This paper attempts to examine and compare prevalence rates and symptom patterns of DSM substance-induced and other mood disorders. 243 cocaine-dependent outpatients with cocaine-induced mood disorder (CIMD), other mood disorders, or no mood disorder were compared on measures of psychiatric symptoms. The prevalence rate for CIMD was 12% at baseline. Introduction of the DSM-IV diagnosis of CIMD did not substantially affect rates of the other depressive disorders. Patients with CIMD had symptom severity levels between those of patients with and without a mood disorder. These findings suggest some validity for the new DSM-IV diagnosis of CIMD, but also suggest that it requires further specification and replication.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "Hemolysis", "mention_text": "Hemolysis of human erythrocytes induced by tamoxifen is related to disruption of membrane structure.", "entity": "Hemolysis", "aliases": "Hemolysis", "definition": "The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.\n    ", "id": "MESH:D006461"}
{"mention": "tamoxifen", "mention_text": "Hemolysis of human erythrocytes induced by tamoxifen is related to disruption of membrane structure.", "entity": "Tamoxifen", "aliases": "Citrate Tamoxifen ICI 46,474 46474 47699 ICI-46,474 ICI-46474 ICI-47699 ICI46,474 ICI46474 ICI47699 Nolvadex Novaldex Savient brand of Soltamox Tomaxithen Zitazonium", "definition": "One of the SELECTIVE ESTROGEN RECEPTOR MODULATORS with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the ENDOMETRIUM.\n    ", "id": "MESH:D013629"}
{"mention": "Tamoxifen", "mention_text": "Tamoxifen (TAM), the antiestrogenic drug most widely prescribed in the chemotherapy of breast cancer, induces changes in normal discoid shape of erythrocytes and hemolytic anemia. This work evaluates the effects of TAM on isolated human erythrocytes, attempting to identify the underlying mechanisms on TAM-induced hemolytic anemia and the involvement of biomembranes in its cytostatic action mechanisms. TAM induces hemolysis of erythrocytes as a function of concentration. The extension of hemolysis is variable with erythrocyte samples, but 12.5 microM TAM induces total hemolysis of all tested suspensions. Despite inducing extensive erythrocyte lysis, TAM does not shift the osmotic fragility curves of erythrocytes. The hemolytic effect of TAM is prevented by low concentrations of alpha-tocopherol (alpha-T) and alpha-tocopherol acetate (alpha-TAc) (inactivated functional hydroxyl) indicating that TAM-induced hemolysis is not related to oxidative membrane damage. This was further evidenced by absence of oxygen consumption and hemoglobin oxidation both determined in parallel with TAM-induced hemolysis. Furthermore, it was observed that TAM inhibits the peroxidation of human erythrocytes induced by AAPH, thus ruling out TAM-induced cell oxidative stress. Hemolysis caused by TAM was not preceded by the leakage of K(+) from the cells, also excluding a colloid-osmotic type mechanism of hemolysis, according to the effects on osmotic fragility curves. However, TAM induces release of peripheral proteins of membrane-cytoskeleton and cytosol proteins essentially bound to band 3. Either alpha-T or alpha-TAc increases membrane packing and prevents TAM partition into model membranes. These effects suggest that the protection from hemolysis by tocopherols is related to a decreased TAM incorporation in condensed membranes and the structural damage of the erythrocyte membrane is consequently avoided. Therefore, TAM-induced hemolysis results from a structural perturbation of red cell membrane, leading to changes in the framework of the erythrocyte membrane and its cytoskeleton caused by its high partition in the membrane. These defects explain the abnormal erythrocyte shape and decreased mechanical stability promoted by TAM, resulting in hemolytic anemia. Additionally, since membrane leakage is a final stage of cytotoxicity, the disruption of the structural characteristics of biomembranes by TAM may contribute to the multiple mechanisms of its anticancer action.", "entity": "Tamoxifen", "aliases": "Citrate Tamoxifen ICI 46,474 46474 47699 ICI-46,474 ICI-46474 ICI-47699 ICI46,474 ICI46474 ICI47699 Nolvadex Novaldex Savient brand of Soltamox Tomaxithen Zitazonium", "definition": "One of the SELECTIVE ESTROGEN RECEPTOR MODULATORS with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the ENDOMETRIUM.\n    ", "id": "MESH:D013629"}
{"mention": "TAM", "mention_text": "Tamoxifen (TAM), the antiestrogenic drug most widely prescribed in the chemotherapy of breast cancer, induces changes in normal discoid shape of erythrocytes and hemolytic anemia. This work evaluates the effects of TAM on isolated human erythrocytes, attempting to identify the underlying mechanisms on TAM-induced hemolytic anemia and the involvement of biomembranes in its cytostatic action mechanisms. TAM induces hemolysis of erythrocytes as a function of concentration. The extension of hemolysis is variable with erythrocyte samples, but 12.5 microM TAM induces total hemolysis of all tested suspensions. Despite inducing extensive erythrocyte lysis, TAM does not shift the osmotic fragility curves of erythrocytes. The hemolytic effect of TAM is prevented by low concentrations of alpha-tocopherol (alpha-T) and alpha-tocopherol acetate (alpha-TAc) (inactivated functional hydroxyl) indicating that TAM-induced hemolysis is not related to oxidative membrane damage. This was further evidenced by absence of oxygen consumption and hemoglobin oxidation both determined in parallel with TAM-induced hemolysis. Furthermore, it was observed that TAM inhibits the peroxidation of human erythrocytes induced by AAPH, thus ruling out TAM-induced cell oxidative stress. Hemolysis caused by TAM was not preceded by the leakage of K(+) from the cells, also excluding a colloid-osmotic type mechanism of hemolysis, according to the effects on osmotic fragility curves. However, TAM induces release of peripheral proteins of membrane-cytoskeleton and cytosol proteins essentially bound to band 3. Either alpha-T or alpha-TAc increases membrane packing and prevents TAM partition into model membranes. These effects suggest that the protection from hemolysis by tocopherols is related to a decreased TAM incorporation in condensed membranes and the structural damage of the erythrocyte membrane is consequently avoided. Therefore, TAM-induced hemolysis results from a structural perturbation of red cell membrane, leading to changes in the framework of the erythrocyte membrane and its cytoskeleton caused by its high partition in the membrane. These defects explain the abnormal erythrocyte shape and decreased mechanical stability promoted by TAM, resulting in hemolytic anemia. Additionally, since membrane leakage is a final stage of cytotoxicity, the disruption of the structural characteristics of biomembranes by TAM may contribute to the multiple mechanisms of its anticancer action.", "entity": "Tamoxifen", "aliases": "Citrate Tamoxifen ICI 46,474 46474 47699 ICI-46,474 ICI-46474 ICI-47699 ICI46,474 ICI46474 ICI47699 Nolvadex Novaldex Savient brand of Soltamox Tomaxithen Zitazonium", "definition": "One of the SELECTIVE ESTROGEN RECEPTOR MODULATORS with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the ENDOMETRIUM.\n    ", "id": "MESH:D013629"}
{"mention": "breast cancer", "mention_text": "Tamoxifen (TAM), the antiestrogenic drug most widely prescribed in the chemotherapy of breast cancer, induces changes in normal discoid shape of erythrocytes and hemolytic anemia. This work evaluates the effects of TAM on isolated human erythrocytes, attempting to identify the underlying mechanisms on TAM-induced hemolytic anemia and the involvement of biomembranes in its cytostatic action mechanisms. TAM induces hemolysis of erythrocytes as a function of concentration. The extension of hemolysis is variable with erythrocyte samples, but 12.5 microM TAM induces total hemolysis of all tested suspensions. Despite inducing extensive erythrocyte lysis, TAM does not shift the osmotic fragility curves of erythrocytes. The hemolytic effect of TAM is prevented by low concentrations of alpha-tocopherol (alpha-T) and alpha-tocopherol acetate (alpha-TAc) (inactivated functional hydroxyl) indicating that TAM-induced hemolysis is not related to oxidative membrane damage. This was further evidenced by absence of oxygen consumption and hemoglobin oxidation both determined in parallel with TAM-induced hemolysis. Furthermore, it was observed that TAM inhibits the peroxidation of human erythrocytes induced by AAPH, thus ruling out TAM-induced cell oxidative stress. Hemolysis caused by TAM was not preceded by the leakage of K(+) from the cells, also excluding a colloid-osmotic type mechanism of hemolysis, according to the effects on osmotic fragility curves. However, TAM induces release of peripheral proteins of membrane-cytoskeleton and cytosol proteins essentially bound to band 3. Either alpha-T or alpha-TAc increases membrane packing and prevents TAM partition into model membranes. These effects suggest that the protection from hemolysis by tocopherols is related to a decreased TAM incorporation in condensed membranes and the structural damage of the erythrocyte membrane is consequently avoided. Therefore, TAM-induced hemolysis results from a structural perturbation of red cell membrane, leading to changes in the framework of the erythrocyte membrane and its cytoskeleton caused by its high partition in the membrane. These defects explain the abnormal erythrocyte shape and decreased mechanical stability promoted by TAM, resulting in hemolytic anemia. Additionally, since membrane leakage is a final stage of cytotoxicity, the disruption of the structural characteristics of biomembranes by TAM may contribute to the multiple mechanisms of its anticancer action.", "entity": "Breast Neoplasms", "aliases": "Breast Cancer Carcinoma Neoplasm Neoplasms Tumor Tumors of the Human Mammary Carcinomas Malignant", "definition": "Tumors or cancer of the human BREAST.\n    ", "id": "MESH:D001943"}
{"mention": "hemolytic anemia", "mention_text": "Tamoxifen (TAM), the antiestrogenic drug most widely prescribed in the chemotherapy of breast cancer, induces changes in normal discoid shape of erythrocytes and hemolytic anemia. This work evaluates the effects of TAM on isolated human erythrocytes, attempting to identify the underlying mechanisms on TAM-induced hemolytic anemia and the involvement of biomembranes in its cytostatic action mechanisms. TAM induces hemolysis of erythrocytes as a function of concentration. The extension of hemolysis is variable with erythrocyte samples, but 12.5 microM TAM induces total hemolysis of all tested suspensions. Despite inducing extensive erythrocyte lysis, TAM does not shift the osmotic fragility curves of erythrocytes. The hemolytic effect of TAM is prevented by low concentrations of alpha-tocopherol (alpha-T) and alpha-tocopherol acetate (alpha-TAc) (inactivated functional hydroxyl) indicating that TAM-induced hemolysis is not related to oxidative membrane damage. This was further evidenced by absence of oxygen consumption and hemoglobin oxidation both determined in parallel with TAM-induced hemolysis. Furthermore, it was observed that TAM inhibits the peroxidation of human erythrocytes induced by AAPH, thus ruling out TAM-induced cell oxidative stress. Hemolysis caused by TAM was not preceded by the leakage of K(+) from the cells, also excluding a colloid-osmotic type mechanism of hemolysis, according to the effects on osmotic fragility curves. However, TAM induces release of peripheral proteins of membrane-cytoskeleton and cytosol proteins essentially bound to band 3. Either alpha-T or alpha-TAc increases membrane packing and prevents TAM partition into model membranes. These effects suggest that the protection from hemolysis by tocopherols is related to a decreased TAM incorporation in condensed membranes and the structural damage of the erythrocyte membrane is consequently avoided. Therefore, TAM-induced hemolysis results from a structural perturbation of red cell membrane, leading to changes in the framework of the erythrocyte membrane and its cytoskeleton caused by its high partition in the membrane. These defects explain the abnormal erythrocyte shape and decreased mechanical stability promoted by TAM, resulting in hemolytic anemia. Additionally, since membrane leakage is a final stage of cytotoxicity, the disruption of the structural characteristics of biomembranes by TAM may contribute to the multiple mechanisms of its anticancer action.", "entity": "Anemia, Hemolytic", "aliases": "Acquired Hemolytic Anemia Microangiopathic", "definition": "A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES).\n    ", "id": "MESH:D000743"}
{"mention": "hemolysis", "mention_text": "Tamoxifen (TAM), the antiestrogenic drug most widely prescribed in the chemotherapy of breast cancer, induces changes in normal discoid shape of erythrocytes and hemolytic anemia. This work evaluates the effects of TAM on isolated human erythrocytes, attempting to identify the underlying mechanisms on TAM-induced hemolytic anemia and the involvement of biomembranes in its cytostatic action mechanisms. TAM induces hemolysis of erythrocytes as a function of concentration. The extension of hemolysis is variable with erythrocyte samples, but 12.5 microM TAM induces total hemolysis of all tested suspensions. Despite inducing extensive erythrocyte lysis, TAM does not shift the osmotic fragility curves of erythrocytes. The hemolytic effect of TAM is prevented by low concentrations of alpha-tocopherol (alpha-T) and alpha-tocopherol acetate (alpha-TAc) (inactivated functional hydroxyl) indicating that TAM-induced hemolysis is not related to oxidative membrane damage. This was further evidenced by absence of oxygen consumption and hemoglobin oxidation both determined in parallel with TAM-induced hemolysis. Furthermore, it was observed that TAM inhibits the peroxidation of human erythrocytes induced by AAPH, thus ruling out TAM-induced cell oxidative stress. Hemolysis caused by TAM was not preceded by the leakage of K(+) from the cells, also excluding a colloid-osmotic type mechanism of hemolysis, according to the effects on osmotic fragility curves. However, TAM induces release of peripheral proteins of membrane-cytoskeleton and cytosol proteins essentially bound to band 3. Either alpha-T or alpha-TAc increases membrane packing and prevents TAM partition into model membranes. These effects suggest that the protection from hemolysis by tocopherols is related to a decreased TAM incorporation in condensed membranes and the structural damage of the erythrocyte membrane is consequently avoided. Therefore, TAM-induced hemolysis results from a structural perturbation of red cell membrane, leading to changes in the framework of the erythrocyte membrane and its cytoskeleton caused by its high partition in the membrane. These defects explain the abnormal erythrocyte shape and decreased mechanical stability promoted by TAM, resulting in hemolytic anemia. Additionally, since membrane leakage is a final stage of cytotoxicity, the disruption of the structural characteristics of biomembranes by TAM may contribute to the multiple mechanisms of its anticancer action.", "entity": "Hemolysis", "aliases": "Hemolysis", "definition": "The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.\n    ", "id": "MESH:D006461"}
{"mention": "hemolytic", "mention_text": "Tamoxifen (TAM), the antiestrogenic drug most widely prescribed in the chemotherapy of breast cancer, induces changes in normal discoid shape of erythrocytes and hemolytic anemia. This work evaluates the effects of TAM on isolated human erythrocytes, attempting to identify the underlying mechanisms on TAM-induced hemolytic anemia and the involvement of biomembranes in its cytostatic action mechanisms. TAM induces hemolysis of erythrocytes as a function of concentration. The extension of hemolysis is variable with erythrocyte samples, but 12.5 microM TAM induces total hemolysis of all tested suspensions. Despite inducing extensive erythrocyte lysis, TAM does not shift the osmotic fragility curves of erythrocytes. The hemolytic effect of TAM is prevented by low concentrations of alpha-tocopherol (alpha-T) and alpha-tocopherol acetate (alpha-TAc) (inactivated functional hydroxyl) indicating that TAM-induced hemolysis is not related to oxidative membrane damage. This was further evidenced by absence of oxygen consumption and hemoglobin oxidation both determined in parallel with TAM-induced hemolysis. Furthermore, it was observed that TAM inhibits the peroxidation of human erythrocytes induced by AAPH, thus ruling out TAM-induced cell oxidative stress. Hemolysis caused by TAM was not preceded by the leakage of K(+) from the cells, also excluding a colloid-osmotic type mechanism of hemolysis, according to the effects on osmotic fragility curves. However, TAM induces release of peripheral proteins of membrane-cytoskeleton and cytosol proteins essentially bound to band 3. Either alpha-T or alpha-TAc increases membrane packing and prevents TAM partition into model membranes. These effects suggest that the protection from hemolysis by tocopherols is related to a decreased TAM incorporation in condensed membranes and the structural damage of the erythrocyte membrane is consequently avoided. Therefore, TAM-induced hemolysis results from a structural perturbation of red cell membrane, leading to changes in the framework of the erythrocyte membrane and its cytoskeleton caused by its high partition in the membrane. These defects explain the abnormal erythrocyte shape and decreased mechanical stability promoted by TAM, resulting in hemolytic anemia. Additionally, since membrane leakage is a final stage of cytotoxicity, the disruption of the structural characteristics of biomembranes by TAM may contribute to the multiple mechanisms of its anticancer action.", "entity": "Hemolysis", "aliases": "Hemolysis", "definition": "The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.\n    ", "id": "MESH:D006461"}
{"mention": "alpha-tocopherol", "mention_text": "Tamoxifen (TAM), the antiestrogenic drug most widely prescribed in the chemotherapy of breast cancer, induces changes in normal discoid shape of erythrocytes and hemolytic anemia. This work evaluates the effects of TAM on isolated human erythrocytes, attempting to identify the underlying mechanisms on TAM-induced hemolytic anemia and the involvement of biomembranes in its cytostatic action mechanisms. TAM induces hemolysis of erythrocytes as a function of concentration. The extension of hemolysis is variable with erythrocyte samples, but 12.5 microM TAM induces total hemolysis of all tested suspensions. Despite inducing extensive erythrocyte lysis, TAM does not shift the osmotic fragility curves of erythrocytes. The hemolytic effect of TAM is prevented by low concentrations of alpha-tocopherol (alpha-T) and alpha-tocopherol acetate (alpha-TAc) (inactivated functional hydroxyl) indicating that TAM-induced hemolysis is not related to oxidative membrane damage. This was further evidenced by absence of oxygen consumption and hemoglobin oxidation both determined in parallel with TAM-induced hemolysis. Furthermore, it was observed that TAM inhibits the peroxidation of human erythrocytes induced by AAPH, thus ruling out TAM-induced cell oxidative stress. Hemolysis caused by TAM was not preceded by the leakage of K(+) from the cells, also excluding a colloid-osmotic type mechanism of hemolysis, according to the effects on osmotic fragility curves. However, TAM induces release of peripheral proteins of membrane-cytoskeleton and cytosol proteins essentially bound to band 3. Either alpha-T or alpha-TAc increases membrane packing and prevents TAM partition into model membranes. These effects suggest that the protection from hemolysis by tocopherols is related to a decreased TAM incorporation in condensed membranes and the structural damage of the erythrocyte membrane is consequently avoided. Therefore, TAM-induced hemolysis results from a structural perturbation of red cell membrane, leading to changes in the framework of the erythrocyte membrane and its cytoskeleton caused by its high partition in the membrane. These defects explain the abnormal erythrocyte shape and decreased mechanical stability promoted by TAM, resulting in hemolytic anemia. Additionally, since membrane leakage is a final stage of cytotoxicity, the disruption of the structural characteristics of biomembranes by TAM may contribute to the multiple mechanisms of its anticancer action.", "entity": "alpha-Tocopherol", "aliases": "3,4-Dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-ol Acetate Tocopherol Calcium Succinate alpha-Tocopheryl R,R,R-alpha-Tocopherol d-alpha Tocopheryl alpha Hemisuccinate alpha-Tocopherol d d-alpha-Tocopheryl", "definition": "A natural tocopherol and one of the most potent antioxidant tocopherols. It exhibits antioxidant activity by virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus. It has four methyl groups on the 6-chromanol nucleus. The natural d form of alpha-tocopherol is more active than its synthetic dl-alpha-tocopherol racemic mixture.\n    ", "id": "MESH:D024502"}
{"mention": "alpha-T", "mention_text": "Tamoxifen (TAM), the antiestrogenic drug most widely prescribed in the chemotherapy of breast cancer, induces changes in normal discoid shape of erythrocytes and hemolytic anemia. This work evaluates the effects of TAM on isolated human erythrocytes, attempting to identify the underlying mechanisms on TAM-induced hemolytic anemia and the involvement of biomembranes in its cytostatic action mechanisms. TAM induces hemolysis of erythrocytes as a function of concentration. The extension of hemolysis is variable with erythrocyte samples, but 12.5 microM TAM induces total hemolysis of all tested suspensions. Despite inducing extensive erythrocyte lysis, TAM does not shift the osmotic fragility curves of erythrocytes. The hemolytic effect of TAM is prevented by low concentrations of alpha-tocopherol (alpha-T) and alpha-tocopherol acetate (alpha-TAc) (inactivated functional hydroxyl) indicating that TAM-induced hemolysis is not related to oxidative membrane damage. This was further evidenced by absence of oxygen consumption and hemoglobin oxidation both determined in parallel with TAM-induced hemolysis. Furthermore, it was observed that TAM inhibits the peroxidation of human erythrocytes induced by AAPH, thus ruling out TAM-induced cell oxidative stress. Hemolysis caused by TAM was not preceded by the leakage of K(+) from the cells, also excluding a colloid-osmotic type mechanism of hemolysis, according to the effects on osmotic fragility curves. However, TAM induces release of peripheral proteins of membrane-cytoskeleton and cytosol proteins essentially bound to band 3. Either alpha-T or alpha-TAc increases membrane packing and prevents TAM partition into model membranes. These effects suggest that the protection from hemolysis by tocopherols is related to a decreased TAM incorporation in condensed membranes and the structural damage of the erythrocyte membrane is consequently avoided. Therefore, TAM-induced hemolysis results from a structural perturbation of red cell membrane, leading to changes in the framework of the erythrocyte membrane and its cytoskeleton caused by its high partition in the membrane. These defects explain the abnormal erythrocyte shape and decreased mechanical stability promoted by TAM, resulting in hemolytic anemia. Additionally, since membrane leakage is a final stage of cytotoxicity, the disruption of the structural characteristics of biomembranes by TAM may contribute to the multiple mechanisms of its anticancer action.", "entity": "alpha-Tocopherol", "aliases": "3,4-Dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-ol Acetate Tocopherol Calcium Succinate alpha-Tocopheryl R,R,R-alpha-Tocopherol d-alpha Tocopheryl alpha Hemisuccinate alpha-Tocopherol d d-alpha-Tocopheryl", "definition": "A natural tocopherol and one of the most potent antioxidant tocopherols. It exhibits antioxidant activity by virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus. It has four methyl groups on the 6-chromanol nucleus. The natural d form of alpha-tocopherol is more active than its synthetic dl-alpha-tocopherol racemic mixture.\n    ", "id": "MESH:D024502"}
{"mention": "alpha-tocopherol acetate", "mention_text": "Tamoxifen (TAM), the antiestrogenic drug most widely prescribed in the chemotherapy of breast cancer, induces changes in normal discoid shape of erythrocytes and hemolytic anemia. This work evaluates the effects of TAM on isolated human erythrocytes, attempting to identify the underlying mechanisms on TAM-induced hemolytic anemia and the involvement of biomembranes in its cytostatic action mechanisms. TAM induces hemolysis of erythrocytes as a function of concentration. The extension of hemolysis is variable with erythrocyte samples, but 12.5 microM TAM induces total hemolysis of all tested suspensions. Despite inducing extensive erythrocyte lysis, TAM does not shift the osmotic fragility curves of erythrocytes. The hemolytic effect of TAM is prevented by low concentrations of alpha-tocopherol (alpha-T) and alpha-tocopherol acetate (alpha-TAc) (inactivated functional hydroxyl) indicating that TAM-induced hemolysis is not related to oxidative membrane damage. This was further evidenced by absence of oxygen consumption and hemoglobin oxidation both determined in parallel with TAM-induced hemolysis. Furthermore, it was observed that TAM inhibits the peroxidation of human erythrocytes induced by AAPH, thus ruling out TAM-induced cell oxidative stress. Hemolysis caused by TAM was not preceded by the leakage of K(+) from the cells, also excluding a colloid-osmotic type mechanism of hemolysis, according to the effects on osmotic fragility curves. However, TAM induces release of peripheral proteins of membrane-cytoskeleton and cytosol proteins essentially bound to band 3. Either alpha-T or alpha-TAc increases membrane packing and prevents TAM partition into model membranes. These effects suggest that the protection from hemolysis by tocopherols is related to a decreased TAM incorporation in condensed membranes and the structural damage of the erythrocyte membrane is consequently avoided. Therefore, TAM-induced hemolysis results from a structural perturbation of red cell membrane, leading to changes in the framework of the erythrocyte membrane and its cytoskeleton caused by its high partition in the membrane. These defects explain the abnormal erythrocyte shape and decreased mechanical stability promoted by TAM, resulting in hemolytic anemia. Additionally, since membrane leakage is a final stage of cytotoxicity, the disruption of the structural characteristics of biomembranes by TAM may contribute to the multiple mechanisms of its anticancer action.", "entity": "alpha-Tocopherol", "aliases": "3,4-Dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-ol Acetate Tocopherol Calcium Succinate alpha-Tocopheryl R,R,R-alpha-Tocopherol d-alpha Tocopheryl alpha Hemisuccinate alpha-Tocopherol d d-alpha-Tocopheryl", "definition": "A natural tocopherol and one of the most potent antioxidant tocopherols. It exhibits antioxidant activity by virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus. It has four methyl groups on the 6-chromanol nucleus. The natural d form of alpha-tocopherol is more active than its synthetic dl-alpha-tocopherol racemic mixture.\n    ", "id": "MESH:D024502"}
{"mention": "alpha-TAc", "mention_text": "Tamoxifen (TAM), the antiestrogenic drug most widely prescribed in the chemotherapy of breast cancer, induces changes in normal discoid shape of erythrocytes and hemolytic anemia. This work evaluates the effects of TAM on isolated human erythrocytes, attempting to identify the underlying mechanisms on TAM-induced hemolytic anemia and the involvement of biomembranes in its cytostatic action mechanisms. TAM induces hemolysis of erythrocytes as a function of concentration. The extension of hemolysis is variable with erythrocyte samples, but 12.5 microM TAM induces total hemolysis of all tested suspensions. Despite inducing extensive erythrocyte lysis, TAM does not shift the osmotic fragility curves of erythrocytes. The hemolytic effect of TAM is prevented by low concentrations of alpha-tocopherol (alpha-T) and alpha-tocopherol acetate (alpha-TAc) (inactivated functional hydroxyl) indicating that TAM-induced hemolysis is not related to oxidative membrane damage. This was further evidenced by absence of oxygen consumption and hemoglobin oxidation both determined in parallel with TAM-induced hemolysis. Furthermore, it was observed that TAM inhibits the peroxidation of human erythrocytes induced by AAPH, thus ruling out TAM-induced cell oxidative stress. Hemolysis caused by TAM was not preceded by the leakage of K(+) from the cells, also excluding a colloid-osmotic type mechanism of hemolysis, according to the effects on osmotic fragility curves. However, TAM induces release of peripheral proteins of membrane-cytoskeleton and cytosol proteins essentially bound to band 3. Either alpha-T or alpha-TAc increases membrane packing and prevents TAM partition into model membranes. These effects suggest that the protection from hemolysis by tocopherols is related to a decreased TAM incorporation in condensed membranes and the structural damage of the erythrocyte membrane is consequently avoided. Therefore, TAM-induced hemolysis results from a structural perturbation of red cell membrane, leading to changes in the framework of the erythrocyte membrane and its cytoskeleton caused by its high partition in the membrane. These defects explain the abnormal erythrocyte shape and decreased mechanical stability promoted by TAM, resulting in hemolytic anemia. Additionally, since membrane leakage is a final stage of cytotoxicity, the disruption of the structural characteristics of biomembranes by TAM may contribute to the multiple mechanisms of its anticancer action.", "entity": "alpha-Tocopherol", "aliases": "3,4-Dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-ol Acetate Tocopherol Calcium Succinate alpha-Tocopheryl R,R,R-alpha-Tocopherol d-alpha Tocopheryl alpha Hemisuccinate alpha-Tocopherol d d-alpha-Tocopheryl", "definition": "A natural tocopherol and one of the most potent antioxidant tocopherols. It exhibits antioxidant activity by virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus. It has four methyl groups on the 6-chromanol nucleus. The natural d form of alpha-tocopherol is more active than its synthetic dl-alpha-tocopherol racemic mixture.\n    ", "id": "MESH:D024502"}
{"mention": "hydroxyl", "mention_text": "Tamoxifen (TAM), the antiestrogenic drug most widely prescribed in the chemotherapy of breast cancer, induces changes in normal discoid shape of erythrocytes and hemolytic anemia. This work evaluates the effects of TAM on isolated human erythrocytes, attempting to identify the underlying mechanisms on TAM-induced hemolytic anemia and the involvement of biomembranes in its cytostatic action mechanisms. TAM induces hemolysis of erythrocytes as a function of concentration. The extension of hemolysis is variable with erythrocyte samples, but 12.5 microM TAM induces total hemolysis of all tested suspensions. Despite inducing extensive erythrocyte lysis, TAM does not shift the osmotic fragility curves of erythrocytes. The hemolytic effect of TAM is prevented by low concentrations of alpha-tocopherol (alpha-T) and alpha-tocopherol acetate (alpha-TAc) (inactivated functional hydroxyl) indicating that TAM-induced hemolysis is not related to oxidative membrane damage. This was further evidenced by absence of oxygen consumption and hemoglobin oxidation both determined in parallel with TAM-induced hemolysis. Furthermore, it was observed that TAM inhibits the peroxidation of human erythrocytes induced by AAPH, thus ruling out TAM-induced cell oxidative stress. Hemolysis caused by TAM was not preceded by the leakage of K(+) from the cells, also excluding a colloid-osmotic type mechanism of hemolysis, according to the effects on osmotic fragility curves. However, TAM induces release of peripheral proteins of membrane-cytoskeleton and cytosol proteins essentially bound to band 3. Either alpha-T or alpha-TAc increases membrane packing and prevents TAM partition into model membranes. These effects suggest that the protection from hemolysis by tocopherols is related to a decreased TAM incorporation in condensed membranes and the structural damage of the erythrocyte membrane is consequently avoided. Therefore, TAM-induced hemolysis results from a structural perturbation of red cell membrane, leading to changes in the framework of the erythrocyte membrane and its cytoskeleton caused by its high partition in the membrane. These defects explain the abnormal erythrocyte shape and decreased mechanical stability promoted by TAM, resulting in hemolytic anemia. Additionally, since membrane leakage is a final stage of cytotoxicity, the disruption of the structural characteristics of biomembranes by TAM may contribute to the multiple mechanisms of its anticancer action.", "entity": "Hydroxyl Radical", "aliases": "Hydroxyl Radical", "definition": "The univalent radical OH. Hydroxyl radical is a potent oxidizing agent.\n    ", "id": "MESH:D017665"}
{"mention": "oxygen", "mention_text": "Tamoxifen (TAM), the antiestrogenic drug most widely prescribed in the chemotherapy of breast cancer, induces changes in normal discoid shape of erythrocytes and hemolytic anemia. This work evaluates the effects of TAM on isolated human erythrocytes, attempting to identify the underlying mechanisms on TAM-induced hemolytic anemia and the involvement of biomembranes in its cytostatic action mechanisms. TAM induces hemolysis of erythrocytes as a function of concentration. The extension of hemolysis is variable with erythrocyte samples, but 12.5 microM TAM induces total hemolysis of all tested suspensions. Despite inducing extensive erythrocyte lysis, TAM does not shift the osmotic fragility curves of erythrocytes. The hemolytic effect of TAM is prevented by low concentrations of alpha-tocopherol (alpha-T) and alpha-tocopherol acetate (alpha-TAc) (inactivated functional hydroxyl) indicating that TAM-induced hemolysis is not related to oxidative membrane damage. This was further evidenced by absence of oxygen consumption and hemoglobin oxidation both determined in parallel with TAM-induced hemolysis. Furthermore, it was observed that TAM inhibits the peroxidation of human erythrocytes induced by AAPH, thus ruling out TAM-induced cell oxidative stress. Hemolysis caused by TAM was not preceded by the leakage of K(+) from the cells, also excluding a colloid-osmotic type mechanism of hemolysis, according to the effects on osmotic fragility curves. However, TAM induces release of peripheral proteins of membrane-cytoskeleton and cytosol proteins essentially bound to band 3. Either alpha-T or alpha-TAc increases membrane packing and prevents TAM partition into model membranes. These effects suggest that the protection from hemolysis by tocopherols is related to a decreased TAM incorporation in condensed membranes and the structural damage of the erythrocyte membrane is consequently avoided. Therefore, TAM-induced hemolysis results from a structural perturbation of red cell membrane, leading to changes in the framework of the erythrocyte membrane and its cytoskeleton caused by its high partition in the membrane. These defects explain the abnormal erythrocyte shape and decreased mechanical stability promoted by TAM, resulting in hemolytic anemia. Additionally, since membrane leakage is a final stage of cytotoxicity, the disruption of the structural characteristics of biomembranes by TAM may contribute to the multiple mechanisms of its anticancer action.", "entity": "Oxygen", "aliases": "Dioxygen Oxygen", "definition": "An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.\n    ", "id": "MESH:D010100"}
{"mention": "AAPH", "mention_text": "Tamoxifen (TAM), the antiestrogenic drug most widely prescribed in the chemotherapy of breast cancer, induces changes in normal discoid shape of erythrocytes and hemolytic anemia. This work evaluates the effects of TAM on isolated human erythrocytes, attempting to identify the underlying mechanisms on TAM-induced hemolytic anemia and the involvement of biomembranes in its cytostatic action mechanisms. TAM induces hemolysis of erythrocytes as a function of concentration. The extension of hemolysis is variable with erythrocyte samples, but 12.5 microM TAM induces total hemolysis of all tested suspensions. Despite inducing extensive erythrocyte lysis, TAM does not shift the osmotic fragility curves of erythrocytes. The hemolytic effect of TAM is prevented by low concentrations of alpha-tocopherol (alpha-T) and alpha-tocopherol acetate (alpha-TAc) (inactivated functional hydroxyl) indicating that TAM-induced hemolysis is not related to oxidative membrane damage. This was further evidenced by absence of oxygen consumption and hemoglobin oxidation both determined in parallel with TAM-induced hemolysis. Furthermore, it was observed that TAM inhibits the peroxidation of human erythrocytes induced by AAPH, thus ruling out TAM-induced cell oxidative stress. Hemolysis caused by TAM was not preceded by the leakage of K(+) from the cells, also excluding a colloid-osmotic type mechanism of hemolysis, according to the effects on osmotic fragility curves. However, TAM induces release of peripheral proteins of membrane-cytoskeleton and cytosol proteins essentially bound to band 3. Either alpha-T or alpha-TAc increases membrane packing and prevents TAM partition into model membranes. These effects suggest that the protection from hemolysis by tocopherols is related to a decreased TAM incorporation in condensed membranes and the structural damage of the erythrocyte membrane is consequently avoided. Therefore, TAM-induced hemolysis results from a structural perturbation of red cell membrane, leading to changes in the framework of the erythrocyte membrane and its cytoskeleton caused by its high partition in the membrane. These defects explain the abnormal erythrocyte shape and decreased mechanical stability promoted by TAM, resulting in hemolytic anemia. Additionally, since membrane leakage is a final stage of cytotoxicity, the disruption of the structural characteristics of biomembranes by TAM may contribute to the multiple mechanisms of its anticancer action.", "entity": "2,2'-azobis(2-amidinopropane)", "aliases": "2,2'-azo-bis(2-amidinopropane) 2,2'-azobis(2-amidinopropane) acetate dihydrochloride monohydrochloride 2,2'-azobis(2-amidinopropane)dihydrochloride 2,2'-azobis(2-methylpropionamidine) AAPH ABAP ABAPH AMPH cpd", "definition": "", "id": "MESH:C046728"}
{"mention": "Hemolysis", "mention_text": "Tamoxifen (TAM), the antiestrogenic drug most widely prescribed in the chemotherapy of breast cancer, induces changes in normal discoid shape of erythrocytes and hemolytic anemia. This work evaluates the effects of TAM on isolated human erythrocytes, attempting to identify the underlying mechanisms on TAM-induced hemolytic anemia and the involvement of biomembranes in its cytostatic action mechanisms. TAM induces hemolysis of erythrocytes as a function of concentration. The extension of hemolysis is variable with erythrocyte samples, but 12.5 microM TAM induces total hemolysis of all tested suspensions. Despite inducing extensive erythrocyte lysis, TAM does not shift the osmotic fragility curves of erythrocytes. The hemolytic effect of TAM is prevented by low concentrations of alpha-tocopherol (alpha-T) and alpha-tocopherol acetate (alpha-TAc) (inactivated functional hydroxyl) indicating that TAM-induced hemolysis is not related to oxidative membrane damage. This was further evidenced by absence of oxygen consumption and hemoglobin oxidation both determined in parallel with TAM-induced hemolysis. Furthermore, it was observed that TAM inhibits the peroxidation of human erythrocytes induced by AAPH, thus ruling out TAM-induced cell oxidative stress. Hemolysis caused by TAM was not preceded by the leakage of K(+) from the cells, also excluding a colloid-osmotic type mechanism of hemolysis, according to the effects on osmotic fragility curves. However, TAM induces release of peripheral proteins of membrane-cytoskeleton and cytosol proteins essentially bound to band 3. Either alpha-T or alpha-TAc increases membrane packing and prevents TAM partition into model membranes. These effects suggest that the protection from hemolysis by tocopherols is related to a decreased TAM incorporation in condensed membranes and the structural damage of the erythrocyte membrane is consequently avoided. Therefore, TAM-induced hemolysis results from a structural perturbation of red cell membrane, leading to changes in the framework of the erythrocyte membrane and its cytoskeleton caused by its high partition in the membrane. These defects explain the abnormal erythrocyte shape and decreased mechanical stability promoted by TAM, resulting in hemolytic anemia. Additionally, since membrane leakage is a final stage of cytotoxicity, the disruption of the structural characteristics of biomembranes by TAM may contribute to the multiple mechanisms of its anticancer action.", "entity": "Hemolysis", "aliases": "Hemolysis", "definition": "The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.\n    ", "id": "MESH:D006461"}
{"mention": "K", "mention_text": "Tamoxifen (TAM), the antiestrogenic drug most widely prescribed in the chemotherapy of breast cancer, induces changes in normal discoid shape of erythrocytes and hemolytic anemia. This work evaluates the effects of TAM on isolated human erythrocytes, attempting to identify the underlying mechanisms on TAM-induced hemolytic anemia and the involvement of biomembranes in its cytostatic action mechanisms. TAM induces hemolysis of erythrocytes as a function of concentration. The extension of hemolysis is variable with erythrocyte samples, but 12.5 microM TAM induces total hemolysis of all tested suspensions. Despite inducing extensive erythrocyte lysis, TAM does not shift the osmotic fragility curves of erythrocytes. The hemolytic effect of TAM is prevented by low concentrations of alpha-tocopherol (alpha-T) and alpha-tocopherol acetate (alpha-TAc) (inactivated functional hydroxyl) indicating that TAM-induced hemolysis is not related to oxidative membrane damage. This was further evidenced by absence of oxygen consumption and hemoglobin oxidation both determined in parallel with TAM-induced hemolysis. Furthermore, it was observed that TAM inhibits the peroxidation of human erythrocytes induced by AAPH, thus ruling out TAM-induced cell oxidative stress. Hemolysis caused by TAM was not preceded by the leakage of K(+) from the cells, also excluding a colloid-osmotic type mechanism of hemolysis, according to the effects on osmotic fragility curves. However, TAM induces release of peripheral proteins of membrane-cytoskeleton and cytosol proteins essentially bound to band 3. Either alpha-T or alpha-TAc increases membrane packing and prevents TAM partition into model membranes. These effects suggest that the protection from hemolysis by tocopherols is related to a decreased TAM incorporation in condensed membranes and the structural damage of the erythrocyte membrane is consequently avoided. Therefore, TAM-induced hemolysis results from a structural perturbation of red cell membrane, leading to changes in the framework of the erythrocyte membrane and its cytoskeleton caused by its high partition in the membrane. These defects explain the abnormal erythrocyte shape and decreased mechanical stability promoted by TAM, resulting in hemolytic anemia. Additionally, since membrane leakage is a final stage of cytotoxicity, the disruption of the structural characteristics of biomembranes by TAM may contribute to the multiple mechanisms of its anticancer action.", "entity": "Potassium", "aliases": "Potassium", "definition": "An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.\n    ", "id": "MESH:D011188"}
{"mention": "tocopherols", "mention_text": "Tamoxifen (TAM), the antiestrogenic drug most widely prescribed in the chemotherapy of breast cancer, induces changes in normal discoid shape of erythrocytes and hemolytic anemia. This work evaluates the effects of TAM on isolated human erythrocytes, attempting to identify the underlying mechanisms on TAM-induced hemolytic anemia and the involvement of biomembranes in its cytostatic action mechanisms. TAM induces hemolysis of erythrocytes as a function of concentration. The extension of hemolysis is variable with erythrocyte samples, but 12.5 microM TAM induces total hemolysis of all tested suspensions. Despite inducing extensive erythrocyte lysis, TAM does not shift the osmotic fragility curves of erythrocytes. The hemolytic effect of TAM is prevented by low concentrations of alpha-tocopherol (alpha-T) and alpha-tocopherol acetate (alpha-TAc) (inactivated functional hydroxyl) indicating that TAM-induced hemolysis is not related to oxidative membrane damage. This was further evidenced by absence of oxygen consumption and hemoglobin oxidation both determined in parallel with TAM-induced hemolysis. Furthermore, it was observed that TAM inhibits the peroxidation of human erythrocytes induced by AAPH, thus ruling out TAM-induced cell oxidative stress. Hemolysis caused by TAM was not preceded by the leakage of K(+) from the cells, also excluding a colloid-osmotic type mechanism of hemolysis, according to the effects on osmotic fragility curves. However, TAM induces release of peripheral proteins of membrane-cytoskeleton and cytosol proteins essentially bound to band 3. Either alpha-T or alpha-TAc increases membrane packing and prevents TAM partition into model membranes. These effects suggest that the protection from hemolysis by tocopherols is related to a decreased TAM incorporation in condensed membranes and the structural damage of the erythrocyte membrane is consequently avoided. Therefore, TAM-induced hemolysis results from a structural perturbation of red cell membrane, leading to changes in the framework of the erythrocyte membrane and its cytoskeleton caused by its high partition in the membrane. These defects explain the abnormal erythrocyte shape and decreased mechanical stability promoted by TAM, resulting in hemolytic anemia. Additionally, since membrane leakage is a final stage of cytotoxicity, the disruption of the structural characteristics of biomembranes by TAM may contribute to the multiple mechanisms of its anticancer action.", "entity": "Tocopherols", "aliases": "Abortosan Adisseo Brand of Tocopherol Alcala Acetate Aliud Antioxidans E-Hevert Aquasol E Arkopharma AstraZeneca Atarost Ausrichter Auxina Balkanpharma Bayer Bio Biocur Biopto-E Biosan Bioweyxin Blackmores Bottger Cambridge Laboratories Actetate Dal Vita Vitamin Succinate Dal-E Dal-Vita Davitamon Dermorelle Detulin Dragees Vitamin-E Mulsin Vicotrat ferol E-Mulsin E-Vicotrat E-Vitamin-ratiopharm E-ferol EUNOVA EVI-MIRALE Ecoro Elex Verla Embial Ephynal Eplonat Equivit Eu Rho Eusovit Evion GNR Pha", "definition": "A collective name for a group of closely related lipids that contain substitutions on the 2H-1-benzopyran-6-ol nucleus and a long hydrocarbon chain of isoprenoid units. They are antioxidants by virtue of the phenolic hydrogen. Tocopherols react with the most reactive form of oxygen and protect unsaturated fatty acids from oxidation.\n    ", "id": "MESH:D024505"}
{"mention": "sodium", "mention_text": "Changes of sodium and ATP affinities of the cardiac (Na,K)-ATPase during and after nitric oxide deficient hypertension.", "entity": "Sodium", "aliases": "Ion Level Sodium", "definition": "A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.\n    ", "id": "MESH:D012964"}
{"mention": "ATP", "mention_text": "Changes of sodium and ATP affinities of the cardiac (Na,K)-ATPase during and after nitric oxide deficient hypertension.", "entity": "Adenosine Triphosphate", "aliases": "ATP MgCl2 ATP-MgCl2 Adenosine Triphosphate Calcium Salt Chromium Ammonium Magnesium Chloride Manganese Adenylpyrophosphate Atriphos CaATP Cr(H2O)4 CrATP MgATP MnATP Striadyne", "definition": "An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.\n    ", "id": "MESH:D000255"}
{"mention": "Na", "mention_text": "Changes of sodium and ATP affinities of the cardiac (Na,K)-ATPase during and after nitric oxide deficient hypertension.", "entity": "Sodium", "aliases": "Ion Level Sodium", "definition": "A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.\n    ", "id": "MESH:D012964"}
{"mention": "K", "mention_text": "Changes of sodium and ATP affinities of the cardiac (Na,K)-ATPase during and after nitric oxide deficient hypertension.", "entity": "Potassium", "aliases": "Potassium", "definition": "An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.\n    ", "id": "MESH:D011188"}
{"mention": "nitric oxide", "mention_text": "Changes of sodium and ATP affinities of the cardiac (Na,K)-ATPase during and after nitric oxide deficient hypertension.", "entity": "Nitric Oxide", "aliases": "Endogenous Nitrate Vasodilator Endothelium-Derived Nitric Oxide Mononitrogen Monoxide Nitrogen Endothelium Derived", "definition": "A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.\n    ", "id": "MESH:D009569"}
{"mention": "hypertension", "mention_text": "Changes of sodium and ATP affinities of the cardiac (Na,K)-ATPase during and after nitric oxide deficient hypertension.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "NO", "mention_text": "In the cardiovascular system, NO is involved in the regulation of a variety of functions. Inhibition of NO synthesis induces sustained hypertension. In several models of hypertension, elevation of intracellular sodium level was documented in cardiac tissue. To assess the molecular basis of disturbances in transmembraneous transport of Na+, we studied the response of cardiac (Na,K)-ATPase to NO-deficient hypertension induced in rats by NO-synthase inhibition with 40 mg/kg/day N(G)-nitro-L-arginine methyl ester (L-NAME) for 4 four weeks. After 4-week administration of L-NAME, the systolic blood pressure (SBP) increased by 36%. Two weeks after terminating the treatment, the SBP recovered to control value. When activating the (Na,K)-ATPase with its substrate ATP, no changes in Km and Vmax values were observed in NO-deficient rats. During activation with Na+, the Vmax remained unchanged, however the K(Na) increased by 50%, indicating a profound decrease in the affinity of the Na+-binding site in NO-deficient rats. After recovery from hypertension, the activity of (Na,K)-ATPase increased, due to higher affinity of the ATP-binding site, as revealed from the lowered Km value for ATP. The K(Na) value for Na+ returned to control value. Inhibition of NO-synthase induced a reversible hypertension accompanied by depressed Na+-extrusion from cardiac cells as a consequence of deteriorated Na+-binding properties of the (Na,K)-ATPase. After recovery of blood pressure to control values, the extrusion of Na+ from cardiac cells was normalized, as revealed by restoration of the (Na,K)-ATPase activity.", "entity": "Nitric Oxide", "aliases": "Endogenous Nitrate Vasodilator Endothelium-Derived Nitric Oxide Mononitrogen Monoxide Nitrogen Endothelium Derived", "definition": "A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.\n    ", "id": "MESH:D009569"}
{"mention": "hypertension", "mention_text": "In the cardiovascular system, NO is involved in the regulation of a variety of functions. Inhibition of NO synthesis induces sustained hypertension. In several models of hypertension, elevation of intracellular sodium level was documented in cardiac tissue. To assess the molecular basis of disturbances in transmembraneous transport of Na+, we studied the response of cardiac (Na,K)-ATPase to NO-deficient hypertension induced in rats by NO-synthase inhibition with 40 mg/kg/day N(G)-nitro-L-arginine methyl ester (L-NAME) for 4 four weeks. After 4-week administration of L-NAME, the systolic blood pressure (SBP) increased by 36%. Two weeks after terminating the treatment, the SBP recovered to control value. When activating the (Na,K)-ATPase with its substrate ATP, no changes in Km and Vmax values were observed in NO-deficient rats. During activation with Na+, the Vmax remained unchanged, however the K(Na) increased by 50%, indicating a profound decrease in the affinity of the Na+-binding site in NO-deficient rats. After recovery from hypertension, the activity of (Na,K)-ATPase increased, due to higher affinity of the ATP-binding site, as revealed from the lowered Km value for ATP. The K(Na) value for Na+ returned to control value. Inhibition of NO-synthase induced a reversible hypertension accompanied by depressed Na+-extrusion from cardiac cells as a consequence of deteriorated Na+-binding properties of the (Na,K)-ATPase. After recovery of blood pressure to control values, the extrusion of Na+ from cardiac cells was normalized, as revealed by restoration of the (Na,K)-ATPase activity.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "sodium", "mention_text": "In the cardiovascular system, NO is involved in the regulation of a variety of functions. Inhibition of NO synthesis induces sustained hypertension. In several models of hypertension, elevation of intracellular sodium level was documented in cardiac tissue. To assess the molecular basis of disturbances in transmembraneous transport of Na+, we studied the response of cardiac (Na,K)-ATPase to NO-deficient hypertension induced in rats by NO-synthase inhibition with 40 mg/kg/day N(G)-nitro-L-arginine methyl ester (L-NAME) for 4 four weeks. After 4-week administration of L-NAME, the systolic blood pressure (SBP) increased by 36%. Two weeks after terminating the treatment, the SBP recovered to control value. When activating the (Na,K)-ATPase with its substrate ATP, no changes in Km and Vmax values were observed in NO-deficient rats. During activation with Na+, the Vmax remained unchanged, however the K(Na) increased by 50%, indicating a profound decrease in the affinity of the Na+-binding site in NO-deficient rats. After recovery from hypertension, the activity of (Na,K)-ATPase increased, due to higher affinity of the ATP-binding site, as revealed from the lowered Km value for ATP. The K(Na) value for Na+ returned to control value. Inhibition of NO-synthase induced a reversible hypertension accompanied by depressed Na+-extrusion from cardiac cells as a consequence of deteriorated Na+-binding properties of the (Na,K)-ATPase. After recovery of blood pressure to control values, the extrusion of Na+ from cardiac cells was normalized, as revealed by restoration of the (Na,K)-ATPase activity.", "entity": "Sodium", "aliases": "Ion Level Sodium", "definition": "A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.\n    ", "id": "MESH:D012964"}
{"mention": "Na", "mention_text": "In the cardiovascular system, NO is involved in the regulation of a variety of functions. Inhibition of NO synthesis induces sustained hypertension. In several models of hypertension, elevation of intracellular sodium level was documented in cardiac tissue. To assess the molecular basis of disturbances in transmembraneous transport of Na+, we studied the response of cardiac (Na,K)-ATPase to NO-deficient hypertension induced in rats by NO-synthase inhibition with 40 mg/kg/day N(G)-nitro-L-arginine methyl ester (L-NAME) for 4 four weeks. After 4-week administration of L-NAME, the systolic blood pressure (SBP) increased by 36%. Two weeks after terminating the treatment, the SBP recovered to control value. When activating the (Na,K)-ATPase with its substrate ATP, no changes in Km and Vmax values were observed in NO-deficient rats. During activation with Na+, the Vmax remained unchanged, however the K(Na) increased by 50%, indicating a profound decrease in the affinity of the Na+-binding site in NO-deficient rats. After recovery from hypertension, the activity of (Na,K)-ATPase increased, due to higher affinity of the ATP-binding site, as revealed from the lowered Km value for ATP. The K(Na) value for Na+ returned to control value. Inhibition of NO-synthase induced a reversible hypertension accompanied by depressed Na+-extrusion from cardiac cells as a consequence of deteriorated Na+-binding properties of the (Na,K)-ATPase. After recovery of blood pressure to control values, the extrusion of Na+ from cardiac cells was normalized, as revealed by restoration of the (Na,K)-ATPase activity.", "entity": "Sodium", "aliases": "Ion Level Sodium", "definition": "A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.\n    ", "id": "MESH:D012964"}
{"mention": "K", "mention_text": "In the cardiovascular system, NO is involved in the regulation of a variety of functions. Inhibition of NO synthesis induces sustained hypertension. In several models of hypertension, elevation of intracellular sodium level was documented in cardiac tissue. To assess the molecular basis of disturbances in transmembraneous transport of Na+, we studied the response of cardiac (Na,K)-ATPase to NO-deficient hypertension induced in rats by NO-synthase inhibition with 40 mg/kg/day N(G)-nitro-L-arginine methyl ester (L-NAME) for 4 four weeks. After 4-week administration of L-NAME, the systolic blood pressure (SBP) increased by 36%. Two weeks after terminating the treatment, the SBP recovered to control value. When activating the (Na,K)-ATPase with its substrate ATP, no changes in Km and Vmax values were observed in NO-deficient rats. During activation with Na+, the Vmax remained unchanged, however the K(Na) increased by 50%, indicating a profound decrease in the affinity of the Na+-binding site in NO-deficient rats. After recovery from hypertension, the activity of (Na,K)-ATPase increased, due to higher affinity of the ATP-binding site, as revealed from the lowered Km value for ATP. The K(Na) value for Na+ returned to control value. Inhibition of NO-synthase induced a reversible hypertension accompanied by depressed Na+-extrusion from cardiac cells as a consequence of deteriorated Na+-binding properties of the (Na,K)-ATPase. After recovery of blood pressure to control values, the extrusion of Na+ from cardiac cells was normalized, as revealed by restoration of the (Na,K)-ATPase activity.", "entity": "Potassium", "aliases": "Potassium", "definition": "An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.\n    ", "id": "MESH:D011188"}
{"mention": "N(G)-nitro-L-arginine methyl ester", "mention_text": "In the cardiovascular system, NO is involved in the regulation of a variety of functions. Inhibition of NO synthesis induces sustained hypertension. In several models of hypertension, elevation of intracellular sodium level was documented in cardiac tissue. To assess the molecular basis of disturbances in transmembraneous transport of Na+, we studied the response of cardiac (Na,K)-ATPase to NO-deficient hypertension induced in rats by NO-synthase inhibition with 40 mg/kg/day N(G)-nitro-L-arginine methyl ester (L-NAME) for 4 four weeks. After 4-week administration of L-NAME, the systolic blood pressure (SBP) increased by 36%. Two weeks after terminating the treatment, the SBP recovered to control value. When activating the (Na,K)-ATPase with its substrate ATP, no changes in Km and Vmax values were observed in NO-deficient rats. During activation with Na+, the Vmax remained unchanged, however the K(Na) increased by 50%, indicating a profound decrease in the affinity of the Na+-binding site in NO-deficient rats. After recovery from hypertension, the activity of (Na,K)-ATPase increased, due to higher affinity of the ATP-binding site, as revealed from the lowered Km value for ATP. The K(Na) value for Na+ returned to control value. Inhibition of NO-synthase induced a reversible hypertension accompanied by depressed Na+-extrusion from cardiac cells as a consequence of deteriorated Na+-binding properties of the (Na,K)-ATPase. After recovery of blood pressure to control values, the extrusion of Na+ from cardiac cells was normalized, as revealed by restoration of the (Na,K)-ATPase activity.", "entity": "NG-Nitroarginine Methyl Ester", "aliases": "L-NAME Methyl Ester NG-Nitro-L-Arginine NG-Nitroarginine N omega Nitro L arginine omega-Nitro-L-arginine N(G)-Nitro-L-arginine N(G)-Nitroarginine N(omega)-Nitro-L-arginine NG Arginine Nitroarginine D Orn Isomer D-Orn-Isomer L-Orn-Isomer Monohydrochloride", "definition": "A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.\n    ", "id": "MESH:D019331"}
{"mention": "L-NAME", "mention_text": "In the cardiovascular system, NO is involved in the regulation of a variety of functions. Inhibition of NO synthesis induces sustained hypertension. In several models of hypertension, elevation of intracellular sodium level was documented in cardiac tissue. To assess the molecular basis of disturbances in transmembraneous transport of Na+, we studied the response of cardiac (Na,K)-ATPase to NO-deficient hypertension induced in rats by NO-synthase inhibition with 40 mg/kg/day N(G)-nitro-L-arginine methyl ester (L-NAME) for 4 four weeks. After 4-week administration of L-NAME, the systolic blood pressure (SBP) increased by 36%. Two weeks after terminating the treatment, the SBP recovered to control value. When activating the (Na,K)-ATPase with its substrate ATP, no changes in Km and Vmax values were observed in NO-deficient rats. During activation with Na+, the Vmax remained unchanged, however the K(Na) increased by 50%, indicating a profound decrease in the affinity of the Na+-binding site in NO-deficient rats. After recovery from hypertension, the activity of (Na,K)-ATPase increased, due to higher affinity of the ATP-binding site, as revealed from the lowered Km value for ATP. The K(Na) value for Na+ returned to control value. Inhibition of NO-synthase induced a reversible hypertension accompanied by depressed Na+-extrusion from cardiac cells as a consequence of deteriorated Na+-binding properties of the (Na,K)-ATPase. After recovery of blood pressure to control values, the extrusion of Na+ from cardiac cells was normalized, as revealed by restoration of the (Na,K)-ATPase activity.", "entity": "NG-Nitroarginine Methyl Ester", "aliases": "L-NAME Methyl Ester NG-Nitro-L-Arginine NG-Nitroarginine N omega Nitro L arginine omega-Nitro-L-arginine N(G)-Nitro-L-arginine N(G)-Nitroarginine N(omega)-Nitro-L-arginine NG Arginine Nitroarginine D Orn Isomer D-Orn-Isomer L-Orn-Isomer Monohydrochloride", "definition": "A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.\n    ", "id": "MESH:D019331"}
{"mention": "ATP", "mention_text": "In the cardiovascular system, NO is involved in the regulation of a variety of functions. Inhibition of NO synthesis induces sustained hypertension. In several models of hypertension, elevation of intracellular sodium level was documented in cardiac tissue. To assess the molecular basis of disturbances in transmembraneous transport of Na+, we studied the response of cardiac (Na,K)-ATPase to NO-deficient hypertension induced in rats by NO-synthase inhibition with 40 mg/kg/day N(G)-nitro-L-arginine methyl ester (L-NAME) for 4 four weeks. After 4-week administration of L-NAME, the systolic blood pressure (SBP) increased by 36%. Two weeks after terminating the treatment, the SBP recovered to control value. When activating the (Na,K)-ATPase with its substrate ATP, no changes in Km and Vmax values were observed in NO-deficient rats. During activation with Na+, the Vmax remained unchanged, however the K(Na) increased by 50%, indicating a profound decrease in the affinity of the Na+-binding site in NO-deficient rats. After recovery from hypertension, the activity of (Na,K)-ATPase increased, due to higher affinity of the ATP-binding site, as revealed from the lowered Km value for ATP. The K(Na) value for Na+ returned to control value. Inhibition of NO-synthase induced a reversible hypertension accompanied by depressed Na+-extrusion from cardiac cells as a consequence of deteriorated Na+-binding properties of the (Na,K)-ATPase. After recovery of blood pressure to control values, the extrusion of Na+ from cardiac cells was normalized, as revealed by restoration of the (Na,K)-ATPase activity.", "entity": "Adenosine Triphosphate", "aliases": "ATP MgCl2 ATP-MgCl2 Adenosine Triphosphate Calcium Salt Chromium Ammonium Magnesium Chloride Manganese Adenylpyrophosphate Atriphos CaATP Cr(H2O)4 CrATP MgATP MnATP Striadyne", "definition": "An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.\n    ", "id": "MESH:D000255"}
{"mention": "depressed", "mention_text": "In the cardiovascular system, NO is involved in the regulation of a variety of functions. Inhibition of NO synthesis induces sustained hypertension. In several models of hypertension, elevation of intracellular sodium level was documented in cardiac tissue. To assess the molecular basis of disturbances in transmembraneous transport of Na+, we studied the response of cardiac (Na,K)-ATPase to NO-deficient hypertension induced in rats by NO-synthase inhibition with 40 mg/kg/day N(G)-nitro-L-arginine methyl ester (L-NAME) for 4 four weeks. After 4-week administration of L-NAME, the systolic blood pressure (SBP) increased by 36%. Two weeks after terminating the treatment, the SBP recovered to control value. When activating the (Na,K)-ATPase with its substrate ATP, no changes in Km and Vmax values were observed in NO-deficient rats. During activation with Na+, the Vmax remained unchanged, however the K(Na) increased by 50%, indicating a profound decrease in the affinity of the Na+-binding site in NO-deficient rats. After recovery from hypertension, the activity of (Na,K)-ATPase increased, due to higher affinity of the ATP-binding site, as revealed from the lowered Km value for ATP. The K(Na) value for Na+ returned to control value. Inhibition of NO-synthase induced a reversible hypertension accompanied by depressed Na+-extrusion from cardiac cells as a consequence of deteriorated Na+-binding properties of the (Na,K)-ATPase. After recovery of blood pressure to control values, the extrusion of Na+ from cardiac cells was normalized, as revealed by restoration of the (Na,K)-ATPase activity.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "isoproterenol", "mention_text": "Effects of long-term pretreatment with isoproterenol on bromocriptine-induced tachycardia in conscious rats.", "entity": "Isoproterenol", "aliases": "4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol Euspiran Hydrochloride Isoproterenol Isadrin Isadrine Isoprenaline Isopropyl Noradrenaline Isopropylarterenol Isopropylnoradrenaline Isopropylnorepinephrine Sulfate Isuprel Izadrin Norisodrine Novodrin", "definition": "Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.\n    ", "id": "MESH:D007545"}
{"mention": "bromocriptine", "mention_text": "Effects of long-term pretreatment with isoproterenol on bromocriptine-induced tachycardia in conscious rats.", "entity": "Bromocriptine", "aliases": "2 Bromo alpha ergocryptine ergokryptine Bromoergocryptine Mesylate Methanesulfonate Bromoergokryptine 2-Bromo-alpha-ergocryptine 2-Bromo-alpha-ergokryptine 2-Bromoergocryptine 2-Bromoergokryptine Bromocriptin Bromocriptine Bromocryptin CB 154 CB-154 CB154 Parlodel", "definition": "A semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion.\n    ", "id": "MESH:D001971"}
{"mention": "tachycardia", "mention_text": "Effects of long-term pretreatment with isoproterenol on bromocriptine-induced tachycardia in conscious rats.", "entity": "Tachycardia", "aliases": "Tachyarrhythmia Tachyarrhythmias Tachycardia Tachycardias", "definition": "Abnormally rapid heartbeat, usually with a HEART RATE above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia.\n    ", "id": "MESH:D013610"}
{"mention": "bromocriptine", "mention_text": "It has been shown that bromocriptine-induced tachycardia, which persisted after adrenalectomy, is (i) mediated by central dopamine D2 receptor activation and (ii) reduced by 5-day isoproterenol pretreatment, supporting therefore the hypothesis that this effect is dependent on sympathetic outflow to the heart. This study was conducted to examine whether prolonged pretreatment with isoproterenol could abolish bromocriptine-induced tachycardia in conscious rats. Isoproterenol pretreatment for 15 days caused cardiac hypertrophy without affecting baseline blood pressure and heart rate. In control rats, intravenous bromocriptine (150 microg/kg) induced significant hypotension and tachycardia. Bromocriptine-induced hypotension was unaffected by isoproterenol pretreatment, while tachycardia was reversed to significant bradycardia, an effect that was partly reduced by i.v. domperidone (0.5 mg/kg). Neither cardiac vagal nor sympathetic tone was altered by isoproterenol pretreatment. In isolated perfused heart preparations from isoproterenol-pretreated rats, the isoproterenol-induced maximal increase in left ventricular systolic pressure was significantly reduced, compared with saline-pretreated rats (the EC50 of the isoproterenol-induced increase in left ventricular systolic pressure was enhanced approximately 22-fold). These results show that 15-day isoproterenol pretreatment not only abolished but reversed bromocriptine-induced tachycardia to bradycardia, an effect that is mainly related to further cardiac beta-adrenoceptor desensitization rather than to impairment of autonomic regulation of the heart. They suggest that, in normal conscious rats, the central tachycardia of bromocriptine appears to predominate and to mask the bradycardia of this agonist at peripheral dopamine D2 receptors.", "entity": "Bromocriptine", "aliases": "2 Bromo alpha ergocryptine ergokryptine Bromoergocryptine Mesylate Methanesulfonate Bromoergokryptine 2-Bromo-alpha-ergocryptine 2-Bromo-alpha-ergokryptine 2-Bromoergocryptine 2-Bromoergokryptine Bromocriptin Bromocriptine Bromocryptin CB 154 CB-154 CB154 Parlodel", "definition": "A semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion.\n    ", "id": "MESH:D001971"}
{"mention": "tachycardia", "mention_text": "It has been shown that bromocriptine-induced tachycardia, which persisted after adrenalectomy, is (i) mediated by central dopamine D2 receptor activation and (ii) reduced by 5-day isoproterenol pretreatment, supporting therefore the hypothesis that this effect is dependent on sympathetic outflow to the heart. This study was conducted to examine whether prolonged pretreatment with isoproterenol could abolish bromocriptine-induced tachycardia in conscious rats. Isoproterenol pretreatment for 15 days caused cardiac hypertrophy without affecting baseline blood pressure and heart rate. In control rats, intravenous bromocriptine (150 microg/kg) induced significant hypotension and tachycardia. Bromocriptine-induced hypotension was unaffected by isoproterenol pretreatment, while tachycardia was reversed to significant bradycardia, an effect that was partly reduced by i.v. domperidone (0.5 mg/kg). Neither cardiac vagal nor sympathetic tone was altered by isoproterenol pretreatment. In isolated perfused heart preparations from isoproterenol-pretreated rats, the isoproterenol-induced maximal increase in left ventricular systolic pressure was significantly reduced, compared with saline-pretreated rats (the EC50 of the isoproterenol-induced increase in left ventricular systolic pressure was enhanced approximately 22-fold). These results show that 15-day isoproterenol pretreatment not only abolished but reversed bromocriptine-induced tachycardia to bradycardia, an effect that is mainly related to further cardiac beta-adrenoceptor desensitization rather than to impairment of autonomic regulation of the heart. They suggest that, in normal conscious rats, the central tachycardia of bromocriptine appears to predominate and to mask the bradycardia of this agonist at peripheral dopamine D2 receptors.", "entity": "Tachycardia", "aliases": "Tachyarrhythmia Tachyarrhythmias Tachycardia Tachycardias", "definition": "Abnormally rapid heartbeat, usually with a HEART RATE above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia.\n    ", "id": "MESH:D013610"}
{"mention": "dopamine", "mention_text": "It has been shown that bromocriptine-induced tachycardia, which persisted after adrenalectomy, is (i) mediated by central dopamine D2 receptor activation and (ii) reduced by 5-day isoproterenol pretreatment, supporting therefore the hypothesis that this effect is dependent on sympathetic outflow to the heart. This study was conducted to examine whether prolonged pretreatment with isoproterenol could abolish bromocriptine-induced tachycardia in conscious rats. Isoproterenol pretreatment for 15 days caused cardiac hypertrophy without affecting baseline blood pressure and heart rate. In control rats, intravenous bromocriptine (150 microg/kg) induced significant hypotension and tachycardia. Bromocriptine-induced hypotension was unaffected by isoproterenol pretreatment, while tachycardia was reversed to significant bradycardia, an effect that was partly reduced by i.v. domperidone (0.5 mg/kg). Neither cardiac vagal nor sympathetic tone was altered by isoproterenol pretreatment. In isolated perfused heart preparations from isoproterenol-pretreated rats, the isoproterenol-induced maximal increase in left ventricular systolic pressure was significantly reduced, compared with saline-pretreated rats (the EC50 of the isoproterenol-induced increase in left ventricular systolic pressure was enhanced approximately 22-fold). These results show that 15-day isoproterenol pretreatment not only abolished but reversed bromocriptine-induced tachycardia to bradycardia, an effect that is mainly related to further cardiac beta-adrenoceptor desensitization rather than to impairment of autonomic regulation of the heart. They suggest that, in normal conscious rats, the central tachycardia of bromocriptine appears to predominate and to mask the bradycardia of this agonist at peripheral dopamine D2 receptors.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "isoproterenol", "mention_text": "It has been shown that bromocriptine-induced tachycardia, which persisted after adrenalectomy, is (i) mediated by central dopamine D2 receptor activation and (ii) reduced by 5-day isoproterenol pretreatment, supporting therefore the hypothesis that this effect is dependent on sympathetic outflow to the heart. This study was conducted to examine whether prolonged pretreatment with isoproterenol could abolish bromocriptine-induced tachycardia in conscious rats. Isoproterenol pretreatment for 15 days caused cardiac hypertrophy without affecting baseline blood pressure and heart rate. In control rats, intravenous bromocriptine (150 microg/kg) induced significant hypotension and tachycardia. Bromocriptine-induced hypotension was unaffected by isoproterenol pretreatment, while tachycardia was reversed to significant bradycardia, an effect that was partly reduced by i.v. domperidone (0.5 mg/kg). Neither cardiac vagal nor sympathetic tone was altered by isoproterenol pretreatment. In isolated perfused heart preparations from isoproterenol-pretreated rats, the isoproterenol-induced maximal increase in left ventricular systolic pressure was significantly reduced, compared with saline-pretreated rats (the EC50 of the isoproterenol-induced increase in left ventricular systolic pressure was enhanced approximately 22-fold). These results show that 15-day isoproterenol pretreatment not only abolished but reversed bromocriptine-induced tachycardia to bradycardia, an effect that is mainly related to further cardiac beta-adrenoceptor desensitization rather than to impairment of autonomic regulation of the heart. They suggest that, in normal conscious rats, the central tachycardia of bromocriptine appears to predominate and to mask the bradycardia of this agonist at peripheral dopamine D2 receptors.", "entity": "Isoproterenol", "aliases": "4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol Euspiran Hydrochloride Isoproterenol Isadrin Isadrine Isoprenaline Isopropyl Noradrenaline Isopropylarterenol Isopropylnoradrenaline Isopropylnorepinephrine Sulfate Isuprel Izadrin Norisodrine Novodrin", "definition": "Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.\n    ", "id": "MESH:D007545"}
{"mention": "Isoproterenol", "mention_text": "It has been shown that bromocriptine-induced tachycardia, which persisted after adrenalectomy, is (i) mediated by central dopamine D2 receptor activation and (ii) reduced by 5-day isoproterenol pretreatment, supporting therefore the hypothesis that this effect is dependent on sympathetic outflow to the heart. This study was conducted to examine whether prolonged pretreatment with isoproterenol could abolish bromocriptine-induced tachycardia in conscious rats. Isoproterenol pretreatment for 15 days caused cardiac hypertrophy without affecting baseline blood pressure and heart rate. In control rats, intravenous bromocriptine (150 microg/kg) induced significant hypotension and tachycardia. Bromocriptine-induced hypotension was unaffected by isoproterenol pretreatment, while tachycardia was reversed to significant bradycardia, an effect that was partly reduced by i.v. domperidone (0.5 mg/kg). Neither cardiac vagal nor sympathetic tone was altered by isoproterenol pretreatment. In isolated perfused heart preparations from isoproterenol-pretreated rats, the isoproterenol-induced maximal increase in left ventricular systolic pressure was significantly reduced, compared with saline-pretreated rats (the EC50 of the isoproterenol-induced increase in left ventricular systolic pressure was enhanced approximately 22-fold). These results show that 15-day isoproterenol pretreatment not only abolished but reversed bromocriptine-induced tachycardia to bradycardia, an effect that is mainly related to further cardiac beta-adrenoceptor desensitization rather than to impairment of autonomic regulation of the heart. They suggest that, in normal conscious rats, the central tachycardia of bromocriptine appears to predominate and to mask the bradycardia of this agonist at peripheral dopamine D2 receptors.", "entity": "Isoproterenol", "aliases": "4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol Euspiran Hydrochloride Isoproterenol Isadrin Isadrine Isoprenaline Isopropyl Noradrenaline Isopropylarterenol Isopropylnoradrenaline Isopropylnorepinephrine Sulfate Isuprel Izadrin Norisodrine Novodrin", "definition": "Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.\n    ", "id": "MESH:D007545"}
{"mention": "cardiac hypertrophy", "mention_text": "It has been shown that bromocriptine-induced tachycardia, which persisted after adrenalectomy, is (i) mediated by central dopamine D2 receptor activation and (ii) reduced by 5-day isoproterenol pretreatment, supporting therefore the hypothesis that this effect is dependent on sympathetic outflow to the heart. This study was conducted to examine whether prolonged pretreatment with isoproterenol could abolish bromocriptine-induced tachycardia in conscious rats. Isoproterenol pretreatment for 15 days caused cardiac hypertrophy without affecting baseline blood pressure and heart rate. In control rats, intravenous bromocriptine (150 microg/kg) induced significant hypotension and tachycardia. Bromocriptine-induced hypotension was unaffected by isoproterenol pretreatment, while tachycardia was reversed to significant bradycardia, an effect that was partly reduced by i.v. domperidone (0.5 mg/kg). Neither cardiac vagal nor sympathetic tone was altered by isoproterenol pretreatment. In isolated perfused heart preparations from isoproterenol-pretreated rats, the isoproterenol-induced maximal increase in left ventricular systolic pressure was significantly reduced, compared with saline-pretreated rats (the EC50 of the isoproterenol-induced increase in left ventricular systolic pressure was enhanced approximately 22-fold). These results show that 15-day isoproterenol pretreatment not only abolished but reversed bromocriptine-induced tachycardia to bradycardia, an effect that is mainly related to further cardiac beta-adrenoceptor desensitization rather than to impairment of autonomic regulation of the heart. They suggest that, in normal conscious rats, the central tachycardia of bromocriptine appears to predominate and to mask the bradycardia of this agonist at peripheral dopamine D2 receptors.", "entity": "Cardiomegaly", "aliases": "Cardiac Hypertrophy Cardiomegaly Enlarged Heart Enlargement", "definition": "Enlargement of the HEART, usually indicated by a cardiothoracic ratio above 0.50. Heart enlargement may involve the right, the left, or both HEART VENTRICLES or HEART ATRIA. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (HEART FAILURE) or several forms of CARDIOMYOPATHIES.\n    ", "id": "MESH:D006332"}
{"mention": "hypotension", "mention_text": "It has been shown that bromocriptine-induced tachycardia, which persisted after adrenalectomy, is (i) mediated by central dopamine D2 receptor activation and (ii) reduced by 5-day isoproterenol pretreatment, supporting therefore the hypothesis that this effect is dependent on sympathetic outflow to the heart. This study was conducted to examine whether prolonged pretreatment with isoproterenol could abolish bromocriptine-induced tachycardia in conscious rats. Isoproterenol pretreatment for 15 days caused cardiac hypertrophy without affecting baseline blood pressure and heart rate. In control rats, intravenous bromocriptine (150 microg/kg) induced significant hypotension and tachycardia. Bromocriptine-induced hypotension was unaffected by isoproterenol pretreatment, while tachycardia was reversed to significant bradycardia, an effect that was partly reduced by i.v. domperidone (0.5 mg/kg). Neither cardiac vagal nor sympathetic tone was altered by isoproterenol pretreatment. In isolated perfused heart preparations from isoproterenol-pretreated rats, the isoproterenol-induced maximal increase in left ventricular systolic pressure was significantly reduced, compared with saline-pretreated rats (the EC50 of the isoproterenol-induced increase in left ventricular systolic pressure was enhanced approximately 22-fold). These results show that 15-day isoproterenol pretreatment not only abolished but reversed bromocriptine-induced tachycardia to bradycardia, an effect that is mainly related to further cardiac beta-adrenoceptor desensitization rather than to impairment of autonomic regulation of the heart. They suggest that, in normal conscious rats, the central tachycardia of bromocriptine appears to predominate and to mask the bradycardia of this agonist at peripheral dopamine D2 receptors.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "Bromocriptine", "mention_text": "It has been shown that bromocriptine-induced tachycardia, which persisted after adrenalectomy, is (i) mediated by central dopamine D2 receptor activation and (ii) reduced by 5-day isoproterenol pretreatment, supporting therefore the hypothesis that this effect is dependent on sympathetic outflow to the heart. This study was conducted to examine whether prolonged pretreatment with isoproterenol could abolish bromocriptine-induced tachycardia in conscious rats. Isoproterenol pretreatment for 15 days caused cardiac hypertrophy without affecting baseline blood pressure and heart rate. In control rats, intravenous bromocriptine (150 microg/kg) induced significant hypotension and tachycardia. Bromocriptine-induced hypotension was unaffected by isoproterenol pretreatment, while tachycardia was reversed to significant bradycardia, an effect that was partly reduced by i.v. domperidone (0.5 mg/kg). Neither cardiac vagal nor sympathetic tone was altered by isoproterenol pretreatment. In isolated perfused heart preparations from isoproterenol-pretreated rats, the isoproterenol-induced maximal increase in left ventricular systolic pressure was significantly reduced, compared with saline-pretreated rats (the EC50 of the isoproterenol-induced increase in left ventricular systolic pressure was enhanced approximately 22-fold). These results show that 15-day isoproterenol pretreatment not only abolished but reversed bromocriptine-induced tachycardia to bradycardia, an effect that is mainly related to further cardiac beta-adrenoceptor desensitization rather than to impairment of autonomic regulation of the heart. They suggest that, in normal conscious rats, the central tachycardia of bromocriptine appears to predominate and to mask the bradycardia of this agonist at peripheral dopamine D2 receptors.", "entity": "Bromocriptine", "aliases": "2 Bromo alpha ergocryptine ergokryptine Bromoergocryptine Mesylate Methanesulfonate Bromoergokryptine 2-Bromo-alpha-ergocryptine 2-Bromo-alpha-ergokryptine 2-Bromoergocryptine 2-Bromoergokryptine Bromocriptin Bromocriptine Bromocryptin CB 154 CB-154 CB154 Parlodel", "definition": "A semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion.\n    ", "id": "MESH:D001971"}
{"mention": "bradycardia", "mention_text": "It has been shown that bromocriptine-induced tachycardia, which persisted after adrenalectomy, is (i) mediated by central dopamine D2 receptor activation and (ii) reduced by 5-day isoproterenol pretreatment, supporting therefore the hypothesis that this effect is dependent on sympathetic outflow to the heart. This study was conducted to examine whether prolonged pretreatment with isoproterenol could abolish bromocriptine-induced tachycardia in conscious rats. Isoproterenol pretreatment for 15 days caused cardiac hypertrophy without affecting baseline blood pressure and heart rate. In control rats, intravenous bromocriptine (150 microg/kg) induced significant hypotension and tachycardia. Bromocriptine-induced hypotension was unaffected by isoproterenol pretreatment, while tachycardia was reversed to significant bradycardia, an effect that was partly reduced by i.v. domperidone (0.5 mg/kg). Neither cardiac vagal nor sympathetic tone was altered by isoproterenol pretreatment. In isolated perfused heart preparations from isoproterenol-pretreated rats, the isoproterenol-induced maximal increase in left ventricular systolic pressure was significantly reduced, compared with saline-pretreated rats (the EC50 of the isoproterenol-induced increase in left ventricular systolic pressure was enhanced approximately 22-fold). These results show that 15-day isoproterenol pretreatment not only abolished but reversed bromocriptine-induced tachycardia to bradycardia, an effect that is mainly related to further cardiac beta-adrenoceptor desensitization rather than to impairment of autonomic regulation of the heart. They suggest that, in normal conscious rats, the central tachycardia of bromocriptine appears to predominate and to mask the bradycardia of this agonist at peripheral dopamine D2 receptors.", "entity": "Bradycardia", "aliases": "Bradyarrhythmia Bradyarrhythmias Bradycardia Bradycardias", "definition": "Cardiac arrhythmias that are characterized by excessively slow HEART RATE, usually below 50 beats per minute in human adults. They can be classified broadly into SINOATRIAL NODE dysfunction and ATRIOVENTRICULAR BLOCK.\n    ", "id": "MESH:D001919"}
{"mention": "domperidone", "mention_text": "It has been shown that bromocriptine-induced tachycardia, which persisted after adrenalectomy, is (i) mediated by central dopamine D2 receptor activation and (ii) reduced by 5-day isoproterenol pretreatment, supporting therefore the hypothesis that this effect is dependent on sympathetic outflow to the heart. This study was conducted to examine whether prolonged pretreatment with isoproterenol could abolish bromocriptine-induced tachycardia in conscious rats. Isoproterenol pretreatment for 15 days caused cardiac hypertrophy without affecting baseline blood pressure and heart rate. In control rats, intravenous bromocriptine (150 microg/kg) induced significant hypotension and tachycardia. Bromocriptine-induced hypotension was unaffected by isoproterenol pretreatment, while tachycardia was reversed to significant bradycardia, an effect that was partly reduced by i.v. domperidone (0.5 mg/kg). Neither cardiac vagal nor sympathetic tone was altered by isoproterenol pretreatment. In isolated perfused heart preparations from isoproterenol-pretreated rats, the isoproterenol-induced maximal increase in left ventricular systolic pressure was significantly reduced, compared with saline-pretreated rats (the EC50 of the isoproterenol-induced increase in left ventricular systolic pressure was enhanced approximately 22-fold). These results show that 15-day isoproterenol pretreatment not only abolished but reversed bromocriptine-induced tachycardia to bradycardia, an effect that is mainly related to further cardiac beta-adrenoceptor desensitization rather than to impairment of autonomic regulation of the heart. They suggest that, in normal conscious rats, the central tachycardia of bromocriptine appears to predominate and to mask the bradycardia of this agonist at peripheral dopamine D2 receptors.", "entity": "Domperidone", "aliases": "Aliud Brand of Domperidone Maleate Apo Apo-Domperidone Apotex Domidon Domperidon AL Hexal Stada TEVA Domperidon-TEVA Domperidona Gamir (1:1) Monohydrochloride Gastrocure Gry Janssen Motilium Nauzelin Novo Novo-Domperidone Novopharm Nu Pharm Nu-Domperidone Nu-Pharm PMS PMS-Domperidone Pharmascience Pierre Fabre Péridys R-33,812 R-33812 R33,812 R33812 Ratiopharm Rottapharm Stadapharm Taxandria Teva ratio ratio-Domperidone", "definition": "A specific blocker of dopamine receptors. It speeds gastrointestinal peristalsis, causes prolactin release, and is used as antiemetic and tool in the study of dopaminergic mechanisms.\n    ", "id": "MESH:D004294"}
{"mention": "clonidine", "mention_text": "A developmental analysis of clonidine's effects on cardiac rate and ultrasound production in infant rats.", "entity": "Clonidine", "aliases": "Boehringer Ingelheim Brand of Clonidine Hydrochloride Catapres Catapresan Catapressan Chlophazolin Clofelin Clofenil Dihydrochloride Monohydrobromide Monohydrochloride Clopheline Dixarit Gemiton Hemiton Isoglaucon Klofelin Klofenil M 5041T M-5041T M5041T ST 155 ST-155 ST155", "definition": "An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.\n    ", "id": "MESH:D003000"}
{"mention": "clonidine", "mention_text": "Under controlled conditions, infant rats emit ultrasonic vocalizations during extreme cold exposure and after administration of the alpha(2) adrenoceptor agonist, clonidine. Previous investigations have determined that, in response to clonidine, ultrasound production increases through the 2nd-week postpartum and decreases thereafter. Given that sympathetic neural dominance exhibits a similar developmental pattern, and given that clonidine induces sympathetic withdrawal and bradycardia, we hypothesized that clonidine's developmental effects on cardiac rate and ultrasound production would mirror each other. Therefore, in the present experiment, the effects of clonidine administration (0.5 mg/kg) on cardiac rate and ultrasound production were examined in 2-, 8-, 15-, and 20-day-old rats. Age-related changes in ultrasound production corresponded with changes in cardiovascular variables, including baseline cardiac rate and clonidine-induced bradycardia. This experiment is discussed with regard to the hypothesis that ultrasound production is the acoustic by-product of a physiological maneuver that compensates for clonidine's detrimental effects on cardiovascular function.", "entity": "Clonidine", "aliases": "Boehringer Ingelheim Brand of Clonidine Hydrochloride Catapres Catapresan Catapressan Chlophazolin Clofelin Clofenil Dihydrochloride Monohydrobromide Monohydrochloride Clopheline Dixarit Gemiton Hemiton Isoglaucon Klofelin Klofenil M 5041T M-5041T M5041T ST 155 ST-155 ST155", "definition": "An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.\n    ", "id": "MESH:D003000"}
{"mention": "bradycardia", "mention_text": "Under controlled conditions, infant rats emit ultrasonic vocalizations during extreme cold exposure and after administration of the alpha(2) adrenoceptor agonist, clonidine. Previous investigations have determined that, in response to clonidine, ultrasound production increases through the 2nd-week postpartum and decreases thereafter. Given that sympathetic neural dominance exhibits a similar developmental pattern, and given that clonidine induces sympathetic withdrawal and bradycardia, we hypothesized that clonidine's developmental effects on cardiac rate and ultrasound production would mirror each other. Therefore, in the present experiment, the effects of clonidine administration (0.5 mg/kg) on cardiac rate and ultrasound production were examined in 2-, 8-, 15-, and 20-day-old rats. Age-related changes in ultrasound production corresponded with changes in cardiovascular variables, including baseline cardiac rate and clonidine-induced bradycardia. This experiment is discussed with regard to the hypothesis that ultrasound production is the acoustic by-product of a physiological maneuver that compensates for clonidine's detrimental effects on cardiovascular function.", "entity": "Bradycardia", "aliases": "Bradyarrhythmia Bradyarrhythmias Bradycardia Bradycardias", "definition": "Cardiac arrhythmias that are characterized by excessively slow HEART RATE, usually below 50 beats per minute in human adults. They can be classified broadly into SINOATRIAL NODE dysfunction and ATRIOVENTRICULAR BLOCK.\n    ", "id": "MESH:D001919"}
{"mention": "ketamine", "mention_text": "Differential effects of systemically administered ketamine and lidocaine on dynamic and static hyperalgesia induced by intradermal capsaicin in humans.", "entity": "Ketamine", "aliases": "2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone CI 581 CI-581 CI581 Calipsol Calypsol Kalipsol Ketalar Ketamine Hydrochloride Ketanest Ketaset", "definition": "A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors.\n    ", "id": "MESH:D007649"}
{"mention": "lidocaine", "mention_text": "Differential effects of systemically administered ketamine and lidocaine on dynamic and static hyperalgesia induced by intradermal capsaicin in humans.", "entity": "Lidocaine", "aliases": "2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide 2-2EtN-2MePhAcN Astrazeneca Brand of Lidocaine Dalcaine Jenapharm Lidocanine Hydrochloride Carbonate (2:1) Hydrocarbonate Monoacetate Monohydrochloride Monohydrate Sulfate (1:1) Lignocaine Novocol Octocaine Strathmann Xylesthesin Xylocaine Xylocitin Xyloneural", "definition": "A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.\n    ", "id": "MESH:D008012"}
{"mention": "hyperalgesia", "mention_text": "Differential effects of systemically administered ketamine and lidocaine on dynamic and static hyperalgesia induced by intradermal capsaicin in humans.", "entity": "Hyperalgesia", "aliases": "Allodynia Mechanical Tactile Thermal Allodynias Hyperalgesia Primary Secondary Hyperalgesias Hyperalgesic Sensations", "definition": "An increased sensation of pain or discomfort produced by mimimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve.\n    ", "id": "MESH:D006930"}
{"mention": "capsaicin", "mention_text": "Differential effects of systemically administered ketamine and lidocaine on dynamic and static hyperalgesia induced by intradermal capsaicin in humans.", "entity": "Capsaicin", "aliases": "8 Methyl N Vanillyl 6 Nonenamide 8-Methyl-N-Vanillyl-6-Nonenamide Alacan Brand of Capsaicin Antiphlogistine Rub A-535 Axsain Capsaicine Capsicum Farmaya Capsidol Capsin Capzasin Carter Horner Centrum Elan Flemming Gelcen Katrum Link Medicis NGX 4010 NGX-4010 NGX4010 Smaller Thompson Vinas Zacin Zostrix", "definition": "An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.\n    ", "id": "MESH:D002211"}
{"mention": "ketamine", "mention_text": "We have examined the effect of systemic administration of ketamine and lidocaine on brush-evoked (dynamic) pain and punctate-evoked (static) hyperalgesia induced by capsaicin. In a randomized, double-blind, placebo-controlled, crossover study, we studied 12 volunteers in three experiments. Capsaicin 100 micrograms was injected intradermally on the volar forearm followed by an i.v. infusion of ketamine (bolus 0.1 mg kg-1 over 10 min followed by infusion of 7 micrograms kg-1 min-1), lidocaine 5 mg kg-1 or saline for 50 min. Infusion started 15 min after injection of capsaicin. The following were measured: spontaneous pain, pain evoked by punctate and brush stimuli (VAS), and areas of brush-evoked and punctate-evoked hyperalgesia. Ketamine reduced both the area of brush-evoked and punctate-evoked hyperalgesia significantly and it tended to reduce brush-evoked pain. Lidocaine reduced the area of punctate-evoked hyperalgesia significantly. It tended to reduce VAS scores of spontaneous pain but had no effect on evoked pain. The differential effects of ketamine and lidocaine on static and dynamic hyperalgesia suggest that the two types of hyperalgesia are mediated by separate mechanisms and have a distinct pharmacology.", "entity": "Ketamine", "aliases": "2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone CI 581 CI-581 CI581 Calipsol Calypsol Kalipsol Ketalar Ketamine Hydrochloride Ketanest Ketaset", "definition": "A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors.\n    ", "id": "MESH:D007649"}
{"mention": "lidocaine", "mention_text": "We have examined the effect of systemic administration of ketamine and lidocaine on brush-evoked (dynamic) pain and punctate-evoked (static) hyperalgesia induced by capsaicin. In a randomized, double-blind, placebo-controlled, crossover study, we studied 12 volunteers in three experiments. Capsaicin 100 micrograms was injected intradermally on the volar forearm followed by an i.v. infusion of ketamine (bolus 0.1 mg kg-1 over 10 min followed by infusion of 7 micrograms kg-1 min-1), lidocaine 5 mg kg-1 or saline for 50 min. Infusion started 15 min after injection of capsaicin. The following were measured: spontaneous pain, pain evoked by punctate and brush stimuli (VAS), and areas of brush-evoked and punctate-evoked hyperalgesia. Ketamine reduced both the area of brush-evoked and punctate-evoked hyperalgesia significantly and it tended to reduce brush-evoked pain. Lidocaine reduced the area of punctate-evoked hyperalgesia significantly. It tended to reduce VAS scores of spontaneous pain but had no effect on evoked pain. The differential effects of ketamine and lidocaine on static and dynamic hyperalgesia suggest that the two types of hyperalgesia are mediated by separate mechanisms and have a distinct pharmacology.", "entity": "Lidocaine", "aliases": "2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide 2-2EtN-2MePhAcN Astrazeneca Brand of Lidocaine Dalcaine Jenapharm Lidocanine Hydrochloride Carbonate (2:1) Hydrocarbonate Monoacetate Monohydrochloride Monohydrate Sulfate (1:1) Lignocaine Novocol Octocaine Strathmann Xylesthesin Xylocaine Xylocitin Xyloneural", "definition": "A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.\n    ", "id": "MESH:D008012"}
{"mention": "pain", "mention_text": "We have examined the effect of systemic administration of ketamine and lidocaine on brush-evoked (dynamic) pain and punctate-evoked (static) hyperalgesia induced by capsaicin. In a randomized, double-blind, placebo-controlled, crossover study, we studied 12 volunteers in three experiments. Capsaicin 100 micrograms was injected intradermally on the volar forearm followed by an i.v. infusion of ketamine (bolus 0.1 mg kg-1 over 10 min followed by infusion of 7 micrograms kg-1 min-1), lidocaine 5 mg kg-1 or saline for 50 min. Infusion started 15 min after injection of capsaicin. The following were measured: spontaneous pain, pain evoked by punctate and brush stimuli (VAS), and areas of brush-evoked and punctate-evoked hyperalgesia. Ketamine reduced both the area of brush-evoked and punctate-evoked hyperalgesia significantly and it tended to reduce brush-evoked pain. Lidocaine reduced the area of punctate-evoked hyperalgesia significantly. It tended to reduce VAS scores of spontaneous pain but had no effect on evoked pain. The differential effects of ketamine and lidocaine on static and dynamic hyperalgesia suggest that the two types of hyperalgesia are mediated by separate mechanisms and have a distinct pharmacology.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "hyperalgesia", "mention_text": "We have examined the effect of systemic administration of ketamine and lidocaine on brush-evoked (dynamic) pain and punctate-evoked (static) hyperalgesia induced by capsaicin. In a randomized, double-blind, placebo-controlled, crossover study, we studied 12 volunteers in three experiments. Capsaicin 100 micrograms was injected intradermally on the volar forearm followed by an i.v. infusion of ketamine (bolus 0.1 mg kg-1 over 10 min followed by infusion of 7 micrograms kg-1 min-1), lidocaine 5 mg kg-1 or saline for 50 min. Infusion started 15 min after injection of capsaicin. The following were measured: spontaneous pain, pain evoked by punctate and brush stimuli (VAS), and areas of brush-evoked and punctate-evoked hyperalgesia. Ketamine reduced both the area of brush-evoked and punctate-evoked hyperalgesia significantly and it tended to reduce brush-evoked pain. Lidocaine reduced the area of punctate-evoked hyperalgesia significantly. It tended to reduce VAS scores of spontaneous pain but had no effect on evoked pain. The differential effects of ketamine and lidocaine on static and dynamic hyperalgesia suggest that the two types of hyperalgesia are mediated by separate mechanisms and have a distinct pharmacology.", "entity": "Hyperalgesia", "aliases": "Allodynia Mechanical Tactile Thermal Allodynias Hyperalgesia Primary Secondary Hyperalgesias Hyperalgesic Sensations", "definition": "An increased sensation of pain or discomfort produced by mimimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve.\n    ", "id": "MESH:D006930"}
{"mention": "capsaicin", "mention_text": "We have examined the effect of systemic administration of ketamine and lidocaine on brush-evoked (dynamic) pain and punctate-evoked (static) hyperalgesia induced by capsaicin. In a randomized, double-blind, placebo-controlled, crossover study, we studied 12 volunteers in three experiments. Capsaicin 100 micrograms was injected intradermally on the volar forearm followed by an i.v. infusion of ketamine (bolus 0.1 mg kg-1 over 10 min followed by infusion of 7 micrograms kg-1 min-1), lidocaine 5 mg kg-1 or saline for 50 min. Infusion started 15 min after injection of capsaicin. The following were measured: spontaneous pain, pain evoked by punctate and brush stimuli (VAS), and areas of brush-evoked and punctate-evoked hyperalgesia. Ketamine reduced both the area of brush-evoked and punctate-evoked hyperalgesia significantly and it tended to reduce brush-evoked pain. Lidocaine reduced the area of punctate-evoked hyperalgesia significantly. It tended to reduce VAS scores of spontaneous pain but had no effect on evoked pain. The differential effects of ketamine and lidocaine on static and dynamic hyperalgesia suggest that the two types of hyperalgesia are mediated by separate mechanisms and have a distinct pharmacology.", "entity": "Capsaicin", "aliases": "8 Methyl N Vanillyl 6 Nonenamide 8-Methyl-N-Vanillyl-6-Nonenamide Alacan Brand of Capsaicin Antiphlogistine Rub A-535 Axsain Capsaicine Capsicum Farmaya Capsidol Capsin Capzasin Carter Horner Centrum Elan Flemming Gelcen Katrum Link Medicis NGX 4010 NGX-4010 NGX4010 Smaller Thompson Vinas Zacin Zostrix", "definition": "An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.\n    ", "id": "MESH:D002211"}
{"mention": "Capsaicin", "mention_text": "We have examined the effect of systemic administration of ketamine and lidocaine on brush-evoked (dynamic) pain and punctate-evoked (static) hyperalgesia induced by capsaicin. In a randomized, double-blind, placebo-controlled, crossover study, we studied 12 volunteers in three experiments. Capsaicin 100 micrograms was injected intradermally on the volar forearm followed by an i.v. infusion of ketamine (bolus 0.1 mg kg-1 over 10 min followed by infusion of 7 micrograms kg-1 min-1), lidocaine 5 mg kg-1 or saline for 50 min. Infusion started 15 min after injection of capsaicin. The following were measured: spontaneous pain, pain evoked by punctate and brush stimuli (VAS), and areas of brush-evoked and punctate-evoked hyperalgesia. Ketamine reduced both the area of brush-evoked and punctate-evoked hyperalgesia significantly and it tended to reduce brush-evoked pain. Lidocaine reduced the area of punctate-evoked hyperalgesia significantly. It tended to reduce VAS scores of spontaneous pain but had no effect on evoked pain. The differential effects of ketamine and lidocaine on static and dynamic hyperalgesia suggest that the two types of hyperalgesia are mediated by separate mechanisms and have a distinct pharmacology.", "entity": "Capsaicin", "aliases": "8 Methyl N Vanillyl 6 Nonenamide 8-Methyl-N-Vanillyl-6-Nonenamide Alacan Brand of Capsaicin Antiphlogistine Rub A-535 Axsain Capsaicine Capsicum Farmaya Capsidol Capsin Capzasin Carter Horner Centrum Elan Flemming Gelcen Katrum Link Medicis NGX 4010 NGX-4010 NGX4010 Smaller Thompson Vinas Zacin Zostrix", "definition": "An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.\n    ", "id": "MESH:D002211"}
{"mention": "Ketamine", "mention_text": "We have examined the effect of systemic administration of ketamine and lidocaine on brush-evoked (dynamic) pain and punctate-evoked (static) hyperalgesia induced by capsaicin. In a randomized, double-blind, placebo-controlled, crossover study, we studied 12 volunteers in three experiments. Capsaicin 100 micrograms was injected intradermally on the volar forearm followed by an i.v. infusion of ketamine (bolus 0.1 mg kg-1 over 10 min followed by infusion of 7 micrograms kg-1 min-1), lidocaine 5 mg kg-1 or saline for 50 min. Infusion started 15 min after injection of capsaicin. The following were measured: spontaneous pain, pain evoked by punctate and brush stimuli (VAS), and areas of brush-evoked and punctate-evoked hyperalgesia. Ketamine reduced both the area of brush-evoked and punctate-evoked hyperalgesia significantly and it tended to reduce brush-evoked pain. Lidocaine reduced the area of punctate-evoked hyperalgesia significantly. It tended to reduce VAS scores of spontaneous pain but had no effect on evoked pain. The differential effects of ketamine and lidocaine on static and dynamic hyperalgesia suggest that the two types of hyperalgesia are mediated by separate mechanisms and have a distinct pharmacology.", "entity": "Ketamine", "aliases": "2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone CI 581 CI-581 CI581 Calipsol Calypsol Kalipsol Ketalar Ketamine Hydrochloride Ketanest Ketaset", "definition": "A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors.\n    ", "id": "MESH:D007649"}
{"mention": "Lidocaine", "mention_text": "We have examined the effect of systemic administration of ketamine and lidocaine on brush-evoked (dynamic) pain and punctate-evoked (static) hyperalgesia induced by capsaicin. In a randomized, double-blind, placebo-controlled, crossover study, we studied 12 volunteers in three experiments. Capsaicin 100 micrograms was injected intradermally on the volar forearm followed by an i.v. infusion of ketamine (bolus 0.1 mg kg-1 over 10 min followed by infusion of 7 micrograms kg-1 min-1), lidocaine 5 mg kg-1 or saline for 50 min. Infusion started 15 min after injection of capsaicin. The following were measured: spontaneous pain, pain evoked by punctate and brush stimuli (VAS), and areas of brush-evoked and punctate-evoked hyperalgesia. Ketamine reduced both the area of brush-evoked and punctate-evoked hyperalgesia significantly and it tended to reduce brush-evoked pain. Lidocaine reduced the area of punctate-evoked hyperalgesia significantly. It tended to reduce VAS scores of spontaneous pain but had no effect on evoked pain. The differential effects of ketamine and lidocaine on static and dynamic hyperalgesia suggest that the two types of hyperalgesia are mediated by separate mechanisms and have a distinct pharmacology.", "entity": "Lidocaine", "aliases": "2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide 2-2EtN-2MePhAcN Astrazeneca Brand of Lidocaine Dalcaine Jenapharm Lidocanine Hydrochloride Carbonate (2:1) Hydrocarbonate Monoacetate Monohydrochloride Monohydrate Sulfate (1:1) Lignocaine Novocol Octocaine Strathmann Xylesthesin Xylocaine Xylocitin Xyloneural", "definition": "A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.\n    ", "id": "MESH:D008012"}
{"mention": "Cyclosporine", "mention_text": "Cyclosporine and tacrolimus-associated thrombotic microangiopathy.", "entity": "Cyclosporine", "aliases": "Ciclosporin CsA Neoral CsA-Neoral CsANeoral CyA NOF CyA-NOF Cyclosporin A Cyclosporine OL 27 400 27-400 27400 Sandimmun Sandimmune", "definition": "A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).\n    ", "id": "MESH:D016572"}
{"mention": "tacrolimus", "mention_text": "Cyclosporine and tacrolimus-associated thrombotic microangiopathy.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "thrombotic microangiopathy", "mention_text": "Cyclosporine and tacrolimus-associated thrombotic microangiopathy.", "entity": "Thrombotic Microangiopathies", "aliases": "Microangiopathies Thrombotic Microangiopathy", "definition": "Diseases that result in THROMBOSIS in MICROVASCULATURE. The two most prominent diseases are PURPURA, THROMBOTIC THROMBOCYTOPENIC; and HEMOLYTIC-UREMIC SYNDROME. Multiple etiological factors include VASCULAR ENDOTHELIAL CELL damage due to SHIGA TOXIN; FACTOR H deficiency; and aberrant VON WILLEBRAND FACTOR formation.\n    ", "id": "MESH:D057049"}
{"mention": "thrombotic microangiopathy", "mention_text": "The development of thrombotic microangiopathy (TMA) associated with the use of cyclosporine has been well documented. Treatments have included discontinuation or reduction of cyclosporine dose with or without concurrent plasma exchange, plasma infusion, anticoagulation, and intravenous immunoglobulin G infusion. However, for recipients of organ transplantation, removing the inciting agent is not without the attendant risk of precipitating acute rejection and graft loss. The last decade has seen the emergence of tacrolimus as a potent immunosuppressive agent with mechanisms of action virtually identical to those of cyclosporine. As a result, switching to tacrolimus has been reported to be a viable therapeutic option in the setting of cyclosporine-induced TMA. With the more widespread application of tacrolimus in organ transplantation, tacrolimus-associated TMA has also been recognized. However, literature regarding the incidence of the recurrence of TMA in patients exposed sequentially to cyclosporine and tacrolimus is limited. We report a case of a living donor renal transplant recipient who developed cyclosporine-induced TMA that responded to the withdrawal of cyclosporine in conjunction with plasmapheresis and fresh frozen plasma replacement therapy. Introduction of tacrolimus as an alternative immunosuppressive agent resulted in the recurrence of TMA and the subsequent loss of the renal allograft. Patients who are switched from cyclosporine to tacrolimus or vice versa should be closely monitored for the signs and symptoms of recurrent TMA.", "entity": "Thrombotic Microangiopathies", "aliases": "Microangiopathies Thrombotic Microangiopathy", "definition": "Diseases that result in THROMBOSIS in MICROVASCULATURE. The two most prominent diseases are PURPURA, THROMBOTIC THROMBOCYTOPENIC; and HEMOLYTIC-UREMIC SYNDROME. Multiple etiological factors include VASCULAR ENDOTHELIAL CELL damage due to SHIGA TOXIN; FACTOR H deficiency; and aberrant VON WILLEBRAND FACTOR formation.\n    ", "id": "MESH:D057049"}
{"mention": "TMA", "mention_text": "The development of thrombotic microangiopathy (TMA) associated with the use of cyclosporine has been well documented. Treatments have included discontinuation or reduction of cyclosporine dose with or without concurrent plasma exchange, plasma infusion, anticoagulation, and intravenous immunoglobulin G infusion. However, for recipients of organ transplantation, removing the inciting agent is not without the attendant risk of precipitating acute rejection and graft loss. The last decade has seen the emergence of tacrolimus as a potent immunosuppressive agent with mechanisms of action virtually identical to those of cyclosporine. As a result, switching to tacrolimus has been reported to be a viable therapeutic option in the setting of cyclosporine-induced TMA. With the more widespread application of tacrolimus in organ transplantation, tacrolimus-associated TMA has also been recognized. However, literature regarding the incidence of the recurrence of TMA in patients exposed sequentially to cyclosporine and tacrolimus is limited. We report a case of a living donor renal transplant recipient who developed cyclosporine-induced TMA that responded to the withdrawal of cyclosporine in conjunction with plasmapheresis and fresh frozen plasma replacement therapy. Introduction of tacrolimus as an alternative immunosuppressive agent resulted in the recurrence of TMA and the subsequent loss of the renal allograft. Patients who are switched from cyclosporine to tacrolimus or vice versa should be closely monitored for the signs and symptoms of recurrent TMA.", "entity": "Thrombotic Microangiopathies", "aliases": "Microangiopathies Thrombotic Microangiopathy", "definition": "Diseases that result in THROMBOSIS in MICROVASCULATURE. The two most prominent diseases are PURPURA, THROMBOTIC THROMBOCYTOPENIC; and HEMOLYTIC-UREMIC SYNDROME. Multiple etiological factors include VASCULAR ENDOTHELIAL CELL damage due to SHIGA TOXIN; FACTOR H deficiency; and aberrant VON WILLEBRAND FACTOR formation.\n    ", "id": "MESH:D057049"}
{"mention": "cyclosporine", "mention_text": "The development of thrombotic microangiopathy (TMA) associated with the use of cyclosporine has been well documented. Treatments have included discontinuation or reduction of cyclosporine dose with or without concurrent plasma exchange, plasma infusion, anticoagulation, and intravenous immunoglobulin G infusion. However, for recipients of organ transplantation, removing the inciting agent is not without the attendant risk of precipitating acute rejection and graft loss. The last decade has seen the emergence of tacrolimus as a potent immunosuppressive agent with mechanisms of action virtually identical to those of cyclosporine. As a result, switching to tacrolimus has been reported to be a viable therapeutic option in the setting of cyclosporine-induced TMA. With the more widespread application of tacrolimus in organ transplantation, tacrolimus-associated TMA has also been recognized. However, literature regarding the incidence of the recurrence of TMA in patients exposed sequentially to cyclosporine and tacrolimus is limited. We report a case of a living donor renal transplant recipient who developed cyclosporine-induced TMA that responded to the withdrawal of cyclosporine in conjunction with plasmapheresis and fresh frozen plasma replacement therapy. Introduction of tacrolimus as an alternative immunosuppressive agent resulted in the recurrence of TMA and the subsequent loss of the renal allograft. Patients who are switched from cyclosporine to tacrolimus or vice versa should be closely monitored for the signs and symptoms of recurrent TMA.", "entity": "Cyclosporine", "aliases": "Ciclosporin CsA Neoral CsA-Neoral CsANeoral CyA NOF CyA-NOF Cyclosporin A Cyclosporine OL 27 400 27-400 27400 Sandimmun Sandimmune", "definition": "A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).\n    ", "id": "MESH:D016572"}
{"mention": "tacrolimus", "mention_text": "The development of thrombotic microangiopathy (TMA) associated with the use of cyclosporine has been well documented. Treatments have included discontinuation or reduction of cyclosporine dose with or without concurrent plasma exchange, plasma infusion, anticoagulation, and intravenous immunoglobulin G infusion. However, for recipients of organ transplantation, removing the inciting agent is not without the attendant risk of precipitating acute rejection and graft loss. The last decade has seen the emergence of tacrolimus as a potent immunosuppressive agent with mechanisms of action virtually identical to those of cyclosporine. As a result, switching to tacrolimus has been reported to be a viable therapeutic option in the setting of cyclosporine-induced TMA. With the more widespread application of tacrolimus in organ transplantation, tacrolimus-associated TMA has also been recognized. However, literature regarding the incidence of the recurrence of TMA in patients exposed sequentially to cyclosporine and tacrolimus is limited. We report a case of a living donor renal transplant recipient who developed cyclosporine-induced TMA that responded to the withdrawal of cyclosporine in conjunction with plasmapheresis and fresh frozen plasma replacement therapy. Introduction of tacrolimus as an alternative immunosuppressive agent resulted in the recurrence of TMA and the subsequent loss of the renal allograft. Patients who are switched from cyclosporine to tacrolimus or vice versa should be closely monitored for the signs and symptoms of recurrent TMA.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "anuria", "mention_text": "Repeated transient anuria following losartan administration in a patient with a solitary kidney.", "entity": "Anuria", "aliases": "Anuria Anurias", "definition": "Absence of urine formation. It is usually associated with complete bilateral ureteral (URETER) obstruction, complete lower urinary tract obstruction, or unilateral ureteral obstruction when a solitary kidney is present.\n    ", "id": "MESH:D001002"}
{"mention": "losartan", "mention_text": "Repeated transient anuria following losartan administration in a patient with a solitary kidney.", "entity": "Losartan", "aliases": "2-Butyl-4-chloro-1-((2'-(1H-etrazol-5-yl) (1,1'-biphenyl)-4-yl)methyl)-1H-imidazole-5-methanol Cozaar DuP 753 DuP-753 DuP753 Losartan Monopotassium Salt Potassium MK 954 MK-954 MK954", "definition": "An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.\n    ", "id": "MESH:D019808"}
{"mention": "hypertensive", "mention_text": "We report the case of a 70-year-old hypertensive man with a solitary kidney and chronic renal insufficiency who developed two episodes of transient anuria after losartan administration. He was hospitalized for a myocardial infarction with pulmonary edema, treated with high-dose diuretics. Due to severe systolic dysfunction losartan was prescribed. Surprisingly, the first dose of 50 mg of losartan resulted in a sudden anuria, which lasted eight hours despite high-dose furosemide and amine infusion. One week later, by mistake, losartan was prescribed again and after the second dose of 50 mg, the patient developed a second episode of transient anuria lasting 10 hours. During these two episodes, his blood pressure diminished but no severe hypotension was noted. Ultimately, an arteriography showed a 70-80% renal artery stenosis. In this patient, renal artery stenosis combined with heart failure and diuretic therapy certainly resulted in a strong activation of the renin-angiotensin system (RAS). Under such conditions, angiotensin II receptor blockade by losartan probably induced a critical fall in glomerular filtration pressure. This case report highlights the fact that the angiotensin II receptor antagonist losartan can cause serious unexpected complications in patients with renovascular disease and should be used with extreme caution in this setting.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "chronic renal insufficiency", "mention_text": "We report the case of a 70-year-old hypertensive man with a solitary kidney and chronic renal insufficiency who developed two episodes of transient anuria after losartan administration. He was hospitalized for a myocardial infarction with pulmonary edema, treated with high-dose diuretics. Due to severe systolic dysfunction losartan was prescribed. Surprisingly, the first dose of 50 mg of losartan resulted in a sudden anuria, which lasted eight hours despite high-dose furosemide and amine infusion. One week later, by mistake, losartan was prescribed again and after the second dose of 50 mg, the patient developed a second episode of transient anuria lasting 10 hours. During these two episodes, his blood pressure diminished but no severe hypotension was noted. Ultimately, an arteriography showed a 70-80% renal artery stenosis. In this patient, renal artery stenosis combined with heart failure and diuretic therapy certainly resulted in a strong activation of the renin-angiotensin system (RAS). Under such conditions, angiotensin II receptor blockade by losartan probably induced a critical fall in glomerular filtration pressure. This case report highlights the fact that the angiotensin II receptor antagonist losartan can cause serious unexpected complications in patients with renovascular disease and should be used with extreme caution in this setting.", "entity": "Renal Insufficiency, Chronic", "aliases": "Chronic Kidney Disease Diseases Insufficiencies Insufficiency Renal", "definition": "Conditions in which the KIDNEYS perform below the normal level for more than three months. Chronic kidney insufficiency is classified by five stages according to the decline in GLOMERULAR FILTRATION RATE and the degree of kidney damage (as measured by the level of PROTEINURIA). The most severe form is the end-stage renal disease (CHRONIC KIDNEY FAILURE). (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002)\n    ", "id": "MESH:D051436"}
{"mention": "anuria", "mention_text": "We report the case of a 70-year-old hypertensive man with a solitary kidney and chronic renal insufficiency who developed two episodes of transient anuria after losartan administration. He was hospitalized for a myocardial infarction with pulmonary edema, treated with high-dose diuretics. Due to severe systolic dysfunction losartan was prescribed. Surprisingly, the first dose of 50 mg of losartan resulted in a sudden anuria, which lasted eight hours despite high-dose furosemide and amine infusion. One week later, by mistake, losartan was prescribed again and after the second dose of 50 mg, the patient developed a second episode of transient anuria lasting 10 hours. During these two episodes, his blood pressure diminished but no severe hypotension was noted. Ultimately, an arteriography showed a 70-80% renal artery stenosis. In this patient, renal artery stenosis combined with heart failure and diuretic therapy certainly resulted in a strong activation of the renin-angiotensin system (RAS). Under such conditions, angiotensin II receptor blockade by losartan probably induced a critical fall in glomerular filtration pressure. This case report highlights the fact that the angiotensin II receptor antagonist losartan can cause serious unexpected complications in patients with renovascular disease and should be used with extreme caution in this setting.", "entity": "Anuria", "aliases": "Anuria Anurias", "definition": "Absence of urine formation. It is usually associated with complete bilateral ureteral (URETER) obstruction, complete lower urinary tract obstruction, or unilateral ureteral obstruction when a solitary kidney is present.\n    ", "id": "MESH:D001002"}
{"mention": "losartan", "mention_text": "We report the case of a 70-year-old hypertensive man with a solitary kidney and chronic renal insufficiency who developed two episodes of transient anuria after losartan administration. He was hospitalized for a myocardial infarction with pulmonary edema, treated with high-dose diuretics. Due to severe systolic dysfunction losartan was prescribed. Surprisingly, the first dose of 50 mg of losartan resulted in a sudden anuria, which lasted eight hours despite high-dose furosemide and amine infusion. One week later, by mistake, losartan was prescribed again and after the second dose of 50 mg, the patient developed a second episode of transient anuria lasting 10 hours. During these two episodes, his blood pressure diminished but no severe hypotension was noted. Ultimately, an arteriography showed a 70-80% renal artery stenosis. In this patient, renal artery stenosis combined with heart failure and diuretic therapy certainly resulted in a strong activation of the renin-angiotensin system (RAS). Under such conditions, angiotensin II receptor blockade by losartan probably induced a critical fall in glomerular filtration pressure. This case report highlights the fact that the angiotensin II receptor antagonist losartan can cause serious unexpected complications in patients with renovascular disease and should be used with extreme caution in this setting.", "entity": "Losartan", "aliases": "2-Butyl-4-chloro-1-((2'-(1H-etrazol-5-yl) (1,1'-biphenyl)-4-yl)methyl)-1H-imidazole-5-methanol Cozaar DuP 753 DuP-753 DuP753 Losartan Monopotassium Salt Potassium MK 954 MK-954 MK954", "definition": "An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.\n    ", "id": "MESH:D019808"}
{"mention": "myocardial infarction", "mention_text": "We report the case of a 70-year-old hypertensive man with a solitary kidney and chronic renal insufficiency who developed two episodes of transient anuria after losartan administration. He was hospitalized for a myocardial infarction with pulmonary edema, treated with high-dose diuretics. Due to severe systolic dysfunction losartan was prescribed. Surprisingly, the first dose of 50 mg of losartan resulted in a sudden anuria, which lasted eight hours despite high-dose furosemide and amine infusion. One week later, by mistake, losartan was prescribed again and after the second dose of 50 mg, the patient developed a second episode of transient anuria lasting 10 hours. During these two episodes, his blood pressure diminished but no severe hypotension was noted. Ultimately, an arteriography showed a 70-80% renal artery stenosis. In this patient, renal artery stenosis combined with heart failure and diuretic therapy certainly resulted in a strong activation of the renin-angiotensin system (RAS). Under such conditions, angiotensin II receptor blockade by losartan probably induced a critical fall in glomerular filtration pressure. This case report highlights the fact that the angiotensin II receptor antagonist losartan can cause serious unexpected complications in patients with renovascular disease and should be used with extreme caution in this setting.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "pulmonary edema", "mention_text": "We report the case of a 70-year-old hypertensive man with a solitary kidney and chronic renal insufficiency who developed two episodes of transient anuria after losartan administration. He was hospitalized for a myocardial infarction with pulmonary edema, treated with high-dose diuretics. Due to severe systolic dysfunction losartan was prescribed. Surprisingly, the first dose of 50 mg of losartan resulted in a sudden anuria, which lasted eight hours despite high-dose furosemide and amine infusion. One week later, by mistake, losartan was prescribed again and after the second dose of 50 mg, the patient developed a second episode of transient anuria lasting 10 hours. During these two episodes, his blood pressure diminished but no severe hypotension was noted. Ultimately, an arteriography showed a 70-80% renal artery stenosis. In this patient, renal artery stenosis combined with heart failure and diuretic therapy certainly resulted in a strong activation of the renin-angiotensin system (RAS). Under such conditions, angiotensin II receptor blockade by losartan probably induced a critical fall in glomerular filtration pressure. This case report highlights the fact that the angiotensin II receptor antagonist losartan can cause serious unexpected complications in patients with renovascular disease and should be used with extreme caution in this setting.", "entity": "Pulmonary Edema", "aliases": "Edema Pulmonary Edemas Lung Wet Lungs", "definition": "Excessive accumulation of extravascular fluid in the lung, an indication of a serious underlying disease or disorder. Pulmonary edema prevents efficient PULMONARY GAS EXCHANGE in the PULMONARY ALVEOLI, and can be life-threatening.\n    ", "id": "MESH:D011654"}
{"mention": "systolic dysfunction", "mention_text": "We report the case of a 70-year-old hypertensive man with a solitary kidney and chronic renal insufficiency who developed two episodes of transient anuria after losartan administration. He was hospitalized for a myocardial infarction with pulmonary edema, treated with high-dose diuretics. Due to severe systolic dysfunction losartan was prescribed. Surprisingly, the first dose of 50 mg of losartan resulted in a sudden anuria, which lasted eight hours despite high-dose furosemide and amine infusion. One week later, by mistake, losartan was prescribed again and after the second dose of 50 mg, the patient developed a second episode of transient anuria lasting 10 hours. During these two episodes, his blood pressure diminished but no severe hypotension was noted. Ultimately, an arteriography showed a 70-80% renal artery stenosis. In this patient, renal artery stenosis combined with heart failure and diuretic therapy certainly resulted in a strong activation of the renin-angiotensin system (RAS). Under such conditions, angiotensin II receptor blockade by losartan probably induced a critical fall in glomerular filtration pressure. This case report highlights the fact that the angiotensin II receptor antagonist losartan can cause serious unexpected complications in patients with renovascular disease and should be used with extreme caution in this setting.", "entity": "Heart Diseases", "aliases": "Cardiac Disease Diseases Heart", "definition": "Pathological conditions involving the HEART including its structural and functional abnormalities.\n    ", "id": "MESH:D006331"}
{"mention": "furosemide", "mention_text": "We report the case of a 70-year-old hypertensive man with a solitary kidney and chronic renal insufficiency who developed two episodes of transient anuria after losartan administration. He was hospitalized for a myocardial infarction with pulmonary edema, treated with high-dose diuretics. Due to severe systolic dysfunction losartan was prescribed. Surprisingly, the first dose of 50 mg of losartan resulted in a sudden anuria, which lasted eight hours despite high-dose furosemide and amine infusion. One week later, by mistake, losartan was prescribed again and after the second dose of 50 mg, the patient developed a second episode of transient anuria lasting 10 hours. During these two episodes, his blood pressure diminished but no severe hypotension was noted. Ultimately, an arteriography showed a 70-80% renal artery stenosis. In this patient, renal artery stenosis combined with heart failure and diuretic therapy certainly resulted in a strong activation of the renin-angiotensin system (RAS). Under such conditions, angiotensin II receptor blockade by losartan probably induced a critical fall in glomerular filtration pressure. This case report highlights the fact that the angiotensin II receptor antagonist losartan can cause serious unexpected complications in patients with renovascular disease and should be used with extreme caution in this setting.", "entity": "Furosemide", "aliases": "Errolon Frusemid Frusemide Furanthril Furantral Furosemide Monohydrochloride Monosodium Salt Fursemide Fusid Lasix Salix (brand of furosemide)", "definition": "A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for EDEMA and chronic RENAL INSUFFICIENCY.\n    ", "id": "MESH:D005665"}
{"mention": "amine", "mention_text": "We report the case of a 70-year-old hypertensive man with a solitary kidney and chronic renal insufficiency who developed two episodes of transient anuria after losartan administration. He was hospitalized for a myocardial infarction with pulmonary edema, treated with high-dose diuretics. Due to severe systolic dysfunction losartan was prescribed. Surprisingly, the first dose of 50 mg of losartan resulted in a sudden anuria, which lasted eight hours despite high-dose furosemide and amine infusion. One week later, by mistake, losartan was prescribed again and after the second dose of 50 mg, the patient developed a second episode of transient anuria lasting 10 hours. During these two episodes, his blood pressure diminished but no severe hypotension was noted. Ultimately, an arteriography showed a 70-80% renal artery stenosis. In this patient, renal artery stenosis combined with heart failure and diuretic therapy certainly resulted in a strong activation of the renin-angiotensin system (RAS). Under such conditions, angiotensin II receptor blockade by losartan probably induced a critical fall in glomerular filtration pressure. This case report highlights the fact that the angiotensin II receptor antagonist losartan can cause serious unexpected complications in patients with renovascular disease and should be used with extreme caution in this setting.", "entity": "Amines", "aliases": "Amines", "definition": "A group of compounds derived from ammonia by substituting organic radicals for the hydrogens. (From Grant & Hackh's Chemical Dictionary, 5th ed)\n    ", "id": "MESH:D000588"}
{"mention": "hypotension", "mention_text": "We report the case of a 70-year-old hypertensive man with a solitary kidney and chronic renal insufficiency who developed two episodes of transient anuria after losartan administration. He was hospitalized for a myocardial infarction with pulmonary edema, treated with high-dose diuretics. Due to severe systolic dysfunction losartan was prescribed. Surprisingly, the first dose of 50 mg of losartan resulted in a sudden anuria, which lasted eight hours despite high-dose furosemide and amine infusion. One week later, by mistake, losartan was prescribed again and after the second dose of 50 mg, the patient developed a second episode of transient anuria lasting 10 hours. During these two episodes, his blood pressure diminished but no severe hypotension was noted. Ultimately, an arteriography showed a 70-80% renal artery stenosis. In this patient, renal artery stenosis combined with heart failure and diuretic therapy certainly resulted in a strong activation of the renin-angiotensin system (RAS). Under such conditions, angiotensin II receptor blockade by losartan probably induced a critical fall in glomerular filtration pressure. This case report highlights the fact that the angiotensin II receptor antagonist losartan can cause serious unexpected complications in patients with renovascular disease and should be used with extreme caution in this setting.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "renal artery stenosis", "mention_text": "We report the case of a 70-year-old hypertensive man with a solitary kidney and chronic renal insufficiency who developed two episodes of transient anuria after losartan administration. He was hospitalized for a myocardial infarction with pulmonary edema, treated with high-dose diuretics. Due to severe systolic dysfunction losartan was prescribed. Surprisingly, the first dose of 50 mg of losartan resulted in a sudden anuria, which lasted eight hours despite high-dose furosemide and amine infusion. One week later, by mistake, losartan was prescribed again and after the second dose of 50 mg, the patient developed a second episode of transient anuria lasting 10 hours. During these two episodes, his blood pressure diminished but no severe hypotension was noted. Ultimately, an arteriography showed a 70-80% renal artery stenosis. In this patient, renal artery stenosis combined with heart failure and diuretic therapy certainly resulted in a strong activation of the renin-angiotensin system (RAS). Under such conditions, angiotensin II receptor blockade by losartan probably induced a critical fall in glomerular filtration pressure. This case report highlights the fact that the angiotensin II receptor antagonist losartan can cause serious unexpected complications in patients with renovascular disease and should be used with extreme caution in this setting.", "entity": "Renal Artery Obstruction", "aliases": "Obstruction Renal Artery Obstructions Stenoses Stenosis", "definition": "Narrowing or occlusion of the RENAL ARTERY or arteries. It is due usually to ATHEROSCLEROSIS; FIBROMUSCULAR DYSPLASIA; THROMBOSIS; EMBOLISM, or external pressure. The reduced renal perfusion can lead to renovascular hypertension (HYPERTENSION, RENOVASCULAR).\n    ", "id": "MESH:D012078"}
{"mention": "heart failure", "mention_text": "We report the case of a 70-year-old hypertensive man with a solitary kidney and chronic renal insufficiency who developed two episodes of transient anuria after losartan administration. He was hospitalized for a myocardial infarction with pulmonary edema, treated with high-dose diuretics. Due to severe systolic dysfunction losartan was prescribed. Surprisingly, the first dose of 50 mg of losartan resulted in a sudden anuria, which lasted eight hours despite high-dose furosemide and amine infusion. One week later, by mistake, losartan was prescribed again and after the second dose of 50 mg, the patient developed a second episode of transient anuria lasting 10 hours. During these two episodes, his blood pressure diminished but no severe hypotension was noted. Ultimately, an arteriography showed a 70-80% renal artery stenosis. In this patient, renal artery stenosis combined with heart failure and diuretic therapy certainly resulted in a strong activation of the renin-angiotensin system (RAS). Under such conditions, angiotensin II receptor blockade by losartan probably induced a critical fall in glomerular filtration pressure. This case report highlights the fact that the angiotensin II receptor antagonist losartan can cause serious unexpected complications in patients with renovascular disease and should be used with extreme caution in this setting.", "entity": "Heart Failure", "aliases": "Cardiac Failure Congestive Heart Decompensation Left Sided Left-Sided Right Right-Sided Myocardial", "definition": "A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.\n    ", "id": "MESH:D006333"}
{"mention": "angiotensin", "mention_text": "We report the case of a 70-year-old hypertensive man with a solitary kidney and chronic renal insufficiency who developed two episodes of transient anuria after losartan administration. He was hospitalized for a myocardial infarction with pulmonary edema, treated with high-dose diuretics. Due to severe systolic dysfunction losartan was prescribed. Surprisingly, the first dose of 50 mg of losartan resulted in a sudden anuria, which lasted eight hours despite high-dose furosemide and amine infusion. One week later, by mistake, losartan was prescribed again and after the second dose of 50 mg, the patient developed a second episode of transient anuria lasting 10 hours. During these two episodes, his blood pressure diminished but no severe hypotension was noted. Ultimately, an arteriography showed a 70-80% renal artery stenosis. In this patient, renal artery stenosis combined with heart failure and diuretic therapy certainly resulted in a strong activation of the renin-angiotensin system (RAS). Under such conditions, angiotensin II receptor blockade by losartan probably induced a critical fall in glomerular filtration pressure. This case report highlights the fact that the angiotensin II receptor antagonist losartan can cause serious unexpected complications in patients with renovascular disease and should be used with extreme caution in this setting.", "entity": "Angiotensins", "aliases": "Angiotensin Angiotensins", "definition": "Oligopeptides which are important in the regulation of blood pressure (VASOCONSTRICTION) and fluid homeostasis via the RENIN-ANGIOTENSIN SYSTEM. These include angiotensins derived naturally from precursor ANGIOTENSINOGEN, and those synthesized.\n    ", "id": "MESH:D000809"}
{"mention": "angiotensin II", "mention_text": "We report the case of a 70-year-old hypertensive man with a solitary kidney and chronic renal insufficiency who developed two episodes of transient anuria after losartan administration. He was hospitalized for a myocardial infarction with pulmonary edema, treated with high-dose diuretics. Due to severe systolic dysfunction losartan was prescribed. Surprisingly, the first dose of 50 mg of losartan resulted in a sudden anuria, which lasted eight hours despite high-dose furosemide and amine infusion. One week later, by mistake, losartan was prescribed again and after the second dose of 50 mg, the patient developed a second episode of transient anuria lasting 10 hours. During these two episodes, his blood pressure diminished but no severe hypotension was noted. Ultimately, an arteriography showed a 70-80% renal artery stenosis. In this patient, renal artery stenosis combined with heart failure and diuretic therapy certainly resulted in a strong activation of the renin-angiotensin system (RAS). Under such conditions, angiotensin II receptor blockade by losartan probably induced a critical fall in glomerular filtration pressure. This case report highlights the fact that the angiotensin II receptor antagonist losartan can cause serious unexpected complications in patients with renovascular disease and should be used with extreme caution in this setting.", "entity": "Angiotensin II", "aliases": "5 L Isoleucine Angiotensin II 5-L-Isoleucine ANG-(1-8)Octapeptide Ile(5)- Isoleucine(5)- Val(5)- Valine(5)- Angiotensin-(1-8) Octapeptide Isoleucine(5)-Angiotensin Isoleucyl(5)-Angiotensin Valyl(5)-Angiotensin", "definition": "An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.\n    ", "id": "MESH:D000804"}
{"mention": "renovascular disease", "mention_text": "We report the case of a 70-year-old hypertensive man with a solitary kidney and chronic renal insufficiency who developed two episodes of transient anuria after losartan administration. He was hospitalized for a myocardial infarction with pulmonary edema, treated with high-dose diuretics. Due to severe systolic dysfunction losartan was prescribed. Surprisingly, the first dose of 50 mg of losartan resulted in a sudden anuria, which lasted eight hours despite high-dose furosemide and amine infusion. One week later, by mistake, losartan was prescribed again and after the second dose of 50 mg, the patient developed a second episode of transient anuria lasting 10 hours. During these two episodes, his blood pressure diminished but no severe hypotension was noted. Ultimately, an arteriography showed a 70-80% renal artery stenosis. In this patient, renal artery stenosis combined with heart failure and diuretic therapy certainly resulted in a strong activation of the renin-angiotensin system (RAS). Under such conditions, angiotensin II receptor blockade by losartan probably induced a critical fall in glomerular filtration pressure. This case report highlights the fact that the angiotensin II receptor antagonist losartan can cause serious unexpected complications in patients with renovascular disease and should be used with extreme caution in this setting.", "entity": "Vascular Diseases", "aliases": "Disease Vascular Diseases", "definition": "Pathological processes involving any of the BLOOD VESSELS in the cardiac or peripheral circulation. They include diseases of ARTERIES; VEINS; and rest of the vasculature system in the body.\n    ", "id": "MESH:D014652"}
{"mention": "necrotic", "mention_text": "In vivo protection of dna damage associated apoptotic and necrotic cell deaths during acetaminophen-induced nephrotoxicity, amiodarone-induced lung toxicity and doxorubicin-induced cardiotoxicity by a novel IH636 grape seed proanthocyanidin extract.", "entity": "Necrosis", "aliases": "Necroses Necrosis", "definition": "The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. Distinguish it from APOPTOSIS which is a normal, regulated cellular process.\n    ", "id": "MESH:D009336"}
{"mention": "acetaminophen", "mention_text": "In vivo protection of dna damage associated apoptotic and necrotic cell deaths during acetaminophen-induced nephrotoxicity, amiodarone-induced lung toxicity and doxorubicin-induced cardiotoxicity by a novel IH636 grape seed proanthocyanidin extract.", "entity": "Acetaminophen", "aliases": "APAP Acamol Acephen Acetaco Acetamidophenol Acetaminophen Acetominophen Algotropyl Anacin 3 Anacin-3 Anacin3 Datril Hydroxyacetanilide N-(4-Hydroxyphenyl)acetanilide N-Acetyl-p-aminophenol Panadol Paracetamol Tylenol p-Acetamidophenol p-Hydroxyacetanilide", "definition": "Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.\n    ", "id": "MESH:D000082"}
{"mention": "nephrotoxicity", "mention_text": "In vivo protection of dna damage associated apoptotic and necrotic cell deaths during acetaminophen-induced nephrotoxicity, amiodarone-induced lung toxicity and doxorubicin-induced cardiotoxicity by a novel IH636 grape seed proanthocyanidin extract.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "amiodarone", "mention_text": "In vivo protection of dna damage associated apoptotic and necrotic cell deaths during acetaminophen-induced nephrotoxicity, amiodarone-induced lung toxicity and doxorubicin-induced cardiotoxicity by a novel IH636 grape seed proanthocyanidin extract.", "entity": "Amiodarone", "aliases": "ASTA Medica Brand of Amiodarone Hydrochloride Alphapharm Amiobeta Amiodarex Amiodarona Amiohexal Aratac Armstrong Berenguer Infale Betapharm Braxan Corbionax Cordarex Cordarone G Gam Hexal Kordaron L 3428 L-3428 L3428 Leurquin Ortacrone Pharma Investi Rytmarone SKF 33134 A 33134-A 33134A Sanofi Winthrop Tachydaron Trangorex Wyeth", "definition": "An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.\n    ", "id": "MESH:D000638"}
{"mention": "lung toxicity", "mention_text": "In vivo protection of dna damage associated apoptotic and necrotic cell deaths during acetaminophen-induced nephrotoxicity, amiodarone-induced lung toxicity and doxorubicin-induced cardiotoxicity by a novel IH636 grape seed proanthocyanidin extract.", "entity": "Lung Diseases", "aliases": "Disease Lung Pulmonary Diseases", "definition": "Pathological processes involving any part of the LUNG.\n    ", "id": "MESH:D008171"}
{"mention": "doxorubicin", "mention_text": "In vivo protection of dna damage associated apoptotic and necrotic cell deaths during acetaminophen-induced nephrotoxicity, amiodarone-induced lung toxicity and doxorubicin-induced cardiotoxicity by a novel IH636 grape seed proanthocyanidin extract.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "cardiotoxicity", "mention_text": "In vivo protection of dna damage associated apoptotic and necrotic cell deaths during acetaminophen-induced nephrotoxicity, amiodarone-induced lung toxicity and doxorubicin-induced cardiotoxicity by a novel IH636 grape seed proanthocyanidin extract.", "entity": "Cardiotoxicity", "aliases": "Cardiac Toxicities Toxicity Cardiotoxicities Cardiotoxicity", "definition": "Damage to the heart or its function secondary to exposure to toxic substances such as drugs used in CHEMOTHERAPY; IMMUNOTHERAPY; or RADIATION.\n    ", "id": "MESH:D066126"}
{"mention": "IH636 grape seed proanthocyanidin extract", "mention_text": "In vivo protection of dna damage associated apoptotic and necrotic cell deaths during acetaminophen-induced nephrotoxicity, amiodarone-induced lung toxicity and doxorubicin-induced cardiotoxicity by a novel IH636 grape seed proanthocyanidin extract.", "entity": "Grape Seed Proanthocyanidins", "aliases": "Grape Seed Proanthocyanidins IH636 ActiVin GSPE grape seed proanthocyanidin extract", "definition": "", "id": "MESH:C511402"}
{"mention": "Grape seed extract", "mention_text": "Grape seed extract, primarily a mixture of proanthocyanidins, has been shown to modulate a wide-range of biological, pharmacological and toxicological effects which are mainly cytoprotective. This study assessed the ability of IH636 grape seed proanthocyanidin extract (GSPE) to prevent acetaminophen (AAP)-induced nephrotoxicity, amiodarone (AMI)-induced lung toxicity, and doxorubicin (DOX)-induced cardiotoxicity in mice. Experimental design consisted of four groups: control (vehicle alone), GSPE alone, drug alone and GSPE+drug. For the cytoprotection study, animals were orally gavaged 100 mg/Kg GSPE for 7-10 days followed by i.p. injections of organ specific three drugs (AAP: 500 mg/Kg for 24 h; AMI: 50 mg/Kg/day for four days; DOX: 20 mg/Kg for 48 h). Parameters of study included analysis of serum chemistry (ALT, BUN and CPK), and orderly fragmentation of genomic DNA (both endonuclease-dependent and independent) in addition to microscopic evaluation of damage and/or protection in corresponding PAS stained tissues. Results indicate that GSPE preexposure prior to AAP, AMI and DOX, provided near complete protection in terms of serum chemistry changes (ALT, BUN and CPK), and significantly reduced DNA fragmentation. Histopathological examination of kidney, heart and lung sections revealed moderate to massive tissue damage with a variety of morphological aberrations by all the three drugs in the absence of GSPE preexposure than in its presence. GSPE+drug exposed tissues exhibited minor residual damage or near total recovery. Additionally, histopathological alterations mirrored both serum chemistry changes and the pattern of DNA fragmentation. Interestingly, all the drugs, such as, AAP, AMI and DOX induced apoptotic death in addition to necrosis in the respective organs which was very effectively blocked by GSPE. Since AAP, AMI and DOX undergo biotransformation and are known to produce damaging radicals in vivo, the protection by GSPE may be linked to both inhibition of metabolism and/or detoxification of cytotoxic radicals. In addition, its' presumed contribution to DNA repair may be another important attribute, which played a role in the chemoprevention process. Additionally, this may have been the first report on AMI-induced apoptotic death in the lung tissue. Taken together, these events undoubtedly establish GSPE's abundant bioavailability, and the power to defend multiple target organs from toxic assaults induced by structurally diverse and functionally different entities in vivo.", "entity": "Grape Seed Proanthocyanidins", "aliases": "Grape Seed Proanthocyanidins IH636 ActiVin GSPE grape seed proanthocyanidin extract", "definition": "", "id": "MESH:C511402"}
{"mention": "proanthocyanidins", "mention_text": "Grape seed extract, primarily a mixture of proanthocyanidins, has been shown to modulate a wide-range of biological, pharmacological and toxicological effects which are mainly cytoprotective. This study assessed the ability of IH636 grape seed proanthocyanidin extract (GSPE) to prevent acetaminophen (AAP)-induced nephrotoxicity, amiodarone (AMI)-induced lung toxicity, and doxorubicin (DOX)-induced cardiotoxicity in mice. Experimental design consisted of four groups: control (vehicle alone), GSPE alone, drug alone and GSPE+drug. For the cytoprotection study, animals were orally gavaged 100 mg/Kg GSPE for 7-10 days followed by i.p. injections of organ specific three drugs (AAP: 500 mg/Kg for 24 h; AMI: 50 mg/Kg/day for four days; DOX: 20 mg/Kg for 48 h). Parameters of study included analysis of serum chemistry (ALT, BUN and CPK), and orderly fragmentation of genomic DNA (both endonuclease-dependent and independent) in addition to microscopic evaluation of damage and/or protection in corresponding PAS stained tissues. Results indicate that GSPE preexposure prior to AAP, AMI and DOX, provided near complete protection in terms of serum chemistry changes (ALT, BUN and CPK), and significantly reduced DNA fragmentation. Histopathological examination of kidney, heart and lung sections revealed moderate to massive tissue damage with a variety of morphological aberrations by all the three drugs in the absence of GSPE preexposure than in its presence. GSPE+drug exposed tissues exhibited minor residual damage or near total recovery. Additionally, histopathological alterations mirrored both serum chemistry changes and the pattern of DNA fragmentation. Interestingly, all the drugs, such as, AAP, AMI and DOX induced apoptotic death in addition to necrosis in the respective organs which was very effectively blocked by GSPE. Since AAP, AMI and DOX undergo biotransformation and are known to produce damaging radicals in vivo, the protection by GSPE may be linked to both inhibition of metabolism and/or detoxification of cytotoxic radicals. In addition, its' presumed contribution to DNA repair may be another important attribute, which played a role in the chemoprevention process. Additionally, this may have been the first report on AMI-induced apoptotic death in the lung tissue. Taken together, these events undoubtedly establish GSPE's abundant bioavailability, and the power to defend multiple target organs from toxic assaults induced by structurally diverse and functionally different entities in vivo.", "entity": "Proanthocyanidins", "aliases": "Anthocyanidin Polymers Condensed Tannin Tannins Proanthocyanidins Procyanidins", "definition": "Dimers and oligomers of flavan-3-ol units (CATECHIN analogs) linked mainly through C4 to C8 bonds to leucoanthocyanidins. They are structurally similar to ANTHOCYANINS but are the result of a different fork in biosynthetic pathways.\n    ", "id": "MESH:D044945"}
{"mention": "IH636 grape seed proanthocyanidin extract", "mention_text": "Grape seed extract, primarily a mixture of proanthocyanidins, has been shown to modulate a wide-range of biological, pharmacological and toxicological effects which are mainly cytoprotective. This study assessed the ability of IH636 grape seed proanthocyanidin extract (GSPE) to prevent acetaminophen (AAP)-induced nephrotoxicity, amiodarone (AMI)-induced lung toxicity, and doxorubicin (DOX)-induced cardiotoxicity in mice. Experimental design consisted of four groups: control (vehicle alone), GSPE alone, drug alone and GSPE+drug. For the cytoprotection study, animals were orally gavaged 100 mg/Kg GSPE for 7-10 days followed by i.p. injections of organ specific three drugs (AAP: 500 mg/Kg for 24 h; AMI: 50 mg/Kg/day for four days; DOX: 20 mg/Kg for 48 h). Parameters of study included analysis of serum chemistry (ALT, BUN and CPK), and orderly fragmentation of genomic DNA (both endonuclease-dependent and independent) in addition to microscopic evaluation of damage and/or protection in corresponding PAS stained tissues. Results indicate that GSPE preexposure prior to AAP, AMI and DOX, provided near complete protection in terms of serum chemistry changes (ALT, BUN and CPK), and significantly reduced DNA fragmentation. Histopathological examination of kidney, heart and lung sections revealed moderate to massive tissue damage with a variety of morphological aberrations by all the three drugs in the absence of GSPE preexposure than in its presence. GSPE+drug exposed tissues exhibited minor residual damage or near total recovery. Additionally, histopathological alterations mirrored both serum chemistry changes and the pattern of DNA fragmentation. Interestingly, all the drugs, such as, AAP, AMI and DOX induced apoptotic death in addition to necrosis in the respective organs which was very effectively blocked by GSPE. Since AAP, AMI and DOX undergo biotransformation and are known to produce damaging radicals in vivo, the protection by GSPE may be linked to both inhibition of metabolism and/or detoxification of cytotoxic radicals. In addition, its' presumed contribution to DNA repair may be another important attribute, which played a role in the chemoprevention process. Additionally, this may have been the first report on AMI-induced apoptotic death in the lung tissue. Taken together, these events undoubtedly establish GSPE's abundant bioavailability, and the power to defend multiple target organs from toxic assaults induced by structurally diverse and functionally different entities in vivo.", "entity": "Grape Seed Proanthocyanidins", "aliases": "Grape Seed Proanthocyanidins IH636 ActiVin GSPE grape seed proanthocyanidin extract", "definition": "", "id": "MESH:C511402"}
{"mention": "GSPE", "mention_text": "Grape seed extract, primarily a mixture of proanthocyanidins, has been shown to modulate a wide-range of biological, pharmacological and toxicological effects which are mainly cytoprotective. This study assessed the ability of IH636 grape seed proanthocyanidin extract (GSPE) to prevent acetaminophen (AAP)-induced nephrotoxicity, amiodarone (AMI)-induced lung toxicity, and doxorubicin (DOX)-induced cardiotoxicity in mice. Experimental design consisted of four groups: control (vehicle alone), GSPE alone, drug alone and GSPE+drug. For the cytoprotection study, animals were orally gavaged 100 mg/Kg GSPE for 7-10 days followed by i.p. injections of organ specific three drugs (AAP: 500 mg/Kg for 24 h; AMI: 50 mg/Kg/day for four days; DOX: 20 mg/Kg for 48 h). Parameters of study included analysis of serum chemistry (ALT, BUN and CPK), and orderly fragmentation of genomic DNA (both endonuclease-dependent and independent) in addition to microscopic evaluation of damage and/or protection in corresponding PAS stained tissues. Results indicate that GSPE preexposure prior to AAP, AMI and DOX, provided near complete protection in terms of serum chemistry changes (ALT, BUN and CPK), and significantly reduced DNA fragmentation. Histopathological examination of kidney, heart and lung sections revealed moderate to massive tissue damage with a variety of morphological aberrations by all the three drugs in the absence of GSPE preexposure than in its presence. GSPE+drug exposed tissues exhibited minor residual damage or near total recovery. Additionally, histopathological alterations mirrored both serum chemistry changes and the pattern of DNA fragmentation. Interestingly, all the drugs, such as, AAP, AMI and DOX induced apoptotic death in addition to necrosis in the respective organs which was very effectively blocked by GSPE. Since AAP, AMI and DOX undergo biotransformation and are known to produce damaging radicals in vivo, the protection by GSPE may be linked to both inhibition of metabolism and/or detoxification of cytotoxic radicals. In addition, its' presumed contribution to DNA repair may be another important attribute, which played a role in the chemoprevention process. Additionally, this may have been the first report on AMI-induced apoptotic death in the lung tissue. Taken together, these events undoubtedly establish GSPE's abundant bioavailability, and the power to defend multiple target organs from toxic assaults induced by structurally diverse and functionally different entities in vivo.", "entity": "Grape Seed Proanthocyanidins", "aliases": "Grape Seed Proanthocyanidins IH636 ActiVin GSPE grape seed proanthocyanidin extract", "definition": "", "id": "MESH:C511402"}
{"mention": "acetaminophen", "mention_text": "Grape seed extract, primarily a mixture of proanthocyanidins, has been shown to modulate a wide-range of biological, pharmacological and toxicological effects which are mainly cytoprotective. This study assessed the ability of IH636 grape seed proanthocyanidin extract (GSPE) to prevent acetaminophen (AAP)-induced nephrotoxicity, amiodarone (AMI)-induced lung toxicity, and doxorubicin (DOX)-induced cardiotoxicity in mice. Experimental design consisted of four groups: control (vehicle alone), GSPE alone, drug alone and GSPE+drug. For the cytoprotection study, animals were orally gavaged 100 mg/Kg GSPE for 7-10 days followed by i.p. injections of organ specific three drugs (AAP: 500 mg/Kg for 24 h; AMI: 50 mg/Kg/day for four days; DOX: 20 mg/Kg for 48 h). Parameters of study included analysis of serum chemistry (ALT, BUN and CPK), and orderly fragmentation of genomic DNA (both endonuclease-dependent and independent) in addition to microscopic evaluation of damage and/or protection in corresponding PAS stained tissues. Results indicate that GSPE preexposure prior to AAP, AMI and DOX, provided near complete protection in terms of serum chemistry changes (ALT, BUN and CPK), and significantly reduced DNA fragmentation. Histopathological examination of kidney, heart and lung sections revealed moderate to massive tissue damage with a variety of morphological aberrations by all the three drugs in the absence of GSPE preexposure than in its presence. GSPE+drug exposed tissues exhibited minor residual damage or near total recovery. Additionally, histopathological alterations mirrored both serum chemistry changes and the pattern of DNA fragmentation. Interestingly, all the drugs, such as, AAP, AMI and DOX induced apoptotic death in addition to necrosis in the respective organs which was very effectively blocked by GSPE. Since AAP, AMI and DOX undergo biotransformation and are known to produce damaging radicals in vivo, the protection by GSPE may be linked to both inhibition of metabolism and/or detoxification of cytotoxic radicals. In addition, its' presumed contribution to DNA repair may be another important attribute, which played a role in the chemoprevention process. Additionally, this may have been the first report on AMI-induced apoptotic death in the lung tissue. Taken together, these events undoubtedly establish GSPE's abundant bioavailability, and the power to defend multiple target organs from toxic assaults induced by structurally diverse and functionally different entities in vivo.", "entity": "Acetaminophen", "aliases": "APAP Acamol Acephen Acetaco Acetamidophenol Acetaminophen Acetominophen Algotropyl Anacin 3 Anacin-3 Anacin3 Datril Hydroxyacetanilide N-(4-Hydroxyphenyl)acetanilide N-Acetyl-p-aminophenol Panadol Paracetamol Tylenol p-Acetamidophenol p-Hydroxyacetanilide", "definition": "Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.\n    ", "id": "MESH:D000082"}
{"mention": "AAP", "mention_text": "Grape seed extract, primarily a mixture of proanthocyanidins, has been shown to modulate a wide-range of biological, pharmacological and toxicological effects which are mainly cytoprotective. This study assessed the ability of IH636 grape seed proanthocyanidin extract (GSPE) to prevent acetaminophen (AAP)-induced nephrotoxicity, amiodarone (AMI)-induced lung toxicity, and doxorubicin (DOX)-induced cardiotoxicity in mice. Experimental design consisted of four groups: control (vehicle alone), GSPE alone, drug alone and GSPE+drug. For the cytoprotection study, animals were orally gavaged 100 mg/Kg GSPE for 7-10 days followed by i.p. injections of organ specific three drugs (AAP: 500 mg/Kg for 24 h; AMI: 50 mg/Kg/day for four days; DOX: 20 mg/Kg for 48 h). Parameters of study included analysis of serum chemistry (ALT, BUN and CPK), and orderly fragmentation of genomic DNA (both endonuclease-dependent and independent) in addition to microscopic evaluation of damage and/or protection in corresponding PAS stained tissues. Results indicate that GSPE preexposure prior to AAP, AMI and DOX, provided near complete protection in terms of serum chemistry changes (ALT, BUN and CPK), and significantly reduced DNA fragmentation. Histopathological examination of kidney, heart and lung sections revealed moderate to massive tissue damage with a variety of morphological aberrations by all the three drugs in the absence of GSPE preexposure than in its presence. GSPE+drug exposed tissues exhibited minor residual damage or near total recovery. Additionally, histopathological alterations mirrored both serum chemistry changes and the pattern of DNA fragmentation. Interestingly, all the drugs, such as, AAP, AMI and DOX induced apoptotic death in addition to necrosis in the respective organs which was very effectively blocked by GSPE. Since AAP, AMI and DOX undergo biotransformation and are known to produce damaging radicals in vivo, the protection by GSPE may be linked to both inhibition of metabolism and/or detoxification of cytotoxic radicals. In addition, its' presumed contribution to DNA repair may be another important attribute, which played a role in the chemoprevention process. Additionally, this may have been the first report on AMI-induced apoptotic death in the lung tissue. Taken together, these events undoubtedly establish GSPE's abundant bioavailability, and the power to defend multiple target organs from toxic assaults induced by structurally diverse and functionally different entities in vivo.", "entity": "Acetaminophen", "aliases": "APAP Acamol Acephen Acetaco Acetamidophenol Acetaminophen Acetominophen Algotropyl Anacin 3 Anacin-3 Anacin3 Datril Hydroxyacetanilide N-(4-Hydroxyphenyl)acetanilide N-Acetyl-p-aminophenol Panadol Paracetamol Tylenol p-Acetamidophenol p-Hydroxyacetanilide", "definition": "Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.\n    ", "id": "MESH:D000082"}
{"mention": "nephrotoxicity", "mention_text": "Grape seed extract, primarily a mixture of proanthocyanidins, has been shown to modulate a wide-range of biological, pharmacological and toxicological effects which are mainly cytoprotective. This study assessed the ability of IH636 grape seed proanthocyanidin extract (GSPE) to prevent acetaminophen (AAP)-induced nephrotoxicity, amiodarone (AMI)-induced lung toxicity, and doxorubicin (DOX)-induced cardiotoxicity in mice. Experimental design consisted of four groups: control (vehicle alone), GSPE alone, drug alone and GSPE+drug. For the cytoprotection study, animals were orally gavaged 100 mg/Kg GSPE for 7-10 days followed by i.p. injections of organ specific three drugs (AAP: 500 mg/Kg for 24 h; AMI: 50 mg/Kg/day for four days; DOX: 20 mg/Kg for 48 h). Parameters of study included analysis of serum chemistry (ALT, BUN and CPK), and orderly fragmentation of genomic DNA (both endonuclease-dependent and independent) in addition to microscopic evaluation of damage and/or protection in corresponding PAS stained tissues. Results indicate that GSPE preexposure prior to AAP, AMI and DOX, provided near complete protection in terms of serum chemistry changes (ALT, BUN and CPK), and significantly reduced DNA fragmentation. Histopathological examination of kidney, heart and lung sections revealed moderate to massive tissue damage with a variety of morphological aberrations by all the three drugs in the absence of GSPE preexposure than in its presence. GSPE+drug exposed tissues exhibited minor residual damage or near total recovery. Additionally, histopathological alterations mirrored both serum chemistry changes and the pattern of DNA fragmentation. Interestingly, all the drugs, such as, AAP, AMI and DOX induced apoptotic death in addition to necrosis in the respective organs which was very effectively blocked by GSPE. Since AAP, AMI and DOX undergo biotransformation and are known to produce damaging radicals in vivo, the protection by GSPE may be linked to both inhibition of metabolism and/or detoxification of cytotoxic radicals. In addition, its' presumed contribution to DNA repair may be another important attribute, which played a role in the chemoprevention process. Additionally, this may have been the first report on AMI-induced apoptotic death in the lung tissue. Taken together, these events undoubtedly establish GSPE's abundant bioavailability, and the power to defend multiple target organs from toxic assaults induced by structurally diverse and functionally different entities in vivo.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "amiodarone", "mention_text": "Grape seed extract, primarily a mixture of proanthocyanidins, has been shown to modulate a wide-range of biological, pharmacological and toxicological effects which are mainly cytoprotective. This study assessed the ability of IH636 grape seed proanthocyanidin extract (GSPE) to prevent acetaminophen (AAP)-induced nephrotoxicity, amiodarone (AMI)-induced lung toxicity, and doxorubicin (DOX)-induced cardiotoxicity in mice. Experimental design consisted of four groups: control (vehicle alone), GSPE alone, drug alone and GSPE+drug. For the cytoprotection study, animals were orally gavaged 100 mg/Kg GSPE for 7-10 days followed by i.p. injections of organ specific three drugs (AAP: 500 mg/Kg for 24 h; AMI: 50 mg/Kg/day for four days; DOX: 20 mg/Kg for 48 h). Parameters of study included analysis of serum chemistry (ALT, BUN and CPK), and orderly fragmentation of genomic DNA (both endonuclease-dependent and independent) in addition to microscopic evaluation of damage and/or protection in corresponding PAS stained tissues. Results indicate that GSPE preexposure prior to AAP, AMI and DOX, provided near complete protection in terms of serum chemistry changes (ALT, BUN and CPK), and significantly reduced DNA fragmentation. Histopathological examination of kidney, heart and lung sections revealed moderate to massive tissue damage with a variety of morphological aberrations by all the three drugs in the absence of GSPE preexposure than in its presence. GSPE+drug exposed tissues exhibited minor residual damage or near total recovery. Additionally, histopathological alterations mirrored both serum chemistry changes and the pattern of DNA fragmentation. Interestingly, all the drugs, such as, AAP, AMI and DOX induced apoptotic death in addition to necrosis in the respective organs which was very effectively blocked by GSPE. Since AAP, AMI and DOX undergo biotransformation and are known to produce damaging radicals in vivo, the protection by GSPE may be linked to both inhibition of metabolism and/or detoxification of cytotoxic radicals. In addition, its' presumed contribution to DNA repair may be another important attribute, which played a role in the chemoprevention process. Additionally, this may have been the first report on AMI-induced apoptotic death in the lung tissue. Taken together, these events undoubtedly establish GSPE's abundant bioavailability, and the power to defend multiple target organs from toxic assaults induced by structurally diverse and functionally different entities in vivo.", "entity": "Amiodarone", "aliases": "ASTA Medica Brand of Amiodarone Hydrochloride Alphapharm Amiobeta Amiodarex Amiodarona Amiohexal Aratac Armstrong Berenguer Infale Betapharm Braxan Corbionax Cordarex Cordarone G Gam Hexal Kordaron L 3428 L-3428 L3428 Leurquin Ortacrone Pharma Investi Rytmarone SKF 33134 A 33134-A 33134A Sanofi Winthrop Tachydaron Trangorex Wyeth", "definition": "An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.\n    ", "id": "MESH:D000638"}
{"mention": "AMI", "mention_text": "Grape seed extract, primarily a mixture of proanthocyanidins, has been shown to modulate a wide-range of biological, pharmacological and toxicological effects which are mainly cytoprotective. This study assessed the ability of IH636 grape seed proanthocyanidin extract (GSPE) to prevent acetaminophen (AAP)-induced nephrotoxicity, amiodarone (AMI)-induced lung toxicity, and doxorubicin (DOX)-induced cardiotoxicity in mice. Experimental design consisted of four groups: control (vehicle alone), GSPE alone, drug alone and GSPE+drug. For the cytoprotection study, animals were orally gavaged 100 mg/Kg GSPE for 7-10 days followed by i.p. injections of organ specific three drugs (AAP: 500 mg/Kg for 24 h; AMI: 50 mg/Kg/day for four days; DOX: 20 mg/Kg for 48 h). Parameters of study included analysis of serum chemistry (ALT, BUN and CPK), and orderly fragmentation of genomic DNA (both endonuclease-dependent and independent) in addition to microscopic evaluation of damage and/or protection in corresponding PAS stained tissues. Results indicate that GSPE preexposure prior to AAP, AMI and DOX, provided near complete protection in terms of serum chemistry changes (ALT, BUN and CPK), and significantly reduced DNA fragmentation. Histopathological examination of kidney, heart and lung sections revealed moderate to massive tissue damage with a variety of morphological aberrations by all the three drugs in the absence of GSPE preexposure than in its presence. GSPE+drug exposed tissues exhibited minor residual damage or near total recovery. Additionally, histopathological alterations mirrored both serum chemistry changes and the pattern of DNA fragmentation. Interestingly, all the drugs, such as, AAP, AMI and DOX induced apoptotic death in addition to necrosis in the respective organs which was very effectively blocked by GSPE. Since AAP, AMI and DOX undergo biotransformation and are known to produce damaging radicals in vivo, the protection by GSPE may be linked to both inhibition of metabolism and/or detoxification of cytotoxic radicals. In addition, its' presumed contribution to DNA repair may be another important attribute, which played a role in the chemoprevention process. Additionally, this may have been the first report on AMI-induced apoptotic death in the lung tissue. Taken together, these events undoubtedly establish GSPE's abundant bioavailability, and the power to defend multiple target organs from toxic assaults induced by structurally diverse and functionally different entities in vivo.", "entity": "Amiodarone", "aliases": "ASTA Medica Brand of Amiodarone Hydrochloride Alphapharm Amiobeta Amiodarex Amiodarona Amiohexal Aratac Armstrong Berenguer Infale Betapharm Braxan Corbionax Cordarex Cordarone G Gam Hexal Kordaron L 3428 L-3428 L3428 Leurquin Ortacrone Pharma Investi Rytmarone SKF 33134 A 33134-A 33134A Sanofi Winthrop Tachydaron Trangorex Wyeth", "definition": "An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.\n    ", "id": "MESH:D000638"}
{"mention": "lung toxicity", "mention_text": "Grape seed extract, primarily a mixture of proanthocyanidins, has been shown to modulate a wide-range of biological, pharmacological and toxicological effects which are mainly cytoprotective. This study assessed the ability of IH636 grape seed proanthocyanidin extract (GSPE) to prevent acetaminophen (AAP)-induced nephrotoxicity, amiodarone (AMI)-induced lung toxicity, and doxorubicin (DOX)-induced cardiotoxicity in mice. Experimental design consisted of four groups: control (vehicle alone), GSPE alone, drug alone and GSPE+drug. For the cytoprotection study, animals were orally gavaged 100 mg/Kg GSPE for 7-10 days followed by i.p. injections of organ specific three drugs (AAP: 500 mg/Kg for 24 h; AMI: 50 mg/Kg/day for four days; DOX: 20 mg/Kg for 48 h). Parameters of study included analysis of serum chemistry (ALT, BUN and CPK), and orderly fragmentation of genomic DNA (both endonuclease-dependent and independent) in addition to microscopic evaluation of damage and/or protection in corresponding PAS stained tissues. Results indicate that GSPE preexposure prior to AAP, AMI and DOX, provided near complete protection in terms of serum chemistry changes (ALT, BUN and CPK), and significantly reduced DNA fragmentation. Histopathological examination of kidney, heart and lung sections revealed moderate to massive tissue damage with a variety of morphological aberrations by all the three drugs in the absence of GSPE preexposure than in its presence. GSPE+drug exposed tissues exhibited minor residual damage or near total recovery. Additionally, histopathological alterations mirrored both serum chemistry changes and the pattern of DNA fragmentation. Interestingly, all the drugs, such as, AAP, AMI and DOX induced apoptotic death in addition to necrosis in the respective organs which was very effectively blocked by GSPE. Since AAP, AMI and DOX undergo biotransformation and are known to produce damaging radicals in vivo, the protection by GSPE may be linked to both inhibition of metabolism and/or detoxification of cytotoxic radicals. In addition, its' presumed contribution to DNA repair may be another important attribute, which played a role in the chemoprevention process. Additionally, this may have been the first report on AMI-induced apoptotic death in the lung tissue. Taken together, these events undoubtedly establish GSPE's abundant bioavailability, and the power to defend multiple target organs from toxic assaults induced by structurally diverse and functionally different entities in vivo.", "entity": "Lung Diseases", "aliases": "Disease Lung Pulmonary Diseases", "definition": "Pathological processes involving any part of the LUNG.\n    ", "id": "MESH:D008171"}
{"mention": "doxorubicin", "mention_text": "Grape seed extract, primarily a mixture of proanthocyanidins, has been shown to modulate a wide-range of biological, pharmacological and toxicological effects which are mainly cytoprotective. This study assessed the ability of IH636 grape seed proanthocyanidin extract (GSPE) to prevent acetaminophen (AAP)-induced nephrotoxicity, amiodarone (AMI)-induced lung toxicity, and doxorubicin (DOX)-induced cardiotoxicity in mice. Experimental design consisted of four groups: control (vehicle alone), GSPE alone, drug alone and GSPE+drug. For the cytoprotection study, animals were orally gavaged 100 mg/Kg GSPE for 7-10 days followed by i.p. injections of organ specific three drugs (AAP: 500 mg/Kg for 24 h; AMI: 50 mg/Kg/day for four days; DOX: 20 mg/Kg for 48 h). Parameters of study included analysis of serum chemistry (ALT, BUN and CPK), and orderly fragmentation of genomic DNA (both endonuclease-dependent and independent) in addition to microscopic evaluation of damage and/or protection in corresponding PAS stained tissues. Results indicate that GSPE preexposure prior to AAP, AMI and DOX, provided near complete protection in terms of serum chemistry changes (ALT, BUN and CPK), and significantly reduced DNA fragmentation. Histopathological examination of kidney, heart and lung sections revealed moderate to massive tissue damage with a variety of morphological aberrations by all the three drugs in the absence of GSPE preexposure than in its presence. GSPE+drug exposed tissues exhibited minor residual damage or near total recovery. Additionally, histopathological alterations mirrored both serum chemistry changes and the pattern of DNA fragmentation. Interestingly, all the drugs, such as, AAP, AMI and DOX induced apoptotic death in addition to necrosis in the respective organs which was very effectively blocked by GSPE. Since AAP, AMI and DOX undergo biotransformation and are known to produce damaging radicals in vivo, the protection by GSPE may be linked to both inhibition of metabolism and/or detoxification of cytotoxic radicals. In addition, its' presumed contribution to DNA repair may be another important attribute, which played a role in the chemoprevention process. Additionally, this may have been the first report on AMI-induced apoptotic death in the lung tissue. Taken together, these events undoubtedly establish GSPE's abundant bioavailability, and the power to defend multiple target organs from toxic assaults induced by structurally diverse and functionally different entities in vivo.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "DOX", "mention_text": "Grape seed extract, primarily a mixture of proanthocyanidins, has been shown to modulate a wide-range of biological, pharmacological and toxicological effects which are mainly cytoprotective. This study assessed the ability of IH636 grape seed proanthocyanidin extract (GSPE) to prevent acetaminophen (AAP)-induced nephrotoxicity, amiodarone (AMI)-induced lung toxicity, and doxorubicin (DOX)-induced cardiotoxicity in mice. Experimental design consisted of four groups: control (vehicle alone), GSPE alone, drug alone and GSPE+drug. For the cytoprotection study, animals were orally gavaged 100 mg/Kg GSPE for 7-10 days followed by i.p. injections of organ specific three drugs (AAP: 500 mg/Kg for 24 h; AMI: 50 mg/Kg/day for four days; DOX: 20 mg/Kg for 48 h). Parameters of study included analysis of serum chemistry (ALT, BUN and CPK), and orderly fragmentation of genomic DNA (both endonuclease-dependent and independent) in addition to microscopic evaluation of damage and/or protection in corresponding PAS stained tissues. Results indicate that GSPE preexposure prior to AAP, AMI and DOX, provided near complete protection in terms of serum chemistry changes (ALT, BUN and CPK), and significantly reduced DNA fragmentation. Histopathological examination of kidney, heart and lung sections revealed moderate to massive tissue damage with a variety of morphological aberrations by all the three drugs in the absence of GSPE preexposure than in its presence. GSPE+drug exposed tissues exhibited minor residual damage or near total recovery. Additionally, histopathological alterations mirrored both serum chemistry changes and the pattern of DNA fragmentation. Interestingly, all the drugs, such as, AAP, AMI and DOX induced apoptotic death in addition to necrosis in the respective organs which was very effectively blocked by GSPE. Since AAP, AMI and DOX undergo biotransformation and are known to produce damaging radicals in vivo, the protection by GSPE may be linked to both inhibition of metabolism and/or detoxification of cytotoxic radicals. In addition, its' presumed contribution to DNA repair may be another important attribute, which played a role in the chemoprevention process. Additionally, this may have been the first report on AMI-induced apoptotic death in the lung tissue. Taken together, these events undoubtedly establish GSPE's abundant bioavailability, and the power to defend multiple target organs from toxic assaults induced by structurally diverse and functionally different entities in vivo.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "cardiotoxicity", "mention_text": "Grape seed extract, primarily a mixture of proanthocyanidins, has been shown to modulate a wide-range of biological, pharmacological and toxicological effects which are mainly cytoprotective. This study assessed the ability of IH636 grape seed proanthocyanidin extract (GSPE) to prevent acetaminophen (AAP)-induced nephrotoxicity, amiodarone (AMI)-induced lung toxicity, and doxorubicin (DOX)-induced cardiotoxicity in mice. Experimental design consisted of four groups: control (vehicle alone), GSPE alone, drug alone and GSPE+drug. For the cytoprotection study, animals were orally gavaged 100 mg/Kg GSPE for 7-10 days followed by i.p. injections of organ specific three drugs (AAP: 500 mg/Kg for 24 h; AMI: 50 mg/Kg/day for four days; DOX: 20 mg/Kg for 48 h). Parameters of study included analysis of serum chemistry (ALT, BUN and CPK), and orderly fragmentation of genomic DNA (both endonuclease-dependent and independent) in addition to microscopic evaluation of damage and/or protection in corresponding PAS stained tissues. Results indicate that GSPE preexposure prior to AAP, AMI and DOX, provided near complete protection in terms of serum chemistry changes (ALT, BUN and CPK), and significantly reduced DNA fragmentation. Histopathological examination of kidney, heart and lung sections revealed moderate to massive tissue damage with a variety of morphological aberrations by all the three drugs in the absence of GSPE preexposure than in its presence. GSPE+drug exposed tissues exhibited minor residual damage or near total recovery. Additionally, histopathological alterations mirrored both serum chemistry changes and the pattern of DNA fragmentation. Interestingly, all the drugs, such as, AAP, AMI and DOX induced apoptotic death in addition to necrosis in the respective organs which was very effectively blocked by GSPE. Since AAP, AMI and DOX undergo biotransformation and are known to produce damaging radicals in vivo, the protection by GSPE may be linked to both inhibition of metabolism and/or detoxification of cytotoxic radicals. In addition, its' presumed contribution to DNA repair may be another important attribute, which played a role in the chemoprevention process. Additionally, this may have been the first report on AMI-induced apoptotic death in the lung tissue. Taken together, these events undoubtedly establish GSPE's abundant bioavailability, and the power to defend multiple target organs from toxic assaults induced by structurally diverse and functionally different entities in vivo.", "entity": "Cardiotoxicity", "aliases": "Cardiac Toxicities Toxicity Cardiotoxicities Cardiotoxicity", "definition": "Damage to the heart or its function secondary to exposure to toxic substances such as drugs used in CHEMOTHERAPY; IMMUNOTHERAPY; or RADIATION.\n    ", "id": "MESH:D066126"}
{"mention": "tissue damage", "mention_text": "Grape seed extract, primarily a mixture of proanthocyanidins, has been shown to modulate a wide-range of biological, pharmacological and toxicological effects which are mainly cytoprotective. This study assessed the ability of IH636 grape seed proanthocyanidin extract (GSPE) to prevent acetaminophen (AAP)-induced nephrotoxicity, amiodarone (AMI)-induced lung toxicity, and doxorubicin (DOX)-induced cardiotoxicity in mice. Experimental design consisted of four groups: control (vehicle alone), GSPE alone, drug alone and GSPE+drug. For the cytoprotection study, animals were orally gavaged 100 mg/Kg GSPE for 7-10 days followed by i.p. injections of organ specific three drugs (AAP: 500 mg/Kg for 24 h; AMI: 50 mg/Kg/day for four days; DOX: 20 mg/Kg for 48 h). Parameters of study included analysis of serum chemistry (ALT, BUN and CPK), and orderly fragmentation of genomic DNA (both endonuclease-dependent and independent) in addition to microscopic evaluation of damage and/or protection in corresponding PAS stained tissues. Results indicate that GSPE preexposure prior to AAP, AMI and DOX, provided near complete protection in terms of serum chemistry changes (ALT, BUN and CPK), and significantly reduced DNA fragmentation. Histopathological examination of kidney, heart and lung sections revealed moderate to massive tissue damage with a variety of morphological aberrations by all the three drugs in the absence of GSPE preexposure than in its presence. GSPE+drug exposed tissues exhibited minor residual damage or near total recovery. Additionally, histopathological alterations mirrored both serum chemistry changes and the pattern of DNA fragmentation. Interestingly, all the drugs, such as, AAP, AMI and DOX induced apoptotic death in addition to necrosis in the respective organs which was very effectively blocked by GSPE. Since AAP, AMI and DOX undergo biotransformation and are known to produce damaging radicals in vivo, the protection by GSPE may be linked to both inhibition of metabolism and/or detoxification of cytotoxic radicals. In addition, its' presumed contribution to DNA repair may be another important attribute, which played a role in the chemoprevention process. Additionally, this may have been the first report on AMI-induced apoptotic death in the lung tissue. Taken together, these events undoubtedly establish GSPE's abundant bioavailability, and the power to defend multiple target organs from toxic assaults induced by structurally diverse and functionally different entities in vivo.", "entity": "Soft Tissue Injuries", "aliases": "Injuries Soft Tissue Injury", "definition": "Injuries of tissue other than bone. The concept is usually general and does not customarily refer to internal organs or viscera. It is meaningful with reference to regions or organs where soft tissue (muscle, fat, skin) should be differentiated from bones or bone tissue, as \"soft tissue injuries of the hand\".\n    ", "id": "MESH:D017695"}
{"mention": "necrosis", "mention_text": "Grape seed extract, primarily a mixture of proanthocyanidins, has been shown to modulate a wide-range of biological, pharmacological and toxicological effects which are mainly cytoprotective. This study assessed the ability of IH636 grape seed proanthocyanidin extract (GSPE) to prevent acetaminophen (AAP)-induced nephrotoxicity, amiodarone (AMI)-induced lung toxicity, and doxorubicin (DOX)-induced cardiotoxicity in mice. Experimental design consisted of four groups: control (vehicle alone), GSPE alone, drug alone and GSPE+drug. For the cytoprotection study, animals were orally gavaged 100 mg/Kg GSPE for 7-10 days followed by i.p. injections of organ specific three drugs (AAP: 500 mg/Kg for 24 h; AMI: 50 mg/Kg/day for four days; DOX: 20 mg/Kg for 48 h). Parameters of study included analysis of serum chemistry (ALT, BUN and CPK), and orderly fragmentation of genomic DNA (both endonuclease-dependent and independent) in addition to microscopic evaluation of damage and/or protection in corresponding PAS stained tissues. Results indicate that GSPE preexposure prior to AAP, AMI and DOX, provided near complete protection in terms of serum chemistry changes (ALT, BUN and CPK), and significantly reduced DNA fragmentation. Histopathological examination of kidney, heart and lung sections revealed moderate to massive tissue damage with a variety of morphological aberrations by all the three drugs in the absence of GSPE preexposure than in its presence. GSPE+drug exposed tissues exhibited minor residual damage or near total recovery. Additionally, histopathological alterations mirrored both serum chemistry changes and the pattern of DNA fragmentation. Interestingly, all the drugs, such as, AAP, AMI and DOX induced apoptotic death in addition to necrosis in the respective organs which was very effectively blocked by GSPE. Since AAP, AMI and DOX undergo biotransformation and are known to produce damaging radicals in vivo, the protection by GSPE may be linked to both inhibition of metabolism and/or detoxification of cytotoxic radicals. In addition, its' presumed contribution to DNA repair may be another important attribute, which played a role in the chemoprevention process. Additionally, this may have been the first report on AMI-induced apoptotic death in the lung tissue. Taken together, these events undoubtedly establish GSPE's abundant bioavailability, and the power to defend multiple target organs from toxic assaults induced by structurally diverse and functionally different entities in vivo.", "entity": "Necrosis", "aliases": "Necroses Necrosis", "definition": "The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. Distinguish it from APOPTOSIS which is a normal, regulated cellular process.\n    ", "id": "MESH:D009336"}
{"mention": "Palpebral twitching", "mention_text": "Palpebral twitching in a depressed adolescent on citalopram.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "depressed", "mention_text": "Palpebral twitching in a depressed adolescent on citalopram.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "citalopram", "mention_text": "Palpebral twitching in a depressed adolescent on citalopram.", "entity": "Citalopram", "aliases": "Citalopram Cytalopram Escitalopram Lexapro Lu-10-171 Lu10171", "definition": "A furancarbonitrile that is one of the SEROTONIN UPTAKE INHIBITORS used as an antidepressant. The drug is also effective in reducing ethanol uptake in alcoholics and is used in depressed patients who also suffer from tardive dyskinesia in preference to tricyclic antidepressants, which aggravate this condition.\n    ", "id": "MESH:D015283"}
{"mention": "major depression", "mention_text": "Current estimates suggest that between 0.4% and 8.3% of children and adolescents are affected by major depression. We report a favorable response to treatment with citalopram by a 15-year-old boy with major depression who exhibited palpebral twitching during his first 2 weeks of treatment. This may have been a side effect of citalopram as it remitted with redistribution of doses.", "entity": "Depressive Disorder, Major", "aliases": "Depression Involutional Depressive Disorder Major Disorders Melancholia Psychoses Psychosis Paraphrenia", "definition": "Marked depression appearing in the involution period and characterized by hallucinations, delusions, paranoia, and agitation.\n    ", "id": "MESH:D003865"}
{"mention": "citalopram", "mention_text": "Current estimates suggest that between 0.4% and 8.3% of children and adolescents are affected by major depression. We report a favorable response to treatment with citalopram by a 15-year-old boy with major depression who exhibited palpebral twitching during his first 2 weeks of treatment. This may have been a side effect of citalopram as it remitted with redistribution of doses.", "entity": "Citalopram", "aliases": "Citalopram Cytalopram Escitalopram Lexapro Lu-10-171 Lu10171", "definition": "A furancarbonitrile that is one of the SEROTONIN UPTAKE INHIBITORS used as an antidepressant. The drug is also effective in reducing ethanol uptake in alcoholics and is used in depressed patients who also suffer from tardive dyskinesia in preference to tricyclic antidepressants, which aggravate this condition.\n    ", "id": "MESH:D015283"}
{"mention": "palpebral twitching", "mention_text": "Current estimates suggest that between 0.4% and 8.3% of children and adolescents are affected by major depression. We report a favorable response to treatment with citalopram by a 15-year-old boy with major depression who exhibited palpebral twitching during his first 2 weeks of treatment. This may have been a side effect of citalopram as it remitted with redistribution of doses.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "Metamizol", "mention_text": "Metamizol potentiates morphine antinociception but not constipation after chronic treatment.", "entity": "Dipyrone", "aliases": "Algopyrin Analgin Biopyrin Dipyrone Dipyronium Metamizol Metamizole Methamizole Methampyrone Methanesulfonate Sodium Noramidopyrine Narone Normelubrine Novalgetol Novalgin Novamidazophen Novaminsulfone Optalgin Pyralgin Sulpyrin Sulpyrine", "definition": "A drug that has analgesic, anti-inflammatory, and antipyretic properties. It is the sodium sulfonate of AMINOPYRINE. Because of the risk of serious adverse effects its use is justified only in serious situations where no alternative is available or suitable. (From Martindale, The Extra Pharmacopoeia, 30th ed, p13)\n    ", "id": "MESH:D004177"}
{"mention": "morphine", "mention_text": "Metamizol potentiates morphine antinociception but not constipation after chronic treatment.", "entity": "Morphine", "aliases": "Chloride Morphine Contin MS Duramorph Morphia Sulfate (2:1) Anhydrous Pentahydrate Oramorph SR SDZ 202 250 202-250 202250 SDZ202 SDZ202-250 SDZ202250", "definition": "The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.\n    ", "id": "MESH:D009020"}
{"mention": "constipation", "mention_text": "Metamizol potentiates morphine antinociception but not constipation after chronic treatment.", "entity": "Constipation", "aliases": "Colonic Inertia Constipation Dyschezia", "definition": "Infrequent or difficult evacuation of FECES. These symptoms are associated with a variety of causes, including low DIETARY FIBER intake, emotional or nervous disturbances, systemic and structural disorders, drug-induced aggravation, and infections.\n    ", "id": "MESH:D003248"}
{"mention": "constipating", "mention_text": "This work evaluates the antinociceptive and constipating effects of the combination of 3.2 mg/kg s.c. morphine with 177.8 mg/kg s.c. metamizol in acutely and chronically treated (once a day for 12 days) rats. On the 13th day, antinociceptive effects were assessed using a model of inflammatory nociception, pain-induced functional impairment model, and the charcoal meal test was used to evaluate the intestinal transit. Simultaneous administration of morphine with metamizol resulted in a markedly antinociceptive potentiation and an increasing of the duration of action after a single (298+/-7 vs. 139+/-36 units area (ua); P<0.001) and repeated administration (280+/-17 vs. 131+/-22 ua; P<0.001). Antinociceptive effect of morphine was reduced in chronically treated rats (39+/-10 vs. 18+/-5 au) while the combination-induced antinociception was remained similar as an acute treatment (298+/-7 vs. 280+/-17 au). Acute antinociceptive effects of the combination were partially prevented by 3.2 mg/kg naloxone s.c. (P<0.05), suggesting the partial involvement of the opioidergic system in the synergism observed. In independent groups, morphine inhibited the intestinal transit in 48+/-4% and 38+/-4% after acute and chronic treatment, respectively, suggesting that tolerance did not develop to the constipating effects. The combination inhibited intestinal transit similar to that produced by morphine regardless of the time of treatment, suggesting that metamizol did not potentiate morphine-induced constipation. These findings show a significant interaction between morphine and metamizol in chronically treated rats, suggesting that this combination could be useful for the treatment of chronic pain.", "entity": "Constipation", "aliases": "Colonic Inertia Constipation Dyschezia", "definition": "Infrequent or difficult evacuation of FECES. These symptoms are associated with a variety of causes, including low DIETARY FIBER intake, emotional or nervous disturbances, systemic and structural disorders, drug-induced aggravation, and infections.\n    ", "id": "MESH:D003248"}
{"mention": "morphine", "mention_text": "This work evaluates the antinociceptive and constipating effects of the combination of 3.2 mg/kg s.c. morphine with 177.8 mg/kg s.c. metamizol in acutely and chronically treated (once a day for 12 days) rats. On the 13th day, antinociceptive effects were assessed using a model of inflammatory nociception, pain-induced functional impairment model, and the charcoal meal test was used to evaluate the intestinal transit. Simultaneous administration of morphine with metamizol resulted in a markedly antinociceptive potentiation and an increasing of the duration of action after a single (298+/-7 vs. 139+/-36 units area (ua); P<0.001) and repeated administration (280+/-17 vs. 131+/-22 ua; P<0.001). Antinociceptive effect of morphine was reduced in chronically treated rats (39+/-10 vs. 18+/-5 au) while the combination-induced antinociception was remained similar as an acute treatment (298+/-7 vs. 280+/-17 au). Acute antinociceptive effects of the combination were partially prevented by 3.2 mg/kg naloxone s.c. (P<0.05), suggesting the partial involvement of the opioidergic system in the synergism observed. In independent groups, morphine inhibited the intestinal transit in 48+/-4% and 38+/-4% after acute and chronic treatment, respectively, suggesting that tolerance did not develop to the constipating effects. The combination inhibited intestinal transit similar to that produced by morphine regardless of the time of treatment, suggesting that metamizol did not potentiate morphine-induced constipation. These findings show a significant interaction between morphine and metamizol in chronically treated rats, suggesting that this combination could be useful for the treatment of chronic pain.", "entity": "Morphine", "aliases": "Chloride Morphine Contin MS Duramorph Morphia Sulfate (2:1) Anhydrous Pentahydrate Oramorph SR SDZ 202 250 202-250 202250 SDZ202 SDZ202-250 SDZ202250", "definition": "The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.\n    ", "id": "MESH:D009020"}
{"mention": "metamizol", "mention_text": "This work evaluates the antinociceptive and constipating effects of the combination of 3.2 mg/kg s.c. morphine with 177.8 mg/kg s.c. metamizol in acutely and chronically treated (once a day for 12 days) rats. On the 13th day, antinociceptive effects were assessed using a model of inflammatory nociception, pain-induced functional impairment model, and the charcoal meal test was used to evaluate the intestinal transit. Simultaneous administration of morphine with metamizol resulted in a markedly antinociceptive potentiation and an increasing of the duration of action after a single (298+/-7 vs. 139+/-36 units area (ua); P<0.001) and repeated administration (280+/-17 vs. 131+/-22 ua; P<0.001). Antinociceptive effect of morphine was reduced in chronically treated rats (39+/-10 vs. 18+/-5 au) while the combination-induced antinociception was remained similar as an acute treatment (298+/-7 vs. 280+/-17 au). Acute antinociceptive effects of the combination were partially prevented by 3.2 mg/kg naloxone s.c. (P<0.05), suggesting the partial involvement of the opioidergic system in the synergism observed. In independent groups, morphine inhibited the intestinal transit in 48+/-4% and 38+/-4% after acute and chronic treatment, respectively, suggesting that tolerance did not develop to the constipating effects. The combination inhibited intestinal transit similar to that produced by morphine regardless of the time of treatment, suggesting that metamizol did not potentiate morphine-induced constipation. These findings show a significant interaction between morphine and metamizol in chronically treated rats, suggesting that this combination could be useful for the treatment of chronic pain.", "entity": "Dipyrone", "aliases": "Algopyrin Analgin Biopyrin Dipyrone Dipyronium Metamizol Metamizole Methamizole Methampyrone Methanesulfonate Sodium Noramidopyrine Narone Normelubrine Novalgetol Novalgin Novamidazophen Novaminsulfone Optalgin Pyralgin Sulpyrin Sulpyrine", "definition": "A drug that has analgesic, anti-inflammatory, and antipyretic properties. It is the sodium sulfonate of AMINOPYRINE. Because of the risk of serious adverse effects its use is justified only in serious situations where no alternative is available or suitable. (From Martindale, The Extra Pharmacopoeia, 30th ed, p13)\n    ", "id": "MESH:D004177"}
{"mention": "pain", "mention_text": "This work evaluates the antinociceptive and constipating effects of the combination of 3.2 mg/kg s.c. morphine with 177.8 mg/kg s.c. metamizol in acutely and chronically treated (once a day for 12 days) rats. On the 13th day, antinociceptive effects were assessed using a model of inflammatory nociception, pain-induced functional impairment model, and the charcoal meal test was used to evaluate the intestinal transit. Simultaneous administration of morphine with metamizol resulted in a markedly antinociceptive potentiation and an increasing of the duration of action after a single (298+/-7 vs. 139+/-36 units area (ua); P<0.001) and repeated administration (280+/-17 vs. 131+/-22 ua; P<0.001). Antinociceptive effect of morphine was reduced in chronically treated rats (39+/-10 vs. 18+/-5 au) while the combination-induced antinociception was remained similar as an acute treatment (298+/-7 vs. 280+/-17 au). Acute antinociceptive effects of the combination were partially prevented by 3.2 mg/kg naloxone s.c. (P<0.05), suggesting the partial involvement of the opioidergic system in the synergism observed. In independent groups, morphine inhibited the intestinal transit in 48+/-4% and 38+/-4% after acute and chronic treatment, respectively, suggesting that tolerance did not develop to the constipating effects. The combination inhibited intestinal transit similar to that produced by morphine regardless of the time of treatment, suggesting that metamizol did not potentiate morphine-induced constipation. These findings show a significant interaction between morphine and metamizol in chronically treated rats, suggesting that this combination could be useful for the treatment of chronic pain.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "charcoal", "mention_text": "This work evaluates the antinociceptive and constipating effects of the combination of 3.2 mg/kg s.c. morphine with 177.8 mg/kg s.c. metamizol in acutely and chronically treated (once a day for 12 days) rats. On the 13th day, antinociceptive effects were assessed using a model of inflammatory nociception, pain-induced functional impairment model, and the charcoal meal test was used to evaluate the intestinal transit. Simultaneous administration of morphine with metamizol resulted in a markedly antinociceptive potentiation and an increasing of the duration of action after a single (298+/-7 vs. 139+/-36 units area (ua); P<0.001) and repeated administration (280+/-17 vs. 131+/-22 ua; P<0.001). Antinociceptive effect of morphine was reduced in chronically treated rats (39+/-10 vs. 18+/-5 au) while the combination-induced antinociception was remained similar as an acute treatment (298+/-7 vs. 280+/-17 au). Acute antinociceptive effects of the combination were partially prevented by 3.2 mg/kg naloxone s.c. (P<0.05), suggesting the partial involvement of the opioidergic system in the synergism observed. In independent groups, morphine inhibited the intestinal transit in 48+/-4% and 38+/-4% after acute and chronic treatment, respectively, suggesting that tolerance did not develop to the constipating effects. The combination inhibited intestinal transit similar to that produced by morphine regardless of the time of treatment, suggesting that metamizol did not potentiate morphine-induced constipation. These findings show a significant interaction between morphine and metamizol in chronically treated rats, suggesting that this combination could be useful for the treatment of chronic pain.", "entity": "Charcoal", "aliases": "Actidose Actidose-Aqua Activated Charcoal Adsorba Cambridge Laboratories Brand of Carbomix Central Charbon CharcoAid CharcoCaps Charcodote Chefaro Cheplapharm Formocarbine Gambro GlaxoSmithKline Hevert Insta-Char Kerr Kohle-Compretten Kohle-Hevert Kohle-Pulvis Kohle-Tabletten Boxo-Pharm Köhler Liqui-Char Little Remedies Merck Selbstmedikation Monarch Norit Paddock 1 2 Penn Pharmascience Pharmygiène Requa Ultracarbon", "definition": "An amorphous form of carbon prepared from the incomplete combustion of animal or vegetable matter, e.g., wood. The activated form of charcoal is used in the treatment of poisoning. (Grant & Hackh's Chemical Dictionary, 5th ed)\n    ", "id": "MESH:D002606"}
{"mention": "naloxone", "mention_text": "This work evaluates the antinociceptive and constipating effects of the combination of 3.2 mg/kg s.c. morphine with 177.8 mg/kg s.c. metamizol in acutely and chronically treated (once a day for 12 days) rats. On the 13th day, antinociceptive effects were assessed using a model of inflammatory nociception, pain-induced functional impairment model, and the charcoal meal test was used to evaluate the intestinal transit. Simultaneous administration of morphine with metamizol resulted in a markedly antinociceptive potentiation and an increasing of the duration of action after a single (298+/-7 vs. 139+/-36 units area (ua); P<0.001) and repeated administration (280+/-17 vs. 131+/-22 ua; P<0.001). Antinociceptive effect of morphine was reduced in chronically treated rats (39+/-10 vs. 18+/-5 au) while the combination-induced antinociception was remained similar as an acute treatment (298+/-7 vs. 280+/-17 au). Acute antinociceptive effects of the combination were partially prevented by 3.2 mg/kg naloxone s.c. (P<0.05), suggesting the partial involvement of the opioidergic system in the synergism observed. In independent groups, morphine inhibited the intestinal transit in 48+/-4% and 38+/-4% after acute and chronic treatment, respectively, suggesting that tolerance did not develop to the constipating effects. The combination inhibited intestinal transit similar to that produced by morphine regardless of the time of treatment, suggesting that metamizol did not potentiate morphine-induced constipation. These findings show a significant interaction between morphine and metamizol in chronically treated rats, suggesting that this combination could be useful for the treatment of chronic pain.", "entity": "Naloxone", "aliases": "Abello Brand of Naloxone Hydrochloride Boots Bristol Myers Squibb Bristol-Myers Curamed Naloxon Dihydride Endo Hydrobromide Lamepro MRZ 2593 Br 2593-Br 2593Br MRZ-2593 MRZ2593 Nalone ratiopharm Naloxon-ratiopharm (5 beta,9 alpha,13 alpha,14 alpha)-Isomer Naloxonratiopharm Narcan Narcanti SERB United Drug", "definition": "A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.\n    ", "id": "MESH:D009270"}
{"mention": "constipation", "mention_text": "This work evaluates the antinociceptive and constipating effects of the combination of 3.2 mg/kg s.c. morphine with 177.8 mg/kg s.c. metamizol in acutely and chronically treated (once a day for 12 days) rats. On the 13th day, antinociceptive effects were assessed using a model of inflammatory nociception, pain-induced functional impairment model, and the charcoal meal test was used to evaluate the intestinal transit. Simultaneous administration of morphine with metamizol resulted in a markedly antinociceptive potentiation and an increasing of the duration of action after a single (298+/-7 vs. 139+/-36 units area (ua); P<0.001) and repeated administration (280+/-17 vs. 131+/-22 ua; P<0.001). Antinociceptive effect of morphine was reduced in chronically treated rats (39+/-10 vs. 18+/-5 au) while the combination-induced antinociception was remained similar as an acute treatment (298+/-7 vs. 280+/-17 au). Acute antinociceptive effects of the combination were partially prevented by 3.2 mg/kg naloxone s.c. (P<0.05), suggesting the partial involvement of the opioidergic system in the synergism observed. In independent groups, morphine inhibited the intestinal transit in 48+/-4% and 38+/-4% after acute and chronic treatment, respectively, suggesting that tolerance did not develop to the constipating effects. The combination inhibited intestinal transit similar to that produced by morphine regardless of the time of treatment, suggesting that metamizol did not potentiate morphine-induced constipation. These findings show a significant interaction between morphine and metamizol in chronically treated rats, suggesting that this combination could be useful for the treatment of chronic pain.", "entity": "Constipation", "aliases": "Colonic Inertia Constipation Dyschezia", "definition": "Infrequent or difficult evacuation of FECES. These symptoms are associated with a variety of causes, including low DIETARY FIBER intake, emotional or nervous disturbances, systemic and structural disorders, drug-induced aggravation, and infections.\n    ", "id": "MESH:D003248"}
{"mention": "chronic pain", "mention_text": "This work evaluates the antinociceptive and constipating effects of the combination of 3.2 mg/kg s.c. morphine with 177.8 mg/kg s.c. metamizol in acutely and chronically treated (once a day for 12 days) rats. On the 13th day, antinociceptive effects were assessed using a model of inflammatory nociception, pain-induced functional impairment model, and the charcoal meal test was used to evaluate the intestinal transit. Simultaneous administration of morphine with metamizol resulted in a markedly antinociceptive potentiation and an increasing of the duration of action after a single (298+/-7 vs. 139+/-36 units area (ua); P<0.001) and repeated administration (280+/-17 vs. 131+/-22 ua; P<0.001). Antinociceptive effect of morphine was reduced in chronically treated rats (39+/-10 vs. 18+/-5 au) while the combination-induced antinociception was remained similar as an acute treatment (298+/-7 vs. 280+/-17 au). Acute antinociceptive effects of the combination were partially prevented by 3.2 mg/kg naloxone s.c. (P<0.05), suggesting the partial involvement of the opioidergic system in the synergism observed. In independent groups, morphine inhibited the intestinal transit in 48+/-4% and 38+/-4% after acute and chronic treatment, respectively, suggesting that tolerance did not develop to the constipating effects. The combination inhibited intestinal transit similar to that produced by morphine regardless of the time of treatment, suggesting that metamizol did not potentiate morphine-induced constipation. These findings show a significant interaction between morphine and metamizol in chronically treated rats, suggesting that this combination could be useful for the treatment of chronic pain.", "entity": "Chronic Pain", "aliases": "Chronic Pain Widespread Pains", "definition": "Aching sensation that persists for more than a few months. It may or may not be associated with trauma or disease, and may persist after the initial injury has healed. Its localization, character, and timing are more vague than with acute pain.\n    ", "id": "MESH:D059350"}
{"mention": "Ifosfamide", "mention_text": "Ifosfamide encephalopathy presenting with asterixis.", "entity": "Ifosfamide", "aliases": "Asta Z 4942 Holoxan Ifosfamide Iphosphamide Iso Endoxan Iso-Endoxan Isofosfamide Isophosphamide NSC 109,724 109724 NSC-109,724 NSC-109724 NSC109,724 NSC109724", "definition": "Positional isomer of CYCLOPHOSPHAMIDE which is active as an alkylating agent and an immunosuppressive agent.\n    ", "id": "MESH:D007069"}
{"mention": "encephalopathy", "mention_text": "Ifosfamide encephalopathy presenting with asterixis.", "entity": "Brain Diseases", "aliases": "Brain Disease Diseases Disorder Disorders CNS Intracranial Central Nervous System Encephalon", "definition": "Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.\n    ", "id": "MESH:D001927"}
{"mention": "asterixis", "mention_text": "Ifosfamide encephalopathy presenting with asterixis.", "entity": "Dyskinesias", "aliases": "Abnormal Movement Movements Asterixis Ballismus Dyskinesia Dyskinesias Hemiballism Hemiballismus Involuntary", "definition": "Abnormal involuntary movements which primarily affect the extremities, trunk, or jaw that occur as a manifestation of an underlying disease process. Conditions which feature recurrent or persistent episodes of dyskinesia as a primary manifestation of disease may be referred to as dyskinesia syndromes (see MOVEMENT DISORDERS). Dyskinesias are also a relatively common manifestation of BASAL GANGLIA DISEASES.\n    ", "id": "MESH:D020820"}
{"mention": "ifosfamide", "mention_text": "CNS toxic effects of the antineoplastic agent ifosfamide (IFX) are frequent and include a variety of neurological symptoms that can limit drug use. We report a case of a 51-year-old man who developed severe, disabling negative myoclonus of the upper and lower extremities after the infusion of ifosfamide for plasmacytoma. He was awake, revealed no changes of mental status and at rest there were no further motor symptoms. Cranial magnetic resonance imaging and extensive laboratory studies failed to reveal structural lesions of the brain and metabolic abnormalities. An electroencephalogram showed continuous, generalized irregular slowing with admixed periodic triphasic waves indicating symptomatic encephalopathy. The administration of ifosfamide was discontinued and within 12 h the asterixis resolved completely. In the patient described, the presence of asterixis during infusion of ifosfamide, normal laboratory findings and imaging studies and the resolution of symptoms following the discontinuation of the drug suggest that negative myoclonus is associated with the use of IFX.", "entity": "Ifosfamide", "aliases": "Asta Z 4942 Holoxan Ifosfamide Iphosphamide Iso Endoxan Iso-Endoxan Isofosfamide Isophosphamide NSC 109,724 109724 NSC-109,724 NSC-109724 NSC109,724 NSC109724", "definition": "Positional isomer of CYCLOPHOSPHAMIDE which is active as an alkylating agent and an immunosuppressive agent.\n    ", "id": "MESH:D007069"}
{"mention": "IFX", "mention_text": "CNS toxic effects of the antineoplastic agent ifosfamide (IFX) are frequent and include a variety of neurological symptoms that can limit drug use. We report a case of a 51-year-old man who developed severe, disabling negative myoclonus of the upper and lower extremities after the infusion of ifosfamide for plasmacytoma. He was awake, revealed no changes of mental status and at rest there were no further motor symptoms. Cranial magnetic resonance imaging and extensive laboratory studies failed to reveal structural lesions of the brain and metabolic abnormalities. An electroencephalogram showed continuous, generalized irregular slowing with admixed periodic triphasic waves indicating symptomatic encephalopathy. The administration of ifosfamide was discontinued and within 12 h the asterixis resolved completely. In the patient described, the presence of asterixis during infusion of ifosfamide, normal laboratory findings and imaging studies and the resolution of symptoms following the discontinuation of the drug suggest that negative myoclonus is associated with the use of IFX.", "entity": "Ifosfamide", "aliases": "Asta Z 4942 Holoxan Ifosfamide Iphosphamide Iso Endoxan Iso-Endoxan Isofosfamide Isophosphamide NSC 109,724 109724 NSC-109,724 NSC-109724 NSC109,724 NSC109724", "definition": "Positional isomer of CYCLOPHOSPHAMIDE which is active as an alkylating agent and an immunosuppressive agent.\n    ", "id": "MESH:D007069"}
{"mention": "myoclonus", "mention_text": "CNS toxic effects of the antineoplastic agent ifosfamide (IFX) are frequent and include a variety of neurological symptoms that can limit drug use. We report a case of a 51-year-old man who developed severe, disabling negative myoclonus of the upper and lower extremities after the infusion of ifosfamide for plasmacytoma. He was awake, revealed no changes of mental status and at rest there were no further motor symptoms. Cranial magnetic resonance imaging and extensive laboratory studies failed to reveal structural lesions of the brain and metabolic abnormalities. An electroencephalogram showed continuous, generalized irregular slowing with admixed periodic triphasic waves indicating symptomatic encephalopathy. The administration of ifosfamide was discontinued and within 12 h the asterixis resolved completely. In the patient described, the presence of asterixis during infusion of ifosfamide, normal laboratory findings and imaging studies and the resolution of symptoms following the discontinuation of the drug suggest that negative myoclonus is associated with the use of IFX.", "entity": "Myoclonus", "aliases": "Action Myoclonus Extremity Lower Upper Eyelid Intention Jerk Myoclonic Jerking Jerks Simplex Nocturnal Oculopalatal Palatal Segmental Sleep Polymyoclonus", "definition": "Involuntary shock-like contractions, irregular in rhythm and amplitude, followed by relaxation, of a muscle or a group of muscles. This condition may be a feature of some CENTRAL NERVOUS SYSTEM DISEASES; (e.g., EPILEPSY, MYOCLONIC). Nocturnal myoclonus is the principal feature of the NOCTURNAL MYOCLONUS SYNDROME. (From Adams et al., Principles of Neurology, 6th ed, pp102-3).\n    ", "id": "MESH:D009207"}
{"mention": "plasmacytoma", "mention_text": "CNS toxic effects of the antineoplastic agent ifosfamide (IFX) are frequent and include a variety of neurological symptoms that can limit drug use. We report a case of a 51-year-old man who developed severe, disabling negative myoclonus of the upper and lower extremities after the infusion of ifosfamide for plasmacytoma. He was awake, revealed no changes of mental status and at rest there were no further motor symptoms. Cranial magnetic resonance imaging and extensive laboratory studies failed to reveal structural lesions of the brain and metabolic abnormalities. An electroencephalogram showed continuous, generalized irregular slowing with admixed periodic triphasic waves indicating symptomatic encephalopathy. The administration of ifosfamide was discontinued and within 12 h the asterixis resolved completely. In the patient described, the presence of asterixis during infusion of ifosfamide, normal laboratory findings and imaging studies and the resolution of symptoms following the discontinuation of the drug suggest that negative myoclonus is associated with the use of IFX.", "entity": "Plasmacytoma", "aliases": "Plasma Cell Tumor Tumors Plasmacytoma Plasmacytomas Plasmocytoma Plasmocytomas", "definition": "Any discrete, presumably solitary, mass of neoplastic PLASMA CELLS either in BONE MARROW or various extramedullary sites.\n    ", "id": "MESH:D010954"}
{"mention": "structural lesions of the brain", "mention_text": "CNS toxic effects of the antineoplastic agent ifosfamide (IFX) are frequent and include a variety of neurological symptoms that can limit drug use. We report a case of a 51-year-old man who developed severe, disabling negative myoclonus of the upper and lower extremities after the infusion of ifosfamide for plasmacytoma. He was awake, revealed no changes of mental status and at rest there were no further motor symptoms. Cranial magnetic resonance imaging and extensive laboratory studies failed to reveal structural lesions of the brain and metabolic abnormalities. An electroencephalogram showed continuous, generalized irregular slowing with admixed periodic triphasic waves indicating symptomatic encephalopathy. The administration of ifosfamide was discontinued and within 12 h the asterixis resolved completely. In the patient described, the presence of asterixis during infusion of ifosfamide, normal laboratory findings and imaging studies and the resolution of symptoms following the discontinuation of the drug suggest that negative myoclonus is associated with the use of IFX.", "entity": "Brain Diseases", "aliases": "Brain Disease Diseases Disorder Disorders CNS Intracranial Central Nervous System Encephalon", "definition": "Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.\n    ", "id": "MESH:D001927"}
{"mention": "metabolic abnormalities", "mention_text": "CNS toxic effects of the antineoplastic agent ifosfamide (IFX) are frequent and include a variety of neurological symptoms that can limit drug use. We report a case of a 51-year-old man who developed severe, disabling negative myoclonus of the upper and lower extremities after the infusion of ifosfamide for plasmacytoma. He was awake, revealed no changes of mental status and at rest there were no further motor symptoms. Cranial magnetic resonance imaging and extensive laboratory studies failed to reveal structural lesions of the brain and metabolic abnormalities. An electroencephalogram showed continuous, generalized irregular slowing with admixed periodic triphasic waves indicating symptomatic encephalopathy. The administration of ifosfamide was discontinued and within 12 h the asterixis resolved completely. In the patient described, the presence of asterixis during infusion of ifosfamide, normal laboratory findings and imaging studies and the resolution of symptoms following the discontinuation of the drug suggest that negative myoclonus is associated with the use of IFX.", "entity": "Metabolic Diseases", "aliases": "Disease Metabolic Diseases Thesaurismoses Thesaurismosis", "definition": "Generic term for diseases caused by an abnormal metabolic process. It can be congenital due to inherited enzyme abnormality (METABOLISM, INBORN ERRORS) or acquired due to disease of an endocrine organ or failure of a metabolically important organ such as the liver. (Stedman, 26th ed)\n    ", "id": "MESH:D008659"}
{"mention": "encephalopathy", "mention_text": "CNS toxic effects of the antineoplastic agent ifosfamide (IFX) are frequent and include a variety of neurological symptoms that can limit drug use. We report a case of a 51-year-old man who developed severe, disabling negative myoclonus of the upper and lower extremities after the infusion of ifosfamide for plasmacytoma. He was awake, revealed no changes of mental status and at rest there were no further motor symptoms. Cranial magnetic resonance imaging and extensive laboratory studies failed to reveal structural lesions of the brain and metabolic abnormalities. An electroencephalogram showed continuous, generalized irregular slowing with admixed periodic triphasic waves indicating symptomatic encephalopathy. The administration of ifosfamide was discontinued and within 12 h the asterixis resolved completely. In the patient described, the presence of asterixis during infusion of ifosfamide, normal laboratory findings and imaging studies and the resolution of symptoms following the discontinuation of the drug suggest that negative myoclonus is associated with the use of IFX.", "entity": "Brain Diseases", "aliases": "Brain Disease Diseases Disorder Disorders CNS Intracranial Central Nervous System Encephalon", "definition": "Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.\n    ", "id": "MESH:D001927"}
{"mention": "asterixis", "mention_text": "CNS toxic effects of the antineoplastic agent ifosfamide (IFX) are frequent and include a variety of neurological symptoms that can limit drug use. We report a case of a 51-year-old man who developed severe, disabling negative myoclonus of the upper and lower extremities after the infusion of ifosfamide for plasmacytoma. He was awake, revealed no changes of mental status and at rest there were no further motor symptoms. Cranial magnetic resonance imaging and extensive laboratory studies failed to reveal structural lesions of the brain and metabolic abnormalities. An electroencephalogram showed continuous, generalized irregular slowing with admixed periodic triphasic waves indicating symptomatic encephalopathy. The administration of ifosfamide was discontinued and within 12 h the asterixis resolved completely. In the patient described, the presence of asterixis during infusion of ifosfamide, normal laboratory findings and imaging studies and the resolution of symptoms following the discontinuation of the drug suggest that negative myoclonus is associated with the use of IFX.", "entity": "Dyskinesias", "aliases": "Abnormal Movement Movements Asterixis Ballismus Dyskinesia Dyskinesias Hemiballism Hemiballismus Involuntary", "definition": "Abnormal involuntary movements which primarily affect the extremities, trunk, or jaw that occur as a manifestation of an underlying disease process. Conditions which feature recurrent or persistent episodes of dyskinesia as a primary manifestation of disease may be referred to as dyskinesia syndromes (see MOVEMENT DISORDERS). Dyskinesias are also a relatively common manifestation of BASAL GANGLIA DISEASES.\n    ", "id": "MESH:D020820"}
{"mention": "gamma-vinyl GABA", "mention_text": "Sub-chronic low dose gamma-vinyl GABA (vigabatrin) inhibits cocaine-induced increases in nucleus accumbens dopamine.", "entity": "Vigabatrin", "aliases": "Acid gamma-Vinyl-gamma-Aminobutyric Aventis Brand of Vigabatrin Hoechst Sabril Sabrilex Yamanouchi gamma Vinyl GABA Aminobutyric gamma-Vinyl-GABA", "definition": "An analogue of GAMMA-AMINOBUTYRIC ACID. It is an irreversible inhibitor of 4-AMINOBUTYRATE TRANSAMINASE, the enzyme responsible for the catabolism of GAMMA-AMINOBUTYRIC ACID. (From Martindale The Extra Pharmacopoeia, 31st ed)\n    ", "id": "MESH:D020888"}
{"mention": "vigabatrin", "mention_text": "Sub-chronic low dose gamma-vinyl GABA (vigabatrin) inhibits cocaine-induced increases in nucleus accumbens dopamine.", "entity": "Vigabatrin", "aliases": "Acid gamma-Vinyl-gamma-Aminobutyric Aventis Brand of Vigabatrin Hoechst Sabril Sabrilex Yamanouchi gamma Vinyl GABA Aminobutyric gamma-Vinyl-GABA", "definition": "An analogue of GAMMA-AMINOBUTYRIC ACID. It is an irreversible inhibitor of 4-AMINOBUTYRATE TRANSAMINASE, the enzyme responsible for the catabolism of GAMMA-AMINOBUTYRIC ACID. (From Martindale The Extra Pharmacopoeia, 31st ed)\n    ", "id": "MESH:D020888"}
{"mention": "cocaine", "mention_text": "Sub-chronic low dose gamma-vinyl GABA (vigabatrin) inhibits cocaine-induced increases in nucleus accumbens dopamine.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "dopamine", "mention_text": "Sub-chronic low dose gamma-vinyl GABA (vigabatrin) inhibits cocaine-induced increases in nucleus accumbens dopamine.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "gamma-Vinyl GABA", "mention_text": "RATIONALE: gamma-Vinyl GABA (GVG) irreversibly inhibits GABA-transaminase. This non-receptor mediated inhibition requires de novo synthesis for restoration of functional GABA catabolism. OBJECTIVES: Given its preclinical success for treating substance abuse and the increased risk of visual field defects (VFD) associated with cumulative lifetime exposure, we explored the effects of sub-chronic low dose GVG on cocaine-induced increases in nucleus accumbens (NAcc) dopamine (DA). METHODS: Using in vivo microdialysis, we compared acute exposure (450 mg/kg) to an identical sub-chronic exposure (150 mg/kg per day for 3 days), followed by 1- or 3-day washout. Finally, we examined the low dose of 150 mg/kg (50 mg/kg per day) using a similar washout period. RESULTS: Sub-chronic GVG exposure inhibited the effect of cocaine for 3 days, which exceeded in magnitude and duration the identical acute dose. CONCLUSIONS: Sub-chronic low dose GVG potentiates and extends the inhibition of cocaine-induced increases in dopamine, effectively reducing cumulative exposures and the risk for VFDS.", "entity": "Vigabatrin", "aliases": "Acid gamma-Vinyl-gamma-Aminobutyric Aventis Brand of Vigabatrin Hoechst Sabril Sabrilex Yamanouchi gamma Vinyl GABA Aminobutyric gamma-Vinyl-GABA", "definition": "An analogue of GAMMA-AMINOBUTYRIC ACID. It is an irreversible inhibitor of 4-AMINOBUTYRATE TRANSAMINASE, the enzyme responsible for the catabolism of GAMMA-AMINOBUTYRIC ACID. (From Martindale The Extra Pharmacopoeia, 31st ed)\n    ", "id": "MESH:D020888"}
{"mention": "GVG", "mention_text": "RATIONALE: gamma-Vinyl GABA (GVG) irreversibly inhibits GABA-transaminase. This non-receptor mediated inhibition requires de novo synthesis for restoration of functional GABA catabolism. OBJECTIVES: Given its preclinical success for treating substance abuse and the increased risk of visual field defects (VFD) associated with cumulative lifetime exposure, we explored the effects of sub-chronic low dose GVG on cocaine-induced increases in nucleus accumbens (NAcc) dopamine (DA). METHODS: Using in vivo microdialysis, we compared acute exposure (450 mg/kg) to an identical sub-chronic exposure (150 mg/kg per day for 3 days), followed by 1- or 3-day washout. Finally, we examined the low dose of 150 mg/kg (50 mg/kg per day) using a similar washout period. RESULTS: Sub-chronic GVG exposure inhibited the effect of cocaine for 3 days, which exceeded in magnitude and duration the identical acute dose. CONCLUSIONS: Sub-chronic low dose GVG potentiates and extends the inhibition of cocaine-induced increases in dopamine, effectively reducing cumulative exposures and the risk for VFDS.", "entity": "Vigabatrin", "aliases": "Acid gamma-Vinyl-gamma-Aminobutyric Aventis Brand of Vigabatrin Hoechst Sabril Sabrilex Yamanouchi gamma Vinyl GABA Aminobutyric gamma-Vinyl-GABA", "definition": "An analogue of GAMMA-AMINOBUTYRIC ACID. It is an irreversible inhibitor of 4-AMINOBUTYRATE TRANSAMINASE, the enzyme responsible for the catabolism of GAMMA-AMINOBUTYRIC ACID. (From Martindale The Extra Pharmacopoeia, 31st ed)\n    ", "id": "MESH:D020888"}
{"mention": "GABA", "mention_text": "RATIONALE: gamma-Vinyl GABA (GVG) irreversibly inhibits GABA-transaminase. This non-receptor mediated inhibition requires de novo synthesis for restoration of functional GABA catabolism. OBJECTIVES: Given its preclinical success for treating substance abuse and the increased risk of visual field defects (VFD) associated with cumulative lifetime exposure, we explored the effects of sub-chronic low dose GVG on cocaine-induced increases in nucleus accumbens (NAcc) dopamine (DA). METHODS: Using in vivo microdialysis, we compared acute exposure (450 mg/kg) to an identical sub-chronic exposure (150 mg/kg per day for 3 days), followed by 1- or 3-day washout. Finally, we examined the low dose of 150 mg/kg (50 mg/kg per day) using a similar washout period. RESULTS: Sub-chronic GVG exposure inhibited the effect of cocaine for 3 days, which exceeded in magnitude and duration the identical acute dose. CONCLUSIONS: Sub-chronic low dose GVG potentiates and extends the inhibition of cocaine-induced increases in dopamine, effectively reducing cumulative exposures and the risk for VFDS.", "entity": "gamma-Aminobutyric Acid", "aliases": "4 Aminobutanoic Acid Aminobutyric 4-Aminobutanoic 4-Aminobutyric Hydrochloride gamma-Aminobutyric Aminalon Aminalone GABA Lithium Gammalon gamma Monolithium Salt Monosodium Calcium (2:1) Zinc", "definition": "The most common inhibitory neurotransmitter in the central nervous system.\n    ", "id": "MESH:D005680"}
{"mention": "substance abuse", "mention_text": "RATIONALE: gamma-Vinyl GABA (GVG) irreversibly inhibits GABA-transaminase. This non-receptor mediated inhibition requires de novo synthesis for restoration of functional GABA catabolism. OBJECTIVES: Given its preclinical success for treating substance abuse and the increased risk of visual field defects (VFD) associated with cumulative lifetime exposure, we explored the effects of sub-chronic low dose GVG on cocaine-induced increases in nucleus accumbens (NAcc) dopamine (DA). METHODS: Using in vivo microdialysis, we compared acute exposure (450 mg/kg) to an identical sub-chronic exposure (150 mg/kg per day for 3 days), followed by 1- or 3-day washout. Finally, we examined the low dose of 150 mg/kg (50 mg/kg per day) using a similar washout period. RESULTS: Sub-chronic GVG exposure inhibited the effect of cocaine for 3 days, which exceeded in magnitude and duration the identical acute dose. CONCLUSIONS: Sub-chronic low dose GVG potentiates and extends the inhibition of cocaine-induced increases in dopamine, effectively reducing cumulative exposures and the risk for VFDS.", "entity": "Substance-Related Disorders", "aliases": "Abuse Drug Substance Abuses Addiction Dependence Disorder Use Habituation Disorders Organic Mental Induced Substance-Induced Substance-Related", "definition": "Disorders related to substance abuse.\n    ", "id": "MESH:D019966"}
{"mention": "visual field defects", "mention_text": "RATIONALE: gamma-Vinyl GABA (GVG) irreversibly inhibits GABA-transaminase. This non-receptor mediated inhibition requires de novo synthesis for restoration of functional GABA catabolism. OBJECTIVES: Given its preclinical success for treating substance abuse and the increased risk of visual field defects (VFD) associated with cumulative lifetime exposure, we explored the effects of sub-chronic low dose GVG on cocaine-induced increases in nucleus accumbens (NAcc) dopamine (DA). METHODS: Using in vivo microdialysis, we compared acute exposure (450 mg/kg) to an identical sub-chronic exposure (150 mg/kg per day for 3 days), followed by 1- or 3-day washout. Finally, we examined the low dose of 150 mg/kg (50 mg/kg per day) using a similar washout period. RESULTS: Sub-chronic GVG exposure inhibited the effect of cocaine for 3 days, which exceeded in magnitude and duration the identical acute dose. CONCLUSIONS: Sub-chronic low dose GVG potentiates and extends the inhibition of cocaine-induced increases in dopamine, effectively reducing cumulative exposures and the risk for VFDS.", "entity": "Eye Diseases", "aliases": "Disease Eye Diseases", "definition": "Diseases affecting the eye.\n    ", "id": "MESH:D005128"}
{"mention": "VFD", "mention_text": "RATIONALE: gamma-Vinyl GABA (GVG) irreversibly inhibits GABA-transaminase. This non-receptor mediated inhibition requires de novo synthesis for restoration of functional GABA catabolism. OBJECTIVES: Given its preclinical success for treating substance abuse and the increased risk of visual field defects (VFD) associated with cumulative lifetime exposure, we explored the effects of sub-chronic low dose GVG on cocaine-induced increases in nucleus accumbens (NAcc) dopamine (DA). METHODS: Using in vivo microdialysis, we compared acute exposure (450 mg/kg) to an identical sub-chronic exposure (150 mg/kg per day for 3 days), followed by 1- or 3-day washout. Finally, we examined the low dose of 150 mg/kg (50 mg/kg per day) using a similar washout period. RESULTS: Sub-chronic GVG exposure inhibited the effect of cocaine for 3 days, which exceeded in magnitude and duration the identical acute dose. CONCLUSIONS: Sub-chronic low dose GVG potentiates and extends the inhibition of cocaine-induced increases in dopamine, effectively reducing cumulative exposures and the risk for VFDS.", "entity": "Eye Diseases", "aliases": "Disease Eye Diseases", "definition": "Diseases affecting the eye.\n    ", "id": "MESH:D005128"}
{"mention": "cocaine", "mention_text": "RATIONALE: gamma-Vinyl GABA (GVG) irreversibly inhibits GABA-transaminase. This non-receptor mediated inhibition requires de novo synthesis for restoration of functional GABA catabolism. OBJECTIVES: Given its preclinical success for treating substance abuse and the increased risk of visual field defects (VFD) associated with cumulative lifetime exposure, we explored the effects of sub-chronic low dose GVG on cocaine-induced increases in nucleus accumbens (NAcc) dopamine (DA). METHODS: Using in vivo microdialysis, we compared acute exposure (450 mg/kg) to an identical sub-chronic exposure (150 mg/kg per day for 3 days), followed by 1- or 3-day washout. Finally, we examined the low dose of 150 mg/kg (50 mg/kg per day) using a similar washout period. RESULTS: Sub-chronic GVG exposure inhibited the effect of cocaine for 3 days, which exceeded in magnitude and duration the identical acute dose. CONCLUSIONS: Sub-chronic low dose GVG potentiates and extends the inhibition of cocaine-induced increases in dopamine, effectively reducing cumulative exposures and the risk for VFDS.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "dopamine", "mention_text": "RATIONALE: gamma-Vinyl GABA (GVG) irreversibly inhibits GABA-transaminase. This non-receptor mediated inhibition requires de novo synthesis for restoration of functional GABA catabolism. OBJECTIVES: Given its preclinical success for treating substance abuse and the increased risk of visual field defects (VFD) associated with cumulative lifetime exposure, we explored the effects of sub-chronic low dose GVG on cocaine-induced increases in nucleus accumbens (NAcc) dopamine (DA). METHODS: Using in vivo microdialysis, we compared acute exposure (450 mg/kg) to an identical sub-chronic exposure (150 mg/kg per day for 3 days), followed by 1- or 3-day washout. Finally, we examined the low dose of 150 mg/kg (50 mg/kg per day) using a similar washout period. RESULTS: Sub-chronic GVG exposure inhibited the effect of cocaine for 3 days, which exceeded in magnitude and duration the identical acute dose. CONCLUSIONS: Sub-chronic low dose GVG potentiates and extends the inhibition of cocaine-induced increases in dopamine, effectively reducing cumulative exposures and the risk for VFDS.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "DA", "mention_text": "RATIONALE: gamma-Vinyl GABA (GVG) irreversibly inhibits GABA-transaminase. This non-receptor mediated inhibition requires de novo synthesis for restoration of functional GABA catabolism. OBJECTIVES: Given its preclinical success for treating substance abuse and the increased risk of visual field defects (VFD) associated with cumulative lifetime exposure, we explored the effects of sub-chronic low dose GVG on cocaine-induced increases in nucleus accumbens (NAcc) dopamine (DA). METHODS: Using in vivo microdialysis, we compared acute exposure (450 mg/kg) to an identical sub-chronic exposure (150 mg/kg per day for 3 days), followed by 1- or 3-day washout. Finally, we examined the low dose of 150 mg/kg (50 mg/kg per day) using a similar washout period. RESULTS: Sub-chronic GVG exposure inhibited the effect of cocaine for 3 days, which exceeded in magnitude and duration the identical acute dose. CONCLUSIONS: Sub-chronic low dose GVG potentiates and extends the inhibition of cocaine-induced increases in dopamine, effectively reducing cumulative exposures and the risk for VFDS.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "bleeding", "mention_text": "Amount of bleeding and hematoma size in the collagenase-induced intracerebral hemorrhage rat model.", "entity": "Hemorrhage", "aliases": "Bleeding Hemorrhage Hemorrhages", "definition": "Bleeding or escape of blood from a vessel.\n    ", "id": "MESH:D006470"}
{"mention": "hematoma", "mention_text": "Amount of bleeding and hematoma size in the collagenase-induced intracerebral hemorrhage rat model.", "entity": "Hematoma", "aliases": "Hematoma Hematomas", "definition": "A collection of blood outside the BLOOD VESSELS. Hematoma can be localized in an organ, space, or tissue.\n    ", "id": "MESH:D006406"}
{"mention": "intracerebral hemorrhage", "mention_text": "Amount of bleeding and hematoma size in the collagenase-induced intracerebral hemorrhage rat model.", "entity": "Cerebral Hemorrhage", "aliases": "Brain Hemorrhage Cerebral Hemorrhages Parenchymal Cerebrum Intracerebral", "definition": "Bleeding into one or both CEREBRAL HEMISPHERES including the BASAL GANGLIA and the CEREBRAL CORTEX. It is often associated with HYPERTENSION and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D002543"}
{"mention": "intracerebral hemorrhage", "mention_text": "The aggravated risk on intracerebral hemorrhage (ICH) with drugs used for stroke patients should be estimated carefully. We therefore established sensitive quantification methods and provided a rat ICH model for detection of ICH deterioration. In ICH intrastriatally induced by 0.014-unit, 0.070-unit, and 0.350-unit collagenase, the amount of bleeding was measured using a hemoglobin assay developed in the present study and was compared with the morphologically determined hematoma volume. The blood amounts and hematoma volumes were significantly correlated, and the hematoma induced by 0.014-unit collagenase was adequate to detect ICH deterioration. In ICH induction using 0.014-unit collagenase, heparin enhanced the hematoma volume 3.4-fold over that seen in control ICH animals and the bleeding 7.6-fold. Data suggest that this sensitive hemoglobin assay is useful for ICH detection, and that a model with a small ICH induced with a low-dose collagenase should be used for evaluation of drugs that may affect ICH.", "entity": "Cerebral Hemorrhage", "aliases": "Brain Hemorrhage Cerebral Hemorrhages Parenchymal Cerebrum Intracerebral", "definition": "Bleeding into one or both CEREBRAL HEMISPHERES including the BASAL GANGLIA and the CEREBRAL CORTEX. It is often associated with HYPERTENSION and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D002543"}
{"mention": "ICH", "mention_text": "The aggravated risk on intracerebral hemorrhage (ICH) with drugs used for stroke patients should be estimated carefully. We therefore established sensitive quantification methods and provided a rat ICH model for detection of ICH deterioration. In ICH intrastriatally induced by 0.014-unit, 0.070-unit, and 0.350-unit collagenase, the amount of bleeding was measured using a hemoglobin assay developed in the present study and was compared with the morphologically determined hematoma volume. The blood amounts and hematoma volumes were significantly correlated, and the hematoma induced by 0.014-unit collagenase was adequate to detect ICH deterioration. In ICH induction using 0.014-unit collagenase, heparin enhanced the hematoma volume 3.4-fold over that seen in control ICH animals and the bleeding 7.6-fold. Data suggest that this sensitive hemoglobin assay is useful for ICH detection, and that a model with a small ICH induced with a low-dose collagenase should be used for evaluation of drugs that may affect ICH.", "entity": "Cerebral Hemorrhage", "aliases": "Brain Hemorrhage Cerebral Hemorrhages Parenchymal Cerebrum Intracerebral", "definition": "Bleeding into one or both CEREBRAL HEMISPHERES including the BASAL GANGLIA and the CEREBRAL CORTEX. It is often associated with HYPERTENSION and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D002543"}
{"mention": "stroke", "mention_text": "The aggravated risk on intracerebral hemorrhage (ICH) with drugs used for stroke patients should be estimated carefully. We therefore established sensitive quantification methods and provided a rat ICH model for detection of ICH deterioration. In ICH intrastriatally induced by 0.014-unit, 0.070-unit, and 0.350-unit collagenase, the amount of bleeding was measured using a hemoglobin assay developed in the present study and was compared with the morphologically determined hematoma volume. The blood amounts and hematoma volumes were significantly correlated, and the hematoma induced by 0.014-unit collagenase was adequate to detect ICH deterioration. In ICH induction using 0.014-unit collagenase, heparin enhanced the hematoma volume 3.4-fold over that seen in control ICH animals and the bleeding 7.6-fold. Data suggest that this sensitive hemoglobin assay is useful for ICH detection, and that a model with a small ICH induced with a low-dose collagenase should be used for evaluation of drugs that may affect ICH.", "entity": "Stroke", "aliases": "Acute Cerebrovascular Accident Accidents Stroke Strokes Apoplexy Brain Vascular CVA (Cerebrovascular Accident) CVAs Cerebral", "definition": "A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)\n    ", "id": "MESH:D020521"}
{"mention": "bleeding", "mention_text": "The aggravated risk on intracerebral hemorrhage (ICH) with drugs used for stroke patients should be estimated carefully. We therefore established sensitive quantification methods and provided a rat ICH model for detection of ICH deterioration. In ICH intrastriatally induced by 0.014-unit, 0.070-unit, and 0.350-unit collagenase, the amount of bleeding was measured using a hemoglobin assay developed in the present study and was compared with the morphologically determined hematoma volume. The blood amounts and hematoma volumes were significantly correlated, and the hematoma induced by 0.014-unit collagenase was adequate to detect ICH deterioration. In ICH induction using 0.014-unit collagenase, heparin enhanced the hematoma volume 3.4-fold over that seen in control ICH animals and the bleeding 7.6-fold. Data suggest that this sensitive hemoglobin assay is useful for ICH detection, and that a model with a small ICH induced with a low-dose collagenase should be used for evaluation of drugs that may affect ICH.", "entity": "Hemorrhage", "aliases": "Bleeding Hemorrhage Hemorrhages", "definition": "Bleeding or escape of blood from a vessel.\n    ", "id": "MESH:D006470"}
{"mention": "hematoma", "mention_text": "The aggravated risk on intracerebral hemorrhage (ICH) with drugs used for stroke patients should be estimated carefully. We therefore established sensitive quantification methods and provided a rat ICH model for detection of ICH deterioration. In ICH intrastriatally induced by 0.014-unit, 0.070-unit, and 0.350-unit collagenase, the amount of bleeding was measured using a hemoglobin assay developed in the present study and was compared with the morphologically determined hematoma volume. The blood amounts and hematoma volumes were significantly correlated, and the hematoma induced by 0.014-unit collagenase was adequate to detect ICH deterioration. In ICH induction using 0.014-unit collagenase, heparin enhanced the hematoma volume 3.4-fold over that seen in control ICH animals and the bleeding 7.6-fold. Data suggest that this sensitive hemoglobin assay is useful for ICH detection, and that a model with a small ICH induced with a low-dose collagenase should be used for evaluation of drugs that may affect ICH.", "entity": "Hematoma", "aliases": "Hematoma Hematomas", "definition": "A collection of blood outside the BLOOD VESSELS. Hematoma can be localized in an organ, space, or tissue.\n    ", "id": "MESH:D006406"}
{"mention": "heparin", "mention_text": "The aggravated risk on intracerebral hemorrhage (ICH) with drugs used for stroke patients should be estimated carefully. We therefore established sensitive quantification methods and provided a rat ICH model for detection of ICH deterioration. In ICH intrastriatally induced by 0.014-unit, 0.070-unit, and 0.350-unit collagenase, the amount of bleeding was measured using a hemoglobin assay developed in the present study and was compared with the morphologically determined hematoma volume. The blood amounts and hematoma volumes were significantly correlated, and the hematoma induced by 0.014-unit collagenase was adequate to detect ICH deterioration. In ICH induction using 0.014-unit collagenase, heparin enhanced the hematoma volume 3.4-fold over that seen in control ICH animals and the bleeding 7.6-fold. Data suggest that this sensitive hemoglobin assay is useful for ICH detection, and that a model with a small ICH induced with a low-dose collagenase should be used for evaluation of drugs that may affect ICH.", "entity": "Heparin", "aliases": "Heparin Sodium Unfractionated Heparinic Acid Liquaemin alpha alpha-Heparin", "definition": "A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.\n    ", "id": "MESH:D006493"}
{"mention": "Estradiol", "mention_text": "Estradiol reduces seizure-induced hippocampal injury in ovariectomized female but not in male rats.", "entity": "Estradiol", "aliases": "17 beta Estradiol Oestradiol beta-Estradiol beta-Oestradiol Aerodiol Estrace Estraderm TTS alpha 17beta Anhydrous Hemihydrate (17 alpha)-Isomer Monohydrate Orion Brand (+-)-Isomer (-)-Isomer (16 alpha,17 beta)-Isomer (17-alpha)-Isomer (8 beta)-(+-)-Isomer (9 beta,17 Monosodium Salt Sodium Estradiol-17 Estradiol-17beta Novartis Pharmaceuticals of Ovocyclin Vivelle", "definition": "The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.\n    ", "id": "MESH:D004958"}
{"mention": "seizure", "mention_text": "Estradiol reduces seizure-induced hippocampal injury in ovariectomized female but not in male rats.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "hippocampal injury", "mention_text": "Estradiol reduces seizure-induced hippocampal injury in ovariectomized female but not in male rats.", "entity": "Brain Injuries", "aliases": "Acute Brain Injuries Injury Contusion Contusions Diffuse Focal Traumatic Laceration Lacerations Trauma Traumas Cortical Encephalopathies Post-Concussive Post-Traumatic Encephalopathy Post Concussive Mild TBI (Traumatic Injury) TBIs", "definition": "Acute and chronic (see also BRAIN INJURIES, CHRONIC) injuries to the brain, including the cerebral hemispheres, CEREBELLUM, and BRAIN STEM. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with DIFFUSE AXONAL INJURY or COMA, POST-TRAUMATIC. Localized injuries may be associated with NEUROBEHAVIORAL MANIFESTATIONS; HEMIPARESIS, or other focal neurologic deficits.\n    ", "id": "MESH:D001930"}
{"mention": "hippocampal injury", "mention_text": "Estrogens protect ovariectomized rats from hippocampal injury induced by kainic acid-induced status epilepticus (SE). We compared the effects of 17beta-estradiol in adult male and ovariectomized female rats subjected to lithium-pilocarpine-induced SE. Rats received subcutaneous injections of 17beta-estradiol (2 microg/rat) or oil once daily for four consecutive days. SE was induced 20 h following the second injection and terminated 3 h later. The extent of silver-stained CA3 and CA1 hippocampal neurons was evaluated 2 days after SE. 17beta-Estradiol did not alter the onset of first clonus in ovariectomized rats but accelerated it in males. 17beta-Estradiol reduced the argyrophilic neurons in the CA1 and CA3-C sectors of ovariectomized rats. In males, estradiol increased the total damage score. These findings suggest that the effects of estradiol on seizure threshold and damage may be altered by sex-related differences in the hormonal environment.", "entity": "Brain Injuries", "aliases": "Acute Brain Injuries Injury Contusion Contusions Diffuse Focal Traumatic Laceration Lacerations Trauma Traumas Cortical Encephalopathies Post-Concussive Post-Traumatic Encephalopathy Post Concussive Mild TBI (Traumatic Injury) TBIs", "definition": "Acute and chronic (see also BRAIN INJURIES, CHRONIC) injuries to the brain, including the cerebral hemispheres, CEREBELLUM, and BRAIN STEM. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with DIFFUSE AXONAL INJURY or COMA, POST-TRAUMATIC. Localized injuries may be associated with NEUROBEHAVIORAL MANIFESTATIONS; HEMIPARESIS, or other focal neurologic deficits.\n    ", "id": "MESH:D001930"}
{"mention": "kainic acid", "mention_text": "Estrogens protect ovariectomized rats from hippocampal injury induced by kainic acid-induced status epilepticus (SE). We compared the effects of 17beta-estradiol in adult male and ovariectomized female rats subjected to lithium-pilocarpine-induced SE. Rats received subcutaneous injections of 17beta-estradiol (2 microg/rat) or oil once daily for four consecutive days. SE was induced 20 h following the second injection and terminated 3 h later. The extent of silver-stained CA3 and CA1 hippocampal neurons was evaluated 2 days after SE. 17beta-Estradiol did not alter the onset of first clonus in ovariectomized rats but accelerated it in males. 17beta-Estradiol reduced the argyrophilic neurons in the CA1 and CA3-C sectors of ovariectomized rats. In males, estradiol increased the total damage score. These findings suggest that the effects of estradiol on seizure threshold and damage may be altered by sex-related differences in the hormonal environment.", "entity": "Kainic Acid", "aliases": "Acid Digenic Kainic Kainate", "definition": "(2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose.\n    ", "id": "MESH:D007608"}
{"mention": "status epilepticus", "mention_text": "Estrogens protect ovariectomized rats from hippocampal injury induced by kainic acid-induced status epilepticus (SE). We compared the effects of 17beta-estradiol in adult male and ovariectomized female rats subjected to lithium-pilocarpine-induced SE. Rats received subcutaneous injections of 17beta-estradiol (2 microg/rat) or oil once daily for four consecutive days. SE was induced 20 h following the second injection and terminated 3 h later. The extent of silver-stained CA3 and CA1 hippocampal neurons was evaluated 2 days after SE. 17beta-Estradiol did not alter the onset of first clonus in ovariectomized rats but accelerated it in males. 17beta-Estradiol reduced the argyrophilic neurons in the CA1 and CA3-C sectors of ovariectomized rats. In males, estradiol increased the total damage score. These findings suggest that the effects of estradiol on seizure threshold and damage may be altered by sex-related differences in the hormonal environment.", "entity": "Status Epilepticus", "aliases": "Absence Status Complex Partial Epilepticus Electrographic Generalized Convulsive Grand Mal Non Non-Convulsive Petit Simple Subclinical", "definition": "A prolonged seizure or seizures repeated frequently enough to prevent recovery between episodes occurring over a period of 20-30 minutes. The most common subtype is generalized tonic-clonic status epilepticus, a potentially fatal condition associated with neuronal injury and respiratory and metabolic dysfunction. Nonconvulsive forms include petit mal status and complex partial status, which may manifest as behavioral disturbances. Simple partial status epilepticus consists of persistent motor, sensory, or autonomic seizures that do not impair cognition (see also EPILEPSIA PARTIALIS CONTINUA). Subclinical status epilepticus generally refers to seizures occurring in an unresponsive or comatose individual in the absence of overt signs of seizure activity. (From N Engl J Med 1998 Apr 2;338(14):970-6; Neurologia 1997 Dec;12 Suppl 6:25-30)\n    ", "id": "MESH:D013226"}
{"mention": "SE", "mention_text": "Estrogens protect ovariectomized rats from hippocampal injury induced by kainic acid-induced status epilepticus (SE). We compared the effects of 17beta-estradiol in adult male and ovariectomized female rats subjected to lithium-pilocarpine-induced SE. Rats received subcutaneous injections of 17beta-estradiol (2 microg/rat) or oil once daily for four consecutive days. SE was induced 20 h following the second injection and terminated 3 h later. The extent of silver-stained CA3 and CA1 hippocampal neurons was evaluated 2 days after SE. 17beta-Estradiol did not alter the onset of first clonus in ovariectomized rats but accelerated it in males. 17beta-Estradiol reduced the argyrophilic neurons in the CA1 and CA3-C sectors of ovariectomized rats. In males, estradiol increased the total damage score. These findings suggest that the effects of estradiol on seizure threshold and damage may be altered by sex-related differences in the hormonal environment.", "entity": "Status Epilepticus", "aliases": "Absence Status Complex Partial Epilepticus Electrographic Generalized Convulsive Grand Mal Non Non-Convulsive Petit Simple Subclinical", "definition": "A prolonged seizure or seizures repeated frequently enough to prevent recovery between episodes occurring over a period of 20-30 minutes. The most common subtype is generalized tonic-clonic status epilepticus, a potentially fatal condition associated with neuronal injury and respiratory and metabolic dysfunction. Nonconvulsive forms include petit mal status and complex partial status, which may manifest as behavioral disturbances. Simple partial status epilepticus consists of persistent motor, sensory, or autonomic seizures that do not impair cognition (see also EPILEPSIA PARTIALIS CONTINUA). Subclinical status epilepticus generally refers to seizures occurring in an unresponsive or comatose individual in the absence of overt signs of seizure activity. (From N Engl J Med 1998 Apr 2;338(14):970-6; Neurologia 1997 Dec;12 Suppl 6:25-30)\n    ", "id": "MESH:D013226"}
{"mention": "17beta-estradiol", "mention_text": "Estrogens protect ovariectomized rats from hippocampal injury induced by kainic acid-induced status epilepticus (SE). We compared the effects of 17beta-estradiol in adult male and ovariectomized female rats subjected to lithium-pilocarpine-induced SE. Rats received subcutaneous injections of 17beta-estradiol (2 microg/rat) or oil once daily for four consecutive days. SE was induced 20 h following the second injection and terminated 3 h later. The extent of silver-stained CA3 and CA1 hippocampal neurons was evaluated 2 days after SE. 17beta-Estradiol did not alter the onset of first clonus in ovariectomized rats but accelerated it in males. 17beta-Estradiol reduced the argyrophilic neurons in the CA1 and CA3-C sectors of ovariectomized rats. In males, estradiol increased the total damage score. These findings suggest that the effects of estradiol on seizure threshold and damage may be altered by sex-related differences in the hormonal environment.", "entity": "Estradiol", "aliases": "17 beta Estradiol Oestradiol beta-Estradiol beta-Oestradiol Aerodiol Estrace Estraderm TTS alpha 17beta Anhydrous Hemihydrate (17 alpha)-Isomer Monohydrate Orion Brand (+-)-Isomer (-)-Isomer (16 alpha,17 beta)-Isomer (17-alpha)-Isomer (8 beta)-(+-)-Isomer (9 beta,17 Monosodium Salt Sodium Estradiol-17 Estradiol-17beta Novartis Pharmaceuticals of Ovocyclin Vivelle", "definition": "The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.\n    ", "id": "MESH:D004958"}
{"mention": "lithium", "mention_text": "Estrogens protect ovariectomized rats from hippocampal injury induced by kainic acid-induced status epilepticus (SE). We compared the effects of 17beta-estradiol in adult male and ovariectomized female rats subjected to lithium-pilocarpine-induced SE. Rats received subcutaneous injections of 17beta-estradiol (2 microg/rat) or oil once daily for four consecutive days. SE was induced 20 h following the second injection and terminated 3 h later. The extent of silver-stained CA3 and CA1 hippocampal neurons was evaluated 2 days after SE. 17beta-Estradiol did not alter the onset of first clonus in ovariectomized rats but accelerated it in males. 17beta-Estradiol reduced the argyrophilic neurons in the CA1 and CA3-C sectors of ovariectomized rats. In males, estradiol increased the total damage score. These findings suggest that the effects of estradiol on seizure threshold and damage may be altered by sex-related differences in the hormonal environment.", "entity": "Lithium", "aliases": "Lithium", "definition": "An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.\n    ", "id": "MESH:D008094"}
{"mention": "pilocarpine", "mention_text": "Estrogens protect ovariectomized rats from hippocampal injury induced by kainic acid-induced status epilepticus (SE). We compared the effects of 17beta-estradiol in adult male and ovariectomized female rats subjected to lithium-pilocarpine-induced SE. Rats received subcutaneous injections of 17beta-estradiol (2 microg/rat) or oil once daily for four consecutive days. SE was induced 20 h following the second injection and terminated 3 h later. The extent of silver-stained CA3 and CA1 hippocampal neurons was evaluated 2 days after SE. 17beta-Estradiol did not alter the onset of first clonus in ovariectomized rats but accelerated it in males. 17beta-Estradiol reduced the argyrophilic neurons in the CA1 and CA3-C sectors of ovariectomized rats. In males, estradiol increased the total damage score. These findings suggest that the effects of estradiol on seizure threshold and damage may be altered by sex-related differences in the hormonal environment.", "entity": "Pilocarpine", "aliases": "Hydrochloride Pilocarpine Isopilocarpine Isoptocarpine Nitrate Ocusert Mononitrate (3S-cis)-Isomer Monohydrochloride Salagen", "definition": "A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma.\n    ", "id": "MESH:D010862"}
{"mention": "silver", "mention_text": "Estrogens protect ovariectomized rats from hippocampal injury induced by kainic acid-induced status epilepticus (SE). We compared the effects of 17beta-estradiol in adult male and ovariectomized female rats subjected to lithium-pilocarpine-induced SE. Rats received subcutaneous injections of 17beta-estradiol (2 microg/rat) or oil once daily for four consecutive days. SE was induced 20 h following the second injection and terminated 3 h later. The extent of silver-stained CA3 and CA1 hippocampal neurons was evaluated 2 days after SE. 17beta-Estradiol did not alter the onset of first clonus in ovariectomized rats but accelerated it in males. 17beta-Estradiol reduced the argyrophilic neurons in the CA1 and CA3-C sectors of ovariectomized rats. In males, estradiol increased the total damage score. These findings suggest that the effects of estradiol on seizure threshold and damage may be altered by sex-related differences in the hormonal environment.", "entity": "Silver", "aliases": "Silver", "definition": "Silver. An element with the atomic symbol Ag, atomic number 47, and atomic weight 107.87. It is a soft metal that is used medically in surgical instruments, dental prostheses, and alloys. Long-continued use of silver salts can lead to a form of poisoning known as ARGYRIA.\n    ", "id": "MESH:D012834"}
{"mention": "17beta-Estradiol", "mention_text": "Estrogens protect ovariectomized rats from hippocampal injury induced by kainic acid-induced status epilepticus (SE). We compared the effects of 17beta-estradiol in adult male and ovariectomized female rats subjected to lithium-pilocarpine-induced SE. Rats received subcutaneous injections of 17beta-estradiol (2 microg/rat) or oil once daily for four consecutive days. SE was induced 20 h following the second injection and terminated 3 h later. The extent of silver-stained CA3 and CA1 hippocampal neurons was evaluated 2 days after SE. 17beta-Estradiol did not alter the onset of first clonus in ovariectomized rats but accelerated it in males. 17beta-Estradiol reduced the argyrophilic neurons in the CA1 and CA3-C sectors of ovariectomized rats. In males, estradiol increased the total damage score. These findings suggest that the effects of estradiol on seizure threshold and damage may be altered by sex-related differences in the hormonal environment.", "entity": "Estradiol", "aliases": "17 beta Estradiol Oestradiol beta-Estradiol beta-Oestradiol Aerodiol Estrace Estraderm TTS alpha 17beta Anhydrous Hemihydrate (17 alpha)-Isomer Monohydrate Orion Brand (+-)-Isomer (-)-Isomer (16 alpha,17 beta)-Isomer (17-alpha)-Isomer (8 beta)-(+-)-Isomer (9 beta,17 Monosodium Salt Sodium Estradiol-17 Estradiol-17beta Novartis Pharmaceuticals of Ovocyclin Vivelle", "definition": "The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.\n    ", "id": "MESH:D004958"}
{"mention": "estradiol", "mention_text": "Estrogens protect ovariectomized rats from hippocampal injury induced by kainic acid-induced status epilepticus (SE). We compared the effects of 17beta-estradiol in adult male and ovariectomized female rats subjected to lithium-pilocarpine-induced SE. Rats received subcutaneous injections of 17beta-estradiol (2 microg/rat) or oil once daily for four consecutive days. SE was induced 20 h following the second injection and terminated 3 h later. The extent of silver-stained CA3 and CA1 hippocampal neurons was evaluated 2 days after SE. 17beta-Estradiol did not alter the onset of first clonus in ovariectomized rats but accelerated it in males. 17beta-Estradiol reduced the argyrophilic neurons in the CA1 and CA3-C sectors of ovariectomized rats. In males, estradiol increased the total damage score. These findings suggest that the effects of estradiol on seizure threshold and damage may be altered by sex-related differences in the hormonal environment.", "entity": "Estradiol", "aliases": "17 beta Estradiol Oestradiol beta-Estradiol beta-Oestradiol Aerodiol Estrace Estraderm TTS alpha 17beta Anhydrous Hemihydrate (17 alpha)-Isomer Monohydrate Orion Brand (+-)-Isomer (-)-Isomer (16 alpha,17 beta)-Isomer (17-alpha)-Isomer (8 beta)-(+-)-Isomer (9 beta,17 Monosodium Salt Sodium Estradiol-17 Estradiol-17beta Novartis Pharmaceuticals of Ovocyclin Vivelle", "definition": "The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.\n    ", "id": "MESH:D004958"}
{"mention": "seizure", "mention_text": "Estrogens protect ovariectomized rats from hippocampal injury induced by kainic acid-induced status epilepticus (SE). We compared the effects of 17beta-estradiol in adult male and ovariectomized female rats subjected to lithium-pilocarpine-induced SE. Rats received subcutaneous injections of 17beta-estradiol (2 microg/rat) or oil once daily for four consecutive days. SE was induced 20 h following the second injection and terminated 3 h later. The extent of silver-stained CA3 and CA1 hippocampal neurons was evaluated 2 days after SE. 17beta-Estradiol did not alter the onset of first clonus in ovariectomized rats but accelerated it in males. 17beta-Estradiol reduced the argyrophilic neurons in the CA1 and CA3-C sectors of ovariectomized rats. In males, estradiol increased the total damage score. These findings suggest that the effects of estradiol on seizure threshold and damage may be altered by sex-related differences in the hormonal environment.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "Delirium", "mention_text": "Delirium during clozapine treatment: incidence and associated risk factors.", "entity": "Delirium", "aliases": "Delirium of Mixed Origin Subacute Deliriums", "definition": "A disorder characterized by CONFUSION; inattentiveness; disorientation; ILLUSIONS; HALLUCINATIONS; agitation; and in some instances autonomic nervous system overactivity. It may result from toxic/metabolic conditions or structural brain lesions. (From Adams et al., Principles of Neurology, 6th ed, pp411-2)\n    ", "id": "MESH:D003693"}
{"mention": "clozapine", "mention_text": "Delirium during clozapine treatment: incidence and associated risk factors.", "entity": "Clozapine", "aliases": "Clozapine Clozaril Leponex", "definition": "A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.\n    ", "id": "MESH:D003024"}
{"mention": "delirium", "mention_text": "BACKGROUND: Incidence and risk factors for delirium during clozapine treatment require further clarification. METHODS: We used computerized pharmacy records to identify all adult psychiatric inpatients treated with clozapine (1995-96), reviewed their medical records to score incidence and severity of delirium, and tested associations with potential risk factors. RESULTS: Subjects (n = 139) were 72 women and 67 men, aged 40.8 +/- 12.1 years, hospitalized for 24.9 +/- 23.3 days, and given clozapine, gradually increased to an average daily dose of 282 +/- 203 mg (3.45 +/- 2.45 mg/kg) for 18.9 +/- 16.4 days. Delirium was diagnosed in 14 (10.1 % incidence, or 1.48 cases/person-years of exposure); 71.4 % of cases were moderate or severe. Associated factors were co-treatment with other centrally antimuscarinic agents, poor clinical outcome, older age, and longer hospitalization (by 17.5 days, increasing cost); sex, diagnosis or medical co-morbidity, and daily clozapine dose, which fell with age, were unrelated. CONCLUSIONS: Delirium was found in 10 % of clozapine-treated inpatients, particularly in older patients exposed to other central anticholinergics. Delirium was inconsistently recognized clinically in milder cases and was associated with increased length-of-stay and higher costs, and inferior clinical outcome.", "entity": "Delirium", "aliases": "Delirium of Mixed Origin Subacute Deliriums", "definition": "A disorder characterized by CONFUSION; inattentiveness; disorientation; ILLUSIONS; HALLUCINATIONS; agitation; and in some instances autonomic nervous system overactivity. It may result from toxic/metabolic conditions or structural brain lesions. (From Adams et al., Principles of Neurology, 6th ed, pp411-2)\n    ", "id": "MESH:D003693"}
{"mention": "clozapine", "mention_text": "BACKGROUND: Incidence and risk factors for delirium during clozapine treatment require further clarification. METHODS: We used computerized pharmacy records to identify all adult psychiatric inpatients treated with clozapine (1995-96), reviewed their medical records to score incidence and severity of delirium, and tested associations with potential risk factors. RESULTS: Subjects (n = 139) were 72 women and 67 men, aged 40.8 +/- 12.1 years, hospitalized for 24.9 +/- 23.3 days, and given clozapine, gradually increased to an average daily dose of 282 +/- 203 mg (3.45 +/- 2.45 mg/kg) for 18.9 +/- 16.4 days. Delirium was diagnosed in 14 (10.1 % incidence, or 1.48 cases/person-years of exposure); 71.4 % of cases were moderate or severe. Associated factors were co-treatment with other centrally antimuscarinic agents, poor clinical outcome, older age, and longer hospitalization (by 17.5 days, increasing cost); sex, diagnosis or medical co-morbidity, and daily clozapine dose, which fell with age, were unrelated. CONCLUSIONS: Delirium was found in 10 % of clozapine-treated inpatients, particularly in older patients exposed to other central anticholinergics. Delirium was inconsistently recognized clinically in milder cases and was associated with increased length-of-stay and higher costs, and inferior clinical outcome.", "entity": "Clozapine", "aliases": "Clozapine Clozaril Leponex", "definition": "A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.\n    ", "id": "MESH:D003024"}
{"mention": "psychiatric", "mention_text": "BACKGROUND: Incidence and risk factors for delirium during clozapine treatment require further clarification. METHODS: We used computerized pharmacy records to identify all adult psychiatric inpatients treated with clozapine (1995-96), reviewed their medical records to score incidence and severity of delirium, and tested associations with potential risk factors. RESULTS: Subjects (n = 139) were 72 women and 67 men, aged 40.8 +/- 12.1 years, hospitalized for 24.9 +/- 23.3 days, and given clozapine, gradually increased to an average daily dose of 282 +/- 203 mg (3.45 +/- 2.45 mg/kg) for 18.9 +/- 16.4 days. Delirium was diagnosed in 14 (10.1 % incidence, or 1.48 cases/person-years of exposure); 71.4 % of cases were moderate or severe. Associated factors were co-treatment with other centrally antimuscarinic agents, poor clinical outcome, older age, and longer hospitalization (by 17.5 days, increasing cost); sex, diagnosis or medical co-morbidity, and daily clozapine dose, which fell with age, were unrelated. CONCLUSIONS: Delirium was found in 10 % of clozapine-treated inpatients, particularly in older patients exposed to other central anticholinergics. Delirium was inconsistently recognized clinically in milder cases and was associated with increased length-of-stay and higher costs, and inferior clinical outcome.", "entity": "Mental Disorders", "aliases": "Behavior Disorders Diagnosis Psychiatric Disorder Mental", "definition": "Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.\n    ", "id": "MESH:D001523"}
{"mention": "Delirium", "mention_text": "BACKGROUND: Incidence and risk factors for delirium during clozapine treatment require further clarification. METHODS: We used computerized pharmacy records to identify all adult psychiatric inpatients treated with clozapine (1995-96), reviewed their medical records to score incidence and severity of delirium, and tested associations with potential risk factors. RESULTS: Subjects (n = 139) were 72 women and 67 men, aged 40.8 +/- 12.1 years, hospitalized for 24.9 +/- 23.3 days, and given clozapine, gradually increased to an average daily dose of 282 +/- 203 mg (3.45 +/- 2.45 mg/kg) for 18.9 +/- 16.4 days. Delirium was diagnosed in 14 (10.1 % incidence, or 1.48 cases/person-years of exposure); 71.4 % of cases were moderate or severe. Associated factors were co-treatment with other centrally antimuscarinic agents, poor clinical outcome, older age, and longer hospitalization (by 17.5 days, increasing cost); sex, diagnosis or medical co-morbidity, and daily clozapine dose, which fell with age, were unrelated. CONCLUSIONS: Delirium was found in 10 % of clozapine-treated inpatients, particularly in older patients exposed to other central anticholinergics. Delirium was inconsistently recognized clinically in milder cases and was associated with increased length-of-stay and higher costs, and inferior clinical outcome.", "entity": "Delirium", "aliases": "Delirium of Mixed Origin Subacute Deliriums", "definition": "A disorder characterized by CONFUSION; inattentiveness; disorientation; ILLUSIONS; HALLUCINATIONS; agitation; and in some instances autonomic nervous system overactivity. It may result from toxic/metabolic conditions or structural brain lesions. (From Adams et al., Principles of Neurology, 6th ed, pp411-2)\n    ", "id": "MESH:D003693"}
{"mention": "Ketoconazole", "mention_text": "Ketoconazole-induced neurologic sequelae.", "entity": "Ketoconazole", "aliases": "Janssen Brand of Ketoconazole Nizoral R 41400 R-41400 R41,400 R41400", "definition": "Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.\n    ", "id": "MESH:D007654"}
{"mention": "neurologic sequelae", "mention_text": "Ketoconazole-induced neurologic sequelae.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "weakness of extremities", "mention_text": "A 77-y-old patient developed weakness of extremities, legs paralysis, dysarthria and tremor 1 h after ingestion of 200 mg ketoconazole for the first time in his life. All complaints faded away within 24 h. Few days later, the patient used another 200 mg ketoconazole tablet, and within an hour experienced a similar clinical picture, which resolved again spontaneously within hours. Laboratory evaluations, including head CT scan, were normal. This case illustrates the need for close vigilance in adverse drug reactions, particularly in the elderly.", "entity": "Muscle Weakness", "aliases": "Muscle Weakness Weaknesses Muscular", "definition": "A vague complaint of debility, fatigue, or exhaustion attributable to weakness of various muscles. The weakness can be characterized as subacute or chronic, often progressive, and is a manifestation of many muscle and neuromuscular diseases. (From Wyngaarden et al., Cecil Textbook of Medicine, 19th ed, p2251)\n    ", "id": "MESH:D018908"}
{"mention": "legs paralysis", "mention_text": "A 77-y-old patient developed weakness of extremities, legs paralysis, dysarthria and tremor 1 h after ingestion of 200 mg ketoconazole for the first time in his life. All complaints faded away within 24 h. Few days later, the patient used another 200 mg ketoconazole tablet, and within an hour experienced a similar clinical picture, which resolved again spontaneously within hours. Laboratory evaluations, including head CT scan, were normal. This case illustrates the need for close vigilance in adverse drug reactions, particularly in the elderly.", "entity": "Paralysis", "aliases": "Palsies Palsy Paralyses Paralysis Todd Todd's Plegia Plegias Todds", "definition": "A general term most often used to describe severe or complete loss of muscle strength due to motor system disease from the level of the cerebral cortex to the muscle fiber. This term may also occasionally refer to a loss of sensory function. (From Adams et al., Principles of Neurology, 6th ed, p45)\n    ", "id": "MESH:D010243"}
{"mention": "dysarthria", "mention_text": "A 77-y-old patient developed weakness of extremities, legs paralysis, dysarthria and tremor 1 h after ingestion of 200 mg ketoconazole for the first time in his life. All complaints faded away within 24 h. Few days later, the patient used another 200 mg ketoconazole tablet, and within an hour experienced a similar clinical picture, which resolved again spontaneously within hours. Laboratory evaluations, including head CT scan, were normal. This case illustrates the need for close vigilance in adverse drug reactions, particularly in the elderly.", "entity": "Dysarthria", "aliases": "Dysarthoses Dysarthosis Dysarthria Flaccid Guttural Mixed Scanning Spastic Dysarthrias", "definition": "Disorders of speech articulation caused by imperfect coordination of pharynx, larynx, tongue, or face muscles. This may result from CRANIAL NERVE DISEASES; NEUROMUSCULAR DISEASES; CEREBELLAR DISEASES; BASAL GANGLIA DISEASES; BRAIN STEM diseases; or diseases of the corticobulbar tracts (see PYRAMIDAL TRACTS). The cortical language centers are intact in this condition. (From Adams et al., Principles of Neurology, 6th ed, p489)\n    ", "id": "MESH:D004401"}
{"mention": "tremor", "mention_text": "A 77-y-old patient developed weakness of extremities, legs paralysis, dysarthria and tremor 1 h after ingestion of 200 mg ketoconazole for the first time in his life. All complaints faded away within 24 h. Few days later, the patient used another 200 mg ketoconazole tablet, and within an hour experienced a similar clinical picture, which resolved again spontaneously within hours. Laboratory evaluations, including head CT scan, were normal. This case illustrates the need for close vigilance in adverse drug reactions, particularly in the elderly.", "entity": "Tremor", "aliases": "Action Tremor Tremors Coarse Continuous Darkness Fine Intention Intermittent Involuntary Quiver Quivers Limb Massive Muscle Neonatal Nerve Passive Perioral Persistent Pill Rolling Rest Resting Saturnine Semirhythmic Senile Static", "definition": "Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of CEREBELLAR DISEASES, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of PARKINSON DISEASE.\n    ", "id": "MESH:D014202"}
{"mention": "ketoconazole", "mention_text": "A 77-y-old patient developed weakness of extremities, legs paralysis, dysarthria and tremor 1 h after ingestion of 200 mg ketoconazole for the first time in his life. All complaints faded away within 24 h. Few days later, the patient used another 200 mg ketoconazole tablet, and within an hour experienced a similar clinical picture, which resolved again spontaneously within hours. Laboratory evaluations, including head CT scan, were normal. This case illustrates the need for close vigilance in adverse drug reactions, particularly in the elderly.", "entity": "Ketoconazole", "aliases": "Janssen Brand of Ketoconazole Nizoral R 41400 R-41400 R41,400 R41400", "definition": "Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.\n    ", "id": "MESH:D007654"}
{"mention": "adverse drug reactions", "mention_text": "A 77-y-old patient developed weakness of extremities, legs paralysis, dysarthria and tremor 1 h after ingestion of 200 mg ketoconazole for the first time in his life. All complaints faded away within 24 h. Few days later, the patient used another 200 mg ketoconazole tablet, and within an hour experienced a similar clinical picture, which resolved again spontaneously within hours. Laboratory evaluations, including head CT scan, were normal. This case illustrates the need for close vigilance in adverse drug reactions, particularly in the elderly.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "vascular dysfunctions", "mention_text": "Noxious chemical stimulation of rat facial mucosa increases intracranial blood flow through a trigemino-parasympathetic reflex--an experimental model for vascular dysfunctions in cluster headache.", "entity": "Cerebrovascular Disorders", "aliases": "Brain Vascular Disorder Disorders Cerebrovascular Insufficiencies Insufficiency Occlusion Occlusions Intracranial Disease Diseases", "definition": "A spectrum of pathological conditions of impaired blood flow in the brain. They can involve vessels (ARTERIES; or VEINS) in the CEREBRUM, the CEREBELLUM, and the BRAIN STEM. Major categories include INTRACRANIAL ARTERIOVENOUS MALFORMATIONS; BRAIN ISCHEMIA; CEREBRAL HEMORRHAGE; and others.\n    ", "id": "MESH:D002561"}
{"mention": "cluster headache", "mention_text": "Noxious chemical stimulation of rat facial mucosa increases intracranial blood flow through a trigemino-parasympathetic reflex--an experimental model for vascular dysfunctions in cluster headache.", "entity": "Cluster Headache", "aliases": "Atypical Cluster Headache Headaches Cephalgia Histamine Cephalgias Chronic Ciliary Neuralgia Neuralgias Syndrome Syndromes Episodic Horton Horton's Hortons Migraine Neuralgic Migraines", "definition": "A primary headache disorder that is characterized by severe, strictly unilateral PAIN which is orbital, supraorbital, temporal or in any combination of these sites, lasting 15-180 min. occurring 1 to 8 times a day. The attacks are associated with one or more of the following, all of which are ipsilateral: conjunctival injection, lacrimation, nasal congestion, rhinorrhea, facial SWEATING, eyelid EDEMA, and miosis. (International Classification of Headache Disorders, 2nd ed. Cephalalgia 2004: suppl 1)\n    ", "id": "MESH:D003027"}
{"mention": "Cluster headache", "mention_text": "Cluster headache is characterized by typical autonomic dysfunctions including facial and intracranial vascular disturbances. Both the trigeminal and the cranial parasympathetic systems may be involved in mediating these dysfunctions. An experimental model was developed in the rat to measure changes in lacrimation and intracranial blood flow following noxious chemical stimulation of facial mucosa. Blood flow was monitored in arteries of the exposed cranial dura mater and the parietal cortex using laser Doppler flowmetry. Capsaicin (0.01-1 mm) applied to oral or nasal mucosa induced increases in dural and cortical blood flow and provoked lacrimation. These responses were blocked by systemic pre-administration of hexamethonium chloride (20 mg/kg). The evoked increases in dural blood flow were also abolished by topical pre-administration of atropine (1 mm) and [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP (0.1 mm), a vasoactive intestinal polypeptide (VIP) antagonist, onto the exposed dura mater. We conclude that noxious stimulation of facial mucosa increases intracranial blood flow and lacrimation via a trigemino-parasympathetic reflex. The blood flow responses seem to be mediated by the release of acetylcholine and VIP within the meninges. Similar mechanisms may be involved in the pathogenesis of cluster headache.", "entity": "Cluster Headache", "aliases": "Atypical Cluster Headache Headaches Cephalgia Histamine Cephalgias Chronic Ciliary Neuralgia Neuralgias Syndrome Syndromes Episodic Horton Horton's Hortons Migraine Neuralgic Migraines", "definition": "A primary headache disorder that is characterized by severe, strictly unilateral PAIN which is orbital, supraorbital, temporal or in any combination of these sites, lasting 15-180 min. occurring 1 to 8 times a day. The attacks are associated with one or more of the following, all of which are ipsilateral: conjunctival injection, lacrimation, nasal congestion, rhinorrhea, facial SWEATING, eyelid EDEMA, and miosis. (International Classification of Headache Disorders, 2nd ed. Cephalalgia 2004: suppl 1)\n    ", "id": "MESH:D003027"}
{"mention": "intracranial vascular disturbances", "mention_text": "Cluster headache is characterized by typical autonomic dysfunctions including facial and intracranial vascular disturbances. Both the trigeminal and the cranial parasympathetic systems may be involved in mediating these dysfunctions. An experimental model was developed in the rat to measure changes in lacrimation and intracranial blood flow following noxious chemical stimulation of facial mucosa. Blood flow was monitored in arteries of the exposed cranial dura mater and the parietal cortex using laser Doppler flowmetry. Capsaicin (0.01-1 mm) applied to oral or nasal mucosa induced increases in dural and cortical blood flow and provoked lacrimation. These responses were blocked by systemic pre-administration of hexamethonium chloride (20 mg/kg). The evoked increases in dural blood flow were also abolished by topical pre-administration of atropine (1 mm) and [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP (0.1 mm), a vasoactive intestinal polypeptide (VIP) antagonist, onto the exposed dura mater. We conclude that noxious stimulation of facial mucosa increases intracranial blood flow and lacrimation via a trigemino-parasympathetic reflex. The blood flow responses seem to be mediated by the release of acetylcholine and VIP within the meninges. Similar mechanisms may be involved in the pathogenesis of cluster headache.", "entity": "Cerebrovascular Disorders", "aliases": "Brain Vascular Disorder Disorders Cerebrovascular Insufficiencies Insufficiency Occlusion Occlusions Intracranial Disease Diseases", "definition": "A spectrum of pathological conditions of impaired blood flow in the brain. They can involve vessels (ARTERIES; or VEINS) in the CEREBRUM, the CEREBELLUM, and the BRAIN STEM. Major categories include INTRACRANIAL ARTERIOVENOUS MALFORMATIONS; BRAIN ISCHEMIA; CEREBRAL HEMORRHAGE; and others.\n    ", "id": "MESH:D002561"}
{"mention": "Capsaicin", "mention_text": "Cluster headache is characterized by typical autonomic dysfunctions including facial and intracranial vascular disturbances. Both the trigeminal and the cranial parasympathetic systems may be involved in mediating these dysfunctions. An experimental model was developed in the rat to measure changes in lacrimation and intracranial blood flow following noxious chemical stimulation of facial mucosa. Blood flow was monitored in arteries of the exposed cranial dura mater and the parietal cortex using laser Doppler flowmetry. Capsaicin (0.01-1 mm) applied to oral or nasal mucosa induced increases in dural and cortical blood flow and provoked lacrimation. These responses were blocked by systemic pre-administration of hexamethonium chloride (20 mg/kg). The evoked increases in dural blood flow were also abolished by topical pre-administration of atropine (1 mm) and [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP (0.1 mm), a vasoactive intestinal polypeptide (VIP) antagonist, onto the exposed dura mater. We conclude that noxious stimulation of facial mucosa increases intracranial blood flow and lacrimation via a trigemino-parasympathetic reflex. The blood flow responses seem to be mediated by the release of acetylcholine and VIP within the meninges. Similar mechanisms may be involved in the pathogenesis of cluster headache.", "entity": "Capsaicin", "aliases": "8 Methyl N Vanillyl 6 Nonenamide 8-Methyl-N-Vanillyl-6-Nonenamide Alacan Brand of Capsaicin Antiphlogistine Rub A-535 Axsain Capsaicine Capsicum Farmaya Capsidol Capsin Capzasin Carter Horner Centrum Elan Flemming Gelcen Katrum Link Medicis NGX 4010 NGX-4010 NGX4010 Smaller Thompson Vinas Zacin Zostrix", "definition": "An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.\n    ", "id": "MESH:D002211"}
{"mention": "increases in dural and cortical blood flow", "mention_text": "Cluster headache is characterized by typical autonomic dysfunctions including facial and intracranial vascular disturbances. Both the trigeminal and the cranial parasympathetic systems may be involved in mediating these dysfunctions. An experimental model was developed in the rat to measure changes in lacrimation and intracranial blood flow following noxious chemical stimulation of facial mucosa. Blood flow was monitored in arteries of the exposed cranial dura mater and the parietal cortex using laser Doppler flowmetry. Capsaicin (0.01-1 mm) applied to oral or nasal mucosa induced increases in dural and cortical blood flow and provoked lacrimation. These responses were blocked by systemic pre-administration of hexamethonium chloride (20 mg/kg). The evoked increases in dural blood flow were also abolished by topical pre-administration of atropine (1 mm) and [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP (0.1 mm), a vasoactive intestinal polypeptide (VIP) antagonist, onto the exposed dura mater. We conclude that noxious stimulation of facial mucosa increases intracranial blood flow and lacrimation via a trigemino-parasympathetic reflex. The blood flow responses seem to be mediated by the release of acetylcholine and VIP within the meninges. Similar mechanisms may be involved in the pathogenesis of cluster headache.", "entity": "Hyperemia", "aliases": "Active Hyperemia Arterial Congestion Venous Engorgement Passive Reactive Hyperemias", "definition": "The presence of an increased amount of blood in a body part or an organ leading to congestion or engorgement of blood vessels. Hyperemia can be due to increase of blood flow into the area (active or arterial), or due to obstruction of outflow of blood from the area (passive or venous).\n    ", "id": "MESH:D006940"}
{"mention": "hexamethonium chloride", "mention_text": "Cluster headache is characterized by typical autonomic dysfunctions including facial and intracranial vascular disturbances. Both the trigeminal and the cranial parasympathetic systems may be involved in mediating these dysfunctions. An experimental model was developed in the rat to measure changes in lacrimation and intracranial blood flow following noxious chemical stimulation of facial mucosa. Blood flow was monitored in arteries of the exposed cranial dura mater and the parietal cortex using laser Doppler flowmetry. Capsaicin (0.01-1 mm) applied to oral or nasal mucosa induced increases in dural and cortical blood flow and provoked lacrimation. These responses were blocked by systemic pre-administration of hexamethonium chloride (20 mg/kg). The evoked increases in dural blood flow were also abolished by topical pre-administration of atropine (1 mm) and [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP (0.1 mm), a vasoactive intestinal polypeptide (VIP) antagonist, onto the exposed dura mater. We conclude that noxious stimulation of facial mucosa increases intracranial blood flow and lacrimation via a trigemino-parasympathetic reflex. The blood flow responses seem to be mediated by the release of acetylcholine and VIP within the meninges. Similar mechanisms may be involved in the pathogenesis of cluster headache.", "entity": "Hexamethonium", "aliases": "Bitartrate Hexamethonium Bromide Chloride Depressin Dibromide Dihydrate Dichloride Dihydroxide Diiodide Dimethylsulfate Diperchlorate Iodide Monotartrate Hexonium", "definition": "A nicotinic cholinergic antagonist often referred to as the prototypical ganglionic blocker. It is poorly absorbed from the gastrointestinal tract and does not cross the blood-brain barrier. It has been used for a variety of therapeutic purposes including hypertension but, like the other ganglionic blockers, it has been replaced by more specific drugs for most purposes, although it is widely used a research tool.\n    ", "id": "MESH:D018738"}
{"mention": "increases in dural blood flow", "mention_text": "Cluster headache is characterized by typical autonomic dysfunctions including facial and intracranial vascular disturbances. Both the trigeminal and the cranial parasympathetic systems may be involved in mediating these dysfunctions. An experimental model was developed in the rat to measure changes in lacrimation and intracranial blood flow following noxious chemical stimulation of facial mucosa. Blood flow was monitored in arteries of the exposed cranial dura mater and the parietal cortex using laser Doppler flowmetry. Capsaicin (0.01-1 mm) applied to oral or nasal mucosa induced increases in dural and cortical blood flow and provoked lacrimation. These responses were blocked by systemic pre-administration of hexamethonium chloride (20 mg/kg). The evoked increases in dural blood flow were also abolished by topical pre-administration of atropine (1 mm) and [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP (0.1 mm), a vasoactive intestinal polypeptide (VIP) antagonist, onto the exposed dura mater. We conclude that noxious stimulation of facial mucosa increases intracranial blood flow and lacrimation via a trigemino-parasympathetic reflex. The blood flow responses seem to be mediated by the release of acetylcholine and VIP within the meninges. Similar mechanisms may be involved in the pathogenesis of cluster headache.", "entity": "Hyperemia", "aliases": "Active Hyperemia Arterial Congestion Venous Engorgement Passive Reactive Hyperemias", "definition": "The presence of an increased amount of blood in a body part or an organ leading to congestion or engorgement of blood vessels. Hyperemia can be due to increase of blood flow into the area (active or arterial), or due to obstruction of outflow of blood from the area (passive or venous).\n    ", "id": "MESH:D006940"}
{"mention": "atropine", "mention_text": "Cluster headache is characterized by typical autonomic dysfunctions including facial and intracranial vascular disturbances. Both the trigeminal and the cranial parasympathetic systems may be involved in mediating these dysfunctions. An experimental model was developed in the rat to measure changes in lacrimation and intracranial blood flow following noxious chemical stimulation of facial mucosa. Blood flow was monitored in arteries of the exposed cranial dura mater and the parietal cortex using laser Doppler flowmetry. Capsaicin (0.01-1 mm) applied to oral or nasal mucosa induced increases in dural and cortical blood flow and provoked lacrimation. These responses were blocked by systemic pre-administration of hexamethonium chloride (20 mg/kg). The evoked increases in dural blood flow were also abolished by topical pre-administration of atropine (1 mm) and [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP (0.1 mm), a vasoactive intestinal polypeptide (VIP) antagonist, onto the exposed dura mater. We conclude that noxious stimulation of facial mucosa increases intracranial blood flow and lacrimation via a trigemino-parasympathetic reflex. The blood flow responses seem to be mediated by the release of acetylcholine and VIP within the meninges. Similar mechanisms may be involved in the pathogenesis of cluster headache.", "entity": "Atropine", "aliases": "Anhydrous Atropine Sulfate AtroPen Atropin Augenöl Chauvin Brand Winzer Atropinol of Survival Technology", "definition": "An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.\n    ", "id": "MESH:D001285"}
{"mention": "acetylcholine", "mention_text": "Cluster headache is characterized by typical autonomic dysfunctions including facial and intracranial vascular disturbances. Both the trigeminal and the cranial parasympathetic systems may be involved in mediating these dysfunctions. An experimental model was developed in the rat to measure changes in lacrimation and intracranial blood flow following noxious chemical stimulation of facial mucosa. Blood flow was monitored in arteries of the exposed cranial dura mater and the parietal cortex using laser Doppler flowmetry. Capsaicin (0.01-1 mm) applied to oral or nasal mucosa induced increases in dural and cortical blood flow and provoked lacrimation. These responses were blocked by systemic pre-administration of hexamethonium chloride (20 mg/kg). The evoked increases in dural blood flow were also abolished by topical pre-administration of atropine (1 mm) and [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP (0.1 mm), a vasoactive intestinal polypeptide (VIP) antagonist, onto the exposed dura mater. We conclude that noxious stimulation of facial mucosa increases intracranial blood flow and lacrimation via a trigemino-parasympathetic reflex. The blood flow responses seem to be mediated by the release of acetylcholine and VIP within the meninges. Similar mechanisms may be involved in the pathogenesis of cluster headache.", "entity": "Acetylcholine", "aliases": "2-(Acetyloxy)-N,N,N-trimethylethanaminium Acetilcolina Cusi Acetylcholine Bromide Chloride Fluoride Hydroxide Iodide L Tartrate L-Tartrate Perchlorate Picrate (1:1) Sulfate Alcon Brand of Bournonville Bromoacetylcholine Chloroacetylcholine Ciba Vision Iolab Miochol", "definition": "A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.\n    ", "id": "MESH:D000109"}
{"mention": "cluster headache", "mention_text": "Cluster headache is characterized by typical autonomic dysfunctions including facial and intracranial vascular disturbances. Both the trigeminal and the cranial parasympathetic systems may be involved in mediating these dysfunctions. An experimental model was developed in the rat to measure changes in lacrimation and intracranial blood flow following noxious chemical stimulation of facial mucosa. Blood flow was monitored in arteries of the exposed cranial dura mater and the parietal cortex using laser Doppler flowmetry. Capsaicin (0.01-1 mm) applied to oral or nasal mucosa induced increases in dural and cortical blood flow and provoked lacrimation. These responses were blocked by systemic pre-administration of hexamethonium chloride (20 mg/kg). The evoked increases in dural blood flow were also abolished by topical pre-administration of atropine (1 mm) and [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP (0.1 mm), a vasoactive intestinal polypeptide (VIP) antagonist, onto the exposed dura mater. We conclude that noxious stimulation of facial mucosa increases intracranial blood flow and lacrimation via a trigemino-parasympathetic reflex. The blood flow responses seem to be mediated by the release of acetylcholine and VIP within the meninges. Similar mechanisms may be involved in the pathogenesis of cluster headache.", "entity": "Cluster Headache", "aliases": "Atypical Cluster Headache Headaches Cephalgia Histamine Cephalgias Chronic Ciliary Neuralgia Neuralgias Syndrome Syndromes Episodic Horton Horton's Hortons Migraine Neuralgic Migraines", "definition": "A primary headache disorder that is characterized by severe, strictly unilateral PAIN which is orbital, supraorbital, temporal or in any combination of these sites, lasting 15-180 min. occurring 1 to 8 times a day. The attacks are associated with one or more of the following, all of which are ipsilateral: conjunctival injection, lacrimation, nasal congestion, rhinorrhea, facial SWEATING, eyelid EDEMA, and miosis. (International Classification of Headache Disorders, 2nd ed. Cephalalgia 2004: suppl 1)\n    ", "id": "MESH:D003027"}
{"mention": "temporal lobe epilepsy", "mention_text": "Recurrent excitation in the dentate gyrus of a murine model of temporal lobe epilepsy.", "entity": "Epilepsy, Temporal Lobe", "aliases": "Benign Psychomotor Epilepsy Childhood Epilepsies Lateral Temporal Lobe Uncinate", "definition": "A localization-related (focal) form of epilepsy characterized by recurrent seizures that arise from foci within the temporal lobe, most commonly from its mesial aspect. A wide variety of psychic phenomena may be associated, including illusions, hallucinations, dyscognitive states, and affective experiences. The majority of complex partial seizures (see EPILEPSY, COMPLEX PARTIAL) originate from the temporal lobes. Temporal lobe seizures may be classified by etiology as cryptogenic, familial, or symptomatic (i.e., related to an identified disease process or lesion). (From Adams et al., Principles of Neurology, 6th ed, p321)\n    ", "id": "MESH:D004833"}
{"mention": "pilocarpine", "mention_text": "Similar to rats, systemic pilocarpine injection causes status epilepticus (SE) and the eventual development of spontaneous seizures and mossy fiber sprouting in C57BL/6 and CD1 mice, but the physiological correlates of these events have not been identified in mice. Population responses in granule cells of the dentate gyrus were examined in transverse slices of the ventral hippocampus from pilocarpine-treated and untreated mice. In Mg(2+)-free bathing medium containing bicuculline, conditions designed to increase excitability in the slices, electrical stimulation of the hilus resulted in a single population spike in granule cells from control mice and pilocarpine-treated mice that did not experience SE. In SE survivors, similar stimulation resulted in a population spike followed, at a variable latency, by negative DC shifts and repetitive afterdischarges of 3-60 s duration, which were blocked by ionotropic glutamate receptor antagonists. Focal glutamate photostimulation of the granule cell layer at sites distant from the recording pipette resulted in population responses of 1-30 s duration in slices from SE survivors but not other groups. These data support the hypothesis that SE-induced mossy fiber sprouting and synaptic reorganization are relevant characteristics of seizure development in these murine strains, resembling rat models of human temporal lobe epilepsy.", "entity": "Pilocarpine", "aliases": "Hydrochloride Pilocarpine Isopilocarpine Isoptocarpine Nitrate Ocusert Mononitrate (3S-cis)-Isomer Monohydrochloride Salagen", "definition": "A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma.\n    ", "id": "MESH:D010862"}
{"mention": "status epilepticus", "mention_text": "Similar to rats, systemic pilocarpine injection causes status epilepticus (SE) and the eventual development of spontaneous seizures and mossy fiber sprouting in C57BL/6 and CD1 mice, but the physiological correlates of these events have not been identified in mice. Population responses in granule cells of the dentate gyrus were examined in transverse slices of the ventral hippocampus from pilocarpine-treated and untreated mice. In Mg(2+)-free bathing medium containing bicuculline, conditions designed to increase excitability in the slices, electrical stimulation of the hilus resulted in a single population spike in granule cells from control mice and pilocarpine-treated mice that did not experience SE. In SE survivors, similar stimulation resulted in a population spike followed, at a variable latency, by negative DC shifts and repetitive afterdischarges of 3-60 s duration, which were blocked by ionotropic glutamate receptor antagonists. Focal glutamate photostimulation of the granule cell layer at sites distant from the recording pipette resulted in population responses of 1-30 s duration in slices from SE survivors but not other groups. These data support the hypothesis that SE-induced mossy fiber sprouting and synaptic reorganization are relevant characteristics of seizure development in these murine strains, resembling rat models of human temporal lobe epilepsy.", "entity": "Status Epilepticus", "aliases": "Absence Status Complex Partial Epilepticus Electrographic Generalized Convulsive Grand Mal Non Non-Convulsive Petit Simple Subclinical", "definition": "A prolonged seizure or seizures repeated frequently enough to prevent recovery between episodes occurring over a period of 20-30 minutes. The most common subtype is generalized tonic-clonic status epilepticus, a potentially fatal condition associated with neuronal injury and respiratory and metabolic dysfunction. Nonconvulsive forms include petit mal status and complex partial status, which may manifest as behavioral disturbances. Simple partial status epilepticus consists of persistent motor, sensory, or autonomic seizures that do not impair cognition (see also EPILEPSIA PARTIALIS CONTINUA). Subclinical status epilepticus generally refers to seizures occurring in an unresponsive or comatose individual in the absence of overt signs of seizure activity. (From N Engl J Med 1998 Apr 2;338(14):970-6; Neurologia 1997 Dec;12 Suppl 6:25-30)\n    ", "id": "MESH:D013226"}
{"mention": "SE", "mention_text": "Similar to rats, systemic pilocarpine injection causes status epilepticus (SE) and the eventual development of spontaneous seizures and mossy fiber sprouting in C57BL/6 and CD1 mice, but the physiological correlates of these events have not been identified in mice. Population responses in granule cells of the dentate gyrus were examined in transverse slices of the ventral hippocampus from pilocarpine-treated and untreated mice. In Mg(2+)-free bathing medium containing bicuculline, conditions designed to increase excitability in the slices, electrical stimulation of the hilus resulted in a single population spike in granule cells from control mice and pilocarpine-treated mice that did not experience SE. In SE survivors, similar stimulation resulted in a population spike followed, at a variable latency, by negative DC shifts and repetitive afterdischarges of 3-60 s duration, which were blocked by ionotropic glutamate receptor antagonists. Focal glutamate photostimulation of the granule cell layer at sites distant from the recording pipette resulted in population responses of 1-30 s duration in slices from SE survivors but not other groups. These data support the hypothesis that SE-induced mossy fiber sprouting and synaptic reorganization are relevant characteristics of seizure development in these murine strains, resembling rat models of human temporal lobe epilepsy.", "entity": "Status Epilepticus", "aliases": "Absence Status Complex Partial Epilepticus Electrographic Generalized Convulsive Grand Mal Non Non-Convulsive Petit Simple Subclinical", "definition": "A prolonged seizure or seizures repeated frequently enough to prevent recovery between episodes occurring over a period of 20-30 minutes. The most common subtype is generalized tonic-clonic status epilepticus, a potentially fatal condition associated with neuronal injury and respiratory and metabolic dysfunction. Nonconvulsive forms include petit mal status and complex partial status, which may manifest as behavioral disturbances. Simple partial status epilepticus consists of persistent motor, sensory, or autonomic seizures that do not impair cognition (see also EPILEPSIA PARTIALIS CONTINUA). Subclinical status epilepticus generally refers to seizures occurring in an unresponsive or comatose individual in the absence of overt signs of seizure activity. (From N Engl J Med 1998 Apr 2;338(14):970-6; Neurologia 1997 Dec;12 Suppl 6:25-30)\n    ", "id": "MESH:D013226"}
{"mention": "seizures", "mention_text": "Similar to rats, systemic pilocarpine injection causes status epilepticus (SE) and the eventual development of spontaneous seizures and mossy fiber sprouting in C57BL/6 and CD1 mice, but the physiological correlates of these events have not been identified in mice. Population responses in granule cells of the dentate gyrus were examined in transverse slices of the ventral hippocampus from pilocarpine-treated and untreated mice. In Mg(2+)-free bathing medium containing bicuculline, conditions designed to increase excitability in the slices, electrical stimulation of the hilus resulted in a single population spike in granule cells from control mice and pilocarpine-treated mice that did not experience SE. In SE survivors, similar stimulation resulted in a population spike followed, at a variable latency, by negative DC shifts and repetitive afterdischarges of 3-60 s duration, which were blocked by ionotropic glutamate receptor antagonists. Focal glutamate photostimulation of the granule cell layer at sites distant from the recording pipette resulted in population responses of 1-30 s duration in slices from SE survivors but not other groups. These data support the hypothesis that SE-induced mossy fiber sprouting and synaptic reorganization are relevant characteristics of seizure development in these murine strains, resembling rat models of human temporal lobe epilepsy.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "Mg", "mention_text": "Similar to rats, systemic pilocarpine injection causes status epilepticus (SE) and the eventual development of spontaneous seizures and mossy fiber sprouting in C57BL/6 and CD1 mice, but the physiological correlates of these events have not been identified in mice. Population responses in granule cells of the dentate gyrus were examined in transverse slices of the ventral hippocampus from pilocarpine-treated and untreated mice. In Mg(2+)-free bathing medium containing bicuculline, conditions designed to increase excitability in the slices, electrical stimulation of the hilus resulted in a single population spike in granule cells from control mice and pilocarpine-treated mice that did not experience SE. In SE survivors, similar stimulation resulted in a population spike followed, at a variable latency, by negative DC shifts and repetitive afterdischarges of 3-60 s duration, which were blocked by ionotropic glutamate receptor antagonists. Focal glutamate photostimulation of the granule cell layer at sites distant from the recording pipette resulted in population responses of 1-30 s duration in slices from SE survivors but not other groups. These data support the hypothesis that SE-induced mossy fiber sprouting and synaptic reorganization are relevant characteristics of seizure development in these murine strains, resembling rat models of human temporal lobe epilepsy.", "entity": "Magnesium", "aliases": "Magnesium", "definition": "A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.\n    ", "id": "MESH:D008274"}
{"mention": "bicuculline", "mention_text": "Similar to rats, systemic pilocarpine injection causes status epilepticus (SE) and the eventual development of spontaneous seizures and mossy fiber sprouting in C57BL/6 and CD1 mice, but the physiological correlates of these events have not been identified in mice. Population responses in granule cells of the dentate gyrus were examined in transverse slices of the ventral hippocampus from pilocarpine-treated and untreated mice. In Mg(2+)-free bathing medium containing bicuculline, conditions designed to increase excitability in the slices, electrical stimulation of the hilus resulted in a single population spike in granule cells from control mice and pilocarpine-treated mice that did not experience SE. In SE survivors, similar stimulation resulted in a population spike followed, at a variable latency, by negative DC shifts and repetitive afterdischarges of 3-60 s duration, which were blocked by ionotropic glutamate receptor antagonists. Focal glutamate photostimulation of the granule cell layer at sites distant from the recording pipette resulted in population responses of 1-30 s duration in slices from SE survivors but not other groups. These data support the hypothesis that SE-induced mossy fiber sprouting and synaptic reorganization are relevant characteristics of seizure development in these murine strains, resembling rat models of human temporal lobe epilepsy.", "entity": "Bicuculline", "aliases": "6-(5,6,7,8-Tetrahydro-6-methyl-1,3-dioxolo(4,5-g)isoquinolin-5-yl)furo(3,4-e)1,3-benzodioxol-8(6H)one Bicuculline", "definition": "An isoquinoline alkaloid obtained from Dicentra cucullaria and other plants. It is a competitive antagonist for GABA-A receptors.\n    ", "id": "MESH:D001640"}
{"mention": "glutamate", "mention_text": "Similar to rats, systemic pilocarpine injection causes status epilepticus (SE) and the eventual development of spontaneous seizures and mossy fiber sprouting in C57BL/6 and CD1 mice, but the physiological correlates of these events have not been identified in mice. Population responses in granule cells of the dentate gyrus were examined in transverse slices of the ventral hippocampus from pilocarpine-treated and untreated mice. In Mg(2+)-free bathing medium containing bicuculline, conditions designed to increase excitability in the slices, electrical stimulation of the hilus resulted in a single population spike in granule cells from control mice and pilocarpine-treated mice that did not experience SE. In SE survivors, similar stimulation resulted in a population spike followed, at a variable latency, by negative DC shifts and repetitive afterdischarges of 3-60 s duration, which were blocked by ionotropic glutamate receptor antagonists. Focal glutamate photostimulation of the granule cell layer at sites distant from the recording pipette resulted in population responses of 1-30 s duration in slices from SE survivors but not other groups. These data support the hypothesis that SE-induced mossy fiber sprouting and synaptic reorganization are relevant characteristics of seizure development in these murine strains, resembling rat models of human temporal lobe epilepsy.", "entity": "Glutamic Acid", "aliases": "Aluminum L Glutamate L-Glutamate D D-Glutamate Potassium Glutamic Acid (D)-Isomer L-Glutamic", "definition": "A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.\n    ", "id": "MESH:D018698"}
{"mention": "seizure", "mention_text": "Similar to rats, systemic pilocarpine injection causes status epilepticus (SE) and the eventual development of spontaneous seizures and mossy fiber sprouting in C57BL/6 and CD1 mice, but the physiological correlates of these events have not been identified in mice. Population responses in granule cells of the dentate gyrus were examined in transverse slices of the ventral hippocampus from pilocarpine-treated and untreated mice. In Mg(2+)-free bathing medium containing bicuculline, conditions designed to increase excitability in the slices, electrical stimulation of the hilus resulted in a single population spike in granule cells from control mice and pilocarpine-treated mice that did not experience SE. In SE survivors, similar stimulation resulted in a population spike followed, at a variable latency, by negative DC shifts and repetitive afterdischarges of 3-60 s duration, which were blocked by ionotropic glutamate receptor antagonists. Focal glutamate photostimulation of the granule cell layer at sites distant from the recording pipette resulted in population responses of 1-30 s duration in slices from SE survivors but not other groups. These data support the hypothesis that SE-induced mossy fiber sprouting and synaptic reorganization are relevant characteristics of seizure development in these murine strains, resembling rat models of human temporal lobe epilepsy.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "temporal lobe epilepsy", "mention_text": "Similar to rats, systemic pilocarpine injection causes status epilepticus (SE) and the eventual development of spontaneous seizures and mossy fiber sprouting in C57BL/6 and CD1 mice, but the physiological correlates of these events have not been identified in mice. Population responses in granule cells of the dentate gyrus were examined in transverse slices of the ventral hippocampus from pilocarpine-treated and untreated mice. In Mg(2+)-free bathing medium containing bicuculline, conditions designed to increase excitability in the slices, electrical stimulation of the hilus resulted in a single population spike in granule cells from control mice and pilocarpine-treated mice that did not experience SE. In SE survivors, similar stimulation resulted in a population spike followed, at a variable latency, by negative DC shifts and repetitive afterdischarges of 3-60 s duration, which were blocked by ionotropic glutamate receptor antagonists. Focal glutamate photostimulation of the granule cell layer at sites distant from the recording pipette resulted in population responses of 1-30 s duration in slices from SE survivors but not other groups. These data support the hypothesis that SE-induced mossy fiber sprouting and synaptic reorganization are relevant characteristics of seizure development in these murine strains, resembling rat models of human temporal lobe epilepsy.", "entity": "Epilepsy, Temporal Lobe", "aliases": "Benign Psychomotor Epilepsy Childhood Epilepsies Lateral Temporal Lobe Uncinate", "definition": "A localization-related (focal) form of epilepsy characterized by recurrent seizures that arise from foci within the temporal lobe, most commonly from its mesial aspect. A wide variety of psychic phenomena may be associated, including illusions, hallucinations, dyscognitive states, and affective experiences. The majority of complex partial seizures (see EPILEPSY, COMPLEX PARTIAL) originate from the temporal lobes. Temporal lobe seizures may be classified by etiology as cryptogenic, familial, or symptomatic (i.e., related to an identified disease process or lesion). (From Adams et al., Principles of Neurology, 6th ed, p321)\n    ", "id": "MESH:D004833"}
{"mention": "acetylcholine", "mention_text": "The alpha3 and beta4 nicotinic acetylcholine receptor subunits are necessary for nicotine-induced seizures and hypolocomotion in mice.", "entity": "Acetylcholine", "aliases": "2-(Acetyloxy)-N,N,N-trimethylethanaminium Acetilcolina Cusi Acetylcholine Bromide Chloride Fluoride Hydroxide Iodide L Tartrate L-Tartrate Perchlorate Picrate (1:1) Sulfate Alcon Brand of Bournonville Bromoacetylcholine Chloroacetylcholine Ciba Vision Iolab Miochol", "definition": "A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.\n    ", "id": "MESH:D000109"}
{"mention": "nicotine", "mention_text": "The alpha3 and beta4 nicotinic acetylcholine receptor subunits are necessary for nicotine-induced seizures and hypolocomotion in mice.", "entity": "Nicotine", "aliases": "Bitartrate Nicotine Tartrate", "definition": "Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.\n    ", "id": "MESH:D009538"}
{"mention": "seizures", "mention_text": "The alpha3 and beta4 nicotinic acetylcholine receptor subunits are necessary for nicotine-induced seizures and hypolocomotion in mice.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "hypolocomotion", "mention_text": "The alpha3 and beta4 nicotinic acetylcholine receptor subunits are necessary for nicotine-induced seizures and hypolocomotion in mice.", "entity": "Hyperkinesis", "aliases": "Generalized Hyperkinesia Hyperkinesias Hyperactivity Motor Hyperkinesis Hyperkinetic Movement Movements", "definition": "Excessive movement of muscles of the body as a whole, which may be associated with organic or psychological disorders.\n    ", "id": "MESH:D006948"}
{"mention": "nicotine", "mention_text": "Binding of nicotine to nicotinic acetylcholine receptors (nAChRs) elicits a series of dose-dependent behaviors that go from altered exploration, sedation, and tremors, to seizures and death. nAChRs are pentameric ion channels usually composed of alpha and beta subunits. A gene cluster comprises the alpha3, alpha5 and beta4 subunits, which coassemble to form functional receptors. We examined the role of the beta4 subunits in nicotine-induced seizures and hypolocomotion in beta4 homozygous null (beta4 -/-) and alpha3 heterozygous (+/-) mice. beta4 -/- mice were less sensitive to the effects of nicotine both at low doses, measured as decreased exploration in an open field, and at high doses, measured as sensitivity to nicotine-induced seizures. Using in situ hybridization probes for the alpha3 and alpha5 subunits, we showed that alpha5 mRNA levels are unchanged, whereas alpha3 mRNA levels are selectively decreased in the mitral cell layer of the olfactory bulb, and the inferior and the superior colliculus of beta4 -/- brains. alpha3 +/- mice were partially resistant to nicotine-induced seizures when compared to wild-type littermates. mRNA levels for the alpha5 and the beta4 subunits were unchanged in alpha3 +/- brains. Together, these results suggest that the beta4 and the alpha3 subunits are mediators of nicotine-induced seizures and hypolocomotion.", "entity": "Nicotine", "aliases": "Bitartrate Nicotine Tartrate", "definition": "Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.\n    ", "id": "MESH:D009538"}
{"mention": "acetylcholine", "mention_text": "Binding of nicotine to nicotinic acetylcholine receptors (nAChRs) elicits a series of dose-dependent behaviors that go from altered exploration, sedation, and tremors, to seizures and death. nAChRs are pentameric ion channels usually composed of alpha and beta subunits. A gene cluster comprises the alpha3, alpha5 and beta4 subunits, which coassemble to form functional receptors. We examined the role of the beta4 subunits in nicotine-induced seizures and hypolocomotion in beta4 homozygous null (beta4 -/-) and alpha3 heterozygous (+/-) mice. beta4 -/- mice were less sensitive to the effects of nicotine both at low doses, measured as decreased exploration in an open field, and at high doses, measured as sensitivity to nicotine-induced seizures. Using in situ hybridization probes for the alpha3 and alpha5 subunits, we showed that alpha5 mRNA levels are unchanged, whereas alpha3 mRNA levels are selectively decreased in the mitral cell layer of the olfactory bulb, and the inferior and the superior colliculus of beta4 -/- brains. alpha3 +/- mice were partially resistant to nicotine-induced seizures when compared to wild-type littermates. mRNA levels for the alpha5 and the beta4 subunits were unchanged in alpha3 +/- brains. Together, these results suggest that the beta4 and the alpha3 subunits are mediators of nicotine-induced seizures and hypolocomotion.", "entity": "Acetylcholine", "aliases": "2-(Acetyloxy)-N,N,N-trimethylethanaminium Acetilcolina Cusi Acetylcholine Bromide Chloride Fluoride Hydroxide Iodide L Tartrate L-Tartrate Perchlorate Picrate (1:1) Sulfate Alcon Brand of Bournonville Bromoacetylcholine Chloroacetylcholine Ciba Vision Iolab Miochol", "definition": "A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.\n    ", "id": "MESH:D000109"}
{"mention": "tremors", "mention_text": "Binding of nicotine to nicotinic acetylcholine receptors (nAChRs) elicits a series of dose-dependent behaviors that go from altered exploration, sedation, and tremors, to seizures and death. nAChRs are pentameric ion channels usually composed of alpha and beta subunits. A gene cluster comprises the alpha3, alpha5 and beta4 subunits, which coassemble to form functional receptors. We examined the role of the beta4 subunits in nicotine-induced seizures and hypolocomotion in beta4 homozygous null (beta4 -/-) and alpha3 heterozygous (+/-) mice. beta4 -/- mice were less sensitive to the effects of nicotine both at low doses, measured as decreased exploration in an open field, and at high doses, measured as sensitivity to nicotine-induced seizures. Using in situ hybridization probes for the alpha3 and alpha5 subunits, we showed that alpha5 mRNA levels are unchanged, whereas alpha3 mRNA levels are selectively decreased in the mitral cell layer of the olfactory bulb, and the inferior and the superior colliculus of beta4 -/- brains. alpha3 +/- mice were partially resistant to nicotine-induced seizures when compared to wild-type littermates. mRNA levels for the alpha5 and the beta4 subunits were unchanged in alpha3 +/- brains. Together, these results suggest that the beta4 and the alpha3 subunits are mediators of nicotine-induced seizures and hypolocomotion.", "entity": "Tremor", "aliases": "Action Tremor Tremors Coarse Continuous Darkness Fine Intention Intermittent Involuntary Quiver Quivers Limb Massive Muscle Neonatal Nerve Passive Perioral Persistent Pill Rolling Rest Resting Saturnine Semirhythmic Senile Static", "definition": "Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of CEREBELLAR DISEASES, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of PARKINSON DISEASE.\n    ", "id": "MESH:D014202"}
{"mention": "seizures", "mention_text": "Binding of nicotine to nicotinic acetylcholine receptors (nAChRs) elicits a series of dose-dependent behaviors that go from altered exploration, sedation, and tremors, to seizures and death. nAChRs are pentameric ion channels usually composed of alpha and beta subunits. A gene cluster comprises the alpha3, alpha5 and beta4 subunits, which coassemble to form functional receptors. We examined the role of the beta4 subunits in nicotine-induced seizures and hypolocomotion in beta4 homozygous null (beta4 -/-) and alpha3 heterozygous (+/-) mice. beta4 -/- mice were less sensitive to the effects of nicotine both at low doses, measured as decreased exploration in an open field, and at high doses, measured as sensitivity to nicotine-induced seizures. Using in situ hybridization probes for the alpha3 and alpha5 subunits, we showed that alpha5 mRNA levels are unchanged, whereas alpha3 mRNA levels are selectively decreased in the mitral cell layer of the olfactory bulb, and the inferior and the superior colliculus of beta4 -/- brains. alpha3 +/- mice were partially resistant to nicotine-induced seizures when compared to wild-type littermates. mRNA levels for the alpha5 and the beta4 subunits were unchanged in alpha3 +/- brains. Together, these results suggest that the beta4 and the alpha3 subunits are mediators of nicotine-induced seizures and hypolocomotion.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "death", "mention_text": "Binding of nicotine to nicotinic acetylcholine receptors (nAChRs) elicits a series of dose-dependent behaviors that go from altered exploration, sedation, and tremors, to seizures and death. nAChRs are pentameric ion channels usually composed of alpha and beta subunits. A gene cluster comprises the alpha3, alpha5 and beta4 subunits, which coassemble to form functional receptors. We examined the role of the beta4 subunits in nicotine-induced seizures and hypolocomotion in beta4 homozygous null (beta4 -/-) and alpha3 heterozygous (+/-) mice. beta4 -/- mice were less sensitive to the effects of nicotine both at low doses, measured as decreased exploration in an open field, and at high doses, measured as sensitivity to nicotine-induced seizures. Using in situ hybridization probes for the alpha3 and alpha5 subunits, we showed that alpha5 mRNA levels are unchanged, whereas alpha3 mRNA levels are selectively decreased in the mitral cell layer of the olfactory bulb, and the inferior and the superior colliculus of beta4 -/- brains. alpha3 +/- mice were partially resistant to nicotine-induced seizures when compared to wild-type littermates. mRNA levels for the alpha5 and the beta4 subunits were unchanged in alpha3 +/- brains. Together, these results suggest that the beta4 and the alpha3 subunits are mediators of nicotine-induced seizures and hypolocomotion.", "entity": "Death", "aliases": "Cardiac Death Determination of Near-Death Experience", "definition": "Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.\n    ", "id": "MESH:D003643"}
{"mention": "hypolocomotion", "mention_text": "Binding of nicotine to nicotinic acetylcholine receptors (nAChRs) elicits a series of dose-dependent behaviors that go from altered exploration, sedation, and tremors, to seizures and death. nAChRs are pentameric ion channels usually composed of alpha and beta subunits. A gene cluster comprises the alpha3, alpha5 and beta4 subunits, which coassemble to form functional receptors. We examined the role of the beta4 subunits in nicotine-induced seizures and hypolocomotion in beta4 homozygous null (beta4 -/-) and alpha3 heterozygous (+/-) mice. beta4 -/- mice were less sensitive to the effects of nicotine both at low doses, measured as decreased exploration in an open field, and at high doses, measured as sensitivity to nicotine-induced seizures. Using in situ hybridization probes for the alpha3 and alpha5 subunits, we showed that alpha5 mRNA levels are unchanged, whereas alpha3 mRNA levels are selectively decreased in the mitral cell layer of the olfactory bulb, and the inferior and the superior colliculus of beta4 -/- brains. alpha3 +/- mice were partially resistant to nicotine-induced seizures when compared to wild-type littermates. mRNA levels for the alpha5 and the beta4 subunits were unchanged in alpha3 +/- brains. Together, these results suggest that the beta4 and the alpha3 subunits are mediators of nicotine-induced seizures and hypolocomotion.", "entity": "Hyperkinesis", "aliases": "Generalized Hyperkinesia Hyperkinesias Hyperactivity Motor Hyperkinesis Hyperkinetic Movement Movements", "definition": "Excessive movement of muscles of the body as a whole, which may be associated with organic or psychological disorders.\n    ", "id": "MESH:D006948"}
{"mention": "interstitial nephritis", "mention_text": "Recurrent acute interstitial nephritis induced by azithromycin.", "entity": "Nephritis, Interstitial", "aliases": "Interstitial Nephritides Nephritis Tubulointerstitial", "definition": "Inflammation of the interstitial tissue of the kidney. This term is generally used for primary inflammation of KIDNEY TUBULES and/or surrounding interstitium. For primary inflammation of glomerular interstitium, see GLOMERULONEPHRITIS. Infiltration of the inflammatory cells into the interstitial compartment results in EDEMA, increased spaces between the tubules, and tubular renal dysfunction.\n    ", "id": "MESH:D009395"}
{"mention": "azithromycin", "mention_text": "Recurrent acute interstitial nephritis induced by azithromycin.", "entity": "Azithromycin", "aliases": "Azadose Azithromycin Dihydrate Monohydrate Pfizer Brand Azitrocin Azythromycin Bayer of CP 62993 CP-62993 CP62993 Funk Goxal Lesvi Mack Pharmacia Sumamed Toraseptol Ultreon Vinzam Vita Zentavion Zithromax Zitromax", "definition": "A semi-synthetic macrolide antibiotic structurally related to ERYTHROMYCIN. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis.\n    ", "id": "MESH:D017963"}
{"mention": "azithromycin", "mention_text": "A 14-year-old girl is reported with recurrent, azithromycin-induced, acute interstitial nephritis. The second episode was more severe than the first; and although both were treated with intensive corticosteroid therapy, renal function remained impaired. Although most cases of antibiotic induced acute interstitial nephritis are benign and self-limited, some patients are at risk for permanent renal injury.", "entity": "Azithromycin", "aliases": "Azadose Azithromycin Dihydrate Monohydrate Pfizer Brand Azitrocin Azythromycin Bayer of CP 62993 CP-62993 CP62993 Funk Goxal Lesvi Mack Pharmacia Sumamed Toraseptol Ultreon Vinzam Vita Zentavion Zithromax Zitromax", "definition": "A semi-synthetic macrolide antibiotic structurally related to ERYTHROMYCIN. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis.\n    ", "id": "MESH:D017963"}
{"mention": "interstitial nephritis", "mention_text": "A 14-year-old girl is reported with recurrent, azithromycin-induced, acute interstitial nephritis. The second episode was more severe than the first; and although both were treated with intensive corticosteroid therapy, renal function remained impaired. Although most cases of antibiotic induced acute interstitial nephritis are benign and self-limited, some patients are at risk for permanent renal injury.", "entity": "Nephritis, Interstitial", "aliases": "Interstitial Nephritides Nephritis Tubulointerstitial", "definition": "Inflammation of the interstitial tissue of the kidney. This term is generally used for primary inflammation of KIDNEY TUBULES and/or surrounding interstitium. For primary inflammation of glomerular interstitium, see GLOMERULONEPHRITIS. Infiltration of the inflammatory cells into the interstitial compartment results in EDEMA, increased spaces between the tubules, and tubular renal dysfunction.\n    ", "id": "MESH:D009395"}
{"mention": "renal injury", "mention_text": "A 14-year-old girl is reported with recurrent, azithromycin-induced, acute interstitial nephritis. The second episode was more severe than the first; and although both were treated with intensive corticosteroid therapy, renal function remained impaired. Although most cases of antibiotic induced acute interstitial nephritis are benign and self-limited, some patients are at risk for permanent renal injury.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "Valproate", "mention_text": "Valproate-induced encephalopathy.", "entity": "Valproic Acid", "aliases": "2 Propylpentanoic Acid 2-Propylpentanoic Acetate Dipropyl Propylisopropylacetic Valproic Calcium Valproate Convulsofin Depakene Depakine Depakote Divalproex Sodium Ergenyl Magnesium Semisodium Salt (2:1) Vupral", "definition": "A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.\n    ", "id": "MESH:D014635"}
{"mention": "encephalopathy", "mention_text": "Valproate-induced encephalopathy.", "entity": "Brain Diseases", "aliases": "Brain Disease Diseases Disorder Disorders CNS Intracranial Central Nervous System Encephalon", "definition": "Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.\n    ", "id": "MESH:D001927"}
{"mention": "Valproate", "mention_text": "Valproate-induced encephalopathy is a rare syndrome that may manifest in otherwise normal epileptic individuals. It may even present in patients who have tolerated this medicine well in the past. It is usually but not necessarily associated with hyperammonemia. The EEG shows characteristic triphasic waves in most patients with this complication. A case of valproate-induced encephalopathy is presented. The problems in diagnosing this condition are subsequently discussed.", "entity": "Valproic Acid", "aliases": "2 Propylpentanoic Acid 2-Propylpentanoic Acetate Dipropyl Propylisopropylacetic Valproic Calcium Valproate Convulsofin Depakene Depakine Depakote Divalproex Sodium Ergenyl Magnesium Semisodium Salt (2:1) Vupral", "definition": "A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.\n    ", "id": "MESH:D014635"}
{"mention": "encephalopathy", "mention_text": "Valproate-induced encephalopathy is a rare syndrome that may manifest in otherwise normal epileptic individuals. It may even present in patients who have tolerated this medicine well in the past. It is usually but not necessarily associated with hyperammonemia. The EEG shows characteristic triphasic waves in most patients with this complication. A case of valproate-induced encephalopathy is presented. The problems in diagnosing this condition are subsequently discussed.", "entity": "Brain Diseases", "aliases": "Brain Disease Diseases Disorder Disorders CNS Intracranial Central Nervous System Encephalon", "definition": "Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.\n    ", "id": "MESH:D001927"}
{"mention": "epileptic", "mention_text": "Valproate-induced encephalopathy is a rare syndrome that may manifest in otherwise normal epileptic individuals. It may even present in patients who have tolerated this medicine well in the past. It is usually but not necessarily associated with hyperammonemia. The EEG shows characteristic triphasic waves in most patients with this complication. A case of valproate-induced encephalopathy is presented. The problems in diagnosing this condition are subsequently discussed.", "entity": "Epilepsy", "aliases": "Aura Auras Awakening Epilepsy Cryptogenic Epilepsies Epileptic Seizure Seizures Disorder Disorders Single", "definition": "A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313)\n    ", "id": "MESH:D004827"}
{"mention": "hyperammonemia", "mention_text": "Valproate-induced encephalopathy is a rare syndrome that may manifest in otherwise normal epileptic individuals. It may even present in patients who have tolerated this medicine well in the past. It is usually but not necessarily associated with hyperammonemia. The EEG shows characteristic triphasic waves in most patients with this complication. A case of valproate-induced encephalopathy is presented. The problems in diagnosing this condition are subsequently discussed.", "entity": "Hyperammonemia", "aliases": "Hyperammonemia", "definition": "Elevated level of AMMONIA in the blood. It is a sign of defective CATABOLISM of AMINO ACIDS or ammonia to UREA.\n    ", "id": "MESH:D022124"}
{"mention": "valproate", "mention_text": "Valproate-induced encephalopathy is a rare syndrome that may manifest in otherwise normal epileptic individuals. It may even present in patients who have tolerated this medicine well in the past. It is usually but not necessarily associated with hyperammonemia. The EEG shows characteristic triphasic waves in most patients with this complication. A case of valproate-induced encephalopathy is presented. The problems in diagnosing this condition are subsequently discussed.", "entity": "Valproic Acid", "aliases": "2 Propylpentanoic Acid 2-Propylpentanoic Acetate Dipropyl Propylisopropylacetic Valproic Calcium Valproate Convulsofin Depakene Depakine Depakote Divalproex Sodium Ergenyl Magnesium Semisodium Salt (2:1) Vupral", "definition": "A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.\n    ", "id": "MESH:D014635"}
{"mention": "Nitro-L-arginine methyl ester", "mention_text": "Nitro-L-arginine methyl ester: a potential protector against gentamicin ototoxicity.", "entity": "NG-Nitroarginine Methyl Ester", "aliases": "L-NAME Methyl Ester NG-Nitro-L-Arginine NG-Nitroarginine N omega Nitro L arginine omega-Nitro-L-arginine N(G)-Nitro-L-arginine N(G)-Nitroarginine N(omega)-Nitro-L-arginine NG Arginine Nitroarginine D Orn Isomer D-Orn-Isomer L-Orn-Isomer Monohydrochloride", "definition": "A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.\n    ", "id": "MESH:D019331"}
{"mention": "gentamicin", "mention_text": "Nitro-L-arginine methyl ester: a potential protector against gentamicin ototoxicity.", "entity": "Gentamicins", "aliases": "G Myticin G-Myticin GMyticin Garamycin Gentacycol Gentamicin Sulfate (USP) Gentamicins Gentamycin Gentamycins Gentavet Genticin", "definition": "A complex of closely related aminoglycosides obtained from MICROMONOSPORA purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit PROTEIN BIOSYNTHESIS.\n    ", "id": "MESH:D005839"}
{"mention": "ototoxicity", "mention_text": "Nitro-L-arginine methyl ester: a potential protector against gentamicin ototoxicity.", "entity": "Hearing Disorders", "aliases": "Distorted Hearing Dysacusis Disorder Disorders Paracousis Paracusis", "definition": "Conditions that impair the transmission of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways.\n    ", "id": "MESH:D006311"}
{"mention": "nitric oxide", "mention_text": "The nitric oxide (NO) inhibitor nitro-L-arginine methyl ester (L-NAME) may act as an otoprotectant against high-frequency hearing loss caused by gentamicin, but further studies are needed to confirm this.Aminoglycoside antibiotics are still widely used by virtue of their efficacy and low cost. Their ototoxicity is a serious health problem and, as their ototoxic mechanism involves the production of NO, we need to assess the use of NO inhibitors for the prevention of aminoglycoside-induced sensorineural hearing loss. In this experimental study we used 30 Sprague-Dawley rats, 27 of which had gentamicin instilled into the middle ear. The otoprotectant L-NAME was administered topically to 12/27 animals. Its effect was determined in terms of attenuation of hearing loss, measured by shifts in the auditory brainstem response threshold. L-NAME reduced gentamicin-induced hearing loss in the high-frequency range, but gave no protection in the middle or low frequencies.", "entity": "Nitric Oxide", "aliases": "Endogenous Nitrate Vasodilator Endothelium-Derived Nitric Oxide Mononitrogen Monoxide Nitrogen Endothelium Derived", "definition": "A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.\n    ", "id": "MESH:D009569"}
{"mention": "NO", "mention_text": "The nitric oxide (NO) inhibitor nitro-L-arginine methyl ester (L-NAME) may act as an otoprotectant against high-frequency hearing loss caused by gentamicin, but further studies are needed to confirm this.Aminoglycoside antibiotics are still widely used by virtue of their efficacy and low cost. Their ototoxicity is a serious health problem and, as their ototoxic mechanism involves the production of NO, we need to assess the use of NO inhibitors for the prevention of aminoglycoside-induced sensorineural hearing loss. In this experimental study we used 30 Sprague-Dawley rats, 27 of which had gentamicin instilled into the middle ear. The otoprotectant L-NAME was administered topically to 12/27 animals. Its effect was determined in terms of attenuation of hearing loss, measured by shifts in the auditory brainstem response threshold. L-NAME reduced gentamicin-induced hearing loss in the high-frequency range, but gave no protection in the middle or low frequencies.", "entity": "Nitric Oxide", "aliases": "Endogenous Nitrate Vasodilator Endothelium-Derived Nitric Oxide Mononitrogen Monoxide Nitrogen Endothelium Derived", "definition": "A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.\n    ", "id": "MESH:D009569"}
{"mention": "nitro-L-arginine methyl ester", "mention_text": "The nitric oxide (NO) inhibitor nitro-L-arginine methyl ester (L-NAME) may act as an otoprotectant against high-frequency hearing loss caused by gentamicin, but further studies are needed to confirm this.Aminoglycoside antibiotics are still widely used by virtue of their efficacy and low cost. Their ototoxicity is a serious health problem and, as their ototoxic mechanism involves the production of NO, we need to assess the use of NO inhibitors for the prevention of aminoglycoside-induced sensorineural hearing loss. In this experimental study we used 30 Sprague-Dawley rats, 27 of which had gentamicin instilled into the middle ear. The otoprotectant L-NAME was administered topically to 12/27 animals. Its effect was determined in terms of attenuation of hearing loss, measured by shifts in the auditory brainstem response threshold. L-NAME reduced gentamicin-induced hearing loss in the high-frequency range, but gave no protection in the middle or low frequencies.", "entity": "NG-Nitroarginine Methyl Ester", "aliases": "L-NAME Methyl Ester NG-Nitro-L-Arginine NG-Nitroarginine N omega Nitro L arginine omega-Nitro-L-arginine N(G)-Nitro-L-arginine N(G)-Nitroarginine N(omega)-Nitro-L-arginine NG Arginine Nitroarginine D Orn Isomer D-Orn-Isomer L-Orn-Isomer Monohydrochloride", "definition": "A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.\n    ", "id": "MESH:D019331"}
{"mention": "L-NAME", "mention_text": "The nitric oxide (NO) inhibitor nitro-L-arginine methyl ester (L-NAME) may act as an otoprotectant against high-frequency hearing loss caused by gentamicin, but further studies are needed to confirm this.Aminoglycoside antibiotics are still widely used by virtue of their efficacy and low cost. Their ototoxicity is a serious health problem and, as their ototoxic mechanism involves the production of NO, we need to assess the use of NO inhibitors for the prevention of aminoglycoside-induced sensorineural hearing loss. In this experimental study we used 30 Sprague-Dawley rats, 27 of which had gentamicin instilled into the middle ear. The otoprotectant L-NAME was administered topically to 12/27 animals. Its effect was determined in terms of attenuation of hearing loss, measured by shifts in the auditory brainstem response threshold. L-NAME reduced gentamicin-induced hearing loss in the high-frequency range, but gave no protection in the middle or low frequencies.", "entity": "NG-Nitroarginine Methyl Ester", "aliases": "L-NAME Methyl Ester NG-Nitro-L-Arginine NG-Nitroarginine N omega Nitro L arginine omega-Nitro-L-arginine N(G)-Nitro-L-arginine N(G)-Nitroarginine N(omega)-Nitro-L-arginine NG Arginine Nitroarginine D Orn Isomer D-Orn-Isomer L-Orn-Isomer Monohydrochloride", "definition": "A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.\n    ", "id": "MESH:D019331"}
{"mention": "high-frequency hearing loss", "mention_text": "The nitric oxide (NO) inhibitor nitro-L-arginine methyl ester (L-NAME) may act as an otoprotectant against high-frequency hearing loss caused by gentamicin, but further studies are needed to confirm this.Aminoglycoside antibiotics are still widely used by virtue of their efficacy and low cost. Their ototoxicity is a serious health problem and, as their ototoxic mechanism involves the production of NO, we need to assess the use of NO inhibitors for the prevention of aminoglycoside-induced sensorineural hearing loss. In this experimental study we used 30 Sprague-Dawley rats, 27 of which had gentamicin instilled into the middle ear. The otoprotectant L-NAME was administered topically to 12/27 animals. Its effect was determined in terms of attenuation of hearing loss, measured by shifts in the auditory brainstem response threshold. L-NAME reduced gentamicin-induced hearing loss in the high-frequency range, but gave no protection in the middle or low frequencies.", "entity": "Hearing Loss, High-Frequency", "aliases": "Hearing Loss High Frequency High-Frequency", "definition": "Hearing loss in frequencies above 1000 hertz.\n    ", "id": "MESH:D006316"}
{"mention": "gentamicin", "mention_text": "The nitric oxide (NO) inhibitor nitro-L-arginine methyl ester (L-NAME) may act as an otoprotectant against high-frequency hearing loss caused by gentamicin, but further studies are needed to confirm this.Aminoglycoside antibiotics are still widely used by virtue of their efficacy and low cost. Their ototoxicity is a serious health problem and, as their ototoxic mechanism involves the production of NO, we need to assess the use of NO inhibitors for the prevention of aminoglycoside-induced sensorineural hearing loss. In this experimental study we used 30 Sprague-Dawley rats, 27 of which had gentamicin instilled into the middle ear. The otoprotectant L-NAME was administered topically to 12/27 animals. Its effect was determined in terms of attenuation of hearing loss, measured by shifts in the auditory brainstem response threshold. L-NAME reduced gentamicin-induced hearing loss in the high-frequency range, but gave no protection in the middle or low frequencies.", "entity": "Gentamicins", "aliases": "G Myticin G-Myticin GMyticin Garamycin Gentacycol Gentamicin Sulfate (USP) Gentamicins Gentamycin Gentamycins Gentavet Genticin", "definition": "A complex of closely related aminoglycosides obtained from MICROMONOSPORA purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit PROTEIN BIOSYNTHESIS.\n    ", "id": "MESH:D005839"}
{"mention": "Aminoglycoside", "mention_text": "The nitric oxide (NO) inhibitor nitro-L-arginine methyl ester (L-NAME) may act as an otoprotectant against high-frequency hearing loss caused by gentamicin, but further studies are needed to confirm this.Aminoglycoside antibiotics are still widely used by virtue of their efficacy and low cost. Their ototoxicity is a serious health problem and, as their ototoxic mechanism involves the production of NO, we need to assess the use of NO inhibitors for the prevention of aminoglycoside-induced sensorineural hearing loss. In this experimental study we used 30 Sprague-Dawley rats, 27 of which had gentamicin instilled into the middle ear. The otoprotectant L-NAME was administered topically to 12/27 animals. Its effect was determined in terms of attenuation of hearing loss, measured by shifts in the auditory brainstem response threshold. L-NAME reduced gentamicin-induced hearing loss in the high-frequency range, but gave no protection in the middle or low frequencies.", "entity": "Aminoglycosides", "aliases": "Aminoglycosides", "definition": "Glycosylated compounds in which there is an amino substituent on the glycoside. Some of them are clinically important ANTIBIOTICS.\n    ", "id": "MESH:D000617"}
{"mention": "ototoxicity", "mention_text": "The nitric oxide (NO) inhibitor nitro-L-arginine methyl ester (L-NAME) may act as an otoprotectant against high-frequency hearing loss caused by gentamicin, but further studies are needed to confirm this.Aminoglycoside antibiotics are still widely used by virtue of their efficacy and low cost. Their ototoxicity is a serious health problem and, as their ototoxic mechanism involves the production of NO, we need to assess the use of NO inhibitors for the prevention of aminoglycoside-induced sensorineural hearing loss. In this experimental study we used 30 Sprague-Dawley rats, 27 of which had gentamicin instilled into the middle ear. The otoprotectant L-NAME was administered topically to 12/27 animals. Its effect was determined in terms of attenuation of hearing loss, measured by shifts in the auditory brainstem response threshold. L-NAME reduced gentamicin-induced hearing loss in the high-frequency range, but gave no protection in the middle or low frequencies.", "entity": "Hearing Disorders", "aliases": "Distorted Hearing Dysacusis Disorder Disorders Paracousis Paracusis", "definition": "Conditions that impair the transmission of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways.\n    ", "id": "MESH:D006311"}
{"mention": "ototoxic", "mention_text": "The nitric oxide (NO) inhibitor nitro-L-arginine methyl ester (L-NAME) may act as an otoprotectant against high-frequency hearing loss caused by gentamicin, but further studies are needed to confirm this.Aminoglycoside antibiotics are still widely used by virtue of their efficacy and low cost. Their ototoxicity is a serious health problem and, as their ototoxic mechanism involves the production of NO, we need to assess the use of NO inhibitors for the prevention of aminoglycoside-induced sensorineural hearing loss. In this experimental study we used 30 Sprague-Dawley rats, 27 of which had gentamicin instilled into the middle ear. The otoprotectant L-NAME was administered topically to 12/27 animals. Its effect was determined in terms of attenuation of hearing loss, measured by shifts in the auditory brainstem response threshold. L-NAME reduced gentamicin-induced hearing loss in the high-frequency range, but gave no protection in the middle or low frequencies.", "entity": "Hearing Disorders", "aliases": "Distorted Hearing Dysacusis Disorder Disorders Paracousis Paracusis", "definition": "Conditions that impair the transmission of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways.\n    ", "id": "MESH:D006311"}
{"mention": "aminoglycoside", "mention_text": "The nitric oxide (NO) inhibitor nitro-L-arginine methyl ester (L-NAME) may act as an otoprotectant against high-frequency hearing loss caused by gentamicin, but further studies are needed to confirm this.Aminoglycoside antibiotics are still widely used by virtue of their efficacy and low cost. Their ototoxicity is a serious health problem and, as their ototoxic mechanism involves the production of NO, we need to assess the use of NO inhibitors for the prevention of aminoglycoside-induced sensorineural hearing loss. In this experimental study we used 30 Sprague-Dawley rats, 27 of which had gentamicin instilled into the middle ear. The otoprotectant L-NAME was administered topically to 12/27 animals. Its effect was determined in terms of attenuation of hearing loss, measured by shifts in the auditory brainstem response threshold. L-NAME reduced gentamicin-induced hearing loss in the high-frequency range, but gave no protection in the middle or low frequencies.", "entity": "Aminoglycosides", "aliases": "Aminoglycosides", "definition": "Glycosylated compounds in which there is an amino substituent on the glycoside. Some of them are clinically important ANTIBIOTICS.\n    ", "id": "MESH:D000617"}
{"mention": "sensorineural hearing loss", "mention_text": "The nitric oxide (NO) inhibitor nitro-L-arginine methyl ester (L-NAME) may act as an otoprotectant against high-frequency hearing loss caused by gentamicin, but further studies are needed to confirm this.Aminoglycoside antibiotics are still widely used by virtue of their efficacy and low cost. Their ototoxicity is a serious health problem and, as their ototoxic mechanism involves the production of NO, we need to assess the use of NO inhibitors for the prevention of aminoglycoside-induced sensorineural hearing loss. In this experimental study we used 30 Sprague-Dawley rats, 27 of which had gentamicin instilled into the middle ear. The otoprotectant L-NAME was administered topically to 12/27 animals. Its effect was determined in terms of attenuation of hearing loss, measured by shifts in the auditory brainstem response threshold. L-NAME reduced gentamicin-induced hearing loss in the high-frequency range, but gave no protection in the middle or low frequencies.", "entity": "Hearing Loss, Sensorineural", "aliases": "Cochlear Hearing Loss Sensorineural", "definition": "Hearing loss resulting from damage to the COCHLEA and the sensorineural elements which lie internally beyond the oval and round windows. These elements include the AUDITORY NERVE and its connections in the BRAINSTEM.\n    ", "id": "MESH:D006319"}
{"mention": "hearing loss", "mention_text": "The nitric oxide (NO) inhibitor nitro-L-arginine methyl ester (L-NAME) may act as an otoprotectant against high-frequency hearing loss caused by gentamicin, but further studies are needed to confirm this.Aminoglycoside antibiotics are still widely used by virtue of their efficacy and low cost. Their ototoxicity is a serious health problem and, as their ototoxic mechanism involves the production of NO, we need to assess the use of NO inhibitors for the prevention of aminoglycoside-induced sensorineural hearing loss. In this experimental study we used 30 Sprague-Dawley rats, 27 of which had gentamicin instilled into the middle ear. The otoprotectant L-NAME was administered topically to 12/27 animals. Its effect was determined in terms of attenuation of hearing loss, measured by shifts in the auditory brainstem response threshold. L-NAME reduced gentamicin-induced hearing loss in the high-frequency range, but gave no protection in the middle or low frequencies.", "entity": "Hearing Loss", "aliases": "Hearing Impairment Loss Hypoacuses Hypoacusis", "definition": "A general term for the complete or partial loss of the ability to hear from one or both ears.\n    ", "id": "MESH:D034381"}
{"mention": "Cerebral vasculitis", "mention_text": "Cerebral vasculitis following oral methylphenidate intake in an adult: a case report.", "entity": "Vasculitis, Central Nervous System", "aliases": "Angiitis Central Nervous System Cerebral Granulomatous Arteritis Postzoster CNS Vasculitis Primary Secondary", "definition": "Inflammation of blood vessels within the central nervous system. Primary vasculitis is usually caused by autoimmune or idiopathic factors, while secondary vasculitis is caused by existing disease process. Clinical manifestations are highly variable but include HEADACHE; SEIZURES; behavioral alterations; INTRACRANIAL HEMORRHAGES; TRANSIENT ISCHEMIC ATTACK; and BRAIN INFARCTION. (From Adams et al., Principles of Neurology, 6th ed, pp856-61)\n    ", "id": "MESH:D020293"}
{"mention": "methylphenidate", "mention_text": "Cerebral vasculitis following oral methylphenidate intake in an adult: a case report.", "entity": "Methylphenidate", "aliases": "Celltech Brand of Methylphenidate Hydrochloride Centedrin Cephalon Concerta Daytrana Equasym Mallinckrodt Metadate Methylin Novartis 1 2 Phenidylate Ritalin SR Ritalin-SR Ritaline Tsentedrin", "definition": "A central nervous system stimulant used most commonly in the treatment of ATTENTION DEFICIT DISORDER in children and for NARCOLEPSY. Its mechanisms appear to be similar to those of DEXTROAMPHETAMINE. The d-isomer of this drug is referred to as DEXMETHYLPHENIDATE.\n    ", "id": "MESH:D008774"}
{"mention": "Methylphenidate", "mention_text": "Methylphenidate is structurally and functionally similar to amphetamine. Cerebral vasculitis associated with amphetamine abuse is well documented, and in rare cases ischaemic stroke has been reported after methylphenidate intake in children. We report the case of a 63-year-old female who was treated with methylphenidate due to hyperactivity and suffered from multiple ischaemic strokes. We consider drug-induced cerebral vasculitis as the most likely cause of recurrent ischaemic strokes in the absence of any pathological findings during the diagnostic work-up. We conclude that methylphenidate mediated vasculitis should be considered in patients with neurological symptoms and a history of methylphenidate therapy. This potential side-effect, though very rare, represents one more reason to be very restrictive in the use of methylphenidate.", "entity": "Methylphenidate", "aliases": "Celltech Brand of Methylphenidate Hydrochloride Centedrin Cephalon Concerta Daytrana Equasym Mallinckrodt Metadate Methylin Novartis 1 2 Phenidylate Ritalin SR Ritalin-SR Ritaline Tsentedrin", "definition": "A central nervous system stimulant used most commonly in the treatment of ATTENTION DEFICIT DISORDER in children and for NARCOLEPSY. Its mechanisms appear to be similar to those of DEXTROAMPHETAMINE. The d-isomer of this drug is referred to as DEXMETHYLPHENIDATE.\n    ", "id": "MESH:D008774"}
{"mention": "amphetamine", "mention_text": "Methylphenidate is structurally and functionally similar to amphetamine. Cerebral vasculitis associated with amphetamine abuse is well documented, and in rare cases ischaemic stroke has been reported after methylphenidate intake in children. We report the case of a 63-year-old female who was treated with methylphenidate due to hyperactivity and suffered from multiple ischaemic strokes. We consider drug-induced cerebral vasculitis as the most likely cause of recurrent ischaemic strokes in the absence of any pathological findings during the diagnostic work-up. We conclude that methylphenidate mediated vasculitis should be considered in patients with neurological symptoms and a history of methylphenidate therapy. This potential side-effect, though very rare, represents one more reason to be very restrictive in the use of methylphenidate.", "entity": "Amphetamine", "aliases": "Amfetamine Amphetamine Sulfate (2:1) Centramina Desoxynorephedrin Fenamine Levoamphetamine Miquel Brand of Mydrial Phenamine Phenopromin Thyramine l l-Amphetamine levo levo-Amphetamine", "definition": "A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE.\n    ", "id": "MESH:D000661"}
{"mention": "Cerebral vasculitis", "mention_text": "Methylphenidate is structurally and functionally similar to amphetamine. Cerebral vasculitis associated with amphetamine abuse is well documented, and in rare cases ischaemic stroke has been reported after methylphenidate intake in children. We report the case of a 63-year-old female who was treated with methylphenidate due to hyperactivity and suffered from multiple ischaemic strokes. We consider drug-induced cerebral vasculitis as the most likely cause of recurrent ischaemic strokes in the absence of any pathological findings during the diagnostic work-up. We conclude that methylphenidate mediated vasculitis should be considered in patients with neurological symptoms and a history of methylphenidate therapy. This potential side-effect, though very rare, represents one more reason to be very restrictive in the use of methylphenidate.", "entity": "Vasculitis, Central Nervous System", "aliases": "Angiitis Central Nervous System Cerebral Granulomatous Arteritis Postzoster CNS Vasculitis Primary Secondary", "definition": "Inflammation of blood vessels within the central nervous system. Primary vasculitis is usually caused by autoimmune or idiopathic factors, while secondary vasculitis is caused by existing disease process. Clinical manifestations are highly variable but include HEADACHE; SEIZURES; behavioral alterations; INTRACRANIAL HEMORRHAGES; TRANSIENT ISCHEMIC ATTACK; and BRAIN INFARCTION. (From Adams et al., Principles of Neurology, 6th ed, pp856-61)\n    ", "id": "MESH:D020293"}
{"mention": "amphetamine abuse", "mention_text": "Methylphenidate is structurally and functionally similar to amphetamine. Cerebral vasculitis associated with amphetamine abuse is well documented, and in rare cases ischaemic stroke has been reported after methylphenidate intake in children. We report the case of a 63-year-old female who was treated with methylphenidate due to hyperactivity and suffered from multiple ischaemic strokes. We consider drug-induced cerebral vasculitis as the most likely cause of recurrent ischaemic strokes in the absence of any pathological findings during the diagnostic work-up. We conclude that methylphenidate mediated vasculitis should be considered in patients with neurological symptoms and a history of methylphenidate therapy. This potential side-effect, though very rare, represents one more reason to be very restrictive in the use of methylphenidate.", "entity": "Amphetamine-Related Disorders", "aliases": "Abuse Amphetamine Addiction Dependence Related Disorders Amphetamine-Related Disorder", "definition": "Disorders related or resulting from use of amphetamines.\n    ", "id": "MESH:D019969"}
{"mention": "ischaemic stroke", "mention_text": "Methylphenidate is structurally and functionally similar to amphetamine. Cerebral vasculitis associated with amphetamine abuse is well documented, and in rare cases ischaemic stroke has been reported after methylphenidate intake in children. We report the case of a 63-year-old female who was treated with methylphenidate due to hyperactivity and suffered from multiple ischaemic strokes. We consider drug-induced cerebral vasculitis as the most likely cause of recurrent ischaemic strokes in the absence of any pathological findings during the diagnostic work-up. We conclude that methylphenidate mediated vasculitis should be considered in patients with neurological symptoms and a history of methylphenidate therapy. This potential side-effect, though very rare, represents one more reason to be very restrictive in the use of methylphenidate.", "entity": "Cerebral Infarction", "aliases": "Anterior Choroidal Artery Infarction Cerebral Left Hemisphere Right Infarctions Subcortical Posterior", "definition": "The formation of an area of NECROSIS in the CEREBRUM caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., INFARCTION, ANTERIOR CEREBRAL ARTERY), and etiology (e.g., embolic infarction).\n    ", "id": "MESH:D002544"}
{"mention": "methylphenidate", "mention_text": "Methylphenidate is structurally and functionally similar to amphetamine. Cerebral vasculitis associated with amphetamine abuse is well documented, and in rare cases ischaemic stroke has been reported after methylphenidate intake in children. We report the case of a 63-year-old female who was treated with methylphenidate due to hyperactivity and suffered from multiple ischaemic strokes. We consider drug-induced cerebral vasculitis as the most likely cause of recurrent ischaemic strokes in the absence of any pathological findings during the diagnostic work-up. We conclude that methylphenidate mediated vasculitis should be considered in patients with neurological symptoms and a history of methylphenidate therapy. This potential side-effect, though very rare, represents one more reason to be very restrictive in the use of methylphenidate.", "entity": "Methylphenidate", "aliases": "Celltech Brand of Methylphenidate Hydrochloride Centedrin Cephalon Concerta Daytrana Equasym Mallinckrodt Metadate Methylin Novartis 1 2 Phenidylate Ritalin SR Ritalin-SR Ritaline Tsentedrin", "definition": "A central nervous system stimulant used most commonly in the treatment of ATTENTION DEFICIT DISORDER in children and for NARCOLEPSY. Its mechanisms appear to be similar to those of DEXTROAMPHETAMINE. The d-isomer of this drug is referred to as DEXMETHYLPHENIDATE.\n    ", "id": "MESH:D008774"}
{"mention": "hyperactivity", "mention_text": "Methylphenidate is structurally and functionally similar to amphetamine. Cerebral vasculitis associated with amphetamine abuse is well documented, and in rare cases ischaemic stroke has been reported after methylphenidate intake in children. We report the case of a 63-year-old female who was treated with methylphenidate due to hyperactivity and suffered from multiple ischaemic strokes. We consider drug-induced cerebral vasculitis as the most likely cause of recurrent ischaemic strokes in the absence of any pathological findings during the diagnostic work-up. We conclude that methylphenidate mediated vasculitis should be considered in patients with neurological symptoms and a history of methylphenidate therapy. This potential side-effect, though very rare, represents one more reason to be very restrictive in the use of methylphenidate.", "entity": "Hyperkinesis", "aliases": "Generalized Hyperkinesia Hyperkinesias Hyperactivity Motor Hyperkinesis Hyperkinetic Movement Movements", "definition": "Excessive movement of muscles of the body as a whole, which may be associated with organic or psychological disorders.\n    ", "id": "MESH:D006948"}
{"mention": "ischaemic strokes", "mention_text": "Methylphenidate is structurally and functionally similar to amphetamine. Cerebral vasculitis associated with amphetamine abuse is well documented, and in rare cases ischaemic stroke has been reported after methylphenidate intake in children. We report the case of a 63-year-old female who was treated with methylphenidate due to hyperactivity and suffered from multiple ischaemic strokes. We consider drug-induced cerebral vasculitis as the most likely cause of recurrent ischaemic strokes in the absence of any pathological findings during the diagnostic work-up. We conclude that methylphenidate mediated vasculitis should be considered in patients with neurological symptoms and a history of methylphenidate therapy. This potential side-effect, though very rare, represents one more reason to be very restrictive in the use of methylphenidate.", "entity": "Cerebral Infarction", "aliases": "Anterior Choroidal Artery Infarction Cerebral Left Hemisphere Right Infarctions Subcortical Posterior", "definition": "The formation of an area of NECROSIS in the CEREBRUM caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., INFARCTION, ANTERIOR CEREBRAL ARTERY), and etiology (e.g., embolic infarction).\n    ", "id": "MESH:D002544"}
{"mention": "cerebral vasculitis", "mention_text": "Methylphenidate is structurally and functionally similar to amphetamine. Cerebral vasculitis associated with amphetamine abuse is well documented, and in rare cases ischaemic stroke has been reported after methylphenidate intake in children. We report the case of a 63-year-old female who was treated with methylphenidate due to hyperactivity and suffered from multiple ischaemic strokes. We consider drug-induced cerebral vasculitis as the most likely cause of recurrent ischaemic strokes in the absence of any pathological findings during the diagnostic work-up. We conclude that methylphenidate mediated vasculitis should be considered in patients with neurological symptoms and a history of methylphenidate therapy. This potential side-effect, though very rare, represents one more reason to be very restrictive in the use of methylphenidate.", "entity": "Vasculitis, Central Nervous System", "aliases": "Angiitis Central Nervous System Cerebral Granulomatous Arteritis Postzoster CNS Vasculitis Primary Secondary", "definition": "Inflammation of blood vessels within the central nervous system. Primary vasculitis is usually caused by autoimmune or idiopathic factors, while secondary vasculitis is caused by existing disease process. Clinical manifestations are highly variable but include HEADACHE; SEIZURES; behavioral alterations; INTRACRANIAL HEMORRHAGES; TRANSIENT ISCHEMIC ATTACK; and BRAIN INFARCTION. (From Adams et al., Principles of Neurology, 6th ed, pp856-61)\n    ", "id": "MESH:D020293"}
{"mention": "vasculitis", "mention_text": "Methylphenidate is structurally and functionally similar to amphetamine. Cerebral vasculitis associated with amphetamine abuse is well documented, and in rare cases ischaemic stroke has been reported after methylphenidate intake in children. We report the case of a 63-year-old female who was treated with methylphenidate due to hyperactivity and suffered from multiple ischaemic strokes. We consider drug-induced cerebral vasculitis as the most likely cause of recurrent ischaemic strokes in the absence of any pathological findings during the diagnostic work-up. We conclude that methylphenidate mediated vasculitis should be considered in patients with neurological symptoms and a history of methylphenidate therapy. This potential side-effect, though very rare, represents one more reason to be very restrictive in the use of methylphenidate.", "entity": "Vasculitis", "aliases": "Angiitides Angiitis Vasculitides Vasculitis", "definition": "Inflammation of any one of the blood vessels, including the ARTERIES; VEINS; and rest of the vasculature system in the body.\n    ", "id": "MESH:D014657"}
{"mention": "Cerebral haemorrhage", "mention_text": "Cerebral haemorrhage induced by warfarin - the influence of drug-drug interactions.", "entity": "Cerebral Hemorrhage", "aliases": "Brain Hemorrhage Cerebral Hemorrhages Parenchymal Cerebrum Intracerebral", "definition": "Bleeding into one or both CEREBRAL HEMISPHERES including the BASAL GANGLIA and the CEREBRAL CORTEX. It is often associated with HYPERTENSION and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D002543"}
{"mention": "warfarin", "mention_text": "Cerebral haemorrhage induced by warfarin - the influence of drug-drug interactions.", "entity": "Warfarin", "aliases": "4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one Aldo Brand of Warfarin Sodium Aldocumar Antigen Apo-Warfarin Apotex Bailly Boots Bristol-Myers Squibb Coumadin Coumadine Estedi Gen-Warfarin Genpharm Goldshield Marevan Potassium Tedicumar Warfant", "definition": "An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.\n    ", "id": "MESH:D014859"}
{"mention": "warfarin", "mention_text": "PURPOSE: To evaluate the frequency, severity and preventability of warfarin-induced cerebral haemorrhages due to warfarin and warfarin-drug interactions in patients living in the county of Osterg  tland, Sweden. METHODS: All patients with a diagnosed cerebral haemorrhage at three hospitals during the period 2000-2002 were identified. Medical records were studied retrospectively to evaluate whether warfarin and warfarin-drug interactions could have caused the cerebral haemorrhage. The proportion of possibly avoidable cases due to drug interactions was estimated. RESULTS: Among 593 patients with cerebral haemorrhage, 59 (10%) were assessed as related to warfarin treatment. This imply an incidence of 1.7/100,000 treatment years. Of the 59 cases, 26 (44%) had a fatal outcome, compared to 136 (25%) among the non-warfarin patients (p < 0.01). A warfarin-drug interaction could have contributed to the haemorrhage in 24 (41%) of the warfarin patients and in 7 of these (12%) the bleeding complication was considered being possible to avoid. CONCLUSIONS: Warfarin-induced cerebral haemorrhages are a major clinical problem with a high fatality rate. Almost half of the cases was related to a warfarin-drug interaction. A significant proportion of warfarin-related cerebral haemorrhages might have been prevented if greater caution had been taken when prescribing drugs known to interact with warfarin.", "entity": "Warfarin", "aliases": "4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one Aldo Brand of Warfarin Sodium Aldocumar Antigen Apo-Warfarin Apotex Bailly Boots Bristol-Myers Squibb Coumadin Coumadine Estedi Gen-Warfarin Genpharm Goldshield Marevan Potassium Tedicumar Warfant", "definition": "An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.\n    ", "id": "MESH:D014859"}
{"mention": "cerebral haemorrhages", "mention_text": "PURPOSE: To evaluate the frequency, severity and preventability of warfarin-induced cerebral haemorrhages due to warfarin and warfarin-drug interactions in patients living in the county of Osterg  tland, Sweden. METHODS: All patients with a diagnosed cerebral haemorrhage at three hospitals during the period 2000-2002 were identified. Medical records were studied retrospectively to evaluate whether warfarin and warfarin-drug interactions could have caused the cerebral haemorrhage. The proportion of possibly avoidable cases due to drug interactions was estimated. RESULTS: Among 593 patients with cerebral haemorrhage, 59 (10%) were assessed as related to warfarin treatment. This imply an incidence of 1.7/100,000 treatment years. Of the 59 cases, 26 (44%) had a fatal outcome, compared to 136 (25%) among the non-warfarin patients (p < 0.01). A warfarin-drug interaction could have contributed to the haemorrhage in 24 (41%) of the warfarin patients and in 7 of these (12%) the bleeding complication was considered being possible to avoid. CONCLUSIONS: Warfarin-induced cerebral haemorrhages are a major clinical problem with a high fatality rate. Almost half of the cases was related to a warfarin-drug interaction. A significant proportion of warfarin-related cerebral haemorrhages might have been prevented if greater caution had been taken when prescribing drugs known to interact with warfarin.", "entity": "Cerebral Hemorrhage", "aliases": "Brain Hemorrhage Cerebral Hemorrhages Parenchymal Cerebrum Intracerebral", "definition": "Bleeding into one or both CEREBRAL HEMISPHERES including the BASAL GANGLIA and the CEREBRAL CORTEX. It is often associated with HYPERTENSION and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D002543"}
{"mention": "cerebral haemorrhage", "mention_text": "PURPOSE: To evaluate the frequency, severity and preventability of warfarin-induced cerebral haemorrhages due to warfarin and warfarin-drug interactions in patients living in the county of Osterg  tland, Sweden. METHODS: All patients with a diagnosed cerebral haemorrhage at three hospitals during the period 2000-2002 were identified. Medical records were studied retrospectively to evaluate whether warfarin and warfarin-drug interactions could have caused the cerebral haemorrhage. The proportion of possibly avoidable cases due to drug interactions was estimated. RESULTS: Among 593 patients with cerebral haemorrhage, 59 (10%) were assessed as related to warfarin treatment. This imply an incidence of 1.7/100,000 treatment years. Of the 59 cases, 26 (44%) had a fatal outcome, compared to 136 (25%) among the non-warfarin patients (p < 0.01). A warfarin-drug interaction could have contributed to the haemorrhage in 24 (41%) of the warfarin patients and in 7 of these (12%) the bleeding complication was considered being possible to avoid. CONCLUSIONS: Warfarin-induced cerebral haemorrhages are a major clinical problem with a high fatality rate. Almost half of the cases was related to a warfarin-drug interaction. A significant proportion of warfarin-related cerebral haemorrhages might have been prevented if greater caution had been taken when prescribing drugs known to interact with warfarin.", "entity": "Cerebral Hemorrhage", "aliases": "Brain Hemorrhage Cerebral Hemorrhages Parenchymal Cerebrum Intracerebral", "definition": "Bleeding into one or both CEREBRAL HEMISPHERES including the BASAL GANGLIA and the CEREBRAL CORTEX. It is often associated with HYPERTENSION and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D002543"}
{"mention": "haemorrhage", "mention_text": "PURPOSE: To evaluate the frequency, severity and preventability of warfarin-induced cerebral haemorrhages due to warfarin and warfarin-drug interactions in patients living in the county of Osterg  tland, Sweden. METHODS: All patients with a diagnosed cerebral haemorrhage at three hospitals during the period 2000-2002 were identified. Medical records were studied retrospectively to evaluate whether warfarin and warfarin-drug interactions could have caused the cerebral haemorrhage. The proportion of possibly avoidable cases due to drug interactions was estimated. RESULTS: Among 593 patients with cerebral haemorrhage, 59 (10%) were assessed as related to warfarin treatment. This imply an incidence of 1.7/100,000 treatment years. Of the 59 cases, 26 (44%) had a fatal outcome, compared to 136 (25%) among the non-warfarin patients (p < 0.01). A warfarin-drug interaction could have contributed to the haemorrhage in 24 (41%) of the warfarin patients and in 7 of these (12%) the bleeding complication was considered being possible to avoid. CONCLUSIONS: Warfarin-induced cerebral haemorrhages are a major clinical problem with a high fatality rate. Almost half of the cases was related to a warfarin-drug interaction. A significant proportion of warfarin-related cerebral haemorrhages might have been prevented if greater caution had been taken when prescribing drugs known to interact with warfarin.", "entity": "Hemorrhage", "aliases": "Bleeding Hemorrhage Hemorrhages", "definition": "Bleeding or escape of blood from a vessel.\n    ", "id": "MESH:D006470"}
{"mention": "bleeding", "mention_text": "PURPOSE: To evaluate the frequency, severity and preventability of warfarin-induced cerebral haemorrhages due to warfarin and warfarin-drug interactions in patients living in the county of Osterg  tland, Sweden. METHODS: All patients with a diagnosed cerebral haemorrhage at three hospitals during the period 2000-2002 were identified. Medical records were studied retrospectively to evaluate whether warfarin and warfarin-drug interactions could have caused the cerebral haemorrhage. The proportion of possibly avoidable cases due to drug interactions was estimated. RESULTS: Among 593 patients with cerebral haemorrhage, 59 (10%) were assessed as related to warfarin treatment. This imply an incidence of 1.7/100,000 treatment years. Of the 59 cases, 26 (44%) had a fatal outcome, compared to 136 (25%) among the non-warfarin patients (p < 0.01). A warfarin-drug interaction could have contributed to the haemorrhage in 24 (41%) of the warfarin patients and in 7 of these (12%) the bleeding complication was considered being possible to avoid. CONCLUSIONS: Warfarin-induced cerebral haemorrhages are a major clinical problem with a high fatality rate. Almost half of the cases was related to a warfarin-drug interaction. A significant proportion of warfarin-related cerebral haemorrhages might have been prevented if greater caution had been taken when prescribing drugs known to interact with warfarin.", "entity": "Hemorrhage", "aliases": "Bleeding Hemorrhage Hemorrhages", "definition": "Bleeding or escape of blood from a vessel.\n    ", "id": "MESH:D006470"}
{"mention": "Warfarin", "mention_text": "PURPOSE: To evaluate the frequency, severity and preventability of warfarin-induced cerebral haemorrhages due to warfarin and warfarin-drug interactions in patients living in the county of Osterg  tland, Sweden. METHODS: All patients with a diagnosed cerebral haemorrhage at three hospitals during the period 2000-2002 were identified. Medical records were studied retrospectively to evaluate whether warfarin and warfarin-drug interactions could have caused the cerebral haemorrhage. The proportion of possibly avoidable cases due to drug interactions was estimated. RESULTS: Among 593 patients with cerebral haemorrhage, 59 (10%) were assessed as related to warfarin treatment. This imply an incidence of 1.7/100,000 treatment years. Of the 59 cases, 26 (44%) had a fatal outcome, compared to 136 (25%) among the non-warfarin patients (p < 0.01). A warfarin-drug interaction could have contributed to the haemorrhage in 24 (41%) of the warfarin patients and in 7 of these (12%) the bleeding complication was considered being possible to avoid. CONCLUSIONS: Warfarin-induced cerebral haemorrhages are a major clinical problem with a high fatality rate. Almost half of the cases was related to a warfarin-drug interaction. A significant proportion of warfarin-related cerebral haemorrhages might have been prevented if greater caution had been taken when prescribing drugs known to interact with warfarin.", "entity": "Warfarin", "aliases": "4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one Aldo Brand of Warfarin Sodium Aldocumar Antigen Apo-Warfarin Apotex Bailly Boots Bristol-Myers Squibb Coumadin Coumadine Estedi Gen-Warfarin Genpharm Goldshield Marevan Potassium Tedicumar Warfant", "definition": "An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.\n    ", "id": "MESH:D014859"}
{"mention": "methylprednisolone", "mention_text": "Side effects of postoperative administration of methylprednisolone and gentamicin into the posterior sub-Tenon's space.", "entity": "Methylprednisolone", "aliases": "6 Methylprednisolone 6-Methylprednisolone Medrol Metipred Urbason", "definition": "A PREDNISOLONE derivative with similar anti-inflammatory action.\n    ", "id": "MESH:D008775"}
{"mention": "gentamicin", "mention_text": "Side effects of postoperative administration of methylprednisolone and gentamicin into the posterior sub-Tenon's space.", "entity": "Gentamicins", "aliases": "G Myticin G-Myticin GMyticin Garamycin Gentacycol Gentamicin Sulfate (USP) Gentamicins Gentamycin Gentamycins Gentavet Genticin", "definition": "A complex of closely related aminoglycosides obtained from MICROMONOSPORA purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit PROTEIN BIOSYNTHESIS.\n    ", "id": "MESH:D005839"}
{"mention": "methylprednisolone", "mention_text": "PURPOSE: To assess the incidence of postoperative emetic side effects after the administration of methylprednisolone and gentamicin into the posterior sub-Tenon's space at the end of routine cataract surgery. SETTING: St. Luke's Hospital, Gwardamangia, Malta. METHODS: A double-blind double-armed prospective study comprised 40 patients who had uneventful sutureless phacoemulsification under sub-Tenon's local infiltration of 3 mL of plain lignocaine. At the end of the procedure, Group A (n = 20) had 20 mg/0.5 mL of methylprednisolone and 10 mg/0.5 mL of gentamicin injected into the posterior sub-Tenon's space and Group B (n = 20) had the same combination injected into the anterior sub-Tenon's space. Postoperatively, all patients were assessed for symptoms of nausea, vomiting, and headache. A chi-square test was used to assess the statistical significance of results. RESULTS: Sixty percent in Group A developed postoperative emetic symptoms, headache, or both; 1 patient in Group B developed symptoms. CONCLUSIONS: The administration of methylprednisolone and gentamicin in the posterior sub-Tenon's space was related to a high incidence of side effects including nausea, vomiting, and headache. All adverse effects were self-limiting.", "entity": "Methylprednisolone", "aliases": "6 Methylprednisolone 6-Methylprednisolone Medrol Metipred Urbason", "definition": "A PREDNISOLONE derivative with similar anti-inflammatory action.\n    ", "id": "MESH:D008775"}
{"mention": "gentamicin", "mention_text": "PURPOSE: To assess the incidence of postoperative emetic side effects after the administration of methylprednisolone and gentamicin into the posterior sub-Tenon's space at the end of routine cataract surgery. SETTING: St. Luke's Hospital, Gwardamangia, Malta. METHODS: A double-blind double-armed prospective study comprised 40 patients who had uneventful sutureless phacoemulsification under sub-Tenon's local infiltration of 3 mL of plain lignocaine. At the end of the procedure, Group A (n = 20) had 20 mg/0.5 mL of methylprednisolone and 10 mg/0.5 mL of gentamicin injected into the posterior sub-Tenon's space and Group B (n = 20) had the same combination injected into the anterior sub-Tenon's space. Postoperatively, all patients were assessed for symptoms of nausea, vomiting, and headache. A chi-square test was used to assess the statistical significance of results. RESULTS: Sixty percent in Group A developed postoperative emetic symptoms, headache, or both; 1 patient in Group B developed symptoms. CONCLUSIONS: The administration of methylprednisolone and gentamicin in the posterior sub-Tenon's space was related to a high incidence of side effects including nausea, vomiting, and headache. All adverse effects were self-limiting.", "entity": "Gentamicins", "aliases": "G Myticin G-Myticin GMyticin Garamycin Gentacycol Gentamicin Sulfate (USP) Gentamicins Gentamycin Gentamycins Gentavet Genticin", "definition": "A complex of closely related aminoglycosides obtained from MICROMONOSPORA purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit PROTEIN BIOSYNTHESIS.\n    ", "id": "MESH:D005839"}
{"mention": "cataract", "mention_text": "PURPOSE: To assess the incidence of postoperative emetic side effects after the administration of methylprednisolone and gentamicin into the posterior sub-Tenon's space at the end of routine cataract surgery. SETTING: St. Luke's Hospital, Gwardamangia, Malta. METHODS: A double-blind double-armed prospective study comprised 40 patients who had uneventful sutureless phacoemulsification under sub-Tenon's local infiltration of 3 mL of plain lignocaine. At the end of the procedure, Group A (n = 20) had 20 mg/0.5 mL of methylprednisolone and 10 mg/0.5 mL of gentamicin injected into the posterior sub-Tenon's space and Group B (n = 20) had the same combination injected into the anterior sub-Tenon's space. Postoperatively, all patients were assessed for symptoms of nausea, vomiting, and headache. A chi-square test was used to assess the statistical significance of results. RESULTS: Sixty percent in Group A developed postoperative emetic symptoms, headache, or both; 1 patient in Group B developed symptoms. CONCLUSIONS: The administration of methylprednisolone and gentamicin in the posterior sub-Tenon's space was related to a high incidence of side effects including nausea, vomiting, and headache. All adverse effects were self-limiting.", "entity": "Cataract", "aliases": "Cataract Membranous Cataracts Lens Opacities Opacity Pseudoaphakia Pseudoaphakias", "definition": "Partial or complete opacity on or in the lens or capsule of one or both eyes, impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). (Dorland, 27th ed)\n    ", "id": "MESH:D002386"}
{"mention": "lignocaine", "mention_text": "PURPOSE: To assess the incidence of postoperative emetic side effects after the administration of methylprednisolone and gentamicin into the posterior sub-Tenon's space at the end of routine cataract surgery. SETTING: St. Luke's Hospital, Gwardamangia, Malta. METHODS: A double-blind double-armed prospective study comprised 40 patients who had uneventful sutureless phacoemulsification under sub-Tenon's local infiltration of 3 mL of plain lignocaine. At the end of the procedure, Group A (n = 20) had 20 mg/0.5 mL of methylprednisolone and 10 mg/0.5 mL of gentamicin injected into the posterior sub-Tenon's space and Group B (n = 20) had the same combination injected into the anterior sub-Tenon's space. Postoperatively, all patients were assessed for symptoms of nausea, vomiting, and headache. A chi-square test was used to assess the statistical significance of results. RESULTS: Sixty percent in Group A developed postoperative emetic symptoms, headache, or both; 1 patient in Group B developed symptoms. CONCLUSIONS: The administration of methylprednisolone and gentamicin in the posterior sub-Tenon's space was related to a high incidence of side effects including nausea, vomiting, and headache. All adverse effects were self-limiting.", "entity": "Lidocaine", "aliases": "2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide 2-2EtN-2MePhAcN Astrazeneca Brand of Lidocaine Dalcaine Jenapharm Lidocanine Hydrochloride Carbonate (2:1) Hydrocarbonate Monoacetate Monohydrochloride Monohydrate Sulfate (1:1) Lignocaine Novocol Octocaine Strathmann Xylesthesin Xylocaine Xylocitin Xyloneural", "definition": "A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.\n    ", "id": "MESH:D008012"}
{"mention": "nausea, vomiting", "mention_text": "PURPOSE: To assess the incidence of postoperative emetic side effects after the administration of methylprednisolone and gentamicin into the posterior sub-Tenon's space at the end of routine cataract surgery. SETTING: St. Luke's Hospital, Gwardamangia, Malta. METHODS: A double-blind double-armed prospective study comprised 40 patients who had uneventful sutureless phacoemulsification under sub-Tenon's local infiltration of 3 mL of plain lignocaine. At the end of the procedure, Group A (n = 20) had 20 mg/0.5 mL of methylprednisolone and 10 mg/0.5 mL of gentamicin injected into the posterior sub-Tenon's space and Group B (n = 20) had the same combination injected into the anterior sub-Tenon's space. Postoperatively, all patients were assessed for symptoms of nausea, vomiting, and headache. A chi-square test was used to assess the statistical significance of results. RESULTS: Sixty percent in Group A developed postoperative emetic symptoms, headache, or both; 1 patient in Group B developed symptoms. CONCLUSIONS: The administration of methylprednisolone and gentamicin in the posterior sub-Tenon's space was related to a high incidence of side effects including nausea, vomiting, and headache. All adverse effects were self-limiting.", "entity": "Postoperative Nausea and Vomiting", "aliases": "Emeses Postoperative Emesis Nausea and Vomiting PONV", "definition": "Emesis and queasiness occurring after anesthesia.\n    ", "id": "MESH:D020250"}
{"mention": "headache", "mention_text": "PURPOSE: To assess the incidence of postoperative emetic side effects after the administration of methylprednisolone and gentamicin into the posterior sub-Tenon's space at the end of routine cataract surgery. SETTING: St. Luke's Hospital, Gwardamangia, Malta. METHODS: A double-blind double-armed prospective study comprised 40 patients who had uneventful sutureless phacoemulsification under sub-Tenon's local infiltration of 3 mL of plain lignocaine. At the end of the procedure, Group A (n = 20) had 20 mg/0.5 mL of methylprednisolone and 10 mg/0.5 mL of gentamicin injected into the posterior sub-Tenon's space and Group B (n = 20) had the same combination injected into the anterior sub-Tenon's space. Postoperatively, all patients were assessed for symptoms of nausea, vomiting, and headache. A chi-square test was used to assess the statistical significance of results. RESULTS: Sixty percent in Group A developed postoperative emetic symptoms, headache, or both; 1 patient in Group B developed symptoms. CONCLUSIONS: The administration of methylprednisolone and gentamicin in the posterior sub-Tenon's space was related to a high incidence of side effects including nausea, vomiting, and headache. All adverse effects were self-limiting.", "entity": "Headache", "aliases": "Bilateral Headache Headaches Cephalalgia Cephalalgias Cephalgia Cephalgias Cephalodynia Cephalodynias Cranial Pain Pains Generalized Head Ocular Orthostatic Periorbital Retro-Ocular Sharp Throbbing Unilateral Vertex Hemicrania Retro", "definition": "The symptom of PAIN in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of HEADACHE DISORDERS.\n    ", "id": "MESH:D006261"}
{"mention": "postoperative emetic symptoms", "mention_text": "PURPOSE: To assess the incidence of postoperative emetic side effects after the administration of methylprednisolone and gentamicin into the posterior sub-Tenon's space at the end of routine cataract surgery. SETTING: St. Luke's Hospital, Gwardamangia, Malta. METHODS: A double-blind double-armed prospective study comprised 40 patients who had uneventful sutureless phacoemulsification under sub-Tenon's local infiltration of 3 mL of plain lignocaine. At the end of the procedure, Group A (n = 20) had 20 mg/0.5 mL of methylprednisolone and 10 mg/0.5 mL of gentamicin injected into the posterior sub-Tenon's space and Group B (n = 20) had the same combination injected into the anterior sub-Tenon's space. Postoperatively, all patients were assessed for symptoms of nausea, vomiting, and headache. A chi-square test was used to assess the statistical significance of results. RESULTS: Sixty percent in Group A developed postoperative emetic symptoms, headache, or both; 1 patient in Group B developed symptoms. CONCLUSIONS: The administration of methylprednisolone and gentamicin in the posterior sub-Tenon's space was related to a high incidence of side effects including nausea, vomiting, and headache. All adverse effects were self-limiting.", "entity": "Postoperative Nausea and Vomiting", "aliases": "Emeses Postoperative Emesis Nausea and Vomiting PONV", "definition": "Emesis and queasiness occurring after anesthesia.\n    ", "id": "MESH:D020250"}
{"mention": "nephropathy", "mention_text": "Cardiac Angiography in Renally Impaired Patients (CARE) study: a randomized double-blind trial of contrast-induced nephropathy in patients with chronic kidney disease.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "chronic kidney disease", "mention_text": "Cardiac Angiography in Renally Impaired Patients (CARE) study: a randomized double-blind trial of contrast-induced nephropathy in patients with chronic kidney disease.", "entity": "Renal Insufficiency, Chronic", "aliases": "Chronic Kidney Disease Diseases Insufficiencies Insufficiency Renal", "definition": "Conditions in which the KIDNEYS perform below the normal level for more than three months. Chronic kidney insufficiency is classified by five stages according to the decline in GLOMERULAR FILTRATION RATE and the degree of kidney damage (as measured by the level of PROTEINURIA). The most severe form is the end-stage renal disease (CHRONIC KIDNEY FAILURE). (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002)\n    ", "id": "MESH:D051436"}
{"mention": "contrast medium", "mention_text": "BACKGROUND: No direct comparisons exist of the renal tolerability of the low-osmolality contrast medium iopamidol with that of the iso-osmolality contrast medium iodixanol in high-risk patients. METHODS AND RESULTS: The present study is a multicenter, randomized, double-blind comparison of iopamidol and iodixanol in patients with chronic kidney disease (estimated glomerular filtration rate, 20 to 59 mL/min) who underwent cardiac angiography or percutaneous coronary interventions. Serum creatinine (SCr) levels and estimated glomerular filtration rate were assessed at baseline and 2 to 5 days after receiving medications. The primary outcome was a postdose SCr increase > or = 0.5 mg/dL (44.2 micromol/L) over baseline. Secondary outcomes were a postdose SCr increase > or = 25%, a postdose estimated glomerular filtration rate decrease of > or = 25%, and the mean peak change in SCr. In 414 patients, contrast volume, presence of diabetes mellitus, use of N-acetylcysteine, mean baseline SCr, and estimated glomerular filtration rate were comparable in the 2 groups. SCr increases > or = 0.5 mg/dL occurred in 4.4% (9 of 204 patients) after iopamidol and 6.7% (14 of 210 patients) after iodixanol (P=0.39), whereas rates of SCr increases > or = 25% were 9.8% and 12.4%, respectively (P=0.44). In patients with diabetes, SCr increases > or = 0.5 mg/dL were 5.1% (4 of 78 patients) with iopamidol and 13.0% (12 of 92 patients) with iodixanol (P=0.11), whereas SCr increases > or = 25% were 10.3% and 15.2%, respectively (P=0.37). Mean post-SCr increases were significantly less with iopamidol (all patients: 0.07 versus 0.12 mg/dL, 6.2 versus 10.6 micromol/L, P=0.03; patients with diabetes: 0.07 versus 0.16 mg/dL, 6.2 versus 14.1 micromol/L, P=0.01). CONCLUSIONS: The rate of contrast-induced nephropathy, defined by multiple end points, is not statistically different after the intraarterial administration of iopamidol or iodixanol to high-risk patients, with or without diabetes mellitus. Any true difference between the agents is small and not likely to be clinically significant.", "entity": "Contrast Media", "aliases": "Agent Radiocontrast Agents Contrast Materials Media Radiopaque", "definition": "Substances used to allow enhanced visualization of tissues.\n    ", "id": "MESH:D003287"}
{"mention": "iopamidol", "mention_text": "BACKGROUND: No direct comparisons exist of the renal tolerability of the low-osmolality contrast medium iopamidol with that of the iso-osmolality contrast medium iodixanol in high-risk patients. METHODS AND RESULTS: The present study is a multicenter, randomized, double-blind comparison of iopamidol and iodixanol in patients with chronic kidney disease (estimated glomerular filtration rate, 20 to 59 mL/min) who underwent cardiac angiography or percutaneous coronary interventions. Serum creatinine (SCr) levels and estimated glomerular filtration rate were assessed at baseline and 2 to 5 days after receiving medications. The primary outcome was a postdose SCr increase > or = 0.5 mg/dL (44.2 micromol/L) over baseline. Secondary outcomes were a postdose SCr increase > or = 25%, a postdose estimated glomerular filtration rate decrease of > or = 25%, and the mean peak change in SCr. In 414 patients, contrast volume, presence of diabetes mellitus, use of N-acetylcysteine, mean baseline SCr, and estimated glomerular filtration rate were comparable in the 2 groups. SCr increases > or = 0.5 mg/dL occurred in 4.4% (9 of 204 patients) after iopamidol and 6.7% (14 of 210 patients) after iodixanol (P=0.39), whereas rates of SCr increases > or = 25% were 9.8% and 12.4%, respectively (P=0.44). In patients with diabetes, SCr increases > or = 0.5 mg/dL were 5.1% (4 of 78 patients) with iopamidol and 13.0% (12 of 92 patients) with iodixanol (P=0.11), whereas SCr increases > or = 25% were 10.3% and 15.2%, respectively (P=0.37). Mean post-SCr increases were significantly less with iopamidol (all patients: 0.07 versus 0.12 mg/dL, 6.2 versus 10.6 micromol/L, P=0.03; patients with diabetes: 0.07 versus 0.16 mg/dL, 6.2 versus 14.1 micromol/L, P=0.01). CONCLUSIONS: The rate of contrast-induced nephropathy, defined by multiple end points, is not statistically different after the intraarterial administration of iopamidol or iodixanol to high-risk patients, with or without diabetes mellitus. Any true difference between the agents is small and not likely to be clinically significant.", "entity": "Iopamidol", "aliases": "B 15,000 15000 B-15,000 B-15000 B15,000 B15000 Gastromiro Iopamidol (+-)-Isomer (R)-Isomer Sodium Salt (S)-Isomer Iopamiro Isovue 370 Jopamidol Niopam SQ 13,396 Solutrast Gastro", "definition": "A non-ionic, water-soluble contrast agent which is used in myelography, arthrography, nephroangiography, arteriography, and other radiological procedures.\n    ", "id": "MESH:D007479"}
{"mention": "iodixanol", "mention_text": "BACKGROUND: No direct comparisons exist of the renal tolerability of the low-osmolality contrast medium iopamidol with that of the iso-osmolality contrast medium iodixanol in high-risk patients. METHODS AND RESULTS: The present study is a multicenter, randomized, double-blind comparison of iopamidol and iodixanol in patients with chronic kidney disease (estimated glomerular filtration rate, 20 to 59 mL/min) who underwent cardiac angiography or percutaneous coronary interventions. Serum creatinine (SCr) levels and estimated glomerular filtration rate were assessed at baseline and 2 to 5 days after receiving medications. The primary outcome was a postdose SCr increase > or = 0.5 mg/dL (44.2 micromol/L) over baseline. Secondary outcomes were a postdose SCr increase > or = 25%, a postdose estimated glomerular filtration rate decrease of > or = 25%, and the mean peak change in SCr. In 414 patients, contrast volume, presence of diabetes mellitus, use of N-acetylcysteine, mean baseline SCr, and estimated glomerular filtration rate were comparable in the 2 groups. SCr increases > or = 0.5 mg/dL occurred in 4.4% (9 of 204 patients) after iopamidol and 6.7% (14 of 210 patients) after iodixanol (P=0.39), whereas rates of SCr increases > or = 25% were 9.8% and 12.4%, respectively (P=0.44). In patients with diabetes, SCr increases > or = 0.5 mg/dL were 5.1% (4 of 78 patients) with iopamidol and 13.0% (12 of 92 patients) with iodixanol (P=0.11), whereas SCr increases > or = 25% were 10.3% and 15.2%, respectively (P=0.37). Mean post-SCr increases were significantly less with iopamidol (all patients: 0.07 versus 0.12 mg/dL, 6.2 versus 10.6 micromol/L, P=0.03; patients with diabetes: 0.07 versus 0.16 mg/dL, 6.2 versus 14.1 micromol/L, P=0.01). CONCLUSIONS: The rate of contrast-induced nephropathy, defined by multiple end points, is not statistically different after the intraarterial administration of iopamidol or iodixanol to high-risk patients, with or without diabetes mellitus. Any true difference between the agents is small and not likely to be clinically significant.", "entity": "iodixanol", "aliases": "Visipaque Unique Softpac contrast media 2-5410-3 iodixanol iodixanol-320", "definition": "", "id": "MESH:C044834"}
{"mention": "chronic kidney disease", "mention_text": "BACKGROUND: No direct comparisons exist of the renal tolerability of the low-osmolality contrast medium iopamidol with that of the iso-osmolality contrast medium iodixanol in high-risk patients. METHODS AND RESULTS: The present study is a multicenter, randomized, double-blind comparison of iopamidol and iodixanol in patients with chronic kidney disease (estimated glomerular filtration rate, 20 to 59 mL/min) who underwent cardiac angiography or percutaneous coronary interventions. Serum creatinine (SCr) levels and estimated glomerular filtration rate were assessed at baseline and 2 to 5 days after receiving medications. The primary outcome was a postdose SCr increase > or = 0.5 mg/dL (44.2 micromol/L) over baseline. Secondary outcomes were a postdose SCr increase > or = 25%, a postdose estimated glomerular filtration rate decrease of > or = 25%, and the mean peak change in SCr. In 414 patients, contrast volume, presence of diabetes mellitus, use of N-acetylcysteine, mean baseline SCr, and estimated glomerular filtration rate were comparable in the 2 groups. SCr increases > or = 0.5 mg/dL occurred in 4.4% (9 of 204 patients) after iopamidol and 6.7% (14 of 210 patients) after iodixanol (P=0.39), whereas rates of SCr increases > or = 25% were 9.8% and 12.4%, respectively (P=0.44). In patients with diabetes, SCr increases > or = 0.5 mg/dL were 5.1% (4 of 78 patients) with iopamidol and 13.0% (12 of 92 patients) with iodixanol (P=0.11), whereas SCr increases > or = 25% were 10.3% and 15.2%, respectively (P=0.37). Mean post-SCr increases were significantly less with iopamidol (all patients: 0.07 versus 0.12 mg/dL, 6.2 versus 10.6 micromol/L, P=0.03; patients with diabetes: 0.07 versus 0.16 mg/dL, 6.2 versus 14.1 micromol/L, P=0.01). CONCLUSIONS: The rate of contrast-induced nephropathy, defined by multiple end points, is not statistically different after the intraarterial administration of iopamidol or iodixanol to high-risk patients, with or without diabetes mellitus. Any true difference between the agents is small and not likely to be clinically significant.", "entity": "Renal Insufficiency, Chronic", "aliases": "Chronic Kidney Disease Diseases Insufficiencies Insufficiency Renal", "definition": "Conditions in which the KIDNEYS perform below the normal level for more than three months. Chronic kidney insufficiency is classified by five stages according to the decline in GLOMERULAR FILTRATION RATE and the degree of kidney damage (as measured by the level of PROTEINURIA). The most severe form is the end-stage renal disease (CHRONIC KIDNEY FAILURE). (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002)\n    ", "id": "MESH:D051436"}
{"mention": "creatinine", "mention_text": "BACKGROUND: No direct comparisons exist of the renal tolerability of the low-osmolality contrast medium iopamidol with that of the iso-osmolality contrast medium iodixanol in high-risk patients. METHODS AND RESULTS: The present study is a multicenter, randomized, double-blind comparison of iopamidol and iodixanol in patients with chronic kidney disease (estimated glomerular filtration rate, 20 to 59 mL/min) who underwent cardiac angiography or percutaneous coronary interventions. Serum creatinine (SCr) levels and estimated glomerular filtration rate were assessed at baseline and 2 to 5 days after receiving medications. The primary outcome was a postdose SCr increase > or = 0.5 mg/dL (44.2 micromol/L) over baseline. Secondary outcomes were a postdose SCr increase > or = 25%, a postdose estimated glomerular filtration rate decrease of > or = 25%, and the mean peak change in SCr. In 414 patients, contrast volume, presence of diabetes mellitus, use of N-acetylcysteine, mean baseline SCr, and estimated glomerular filtration rate were comparable in the 2 groups. SCr increases > or = 0.5 mg/dL occurred in 4.4% (9 of 204 patients) after iopamidol and 6.7% (14 of 210 patients) after iodixanol (P=0.39), whereas rates of SCr increases > or = 25% were 9.8% and 12.4%, respectively (P=0.44). In patients with diabetes, SCr increases > or = 0.5 mg/dL were 5.1% (4 of 78 patients) with iopamidol and 13.0% (12 of 92 patients) with iodixanol (P=0.11), whereas SCr increases > or = 25% were 10.3% and 15.2%, respectively (P=0.37). Mean post-SCr increases were significantly less with iopamidol (all patients: 0.07 versus 0.12 mg/dL, 6.2 versus 10.6 micromol/L, P=0.03; patients with diabetes: 0.07 versus 0.16 mg/dL, 6.2 versus 14.1 micromol/L, P=0.01). CONCLUSIONS: The rate of contrast-induced nephropathy, defined by multiple end points, is not statistically different after the intraarterial administration of iopamidol or iodixanol to high-risk patients, with or without diabetes mellitus. Any true difference between the agents is small and not likely to be clinically significant.", "entity": "Creatinine", "aliases": "Creatinine Sulfate Salt Krebiozen", "definition": "", "id": "MESH:D003404"}
{"mention": "diabetes mellitus", "mention_text": "BACKGROUND: No direct comparisons exist of the renal tolerability of the low-osmolality contrast medium iopamidol with that of the iso-osmolality contrast medium iodixanol in high-risk patients. METHODS AND RESULTS: The present study is a multicenter, randomized, double-blind comparison of iopamidol and iodixanol in patients with chronic kidney disease (estimated glomerular filtration rate, 20 to 59 mL/min) who underwent cardiac angiography or percutaneous coronary interventions. Serum creatinine (SCr) levels and estimated glomerular filtration rate were assessed at baseline and 2 to 5 days after receiving medications. The primary outcome was a postdose SCr increase > or = 0.5 mg/dL (44.2 micromol/L) over baseline. Secondary outcomes were a postdose SCr increase > or = 25%, a postdose estimated glomerular filtration rate decrease of > or = 25%, and the mean peak change in SCr. In 414 patients, contrast volume, presence of diabetes mellitus, use of N-acetylcysteine, mean baseline SCr, and estimated glomerular filtration rate were comparable in the 2 groups. SCr increases > or = 0.5 mg/dL occurred in 4.4% (9 of 204 patients) after iopamidol and 6.7% (14 of 210 patients) after iodixanol (P=0.39), whereas rates of SCr increases > or = 25% were 9.8% and 12.4%, respectively (P=0.44). In patients with diabetes, SCr increases > or = 0.5 mg/dL were 5.1% (4 of 78 patients) with iopamidol and 13.0% (12 of 92 patients) with iodixanol (P=0.11), whereas SCr increases > or = 25% were 10.3% and 15.2%, respectively (P=0.37). Mean post-SCr increases were significantly less with iopamidol (all patients: 0.07 versus 0.12 mg/dL, 6.2 versus 10.6 micromol/L, P=0.03; patients with diabetes: 0.07 versus 0.16 mg/dL, 6.2 versus 14.1 micromol/L, P=0.01). CONCLUSIONS: The rate of contrast-induced nephropathy, defined by multiple end points, is not statistically different after the intraarterial administration of iopamidol or iodixanol to high-risk patients, with or without diabetes mellitus. Any true difference between the agents is small and not likely to be clinically significant.", "entity": "Diabetes Mellitus", "aliases": "Diabetes Mellitus", "definition": "A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.\n    ", "id": "MESH:D003920"}
{"mention": "N-acetylcysteine", "mention_text": "BACKGROUND: No direct comparisons exist of the renal tolerability of the low-osmolality contrast medium iopamidol with that of the iso-osmolality contrast medium iodixanol in high-risk patients. METHODS AND RESULTS: The present study is a multicenter, randomized, double-blind comparison of iopamidol and iodixanol in patients with chronic kidney disease (estimated glomerular filtration rate, 20 to 59 mL/min) who underwent cardiac angiography or percutaneous coronary interventions. Serum creatinine (SCr) levels and estimated glomerular filtration rate were assessed at baseline and 2 to 5 days after receiving medications. The primary outcome was a postdose SCr increase > or = 0.5 mg/dL (44.2 micromol/L) over baseline. Secondary outcomes were a postdose SCr increase > or = 25%, a postdose estimated glomerular filtration rate decrease of > or = 25%, and the mean peak change in SCr. In 414 patients, contrast volume, presence of diabetes mellitus, use of N-acetylcysteine, mean baseline SCr, and estimated glomerular filtration rate were comparable in the 2 groups. SCr increases > or = 0.5 mg/dL occurred in 4.4% (9 of 204 patients) after iopamidol and 6.7% (14 of 210 patients) after iodixanol (P=0.39), whereas rates of SCr increases > or = 25% were 9.8% and 12.4%, respectively (P=0.44). In patients with diabetes, SCr increases > or = 0.5 mg/dL were 5.1% (4 of 78 patients) with iopamidol and 13.0% (12 of 92 patients) with iodixanol (P=0.11), whereas SCr increases > or = 25% were 10.3% and 15.2%, respectively (P=0.37). Mean post-SCr increases were significantly less with iopamidol (all patients: 0.07 versus 0.12 mg/dL, 6.2 versus 10.6 micromol/L, P=0.03; patients with diabetes: 0.07 versus 0.16 mg/dL, 6.2 versus 14.1 micromol/L, P=0.01). CONCLUSIONS: The rate of contrast-induced nephropathy, defined by multiple end points, is not statistically different after the intraarterial administration of iopamidol or iodixanol to high-risk patients, with or without diabetes mellitus. Any true difference between the agents is small and not likely to be clinically significant.", "entity": "Acetylcysteine", "aliases": "Acemuc Acetabs Acetylcystein AL Atid Heumann Trom mentopin Acetylcysteine Alcon Brand Aluid Azupharma Betapharm Bioiberica Bouchara Centrafarm Disphar Farmasan Fresenius GNR-Pharma Guerbet Génévrier Hermes Hydrochloride Inpharzam Intra Klinge Krewel Lichtenstein Lindopharm Merck Oberlin Pfleger Pharbita Roberts Sodium Temmler Teva Thiemann Trommsdorff UPSA Whitehall Zambon Zinc Zyma ac-Pharma (D)-Isomer (DL)-Isomer Monoammonium Salt Monosodium Acetylin Acetyst Acid Mercapturic Acétylcystéine GNR", "definition": "The N-acetyl derivative of CYSTEINE. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates.\n    ", "id": "MESH:D000111"}
{"mention": "diabetes", "mention_text": "BACKGROUND: No direct comparisons exist of the renal tolerability of the low-osmolality contrast medium iopamidol with that of the iso-osmolality contrast medium iodixanol in high-risk patients. METHODS AND RESULTS: The present study is a multicenter, randomized, double-blind comparison of iopamidol and iodixanol in patients with chronic kidney disease (estimated glomerular filtration rate, 20 to 59 mL/min) who underwent cardiac angiography or percutaneous coronary interventions. Serum creatinine (SCr) levels and estimated glomerular filtration rate were assessed at baseline and 2 to 5 days after receiving medications. The primary outcome was a postdose SCr increase > or = 0.5 mg/dL (44.2 micromol/L) over baseline. Secondary outcomes were a postdose SCr increase > or = 25%, a postdose estimated glomerular filtration rate decrease of > or = 25%, and the mean peak change in SCr. In 414 patients, contrast volume, presence of diabetes mellitus, use of N-acetylcysteine, mean baseline SCr, and estimated glomerular filtration rate were comparable in the 2 groups. SCr increases > or = 0.5 mg/dL occurred in 4.4% (9 of 204 patients) after iopamidol and 6.7% (14 of 210 patients) after iodixanol (P=0.39), whereas rates of SCr increases > or = 25% were 9.8% and 12.4%, respectively (P=0.44). In patients with diabetes, SCr increases > or = 0.5 mg/dL were 5.1% (4 of 78 patients) with iopamidol and 13.0% (12 of 92 patients) with iodixanol (P=0.11), whereas SCr increases > or = 25% were 10.3% and 15.2%, respectively (P=0.37). Mean post-SCr increases were significantly less with iopamidol (all patients: 0.07 versus 0.12 mg/dL, 6.2 versus 10.6 micromol/L, P=0.03; patients with diabetes: 0.07 versus 0.16 mg/dL, 6.2 versus 14.1 micromol/L, P=0.01). CONCLUSIONS: The rate of contrast-induced nephropathy, defined by multiple end points, is not statistically different after the intraarterial administration of iopamidol or iodixanol to high-risk patients, with or without diabetes mellitus. Any true difference between the agents is small and not likely to be clinically significant.", "entity": "Diabetes Mellitus", "aliases": "Diabetes Mellitus", "definition": "A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.\n    ", "id": "MESH:D003920"}
{"mention": "nephropathy", "mention_text": "BACKGROUND: No direct comparisons exist of the renal tolerability of the low-osmolality contrast medium iopamidol with that of the iso-osmolality contrast medium iodixanol in high-risk patients. METHODS AND RESULTS: The present study is a multicenter, randomized, double-blind comparison of iopamidol and iodixanol in patients with chronic kidney disease (estimated glomerular filtration rate, 20 to 59 mL/min) who underwent cardiac angiography or percutaneous coronary interventions. Serum creatinine (SCr) levels and estimated glomerular filtration rate were assessed at baseline and 2 to 5 days after receiving medications. The primary outcome was a postdose SCr increase > or = 0.5 mg/dL (44.2 micromol/L) over baseline. Secondary outcomes were a postdose SCr increase > or = 25%, a postdose estimated glomerular filtration rate decrease of > or = 25%, and the mean peak change in SCr. In 414 patients, contrast volume, presence of diabetes mellitus, use of N-acetylcysteine, mean baseline SCr, and estimated glomerular filtration rate were comparable in the 2 groups. SCr increases > or = 0.5 mg/dL occurred in 4.4% (9 of 204 patients) after iopamidol and 6.7% (14 of 210 patients) after iodixanol (P=0.39), whereas rates of SCr increases > or = 25% were 9.8% and 12.4%, respectively (P=0.44). In patients with diabetes, SCr increases > or = 0.5 mg/dL were 5.1% (4 of 78 patients) with iopamidol and 13.0% (12 of 92 patients) with iodixanol (P=0.11), whereas SCr increases > or = 25% were 10.3% and 15.2%, respectively (P=0.37). Mean post-SCr increases were significantly less with iopamidol (all patients: 0.07 versus 0.12 mg/dL, 6.2 versus 10.6 micromol/L, P=0.03; patients with diabetes: 0.07 versus 0.16 mg/dL, 6.2 versus 14.1 micromol/L, P=0.01). CONCLUSIONS: The rate of contrast-induced nephropathy, defined by multiple end points, is not statistically different after the intraarterial administration of iopamidol or iodixanol to high-risk patients, with or without diabetes mellitus. Any true difference between the agents is small and not likely to be clinically significant.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "maltolyl p-coumarate", "mention_text": "A novel compound, maltolyl p-coumarate, attenuates cognitive deficits and shows neuroprotective effects in vitro and in vivo dementia models.", "entity": "maltolyl p-coumarate", "aliases": "maltolyl p-coumarate", "definition": "", "id": "MESH:C524754"}
{"mention": "cognitive deficits", "mention_text": "A novel compound, maltolyl p-coumarate, attenuates cognitive deficits and shows neuroprotective effects in vitro and in vivo dementia models.", "entity": "Cognition Disorders", "aliases": "Cognition Disorders Disorder Overinclusion", "definition": "Disturbances in the mental process related to thinking, reasoning, and judgment.\n    ", "id": "MESH:D003072"}
{"mention": "dementia", "mention_text": "A novel compound, maltolyl p-coumarate, attenuates cognitive deficits and shows neuroprotective effects in vitro and in vivo dementia models.", "entity": "Dementia", "aliases": "Amentia Amentias Dementia Familial Dementias Senile Paranoid", "definition": "An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness.\n    ", "id": "MESH:D003704"}
{"mention": "maltolyl p-coumarate", "mention_text": "To develop a novel and effective drug that could enhance cognitive function and neuroprotection, we newly synthesized maltolyl p-coumarate by the esterification of maltol and p-coumaric acid. In the present study, we investigated whether maltolyl p-coumarate could improve cognitive decline in scopolamine-injected rats and in amyloid beta peptide(1-42)-infused rats. Maltolyl p-coumarate was found to attenuate cognitive deficits in both rat models using passive avoidance test and to reduce apoptotic cell death observed in the hippocampus of the amyloid beta peptide(1-42)-infused rats. We also examined the neuroprotective effects of maltolyl p-coumarate in vitro using SH-SY5Y cells. Cells were pretreated with maltolyl p-coumarate, before exposed to amyloid beta peptide(1-42), glutamate or H2O2. We found that maltolyl p-coumarate significantly decreased apoptotic cell death and reduced reactive oxygen species, cytochrome c release, and caspase 3 activation. Taking these in vitro and in vivo results together, our study suggests that maltolyl p-coumarate is a potentially effective candidate against Alzheimer's disease that is characterized by wide spread neuronal death and progressive decline of cognitive function.", "entity": "maltolyl p-coumarate", "aliases": "maltolyl p-coumarate", "definition": "", "id": "MESH:C524754"}
{"mention": "maltol", "mention_text": "To develop a novel and effective drug that could enhance cognitive function and neuroprotection, we newly synthesized maltolyl p-coumarate by the esterification of maltol and p-coumaric acid. In the present study, we investigated whether maltolyl p-coumarate could improve cognitive decline in scopolamine-injected rats and in amyloid beta peptide(1-42)-infused rats. Maltolyl p-coumarate was found to attenuate cognitive deficits in both rat models using passive avoidance test and to reduce apoptotic cell death observed in the hippocampus of the amyloid beta peptide(1-42)-infused rats. We also examined the neuroprotective effects of maltolyl p-coumarate in vitro using SH-SY5Y cells. Cells were pretreated with maltolyl p-coumarate, before exposed to amyloid beta peptide(1-42), glutamate or H2O2. We found that maltolyl p-coumarate significantly decreased apoptotic cell death and reduced reactive oxygen species, cytochrome c release, and caspase 3 activation. Taking these in vitro and in vivo results together, our study suggests that maltolyl p-coumarate is a potentially effective candidate against Alzheimer's disease that is characterized by wide spread neuronal death and progressive decline of cognitive function.", "entity": "maltol", "aliases": "3-hydroxy-2-methyl-4-pyrone maltol", "definition": "", "id": "MESH:C008316"}
{"mention": "p-coumaric acid", "mention_text": "To develop a novel and effective drug that could enhance cognitive function and neuroprotection, we newly synthesized maltolyl p-coumarate by the esterification of maltol and p-coumaric acid. In the present study, we investigated whether maltolyl p-coumarate could improve cognitive decline in scopolamine-injected rats and in amyloid beta peptide(1-42)-infused rats. Maltolyl p-coumarate was found to attenuate cognitive deficits in both rat models using passive avoidance test and to reduce apoptotic cell death observed in the hippocampus of the amyloid beta peptide(1-42)-infused rats. We also examined the neuroprotective effects of maltolyl p-coumarate in vitro using SH-SY5Y cells. Cells were pretreated with maltolyl p-coumarate, before exposed to amyloid beta peptide(1-42), glutamate or H2O2. We found that maltolyl p-coumarate significantly decreased apoptotic cell death and reduced reactive oxygen species, cytochrome c release, and caspase 3 activation. Taking these in vitro and in vivo results together, our study suggests that maltolyl p-coumarate is a potentially effective candidate against Alzheimer's disease that is characterized by wide spread neuronal death and progressive decline of cognitive function.", "entity": "4-coumaric acid", "aliases": "4-coumaric acid (E)-isomer (Z)-isomer disodium salt 4-hydroxycinnamic p-coumaric p-hydroxycinnamic para-coumaric", "definition": "", "id": "MESH:C032171"}
{"mention": "cognitive decline", "mention_text": "To develop a novel and effective drug that could enhance cognitive function and neuroprotection, we newly synthesized maltolyl p-coumarate by the esterification of maltol and p-coumaric acid. In the present study, we investigated whether maltolyl p-coumarate could improve cognitive decline in scopolamine-injected rats and in amyloid beta peptide(1-42)-infused rats. Maltolyl p-coumarate was found to attenuate cognitive deficits in both rat models using passive avoidance test and to reduce apoptotic cell death observed in the hippocampus of the amyloid beta peptide(1-42)-infused rats. We also examined the neuroprotective effects of maltolyl p-coumarate in vitro using SH-SY5Y cells. Cells were pretreated with maltolyl p-coumarate, before exposed to amyloid beta peptide(1-42), glutamate or H2O2. We found that maltolyl p-coumarate significantly decreased apoptotic cell death and reduced reactive oxygen species, cytochrome c release, and caspase 3 activation. Taking these in vitro and in vivo results together, our study suggests that maltolyl p-coumarate is a potentially effective candidate against Alzheimer's disease that is characterized by wide spread neuronal death and progressive decline of cognitive function.", "entity": "Cognition Disorders", "aliases": "Cognition Disorders Disorder Overinclusion", "definition": "Disturbances in the mental process related to thinking, reasoning, and judgment.\n    ", "id": "MESH:D003072"}
{"mention": "scopolamine", "mention_text": "To develop a novel and effective drug that could enhance cognitive function and neuroprotection, we newly synthesized maltolyl p-coumarate by the esterification of maltol and p-coumaric acid. In the present study, we investigated whether maltolyl p-coumarate could improve cognitive decline in scopolamine-injected rats and in amyloid beta peptide(1-42)-infused rats. Maltolyl p-coumarate was found to attenuate cognitive deficits in both rat models using passive avoidance test and to reduce apoptotic cell death observed in the hippocampus of the amyloid beta peptide(1-42)-infused rats. We also examined the neuroprotective effects of maltolyl p-coumarate in vitro using SH-SY5Y cells. Cells were pretreated with maltolyl p-coumarate, before exposed to amyloid beta peptide(1-42), glutamate or H2O2. We found that maltolyl p-coumarate significantly decreased apoptotic cell death and reduced reactive oxygen species, cytochrome c release, and caspase 3 activation. Taking these in vitro and in vivo results together, our study suggests that maltolyl p-coumarate is a potentially effective candidate against Alzheimer's disease that is characterized by wide spread neuronal death and progressive decline of cognitive function.", "entity": "Scopolamine Hydrobromide", "aliases": "Alcon Brand of Scopolamine Hydrobromide Boro Scopol Boro-Scopol BoroScopol Bull Cooper Hamilton Hope Hyoscine Inibisa Isopto Kwells Novartis Consumer Health Renaudin Roche Scoburen Scopace Scopoderm TTS Transderm Scop V Transderm-V Travacalm HO Vorigeno Winzer Borate", "definition": "An alkaloid from SOLANACEAE, especially DATURA and SCOPOLIA. Scopolamine and its quaternary derivatives act as antimuscarinics like ATROPINE, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in URINARY INCONTINENCE, in MOTION SICKNESS, as an antispasmodic, and as a mydriatic and cycloplegic.\n    ", "id": "MESH:D012601"}
{"mention": "amyloid beta peptide(1-42)", "mention_text": "To develop a novel and effective drug that could enhance cognitive function and neuroprotection, we newly synthesized maltolyl p-coumarate by the esterification of maltol and p-coumaric acid. In the present study, we investigated whether maltolyl p-coumarate could improve cognitive decline in scopolamine-injected rats and in amyloid beta peptide(1-42)-infused rats. Maltolyl p-coumarate was found to attenuate cognitive deficits in both rat models using passive avoidance test and to reduce apoptotic cell death observed in the hippocampus of the amyloid beta peptide(1-42)-infused rats. We also examined the neuroprotective effects of maltolyl p-coumarate in vitro using SH-SY5Y cells. Cells were pretreated with maltolyl p-coumarate, before exposed to amyloid beta peptide(1-42), glutamate or H2O2. We found that maltolyl p-coumarate significantly decreased apoptotic cell death and reduced reactive oxygen species, cytochrome c release, and caspase 3 activation. Taking these in vitro and in vivo results together, our study suggests that maltolyl p-coumarate is a potentially effective candidate against Alzheimer's disease that is characterized by wide spread neuronal death and progressive decline of cognitive function.", "entity": "beta-amyloid peptide 1-42 (E22delta) click peptide", "aliases": "amyloid beta-protein 1-42 (E22delta) click peptide beta-amyloid", "definition": "", "id": "MESH:C544092"}
{"mention": "Maltolyl p-coumarate", "mention_text": "To develop a novel and effective drug that could enhance cognitive function and neuroprotection, we newly synthesized maltolyl p-coumarate by the esterification of maltol and p-coumaric acid. In the present study, we investigated whether maltolyl p-coumarate could improve cognitive decline in scopolamine-injected rats and in amyloid beta peptide(1-42)-infused rats. Maltolyl p-coumarate was found to attenuate cognitive deficits in both rat models using passive avoidance test and to reduce apoptotic cell death observed in the hippocampus of the amyloid beta peptide(1-42)-infused rats. We also examined the neuroprotective effects of maltolyl p-coumarate in vitro using SH-SY5Y cells. Cells were pretreated with maltolyl p-coumarate, before exposed to amyloid beta peptide(1-42), glutamate or H2O2. We found that maltolyl p-coumarate significantly decreased apoptotic cell death and reduced reactive oxygen species, cytochrome c release, and caspase 3 activation. Taking these in vitro and in vivo results together, our study suggests that maltolyl p-coumarate is a potentially effective candidate against Alzheimer's disease that is characterized by wide spread neuronal death and progressive decline of cognitive function.", "entity": "maltolyl p-coumarate", "aliases": "maltolyl p-coumarate", "definition": "", "id": "MESH:C524754"}
{"mention": "cognitive deficits", "mention_text": "To develop a novel and effective drug that could enhance cognitive function and neuroprotection, we newly synthesized maltolyl p-coumarate by the esterification of maltol and p-coumaric acid. In the present study, we investigated whether maltolyl p-coumarate could improve cognitive decline in scopolamine-injected rats and in amyloid beta peptide(1-42)-infused rats. Maltolyl p-coumarate was found to attenuate cognitive deficits in both rat models using passive avoidance test and to reduce apoptotic cell death observed in the hippocampus of the amyloid beta peptide(1-42)-infused rats. We also examined the neuroprotective effects of maltolyl p-coumarate in vitro using SH-SY5Y cells. Cells were pretreated with maltolyl p-coumarate, before exposed to amyloid beta peptide(1-42), glutamate or H2O2. We found that maltolyl p-coumarate significantly decreased apoptotic cell death and reduced reactive oxygen species, cytochrome c release, and caspase 3 activation. Taking these in vitro and in vivo results together, our study suggests that maltolyl p-coumarate is a potentially effective candidate against Alzheimer's disease that is characterized by wide spread neuronal death and progressive decline of cognitive function.", "entity": "Cognition Disorders", "aliases": "Cognition Disorders Disorder Overinclusion", "definition": "Disturbances in the mental process related to thinking, reasoning, and judgment.\n    ", "id": "MESH:D003072"}
{"mention": "glutamate", "mention_text": "To develop a novel and effective drug that could enhance cognitive function and neuroprotection, we newly synthesized maltolyl p-coumarate by the esterification of maltol and p-coumaric acid. In the present study, we investigated whether maltolyl p-coumarate could improve cognitive decline in scopolamine-injected rats and in amyloid beta peptide(1-42)-infused rats. Maltolyl p-coumarate was found to attenuate cognitive deficits in both rat models using passive avoidance test and to reduce apoptotic cell death observed in the hippocampus of the amyloid beta peptide(1-42)-infused rats. We also examined the neuroprotective effects of maltolyl p-coumarate in vitro using SH-SY5Y cells. Cells were pretreated with maltolyl p-coumarate, before exposed to amyloid beta peptide(1-42), glutamate or H2O2. We found that maltolyl p-coumarate significantly decreased apoptotic cell death and reduced reactive oxygen species, cytochrome c release, and caspase 3 activation. Taking these in vitro and in vivo results together, our study suggests that maltolyl p-coumarate is a potentially effective candidate against Alzheimer's disease that is characterized by wide spread neuronal death and progressive decline of cognitive function.", "entity": "Glutamic Acid", "aliases": "Aluminum L Glutamate L-Glutamate D D-Glutamate Potassium Glutamic Acid (D)-Isomer L-Glutamic", "definition": "A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.\n    ", "id": "MESH:D018698"}
{"mention": "H2O2", "mention_text": "To develop a novel and effective drug that could enhance cognitive function and neuroprotection, we newly synthesized maltolyl p-coumarate by the esterification of maltol and p-coumaric acid. In the present study, we investigated whether maltolyl p-coumarate could improve cognitive decline in scopolamine-injected rats and in amyloid beta peptide(1-42)-infused rats. Maltolyl p-coumarate was found to attenuate cognitive deficits in both rat models using passive avoidance test and to reduce apoptotic cell death observed in the hippocampus of the amyloid beta peptide(1-42)-infused rats. We also examined the neuroprotective effects of maltolyl p-coumarate in vitro using SH-SY5Y cells. Cells were pretreated with maltolyl p-coumarate, before exposed to amyloid beta peptide(1-42), glutamate or H2O2. We found that maltolyl p-coumarate significantly decreased apoptotic cell death and reduced reactive oxygen species, cytochrome c release, and caspase 3 activation. Taking these in vitro and in vivo results together, our study suggests that maltolyl p-coumarate is a potentially effective candidate against Alzheimer's disease that is characterized by wide spread neuronal death and progressive decline of cognitive function.", "entity": "Hydrogen Peroxide", "aliases": "Hydrogen Peroxide (H2O2) Hydroperoxide Oxydol Perhydrol Superoxol", "definition": "A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.\n    ", "id": "MESH:D006861"}
{"mention": "Alzheimer's disease", "mention_text": "To develop a novel and effective drug that could enhance cognitive function and neuroprotection, we newly synthesized maltolyl p-coumarate by the esterification of maltol and p-coumaric acid. In the present study, we investigated whether maltolyl p-coumarate could improve cognitive decline in scopolamine-injected rats and in amyloid beta peptide(1-42)-infused rats. Maltolyl p-coumarate was found to attenuate cognitive deficits in both rat models using passive avoidance test and to reduce apoptotic cell death observed in the hippocampus of the amyloid beta peptide(1-42)-infused rats. We also examined the neuroprotective effects of maltolyl p-coumarate in vitro using SH-SY5Y cells. Cells were pretreated with maltolyl p-coumarate, before exposed to amyloid beta peptide(1-42), glutamate or H2O2. We found that maltolyl p-coumarate significantly decreased apoptotic cell death and reduced reactive oxygen species, cytochrome c release, and caspase 3 activation. Taking these in vitro and in vivo results together, our study suggests that maltolyl p-coumarate is a potentially effective candidate against Alzheimer's disease that is characterized by wide spread neuronal death and progressive decline of cognitive function.", "entity": "Alzheimer Disease", "aliases": "Acute Confusional Senile Dementia Alzheimer (AD) Disease Early Onset Late Sclerosis Syndrome Type (ATD) Alzheimer's Focal Alzheimer-Type Presenile Primary Degenerative Familial (FAD)", "definition": "A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)\n    ", "id": "MESH:D000544"}
{"mention": "neuronal death", "mention_text": "To develop a novel and effective drug that could enhance cognitive function and neuroprotection, we newly synthesized maltolyl p-coumarate by the esterification of maltol and p-coumaric acid. In the present study, we investigated whether maltolyl p-coumarate could improve cognitive decline in scopolamine-injected rats and in amyloid beta peptide(1-42)-infused rats. Maltolyl p-coumarate was found to attenuate cognitive deficits in both rat models using passive avoidance test and to reduce apoptotic cell death observed in the hippocampus of the amyloid beta peptide(1-42)-infused rats. We also examined the neuroprotective effects of maltolyl p-coumarate in vitro using SH-SY5Y cells. Cells were pretreated with maltolyl p-coumarate, before exposed to amyloid beta peptide(1-42), glutamate or H2O2. We found that maltolyl p-coumarate significantly decreased apoptotic cell death and reduced reactive oxygen species, cytochrome c release, and caspase 3 activation. Taking these in vitro and in vivo results together, our study suggests that maltolyl p-coumarate is a potentially effective candidate against Alzheimer's disease that is characterized by wide spread neuronal death and progressive decline of cognitive function.", "entity": "Nerve Degeneration", "aliases": "Degeneration Nerve Neuron Degenerations", "definition": "Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.\n    ", "id": "MESH:D009410"}
{"mention": "decline of cognitive function", "mention_text": "To develop a novel and effective drug that could enhance cognitive function and neuroprotection, we newly synthesized maltolyl p-coumarate by the esterification of maltol and p-coumaric acid. In the present study, we investigated whether maltolyl p-coumarate could improve cognitive decline in scopolamine-injected rats and in amyloid beta peptide(1-42)-infused rats. Maltolyl p-coumarate was found to attenuate cognitive deficits in both rat models using passive avoidance test and to reduce apoptotic cell death observed in the hippocampus of the amyloid beta peptide(1-42)-infused rats. We also examined the neuroprotective effects of maltolyl p-coumarate in vitro using SH-SY5Y cells. Cells were pretreated with maltolyl p-coumarate, before exposed to amyloid beta peptide(1-42), glutamate or H2O2. We found that maltolyl p-coumarate significantly decreased apoptotic cell death and reduced reactive oxygen species, cytochrome c release, and caspase 3 activation. Taking these in vitro and in vivo results together, our study suggests that maltolyl p-coumarate is a potentially effective candidate against Alzheimer's disease that is characterized by wide spread neuronal death and progressive decline of cognitive function.", "entity": "Cognition Disorders", "aliases": "Cognition Disorders Disorder Overinclusion", "definition": "Disturbances in the mental process related to thinking, reasoning, and judgment.\n    ", "id": "MESH:D003072"}
{"mention": "warfarin", "mention_text": "Interaction between warfarin and levofloxacin: case series.", "entity": "Warfarin", "aliases": "4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one Aldo Brand of Warfarin Sodium Aldocumar Antigen Apo-Warfarin Apotex Bailly Boots Bristol-Myers Squibb Coumadin Coumadine Estedi Gen-Warfarin Genpharm Goldshield Marevan Potassium Tedicumar Warfant", "definition": "An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.\n    ", "id": "MESH:D014859"}
{"mention": "levofloxacin", "mention_text": "Interaction between warfarin and levofloxacin: case series.", "entity": "Levofloxacin", "aliases": "Anhydrous Levofloxacin Levaquin Ofloxacin (S)-Isomer Quixin", "definition": "The L-isomer of Ofloxacin.\n    ", "id": "MESH:D064704"}
{"mention": "Warfarin", "mention_text": "Warfarin is the most widely used oral anticoagulant and is indicated for many clinical conditions. Levofloxacin, a fluoroquinolone, is one of the most commonly prescribed antibiotics in clinical practice and is effective against Gram-positive, Gram-negative, and atypical bacteria. While small prospective studies have not revealed any significant drug-drug interaction between warfarin and levofloxacin, several case reports have indicated that levofloxacin may significantly potentiate the anticoagulation effect of warfarin. We report 3 cases of serious bleeding complications that appear to be the result of the interaction between warfarin and levofloxacin. Physicians should be aware of this potential interaction and use caution when prescribing levofloxacin to patients taking warfarin.", "entity": "Warfarin", "aliases": "4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one Aldo Brand of Warfarin Sodium Aldocumar Antigen Apo-Warfarin Apotex Bailly Boots Bristol-Myers Squibb Coumadin Coumadine Estedi Gen-Warfarin Genpharm Goldshield Marevan Potassium Tedicumar Warfant", "definition": "An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.\n    ", "id": "MESH:D014859"}
{"mention": "Levofloxacin", "mention_text": "Warfarin is the most widely used oral anticoagulant and is indicated for many clinical conditions. Levofloxacin, a fluoroquinolone, is one of the most commonly prescribed antibiotics in clinical practice and is effective against Gram-positive, Gram-negative, and atypical bacteria. While small prospective studies have not revealed any significant drug-drug interaction between warfarin and levofloxacin, several case reports have indicated that levofloxacin may significantly potentiate the anticoagulation effect of warfarin. We report 3 cases of serious bleeding complications that appear to be the result of the interaction between warfarin and levofloxacin. Physicians should be aware of this potential interaction and use caution when prescribing levofloxacin to patients taking warfarin.", "entity": "Levofloxacin", "aliases": "Anhydrous Levofloxacin Levaquin Ofloxacin (S)-Isomer Quixin", "definition": "The L-isomer of Ofloxacin.\n    ", "id": "MESH:D064704"}
{"mention": "fluoroquinolone", "mention_text": "Warfarin is the most widely used oral anticoagulant and is indicated for many clinical conditions. Levofloxacin, a fluoroquinolone, is one of the most commonly prescribed antibiotics in clinical practice and is effective against Gram-positive, Gram-negative, and atypical bacteria. While small prospective studies have not revealed any significant drug-drug interaction between warfarin and levofloxacin, several case reports have indicated that levofloxacin may significantly potentiate the anticoagulation effect of warfarin. We report 3 cases of serious bleeding complications that appear to be the result of the interaction between warfarin and levofloxacin. Physicians should be aware of this potential interaction and use caution when prescribing levofloxacin to patients taking warfarin.", "entity": "Fluoroquinolones", "aliases": "Fluoroquinolones", "definition": "A group of QUINOLONES with at least one fluorine atom and a piperazinyl group.\n    ", "id": "MESH:D024841"}
{"mention": "warfarin", "mention_text": "Warfarin is the most widely used oral anticoagulant and is indicated for many clinical conditions. Levofloxacin, a fluoroquinolone, is one of the most commonly prescribed antibiotics in clinical practice and is effective against Gram-positive, Gram-negative, and atypical bacteria. While small prospective studies have not revealed any significant drug-drug interaction between warfarin and levofloxacin, several case reports have indicated that levofloxacin may significantly potentiate the anticoagulation effect of warfarin. We report 3 cases of serious bleeding complications that appear to be the result of the interaction between warfarin and levofloxacin. Physicians should be aware of this potential interaction and use caution when prescribing levofloxacin to patients taking warfarin.", "entity": "Warfarin", "aliases": "4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one Aldo Brand of Warfarin Sodium Aldocumar Antigen Apo-Warfarin Apotex Bailly Boots Bristol-Myers Squibb Coumadin Coumadine Estedi Gen-Warfarin Genpharm Goldshield Marevan Potassium Tedicumar Warfant", "definition": "An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.\n    ", "id": "MESH:D014859"}
{"mention": "levofloxacin", "mention_text": "Warfarin is the most widely used oral anticoagulant and is indicated for many clinical conditions. Levofloxacin, a fluoroquinolone, is one of the most commonly prescribed antibiotics in clinical practice and is effective against Gram-positive, Gram-negative, and atypical bacteria. While small prospective studies have not revealed any significant drug-drug interaction between warfarin and levofloxacin, several case reports have indicated that levofloxacin may significantly potentiate the anticoagulation effect of warfarin. We report 3 cases of serious bleeding complications that appear to be the result of the interaction between warfarin and levofloxacin. Physicians should be aware of this potential interaction and use caution when prescribing levofloxacin to patients taking warfarin.", "entity": "Levofloxacin", "aliases": "Anhydrous Levofloxacin Levaquin Ofloxacin (S)-Isomer Quixin", "definition": "The L-isomer of Ofloxacin.\n    ", "id": "MESH:D064704"}
{"mention": "bleeding", "mention_text": "Warfarin is the most widely used oral anticoagulant and is indicated for many clinical conditions. Levofloxacin, a fluoroquinolone, is one of the most commonly prescribed antibiotics in clinical practice and is effective against Gram-positive, Gram-negative, and atypical bacteria. While small prospective studies have not revealed any significant drug-drug interaction between warfarin and levofloxacin, several case reports have indicated that levofloxacin may significantly potentiate the anticoagulation effect of warfarin. We report 3 cases of serious bleeding complications that appear to be the result of the interaction between warfarin and levofloxacin. Physicians should be aware of this potential interaction and use caution when prescribing levofloxacin to patients taking warfarin.", "entity": "Hemorrhage", "aliases": "Bleeding Hemorrhage Hemorrhages", "definition": "Bleeding or escape of blood from a vessel.\n    ", "id": "MESH:D006470"}
{"mention": "lamivudine", "mention_text": "Mutations associated with lamivudine-resistance in therapy-na  ve hepatitis B virus (HBV) infected patients with and without HIV co-infection: implications for antiretroviral therapy in HBV and HIV co-infected South African patients.", "entity": "Lamivudine", "aliases": "2',3' Dideoxy 3' thiacytidine 2',3'-Dideoxy-3'-thiacytidine 3TC BCH 189 BCH-189 BCH189 Epivir GR-109714X GR109714X Lamivudine (2S-cis)-Isomer", "definition": "A reverse transcriptase inhibitor and ZALCITABINE analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease.\n    ", "id": "MESH:D019259"}
{"mention": "na", "mention_text": "Mutations associated with lamivudine-resistance in therapy-na  ve hepatitis B virus (HBV) infected patients with and without HIV co-infection: implications for antiretroviral therapy in HBV and HIV co-infected South African patients.", "entity": "Sodium", "aliases": "Ion Level Sodium", "definition": "A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.\n    ", "id": "MESH:D012964"}
{"mention": "hepatitis B virus (HBV) infected", "mention_text": "Mutations associated with lamivudine-resistance in therapy-na  ve hepatitis B virus (HBV) infected patients with and without HIV co-infection: implications for antiretroviral therapy in HBV and HIV co-infected South African patients.", "entity": "Hepatitis B", "aliases": "Hepatitis B", "definition": "INFLAMMATION of the LIVER in humans caused by a member of the ORTHOHEPADNAVIRUS genus, HEPATITIS B VIRUS. It is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact.\n    ", "id": "MESH:D006509"}
{"mention": "HIV co-infection", "mention_text": "Mutations associated with lamivudine-resistance in therapy-na  ve hepatitis B virus (HBV) infected patients with and without HIV co-infection: implications for antiretroviral therapy in HBV and HIV co-infected South African patients.", "entity": "HIV Infections", "aliases": "HIV Infection Infections HTLV III LAV HTLV-III HTLV-III-LAV T Lymphotropic Virus Type Human T-Lymphotropic", "definition": "Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).\n    ", "id": "MESH:D015658"}
{"mention": "lamivudine", "mention_text": "This was an exploratory study to investigate lamivudine-resistant hepatitis B virus (HBV) strains in selected lamivudine-na  ve HBV carriers with and without human immunodeficiency virus (HIV) co-infection in South African patients. Thirty-five lamivudine-na  ve HBV infected patients with or without HIV co-infection were studied: 15 chronic HBV mono-infected patients and 20 HBV-HIV co-infected patients. The latter group was further sub-divided into 13 occult HBV (HBsAg-negative) and 7 overt HBV (HBsAg- positive) patients. HBsAg, anti-HBs, anti-HBc, and anti-HIV 1/2 were determined as part of routine diagnosis using Axsym assays (Abbott Laboratories, North Chicago, IL). Serum samples were PCR amplified with HBV reverse transcriptase (RT) primers, followed by direct sequencing across the tyrosine-methionine-aspartate-aspartate (YMDD) motif of the major catalytic region in the C domain of the HBV RT enzyme. HBV viral load was performed with Amplicor HBV Monitor test v2.0 (Roche Diagnostics, Penzberg, Germany). HBV lamivudine-resistant strains were detected in 3 of 15 mono-infected chronic hepatitis B patients and 10 of 20 HBV-HIV co-infected patients. To the best of our knowledge, this constitutes the first report of HBV lamivudine-resistant strains in therapy-na  ve HBV-HIV co-infected patients. The HBV viral loads for mono-infected and co-infected patients ranged from 3.32 x 10(2) to 3.82 x 10(7) and <200 to 4.40 x 10(3) copies/ml, respectively. It remains to be seen whether such pre-existing antiviral mutations could result in widespread emergence of HBV resistant strains when lamivudine-containing highly active antiretroviral (ARV) treatment (HAART) regimens become widely applied in South Africa, as this is likely to have potential implications in the management of HBV-HIV co-infected patients.", "entity": "Lamivudine", "aliases": "2',3' Dideoxy 3' thiacytidine 2',3'-Dideoxy-3'-thiacytidine 3TC BCH 189 BCH-189 BCH189 Epivir GR-109714X GR109714X Lamivudine (2S-cis)-Isomer", "definition": "A reverse transcriptase inhibitor and ZALCITABINE analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease.\n    ", "id": "MESH:D019259"}
{"mention": "hepatitis B", "mention_text": "This was an exploratory study to investigate lamivudine-resistant hepatitis B virus (HBV) strains in selected lamivudine-na  ve HBV carriers with and without human immunodeficiency virus (HIV) co-infection in South African patients. Thirty-five lamivudine-na  ve HBV infected patients with or without HIV co-infection were studied: 15 chronic HBV mono-infected patients and 20 HBV-HIV co-infected patients. The latter group was further sub-divided into 13 occult HBV (HBsAg-negative) and 7 overt HBV (HBsAg- positive) patients. HBsAg, anti-HBs, anti-HBc, and anti-HIV 1/2 were determined as part of routine diagnosis using Axsym assays (Abbott Laboratories, North Chicago, IL). Serum samples were PCR amplified with HBV reverse transcriptase (RT) primers, followed by direct sequencing across the tyrosine-methionine-aspartate-aspartate (YMDD) motif of the major catalytic region in the C domain of the HBV RT enzyme. HBV viral load was performed with Amplicor HBV Monitor test v2.0 (Roche Diagnostics, Penzberg, Germany). HBV lamivudine-resistant strains were detected in 3 of 15 mono-infected chronic hepatitis B patients and 10 of 20 HBV-HIV co-infected patients. To the best of our knowledge, this constitutes the first report of HBV lamivudine-resistant strains in therapy-na  ve HBV-HIV co-infected patients. The HBV viral loads for mono-infected and co-infected patients ranged from 3.32 x 10(2) to 3.82 x 10(7) and <200 to 4.40 x 10(3) copies/ml, respectively. It remains to be seen whether such pre-existing antiviral mutations could result in widespread emergence of HBV resistant strains when lamivudine-containing highly active antiretroviral (ARV) treatment (HAART) regimens become widely applied in South Africa, as this is likely to have potential implications in the management of HBV-HIV co-infected patients.", "entity": "Hepatitis B", "aliases": "Hepatitis B", "definition": "INFLAMMATION of the LIVER in humans caused by a member of the ORTHOHEPADNAVIRUS genus, HEPATITIS B VIRUS. It is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact.\n    ", "id": "MESH:D006509"}
{"mention": "na", "mention_text": "This was an exploratory study to investigate lamivudine-resistant hepatitis B virus (HBV) strains in selected lamivudine-na  ve HBV carriers with and without human immunodeficiency virus (HIV) co-infection in South African patients. Thirty-five lamivudine-na  ve HBV infected patients with or without HIV co-infection were studied: 15 chronic HBV mono-infected patients and 20 HBV-HIV co-infected patients. The latter group was further sub-divided into 13 occult HBV (HBsAg-negative) and 7 overt HBV (HBsAg- positive) patients. HBsAg, anti-HBs, anti-HBc, and anti-HIV 1/2 were determined as part of routine diagnosis using Axsym assays (Abbott Laboratories, North Chicago, IL). Serum samples were PCR amplified with HBV reverse transcriptase (RT) primers, followed by direct sequencing across the tyrosine-methionine-aspartate-aspartate (YMDD) motif of the major catalytic region in the C domain of the HBV RT enzyme. HBV viral load was performed with Amplicor HBV Monitor test v2.0 (Roche Diagnostics, Penzberg, Germany). HBV lamivudine-resistant strains were detected in 3 of 15 mono-infected chronic hepatitis B patients and 10 of 20 HBV-HIV co-infected patients. To the best of our knowledge, this constitutes the first report of HBV lamivudine-resistant strains in therapy-na  ve HBV-HIV co-infected patients. The HBV viral loads for mono-infected and co-infected patients ranged from 3.32 x 10(2) to 3.82 x 10(7) and <200 to 4.40 x 10(3) copies/ml, respectively. It remains to be seen whether such pre-existing antiviral mutations could result in widespread emergence of HBV resistant strains when lamivudine-containing highly active antiretroviral (ARV) treatment (HAART) regimens become widely applied in South Africa, as this is likely to have potential implications in the management of HBV-HIV co-infected patients.", "entity": "Sodium", "aliases": "Ion Level Sodium", "definition": "A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.\n    ", "id": "MESH:D012964"}
{"mention": "human immunodeficiency virus (HIV) co-infection", "mention_text": "This was an exploratory study to investigate lamivudine-resistant hepatitis B virus (HBV) strains in selected lamivudine-na  ve HBV carriers with and without human immunodeficiency virus (HIV) co-infection in South African patients. Thirty-five lamivudine-na  ve HBV infected patients with or without HIV co-infection were studied: 15 chronic HBV mono-infected patients and 20 HBV-HIV co-infected patients. The latter group was further sub-divided into 13 occult HBV (HBsAg-negative) and 7 overt HBV (HBsAg- positive) patients. HBsAg, anti-HBs, anti-HBc, and anti-HIV 1/2 were determined as part of routine diagnosis using Axsym assays (Abbott Laboratories, North Chicago, IL). Serum samples were PCR amplified with HBV reverse transcriptase (RT) primers, followed by direct sequencing across the tyrosine-methionine-aspartate-aspartate (YMDD) motif of the major catalytic region in the C domain of the HBV RT enzyme. HBV viral load was performed with Amplicor HBV Monitor test v2.0 (Roche Diagnostics, Penzberg, Germany). HBV lamivudine-resistant strains were detected in 3 of 15 mono-infected chronic hepatitis B patients and 10 of 20 HBV-HIV co-infected patients. To the best of our knowledge, this constitutes the first report of HBV lamivudine-resistant strains in therapy-na  ve HBV-HIV co-infected patients. The HBV viral loads for mono-infected and co-infected patients ranged from 3.32 x 10(2) to 3.82 x 10(7) and <200 to 4.40 x 10(3) copies/ml, respectively. It remains to be seen whether such pre-existing antiviral mutations could result in widespread emergence of HBV resistant strains when lamivudine-containing highly active antiretroviral (ARV) treatment (HAART) regimens become widely applied in South Africa, as this is likely to have potential implications in the management of HBV-HIV co-infected patients.", "entity": "HIV Infections", "aliases": "HIV Infection Infections HTLV III LAV HTLV-III HTLV-III-LAV T Lymphotropic Virus Type Human T-Lymphotropic", "definition": "Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).\n    ", "id": "MESH:D015658"}
{"mention": "HBV infected", "mention_text": "This was an exploratory study to investigate lamivudine-resistant hepatitis B virus (HBV) strains in selected lamivudine-na  ve HBV carriers with and without human immunodeficiency virus (HIV) co-infection in South African patients. Thirty-five lamivudine-na  ve HBV infected patients with or without HIV co-infection were studied: 15 chronic HBV mono-infected patients and 20 HBV-HIV co-infected patients. The latter group was further sub-divided into 13 occult HBV (HBsAg-negative) and 7 overt HBV (HBsAg- positive) patients. HBsAg, anti-HBs, anti-HBc, and anti-HIV 1/2 were determined as part of routine diagnosis using Axsym assays (Abbott Laboratories, North Chicago, IL). Serum samples were PCR amplified with HBV reverse transcriptase (RT) primers, followed by direct sequencing across the tyrosine-methionine-aspartate-aspartate (YMDD) motif of the major catalytic region in the C domain of the HBV RT enzyme. HBV viral load was performed with Amplicor HBV Monitor test v2.0 (Roche Diagnostics, Penzberg, Germany). HBV lamivudine-resistant strains were detected in 3 of 15 mono-infected chronic hepatitis B patients and 10 of 20 HBV-HIV co-infected patients. To the best of our knowledge, this constitutes the first report of HBV lamivudine-resistant strains in therapy-na  ve HBV-HIV co-infected patients. The HBV viral loads for mono-infected and co-infected patients ranged from 3.32 x 10(2) to 3.82 x 10(7) and <200 to 4.40 x 10(3) copies/ml, respectively. It remains to be seen whether such pre-existing antiviral mutations could result in widespread emergence of HBV resistant strains when lamivudine-containing highly active antiretroviral (ARV) treatment (HAART) regimens become widely applied in South Africa, as this is likely to have potential implications in the management of HBV-HIV co-infected patients.", "entity": "Hepatitis B", "aliases": "Hepatitis B", "definition": "INFLAMMATION of the LIVER in humans caused by a member of the ORTHOHEPADNAVIRUS genus, HEPATITIS B VIRUS. It is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact.\n    ", "id": "MESH:D006509"}
{"mention": "HIV co-infection", "mention_text": "This was an exploratory study to investigate lamivudine-resistant hepatitis B virus (HBV) strains in selected lamivudine-na  ve HBV carriers with and without human immunodeficiency virus (HIV) co-infection in South African patients. Thirty-five lamivudine-na  ve HBV infected patients with or without HIV co-infection were studied: 15 chronic HBV mono-infected patients and 20 HBV-HIV co-infected patients. The latter group was further sub-divided into 13 occult HBV (HBsAg-negative) and 7 overt HBV (HBsAg- positive) patients. HBsAg, anti-HBs, anti-HBc, and anti-HIV 1/2 were determined as part of routine diagnosis using Axsym assays (Abbott Laboratories, North Chicago, IL). Serum samples were PCR amplified with HBV reverse transcriptase (RT) primers, followed by direct sequencing across the tyrosine-methionine-aspartate-aspartate (YMDD) motif of the major catalytic region in the C domain of the HBV RT enzyme. HBV viral load was performed with Amplicor HBV Monitor test v2.0 (Roche Diagnostics, Penzberg, Germany). HBV lamivudine-resistant strains were detected in 3 of 15 mono-infected chronic hepatitis B patients and 10 of 20 HBV-HIV co-infected patients. To the best of our knowledge, this constitutes the first report of HBV lamivudine-resistant strains in therapy-na  ve HBV-HIV co-infected patients. The HBV viral loads for mono-infected and co-infected patients ranged from 3.32 x 10(2) to 3.82 x 10(7) and <200 to 4.40 x 10(3) copies/ml, respectively. It remains to be seen whether such pre-existing antiviral mutations could result in widespread emergence of HBV resistant strains when lamivudine-containing highly active antiretroviral (ARV) treatment (HAART) regimens become widely applied in South Africa, as this is likely to have potential implications in the management of HBV-HIV co-infected patients.", "entity": "HIV Infections", "aliases": "HIV Infection Infections HTLV III LAV HTLV-III HTLV-III-LAV T Lymphotropic Virus Type Human T-Lymphotropic", "definition": "Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).\n    ", "id": "MESH:D015658"}
{"mention": "HBV mono-infected", "mention_text": "This was an exploratory study to investigate lamivudine-resistant hepatitis B virus (HBV) strains in selected lamivudine-na  ve HBV carriers with and without human immunodeficiency virus (HIV) co-infection in South African patients. Thirty-five lamivudine-na  ve HBV infected patients with or without HIV co-infection were studied: 15 chronic HBV mono-infected patients and 20 HBV-HIV co-infected patients. The latter group was further sub-divided into 13 occult HBV (HBsAg-negative) and 7 overt HBV (HBsAg- positive) patients. HBsAg, anti-HBs, anti-HBc, and anti-HIV 1/2 were determined as part of routine diagnosis using Axsym assays (Abbott Laboratories, North Chicago, IL). Serum samples were PCR amplified with HBV reverse transcriptase (RT) primers, followed by direct sequencing across the tyrosine-methionine-aspartate-aspartate (YMDD) motif of the major catalytic region in the C domain of the HBV RT enzyme. HBV viral load was performed with Amplicor HBV Monitor test v2.0 (Roche Diagnostics, Penzberg, Germany). HBV lamivudine-resistant strains were detected in 3 of 15 mono-infected chronic hepatitis B patients and 10 of 20 HBV-HIV co-infected patients. To the best of our knowledge, this constitutes the first report of HBV lamivudine-resistant strains in therapy-na  ve HBV-HIV co-infected patients. The HBV viral loads for mono-infected and co-infected patients ranged from 3.32 x 10(2) to 3.82 x 10(7) and <200 to 4.40 x 10(3) copies/ml, respectively. It remains to be seen whether such pre-existing antiviral mutations could result in widespread emergence of HBV resistant strains when lamivudine-containing highly active antiretroviral (ARV) treatment (HAART) regimens become widely applied in South Africa, as this is likely to have potential implications in the management of HBV-HIV co-infected patients.", "entity": "Hepatitis B", "aliases": "Hepatitis B", "definition": "INFLAMMATION of the LIVER in humans caused by a member of the ORTHOHEPADNAVIRUS genus, HEPATITIS B VIRUS. It is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact.\n    ", "id": "MESH:D006509"}
{"mention": "HBsAg", "mention_text": "This was an exploratory study to investigate lamivudine-resistant hepatitis B virus (HBV) strains in selected lamivudine-na  ve HBV carriers with and without human immunodeficiency virus (HIV) co-infection in South African patients. Thirty-five lamivudine-na  ve HBV infected patients with or without HIV co-infection were studied: 15 chronic HBV mono-infected patients and 20 HBV-HIV co-infected patients. The latter group was further sub-divided into 13 occult HBV (HBsAg-negative) and 7 overt HBV (HBsAg- positive) patients. HBsAg, anti-HBs, anti-HBc, and anti-HIV 1/2 were determined as part of routine diagnosis using Axsym assays (Abbott Laboratories, North Chicago, IL). Serum samples were PCR amplified with HBV reverse transcriptase (RT) primers, followed by direct sequencing across the tyrosine-methionine-aspartate-aspartate (YMDD) motif of the major catalytic region in the C domain of the HBV RT enzyme. HBV viral load was performed with Amplicor HBV Monitor test v2.0 (Roche Diagnostics, Penzberg, Germany). HBV lamivudine-resistant strains were detected in 3 of 15 mono-infected chronic hepatitis B patients and 10 of 20 HBV-HIV co-infected patients. To the best of our knowledge, this constitutes the first report of HBV lamivudine-resistant strains in therapy-na  ve HBV-HIV co-infected patients. The HBV viral loads for mono-infected and co-infected patients ranged from 3.32 x 10(2) to 3.82 x 10(7) and <200 to 4.40 x 10(3) copies/ml, respectively. It remains to be seen whether such pre-existing antiviral mutations could result in widespread emergence of HBV resistant strains when lamivudine-containing highly active antiretroviral (ARV) treatment (HAART) regimens become widely applied in South Africa, as this is likely to have potential implications in the management of HBV-HIV co-infected patients.", "entity": "Hepatitis B Surface Antigens", "aliases": "Antigen Australia HBsAg Hepatitis B Surface Antigens", "definition": "Those hepatitis B antigens found on the surface of the Dane particle and on the 20 nm spherical and tubular particles. Several subspecificities of the surface antigen are known. These were formerly called the Australia antigen.\n    ", "id": "MESH:D006514"}
{"mention": "tyrosine", "mention_text": "This was an exploratory study to investigate lamivudine-resistant hepatitis B virus (HBV) strains in selected lamivudine-na  ve HBV carriers with and without human immunodeficiency virus (HIV) co-infection in South African patients. Thirty-five lamivudine-na  ve HBV infected patients with or without HIV co-infection were studied: 15 chronic HBV mono-infected patients and 20 HBV-HIV co-infected patients. The latter group was further sub-divided into 13 occult HBV (HBsAg-negative) and 7 overt HBV (HBsAg- positive) patients. HBsAg, anti-HBs, anti-HBc, and anti-HIV 1/2 were determined as part of routine diagnosis using Axsym assays (Abbott Laboratories, North Chicago, IL). Serum samples were PCR amplified with HBV reverse transcriptase (RT) primers, followed by direct sequencing across the tyrosine-methionine-aspartate-aspartate (YMDD) motif of the major catalytic region in the C domain of the HBV RT enzyme. HBV viral load was performed with Amplicor HBV Monitor test v2.0 (Roche Diagnostics, Penzberg, Germany). HBV lamivudine-resistant strains were detected in 3 of 15 mono-infected chronic hepatitis B patients and 10 of 20 HBV-HIV co-infected patients. To the best of our knowledge, this constitutes the first report of HBV lamivudine-resistant strains in therapy-na  ve HBV-HIV co-infected patients. The HBV viral loads for mono-infected and co-infected patients ranged from 3.32 x 10(2) to 3.82 x 10(7) and <200 to 4.40 x 10(3) copies/ml, respectively. It remains to be seen whether such pre-existing antiviral mutations could result in widespread emergence of HBV resistant strains when lamivudine-containing highly active antiretroviral (ARV) treatment (HAART) regimens become widely applied in South Africa, as this is likely to have potential implications in the management of HBV-HIV co-infected patients.", "entity": "Tyrosine", "aliases": "L Tyrosine L-Tyrosine isomer L-isomer para para-Tyrosine", "definition": "A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.\n    ", "id": "MESH:D014443"}
{"mention": "methionine", "mention_text": "This was an exploratory study to investigate lamivudine-resistant hepatitis B virus (HBV) strains in selected lamivudine-na  ve HBV carriers with and without human immunodeficiency virus (HIV) co-infection in South African patients. Thirty-five lamivudine-na  ve HBV infected patients with or without HIV co-infection were studied: 15 chronic HBV mono-infected patients and 20 HBV-HIV co-infected patients. The latter group was further sub-divided into 13 occult HBV (HBsAg-negative) and 7 overt HBV (HBsAg- positive) patients. HBsAg, anti-HBs, anti-HBc, and anti-HIV 1/2 were determined as part of routine diagnosis using Axsym assays (Abbott Laboratories, North Chicago, IL). Serum samples were PCR amplified with HBV reverse transcriptase (RT) primers, followed by direct sequencing across the tyrosine-methionine-aspartate-aspartate (YMDD) motif of the major catalytic region in the C domain of the HBV RT enzyme. HBV viral load was performed with Amplicor HBV Monitor test v2.0 (Roche Diagnostics, Penzberg, Germany). HBV lamivudine-resistant strains were detected in 3 of 15 mono-infected chronic hepatitis B patients and 10 of 20 HBV-HIV co-infected patients. To the best of our knowledge, this constitutes the first report of HBV lamivudine-resistant strains in therapy-na  ve HBV-HIV co-infected patients. The HBV viral loads for mono-infected and co-infected patients ranged from 3.32 x 10(2) to 3.82 x 10(7) and <200 to 4.40 x 10(3) copies/ml, respectively. It remains to be seen whether such pre-existing antiviral mutations could result in widespread emergence of HBV resistant strains when lamivudine-containing highly active antiretroviral (ARV) treatment (HAART) regimens become widely applied in South Africa, as this is likely to have potential implications in the management of HBV-HIV co-infected patients.", "entity": "Methionine", "aliases": "L-Isomer Methionine L-Methionine Liquimeth L Isomer Pedameth", "definition": "A sulfur-containing essential L-amino acid that is important in many body functions.\n    ", "id": "MESH:D008715"}
{"mention": "aspartate", "mention_text": "This was an exploratory study to investigate lamivudine-resistant hepatitis B virus (HBV) strains in selected lamivudine-na  ve HBV carriers with and without human immunodeficiency virus (HIV) co-infection in South African patients. Thirty-five lamivudine-na  ve HBV infected patients with or without HIV co-infection were studied: 15 chronic HBV mono-infected patients and 20 HBV-HIV co-infected patients. The latter group was further sub-divided into 13 occult HBV (HBsAg-negative) and 7 overt HBV (HBsAg- positive) patients. HBsAg, anti-HBs, anti-HBc, and anti-HIV 1/2 were determined as part of routine diagnosis using Axsym assays (Abbott Laboratories, North Chicago, IL). Serum samples were PCR amplified with HBV reverse transcriptase (RT) primers, followed by direct sequencing across the tyrosine-methionine-aspartate-aspartate (YMDD) motif of the major catalytic region in the C domain of the HBV RT enzyme. HBV viral load was performed with Amplicor HBV Monitor test v2.0 (Roche Diagnostics, Penzberg, Germany). HBV lamivudine-resistant strains were detected in 3 of 15 mono-infected chronic hepatitis B patients and 10 of 20 HBV-HIV co-infected patients. To the best of our knowledge, this constitutes the first report of HBV lamivudine-resistant strains in therapy-na  ve HBV-HIV co-infected patients. The HBV viral loads for mono-infected and co-infected patients ranged from 3.32 x 10(2) to 3.82 x 10(7) and <200 to 4.40 x 10(3) copies/ml, respectively. It remains to be seen whether such pre-existing antiviral mutations could result in widespread emergence of HBV resistant strains when lamivudine-containing highly active antiretroviral (ARV) treatment (HAART) regimens become widely applied in South Africa, as this is likely to have potential implications in the management of HBV-HIV co-infected patients.", "entity": "Aspartic Acid", "aliases": "(+-)-Aspartic Acid (R,S)-Aspartic Ammonium Aspartate Magnesium Hydrochloride Calcium Dipotassium Disodium Monopotassium Monosodium Potassium Sodium Aspartic Salt Hydrobromide (1:1) Trihydrate (2:1) Magnesium-Potassium (2:1:2) L L-Aspartate L-Aspartic Magnesiocard Mg 5 Longoral Mg-5-Longoral Mg5Longoral", "definition": "One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.\n    ", "id": "MESH:D001224"}
{"mention": "NMDA", "mention_text": "Sex differences in NMDA antagonist enhancement of morphine antihyperalgesia in a capsaicin model of persistent pain: comparisons to two models of acute pain.", "entity": "N-Methylaspartate", "aliases": "Acid N-Methyl-D-aspartic N Methyl D aspartate aspartic Methylaspartate N-Methyl-D-aspartate N-Methylaspartate NMDA", "definition": "An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).\n    ", "id": "MESH:D016202"}
{"mention": "morphine", "mention_text": "Sex differences in NMDA antagonist enhancement of morphine antihyperalgesia in a capsaicin model of persistent pain: comparisons to two models of acute pain.", "entity": "Morphine", "aliases": "Chloride Morphine Contin MS Duramorph Morphia Sulfate (2:1) Anhydrous Pentahydrate Oramorph SR SDZ 202 250 202-250 202250 SDZ202 SDZ202-250 SDZ202250", "definition": "The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.\n    ", "id": "MESH:D009020"}
{"mention": "capsaicin", "mention_text": "Sex differences in NMDA antagonist enhancement of morphine antihyperalgesia in a capsaicin model of persistent pain: comparisons to two models of acute pain.", "entity": "Capsaicin", "aliases": "8 Methyl N Vanillyl 6 Nonenamide 8-Methyl-N-Vanillyl-6-Nonenamide Alacan Brand of Capsaicin Antiphlogistine Rub A-535 Axsain Capsaicine Capsicum Farmaya Capsidol Capsin Capzasin Carter Horner Centrum Elan Flemming Gelcen Katrum Link Medicis NGX 4010 NGX-4010 NGX4010 Smaller Thompson Vinas Zacin Zostrix", "definition": "An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.\n    ", "id": "MESH:D002211"}
{"mention": "pain", "mention_text": "Sex differences in NMDA antagonist enhancement of morphine antihyperalgesia in a capsaicin model of persistent pain: comparisons to two models of acute pain.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "acute pain", "mention_text": "Sex differences in NMDA antagonist enhancement of morphine antihyperalgesia in a capsaicin model of persistent pain: comparisons to two models of acute pain.", "entity": "Acute Pain", "aliases": "Acute Pain Pains", "definition": "Intensely discomforting, distressful, or agonizing sensation associated with trauma or disease, with well-defined location, character, and timing.\n    ", "id": "MESH:D059787"}
{"mention": "acute pain", "mention_text": "In acute pain models, N-methyl-D-aspartate (NMDA) antagonists enhance the antinociceptive effects of morphine to a greater extent in males than females. The purpose of this investigation was to extend these findings to a persistent pain model which could be distinguished from acute pain models on the basis of the nociceptive fibers activated, neurochemical substrates, and duration of the nociceptive stimulus. To this end, persistent hyperalgesia was induced by administration of capsaicin in the tail of gonadally intact F344 rats, following which the tail was immersed in a mildly noxious thermal stimulus, and tail-withdrawal latencies measured. For comparison, tests were conducted in two acute pain models, the hotplate and warm water tail-withdrawal procedures. In males, the non-competitive NMDA antagonist dextromethorphan enhanced the antihyperalgesic effect of low to moderate doses of morphine in a dose-and time-dependent manner. Across the doses and pretreatment times examined, enhancement was not observed in females. Enhancement of morphine antinociception by dextromethorphan was seen in both males and females in the acute pain models, with the magnitude of this effect being greater in males. These findings demonstrate a sexually-dimorphic interaction between NMDA antagonists and morphine in a persistent pain model that can be distinguished from those observed in acute pain models.", "entity": "Acute Pain", "aliases": "Acute Pain Pains", "definition": "Intensely discomforting, distressful, or agonizing sensation associated with trauma or disease, with well-defined location, character, and timing.\n    ", "id": "MESH:D059787"}
{"mention": "N-methyl-D-aspartate", "mention_text": "In acute pain models, N-methyl-D-aspartate (NMDA) antagonists enhance the antinociceptive effects of morphine to a greater extent in males than females. The purpose of this investigation was to extend these findings to a persistent pain model which could be distinguished from acute pain models on the basis of the nociceptive fibers activated, neurochemical substrates, and duration of the nociceptive stimulus. To this end, persistent hyperalgesia was induced by administration of capsaicin in the tail of gonadally intact F344 rats, following which the tail was immersed in a mildly noxious thermal stimulus, and tail-withdrawal latencies measured. For comparison, tests were conducted in two acute pain models, the hotplate and warm water tail-withdrawal procedures. In males, the non-competitive NMDA antagonist dextromethorphan enhanced the antihyperalgesic effect of low to moderate doses of morphine in a dose-and time-dependent manner. Across the doses and pretreatment times examined, enhancement was not observed in females. Enhancement of morphine antinociception by dextromethorphan was seen in both males and females in the acute pain models, with the magnitude of this effect being greater in males. These findings demonstrate a sexually-dimorphic interaction between NMDA antagonists and morphine in a persistent pain model that can be distinguished from those observed in acute pain models.", "entity": "N-Methylaspartate", "aliases": "Acid N-Methyl-D-aspartic N Methyl D aspartate aspartic Methylaspartate N-Methyl-D-aspartate N-Methylaspartate NMDA", "definition": "An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).\n    ", "id": "MESH:D016202"}
{"mention": "NMDA", "mention_text": "In acute pain models, N-methyl-D-aspartate (NMDA) antagonists enhance the antinociceptive effects of morphine to a greater extent in males than females. The purpose of this investigation was to extend these findings to a persistent pain model which could be distinguished from acute pain models on the basis of the nociceptive fibers activated, neurochemical substrates, and duration of the nociceptive stimulus. To this end, persistent hyperalgesia was induced by administration of capsaicin in the tail of gonadally intact F344 rats, following which the tail was immersed in a mildly noxious thermal stimulus, and tail-withdrawal latencies measured. For comparison, tests were conducted in two acute pain models, the hotplate and warm water tail-withdrawal procedures. In males, the non-competitive NMDA antagonist dextromethorphan enhanced the antihyperalgesic effect of low to moderate doses of morphine in a dose-and time-dependent manner. Across the doses and pretreatment times examined, enhancement was not observed in females. Enhancement of morphine antinociception by dextromethorphan was seen in both males and females in the acute pain models, with the magnitude of this effect being greater in males. These findings demonstrate a sexually-dimorphic interaction between NMDA antagonists and morphine in a persistent pain model that can be distinguished from those observed in acute pain models.", "entity": "N-Methylaspartate", "aliases": "Acid N-Methyl-D-aspartic N Methyl D aspartate aspartic Methylaspartate N-Methyl-D-aspartate N-Methylaspartate NMDA", "definition": "An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).\n    ", "id": "MESH:D016202"}
{"mention": "morphine", "mention_text": "In acute pain models, N-methyl-D-aspartate (NMDA) antagonists enhance the antinociceptive effects of morphine to a greater extent in males than females. The purpose of this investigation was to extend these findings to a persistent pain model which could be distinguished from acute pain models on the basis of the nociceptive fibers activated, neurochemical substrates, and duration of the nociceptive stimulus. To this end, persistent hyperalgesia was induced by administration of capsaicin in the tail of gonadally intact F344 rats, following which the tail was immersed in a mildly noxious thermal stimulus, and tail-withdrawal latencies measured. For comparison, tests were conducted in two acute pain models, the hotplate and warm water tail-withdrawal procedures. In males, the non-competitive NMDA antagonist dextromethorphan enhanced the antihyperalgesic effect of low to moderate doses of morphine in a dose-and time-dependent manner. Across the doses and pretreatment times examined, enhancement was not observed in females. Enhancement of morphine antinociception by dextromethorphan was seen in both males and females in the acute pain models, with the magnitude of this effect being greater in males. These findings demonstrate a sexually-dimorphic interaction between NMDA antagonists and morphine in a persistent pain model that can be distinguished from those observed in acute pain models.", "entity": "Morphine", "aliases": "Chloride Morphine Contin MS Duramorph Morphia Sulfate (2:1) Anhydrous Pentahydrate Oramorph SR SDZ 202 250 202-250 202250 SDZ202 SDZ202-250 SDZ202250", "definition": "The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.\n    ", "id": "MESH:D009020"}
{"mention": "pain", "mention_text": "In acute pain models, N-methyl-D-aspartate (NMDA) antagonists enhance the antinociceptive effects of morphine to a greater extent in males than females. The purpose of this investigation was to extend these findings to a persistent pain model which could be distinguished from acute pain models on the basis of the nociceptive fibers activated, neurochemical substrates, and duration of the nociceptive stimulus. To this end, persistent hyperalgesia was induced by administration of capsaicin in the tail of gonadally intact F344 rats, following which the tail was immersed in a mildly noxious thermal stimulus, and tail-withdrawal latencies measured. For comparison, tests were conducted in two acute pain models, the hotplate and warm water tail-withdrawal procedures. In males, the non-competitive NMDA antagonist dextromethorphan enhanced the antihyperalgesic effect of low to moderate doses of morphine in a dose-and time-dependent manner. Across the doses and pretreatment times examined, enhancement was not observed in females. Enhancement of morphine antinociception by dextromethorphan was seen in both males and females in the acute pain models, with the magnitude of this effect being greater in males. These findings demonstrate a sexually-dimorphic interaction between NMDA antagonists and morphine in a persistent pain model that can be distinguished from those observed in acute pain models.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "hyperalgesia", "mention_text": "In acute pain models, N-methyl-D-aspartate (NMDA) antagonists enhance the antinociceptive effects of morphine to a greater extent in males than females. The purpose of this investigation was to extend these findings to a persistent pain model which could be distinguished from acute pain models on the basis of the nociceptive fibers activated, neurochemical substrates, and duration of the nociceptive stimulus. To this end, persistent hyperalgesia was induced by administration of capsaicin in the tail of gonadally intact F344 rats, following which the tail was immersed in a mildly noxious thermal stimulus, and tail-withdrawal latencies measured. For comparison, tests were conducted in two acute pain models, the hotplate and warm water tail-withdrawal procedures. In males, the non-competitive NMDA antagonist dextromethorphan enhanced the antihyperalgesic effect of low to moderate doses of morphine in a dose-and time-dependent manner. Across the doses and pretreatment times examined, enhancement was not observed in females. Enhancement of morphine antinociception by dextromethorphan was seen in both males and females in the acute pain models, with the magnitude of this effect being greater in males. These findings demonstrate a sexually-dimorphic interaction between NMDA antagonists and morphine in a persistent pain model that can be distinguished from those observed in acute pain models.", "entity": "Hyperalgesia", "aliases": "Allodynia Mechanical Tactile Thermal Allodynias Hyperalgesia Primary Secondary Hyperalgesias Hyperalgesic Sensations", "definition": "An increased sensation of pain or discomfort produced by mimimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve.\n    ", "id": "MESH:D006930"}
{"mention": "capsaicin", "mention_text": "In acute pain models, N-methyl-D-aspartate (NMDA) antagonists enhance the antinociceptive effects of morphine to a greater extent in males than females. The purpose of this investigation was to extend these findings to a persistent pain model which could be distinguished from acute pain models on the basis of the nociceptive fibers activated, neurochemical substrates, and duration of the nociceptive stimulus. To this end, persistent hyperalgesia was induced by administration of capsaicin in the tail of gonadally intact F344 rats, following which the tail was immersed in a mildly noxious thermal stimulus, and tail-withdrawal latencies measured. For comparison, tests were conducted in two acute pain models, the hotplate and warm water tail-withdrawal procedures. In males, the non-competitive NMDA antagonist dextromethorphan enhanced the antihyperalgesic effect of low to moderate doses of morphine in a dose-and time-dependent manner. Across the doses and pretreatment times examined, enhancement was not observed in females. Enhancement of morphine antinociception by dextromethorphan was seen in both males and females in the acute pain models, with the magnitude of this effect being greater in males. These findings demonstrate a sexually-dimorphic interaction between NMDA antagonists and morphine in a persistent pain model that can be distinguished from those observed in acute pain models.", "entity": "Capsaicin", "aliases": "8 Methyl N Vanillyl 6 Nonenamide 8-Methyl-N-Vanillyl-6-Nonenamide Alacan Brand of Capsaicin Antiphlogistine Rub A-535 Axsain Capsaicine Capsicum Farmaya Capsidol Capsin Capzasin Carter Horner Centrum Elan Flemming Gelcen Katrum Link Medicis NGX 4010 NGX-4010 NGX4010 Smaller Thompson Vinas Zacin Zostrix", "definition": "An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.\n    ", "id": "MESH:D002211"}
{"mention": "dextromethorphan", "mention_text": "In acute pain models, N-methyl-D-aspartate (NMDA) antagonists enhance the antinociceptive effects of morphine to a greater extent in males than females. The purpose of this investigation was to extend these findings to a persistent pain model which could be distinguished from acute pain models on the basis of the nociceptive fibers activated, neurochemical substrates, and duration of the nociceptive stimulus. To this end, persistent hyperalgesia was induced by administration of capsaicin in the tail of gonadally intact F344 rats, following which the tail was immersed in a mildly noxious thermal stimulus, and tail-withdrawal latencies measured. For comparison, tests were conducted in two acute pain models, the hotplate and warm water tail-withdrawal procedures. In males, the non-competitive NMDA antagonist dextromethorphan enhanced the antihyperalgesic effect of low to moderate doses of morphine in a dose-and time-dependent manner. Across the doses and pretreatment times examined, enhancement was not observed in females. Enhancement of morphine antinociception by dextromethorphan was seen in both males and females in the acute pain models, with the magnitude of this effect being greater in males. These findings demonstrate a sexually-dimorphic interaction between NMDA antagonists and morphine in a persistent pain model that can be distinguished from those observed in acute pain models.", "entity": "Dextromethorphan", "aliases": "Delsym Dextromethorphan Hydrobromide (+-)-Isomer Monohydrate Hydrochloride Levomethorphan Racemethorphan d-Methorphan l-Methorphan", "definition": "Methyl analog of DEXTRORPHAN that shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is an NMDA receptor antagonist (RECEPTORS, N-METHYL-D-ASPARTATE) and acts as a non-competitive channel blocker. It is one of the widely used ANTITUSSIVES, and is also used to study the involvement of glutamate receptors in neurotoxicity.\n    ", "id": "MESH:D003915"}
{"mention": "proteinuria", "mention_text": "Development of proteinuria after switch to sirolimus-based immunosuppression in long-term cardiac transplant patients.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "sirolimus", "mention_text": "Development of proteinuria after switch to sirolimus-based immunosuppression in long-term cardiac transplant patients.", "entity": "Sirolimus", "aliases": "AY 22 989 22-989 22989 I 2190A I-2190A I2190A Rapamune Rapamycin Sirolimus Wyeth Brand of", "definition": "A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.\n    ", "id": "MESH:D020123"}
{"mention": "renal dysfunction", "mention_text": "Calcineurin-inhibitor therapy can lead to renal dysfunction in heart transplantation patients. The novel immunosuppressive (IS) drug sirolmus (Srl) lacks nephrotoxic effects; however, proteinuria associated with Srl has been reported following renal transplantation. In cardiac transplantation, the incidence of proteinuria associated with Srl is unknown. In this study, long-term cardiac transplant patients were switched from cyclosporine to Srl-based IS. Concomitant IS consisted of mycophenolate mofetil +/- steroids. Proteinuria increased significantly from a median of 0.13 g/day (range 0-5.7) preswitch to 0.23 g/day (0-9.88) at 24 months postswitch (p = 0.0024). Before the switch, 11.5% of patients had high-grade proteinuria (>1.0 g/day); this increased to 22.9% postswitch (p = 0.006). ACE inhibitor and angiotensin-releasing blocker (ARB) therapy reduced proteinuria development. Patients without proteinuria had increased renal function (median 42.5 vs. 64.1, p = 0.25), whereas patients who developed high-grade proteinuria showed decreased renal function at the end of follow-up (median 39.6 vs. 29.2, p = 0.125). Thus, proteinuria may develop in cardiac transplant patients after switch to Srl, which may have an adverse effect on renal function in these patients. Srl should be used with ACEi/ARB therapy and patients monitored for proteinuria and increased renal dysfunction.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "sirolmus", "mention_text": "Calcineurin-inhibitor therapy can lead to renal dysfunction in heart transplantation patients. The novel immunosuppressive (IS) drug sirolmus (Srl) lacks nephrotoxic effects; however, proteinuria associated with Srl has been reported following renal transplantation. In cardiac transplantation, the incidence of proteinuria associated with Srl is unknown. In this study, long-term cardiac transplant patients were switched from cyclosporine to Srl-based IS. Concomitant IS consisted of mycophenolate mofetil +/- steroids. Proteinuria increased significantly from a median of 0.13 g/day (range 0-5.7) preswitch to 0.23 g/day (0-9.88) at 24 months postswitch (p = 0.0024). Before the switch, 11.5% of patients had high-grade proteinuria (>1.0 g/day); this increased to 22.9% postswitch (p = 0.006). ACE inhibitor and angiotensin-releasing blocker (ARB) therapy reduced proteinuria development. Patients without proteinuria had increased renal function (median 42.5 vs. 64.1, p = 0.25), whereas patients who developed high-grade proteinuria showed decreased renal function at the end of follow-up (median 39.6 vs. 29.2, p = 0.125). Thus, proteinuria may develop in cardiac transplant patients after switch to Srl, which may have an adverse effect on renal function in these patients. Srl should be used with ACEi/ARB therapy and patients monitored for proteinuria and increased renal dysfunction.", "entity": "Sirolimus", "aliases": "AY 22 989 22-989 22989 I 2190A I-2190A I2190A Rapamune Rapamycin Sirolimus Wyeth Brand of", "definition": "A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.\n    ", "id": "MESH:D020123"}
{"mention": "Srl", "mention_text": "Calcineurin-inhibitor therapy can lead to renal dysfunction in heart transplantation patients. The novel immunosuppressive (IS) drug sirolmus (Srl) lacks nephrotoxic effects; however, proteinuria associated with Srl has been reported following renal transplantation. In cardiac transplantation, the incidence of proteinuria associated with Srl is unknown. In this study, long-term cardiac transplant patients were switched from cyclosporine to Srl-based IS. Concomitant IS consisted of mycophenolate mofetil +/- steroids. Proteinuria increased significantly from a median of 0.13 g/day (range 0-5.7) preswitch to 0.23 g/day (0-9.88) at 24 months postswitch (p = 0.0024). Before the switch, 11.5% of patients had high-grade proteinuria (>1.0 g/day); this increased to 22.9% postswitch (p = 0.006). ACE inhibitor and angiotensin-releasing blocker (ARB) therapy reduced proteinuria development. Patients without proteinuria had increased renal function (median 42.5 vs. 64.1, p = 0.25), whereas patients who developed high-grade proteinuria showed decreased renal function at the end of follow-up (median 39.6 vs. 29.2, p = 0.125). Thus, proteinuria may develop in cardiac transplant patients after switch to Srl, which may have an adverse effect on renal function in these patients. Srl should be used with ACEi/ARB therapy and patients monitored for proteinuria and increased renal dysfunction.", "entity": "Sirolimus", "aliases": "AY 22 989 22-989 22989 I 2190A I-2190A I2190A Rapamune Rapamycin Sirolimus Wyeth Brand of", "definition": "A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.\n    ", "id": "MESH:D020123"}
{"mention": "nephrotoxic", "mention_text": "Calcineurin-inhibitor therapy can lead to renal dysfunction in heart transplantation patients. The novel immunosuppressive (IS) drug sirolmus (Srl) lacks nephrotoxic effects; however, proteinuria associated with Srl has been reported following renal transplantation. In cardiac transplantation, the incidence of proteinuria associated with Srl is unknown. In this study, long-term cardiac transplant patients were switched from cyclosporine to Srl-based IS. Concomitant IS consisted of mycophenolate mofetil +/- steroids. Proteinuria increased significantly from a median of 0.13 g/day (range 0-5.7) preswitch to 0.23 g/day (0-9.88) at 24 months postswitch (p = 0.0024). Before the switch, 11.5% of patients had high-grade proteinuria (>1.0 g/day); this increased to 22.9% postswitch (p = 0.006). ACE inhibitor and angiotensin-releasing blocker (ARB) therapy reduced proteinuria development. Patients without proteinuria had increased renal function (median 42.5 vs. 64.1, p = 0.25), whereas patients who developed high-grade proteinuria showed decreased renal function at the end of follow-up (median 39.6 vs. 29.2, p = 0.125). Thus, proteinuria may develop in cardiac transplant patients after switch to Srl, which may have an adverse effect on renal function in these patients. Srl should be used with ACEi/ARB therapy and patients monitored for proteinuria and increased renal dysfunction.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "proteinuria", "mention_text": "Calcineurin-inhibitor therapy can lead to renal dysfunction in heart transplantation patients. The novel immunosuppressive (IS) drug sirolmus (Srl) lacks nephrotoxic effects; however, proteinuria associated with Srl has been reported following renal transplantation. In cardiac transplantation, the incidence of proteinuria associated with Srl is unknown. In this study, long-term cardiac transplant patients were switched from cyclosporine to Srl-based IS. Concomitant IS consisted of mycophenolate mofetil +/- steroids. Proteinuria increased significantly from a median of 0.13 g/day (range 0-5.7) preswitch to 0.23 g/day (0-9.88) at 24 months postswitch (p = 0.0024). Before the switch, 11.5% of patients had high-grade proteinuria (>1.0 g/day); this increased to 22.9% postswitch (p = 0.006). ACE inhibitor and angiotensin-releasing blocker (ARB) therapy reduced proteinuria development. Patients without proteinuria had increased renal function (median 42.5 vs. 64.1, p = 0.25), whereas patients who developed high-grade proteinuria showed decreased renal function at the end of follow-up (median 39.6 vs. 29.2, p = 0.125). Thus, proteinuria may develop in cardiac transplant patients after switch to Srl, which may have an adverse effect on renal function in these patients. Srl should be used with ACEi/ARB therapy and patients monitored for proteinuria and increased renal dysfunction.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "cyclosporine", "mention_text": "Calcineurin-inhibitor therapy can lead to renal dysfunction in heart transplantation patients. The novel immunosuppressive (IS) drug sirolmus (Srl) lacks nephrotoxic effects; however, proteinuria associated with Srl has been reported following renal transplantation. In cardiac transplantation, the incidence of proteinuria associated with Srl is unknown. In this study, long-term cardiac transplant patients were switched from cyclosporine to Srl-based IS. Concomitant IS consisted of mycophenolate mofetil +/- steroids. Proteinuria increased significantly from a median of 0.13 g/day (range 0-5.7) preswitch to 0.23 g/day (0-9.88) at 24 months postswitch (p = 0.0024). Before the switch, 11.5% of patients had high-grade proteinuria (>1.0 g/day); this increased to 22.9% postswitch (p = 0.006). ACE inhibitor and angiotensin-releasing blocker (ARB) therapy reduced proteinuria development. Patients without proteinuria had increased renal function (median 42.5 vs. 64.1, p = 0.25), whereas patients who developed high-grade proteinuria showed decreased renal function at the end of follow-up (median 39.6 vs. 29.2, p = 0.125). Thus, proteinuria may develop in cardiac transplant patients after switch to Srl, which may have an adverse effect on renal function in these patients. Srl should be used with ACEi/ARB therapy and patients monitored for proteinuria and increased renal dysfunction.", "entity": "Cyclosporine", "aliases": "Ciclosporin CsA Neoral CsA-Neoral CsANeoral CyA NOF CyA-NOF Cyclosporin A Cyclosporine OL 27 400 27-400 27400 Sandimmun Sandimmune", "definition": "A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).\n    ", "id": "MESH:D016572"}
{"mention": "mycophenolate mofetil", "mention_text": "Calcineurin-inhibitor therapy can lead to renal dysfunction in heart transplantation patients. The novel immunosuppressive (IS) drug sirolmus (Srl) lacks nephrotoxic effects; however, proteinuria associated with Srl has been reported following renal transplantation. In cardiac transplantation, the incidence of proteinuria associated with Srl is unknown. In this study, long-term cardiac transplant patients were switched from cyclosporine to Srl-based IS. Concomitant IS consisted of mycophenolate mofetil +/- steroids. Proteinuria increased significantly from a median of 0.13 g/day (range 0-5.7) preswitch to 0.23 g/day (0-9.88) at 24 months postswitch (p = 0.0024). Before the switch, 11.5% of patients had high-grade proteinuria (>1.0 g/day); this increased to 22.9% postswitch (p = 0.006). ACE inhibitor and angiotensin-releasing blocker (ARB) therapy reduced proteinuria development. Patients without proteinuria had increased renal function (median 42.5 vs. 64.1, p = 0.25), whereas patients who developed high-grade proteinuria showed decreased renal function at the end of follow-up (median 39.6 vs. 29.2, p = 0.125). Thus, proteinuria may develop in cardiac transplant patients after switch to Srl, which may have an adverse effect on renal function in these patients. Srl should be used with ACEi/ARB therapy and patients monitored for proteinuria and increased renal dysfunction.", "entity": "mycophenolate mofetil", "aliases": "Cellcept Mycophenolate Sodium Myfortic RS 61443 RS-61443 mycophenolate mofetil hydrochloride mycophenolic acid morpholinoethyl ester", "definition": "", "id": "MESH:C063008"}
{"mention": "steroids", "mention_text": "Calcineurin-inhibitor therapy can lead to renal dysfunction in heart transplantation patients. The novel immunosuppressive (IS) drug sirolmus (Srl) lacks nephrotoxic effects; however, proteinuria associated with Srl has been reported following renal transplantation. In cardiac transplantation, the incidence of proteinuria associated with Srl is unknown. In this study, long-term cardiac transplant patients were switched from cyclosporine to Srl-based IS. Concomitant IS consisted of mycophenolate mofetil +/- steroids. Proteinuria increased significantly from a median of 0.13 g/day (range 0-5.7) preswitch to 0.23 g/day (0-9.88) at 24 months postswitch (p = 0.0024). Before the switch, 11.5% of patients had high-grade proteinuria (>1.0 g/day); this increased to 22.9% postswitch (p = 0.006). ACE inhibitor and angiotensin-releasing blocker (ARB) therapy reduced proteinuria development. Patients without proteinuria had increased renal function (median 42.5 vs. 64.1, p = 0.25), whereas patients who developed high-grade proteinuria showed decreased renal function at the end of follow-up (median 39.6 vs. 29.2, p = 0.125). Thus, proteinuria may develop in cardiac transplant patients after switch to Srl, which may have an adverse effect on renal function in these patients. Srl should be used with ACEi/ARB therapy and patients monitored for proteinuria and increased renal dysfunction.", "entity": "Steroids", "aliases": "Catatoxic Steroids", "definition": "A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)\n    ", "id": "MESH:D013256"}
{"mention": "ACE inhibitor", "mention_text": "Calcineurin-inhibitor therapy can lead to renal dysfunction in heart transplantation patients. The novel immunosuppressive (IS) drug sirolmus (Srl) lacks nephrotoxic effects; however, proteinuria associated with Srl has been reported following renal transplantation. In cardiac transplantation, the incidence of proteinuria associated with Srl is unknown. In this study, long-term cardiac transplant patients were switched from cyclosporine to Srl-based IS. Concomitant IS consisted of mycophenolate mofetil +/- steroids. Proteinuria increased significantly from a median of 0.13 g/day (range 0-5.7) preswitch to 0.23 g/day (0-9.88) at 24 months postswitch (p = 0.0024). Before the switch, 11.5% of patients had high-grade proteinuria (>1.0 g/day); this increased to 22.9% postswitch (p = 0.006). ACE inhibitor and angiotensin-releasing blocker (ARB) therapy reduced proteinuria development. Patients without proteinuria had increased renal function (median 42.5 vs. 64.1, p = 0.25), whereas patients who developed high-grade proteinuria showed decreased renal function at the end of follow-up (median 39.6 vs. 29.2, p = 0.125). Thus, proteinuria may develop in cardiac transplant patients after switch to Srl, which may have an adverse effect on renal function in these patients. Srl should be used with ACEi/ARB therapy and patients monitored for proteinuria and increased renal dysfunction.", "entity": "Angiotensin-Converting Enzyme Inhibitors", "aliases": "ACE Inhibitors Angiotensin Converting Enzyme Antagonists I I-Converting Angiotensin-Converting Kininase II", "definition": "A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility.\n    ", "id": "MESH:D000806"}
{"mention": "angiotensin-releasing blocker", "mention_text": "Calcineurin-inhibitor therapy can lead to renal dysfunction in heart transplantation patients. The novel immunosuppressive (IS) drug sirolmus (Srl) lacks nephrotoxic effects; however, proteinuria associated with Srl has been reported following renal transplantation. In cardiac transplantation, the incidence of proteinuria associated with Srl is unknown. In this study, long-term cardiac transplant patients were switched from cyclosporine to Srl-based IS. Concomitant IS consisted of mycophenolate mofetil +/- steroids. Proteinuria increased significantly from a median of 0.13 g/day (range 0-5.7) preswitch to 0.23 g/day (0-9.88) at 24 months postswitch (p = 0.0024). Before the switch, 11.5% of patients had high-grade proteinuria (>1.0 g/day); this increased to 22.9% postswitch (p = 0.006). ACE inhibitor and angiotensin-releasing blocker (ARB) therapy reduced proteinuria development. Patients without proteinuria had increased renal function (median 42.5 vs. 64.1, p = 0.25), whereas patients who developed high-grade proteinuria showed decreased renal function at the end of follow-up (median 39.6 vs. 29.2, p = 0.125). Thus, proteinuria may develop in cardiac transplant patients after switch to Srl, which may have an adverse effect on renal function in these patients. Srl should be used with ACEi/ARB therapy and patients monitored for proteinuria and increased renal dysfunction.", "entity": "Angiotensin Receptor Antagonists", "aliases": "Angiotensin II Receptor Antagonists Blockers", "definition": "Agents that antagonize ANGIOTENSIN RECEPTORS. Many drugs in this class specifically target the ANGIOTENSIN TYPE 1 RECEPTOR.\n    ", "id": "MESH:D057911"}
{"mention": "ARB", "mention_text": "Calcineurin-inhibitor therapy can lead to renal dysfunction in heart transplantation patients. The novel immunosuppressive (IS) drug sirolmus (Srl) lacks nephrotoxic effects; however, proteinuria associated with Srl has been reported following renal transplantation. In cardiac transplantation, the incidence of proteinuria associated with Srl is unknown. In this study, long-term cardiac transplant patients were switched from cyclosporine to Srl-based IS. Concomitant IS consisted of mycophenolate mofetil +/- steroids. Proteinuria increased significantly from a median of 0.13 g/day (range 0-5.7) preswitch to 0.23 g/day (0-9.88) at 24 months postswitch (p = 0.0024). Before the switch, 11.5% of patients had high-grade proteinuria (>1.0 g/day); this increased to 22.9% postswitch (p = 0.006). ACE inhibitor and angiotensin-releasing blocker (ARB) therapy reduced proteinuria development. Patients without proteinuria had increased renal function (median 42.5 vs. 64.1, p = 0.25), whereas patients who developed high-grade proteinuria showed decreased renal function at the end of follow-up (median 39.6 vs. 29.2, p = 0.125). Thus, proteinuria may develop in cardiac transplant patients after switch to Srl, which may have an adverse effect on renal function in these patients. Srl should be used with ACEi/ARB therapy and patients monitored for proteinuria and increased renal dysfunction.", "entity": "Angiotensin Receptor Antagonists", "aliases": "Angiotensin II Receptor Antagonists Blockers", "definition": "Agents that antagonize ANGIOTENSIN RECEPTORS. Many drugs in this class specifically target the ANGIOTENSIN TYPE 1 RECEPTOR.\n    ", "id": "MESH:D057911"}
{"mention": "ACEi", "mention_text": "Calcineurin-inhibitor therapy can lead to renal dysfunction in heart transplantation patients. The novel immunosuppressive (IS) drug sirolmus (Srl) lacks nephrotoxic effects; however, proteinuria associated with Srl has been reported following renal transplantation. In cardiac transplantation, the incidence of proteinuria associated with Srl is unknown. In this study, long-term cardiac transplant patients were switched from cyclosporine to Srl-based IS. Concomitant IS consisted of mycophenolate mofetil +/- steroids. Proteinuria increased significantly from a median of 0.13 g/day (range 0-5.7) preswitch to 0.23 g/day (0-9.88) at 24 months postswitch (p = 0.0024). Before the switch, 11.5% of patients had high-grade proteinuria (>1.0 g/day); this increased to 22.9% postswitch (p = 0.006). ACE inhibitor and angiotensin-releasing blocker (ARB) therapy reduced proteinuria development. Patients without proteinuria had increased renal function (median 42.5 vs. 64.1, p = 0.25), whereas patients who developed high-grade proteinuria showed decreased renal function at the end of follow-up (median 39.6 vs. 29.2, p = 0.125). Thus, proteinuria may develop in cardiac transplant patients after switch to Srl, which may have an adverse effect on renal function in these patients. Srl should be used with ACEi/ARB therapy and patients monitored for proteinuria and increased renal dysfunction.", "entity": "Angiotensin-Converting Enzyme Inhibitors", "aliases": "ACE Inhibitors Angiotensin Converting Enzyme Antagonists I I-Converting Angiotensin-Converting Kininase II", "definition": "A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility.\n    ", "id": "MESH:D000806"}
{"mention": "N-pyrimidinyl-2-phenoxyacetamides", "mention_text": "Synthesis of N-pyrimidinyl-2-phenoxyacetamides as adenosine A2A receptor antagonists.", "entity": "Phenoxyacetates", "aliases": "Phenoxyacetates", "definition": "", "id": "MESH:D010642"}
{"mention": "adenosine", "mention_text": "Synthesis of N-pyrimidinyl-2-phenoxyacetamides as adenosine A2A receptor antagonists.", "entity": "Adenosine", "aliases": "Adenocard Adenoscan Adenosine", "definition": "A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.\n    ", "id": "MESH:D000241"}
{"mention": "N-pyrimidinyl-2-phenoxyacetamide", "mention_text": "A series of N-pyrimidinyl-2-phenoxyacetamide adenosine A(2A) antagonists is described. SAR studies led to compound 14 with excellent potency (K(i) = 0.4 nM), selectivity (A(1)/A(2A) > 100), and efficacy (MED 10 mg/kg p.o.) in the rat haloperidol-induced catalepsy model for Parkinson's disease.", "entity": "Phenoxyacetates", "aliases": "Phenoxyacetates", "definition": "", "id": "MESH:D010642"}
{"mention": "adenosine", "mention_text": "A series of N-pyrimidinyl-2-phenoxyacetamide adenosine A(2A) antagonists is described. SAR studies led to compound 14 with excellent potency (K(i) = 0.4 nM), selectivity (A(1)/A(2A) > 100), and efficacy (MED 10 mg/kg p.o.) in the rat haloperidol-induced catalepsy model for Parkinson's disease.", "entity": "Adenosine", "aliases": "Adenocard Adenoscan Adenosine", "definition": "A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.\n    ", "id": "MESH:D000241"}
{"mention": "haloperidol", "mention_text": "A series of N-pyrimidinyl-2-phenoxyacetamide adenosine A(2A) antagonists is described. SAR studies led to compound 14 with excellent potency (K(i) = 0.4 nM), selectivity (A(1)/A(2A) > 100), and efficacy (MED 10 mg/kg p.o.) in the rat haloperidol-induced catalepsy model for Parkinson's disease.", "entity": "Haloperidol", "aliases": "Haldol Haloperidol", "definition": "A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)\n    ", "id": "MESH:D006220"}
{"mention": "catalepsy", "mention_text": "A series of N-pyrimidinyl-2-phenoxyacetamide adenosine A(2A) antagonists is described. SAR studies led to compound 14 with excellent potency (K(i) = 0.4 nM), selectivity (A(1)/A(2A) > 100), and efficacy (MED 10 mg/kg p.o.) in the rat haloperidol-induced catalepsy model for Parkinson's disease.", "entity": "Catalepsy", "aliases": "Anochlesia Anochlesias Catalepsies Catalepsy Cerea Flexibilitas Flexibilities Waxy Flexibility", "definition": "A condition characterized by inactivity, decreased responsiveness to stimuli, and a tendency to maintain an immobile posture. The limbs tend to remain in whatever position they are placed (waxy flexibility). Catalepsy may be associated with PSYCHOTIC DISORDERS (e.g., SCHIZOPHRENIA, CATATONIC), nervous system drug toxicity, and other conditions.\n    ", "id": "MESH:D002375"}
{"mention": "Parkinson's disease", "mention_text": "A series of N-pyrimidinyl-2-phenoxyacetamide adenosine A(2A) antagonists is described. SAR studies led to compound 14 with excellent potency (K(i) = 0.4 nM), selectivity (A(1)/A(2A) > 100), and efficacy (MED 10 mg/kg p.o.) in the rat haloperidol-induced catalepsy model for Parkinson's disease.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "Methamphetamine", "mention_text": "Methamphetamine-induced neurotoxicity and microglial activation are not mediated by fractalkine receptor signaling.", "entity": "Methamphetamine", "aliases": "Abbott Brand of Methamphetamine Hydrochloride Deoxyephedrine Desoxyephedrine Desoxyn Langly Madrine Metamfetamine Methylamphetamine N N-Methylamphetamine", "definition": "A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.\n    ", "id": "MESH:D008694"}
{"mention": "neurotoxicity", "mention_text": "Methamphetamine-induced neurotoxicity and microglial activation are not mediated by fractalkine receptor signaling.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "Methamphetamine", "mention_text": "Methamphetamine (METH) damages dopamine (DA) nerve endings by a process that has been linked to microglial activation but the signaling pathways that mediate this response have not yet been delineated. Cardona et al. [Nat. Neurosci. 9 (2006), 917] recently identified the microglial-specific fractalkine receptor (CX3CR1) as an important mediator of MPTP-induced neurodegeneration of DA neurons. Because the CNS damage caused by METH and MPTP is highly selective for the DA neuronal system in mouse models of neurotoxicity, we hypothesized that the CX3CR1 plays a role in METH-induced neurotoxicity and microglial activation. Mice in which the CX3CR1 gene has been deleted and replaced with a cDNA encoding enhanced green fluorescent protein (eGFP) were treated with METH and examined for striatal neurotoxicity. METH depleted DA, caused microglial activation, and increased body temperature in CX3CR1 knockout mice to the same extent and over the same time course seen in wild-type controls. The effects of METH in CX3CR1 knockout mice were not gender-dependent and did not extend beyond the striatum. Striatal microglia expressing eGFP constitutively show morphological changes after METH that are characteristic of activation. This response was restricted to the striatum and contrasted sharply with unresponsive eGFP-microglia in surrounding brain areas that are not damaged by METH. We conclude from these studies that CX3CR1 signaling does not modulate METH neurotoxicity or microglial activation. Furthermore, it appears that striatal-resident microglia respond to METH with an activation cascade and then return to a surveying state without undergoing apoptosis or migration.", "entity": "Methamphetamine", "aliases": "Abbott Brand of Methamphetamine Hydrochloride Deoxyephedrine Desoxyephedrine Desoxyn Langly Madrine Metamfetamine Methylamphetamine N N-Methylamphetamine", "definition": "A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.\n    ", "id": "MESH:D008694"}
{"mention": "METH", "mention_text": "Methamphetamine (METH) damages dopamine (DA) nerve endings by a process that has been linked to microglial activation but the signaling pathways that mediate this response have not yet been delineated. Cardona et al. [Nat. Neurosci. 9 (2006), 917] recently identified the microglial-specific fractalkine receptor (CX3CR1) as an important mediator of MPTP-induced neurodegeneration of DA neurons. Because the CNS damage caused by METH and MPTP is highly selective for the DA neuronal system in mouse models of neurotoxicity, we hypothesized that the CX3CR1 plays a role in METH-induced neurotoxicity and microglial activation. Mice in which the CX3CR1 gene has been deleted and replaced with a cDNA encoding enhanced green fluorescent protein (eGFP) were treated with METH and examined for striatal neurotoxicity. METH depleted DA, caused microglial activation, and increased body temperature in CX3CR1 knockout mice to the same extent and over the same time course seen in wild-type controls. The effects of METH in CX3CR1 knockout mice were not gender-dependent and did not extend beyond the striatum. Striatal microglia expressing eGFP constitutively show morphological changes after METH that are characteristic of activation. This response was restricted to the striatum and contrasted sharply with unresponsive eGFP-microglia in surrounding brain areas that are not damaged by METH. We conclude from these studies that CX3CR1 signaling does not modulate METH neurotoxicity or microglial activation. Furthermore, it appears that striatal-resident microglia respond to METH with an activation cascade and then return to a surveying state without undergoing apoptosis or migration.", "entity": "Methamphetamine", "aliases": "Abbott Brand of Methamphetamine Hydrochloride Deoxyephedrine Desoxyephedrine Desoxyn Langly Madrine Metamfetamine Methylamphetamine N N-Methylamphetamine", "definition": "A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.\n    ", "id": "MESH:D008694"}
{"mention": "dopamine", "mention_text": "Methamphetamine (METH) damages dopamine (DA) nerve endings by a process that has been linked to microglial activation but the signaling pathways that mediate this response have not yet been delineated. Cardona et al. [Nat. Neurosci. 9 (2006), 917] recently identified the microglial-specific fractalkine receptor (CX3CR1) as an important mediator of MPTP-induced neurodegeneration of DA neurons. Because the CNS damage caused by METH and MPTP is highly selective for the DA neuronal system in mouse models of neurotoxicity, we hypothesized that the CX3CR1 plays a role in METH-induced neurotoxicity and microglial activation. Mice in which the CX3CR1 gene has been deleted and replaced with a cDNA encoding enhanced green fluorescent protein (eGFP) were treated with METH and examined for striatal neurotoxicity. METH depleted DA, caused microglial activation, and increased body temperature in CX3CR1 knockout mice to the same extent and over the same time course seen in wild-type controls. The effects of METH in CX3CR1 knockout mice were not gender-dependent and did not extend beyond the striatum. Striatal microglia expressing eGFP constitutively show morphological changes after METH that are characteristic of activation. This response was restricted to the striatum and contrasted sharply with unresponsive eGFP-microglia in surrounding brain areas that are not damaged by METH. We conclude from these studies that CX3CR1 signaling does not modulate METH neurotoxicity or microglial activation. Furthermore, it appears that striatal-resident microglia respond to METH with an activation cascade and then return to a surveying state without undergoing apoptosis or migration.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "DA", "mention_text": "Methamphetamine (METH) damages dopamine (DA) nerve endings by a process that has been linked to microglial activation but the signaling pathways that mediate this response have not yet been delineated. Cardona et al. [Nat. Neurosci. 9 (2006), 917] recently identified the microglial-specific fractalkine receptor (CX3CR1) as an important mediator of MPTP-induced neurodegeneration of DA neurons. Because the CNS damage caused by METH and MPTP is highly selective for the DA neuronal system in mouse models of neurotoxicity, we hypothesized that the CX3CR1 plays a role in METH-induced neurotoxicity and microglial activation. Mice in which the CX3CR1 gene has been deleted and replaced with a cDNA encoding enhanced green fluorescent protein (eGFP) were treated with METH and examined for striatal neurotoxicity. METH depleted DA, caused microglial activation, and increased body temperature in CX3CR1 knockout mice to the same extent and over the same time course seen in wild-type controls. The effects of METH in CX3CR1 knockout mice were not gender-dependent and did not extend beyond the striatum. Striatal microglia expressing eGFP constitutively show morphological changes after METH that are characteristic of activation. This response was restricted to the striatum and contrasted sharply with unresponsive eGFP-microglia in surrounding brain areas that are not damaged by METH. We conclude from these studies that CX3CR1 signaling does not modulate METH neurotoxicity or microglial activation. Furthermore, it appears that striatal-resident microglia respond to METH with an activation cascade and then return to a surveying state without undergoing apoptosis or migration.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "MPTP", "mention_text": "Methamphetamine (METH) damages dopamine (DA) nerve endings by a process that has been linked to microglial activation but the signaling pathways that mediate this response have not yet been delineated. Cardona et al. [Nat. Neurosci. 9 (2006), 917] recently identified the microglial-specific fractalkine receptor (CX3CR1) as an important mediator of MPTP-induced neurodegeneration of DA neurons. Because the CNS damage caused by METH and MPTP is highly selective for the DA neuronal system in mouse models of neurotoxicity, we hypothesized that the CX3CR1 plays a role in METH-induced neurotoxicity and microglial activation. Mice in which the CX3CR1 gene has been deleted and replaced with a cDNA encoding enhanced green fluorescent protein (eGFP) were treated with METH and examined for striatal neurotoxicity. METH depleted DA, caused microglial activation, and increased body temperature in CX3CR1 knockout mice to the same extent and over the same time course seen in wild-type controls. The effects of METH in CX3CR1 knockout mice were not gender-dependent and did not extend beyond the striatum. Striatal microglia expressing eGFP constitutively show morphological changes after METH that are characteristic of activation. This response was restricted to the striatum and contrasted sharply with unresponsive eGFP-microglia in surrounding brain areas that are not damaged by METH. We conclude from these studies that CX3CR1 signaling does not modulate METH neurotoxicity or microglial activation. Furthermore, it appears that striatal-resident microglia respond to METH with an activation cascade and then return to a surveying state without undergoing apoptosis or migration.", "entity": "1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine", "aliases": "1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine MPTP N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine", "definition": "A dopaminergic neurotoxic compound which produces irreversible clinical, chemical, and pathological alterations that mimic those found in Parkinson disease.\n    ", "id": "MESH:D015632"}
{"mention": "neurodegeneration", "mention_text": "Methamphetamine (METH) damages dopamine (DA) nerve endings by a process that has been linked to microglial activation but the signaling pathways that mediate this response have not yet been delineated. Cardona et al. [Nat. Neurosci. 9 (2006), 917] recently identified the microglial-specific fractalkine receptor (CX3CR1) as an important mediator of MPTP-induced neurodegeneration of DA neurons. Because the CNS damage caused by METH and MPTP is highly selective for the DA neuronal system in mouse models of neurotoxicity, we hypothesized that the CX3CR1 plays a role in METH-induced neurotoxicity and microglial activation. Mice in which the CX3CR1 gene has been deleted and replaced with a cDNA encoding enhanced green fluorescent protein (eGFP) were treated with METH and examined for striatal neurotoxicity. METH depleted DA, caused microglial activation, and increased body temperature in CX3CR1 knockout mice to the same extent and over the same time course seen in wild-type controls. The effects of METH in CX3CR1 knockout mice were not gender-dependent and did not extend beyond the striatum. Striatal microglia expressing eGFP constitutively show morphological changes after METH that are characteristic of activation. This response was restricted to the striatum and contrasted sharply with unresponsive eGFP-microglia in surrounding brain areas that are not damaged by METH. We conclude from these studies that CX3CR1 signaling does not modulate METH neurotoxicity or microglial activation. Furthermore, it appears that striatal-resident microglia respond to METH with an activation cascade and then return to a surveying state without undergoing apoptosis or migration.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "CNS damage", "mention_text": "Methamphetamine (METH) damages dopamine (DA) nerve endings by a process that has been linked to microglial activation but the signaling pathways that mediate this response have not yet been delineated. Cardona et al. [Nat. Neurosci. 9 (2006), 917] recently identified the microglial-specific fractalkine receptor (CX3CR1) as an important mediator of MPTP-induced neurodegeneration of DA neurons. Because the CNS damage caused by METH and MPTP is highly selective for the DA neuronal system in mouse models of neurotoxicity, we hypothesized that the CX3CR1 plays a role in METH-induced neurotoxicity and microglial activation. Mice in which the CX3CR1 gene has been deleted and replaced with a cDNA encoding enhanced green fluorescent protein (eGFP) were treated with METH and examined for striatal neurotoxicity. METH depleted DA, caused microglial activation, and increased body temperature in CX3CR1 knockout mice to the same extent and over the same time course seen in wild-type controls. The effects of METH in CX3CR1 knockout mice were not gender-dependent and did not extend beyond the striatum. Striatal microglia expressing eGFP constitutively show morphological changes after METH that are characteristic of activation. This response was restricted to the striatum and contrasted sharply with unresponsive eGFP-microglia in surrounding brain areas that are not damaged by METH. We conclude from these studies that CX3CR1 signaling does not modulate METH neurotoxicity or microglial activation. Furthermore, it appears that striatal-resident microglia respond to METH with an activation cascade and then return to a surveying state without undergoing apoptosis or migration.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "neurotoxicity", "mention_text": "Methamphetamine (METH) damages dopamine (DA) nerve endings by a process that has been linked to microglial activation but the signaling pathways that mediate this response have not yet been delineated. Cardona et al. [Nat. Neurosci. 9 (2006), 917] recently identified the microglial-specific fractalkine receptor (CX3CR1) as an important mediator of MPTP-induced neurodegeneration of DA neurons. Because the CNS damage caused by METH and MPTP is highly selective for the DA neuronal system in mouse models of neurotoxicity, we hypothesized that the CX3CR1 plays a role in METH-induced neurotoxicity and microglial activation. Mice in which the CX3CR1 gene has been deleted and replaced with a cDNA encoding enhanced green fluorescent protein (eGFP) were treated with METH and examined for striatal neurotoxicity. METH depleted DA, caused microglial activation, and increased body temperature in CX3CR1 knockout mice to the same extent and over the same time course seen in wild-type controls. The effects of METH in CX3CR1 knockout mice were not gender-dependent and did not extend beyond the striatum. Striatal microglia expressing eGFP constitutively show morphological changes after METH that are characteristic of activation. This response was restricted to the striatum and contrasted sharply with unresponsive eGFP-microglia in surrounding brain areas that are not damaged by METH. We conclude from these studies that CX3CR1 signaling does not modulate METH neurotoxicity or microglial activation. Furthermore, it appears that striatal-resident microglia respond to METH with an activation cascade and then return to a surveying state without undergoing apoptosis or migration.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "tacrolimus", "mention_text": "Recovery of tacrolimus-associated brachial neuritis after conversion to everolimus in a pediatric renal transplant recipient--case report and review of the literature.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "brachial neuritis", "mention_text": "Recovery of tacrolimus-associated brachial neuritis after conversion to everolimus in a pediatric renal transplant recipient--case report and review of the literature.", "entity": "Brachial Plexus Neuritis", "aliases": "Amyotrophic Neuralgia Neuralgias Amyotrophies Hereditary Neuralgic Amyotrophy with Predilection for Brachial Plexus Neuritides Neuritis Neuropathy Cervico Cervico-Brachial Cervicobrachial Familial Girdle Neuropathies Shoulder Heredofamilial With Shoulder-Girdle Parsonage Aldren Turner Syndrome Parsonage-Aldren-Turner Parsonage-Turner", "definition": "A syndrome associated with inflammation of the BRACHIAL PLEXUS. Clinical features include severe pain in the shoulder region which may be accompanied by MUSCLE WEAKNESS and loss of sensation in the upper extremity. This condition may be associated with VIRUS DISEASES; IMMUNIZATION; SURGERY; heroin use (see HEROIN DEPENDENCE); and other conditions. The term brachial neuralgia generally refers to pain associated with brachial plexus injury. (From Adams et al., Principles of Neurology, 6th ed, pp1355-6)\n    ", "id": "MESH:D020968"}
{"mention": "everolimus", "mention_text": "Recovery of tacrolimus-associated brachial neuritis after conversion to everolimus in a pediatric renal transplant recipient--case report and review of the literature.", "entity": "everolimus", "aliases": "40-O-(2-hydroxyethyl)-rapamycin Certican RAD 001 RAD001 SDZ SDZ-RAD everolimus", "definition": "", "id": "MESH:C107135"}
{"mention": "TAC", "mention_text": "TAC has been shown to be a potent immunosuppressive agent for solid organ transplantation in pediatrics. Neurotoxicity is a potentially serious toxic effect. It is characterized by encephalopathy, headaches, seizures, or neurological deficits. Here, we describe an eight-and-a-half-yr-old male renal transplant recipient with right BN. MRI demonstrated hyperintense T2 signals in the cervical cord and right brachial plexus roots indicative of both myelitis and right brachial plexitis. Symptoms persisted for three months despite TAC dose reduction, administration of IVIG and four doses of methylprednisolone pulse therapy. Improvement and eventually full recovery only occurred after TAC was completely discontinued and successfully replaced by everolimus.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "Neurotoxicity", "mention_text": "TAC has been shown to be a potent immunosuppressive agent for solid organ transplantation in pediatrics. Neurotoxicity is a potentially serious toxic effect. It is characterized by encephalopathy, headaches, seizures, or neurological deficits. Here, we describe an eight-and-a-half-yr-old male renal transplant recipient with right BN. MRI demonstrated hyperintense T2 signals in the cervical cord and right brachial plexus roots indicative of both myelitis and right brachial plexitis. Symptoms persisted for three months despite TAC dose reduction, administration of IVIG and four doses of methylprednisolone pulse therapy. Improvement and eventually full recovery only occurred after TAC was completely discontinued and successfully replaced by everolimus.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "encephalopathy", "mention_text": "TAC has been shown to be a potent immunosuppressive agent for solid organ transplantation in pediatrics. Neurotoxicity is a potentially serious toxic effect. It is characterized by encephalopathy, headaches, seizures, or neurological deficits. Here, we describe an eight-and-a-half-yr-old male renal transplant recipient with right BN. MRI demonstrated hyperintense T2 signals in the cervical cord and right brachial plexus roots indicative of both myelitis and right brachial plexitis. Symptoms persisted for three months despite TAC dose reduction, administration of IVIG and four doses of methylprednisolone pulse therapy. Improvement and eventually full recovery only occurred after TAC was completely discontinued and successfully replaced by everolimus.", "entity": "Brain Diseases", "aliases": "Brain Disease Diseases Disorder Disorders CNS Intracranial Central Nervous System Encephalon", "definition": "Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.\n    ", "id": "MESH:D001927"}
{"mention": "headaches", "mention_text": "TAC has been shown to be a potent immunosuppressive agent for solid organ transplantation in pediatrics. Neurotoxicity is a potentially serious toxic effect. It is characterized by encephalopathy, headaches, seizures, or neurological deficits. Here, we describe an eight-and-a-half-yr-old male renal transplant recipient with right BN. MRI demonstrated hyperintense T2 signals in the cervical cord and right brachial plexus roots indicative of both myelitis and right brachial plexitis. Symptoms persisted for three months despite TAC dose reduction, administration of IVIG and four doses of methylprednisolone pulse therapy. Improvement and eventually full recovery only occurred after TAC was completely discontinued and successfully replaced by everolimus.", "entity": "Headache", "aliases": "Bilateral Headache Headaches Cephalalgia Cephalalgias Cephalgia Cephalgias Cephalodynia Cephalodynias Cranial Pain Pains Generalized Head Ocular Orthostatic Periorbital Retro-Ocular Sharp Throbbing Unilateral Vertex Hemicrania Retro", "definition": "The symptom of PAIN in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of HEADACHE DISORDERS.\n    ", "id": "MESH:D006261"}
{"mention": "seizures", "mention_text": "TAC has been shown to be a potent immunosuppressive agent for solid organ transplantation in pediatrics. Neurotoxicity is a potentially serious toxic effect. It is characterized by encephalopathy, headaches, seizures, or neurological deficits. Here, we describe an eight-and-a-half-yr-old male renal transplant recipient with right BN. MRI demonstrated hyperintense T2 signals in the cervical cord and right brachial plexus roots indicative of both myelitis and right brachial plexitis. Symptoms persisted for three months despite TAC dose reduction, administration of IVIG and four doses of methylprednisolone pulse therapy. Improvement and eventually full recovery only occurred after TAC was completely discontinued and successfully replaced by everolimus.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "neurological deficits", "mention_text": "TAC has been shown to be a potent immunosuppressive agent for solid organ transplantation in pediatrics. Neurotoxicity is a potentially serious toxic effect. It is characterized by encephalopathy, headaches, seizures, or neurological deficits. Here, we describe an eight-and-a-half-yr-old male renal transplant recipient with right BN. MRI demonstrated hyperintense T2 signals in the cervical cord and right brachial plexus roots indicative of both myelitis and right brachial plexitis. Symptoms persisted for three months despite TAC dose reduction, administration of IVIG and four doses of methylprednisolone pulse therapy. Improvement and eventually full recovery only occurred after TAC was completely discontinued and successfully replaced by everolimus.", "entity": "Neurologic Manifestations", "aliases": "Deficit Focal Neurologic Deficits Dysfunction Dysfunctions Finding Findings Manifestation Neurological Manifestations Sign Signs and Symptoms Symptom", "definition": "Clinical signs and symptoms caused by nervous system injury or dysfunction.\n    ", "id": "MESH:D009461"}
{"mention": "myelitis", "mention_text": "TAC has been shown to be a potent immunosuppressive agent for solid organ transplantation in pediatrics. Neurotoxicity is a potentially serious toxic effect. It is characterized by encephalopathy, headaches, seizures, or neurological deficits. Here, we describe an eight-and-a-half-yr-old male renal transplant recipient with right BN. MRI demonstrated hyperintense T2 signals in the cervical cord and right brachial plexus roots indicative of both myelitis and right brachial plexitis. Symptoms persisted for three months despite TAC dose reduction, administration of IVIG and four doses of methylprednisolone pulse therapy. Improvement and eventually full recovery only occurred after TAC was completely discontinued and successfully replaced by everolimus.", "entity": "Myelitis", "aliases": "Infectious Myelitis Inflammation Spinal Cord Inflammations Inflammatory Myelopathies Myelopathy Myelitides Subacute Necrotising", "definition": "Inflammation of the spinal cord. Relatively common etiologies include infections; AUTOIMMUNE DISEASES; SPINAL CORD; and ischemia (see also SPINAL CORD VASCULAR DISEASES). Clinical features generally include weakness, sensory loss, localized pain, incontinence, and other signs of autonomic dysfunction.\n    ", "id": "MESH:D009187"}
{"mention": "brachial plexitis", "mention_text": "TAC has been shown to be a potent immunosuppressive agent for solid organ transplantation in pediatrics. Neurotoxicity is a potentially serious toxic effect. It is characterized by encephalopathy, headaches, seizures, or neurological deficits. Here, we describe an eight-and-a-half-yr-old male renal transplant recipient with right BN. MRI demonstrated hyperintense T2 signals in the cervical cord and right brachial plexus roots indicative of both myelitis and right brachial plexitis. Symptoms persisted for three months despite TAC dose reduction, administration of IVIG and four doses of methylprednisolone pulse therapy. Improvement and eventually full recovery only occurred after TAC was completely discontinued and successfully replaced by everolimus.", "entity": "Brachial Plexus Neuritis", "aliases": "Amyotrophic Neuralgia Neuralgias Amyotrophies Hereditary Neuralgic Amyotrophy with Predilection for Brachial Plexus Neuritides Neuritis Neuropathy Cervico Cervico-Brachial Cervicobrachial Familial Girdle Neuropathies Shoulder Heredofamilial With Shoulder-Girdle Parsonage Aldren Turner Syndrome Parsonage-Aldren-Turner Parsonage-Turner", "definition": "A syndrome associated with inflammation of the BRACHIAL PLEXUS. Clinical features include severe pain in the shoulder region which may be accompanied by MUSCLE WEAKNESS and loss of sensation in the upper extremity. This condition may be associated with VIRUS DISEASES; IMMUNIZATION; SURGERY; heroin use (see HEROIN DEPENDENCE); and other conditions. The term brachial neuralgia generally refers to pain associated with brachial plexus injury. (From Adams et al., Principles of Neurology, 6th ed, pp1355-6)\n    ", "id": "MESH:D020968"}
{"mention": "methylprednisolone", "mention_text": "TAC has been shown to be a potent immunosuppressive agent for solid organ transplantation in pediatrics. Neurotoxicity is a potentially serious toxic effect. It is characterized by encephalopathy, headaches, seizures, or neurological deficits. Here, we describe an eight-and-a-half-yr-old male renal transplant recipient with right BN. MRI demonstrated hyperintense T2 signals in the cervical cord and right brachial plexus roots indicative of both myelitis and right brachial plexitis. Symptoms persisted for three months despite TAC dose reduction, administration of IVIG and four doses of methylprednisolone pulse therapy. Improvement and eventually full recovery only occurred after TAC was completely discontinued and successfully replaced by everolimus.", "entity": "Methylprednisolone", "aliases": "6 Methylprednisolone 6-Methylprednisolone Medrol Metipred Urbason", "definition": "A PREDNISOLONE derivative with similar anti-inflammatory action.\n    ", "id": "MESH:D008775"}
{"mention": "everolimus", "mention_text": "TAC has been shown to be a potent immunosuppressive agent for solid organ transplantation in pediatrics. Neurotoxicity is a potentially serious toxic effect. It is characterized by encephalopathy, headaches, seizures, or neurological deficits. Here, we describe an eight-and-a-half-yr-old male renal transplant recipient with right BN. MRI demonstrated hyperintense T2 signals in the cervical cord and right brachial plexus roots indicative of both myelitis and right brachial plexitis. Symptoms persisted for three months despite TAC dose reduction, administration of IVIG and four doses of methylprednisolone pulse therapy. Improvement and eventually full recovery only occurred after TAC was completely discontinued and successfully replaced by everolimus.", "entity": "everolimus", "aliases": "40-O-(2-hydroxyethyl)-rapamycin Certican RAD 001 RAD001 SDZ SDZ-RAD everolimus", "definition": "", "id": "MESH:C107135"}
{"mention": "Valvular heart disease", "mention_text": "Valvular heart disease in patients with Parkinson's disease treated with pergolide. Course following treatment modifications.", "entity": "Heart Valve Diseases", "aliases": "Disease Heart Valve Valvular Diseases", "definition": "Pathological conditions involving any of the various HEART VALVES and the associated structures (PAPILLARY MUSCLES and CHORDAE TENDINEAE).\n    ", "id": "MESH:D006349"}
{"mention": "Parkinson's disease", "mention_text": "Valvular heart disease in patients with Parkinson's disease treated with pergolide. Course following treatment modifications.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "pergolide", "mention_text": "Valvular heart disease in patients with Parkinson's disease treated with pergolide. Course following treatment modifications.", "entity": "Pergolide", "aliases": "Athena Brand of Pergolide Mesylate Celance Draxis Elanco LY-127,809 LY-127809 LY127,809 LY127809 Lilly Parkotil Permax Pharken", "definition": "A long-acting dopamine agonist which has been used to treat PARKINSON DISEASE and HYPERPROLACTINEMIA but withdrawn from some markets due to potential for HEART VALVE DISEASES.\n    ", "id": "MESH:D010479"}
{"mention": "Valvular heart abnormalities", "mention_text": "Valvular heart abnormalities have been reported in patients with Parkinson's disease (PD) treated with pergolide. However, the incidence and severity of these abnormalities vary from study to study and their course after drug withdrawal has not been systematically assessed. OBJECTIVES: To estimate the frequency and severity of valvular heart abnormality and its possible reversibility after drug withdrawal in a case-control study. METHODS: All PD patients in the Amiens area treated with pergolide were invited to attend a cardiologic assessment including transthoracic echocardiography. Thirty PD patients participated in the study. A second echocardiography was performed (median interval: 13 months) after pergolide withdrawal (n=10 patients). Controls were age- and sex-matched non-PD patients referred to the cardiology department. RESULTS: Compared to controls, aortic regurgitation (OR: 3.1; 95% IC: 1.1-8.8) and mitral regurgitation (OR: 10.7; 95% IC: 2.1-53) were more frequent in PD patients (tricuspid: NS). The number of affected valves (n=2.4+/-0.7) and the sum of regurgitation grades (n=2.8+/-1.09) were higher (p=0.008 and p=0.006, respectively) in the pergolide group. Severity of regurgitation was not correlated with pergolide cumulative dose. A restrictive pattern of valvular regurgitation, suggestive of the role of pergolide, was observed in 12/30 (40%) patients including two with heart failure. Pergolide was discontinued in 10 patients with valvular heart disease, resulting in a lower regurgitation grade (p=0.01) at the second transthoracic echocardiography and the two patients with heart failure returned to nearly normal clinical examination. This study supports the high frequency of restrictive valve regurgitation in PD patients treated with pergolide and reveals that a significant improvement is usual when the treatment is converted to non-ergot dopamine agonists.", "entity": "Heart Valve Diseases", "aliases": "Disease Heart Valve Valvular Diseases", "definition": "Pathological conditions involving any of the various HEART VALVES and the associated structures (PAPILLARY MUSCLES and CHORDAE TENDINEAE).\n    ", "id": "MESH:D006349"}
{"mention": "Parkinson's disease", "mention_text": "Valvular heart abnormalities have been reported in patients with Parkinson's disease (PD) treated with pergolide. However, the incidence and severity of these abnormalities vary from study to study and their course after drug withdrawal has not been systematically assessed. OBJECTIVES: To estimate the frequency and severity of valvular heart abnormality and its possible reversibility after drug withdrawal in a case-control study. METHODS: All PD patients in the Amiens area treated with pergolide were invited to attend a cardiologic assessment including transthoracic echocardiography. Thirty PD patients participated in the study. A second echocardiography was performed (median interval: 13 months) after pergolide withdrawal (n=10 patients). Controls were age- and sex-matched non-PD patients referred to the cardiology department. RESULTS: Compared to controls, aortic regurgitation (OR: 3.1; 95% IC: 1.1-8.8) and mitral regurgitation (OR: 10.7; 95% IC: 2.1-53) were more frequent in PD patients (tricuspid: NS). The number of affected valves (n=2.4+/-0.7) and the sum of regurgitation grades (n=2.8+/-1.09) were higher (p=0.008 and p=0.006, respectively) in the pergolide group. Severity of regurgitation was not correlated with pergolide cumulative dose. A restrictive pattern of valvular regurgitation, suggestive of the role of pergolide, was observed in 12/30 (40%) patients including two with heart failure. Pergolide was discontinued in 10 patients with valvular heart disease, resulting in a lower regurgitation grade (p=0.01) at the second transthoracic echocardiography and the two patients with heart failure returned to nearly normal clinical examination. This study supports the high frequency of restrictive valve regurgitation in PD patients treated with pergolide and reveals that a significant improvement is usual when the treatment is converted to non-ergot dopamine agonists.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "PD", "mention_text": "Valvular heart abnormalities have been reported in patients with Parkinson's disease (PD) treated with pergolide. However, the incidence and severity of these abnormalities vary from study to study and their course after drug withdrawal has not been systematically assessed. OBJECTIVES: To estimate the frequency and severity of valvular heart abnormality and its possible reversibility after drug withdrawal in a case-control study. METHODS: All PD patients in the Amiens area treated with pergolide were invited to attend a cardiologic assessment including transthoracic echocardiography. Thirty PD patients participated in the study. A second echocardiography was performed (median interval: 13 months) after pergolide withdrawal (n=10 patients). Controls were age- and sex-matched non-PD patients referred to the cardiology department. RESULTS: Compared to controls, aortic regurgitation (OR: 3.1; 95% IC: 1.1-8.8) and mitral regurgitation (OR: 10.7; 95% IC: 2.1-53) were more frequent in PD patients (tricuspid: NS). The number of affected valves (n=2.4+/-0.7) and the sum of regurgitation grades (n=2.8+/-1.09) were higher (p=0.008 and p=0.006, respectively) in the pergolide group. Severity of regurgitation was not correlated with pergolide cumulative dose. A restrictive pattern of valvular regurgitation, suggestive of the role of pergolide, was observed in 12/30 (40%) patients including two with heart failure. Pergolide was discontinued in 10 patients with valvular heart disease, resulting in a lower regurgitation grade (p=0.01) at the second transthoracic echocardiography and the two patients with heart failure returned to nearly normal clinical examination. This study supports the high frequency of restrictive valve regurgitation in PD patients treated with pergolide and reveals that a significant improvement is usual when the treatment is converted to non-ergot dopamine agonists.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "pergolide", "mention_text": "Valvular heart abnormalities have been reported in patients with Parkinson's disease (PD) treated with pergolide. However, the incidence and severity of these abnormalities vary from study to study and their course after drug withdrawal has not been systematically assessed. OBJECTIVES: To estimate the frequency and severity of valvular heart abnormality and its possible reversibility after drug withdrawal in a case-control study. METHODS: All PD patients in the Amiens area treated with pergolide were invited to attend a cardiologic assessment including transthoracic echocardiography. Thirty PD patients participated in the study. A second echocardiography was performed (median interval: 13 months) after pergolide withdrawal (n=10 patients). Controls were age- and sex-matched non-PD patients referred to the cardiology department. RESULTS: Compared to controls, aortic regurgitation (OR: 3.1; 95% IC: 1.1-8.8) and mitral regurgitation (OR: 10.7; 95% IC: 2.1-53) were more frequent in PD patients (tricuspid: NS). The number of affected valves (n=2.4+/-0.7) and the sum of regurgitation grades (n=2.8+/-1.09) were higher (p=0.008 and p=0.006, respectively) in the pergolide group. Severity of regurgitation was not correlated with pergolide cumulative dose. A restrictive pattern of valvular regurgitation, suggestive of the role of pergolide, was observed in 12/30 (40%) patients including two with heart failure. Pergolide was discontinued in 10 patients with valvular heart disease, resulting in a lower regurgitation grade (p=0.01) at the second transthoracic echocardiography and the two patients with heart failure returned to nearly normal clinical examination. This study supports the high frequency of restrictive valve regurgitation in PD patients treated with pergolide and reveals that a significant improvement is usual when the treatment is converted to non-ergot dopamine agonists.", "entity": "Pergolide", "aliases": "Athena Brand of Pergolide Mesylate Celance Draxis Elanco LY-127,809 LY-127809 LY127,809 LY127809 Lilly Parkotil Permax Pharken", "definition": "A long-acting dopamine agonist which has been used to treat PARKINSON DISEASE and HYPERPROLACTINEMIA but withdrawn from some markets due to potential for HEART VALVE DISEASES.\n    ", "id": "MESH:D010479"}
{"mention": "valvular heart abnormality", "mention_text": "Valvular heart abnormalities have been reported in patients with Parkinson's disease (PD) treated with pergolide. However, the incidence and severity of these abnormalities vary from study to study and their course after drug withdrawal has not been systematically assessed. OBJECTIVES: To estimate the frequency and severity of valvular heart abnormality and its possible reversibility after drug withdrawal in a case-control study. METHODS: All PD patients in the Amiens area treated with pergolide were invited to attend a cardiologic assessment including transthoracic echocardiography. Thirty PD patients participated in the study. A second echocardiography was performed (median interval: 13 months) after pergolide withdrawal (n=10 patients). Controls were age- and sex-matched non-PD patients referred to the cardiology department. RESULTS: Compared to controls, aortic regurgitation (OR: 3.1; 95% IC: 1.1-8.8) and mitral regurgitation (OR: 10.7; 95% IC: 2.1-53) were more frequent in PD patients (tricuspid: NS). The number of affected valves (n=2.4+/-0.7) and the sum of regurgitation grades (n=2.8+/-1.09) were higher (p=0.008 and p=0.006, respectively) in the pergolide group. Severity of regurgitation was not correlated with pergolide cumulative dose. A restrictive pattern of valvular regurgitation, suggestive of the role of pergolide, was observed in 12/30 (40%) patients including two with heart failure. Pergolide was discontinued in 10 patients with valvular heart disease, resulting in a lower regurgitation grade (p=0.01) at the second transthoracic echocardiography and the two patients with heart failure returned to nearly normal clinical examination. This study supports the high frequency of restrictive valve regurgitation in PD patients treated with pergolide and reveals that a significant improvement is usual when the treatment is converted to non-ergot dopamine agonists.", "entity": "Heart Valve Diseases", "aliases": "Disease Heart Valve Valvular Diseases", "definition": "Pathological conditions involving any of the various HEART VALVES and the associated structures (PAPILLARY MUSCLES and CHORDAE TENDINEAE).\n    ", "id": "MESH:D006349"}
{"mention": "aortic regurgitation", "mention_text": "Valvular heart abnormalities have been reported in patients with Parkinson's disease (PD) treated with pergolide. However, the incidence and severity of these abnormalities vary from study to study and their course after drug withdrawal has not been systematically assessed. OBJECTIVES: To estimate the frequency and severity of valvular heart abnormality and its possible reversibility after drug withdrawal in a case-control study. METHODS: All PD patients in the Amiens area treated with pergolide were invited to attend a cardiologic assessment including transthoracic echocardiography. Thirty PD patients participated in the study. A second echocardiography was performed (median interval: 13 months) after pergolide withdrawal (n=10 patients). Controls were age- and sex-matched non-PD patients referred to the cardiology department. RESULTS: Compared to controls, aortic regurgitation (OR: 3.1; 95% IC: 1.1-8.8) and mitral regurgitation (OR: 10.7; 95% IC: 2.1-53) were more frequent in PD patients (tricuspid: NS). The number of affected valves (n=2.4+/-0.7) and the sum of regurgitation grades (n=2.8+/-1.09) were higher (p=0.008 and p=0.006, respectively) in the pergolide group. Severity of regurgitation was not correlated with pergolide cumulative dose. A restrictive pattern of valvular regurgitation, suggestive of the role of pergolide, was observed in 12/30 (40%) patients including two with heart failure. Pergolide was discontinued in 10 patients with valvular heart disease, resulting in a lower regurgitation grade (p=0.01) at the second transthoracic echocardiography and the two patients with heart failure returned to nearly normal clinical examination. This study supports the high frequency of restrictive valve regurgitation in PD patients treated with pergolide and reveals that a significant improvement is usual when the treatment is converted to non-ergot dopamine agonists.", "entity": "Aortic Valve Insufficiency", "aliases": "Aortic Incompetence Regurgitation Valve Insufficiency", "definition": "Pathological condition characterized by the backflow of blood from the ASCENDING AORTA back into the LEFT VENTRICLE, leading to regurgitation. It is caused by diseases of the AORTIC VALVE or its surrounding tissue (aortic root).\n    ", "id": "MESH:D001022"}
{"mention": "mitral regurgitation", "mention_text": "Valvular heart abnormalities have been reported in patients with Parkinson's disease (PD) treated with pergolide. However, the incidence and severity of these abnormalities vary from study to study and their course after drug withdrawal has not been systematically assessed. OBJECTIVES: To estimate the frequency and severity of valvular heart abnormality and its possible reversibility after drug withdrawal in a case-control study. METHODS: All PD patients in the Amiens area treated with pergolide were invited to attend a cardiologic assessment including transthoracic echocardiography. Thirty PD patients participated in the study. A second echocardiography was performed (median interval: 13 months) after pergolide withdrawal (n=10 patients). Controls were age- and sex-matched non-PD patients referred to the cardiology department. RESULTS: Compared to controls, aortic regurgitation (OR: 3.1; 95% IC: 1.1-8.8) and mitral regurgitation (OR: 10.7; 95% IC: 2.1-53) were more frequent in PD patients (tricuspid: NS). The number of affected valves (n=2.4+/-0.7) and the sum of regurgitation grades (n=2.8+/-1.09) were higher (p=0.008 and p=0.006, respectively) in the pergolide group. Severity of regurgitation was not correlated with pergolide cumulative dose. A restrictive pattern of valvular regurgitation, suggestive of the role of pergolide, was observed in 12/30 (40%) patients including two with heart failure. Pergolide was discontinued in 10 patients with valvular heart disease, resulting in a lower regurgitation grade (p=0.01) at the second transthoracic echocardiography and the two patients with heart failure returned to nearly normal clinical examination. This study supports the high frequency of restrictive valve regurgitation in PD patients treated with pergolide and reveals that a significant improvement is usual when the treatment is converted to non-ergot dopamine agonists.", "entity": "Mitral Valve Insufficiency", "aliases": "Incompetence Mitral Valve Insufficiency Regurgitation", "definition": "Backflow of blood from the LEFT VENTRICLE into the LEFT ATRIUM due to imperfect closure of the MITRAL VALVE. This can lead to mitral valve regurgitation.\n    ", "id": "MESH:D008944"}
{"mention": "valvular regurgitation", "mention_text": "Valvular heart abnormalities have been reported in patients with Parkinson's disease (PD) treated with pergolide. However, the incidence and severity of these abnormalities vary from study to study and their course after drug withdrawal has not been systematically assessed. OBJECTIVES: To estimate the frequency and severity of valvular heart abnormality and its possible reversibility after drug withdrawal in a case-control study. METHODS: All PD patients in the Amiens area treated with pergolide were invited to attend a cardiologic assessment including transthoracic echocardiography. Thirty PD patients participated in the study. A second echocardiography was performed (median interval: 13 months) after pergolide withdrawal (n=10 patients). Controls were age- and sex-matched non-PD patients referred to the cardiology department. RESULTS: Compared to controls, aortic regurgitation (OR: 3.1; 95% IC: 1.1-8.8) and mitral regurgitation (OR: 10.7; 95% IC: 2.1-53) were more frequent in PD patients (tricuspid: NS). The number of affected valves (n=2.4+/-0.7) and the sum of regurgitation grades (n=2.8+/-1.09) were higher (p=0.008 and p=0.006, respectively) in the pergolide group. Severity of regurgitation was not correlated with pergolide cumulative dose. A restrictive pattern of valvular regurgitation, suggestive of the role of pergolide, was observed in 12/30 (40%) patients including two with heart failure. Pergolide was discontinued in 10 patients with valvular heart disease, resulting in a lower regurgitation grade (p=0.01) at the second transthoracic echocardiography and the two patients with heart failure returned to nearly normal clinical examination. This study supports the high frequency of restrictive valve regurgitation in PD patients treated with pergolide and reveals that a significant improvement is usual when the treatment is converted to non-ergot dopamine agonists.", "entity": "Heart Valve Diseases", "aliases": "Disease Heart Valve Valvular Diseases", "definition": "Pathological conditions involving any of the various HEART VALVES and the associated structures (PAPILLARY MUSCLES and CHORDAE TENDINEAE).\n    ", "id": "MESH:D006349"}
{"mention": "heart failure", "mention_text": "Valvular heart abnormalities have been reported in patients with Parkinson's disease (PD) treated with pergolide. However, the incidence and severity of these abnormalities vary from study to study and their course after drug withdrawal has not been systematically assessed. OBJECTIVES: To estimate the frequency and severity of valvular heart abnormality and its possible reversibility after drug withdrawal in a case-control study. METHODS: All PD patients in the Amiens area treated with pergolide were invited to attend a cardiologic assessment including transthoracic echocardiography. Thirty PD patients participated in the study. A second echocardiography was performed (median interval: 13 months) after pergolide withdrawal (n=10 patients). Controls were age- and sex-matched non-PD patients referred to the cardiology department. RESULTS: Compared to controls, aortic regurgitation (OR: 3.1; 95% IC: 1.1-8.8) and mitral regurgitation (OR: 10.7; 95% IC: 2.1-53) were more frequent in PD patients (tricuspid: NS). The number of affected valves (n=2.4+/-0.7) and the sum of regurgitation grades (n=2.8+/-1.09) were higher (p=0.008 and p=0.006, respectively) in the pergolide group. Severity of regurgitation was not correlated with pergolide cumulative dose. A restrictive pattern of valvular regurgitation, suggestive of the role of pergolide, was observed in 12/30 (40%) patients including two with heart failure. Pergolide was discontinued in 10 patients with valvular heart disease, resulting in a lower regurgitation grade (p=0.01) at the second transthoracic echocardiography and the two patients with heart failure returned to nearly normal clinical examination. This study supports the high frequency of restrictive valve regurgitation in PD patients treated with pergolide and reveals that a significant improvement is usual when the treatment is converted to non-ergot dopamine agonists.", "entity": "Heart Failure", "aliases": "Cardiac Failure Congestive Heart Decompensation Left Sided Left-Sided Right Right-Sided Myocardial", "definition": "A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.\n    ", "id": "MESH:D006333"}
{"mention": "Pergolide", "mention_text": "Valvular heart abnormalities have been reported in patients with Parkinson's disease (PD) treated with pergolide. However, the incidence and severity of these abnormalities vary from study to study and their course after drug withdrawal has not been systematically assessed. OBJECTIVES: To estimate the frequency and severity of valvular heart abnormality and its possible reversibility after drug withdrawal in a case-control study. METHODS: All PD patients in the Amiens area treated with pergolide were invited to attend a cardiologic assessment including transthoracic echocardiography. Thirty PD patients participated in the study. A second echocardiography was performed (median interval: 13 months) after pergolide withdrawal (n=10 patients). Controls were age- and sex-matched non-PD patients referred to the cardiology department. RESULTS: Compared to controls, aortic regurgitation (OR: 3.1; 95% IC: 1.1-8.8) and mitral regurgitation (OR: 10.7; 95% IC: 2.1-53) were more frequent in PD patients (tricuspid: NS). The number of affected valves (n=2.4+/-0.7) and the sum of regurgitation grades (n=2.8+/-1.09) were higher (p=0.008 and p=0.006, respectively) in the pergolide group. Severity of regurgitation was not correlated with pergolide cumulative dose. A restrictive pattern of valvular regurgitation, suggestive of the role of pergolide, was observed in 12/30 (40%) patients including two with heart failure. Pergolide was discontinued in 10 patients with valvular heart disease, resulting in a lower regurgitation grade (p=0.01) at the second transthoracic echocardiography and the two patients with heart failure returned to nearly normal clinical examination. This study supports the high frequency of restrictive valve regurgitation in PD patients treated with pergolide and reveals that a significant improvement is usual when the treatment is converted to non-ergot dopamine agonists.", "entity": "Pergolide", "aliases": "Athena Brand of Pergolide Mesylate Celance Draxis Elanco LY-127,809 LY-127809 LY127,809 LY127809 Lilly Parkotil Permax Pharken", "definition": "A long-acting dopamine agonist which has been used to treat PARKINSON DISEASE and HYPERPROLACTINEMIA but withdrawn from some markets due to potential for HEART VALVE DISEASES.\n    ", "id": "MESH:D010479"}
{"mention": "valvular heart disease", "mention_text": "Valvular heart abnormalities have been reported in patients with Parkinson's disease (PD) treated with pergolide. However, the incidence and severity of these abnormalities vary from study to study and their course after drug withdrawal has not been systematically assessed. OBJECTIVES: To estimate the frequency and severity of valvular heart abnormality and its possible reversibility after drug withdrawal in a case-control study. METHODS: All PD patients in the Amiens area treated with pergolide were invited to attend a cardiologic assessment including transthoracic echocardiography. Thirty PD patients participated in the study. A second echocardiography was performed (median interval: 13 months) after pergolide withdrawal (n=10 patients). Controls were age- and sex-matched non-PD patients referred to the cardiology department. RESULTS: Compared to controls, aortic regurgitation (OR: 3.1; 95% IC: 1.1-8.8) and mitral regurgitation (OR: 10.7; 95% IC: 2.1-53) were more frequent in PD patients (tricuspid: NS). The number of affected valves (n=2.4+/-0.7) and the sum of regurgitation grades (n=2.8+/-1.09) were higher (p=0.008 and p=0.006, respectively) in the pergolide group. Severity of regurgitation was not correlated with pergolide cumulative dose. A restrictive pattern of valvular regurgitation, suggestive of the role of pergolide, was observed in 12/30 (40%) patients including two with heart failure. Pergolide was discontinued in 10 patients with valvular heart disease, resulting in a lower regurgitation grade (p=0.01) at the second transthoracic echocardiography and the two patients with heart failure returned to nearly normal clinical examination. This study supports the high frequency of restrictive valve regurgitation in PD patients treated with pergolide and reveals that a significant improvement is usual when the treatment is converted to non-ergot dopamine agonists.", "entity": "Heart Valve Diseases", "aliases": "Disease Heart Valve Valvular Diseases", "definition": "Pathological conditions involving any of the various HEART VALVES and the associated structures (PAPILLARY MUSCLES and CHORDAE TENDINEAE).\n    ", "id": "MESH:D006349"}
{"mention": "valve regurgitation", "mention_text": "Valvular heart abnormalities have been reported in patients with Parkinson's disease (PD) treated with pergolide. However, the incidence and severity of these abnormalities vary from study to study and their course after drug withdrawal has not been systematically assessed. OBJECTIVES: To estimate the frequency and severity of valvular heart abnormality and its possible reversibility after drug withdrawal in a case-control study. METHODS: All PD patients in the Amiens area treated with pergolide were invited to attend a cardiologic assessment including transthoracic echocardiography. Thirty PD patients participated in the study. A second echocardiography was performed (median interval: 13 months) after pergolide withdrawal (n=10 patients). Controls were age- and sex-matched non-PD patients referred to the cardiology department. RESULTS: Compared to controls, aortic regurgitation (OR: 3.1; 95% IC: 1.1-8.8) and mitral regurgitation (OR: 10.7; 95% IC: 2.1-53) were more frequent in PD patients (tricuspid: NS). The number of affected valves (n=2.4+/-0.7) and the sum of regurgitation grades (n=2.8+/-1.09) were higher (p=0.008 and p=0.006, respectively) in the pergolide group. Severity of regurgitation was not correlated with pergolide cumulative dose. A restrictive pattern of valvular regurgitation, suggestive of the role of pergolide, was observed in 12/30 (40%) patients including two with heart failure. Pergolide was discontinued in 10 patients with valvular heart disease, resulting in a lower regurgitation grade (p=0.01) at the second transthoracic echocardiography and the two patients with heart failure returned to nearly normal clinical examination. This study supports the high frequency of restrictive valve regurgitation in PD patients treated with pergolide and reveals that a significant improvement is usual when the treatment is converted to non-ergot dopamine agonists.", "entity": "Heart Valve Diseases", "aliases": "Disease Heart Valve Valvular Diseases", "definition": "Pathological conditions involving any of the various HEART VALVES and the associated structures (PAPILLARY MUSCLES and CHORDAE TENDINEAE).\n    ", "id": "MESH:D006349"}
{"mention": "dopamine", "mention_text": "Valvular heart abnormalities have been reported in patients with Parkinson's disease (PD) treated with pergolide. However, the incidence and severity of these abnormalities vary from study to study and their course after drug withdrawal has not been systematically assessed. OBJECTIVES: To estimate the frequency and severity of valvular heart abnormality and its possible reversibility after drug withdrawal in a case-control study. METHODS: All PD patients in the Amiens area treated with pergolide were invited to attend a cardiologic assessment including transthoracic echocardiography. Thirty PD patients participated in the study. A second echocardiography was performed (median interval: 13 months) after pergolide withdrawal (n=10 patients). Controls were age- and sex-matched non-PD patients referred to the cardiology department. RESULTS: Compared to controls, aortic regurgitation (OR: 3.1; 95% IC: 1.1-8.8) and mitral regurgitation (OR: 10.7; 95% IC: 2.1-53) were more frequent in PD patients (tricuspid: NS). The number of affected valves (n=2.4+/-0.7) and the sum of regurgitation grades (n=2.8+/-1.09) were higher (p=0.008 and p=0.006, respectively) in the pergolide group. Severity of regurgitation was not correlated with pergolide cumulative dose. A restrictive pattern of valvular regurgitation, suggestive of the role of pergolide, was observed in 12/30 (40%) patients including two with heart failure. Pergolide was discontinued in 10 patients with valvular heart disease, resulting in a lower regurgitation grade (p=0.01) at the second transthoracic echocardiography and the two patients with heart failure returned to nearly normal clinical examination. This study supports the high frequency of restrictive valve regurgitation in PD patients treated with pergolide and reveals that a significant improvement is usual when the treatment is converted to non-ergot dopamine agonists.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "papaverine", "mention_text": "Adverse effects of topical papaverine on auditory nerve function.", "entity": "Papaverine", "aliases": "Cerespan Hydrochloride Papaverine Pavabid Pavatym", "definition": "An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels.\n    ", "id": "MESH:D010208"}
{"mention": "Papaverine hydrochloride", "mention_text": "BACKGROUND: Papaverine hydrochloride is a direct-acting vasodilator used to manage vasospasm during various neurosurgical operations. Transient cranial nerve dysfunction has been described in a few cases with topical papaverine. This study supports previous reports and provides neurophysiological evidence of an adverse effect on the auditory nerve. METHODS: We conducted a retrospective review of 70 consecutive microvascular decompression operations and studied those patients who received topical papaverine for vasospasm. Topical papaverine was used as a direct therapeutic action to manage vasospasm in a total of 11 patients. The timing of papaverine application and ongoing operative events was reviewed relative to changes in neurophysiological recordings. Brainstem auditory evoked potentials (BAEPs) were routinely used to monitor cochlear nerve function during these operations. FINDINGS: A temporal relationship was found between topical papaverine and BAEP changes leading to complete waveform loss. The average temporal delay between papaverine and the onset of an adverse BAEP change was 5 min. In 10 of 11 patients, BAEP waves II/III-V completely disappeared within 2 to 25 min after papaverine. Eight of these 10 patients had complete loss of BAEP waveforms within 10 min. One patient showed no recovery of later waves and a delayed profound sensorineural hearing loss. The average recovery time of BAEP waveforms to pre-papaverine baseline values was 39 min. CONCLUSIONS: Topical papaverine for the treatment of vasospasm was associated with the onset of a transient disturbance in neurophysiological function of the ascending auditory brainstem pathway. The complete disappearance of BAEP waveforms with a consistent temporal delay suggests a possible adverse effect on the proximal eighth nerve. Recommendations to avoid potential cranial nerve deficits from papaverine are provided.", "entity": "Papaverine", "aliases": "Cerespan Hydrochloride Papaverine Pavabid Pavatym", "definition": "An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels.\n    ", "id": "MESH:D010208"}
{"mention": "vasospasm", "mention_text": "BACKGROUND: Papaverine hydrochloride is a direct-acting vasodilator used to manage vasospasm during various neurosurgical operations. Transient cranial nerve dysfunction has been described in a few cases with topical papaverine. This study supports previous reports and provides neurophysiological evidence of an adverse effect on the auditory nerve. METHODS: We conducted a retrospective review of 70 consecutive microvascular decompression operations and studied those patients who received topical papaverine for vasospasm. Topical papaverine was used as a direct therapeutic action to manage vasospasm in a total of 11 patients. The timing of papaverine application and ongoing operative events was reviewed relative to changes in neurophysiological recordings. Brainstem auditory evoked potentials (BAEPs) were routinely used to monitor cochlear nerve function during these operations. FINDINGS: A temporal relationship was found between topical papaverine and BAEP changes leading to complete waveform loss. The average temporal delay between papaverine and the onset of an adverse BAEP change was 5 min. In 10 of 11 patients, BAEP waves II/III-V completely disappeared within 2 to 25 min after papaverine. Eight of these 10 patients had complete loss of BAEP waveforms within 10 min. One patient showed no recovery of later waves and a delayed profound sensorineural hearing loss. The average recovery time of BAEP waveforms to pre-papaverine baseline values was 39 min. CONCLUSIONS: Topical papaverine for the treatment of vasospasm was associated with the onset of a transient disturbance in neurophysiological function of the ascending auditory brainstem pathway. The complete disappearance of BAEP waveforms with a consistent temporal delay suggests a possible adverse effect on the proximal eighth nerve. Recommendations to avoid potential cranial nerve deficits from papaverine are provided.", "entity": "Vasospasm, Intracranial", "aliases": "Angiospasm Cerebral Intracranial Angiospasms Artery Spasm Spasms Vasospasm Vasospasms Cerebrovascular Vascular", "definition": "Constriction of arteries in the SKULL due to sudden, sharp, and often persistent smooth muscle contraction in blood vessels. Intracranial vasospasm results in reduced vessel lumen caliber, restricted blood flow to the brain, and BRAIN ISCHEMIA that may lead to hypoxic-ischemic brain injury (HYPOXIA-ISCHEMIA, BRAIN).\n    ", "id": "MESH:D020301"}
{"mention": "cranial nerve dysfunction", "mention_text": "BACKGROUND: Papaverine hydrochloride is a direct-acting vasodilator used to manage vasospasm during various neurosurgical operations. Transient cranial nerve dysfunction has been described in a few cases with topical papaverine. This study supports previous reports and provides neurophysiological evidence of an adverse effect on the auditory nerve. METHODS: We conducted a retrospective review of 70 consecutive microvascular decompression operations and studied those patients who received topical papaverine for vasospasm. Topical papaverine was used as a direct therapeutic action to manage vasospasm in a total of 11 patients. The timing of papaverine application and ongoing operative events was reviewed relative to changes in neurophysiological recordings. Brainstem auditory evoked potentials (BAEPs) were routinely used to monitor cochlear nerve function during these operations. FINDINGS: A temporal relationship was found between topical papaverine and BAEP changes leading to complete waveform loss. The average temporal delay between papaverine and the onset of an adverse BAEP change was 5 min. In 10 of 11 patients, BAEP waves II/III-V completely disappeared within 2 to 25 min after papaverine. Eight of these 10 patients had complete loss of BAEP waveforms within 10 min. One patient showed no recovery of later waves and a delayed profound sensorineural hearing loss. The average recovery time of BAEP waveforms to pre-papaverine baseline values was 39 min. CONCLUSIONS: Topical papaverine for the treatment of vasospasm was associated with the onset of a transient disturbance in neurophysiological function of the ascending auditory brainstem pathway. The complete disappearance of BAEP waveforms with a consistent temporal delay suggests a possible adverse effect on the proximal eighth nerve. Recommendations to avoid potential cranial nerve deficits from papaverine are provided.", "entity": "Cranial Nerve Diseases", "aliases": "Cranial Nerve Disease Diseases Disorder Disorders Palsies Palsy Neuropathies Multiple Neuropathy Nervus Cranialis", "definition": "Disorders of one or more of the twelve cranial nerves. With the exception of the optic and olfactory nerves, this includes disorders of the brain stem nuclei from which the cranial nerves originate or terminate.\n    ", "id": "MESH:D003389"}
{"mention": "papaverine", "mention_text": "BACKGROUND: Papaverine hydrochloride is a direct-acting vasodilator used to manage vasospasm during various neurosurgical operations. Transient cranial nerve dysfunction has been described in a few cases with topical papaverine. This study supports previous reports and provides neurophysiological evidence of an adverse effect on the auditory nerve. METHODS: We conducted a retrospective review of 70 consecutive microvascular decompression operations and studied those patients who received topical papaverine for vasospasm. Topical papaverine was used as a direct therapeutic action to manage vasospasm in a total of 11 patients. The timing of papaverine application and ongoing operative events was reviewed relative to changes in neurophysiological recordings. Brainstem auditory evoked potentials (BAEPs) were routinely used to monitor cochlear nerve function during these operations. FINDINGS: A temporal relationship was found between topical papaverine and BAEP changes leading to complete waveform loss. The average temporal delay between papaverine and the onset of an adverse BAEP change was 5 min. In 10 of 11 patients, BAEP waves II/III-V completely disappeared within 2 to 25 min after papaverine. Eight of these 10 patients had complete loss of BAEP waveforms within 10 min. One patient showed no recovery of later waves and a delayed profound sensorineural hearing loss. The average recovery time of BAEP waveforms to pre-papaverine baseline values was 39 min. CONCLUSIONS: Topical papaverine for the treatment of vasospasm was associated with the onset of a transient disturbance in neurophysiological function of the ascending auditory brainstem pathway. The complete disappearance of BAEP waveforms with a consistent temporal delay suggests a possible adverse effect on the proximal eighth nerve. Recommendations to avoid potential cranial nerve deficits from papaverine are provided.", "entity": "Papaverine", "aliases": "Cerespan Hydrochloride Papaverine Pavabid Pavatym", "definition": "An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels.\n    ", "id": "MESH:D010208"}
{"mention": "sensorineural hearing loss", "mention_text": "BACKGROUND: Papaverine hydrochloride is a direct-acting vasodilator used to manage vasospasm during various neurosurgical operations. Transient cranial nerve dysfunction has been described in a few cases with topical papaverine. This study supports previous reports and provides neurophysiological evidence of an adverse effect on the auditory nerve. METHODS: We conducted a retrospective review of 70 consecutive microvascular decompression operations and studied those patients who received topical papaverine for vasospasm. Topical papaverine was used as a direct therapeutic action to manage vasospasm in a total of 11 patients. The timing of papaverine application and ongoing operative events was reviewed relative to changes in neurophysiological recordings. Brainstem auditory evoked potentials (BAEPs) were routinely used to monitor cochlear nerve function during these operations. FINDINGS: A temporal relationship was found between topical papaverine and BAEP changes leading to complete waveform loss. The average temporal delay between papaverine and the onset of an adverse BAEP change was 5 min. In 10 of 11 patients, BAEP waves II/III-V completely disappeared within 2 to 25 min after papaverine. Eight of these 10 patients had complete loss of BAEP waveforms within 10 min. One patient showed no recovery of later waves and a delayed profound sensorineural hearing loss. The average recovery time of BAEP waveforms to pre-papaverine baseline values was 39 min. CONCLUSIONS: Topical papaverine for the treatment of vasospasm was associated with the onset of a transient disturbance in neurophysiological function of the ascending auditory brainstem pathway. The complete disappearance of BAEP waveforms with a consistent temporal delay suggests a possible adverse effect on the proximal eighth nerve. Recommendations to avoid potential cranial nerve deficits from papaverine are provided.", "entity": "Hearing Loss, Sensorineural", "aliases": "Cochlear Hearing Loss Sensorineural", "definition": "Hearing loss resulting from damage to the COCHLEA and the sensorineural elements which lie internally beyond the oval and round windows. These elements include the AUDITORY NERVE and its connections in the BRAINSTEM.\n    ", "id": "MESH:D006319"}
{"mention": "adverse effect on the proximal eighth nerve", "mention_text": "BACKGROUND: Papaverine hydrochloride is a direct-acting vasodilator used to manage vasospasm during various neurosurgical operations. Transient cranial nerve dysfunction has been described in a few cases with topical papaverine. This study supports previous reports and provides neurophysiological evidence of an adverse effect on the auditory nerve. METHODS: We conducted a retrospective review of 70 consecutive microvascular decompression operations and studied those patients who received topical papaverine for vasospasm. Topical papaverine was used as a direct therapeutic action to manage vasospasm in a total of 11 patients. The timing of papaverine application and ongoing operative events was reviewed relative to changes in neurophysiological recordings. Brainstem auditory evoked potentials (BAEPs) were routinely used to monitor cochlear nerve function during these operations. FINDINGS: A temporal relationship was found between topical papaverine and BAEP changes leading to complete waveform loss. The average temporal delay between papaverine and the onset of an adverse BAEP change was 5 min. In 10 of 11 patients, BAEP waves II/III-V completely disappeared within 2 to 25 min after papaverine. Eight of these 10 patients had complete loss of BAEP waveforms within 10 min. One patient showed no recovery of later waves and a delayed profound sensorineural hearing loss. The average recovery time of BAEP waveforms to pre-papaverine baseline values was 39 min. CONCLUSIONS: Topical papaverine for the treatment of vasospasm was associated with the onset of a transient disturbance in neurophysiological function of the ascending auditory brainstem pathway. The complete disappearance of BAEP waveforms with a consistent temporal delay suggests a possible adverse effect on the proximal eighth nerve. Recommendations to avoid potential cranial nerve deficits from papaverine are provided.", "entity": "Vestibulocochlear Nerve Diseases", "aliases": "Acoustic Nerve Disease Diseases Disorder Disorders Cochlear Neuritides Neuritis Cranial VIII Eighth Vestibular Vestibulocochlear", "definition": "Pathological processes of the VESTIBULOCOCHLEAR NERVE, including the branches of COCHLEAR NERVE and VESTIBULAR NERVE. Common examples are VESTIBULAR NEURITIS, cochlear neuritis, and ACOUSTIC NEUROMA. Clinical signs are varying degree of HEARING LOSS; VERTIGO; and TINNITUS.\n    ", "id": "MESH:D000160"}
{"mention": "cranial nerve deficits", "mention_text": "BACKGROUND: Papaverine hydrochloride is a direct-acting vasodilator used to manage vasospasm during various neurosurgical operations. Transient cranial nerve dysfunction has been described in a few cases with topical papaverine. This study supports previous reports and provides neurophysiological evidence of an adverse effect on the auditory nerve. METHODS: We conducted a retrospective review of 70 consecutive microvascular decompression operations and studied those patients who received topical papaverine for vasospasm. Topical papaverine was used as a direct therapeutic action to manage vasospasm in a total of 11 patients. The timing of papaverine application and ongoing operative events was reviewed relative to changes in neurophysiological recordings. Brainstem auditory evoked potentials (BAEPs) were routinely used to monitor cochlear nerve function during these operations. FINDINGS: A temporal relationship was found between topical papaverine and BAEP changes leading to complete waveform loss. The average temporal delay between papaverine and the onset of an adverse BAEP change was 5 min. In 10 of 11 patients, BAEP waves II/III-V completely disappeared within 2 to 25 min after papaverine. Eight of these 10 patients had complete loss of BAEP waveforms within 10 min. One patient showed no recovery of later waves and a delayed profound sensorineural hearing loss. The average recovery time of BAEP waveforms to pre-papaverine baseline values was 39 min. CONCLUSIONS: Topical papaverine for the treatment of vasospasm was associated with the onset of a transient disturbance in neurophysiological function of the ascending auditory brainstem pathway. The complete disappearance of BAEP waveforms with a consistent temporal delay suggests a possible adverse effect on the proximal eighth nerve. Recommendations to avoid potential cranial nerve deficits from papaverine are provided.", "entity": "Cranial Nerve Diseases", "aliases": "Cranial Nerve Disease Diseases Disorder Disorders Palsies Palsy Neuropathies Multiple Neuropathy Nervus Cranialis", "definition": "Disorders of one or more of the twelve cranial nerves. With the exception of the optic and olfactory nerves, this includes disorders of the brain stem nuclei from which the cranial nerves originate or terminate.\n    ", "id": "MESH:D003389"}
{"mention": "proteinuria", "mention_text": "Massive proteinuria and acute renal failure after oral bisphosphonate (alendronate) administration in a patient with focal segmental glomerulosclerosis.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "acute renal failure", "mention_text": "Massive proteinuria and acute renal failure after oral bisphosphonate (alendronate) administration in a patient with focal segmental glomerulosclerosis.", "entity": "Acute Kidney Injury", "aliases": "Acute Kidney Failure Failures Injuries Injury Insufficiencies Insufficiency Renal", "definition": "Abrupt reduction in kidney function. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions.\n    ", "id": "MESH:D058186"}
{"mention": "bisphosphonate", "mention_text": "Massive proteinuria and acute renal failure after oral bisphosphonate (alendronate) administration in a patient with focal segmental glomerulosclerosis.", "entity": "Diphosphonates", "aliases": "Bisphosphonates Diphosphonates", "definition": "Organic compounds which contain P-C-P bonds, where P stands for phosphonates or phosphonic acids. These compounds affect calcium metabolism. They inhibit ectopic calcification and slow down bone resorption and bone turnover. Technetium complexes of diphosphonates have been used successfully as bone scanning agents.\n    ", "id": "MESH:D004164"}
{"mention": "alendronate", "mention_text": "Massive proteinuria and acute renal failure after oral bisphosphonate (alendronate) administration in a patient with focal segmental glomerulosclerosis.", "entity": "Alendronate", "aliases": "4 Amino 1 Hydroxybutylidene 1,1 Biphosphonate 4-Amino-1-Hydroxybutylidene 1,1-Biphosphonate Alendronate Monosodium Salt Trihydrate Sodium Aminohydroxybutane Bisphosphonate Fosamax MK 217 MK-217 MK217", "definition": "A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis.\n    ", "id": "MESH:D019386"}
{"mention": "focal segmental glomerulosclerosis", "mention_text": "Massive proteinuria and acute renal failure after oral bisphosphonate (alendronate) administration in a patient with focal segmental glomerulosclerosis.", "entity": "Glomerulosclerosis, Focal Segmental", "aliases": "Focal Glomerulosclerosis Sclerosing Glomerulonephritides Glomerulonephritis Segmental Glomerular Hyalinosis", "definition": "A clinicopathological syndrome or diagnostic term for a type of glomerular injury that has multiple causes, primary or secondary. Clinical features include PROTEINURIA, reduced GLOMERULAR FILTRATION RATE, and EDEMA. Kidney biopsy initially indicates focal segmental glomerular consolidation (hyalinosis) or scarring which can progress to globally sclerotic glomeruli leading to eventual KIDNEY FAILURE.\n    ", "id": "MESH:D005923"}
{"mention": "nephrotic syndrome", "mention_text": "A 61-year-old Japanese man with nephrotic syndrome due to focal segmental glomerulosclerosis was initially responding well to steroid therapy. The amount of daily urinary protein decreased from 15.6 to 2.8 g. Within 14 days of the oral bisphosphonate (alendronate sodium) administration, the amount of daily urinary protein increased rapidly up to 12.8 g with acute renal failure. After discontinuing the oral alendronate, the patient underwent six cycles of hemodialysis and four cycles of LDL apheresis. Urinary volume and serum creatinine levels recovered to the normal range, with urinary protein disappearing completely within 40 days. This report demonstrates that not only intravenous, but also oral bisphosphonates can aggravate proteinuria and acute renal failure.", "entity": "Nephrotic Syndrome", "aliases": "Nephrotic Syndrome Syndromes", "definition": "A condition characterized by severe PROTEINURIA, greater than 3.5 g/day in an average adult. The substantial loss of protein in the urine results in complications such as HYPOPROTEINEMIA; generalized EDEMA; HYPERTENSION; and HYPERLIPIDEMIAS. Diseases associated with nephrotic syndrome generally cause chronic kidney dysfunction.\n    ", "id": "MESH:D009404"}
{"mention": "focal segmental glomerulosclerosis", "mention_text": "A 61-year-old Japanese man with nephrotic syndrome due to focal segmental glomerulosclerosis was initially responding well to steroid therapy. The amount of daily urinary protein decreased from 15.6 to 2.8 g. Within 14 days of the oral bisphosphonate (alendronate sodium) administration, the amount of daily urinary protein increased rapidly up to 12.8 g with acute renal failure. After discontinuing the oral alendronate, the patient underwent six cycles of hemodialysis and four cycles of LDL apheresis. Urinary volume and serum creatinine levels recovered to the normal range, with urinary protein disappearing completely within 40 days. This report demonstrates that not only intravenous, but also oral bisphosphonates can aggravate proteinuria and acute renal failure.", "entity": "Glomerulosclerosis, Focal Segmental", "aliases": "Focal Glomerulosclerosis Sclerosing Glomerulonephritides Glomerulonephritis Segmental Glomerular Hyalinosis", "definition": "A clinicopathological syndrome or diagnostic term for a type of glomerular injury that has multiple causes, primary or secondary. Clinical features include PROTEINURIA, reduced GLOMERULAR FILTRATION RATE, and EDEMA. Kidney biopsy initially indicates focal segmental glomerular consolidation (hyalinosis) or scarring which can progress to globally sclerotic glomeruli leading to eventual KIDNEY FAILURE.\n    ", "id": "MESH:D005923"}
{"mention": "steroid", "mention_text": "A 61-year-old Japanese man with nephrotic syndrome due to focal segmental glomerulosclerosis was initially responding well to steroid therapy. The amount of daily urinary protein decreased from 15.6 to 2.8 g. Within 14 days of the oral bisphosphonate (alendronate sodium) administration, the amount of daily urinary protein increased rapidly up to 12.8 g with acute renal failure. After discontinuing the oral alendronate, the patient underwent six cycles of hemodialysis and four cycles of LDL apheresis. Urinary volume and serum creatinine levels recovered to the normal range, with urinary protein disappearing completely within 40 days. This report demonstrates that not only intravenous, but also oral bisphosphonates can aggravate proteinuria and acute renal failure.", "entity": "Steroids", "aliases": "Catatoxic Steroids", "definition": "A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)\n    ", "id": "MESH:D013256"}
{"mention": "bisphosphonate", "mention_text": "A 61-year-old Japanese man with nephrotic syndrome due to focal segmental glomerulosclerosis was initially responding well to steroid therapy. The amount of daily urinary protein decreased from 15.6 to 2.8 g. Within 14 days of the oral bisphosphonate (alendronate sodium) administration, the amount of daily urinary protein increased rapidly up to 12.8 g with acute renal failure. After discontinuing the oral alendronate, the patient underwent six cycles of hemodialysis and four cycles of LDL apheresis. Urinary volume and serum creatinine levels recovered to the normal range, with urinary protein disappearing completely within 40 days. This report demonstrates that not only intravenous, but also oral bisphosphonates can aggravate proteinuria and acute renal failure.", "entity": "Diphosphonates", "aliases": "Bisphosphonates Diphosphonates", "definition": "Organic compounds which contain P-C-P bonds, where P stands for phosphonates or phosphonic acids. These compounds affect calcium metabolism. They inhibit ectopic calcification and slow down bone resorption and bone turnover. Technetium complexes of diphosphonates have been used successfully as bone scanning agents.\n    ", "id": "MESH:D004164"}
{"mention": "alendronate sodium", "mention_text": "A 61-year-old Japanese man with nephrotic syndrome due to focal segmental glomerulosclerosis was initially responding well to steroid therapy. The amount of daily urinary protein decreased from 15.6 to 2.8 g. Within 14 days of the oral bisphosphonate (alendronate sodium) administration, the amount of daily urinary protein increased rapidly up to 12.8 g with acute renal failure. After discontinuing the oral alendronate, the patient underwent six cycles of hemodialysis and four cycles of LDL apheresis. Urinary volume and serum creatinine levels recovered to the normal range, with urinary protein disappearing completely within 40 days. This report demonstrates that not only intravenous, but also oral bisphosphonates can aggravate proteinuria and acute renal failure.", "entity": "Alendronate", "aliases": "4 Amino 1 Hydroxybutylidene 1,1 Biphosphonate 4-Amino-1-Hydroxybutylidene 1,1-Biphosphonate Alendronate Monosodium Salt Trihydrate Sodium Aminohydroxybutane Bisphosphonate Fosamax MK 217 MK-217 MK217", "definition": "A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis.\n    ", "id": "MESH:D019386"}
{"mention": "acute renal failure", "mention_text": "A 61-year-old Japanese man with nephrotic syndrome due to focal segmental glomerulosclerosis was initially responding well to steroid therapy. The amount of daily urinary protein decreased from 15.6 to 2.8 g. Within 14 days of the oral bisphosphonate (alendronate sodium) administration, the amount of daily urinary protein increased rapidly up to 12.8 g with acute renal failure. After discontinuing the oral alendronate, the patient underwent six cycles of hemodialysis and four cycles of LDL apheresis. Urinary volume and serum creatinine levels recovered to the normal range, with urinary protein disappearing completely within 40 days. This report demonstrates that not only intravenous, but also oral bisphosphonates can aggravate proteinuria and acute renal failure.", "entity": "Acute Kidney Injury", "aliases": "Acute Kidney Failure Failures Injuries Injury Insufficiencies Insufficiency Renal", "definition": "Abrupt reduction in kidney function. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions.\n    ", "id": "MESH:D058186"}
{"mention": "alendronate", "mention_text": "A 61-year-old Japanese man with nephrotic syndrome due to focal segmental glomerulosclerosis was initially responding well to steroid therapy. The amount of daily urinary protein decreased from 15.6 to 2.8 g. Within 14 days of the oral bisphosphonate (alendronate sodium) administration, the amount of daily urinary protein increased rapidly up to 12.8 g with acute renal failure. After discontinuing the oral alendronate, the patient underwent six cycles of hemodialysis and four cycles of LDL apheresis. Urinary volume and serum creatinine levels recovered to the normal range, with urinary protein disappearing completely within 40 days. This report demonstrates that not only intravenous, but also oral bisphosphonates can aggravate proteinuria and acute renal failure.", "entity": "Alendronate", "aliases": "4 Amino 1 Hydroxybutylidene 1,1 Biphosphonate 4-Amino-1-Hydroxybutylidene 1,1-Biphosphonate Alendronate Monosodium Salt Trihydrate Sodium Aminohydroxybutane Bisphosphonate Fosamax MK 217 MK-217 MK217", "definition": "A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis.\n    ", "id": "MESH:D019386"}
{"mention": "creatinine", "mention_text": "A 61-year-old Japanese man with nephrotic syndrome due to focal segmental glomerulosclerosis was initially responding well to steroid therapy. The amount of daily urinary protein decreased from 15.6 to 2.8 g. Within 14 days of the oral bisphosphonate (alendronate sodium) administration, the amount of daily urinary protein increased rapidly up to 12.8 g with acute renal failure. After discontinuing the oral alendronate, the patient underwent six cycles of hemodialysis and four cycles of LDL apheresis. Urinary volume and serum creatinine levels recovered to the normal range, with urinary protein disappearing completely within 40 days. This report demonstrates that not only intravenous, but also oral bisphosphonates can aggravate proteinuria and acute renal failure.", "entity": "Creatinine", "aliases": "Creatinine Sulfate Salt Krebiozen", "definition": "", "id": "MESH:D003404"}
{"mention": "bisphosphonates", "mention_text": "A 61-year-old Japanese man with nephrotic syndrome due to focal segmental glomerulosclerosis was initially responding well to steroid therapy. The amount of daily urinary protein decreased from 15.6 to 2.8 g. Within 14 days of the oral bisphosphonate (alendronate sodium) administration, the amount of daily urinary protein increased rapidly up to 12.8 g with acute renal failure. After discontinuing the oral alendronate, the patient underwent six cycles of hemodialysis and four cycles of LDL apheresis. Urinary volume and serum creatinine levels recovered to the normal range, with urinary protein disappearing completely within 40 days. This report demonstrates that not only intravenous, but also oral bisphosphonates can aggravate proteinuria and acute renal failure.", "entity": "Diphosphonates", "aliases": "Bisphosphonates Diphosphonates", "definition": "Organic compounds which contain P-C-P bonds, where P stands for phosphonates or phosphonic acids. These compounds affect calcium metabolism. They inhibit ectopic calcification and slow down bone resorption and bone turnover. Technetium complexes of diphosphonates have been used successfully as bone scanning agents.\n    ", "id": "MESH:D004164"}
{"mention": "proteinuria", "mention_text": "A 61-year-old Japanese man with nephrotic syndrome due to focal segmental glomerulosclerosis was initially responding well to steroid therapy. The amount of daily urinary protein decreased from 15.6 to 2.8 g. Within 14 days of the oral bisphosphonate (alendronate sodium) administration, the amount of daily urinary protein increased rapidly up to 12.8 g with acute renal failure. After discontinuing the oral alendronate, the patient underwent six cycles of hemodialysis and four cycles of LDL apheresis. Urinary volume and serum creatinine levels recovered to the normal range, with urinary protein disappearing completely within 40 days. This report demonstrates that not only intravenous, but also oral bisphosphonates can aggravate proteinuria and acute renal failure.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "doxorubicin", "mention_text": "Serum- and glucocorticoid-inducible kinase 1 in doxorubicin-induced nephrotic syndrome.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "nephrotic syndrome", "mention_text": "Serum- and glucocorticoid-inducible kinase 1 in doxorubicin-induced nephrotic syndrome.", "entity": "Nephrotic Syndrome", "aliases": "Nephrotic Syndrome Syndromes", "definition": "A condition characterized by severe PROTEINURIA, greater than 3.5 g/day in an average adult. The substantial loss of protein in the urine results in complications such as HYPOPROTEINEMIA; generalized EDEMA; HYPERTENSION; and HYPERLIPIDEMIAS. Diseases associated with nephrotic syndrome generally cause chronic kidney dysfunction.\n    ", "id": "MESH:D009404"}
{"mention": "Doxorubicin", "mention_text": "Doxorubicin-induced nephropathy leads to epithelial sodium channel (ENaC)-dependent volume retention and renal fibrosis. The aldosterone-sensitive serum- and glucocorticoid-inducible kinase SGK1 has been shown to participate in the stimulation of ENaC and to mediate renal fibrosis following mineralocorticoid and salt excess. The present study was performed to elucidate the role of SGK1 in the volume retention and fibrosis during nephrotic syndrome. To this end, doxorubicin (15 mug/g body wt) was injected intravenously into gene-targeted mice lacking SGK1 (sgk1(-/-)) and their wild-type littermates (sgk1(+/+)). Doxorubicin treatment resulted in heavy proteinuria (>100 mg protein/mg crea) in 15/44 of sgk1(+/+) and 15/44 of sgk1(-/-) mice leading to severe nephrotic syndrome with ascites, lipidemia, and hypoalbuminemia in both genotypes. Plasma aldosterone levels increased in nephrotic mice of both genotypes and was followed by increased SGK1 protein expression in sgk1(+/+) mice. Urinary sodium excretion reached signficantly lower values in sgk1(+/+) mice (15 +/- 5 mumol/mg crea) than in sgk1(-/-) mice (35 +/- 5 mumol/mg crea) and was associated with a significantly higher body weight gain in sgk1(+/+) compared with sgk1(-/-) mice (+6.6 +/- 0.7 vs. +4.1 +/- 0.8 g). During the course of nephrotic syndrome, serum urea concentrations increased significantly faster in sgk1(-/-) mice than in sgk1(+/+) mice leading to uremia and a reduced median survival in sgk1(-/-) mice (29 vs. 40 days in sgk1(+/+) mice). In conclusion, gene-targeted mice lacking SGK1 showed blunted volume retention, yet were not protected against renal fibrosis during experimental nephrotic syndrome.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "nephropathy", "mention_text": "Doxorubicin-induced nephropathy leads to epithelial sodium channel (ENaC)-dependent volume retention and renal fibrosis. The aldosterone-sensitive serum- and glucocorticoid-inducible kinase SGK1 has been shown to participate in the stimulation of ENaC and to mediate renal fibrosis following mineralocorticoid and salt excess. The present study was performed to elucidate the role of SGK1 in the volume retention and fibrosis during nephrotic syndrome. To this end, doxorubicin (15 mug/g body wt) was injected intravenously into gene-targeted mice lacking SGK1 (sgk1(-/-)) and their wild-type littermates (sgk1(+/+)). Doxorubicin treatment resulted in heavy proteinuria (>100 mg protein/mg crea) in 15/44 of sgk1(+/+) and 15/44 of sgk1(-/-) mice leading to severe nephrotic syndrome with ascites, lipidemia, and hypoalbuminemia in both genotypes. Plasma aldosterone levels increased in nephrotic mice of both genotypes and was followed by increased SGK1 protein expression in sgk1(+/+) mice. Urinary sodium excretion reached signficantly lower values in sgk1(+/+) mice (15 +/- 5 mumol/mg crea) than in sgk1(-/-) mice (35 +/- 5 mumol/mg crea) and was associated with a significantly higher body weight gain in sgk1(+/+) compared with sgk1(-/-) mice (+6.6 +/- 0.7 vs. +4.1 +/- 0.8 g). During the course of nephrotic syndrome, serum urea concentrations increased significantly faster in sgk1(-/-) mice than in sgk1(+/+) mice leading to uremia and a reduced median survival in sgk1(-/-) mice (29 vs. 40 days in sgk1(+/+) mice). In conclusion, gene-targeted mice lacking SGK1 showed blunted volume retention, yet were not protected against renal fibrosis during experimental nephrotic syndrome.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "sodium", "mention_text": "Doxorubicin-induced nephropathy leads to epithelial sodium channel (ENaC)-dependent volume retention and renal fibrosis. The aldosterone-sensitive serum- and glucocorticoid-inducible kinase SGK1 has been shown to participate in the stimulation of ENaC and to mediate renal fibrosis following mineralocorticoid and salt excess. The present study was performed to elucidate the role of SGK1 in the volume retention and fibrosis during nephrotic syndrome. To this end, doxorubicin (15 mug/g body wt) was injected intravenously into gene-targeted mice lacking SGK1 (sgk1(-/-)) and their wild-type littermates (sgk1(+/+)). Doxorubicin treatment resulted in heavy proteinuria (>100 mg protein/mg crea) in 15/44 of sgk1(+/+) and 15/44 of sgk1(-/-) mice leading to severe nephrotic syndrome with ascites, lipidemia, and hypoalbuminemia in both genotypes. Plasma aldosterone levels increased in nephrotic mice of both genotypes and was followed by increased SGK1 protein expression in sgk1(+/+) mice. Urinary sodium excretion reached signficantly lower values in sgk1(+/+) mice (15 +/- 5 mumol/mg crea) than in sgk1(-/-) mice (35 +/- 5 mumol/mg crea) and was associated with a significantly higher body weight gain in sgk1(+/+) compared with sgk1(-/-) mice (+6.6 +/- 0.7 vs. +4.1 +/- 0.8 g). During the course of nephrotic syndrome, serum urea concentrations increased significantly faster in sgk1(-/-) mice than in sgk1(+/+) mice leading to uremia and a reduced median survival in sgk1(-/-) mice (29 vs. 40 days in sgk1(+/+) mice). In conclusion, gene-targeted mice lacking SGK1 showed blunted volume retention, yet were not protected against renal fibrosis during experimental nephrotic syndrome.", "entity": "Sodium", "aliases": "Ion Level Sodium", "definition": "A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.\n    ", "id": "MESH:D012964"}
{"mention": "volume retention", "mention_text": "Doxorubicin-induced nephropathy leads to epithelial sodium channel (ENaC)-dependent volume retention and renal fibrosis. The aldosterone-sensitive serum- and glucocorticoid-inducible kinase SGK1 has been shown to participate in the stimulation of ENaC and to mediate renal fibrosis following mineralocorticoid and salt excess. The present study was performed to elucidate the role of SGK1 in the volume retention and fibrosis during nephrotic syndrome. To this end, doxorubicin (15 mug/g body wt) was injected intravenously into gene-targeted mice lacking SGK1 (sgk1(-/-)) and their wild-type littermates (sgk1(+/+)). Doxorubicin treatment resulted in heavy proteinuria (>100 mg protein/mg crea) in 15/44 of sgk1(+/+) and 15/44 of sgk1(-/-) mice leading to severe nephrotic syndrome with ascites, lipidemia, and hypoalbuminemia in both genotypes. Plasma aldosterone levels increased in nephrotic mice of both genotypes and was followed by increased SGK1 protein expression in sgk1(+/+) mice. Urinary sodium excretion reached signficantly lower values in sgk1(+/+) mice (15 +/- 5 mumol/mg crea) than in sgk1(-/-) mice (35 +/- 5 mumol/mg crea) and was associated with a significantly higher body weight gain in sgk1(+/+) compared with sgk1(-/-) mice (+6.6 +/- 0.7 vs. +4.1 +/- 0.8 g). During the course of nephrotic syndrome, serum urea concentrations increased significantly faster in sgk1(-/-) mice than in sgk1(+/+) mice leading to uremia and a reduced median survival in sgk1(-/-) mice (29 vs. 40 days in sgk1(+/+) mice). In conclusion, gene-targeted mice lacking SGK1 showed blunted volume retention, yet were not protected against renal fibrosis during experimental nephrotic syndrome.", "entity": "Urinary Retention", "aliases": "Retention Urinary", "definition": "Inability to empty the URINARY BLADDER with voiding (URINATION).\n    ", "id": "MESH:D016055"}
{"mention": "fibrosis", "mention_text": "Doxorubicin-induced nephropathy leads to epithelial sodium channel (ENaC)-dependent volume retention and renal fibrosis. The aldosterone-sensitive serum- and glucocorticoid-inducible kinase SGK1 has been shown to participate in the stimulation of ENaC and to mediate renal fibrosis following mineralocorticoid and salt excess. The present study was performed to elucidate the role of SGK1 in the volume retention and fibrosis during nephrotic syndrome. To this end, doxorubicin (15 mug/g body wt) was injected intravenously into gene-targeted mice lacking SGK1 (sgk1(-/-)) and their wild-type littermates (sgk1(+/+)). Doxorubicin treatment resulted in heavy proteinuria (>100 mg protein/mg crea) in 15/44 of sgk1(+/+) and 15/44 of sgk1(-/-) mice leading to severe nephrotic syndrome with ascites, lipidemia, and hypoalbuminemia in both genotypes. Plasma aldosterone levels increased in nephrotic mice of both genotypes and was followed by increased SGK1 protein expression in sgk1(+/+) mice. Urinary sodium excretion reached signficantly lower values in sgk1(+/+) mice (15 +/- 5 mumol/mg crea) than in sgk1(-/-) mice (35 +/- 5 mumol/mg crea) and was associated with a significantly higher body weight gain in sgk1(+/+) compared with sgk1(-/-) mice (+6.6 +/- 0.7 vs. +4.1 +/- 0.8 g). During the course of nephrotic syndrome, serum urea concentrations increased significantly faster in sgk1(-/-) mice than in sgk1(+/+) mice leading to uremia and a reduced median survival in sgk1(-/-) mice (29 vs. 40 days in sgk1(+/+) mice). In conclusion, gene-targeted mice lacking SGK1 showed blunted volume retention, yet were not protected against renal fibrosis during experimental nephrotic syndrome.", "entity": "Fibrosis", "aliases": "Cirrhosis Fibroses Fibrosis", "definition": "Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.\n    ", "id": "MESH:D005355"}
{"mention": "aldosterone", "mention_text": "Doxorubicin-induced nephropathy leads to epithelial sodium channel (ENaC)-dependent volume retention and renal fibrosis. The aldosterone-sensitive serum- and glucocorticoid-inducible kinase SGK1 has been shown to participate in the stimulation of ENaC and to mediate renal fibrosis following mineralocorticoid and salt excess. The present study was performed to elucidate the role of SGK1 in the volume retention and fibrosis during nephrotic syndrome. To this end, doxorubicin (15 mug/g body wt) was injected intravenously into gene-targeted mice lacking SGK1 (sgk1(-/-)) and their wild-type littermates (sgk1(+/+)). Doxorubicin treatment resulted in heavy proteinuria (>100 mg protein/mg crea) in 15/44 of sgk1(+/+) and 15/44 of sgk1(-/-) mice leading to severe nephrotic syndrome with ascites, lipidemia, and hypoalbuminemia in both genotypes. Plasma aldosterone levels increased in nephrotic mice of both genotypes and was followed by increased SGK1 protein expression in sgk1(+/+) mice. Urinary sodium excretion reached signficantly lower values in sgk1(+/+) mice (15 +/- 5 mumol/mg crea) than in sgk1(-/-) mice (35 +/- 5 mumol/mg crea) and was associated with a significantly higher body weight gain in sgk1(+/+) compared with sgk1(-/-) mice (+6.6 +/- 0.7 vs. +4.1 +/- 0.8 g). During the course of nephrotic syndrome, serum urea concentrations increased significantly faster in sgk1(-/-) mice than in sgk1(+/+) mice leading to uremia and a reduced median survival in sgk1(-/-) mice (29 vs. 40 days in sgk1(+/+) mice). In conclusion, gene-targeted mice lacking SGK1 showed blunted volume retention, yet were not protected against renal fibrosis during experimental nephrotic syndrome.", "entity": "Aldosterone", "aliases": "Aldosterone (+-)-Isomer (11 beta,17 alpha)-Isomer", "definition": "A hormone secreted by the ADRENAL CORTEX that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium.\n    ", "id": "MESH:D000450"}
{"mention": "nephrotic syndrome", "mention_text": "Doxorubicin-induced nephropathy leads to epithelial sodium channel (ENaC)-dependent volume retention and renal fibrosis. The aldosterone-sensitive serum- and glucocorticoid-inducible kinase SGK1 has been shown to participate in the stimulation of ENaC and to mediate renal fibrosis following mineralocorticoid and salt excess. The present study was performed to elucidate the role of SGK1 in the volume retention and fibrosis during nephrotic syndrome. To this end, doxorubicin (15 mug/g body wt) was injected intravenously into gene-targeted mice lacking SGK1 (sgk1(-/-)) and their wild-type littermates (sgk1(+/+)). Doxorubicin treatment resulted in heavy proteinuria (>100 mg protein/mg crea) in 15/44 of sgk1(+/+) and 15/44 of sgk1(-/-) mice leading to severe nephrotic syndrome with ascites, lipidemia, and hypoalbuminemia in both genotypes. Plasma aldosterone levels increased in nephrotic mice of both genotypes and was followed by increased SGK1 protein expression in sgk1(+/+) mice. Urinary sodium excretion reached signficantly lower values in sgk1(+/+) mice (15 +/- 5 mumol/mg crea) than in sgk1(-/-) mice (35 +/- 5 mumol/mg crea) and was associated with a significantly higher body weight gain in sgk1(+/+) compared with sgk1(-/-) mice (+6.6 +/- 0.7 vs. +4.1 +/- 0.8 g). During the course of nephrotic syndrome, serum urea concentrations increased significantly faster in sgk1(-/-) mice than in sgk1(+/+) mice leading to uremia and a reduced median survival in sgk1(-/-) mice (29 vs. 40 days in sgk1(+/+) mice). In conclusion, gene-targeted mice lacking SGK1 showed blunted volume retention, yet were not protected against renal fibrosis during experimental nephrotic syndrome.", "entity": "Nephrotic Syndrome", "aliases": "Nephrotic Syndrome Syndromes", "definition": "A condition characterized by severe PROTEINURIA, greater than 3.5 g/day in an average adult. The substantial loss of protein in the urine results in complications such as HYPOPROTEINEMIA; generalized EDEMA; HYPERTENSION; and HYPERLIPIDEMIAS. Diseases associated with nephrotic syndrome generally cause chronic kidney dysfunction.\n    ", "id": "MESH:D009404"}
{"mention": "doxorubicin", "mention_text": "Doxorubicin-induced nephropathy leads to epithelial sodium channel (ENaC)-dependent volume retention and renal fibrosis. The aldosterone-sensitive serum- and glucocorticoid-inducible kinase SGK1 has been shown to participate in the stimulation of ENaC and to mediate renal fibrosis following mineralocorticoid and salt excess. The present study was performed to elucidate the role of SGK1 in the volume retention and fibrosis during nephrotic syndrome. To this end, doxorubicin (15 mug/g body wt) was injected intravenously into gene-targeted mice lacking SGK1 (sgk1(-/-)) and their wild-type littermates (sgk1(+/+)). Doxorubicin treatment resulted in heavy proteinuria (>100 mg protein/mg crea) in 15/44 of sgk1(+/+) and 15/44 of sgk1(-/-) mice leading to severe nephrotic syndrome with ascites, lipidemia, and hypoalbuminemia in both genotypes. Plasma aldosterone levels increased in nephrotic mice of both genotypes and was followed by increased SGK1 protein expression in sgk1(+/+) mice. Urinary sodium excretion reached signficantly lower values in sgk1(+/+) mice (15 +/- 5 mumol/mg crea) than in sgk1(-/-) mice (35 +/- 5 mumol/mg crea) and was associated with a significantly higher body weight gain in sgk1(+/+) compared with sgk1(-/-) mice (+6.6 +/- 0.7 vs. +4.1 +/- 0.8 g). During the course of nephrotic syndrome, serum urea concentrations increased significantly faster in sgk1(-/-) mice than in sgk1(+/+) mice leading to uremia and a reduced median survival in sgk1(-/-) mice (29 vs. 40 days in sgk1(+/+) mice). In conclusion, gene-targeted mice lacking SGK1 showed blunted volume retention, yet were not protected against renal fibrosis during experimental nephrotic syndrome.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "proteinuria", "mention_text": "Doxorubicin-induced nephropathy leads to epithelial sodium channel (ENaC)-dependent volume retention and renal fibrosis. The aldosterone-sensitive serum- and glucocorticoid-inducible kinase SGK1 has been shown to participate in the stimulation of ENaC and to mediate renal fibrosis following mineralocorticoid and salt excess. The present study was performed to elucidate the role of SGK1 in the volume retention and fibrosis during nephrotic syndrome. To this end, doxorubicin (15 mug/g body wt) was injected intravenously into gene-targeted mice lacking SGK1 (sgk1(-/-)) and their wild-type littermates (sgk1(+/+)). Doxorubicin treatment resulted in heavy proteinuria (>100 mg protein/mg crea) in 15/44 of sgk1(+/+) and 15/44 of sgk1(-/-) mice leading to severe nephrotic syndrome with ascites, lipidemia, and hypoalbuminemia in both genotypes. Plasma aldosterone levels increased in nephrotic mice of both genotypes and was followed by increased SGK1 protein expression in sgk1(+/+) mice. Urinary sodium excretion reached signficantly lower values in sgk1(+/+) mice (15 +/- 5 mumol/mg crea) than in sgk1(-/-) mice (35 +/- 5 mumol/mg crea) and was associated with a significantly higher body weight gain in sgk1(+/+) compared with sgk1(-/-) mice (+6.6 +/- 0.7 vs. +4.1 +/- 0.8 g). During the course of nephrotic syndrome, serum urea concentrations increased significantly faster in sgk1(-/-) mice than in sgk1(+/+) mice leading to uremia and a reduced median survival in sgk1(-/-) mice (29 vs. 40 days in sgk1(+/+) mice). In conclusion, gene-targeted mice lacking SGK1 showed blunted volume retention, yet were not protected against renal fibrosis during experimental nephrotic syndrome.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "ascites", "mention_text": "Doxorubicin-induced nephropathy leads to epithelial sodium channel (ENaC)-dependent volume retention and renal fibrosis. The aldosterone-sensitive serum- and glucocorticoid-inducible kinase SGK1 has been shown to participate in the stimulation of ENaC and to mediate renal fibrosis following mineralocorticoid and salt excess. The present study was performed to elucidate the role of SGK1 in the volume retention and fibrosis during nephrotic syndrome. To this end, doxorubicin (15 mug/g body wt) was injected intravenously into gene-targeted mice lacking SGK1 (sgk1(-/-)) and their wild-type littermates (sgk1(+/+)). Doxorubicin treatment resulted in heavy proteinuria (>100 mg protein/mg crea) in 15/44 of sgk1(+/+) and 15/44 of sgk1(-/-) mice leading to severe nephrotic syndrome with ascites, lipidemia, and hypoalbuminemia in both genotypes. Plasma aldosterone levels increased in nephrotic mice of both genotypes and was followed by increased SGK1 protein expression in sgk1(+/+) mice. Urinary sodium excretion reached signficantly lower values in sgk1(+/+) mice (15 +/- 5 mumol/mg crea) than in sgk1(-/-) mice (35 +/- 5 mumol/mg crea) and was associated with a significantly higher body weight gain in sgk1(+/+) compared with sgk1(-/-) mice (+6.6 +/- 0.7 vs. +4.1 +/- 0.8 g). During the course of nephrotic syndrome, serum urea concentrations increased significantly faster in sgk1(-/-) mice than in sgk1(+/+) mice leading to uremia and a reduced median survival in sgk1(-/-) mice (29 vs. 40 days in sgk1(+/+) mice). In conclusion, gene-targeted mice lacking SGK1 showed blunted volume retention, yet were not protected against renal fibrosis during experimental nephrotic syndrome.", "entity": "Ascites", "aliases": "Ascites", "definition": "Accumulation or retention of free fluid within the peritoneal cavity.\n    ", "id": "MESH:D001201"}
{"mention": "lipidemia", "mention_text": "Doxorubicin-induced nephropathy leads to epithelial sodium channel (ENaC)-dependent volume retention and renal fibrosis. The aldosterone-sensitive serum- and glucocorticoid-inducible kinase SGK1 has been shown to participate in the stimulation of ENaC and to mediate renal fibrosis following mineralocorticoid and salt excess. The present study was performed to elucidate the role of SGK1 in the volume retention and fibrosis during nephrotic syndrome. To this end, doxorubicin (15 mug/g body wt) was injected intravenously into gene-targeted mice lacking SGK1 (sgk1(-/-)) and their wild-type littermates (sgk1(+/+)). Doxorubicin treatment resulted in heavy proteinuria (>100 mg protein/mg crea) in 15/44 of sgk1(+/+) and 15/44 of sgk1(-/-) mice leading to severe nephrotic syndrome with ascites, lipidemia, and hypoalbuminemia in both genotypes. Plasma aldosterone levels increased in nephrotic mice of both genotypes and was followed by increased SGK1 protein expression in sgk1(+/+) mice. Urinary sodium excretion reached signficantly lower values in sgk1(+/+) mice (15 +/- 5 mumol/mg crea) than in sgk1(-/-) mice (35 +/- 5 mumol/mg crea) and was associated with a significantly higher body weight gain in sgk1(+/+) compared with sgk1(-/-) mice (+6.6 +/- 0.7 vs. +4.1 +/- 0.8 g). During the course of nephrotic syndrome, serum urea concentrations increased significantly faster in sgk1(-/-) mice than in sgk1(+/+) mice leading to uremia and a reduced median survival in sgk1(-/-) mice (29 vs. 40 days in sgk1(+/+) mice). In conclusion, gene-targeted mice lacking SGK1 showed blunted volume retention, yet were not protected against renal fibrosis during experimental nephrotic syndrome.", "entity": "Hyperlipidemias", "aliases": "Hyperlipemia Hyperlipemias Hyperlipidemia Hyperlipidemias Lipemia Lipemias Lipidemia Lipidemias", "definition": "Conditions with excess LIPIDS in the blood.\n    ", "id": "MESH:D006949"}
{"mention": "hypoalbuminemia", "mention_text": "Doxorubicin-induced nephropathy leads to epithelial sodium channel (ENaC)-dependent volume retention and renal fibrosis. The aldosterone-sensitive serum- and glucocorticoid-inducible kinase SGK1 has been shown to participate in the stimulation of ENaC and to mediate renal fibrosis following mineralocorticoid and salt excess. The present study was performed to elucidate the role of SGK1 in the volume retention and fibrosis during nephrotic syndrome. To this end, doxorubicin (15 mug/g body wt) was injected intravenously into gene-targeted mice lacking SGK1 (sgk1(-/-)) and their wild-type littermates (sgk1(+/+)). Doxorubicin treatment resulted in heavy proteinuria (>100 mg protein/mg crea) in 15/44 of sgk1(+/+) and 15/44 of sgk1(-/-) mice leading to severe nephrotic syndrome with ascites, lipidemia, and hypoalbuminemia in both genotypes. Plasma aldosterone levels increased in nephrotic mice of both genotypes and was followed by increased SGK1 protein expression in sgk1(+/+) mice. Urinary sodium excretion reached signficantly lower values in sgk1(+/+) mice (15 +/- 5 mumol/mg crea) than in sgk1(-/-) mice (35 +/- 5 mumol/mg crea) and was associated with a significantly higher body weight gain in sgk1(+/+) compared with sgk1(-/-) mice (+6.6 +/- 0.7 vs. +4.1 +/- 0.8 g). During the course of nephrotic syndrome, serum urea concentrations increased significantly faster in sgk1(-/-) mice than in sgk1(+/+) mice leading to uremia and a reduced median survival in sgk1(-/-) mice (29 vs. 40 days in sgk1(+/+) mice). In conclusion, gene-targeted mice lacking SGK1 showed blunted volume retention, yet were not protected against renal fibrosis during experimental nephrotic syndrome.", "entity": "Hypoalbuminemia", "aliases": "Hypoalbuminemia", "definition": "A condition in which albumin level in blood (SERUM ALBUMIN) is below the normal range. Hypoalbuminemia may be due to decreased hepatic albumin synthesis, increased albumin catabolism, altered albumin distribution, or albumin loss through the urine (ALBUMINURIA).\n    ", "id": "MESH:D034141"}
{"mention": "nephrotic", "mention_text": "Doxorubicin-induced nephropathy leads to epithelial sodium channel (ENaC)-dependent volume retention and renal fibrosis. The aldosterone-sensitive serum- and glucocorticoid-inducible kinase SGK1 has been shown to participate in the stimulation of ENaC and to mediate renal fibrosis following mineralocorticoid and salt excess. The present study was performed to elucidate the role of SGK1 in the volume retention and fibrosis during nephrotic syndrome. To this end, doxorubicin (15 mug/g body wt) was injected intravenously into gene-targeted mice lacking SGK1 (sgk1(-/-)) and their wild-type littermates (sgk1(+/+)). Doxorubicin treatment resulted in heavy proteinuria (>100 mg protein/mg crea) in 15/44 of sgk1(+/+) and 15/44 of sgk1(-/-) mice leading to severe nephrotic syndrome with ascites, lipidemia, and hypoalbuminemia in both genotypes. Plasma aldosterone levels increased in nephrotic mice of both genotypes and was followed by increased SGK1 protein expression in sgk1(+/+) mice. Urinary sodium excretion reached signficantly lower values in sgk1(+/+) mice (15 +/- 5 mumol/mg crea) than in sgk1(-/-) mice (35 +/- 5 mumol/mg crea) and was associated with a significantly higher body weight gain in sgk1(+/+) compared with sgk1(-/-) mice (+6.6 +/- 0.7 vs. +4.1 +/- 0.8 g). During the course of nephrotic syndrome, serum urea concentrations increased significantly faster in sgk1(-/-) mice than in sgk1(+/+) mice leading to uremia and a reduced median survival in sgk1(-/-) mice (29 vs. 40 days in sgk1(+/+) mice). In conclusion, gene-targeted mice lacking SGK1 showed blunted volume retention, yet were not protected against renal fibrosis during experimental nephrotic syndrome.", "entity": "Nephrotic Syndrome", "aliases": "Nephrotic Syndrome Syndromes", "definition": "A condition characterized by severe PROTEINURIA, greater than 3.5 g/day in an average adult. The substantial loss of protein in the urine results in complications such as HYPOPROTEINEMIA; generalized EDEMA; HYPERTENSION; and HYPERLIPIDEMIAS. Diseases associated with nephrotic syndrome generally cause chronic kidney dysfunction.\n    ", "id": "MESH:D009404"}
{"mention": "weight gain", "mention_text": "Doxorubicin-induced nephropathy leads to epithelial sodium channel (ENaC)-dependent volume retention and renal fibrosis. The aldosterone-sensitive serum- and glucocorticoid-inducible kinase SGK1 has been shown to participate in the stimulation of ENaC and to mediate renal fibrosis following mineralocorticoid and salt excess. The present study was performed to elucidate the role of SGK1 in the volume retention and fibrosis during nephrotic syndrome. To this end, doxorubicin (15 mug/g body wt) was injected intravenously into gene-targeted mice lacking SGK1 (sgk1(-/-)) and their wild-type littermates (sgk1(+/+)). Doxorubicin treatment resulted in heavy proteinuria (>100 mg protein/mg crea) in 15/44 of sgk1(+/+) and 15/44 of sgk1(-/-) mice leading to severe nephrotic syndrome with ascites, lipidemia, and hypoalbuminemia in both genotypes. Plasma aldosterone levels increased in nephrotic mice of both genotypes and was followed by increased SGK1 protein expression in sgk1(+/+) mice. Urinary sodium excretion reached signficantly lower values in sgk1(+/+) mice (15 +/- 5 mumol/mg crea) than in sgk1(-/-) mice (35 +/- 5 mumol/mg crea) and was associated with a significantly higher body weight gain in sgk1(+/+) compared with sgk1(-/-) mice (+6.6 +/- 0.7 vs. +4.1 +/- 0.8 g). During the course of nephrotic syndrome, serum urea concentrations increased significantly faster in sgk1(-/-) mice than in sgk1(+/+) mice leading to uremia and a reduced median survival in sgk1(-/-) mice (29 vs. 40 days in sgk1(+/+) mice). In conclusion, gene-targeted mice lacking SGK1 showed blunted volume retention, yet were not protected against renal fibrosis during experimental nephrotic syndrome.", "entity": "Weight Gain", "aliases": "Gain Weight Gains", "definition": "Increase in BODY WEIGHT over existing weight.\n    ", "id": "MESH:D015430"}
{"mention": "urea", "mention_text": "Doxorubicin-induced nephropathy leads to epithelial sodium channel (ENaC)-dependent volume retention and renal fibrosis. The aldosterone-sensitive serum- and glucocorticoid-inducible kinase SGK1 has been shown to participate in the stimulation of ENaC and to mediate renal fibrosis following mineralocorticoid and salt excess. The present study was performed to elucidate the role of SGK1 in the volume retention and fibrosis during nephrotic syndrome. To this end, doxorubicin (15 mug/g body wt) was injected intravenously into gene-targeted mice lacking SGK1 (sgk1(-/-)) and their wild-type littermates (sgk1(+/+)). Doxorubicin treatment resulted in heavy proteinuria (>100 mg protein/mg crea) in 15/44 of sgk1(+/+) and 15/44 of sgk1(-/-) mice leading to severe nephrotic syndrome with ascites, lipidemia, and hypoalbuminemia in both genotypes. Plasma aldosterone levels increased in nephrotic mice of both genotypes and was followed by increased SGK1 protein expression in sgk1(+/+) mice. Urinary sodium excretion reached signficantly lower values in sgk1(+/+) mice (15 +/- 5 mumol/mg crea) than in sgk1(-/-) mice (35 +/- 5 mumol/mg crea) and was associated with a significantly higher body weight gain in sgk1(+/+) compared with sgk1(-/-) mice (+6.6 +/- 0.7 vs. +4.1 +/- 0.8 g). During the course of nephrotic syndrome, serum urea concentrations increased significantly faster in sgk1(-/-) mice than in sgk1(+/+) mice leading to uremia and a reduced median survival in sgk1(-/-) mice (29 vs. 40 days in sgk1(+/+) mice). In conclusion, gene-targeted mice lacking SGK1 showed blunted volume retention, yet were not protected against renal fibrosis during experimental nephrotic syndrome.", "entity": "Urea", "aliases": "Basodexan Carbamide Carmol Urea", "definition": "A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids.\n    ", "id": "MESH:D014508"}
{"mention": "uremia", "mention_text": "Doxorubicin-induced nephropathy leads to epithelial sodium channel (ENaC)-dependent volume retention and renal fibrosis. The aldosterone-sensitive serum- and glucocorticoid-inducible kinase SGK1 has been shown to participate in the stimulation of ENaC and to mediate renal fibrosis following mineralocorticoid and salt excess. The present study was performed to elucidate the role of SGK1 in the volume retention and fibrosis during nephrotic syndrome. To this end, doxorubicin (15 mug/g body wt) was injected intravenously into gene-targeted mice lacking SGK1 (sgk1(-/-)) and their wild-type littermates (sgk1(+/+)). Doxorubicin treatment resulted in heavy proteinuria (>100 mg protein/mg crea) in 15/44 of sgk1(+/+) and 15/44 of sgk1(-/-) mice leading to severe nephrotic syndrome with ascites, lipidemia, and hypoalbuminemia in both genotypes. Plasma aldosterone levels increased in nephrotic mice of both genotypes and was followed by increased SGK1 protein expression in sgk1(+/+) mice. Urinary sodium excretion reached signficantly lower values in sgk1(+/+) mice (15 +/- 5 mumol/mg crea) than in sgk1(-/-) mice (35 +/- 5 mumol/mg crea) and was associated with a significantly higher body weight gain in sgk1(+/+) compared with sgk1(-/-) mice (+6.6 +/- 0.7 vs. +4.1 +/- 0.8 g). During the course of nephrotic syndrome, serum urea concentrations increased significantly faster in sgk1(-/-) mice than in sgk1(+/+) mice leading to uremia and a reduced median survival in sgk1(-/-) mice (29 vs. 40 days in sgk1(+/+) mice). In conclusion, gene-targeted mice lacking SGK1 showed blunted volume retention, yet were not protected against renal fibrosis during experimental nephrotic syndrome.", "entity": "Uremia", "aliases": "Uremia Uremias", "definition": "A clinical syndrome associated with the retention of renal waste products or uremic toxins in the blood. It is usually the result of RENAL INSUFFICIENCY. Most uremic toxins are end products of protein or nitrogen CATABOLISM, such as UREA or CREATININE. Severe uremia can lead to multiple organ dysfunctions with a constellation of symptoms.\n    ", "id": "MESH:D014511"}
{"mention": "cholestasis", "mention_text": "Severe and long lasting cholestasis after high-dose co-trimoxazole treatment for Pneumocystis pneumonia in HIV-infected patients--a report of two cases.", "entity": "Cholestasis", "aliases": "Bile Duct Obstruction Obstructions Biliary Stases Stasis Cholestases Cholestasis", "definition": "Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).\n    ", "id": "MESH:D002779"}
{"mention": "co-trimoxazole", "mention_text": "Severe and long lasting cholestasis after high-dose co-trimoxazole treatment for Pneumocystis pneumonia in HIV-infected patients--a report of two cases.", "entity": "Trimethoprim-Sulfamethoxazole Combination", "aliases": "Abactrim Bactifor Bactrim Biseptol 480 Biseptol-480 Biseptol480 Centran Centrin Co Trimoxazole Co-Trimoxazole Cotrimoxazole Drylin Eslectin Eusaprim Insozalin Kepinol Forte Lescot Metomide Oriprim Septra Septrin Sulfamethoxazole Trimethoprim Combination Sulfamethoxazole-Trimethoprim Sulprim Sumetrolim TMP SMX TMP-SMX Trimedin Trimethoprim-Sulfamethoxazole Trimethoprimsulfa Trimezole Trimosulfa", "definition": "This drug combination has proved to be an effective therapeutic agent with broad-spectrum antibacterial activity against both gram-positive and gram-negative organisms. It is effective in the treatment of many infections, including PNEUMOCYSTIS PNEUMONIA in AIDS.\n    ", "id": "MESH:D015662"}
{"mention": "Pneumocystis pneumonia", "mention_text": "Severe and long lasting cholestasis after high-dose co-trimoxazole treatment for Pneumocystis pneumonia in HIV-infected patients--a report of two cases.", "entity": "Pneumonia, Pneumocystis", "aliases": "Pneumocystis Pneumonia Pneumonias carinii Pneumocystoses Pneumocystosis Interstitial Plasma Cell", "definition": "A pulmonary disease in humans occurring in immunodeficient or malnourished patients or infants, characterized by DYSPNEA, tachypnea, and HYPOXEMIA. Pneumocystis pneumonia is a frequently seen opportunistic infection in AIDS. It is caused by the fungus PNEUMOCYSTIS JIROVECII. The disease is also found in other MAMMALS where it is caused by related species of Pneumocystis.\n    ", "id": "MESH:D011020"}
{"mention": "HIV-infected", "mention_text": "Severe and long lasting cholestasis after high-dose co-trimoxazole treatment for Pneumocystis pneumonia in HIV-infected patients--a report of two cases.", "entity": "HIV Infections", "aliases": "HIV Infection Infections HTLV III LAV HTLV-III HTLV-III-LAV T Lymphotropic Virus Type Human T-Lymphotropic", "definition": "Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).\n    ", "id": "MESH:D015658"}
{"mention": "Pneumocystis pneumonia", "mention_text": "Pneumocystis pneumonia (PCP), a common opportunistic infection in HIV-infected individuals, is generally treated with high doses of co-trimoxazole. However, treatment is often limited by adverse effects. Here, we report two cases of severely immunocompromised HIV-infected patients who developed severe intrahepatic cholestasis, and in one patient lesions mimicking liver abscess formation on radiologic exams, during co-trimoxazole treatment for PCP. Whereas patient 1 showed lesions of up to 1 cm readily detectable on magnetic resonance imaging under prolonged co-trimoxazole treatment, therapy of patient 2 was switched early.", "entity": "Pneumonia, Pneumocystis", "aliases": "Pneumocystis Pneumonia Pneumonias carinii Pneumocystoses Pneumocystosis Interstitial Plasma Cell", "definition": "A pulmonary disease in humans occurring in immunodeficient or malnourished patients or infants, characterized by DYSPNEA, tachypnea, and HYPOXEMIA. Pneumocystis pneumonia is a frequently seen opportunistic infection in AIDS. It is caused by the fungus PNEUMOCYSTIS JIROVECII. The disease is also found in other MAMMALS where it is caused by related species of Pneumocystis.\n    ", "id": "MESH:D011020"}
{"mention": "PCP", "mention_text": "Pneumocystis pneumonia (PCP), a common opportunistic infection in HIV-infected individuals, is generally treated with high doses of co-trimoxazole. However, treatment is often limited by adverse effects. Here, we report two cases of severely immunocompromised HIV-infected patients who developed severe intrahepatic cholestasis, and in one patient lesions mimicking liver abscess formation on radiologic exams, during co-trimoxazole treatment for PCP. Whereas patient 1 showed lesions of up to 1 cm readily detectable on magnetic resonance imaging under prolonged co-trimoxazole treatment, therapy of patient 2 was switched early.", "entity": "Pneumonia, Pneumocystis", "aliases": "Pneumocystis Pneumonia Pneumonias carinii Pneumocystoses Pneumocystosis Interstitial Plasma Cell", "definition": "A pulmonary disease in humans occurring in immunodeficient or malnourished patients or infants, characterized by DYSPNEA, tachypnea, and HYPOXEMIA. Pneumocystis pneumonia is a frequently seen opportunistic infection in AIDS. It is caused by the fungus PNEUMOCYSTIS JIROVECII. The disease is also found in other MAMMALS where it is caused by related species of Pneumocystis.\n    ", "id": "MESH:D011020"}
{"mention": "opportunistic infection", "mention_text": "Pneumocystis pneumonia (PCP), a common opportunistic infection in HIV-infected individuals, is generally treated with high doses of co-trimoxazole. However, treatment is often limited by adverse effects. Here, we report two cases of severely immunocompromised HIV-infected patients who developed severe intrahepatic cholestasis, and in one patient lesions mimicking liver abscess formation on radiologic exams, during co-trimoxazole treatment for PCP. Whereas patient 1 showed lesions of up to 1 cm readily detectable on magnetic resonance imaging under prolonged co-trimoxazole treatment, therapy of patient 2 was switched early.", "entity": "Opportunistic Infections", "aliases": "Infection Opportunistic Infections", "definition": "An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression.\n    ", "id": "MESH:D009894"}
{"mention": "HIV-infected", "mention_text": "Pneumocystis pneumonia (PCP), a common opportunistic infection in HIV-infected individuals, is generally treated with high doses of co-trimoxazole. However, treatment is often limited by adverse effects. Here, we report two cases of severely immunocompromised HIV-infected patients who developed severe intrahepatic cholestasis, and in one patient lesions mimicking liver abscess formation on radiologic exams, during co-trimoxazole treatment for PCP. Whereas patient 1 showed lesions of up to 1 cm readily detectable on magnetic resonance imaging under prolonged co-trimoxazole treatment, therapy of patient 2 was switched early.", "entity": "HIV Infections", "aliases": "HIV Infection Infections HTLV III LAV HTLV-III HTLV-III-LAV T Lymphotropic Virus Type Human T-Lymphotropic", "definition": "Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).\n    ", "id": "MESH:D015658"}
{"mention": "co-trimoxazole", "mention_text": "Pneumocystis pneumonia (PCP), a common opportunistic infection in HIV-infected individuals, is generally treated with high doses of co-trimoxazole. However, treatment is often limited by adverse effects. Here, we report two cases of severely immunocompromised HIV-infected patients who developed severe intrahepatic cholestasis, and in one patient lesions mimicking liver abscess formation on radiologic exams, during co-trimoxazole treatment for PCP. Whereas patient 1 showed lesions of up to 1 cm readily detectable on magnetic resonance imaging under prolonged co-trimoxazole treatment, therapy of patient 2 was switched early.", "entity": "Trimethoprim-Sulfamethoxazole Combination", "aliases": "Abactrim Bactifor Bactrim Biseptol 480 Biseptol-480 Biseptol480 Centran Centrin Co Trimoxazole Co-Trimoxazole Cotrimoxazole Drylin Eslectin Eusaprim Insozalin Kepinol Forte Lescot Metomide Oriprim Septra Septrin Sulfamethoxazole Trimethoprim Combination Sulfamethoxazole-Trimethoprim Sulprim Sumetrolim TMP SMX TMP-SMX Trimedin Trimethoprim-Sulfamethoxazole Trimethoprimsulfa Trimezole Trimosulfa", "definition": "This drug combination has proved to be an effective therapeutic agent with broad-spectrum antibacterial activity against both gram-positive and gram-negative organisms. It is effective in the treatment of many infections, including PNEUMOCYSTIS PNEUMONIA in AIDS.\n    ", "id": "MESH:D015662"}
{"mention": "intrahepatic cholestasis", "mention_text": "Pneumocystis pneumonia (PCP), a common opportunistic infection in HIV-infected individuals, is generally treated with high doses of co-trimoxazole. However, treatment is often limited by adverse effects. Here, we report two cases of severely immunocompromised HIV-infected patients who developed severe intrahepatic cholestasis, and in one patient lesions mimicking liver abscess formation on radiologic exams, during co-trimoxazole treatment for PCP. Whereas patient 1 showed lesions of up to 1 cm readily detectable on magnetic resonance imaging under prolonged co-trimoxazole treatment, therapy of patient 2 was switched early.", "entity": "Cholestasis, Intrahepatic", "aliases": "Bile Duct Obstruction Intrahepatic Biliary Stases Stasis Cholestases Cholestasis", "definition": "Impairment of bile flow due to injury to the HEPATOCYTES; BILE CANALICULI; or the intrahepatic bile ducts (BILE DUCTS, INTRAHEPATIC).\n    ", "id": "MESH:D002780"}
{"mention": "liver abscess", "mention_text": "Pneumocystis pneumonia (PCP), a common opportunistic infection in HIV-infected individuals, is generally treated with high doses of co-trimoxazole. However, treatment is often limited by adverse effects. Here, we report two cases of severely immunocompromised HIV-infected patients who developed severe intrahepatic cholestasis, and in one patient lesions mimicking liver abscess formation on radiologic exams, during co-trimoxazole treatment for PCP. Whereas patient 1 showed lesions of up to 1 cm readily detectable on magnetic resonance imaging under prolonged co-trimoxazole treatment, therapy of patient 2 was switched early.", "entity": "Liver Abscess", "aliases": "Abscess Hepatic Liver Abscesses", "definition": "Solitary or multiple collections of PUS within the liver as a result of infection by bacteria, protozoa, or other agents.\n    ", "id": "MESH:D008100"}
{"mention": "proteinuria", "mention_text": "Clinically significant proteinuria following the administration of sirolimus to renal transplant recipients.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "sirolimus", "mention_text": "Clinically significant proteinuria following the administration of sirolimus to renal transplant recipients.", "entity": "Sirolimus", "aliases": "AY 22 989 22-989 22989 I 2190A I-2190A I2190A Rapamune Rapamycin Sirolimus Wyeth Brand of", "definition": "A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.\n    ", "id": "MESH:D020123"}
{"mention": "Sirolimus", "mention_text": "BACKGROUND: Sirolimus is the latest immunosuppressive agent used to prevent rejection, and may have less nephrotoxicity than calcineurin inhibitor (CNI)-based regimens. To date there has been little documentation of clinically significant proteinuria linked with the use of sirolimus. We have encountered several patients who developed substantial proteinuria associated with sirolimus use. In each patient, the close temporal association between the commencement of sirolimus therapy and proteinuria implicated sirolimus as the most likely etiology of the proteinuria. METHODS: We analyzed the clinical and laboratory information available for all 119 patients transplanted at the Washington Hospital Center between 1999-2003 for whom sirolimus was a component of their immunosuppressant regimen. In these patients, the magnitude of proteinuria was assessed on morning urine samples by turbidometric measurement or random urine protein:creatinine ratios, an estimate of grams of proteinuria/day. Laboratory results were compared between prior, during and following sirolimus use. RESULTS: Twenty-eight patients (24%) developed increased proteinuria from baseline during their post-transplantation course. In 21 patients an alternative cause of proteinuria was either obvious or insufficient data was available to be conclusive. In 7 of the 28 patients there was a striking temporal association between the initiation of sirolimus and the development of nephrotic-range proteinuria. Proteinuria correlated most strongly with sirolimus therapy when compared to other demographic and clinical variables. In most patients, discontinuation of sirolimus resulted in a decrease, but not resolution, of proteinuria. CONCLUSIONS: Sirolimus induces or aggravates pre-existing proteinuria in an unpredictable subset of renal allograft recipients. Proteinuria may improve, but does not resolve, when sirolimus is withdrawn.", "entity": "Sirolimus", "aliases": "AY 22 989 22-989 22989 I 2190A I-2190A I2190A Rapamune Rapamycin Sirolimus Wyeth Brand of", "definition": "A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.\n    ", "id": "MESH:D020123"}
{"mention": "nephrotoxicity", "mention_text": "BACKGROUND: Sirolimus is the latest immunosuppressive agent used to prevent rejection, and may have less nephrotoxicity than calcineurin inhibitor (CNI)-based regimens. To date there has been little documentation of clinically significant proteinuria linked with the use of sirolimus. We have encountered several patients who developed substantial proteinuria associated with sirolimus use. In each patient, the close temporal association between the commencement of sirolimus therapy and proteinuria implicated sirolimus as the most likely etiology of the proteinuria. METHODS: We analyzed the clinical and laboratory information available for all 119 patients transplanted at the Washington Hospital Center between 1999-2003 for whom sirolimus was a component of their immunosuppressant regimen. In these patients, the magnitude of proteinuria was assessed on morning urine samples by turbidometric measurement or random urine protein:creatinine ratios, an estimate of grams of proteinuria/day. Laboratory results were compared between prior, during and following sirolimus use. RESULTS: Twenty-eight patients (24%) developed increased proteinuria from baseline during their post-transplantation course. In 21 patients an alternative cause of proteinuria was either obvious or insufficient data was available to be conclusive. In 7 of the 28 patients there was a striking temporal association between the initiation of sirolimus and the development of nephrotic-range proteinuria. Proteinuria correlated most strongly with sirolimus therapy when compared to other demographic and clinical variables. In most patients, discontinuation of sirolimus resulted in a decrease, but not resolution, of proteinuria. CONCLUSIONS: Sirolimus induces or aggravates pre-existing proteinuria in an unpredictable subset of renal allograft recipients. Proteinuria may improve, but does not resolve, when sirolimus is withdrawn.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "proteinuria", "mention_text": "BACKGROUND: Sirolimus is the latest immunosuppressive agent used to prevent rejection, and may have less nephrotoxicity than calcineurin inhibitor (CNI)-based regimens. To date there has been little documentation of clinically significant proteinuria linked with the use of sirolimus. We have encountered several patients who developed substantial proteinuria associated with sirolimus use. In each patient, the close temporal association between the commencement of sirolimus therapy and proteinuria implicated sirolimus as the most likely etiology of the proteinuria. METHODS: We analyzed the clinical and laboratory information available for all 119 patients transplanted at the Washington Hospital Center between 1999-2003 for whom sirolimus was a component of their immunosuppressant regimen. In these patients, the magnitude of proteinuria was assessed on morning urine samples by turbidometric measurement or random urine protein:creatinine ratios, an estimate of grams of proteinuria/day. Laboratory results were compared between prior, during and following sirolimus use. RESULTS: Twenty-eight patients (24%) developed increased proteinuria from baseline during their post-transplantation course. In 21 patients an alternative cause of proteinuria was either obvious or insufficient data was available to be conclusive. In 7 of the 28 patients there was a striking temporal association between the initiation of sirolimus and the development of nephrotic-range proteinuria. Proteinuria correlated most strongly with sirolimus therapy when compared to other demographic and clinical variables. In most patients, discontinuation of sirolimus resulted in a decrease, but not resolution, of proteinuria. CONCLUSIONS: Sirolimus induces or aggravates pre-existing proteinuria in an unpredictable subset of renal allograft recipients. Proteinuria may improve, but does not resolve, when sirolimus is withdrawn.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "sirolimus", "mention_text": "BACKGROUND: Sirolimus is the latest immunosuppressive agent used to prevent rejection, and may have less nephrotoxicity than calcineurin inhibitor (CNI)-based regimens. To date there has been little documentation of clinically significant proteinuria linked with the use of sirolimus. We have encountered several patients who developed substantial proteinuria associated with sirolimus use. In each patient, the close temporal association between the commencement of sirolimus therapy and proteinuria implicated sirolimus as the most likely etiology of the proteinuria. METHODS: We analyzed the clinical and laboratory information available for all 119 patients transplanted at the Washington Hospital Center between 1999-2003 for whom sirolimus was a component of their immunosuppressant regimen. In these patients, the magnitude of proteinuria was assessed on morning urine samples by turbidometric measurement or random urine protein:creatinine ratios, an estimate of grams of proteinuria/day. Laboratory results were compared between prior, during and following sirolimus use. RESULTS: Twenty-eight patients (24%) developed increased proteinuria from baseline during their post-transplantation course. In 21 patients an alternative cause of proteinuria was either obvious or insufficient data was available to be conclusive. In 7 of the 28 patients there was a striking temporal association between the initiation of sirolimus and the development of nephrotic-range proteinuria. Proteinuria correlated most strongly with sirolimus therapy when compared to other demographic and clinical variables. In most patients, discontinuation of sirolimus resulted in a decrease, but not resolution, of proteinuria. CONCLUSIONS: Sirolimus induces or aggravates pre-existing proteinuria in an unpredictable subset of renal allograft recipients. Proteinuria may improve, but does not resolve, when sirolimus is withdrawn.", "entity": "Sirolimus", "aliases": "AY 22 989 22-989 22989 I 2190A I-2190A I2190A Rapamune Rapamycin Sirolimus Wyeth Brand of", "definition": "A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.\n    ", "id": "MESH:D020123"}
{"mention": "creatinine", "mention_text": "BACKGROUND: Sirolimus is the latest immunosuppressive agent used to prevent rejection, and may have less nephrotoxicity than calcineurin inhibitor (CNI)-based regimens. To date there has been little documentation of clinically significant proteinuria linked with the use of sirolimus. We have encountered several patients who developed substantial proteinuria associated with sirolimus use. In each patient, the close temporal association between the commencement of sirolimus therapy and proteinuria implicated sirolimus as the most likely etiology of the proteinuria. METHODS: We analyzed the clinical and laboratory information available for all 119 patients transplanted at the Washington Hospital Center between 1999-2003 for whom sirolimus was a component of their immunosuppressant regimen. In these patients, the magnitude of proteinuria was assessed on morning urine samples by turbidometric measurement or random urine protein:creatinine ratios, an estimate of grams of proteinuria/day. Laboratory results were compared between prior, during and following sirolimus use. RESULTS: Twenty-eight patients (24%) developed increased proteinuria from baseline during their post-transplantation course. In 21 patients an alternative cause of proteinuria was either obvious or insufficient data was available to be conclusive. In 7 of the 28 patients there was a striking temporal association between the initiation of sirolimus and the development of nephrotic-range proteinuria. Proteinuria correlated most strongly with sirolimus therapy when compared to other demographic and clinical variables. In most patients, discontinuation of sirolimus resulted in a decrease, but not resolution, of proteinuria. CONCLUSIONS: Sirolimus induces or aggravates pre-existing proteinuria in an unpredictable subset of renal allograft recipients. Proteinuria may improve, but does not resolve, when sirolimus is withdrawn.", "entity": "Creatinine", "aliases": "Creatinine Sulfate Salt Krebiozen", "definition": "", "id": "MESH:D003404"}
{"mention": "nephrotic", "mention_text": "BACKGROUND: Sirolimus is the latest immunosuppressive agent used to prevent rejection, and may have less nephrotoxicity than calcineurin inhibitor (CNI)-based regimens. To date there has been little documentation of clinically significant proteinuria linked with the use of sirolimus. We have encountered several patients who developed substantial proteinuria associated with sirolimus use. In each patient, the close temporal association between the commencement of sirolimus therapy and proteinuria implicated sirolimus as the most likely etiology of the proteinuria. METHODS: We analyzed the clinical and laboratory information available for all 119 patients transplanted at the Washington Hospital Center between 1999-2003 for whom sirolimus was a component of their immunosuppressant regimen. In these patients, the magnitude of proteinuria was assessed on morning urine samples by turbidometric measurement or random urine protein:creatinine ratios, an estimate of grams of proteinuria/day. Laboratory results were compared between prior, during and following sirolimus use. RESULTS: Twenty-eight patients (24%) developed increased proteinuria from baseline during their post-transplantation course. In 21 patients an alternative cause of proteinuria was either obvious or insufficient data was available to be conclusive. In 7 of the 28 patients there was a striking temporal association between the initiation of sirolimus and the development of nephrotic-range proteinuria. Proteinuria correlated most strongly with sirolimus therapy when compared to other demographic and clinical variables. In most patients, discontinuation of sirolimus resulted in a decrease, but not resolution, of proteinuria. CONCLUSIONS: Sirolimus induces or aggravates pre-existing proteinuria in an unpredictable subset of renal allograft recipients. Proteinuria may improve, but does not resolve, when sirolimus is withdrawn.", "entity": "Nephrotic Syndrome", "aliases": "Nephrotic Syndrome Syndromes", "definition": "A condition characterized by severe PROTEINURIA, greater than 3.5 g/day in an average adult. The substantial loss of protein in the urine results in complications such as HYPOPROTEINEMIA; generalized EDEMA; HYPERTENSION; and HYPERLIPIDEMIAS. Diseases associated with nephrotic syndrome generally cause chronic kidney dysfunction.\n    ", "id": "MESH:D009404"}
{"mention": "Proteinuria", "mention_text": "BACKGROUND: Sirolimus is the latest immunosuppressive agent used to prevent rejection, and may have less nephrotoxicity than calcineurin inhibitor (CNI)-based regimens. To date there has been little documentation of clinically significant proteinuria linked with the use of sirolimus. We have encountered several patients who developed substantial proteinuria associated with sirolimus use. In each patient, the close temporal association between the commencement of sirolimus therapy and proteinuria implicated sirolimus as the most likely etiology of the proteinuria. METHODS: We analyzed the clinical and laboratory information available for all 119 patients transplanted at the Washington Hospital Center between 1999-2003 for whom sirolimus was a component of their immunosuppressant regimen. In these patients, the magnitude of proteinuria was assessed on morning urine samples by turbidometric measurement or random urine protein:creatinine ratios, an estimate of grams of proteinuria/day. Laboratory results were compared between prior, during and following sirolimus use. RESULTS: Twenty-eight patients (24%) developed increased proteinuria from baseline during their post-transplantation course. In 21 patients an alternative cause of proteinuria was either obvious or insufficient data was available to be conclusive. In 7 of the 28 patients there was a striking temporal association between the initiation of sirolimus and the development of nephrotic-range proteinuria. Proteinuria correlated most strongly with sirolimus therapy when compared to other demographic and clinical variables. In most patients, discontinuation of sirolimus resulted in a decrease, but not resolution, of proteinuria. CONCLUSIONS: Sirolimus induces or aggravates pre-existing proteinuria in an unpredictable subset of renal allograft recipients. Proteinuria may improve, but does not resolve, when sirolimus is withdrawn.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "oxycodone", "mention_text": "Comparative cognitive and subjective side effects of immediate-release oxycodone in healthy middle-aged and older adults.", "entity": "Oxycodone", "aliases": "Dihydrohydroxycodeinone Dihydrone Dinarkon Eucodal Oxiconum Oxycodeinon Oxycodone Hydrochloride Oxycone Oxycontin Pancodine Purdue Frederick Brand of Theocodin", "definition": "A semisynthetic derivative of CODEINE.\n    ", "id": "MESH:D010098"}
{"mention": "oxycodone", "mention_text": "This study measured the objective and subjective neurocognitive effects of a single 10-mg dose of immediate-release oxycodone in healthy, older (> 65 years), and middle-aged (35 to 55 years) adults who were not suffering from chronic or significant daily pain. Seventy-one participants completed 2 separate study days and were blind to medication condition (placebo, 10-mg oxycodone). Plasma oxycodone concentration peaked between 60 and 90 minutes postdose (P < .01) and pupil size, an indication of physiological effects of the medication, peaked at approximately 90 to 120 minutes postdose (P < .01). Significant declines in simple and sustained attention, working memory, and verbal memory were observed at 1 hour postdose compared to baseline for both age groups with a trend toward return to baseline by 5 hours postdose. For almost all cognitive measures, there were no medication by age-interaction effects, which indicates that the 2 age groups exhibited similar responses to the medication challenge. This study suggests that for healthy older adults who are not suffering from chronic pain, neurocognitive and pharmacodynamic changes in response to a 10-mg dose of immediate-release oxycodone are similar to those observed for middle-aged adults. PERSPECTIVE: Study findings indicate that the metabolism, neurocognitive effects, and physical side effects of oral oxycodone are similar for healthy middle-aged and older adults. Therefore, clinicians should not avoid prescribing oral opioids to older adults based on the belief that older adults are at higher risk for side effects than younger adults.", "entity": "Oxycodone", "aliases": "Dihydrohydroxycodeinone Dihydrone Dinarkon Eucodal Oxiconum Oxycodeinon Oxycodone Hydrochloride Oxycone Oxycontin Pancodine Purdue Frederick Brand of Theocodin", "definition": "A semisynthetic derivative of CODEINE.\n    ", "id": "MESH:D010098"}
{"mention": "pain", "mention_text": "This study measured the objective and subjective neurocognitive effects of a single 10-mg dose of immediate-release oxycodone in healthy, older (> 65 years), and middle-aged (35 to 55 years) adults who were not suffering from chronic or significant daily pain. Seventy-one participants completed 2 separate study days and were blind to medication condition (placebo, 10-mg oxycodone). Plasma oxycodone concentration peaked between 60 and 90 minutes postdose (P < .01) and pupil size, an indication of physiological effects of the medication, peaked at approximately 90 to 120 minutes postdose (P < .01). Significant declines in simple and sustained attention, working memory, and verbal memory were observed at 1 hour postdose compared to baseline for both age groups with a trend toward return to baseline by 5 hours postdose. For almost all cognitive measures, there were no medication by age-interaction effects, which indicates that the 2 age groups exhibited similar responses to the medication challenge. This study suggests that for healthy older adults who are not suffering from chronic pain, neurocognitive and pharmacodynamic changes in response to a 10-mg dose of immediate-release oxycodone are similar to those observed for middle-aged adults. PERSPECTIVE: Study findings indicate that the metabolism, neurocognitive effects, and physical side effects of oral oxycodone are similar for healthy middle-aged and older adults. Therefore, clinicians should not avoid prescribing oral opioids to older adults based on the belief that older adults are at higher risk for side effects than younger adults.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "declines in simple and sustained attention", "mention_text": "This study measured the objective and subjective neurocognitive effects of a single 10-mg dose of immediate-release oxycodone in healthy, older (> 65 years), and middle-aged (35 to 55 years) adults who were not suffering from chronic or significant daily pain. Seventy-one participants completed 2 separate study days and were blind to medication condition (placebo, 10-mg oxycodone). Plasma oxycodone concentration peaked between 60 and 90 minutes postdose (P < .01) and pupil size, an indication of physiological effects of the medication, peaked at approximately 90 to 120 minutes postdose (P < .01). Significant declines in simple and sustained attention, working memory, and verbal memory were observed at 1 hour postdose compared to baseline for both age groups with a trend toward return to baseline by 5 hours postdose. For almost all cognitive measures, there were no medication by age-interaction effects, which indicates that the 2 age groups exhibited similar responses to the medication challenge. This study suggests that for healthy older adults who are not suffering from chronic pain, neurocognitive and pharmacodynamic changes in response to a 10-mg dose of immediate-release oxycodone are similar to those observed for middle-aged adults. PERSPECTIVE: Study findings indicate that the metabolism, neurocognitive effects, and physical side effects of oral oxycodone are similar for healthy middle-aged and older adults. Therefore, clinicians should not avoid prescribing oral opioids to older adults based on the belief that older adults are at higher risk for side effects than younger adults.", "entity": "Cognition Disorders", "aliases": "Cognition Disorders Disorder Overinclusion", "definition": "Disturbances in the mental process related to thinking, reasoning, and judgment.\n    ", "id": "MESH:D003072"}
{"mention": "chronic pain", "mention_text": "This study measured the objective and subjective neurocognitive effects of a single 10-mg dose of immediate-release oxycodone in healthy, older (> 65 years), and middle-aged (35 to 55 years) adults who were not suffering from chronic or significant daily pain. Seventy-one participants completed 2 separate study days and were blind to medication condition (placebo, 10-mg oxycodone). Plasma oxycodone concentration peaked between 60 and 90 minutes postdose (P < .01) and pupil size, an indication of physiological effects of the medication, peaked at approximately 90 to 120 minutes postdose (P < .01). Significant declines in simple and sustained attention, working memory, and verbal memory were observed at 1 hour postdose compared to baseline for both age groups with a trend toward return to baseline by 5 hours postdose. For almost all cognitive measures, there were no medication by age-interaction effects, which indicates that the 2 age groups exhibited similar responses to the medication challenge. This study suggests that for healthy older adults who are not suffering from chronic pain, neurocognitive and pharmacodynamic changes in response to a 10-mg dose of immediate-release oxycodone are similar to those observed for middle-aged adults. PERSPECTIVE: Study findings indicate that the metabolism, neurocognitive effects, and physical side effects of oral oxycodone are similar for healthy middle-aged and older adults. Therefore, clinicians should not avoid prescribing oral opioids to older adults based on the belief that older adults are at higher risk for side effects than younger adults.", "entity": "Chronic Pain", "aliases": "Chronic Pain Widespread Pains", "definition": "Aching sensation that persists for more than a few months. It may or may not be associated with trauma or disease, and may persist after the initial injury has healed. Its localization, character, and timing are more vague than with acute pain.\n    ", "id": "MESH:D059350"}
{"mention": "modafinil", "mention_text": "Normalizing effects of modafinil on sleep in chronic cocaine users.", "entity": "modafinil", "aliases": "2-((diphenylmethyl)sulfinyl)acetamide Alertec CEPA brand of modafinil CRL 40476 CRL-40476 Cephalon reformulated Draxis Lafon Merckle Modiodal Nourypharma Provigil Sparlon Vigil benzhydrylsulfinylacetamide", "definition": "", "id": "MESH:C048833"}
{"mention": "cocaine", "mention_text": "Normalizing effects of modafinil on sleep in chronic cocaine users.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "modafinil", "mention_text": "OBJECTIVE: The purpose of the present study was to determine the effect of morning-dosed modafinil on sleep and daytime sleepiness in chronic cocaine users. METHOD: Twenty cocaine-dependent participants were randomly assigned to receive modafinil, 400 mg (N=10), or placebo (N=10) every morning at 7:30 a.m. for 16 days in an inpatient, double-blind randomized trial. Participants underwent polysomnographic sleep recordings on days 1 to 3, 7 to 9, and 14 to 16 (first, second, and third weeks of abstinence). The Multiple Sleep Latency Test was performed at 11:30 a.m., 2:00 p.m., and 4:30 p.m. on days 2, 8, and 15. For comparison of sleep architecture variables, 12 healthy comparison participants underwent a single night of experimental polysomnography that followed 1 night of accommodation polysomnography. RESULTS: Progressive abstinence from cocaine was associated with worsening of all measured polysomnographic sleep outcomes. Compared with placebo, modafinil decreased nighttime sleep latency and increased slow-wave sleep time in cocaine-dependent participants. The effect of modafinil interacted with the abstinence week and was associated with longer total sleep time and shorter REM sleep latency in the third week of abstinence. Comparison of slow-wave sleep time, total sleep time, and sleep latency in cocaine-dependent and healthy participants revealed a normalizing effect of modafinil in cocaine-dependent participants. Modafinil was associated with increased daytime sleep latency, as measured by the Multiple Sleep Latency Test, and a nearly significant decrease in subjective daytime sleepiness. CONCLUSIONS: Morning-dosed modafinil promotes nocturnal sleep, normalizes sleep architecture, and decreases daytime sleepiness in abstinent cocaine users. These effects may be relevant in the treatment of cocaine dependence.", "entity": "modafinil", "aliases": "2-((diphenylmethyl)sulfinyl)acetamide Alertec CEPA brand of modafinil CRL 40476 CRL-40476 Cephalon reformulated Draxis Lafon Merckle Modiodal Nourypharma Provigil Sparlon Vigil benzhydrylsulfinylacetamide", "definition": "", "id": "MESH:C048833"}
{"mention": "daytime sleepiness", "mention_text": "OBJECTIVE: The purpose of the present study was to determine the effect of morning-dosed modafinil on sleep and daytime sleepiness in chronic cocaine users. METHOD: Twenty cocaine-dependent participants were randomly assigned to receive modafinil, 400 mg (N=10), or placebo (N=10) every morning at 7:30 a.m. for 16 days in an inpatient, double-blind randomized trial. Participants underwent polysomnographic sleep recordings on days 1 to 3, 7 to 9, and 14 to 16 (first, second, and third weeks of abstinence). The Multiple Sleep Latency Test was performed at 11:30 a.m., 2:00 p.m., and 4:30 p.m. on days 2, 8, and 15. For comparison of sleep architecture variables, 12 healthy comparison participants underwent a single night of experimental polysomnography that followed 1 night of accommodation polysomnography. RESULTS: Progressive abstinence from cocaine was associated with worsening of all measured polysomnographic sleep outcomes. Compared with placebo, modafinil decreased nighttime sleep latency and increased slow-wave sleep time in cocaine-dependent participants. The effect of modafinil interacted with the abstinence week and was associated with longer total sleep time and shorter REM sleep latency in the third week of abstinence. Comparison of slow-wave sleep time, total sleep time, and sleep latency in cocaine-dependent and healthy participants revealed a normalizing effect of modafinil in cocaine-dependent participants. Modafinil was associated with increased daytime sleep latency, as measured by the Multiple Sleep Latency Test, and a nearly significant decrease in subjective daytime sleepiness. CONCLUSIONS: Morning-dosed modafinil promotes nocturnal sleep, normalizes sleep architecture, and decreases daytime sleepiness in abstinent cocaine users. These effects may be relevant in the treatment of cocaine dependence.", "entity": "Sleep Disorders", "aliases": "Long Sleeper Syndrome Syndromes Neurogenic Tachypnea Sleep-Related Tachypneas Phenotype Short Sleep Phenotypes Disorders Related Subwakefullness", "definition": "Conditions characterized by disturbances of usual sleep patterns or behaviors. Sleep disorders may be divided into three major categories: DYSSOMNIAS (i.e. disorders characterized by insomnia or hypersomnia), PARASOMNIAS (abnormal sleep behaviors), and sleep disorders secondary to medical or psychiatric disorders. (From Thorpy, Sleep Disorders Medicine, 1994, p187)\n    ", "id": "MESH:D012893"}
{"mention": "cocaine", "mention_text": "OBJECTIVE: The purpose of the present study was to determine the effect of morning-dosed modafinil on sleep and daytime sleepiness in chronic cocaine users. METHOD: Twenty cocaine-dependent participants were randomly assigned to receive modafinil, 400 mg (N=10), or placebo (N=10) every morning at 7:30 a.m. for 16 days in an inpatient, double-blind randomized trial. Participants underwent polysomnographic sleep recordings on days 1 to 3, 7 to 9, and 14 to 16 (first, second, and third weeks of abstinence). The Multiple Sleep Latency Test was performed at 11:30 a.m., 2:00 p.m., and 4:30 p.m. on days 2, 8, and 15. For comparison of sleep architecture variables, 12 healthy comparison participants underwent a single night of experimental polysomnography that followed 1 night of accommodation polysomnography. RESULTS: Progressive abstinence from cocaine was associated with worsening of all measured polysomnographic sleep outcomes. Compared with placebo, modafinil decreased nighttime sleep latency and increased slow-wave sleep time in cocaine-dependent participants. The effect of modafinil interacted with the abstinence week and was associated with longer total sleep time and shorter REM sleep latency in the third week of abstinence. Comparison of slow-wave sleep time, total sleep time, and sleep latency in cocaine-dependent and healthy participants revealed a normalizing effect of modafinil in cocaine-dependent participants. Modafinil was associated with increased daytime sleep latency, as measured by the Multiple Sleep Latency Test, and a nearly significant decrease in subjective daytime sleepiness. CONCLUSIONS: Morning-dosed modafinil promotes nocturnal sleep, normalizes sleep architecture, and decreases daytime sleepiness in abstinent cocaine users. These effects may be relevant in the treatment of cocaine dependence.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "Modafinil", "mention_text": "OBJECTIVE: The purpose of the present study was to determine the effect of morning-dosed modafinil on sleep and daytime sleepiness in chronic cocaine users. METHOD: Twenty cocaine-dependent participants were randomly assigned to receive modafinil, 400 mg (N=10), or placebo (N=10) every morning at 7:30 a.m. for 16 days in an inpatient, double-blind randomized trial. Participants underwent polysomnographic sleep recordings on days 1 to 3, 7 to 9, and 14 to 16 (first, second, and third weeks of abstinence). The Multiple Sleep Latency Test was performed at 11:30 a.m., 2:00 p.m., and 4:30 p.m. on days 2, 8, and 15. For comparison of sleep architecture variables, 12 healthy comparison participants underwent a single night of experimental polysomnography that followed 1 night of accommodation polysomnography. RESULTS: Progressive abstinence from cocaine was associated with worsening of all measured polysomnographic sleep outcomes. Compared with placebo, modafinil decreased nighttime sleep latency and increased slow-wave sleep time in cocaine-dependent participants. The effect of modafinil interacted with the abstinence week and was associated with longer total sleep time and shorter REM sleep latency in the third week of abstinence. Comparison of slow-wave sleep time, total sleep time, and sleep latency in cocaine-dependent and healthy participants revealed a normalizing effect of modafinil in cocaine-dependent participants. Modafinil was associated with increased daytime sleep latency, as measured by the Multiple Sleep Latency Test, and a nearly significant decrease in subjective daytime sleepiness. CONCLUSIONS: Morning-dosed modafinil promotes nocturnal sleep, normalizes sleep architecture, and decreases daytime sleepiness in abstinent cocaine users. These effects may be relevant in the treatment of cocaine dependence.", "entity": "modafinil", "aliases": "2-((diphenylmethyl)sulfinyl)acetamide Alertec CEPA brand of modafinil CRL 40476 CRL-40476 Cephalon reformulated Draxis Lafon Merckle Modiodal Nourypharma Provigil Sparlon Vigil benzhydrylsulfinylacetamide", "definition": "", "id": "MESH:C048833"}
{"mention": "asenapine", "mention_text": "Efficacy and safety of asenapine in a placebo- and haloperidol-controlled trial in patients with acute exacerbation of schizophrenia.", "entity": "Asenapine", "aliases": "5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenz(2,3-6,7)oxepino(4,5-c)pyrrole Asenapine ORG 5222 ORG-5222 asenapine maleate saphris", "definition": "", "id": "MESH:C522667"}
{"mention": "haloperidol", "mention_text": "Efficacy and safety of asenapine in a placebo- and haloperidol-controlled trial in patients with acute exacerbation of schizophrenia.", "entity": "Haloperidol", "aliases": "Haldol Haloperidol", "definition": "A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)\n    ", "id": "MESH:D006220"}
{"mention": "schizophrenia", "mention_text": "Efficacy and safety of asenapine in a placebo- and haloperidol-controlled trial in patients with acute exacerbation of schizophrenia.", "entity": "Schizophrenia", "aliases": "Dementia Praecox Disorder Schizophrenic Disorders Schizophrenia Schizophrenias", "definition": "A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior.\n    ", "id": "MESH:D012559"}
{"mention": "Asenapine", "mention_text": "Asenapine is approved by the Food and Drugs Administration in adults for acute treatment of schizophrenia or of manic or mixed episodes associated with bipolar I disorder with or without psychotic features. In a double-blind 6-week trial, 458 patients with acute schizophrenia were randomly assigned to fixed-dose treatment with asenapine at 5 mg twice daily (BID), asenapine at 10 mg BID, placebo, or haloperidol at 4 mg BID (to verify assay sensitivity). With last observations carried forward (LOCF), mean Positive and Negative Syndrome Scale total score reductions from baseline to endpoint were significantly greater with asenapine at 5 mg BID (-16.2) and haloperidol (-15.4) than placebo (-10.7; both P < 0.05); using mixed model for repeated measures (MMRM), changes at day 42 were significantly greater with asenapine at 5 and 10 mg BID (-21.3 and -19.4, respectively) and haloperidol (-20.0) than placebo (-14.6; all P < 0.05). On the Positive and Negative Syndrome Scale positive subscale, all treatments were superior to placebo with LOCF and MMRM; asenapine at 5 mg BID was superior to placebo on the negative subscale with MMRM and on the general psychopathology subscale with LOCF and MMRM. Treatment-related adverse events (AEs) occurred in 44% and 52%, 57%, and 41% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Extrapyramidal symptoms reported as AEs occurred in 15% and 18%, 34%, and 10% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Across all groups, no more than 5% of patients had clinically significant weight change. Post hoc analyses indicated that efficacy was similar with asenapine and haloperidol; greater contrasts were seen in AEs, especially extrapyramidal symptoms.", "entity": "Asenapine", "aliases": "5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenz(2,3-6,7)oxepino(4,5-c)pyrrole Asenapine ORG 5222 ORG-5222 asenapine maleate saphris", "definition": "", "id": "MESH:C522667"}
{"mention": "schizophrenia", "mention_text": "Asenapine is approved by the Food and Drugs Administration in adults for acute treatment of schizophrenia or of manic or mixed episodes associated with bipolar I disorder with or without psychotic features. In a double-blind 6-week trial, 458 patients with acute schizophrenia were randomly assigned to fixed-dose treatment with asenapine at 5 mg twice daily (BID), asenapine at 10 mg BID, placebo, or haloperidol at 4 mg BID (to verify assay sensitivity). With last observations carried forward (LOCF), mean Positive and Negative Syndrome Scale total score reductions from baseline to endpoint were significantly greater with asenapine at 5 mg BID (-16.2) and haloperidol (-15.4) than placebo (-10.7; both P < 0.05); using mixed model for repeated measures (MMRM), changes at day 42 were significantly greater with asenapine at 5 and 10 mg BID (-21.3 and -19.4, respectively) and haloperidol (-20.0) than placebo (-14.6; all P < 0.05). On the Positive and Negative Syndrome Scale positive subscale, all treatments were superior to placebo with LOCF and MMRM; asenapine at 5 mg BID was superior to placebo on the negative subscale with MMRM and on the general psychopathology subscale with LOCF and MMRM. Treatment-related adverse events (AEs) occurred in 44% and 52%, 57%, and 41% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Extrapyramidal symptoms reported as AEs occurred in 15% and 18%, 34%, and 10% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Across all groups, no more than 5% of patients had clinically significant weight change. Post hoc analyses indicated that efficacy was similar with asenapine and haloperidol; greater contrasts were seen in AEs, especially extrapyramidal symptoms.", "entity": "Schizophrenia", "aliases": "Dementia Praecox Disorder Schizophrenic Disorders Schizophrenia Schizophrenias", "definition": "A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior.\n    ", "id": "MESH:D012559"}
{"mention": "manic", "mention_text": "Asenapine is approved by the Food and Drugs Administration in adults for acute treatment of schizophrenia or of manic or mixed episodes associated with bipolar I disorder with or without psychotic features. In a double-blind 6-week trial, 458 patients with acute schizophrenia were randomly assigned to fixed-dose treatment with asenapine at 5 mg twice daily (BID), asenapine at 10 mg BID, placebo, or haloperidol at 4 mg BID (to verify assay sensitivity). With last observations carried forward (LOCF), mean Positive and Negative Syndrome Scale total score reductions from baseline to endpoint were significantly greater with asenapine at 5 mg BID (-16.2) and haloperidol (-15.4) than placebo (-10.7; both P < 0.05); using mixed model for repeated measures (MMRM), changes at day 42 were significantly greater with asenapine at 5 and 10 mg BID (-21.3 and -19.4, respectively) and haloperidol (-20.0) than placebo (-14.6; all P < 0.05). On the Positive and Negative Syndrome Scale positive subscale, all treatments were superior to placebo with LOCF and MMRM; asenapine at 5 mg BID was superior to placebo on the negative subscale with MMRM and on the general psychopathology subscale with LOCF and MMRM. Treatment-related adverse events (AEs) occurred in 44% and 52%, 57%, and 41% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Extrapyramidal symptoms reported as AEs occurred in 15% and 18%, 34%, and 10% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Across all groups, no more than 5% of patients had clinically significant weight change. Post hoc analyses indicated that efficacy was similar with asenapine and haloperidol; greater contrasts were seen in AEs, especially extrapyramidal symptoms.", "entity": "Bipolar Disorder", "aliases": "Affective Psychosis Bipolar Depression Disorder Disorders Manic Mania Manias Depressive State States Manic-Depressive Psychoses", "definition": "A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.\n    ", "id": "MESH:D001714"}
{"mention": "bipolar I disorder", "mention_text": "Asenapine is approved by the Food and Drugs Administration in adults for acute treatment of schizophrenia or of manic or mixed episodes associated with bipolar I disorder with or without psychotic features. In a double-blind 6-week trial, 458 patients with acute schizophrenia were randomly assigned to fixed-dose treatment with asenapine at 5 mg twice daily (BID), asenapine at 10 mg BID, placebo, or haloperidol at 4 mg BID (to verify assay sensitivity). With last observations carried forward (LOCF), mean Positive and Negative Syndrome Scale total score reductions from baseline to endpoint were significantly greater with asenapine at 5 mg BID (-16.2) and haloperidol (-15.4) than placebo (-10.7; both P < 0.05); using mixed model for repeated measures (MMRM), changes at day 42 were significantly greater with asenapine at 5 and 10 mg BID (-21.3 and -19.4, respectively) and haloperidol (-20.0) than placebo (-14.6; all P < 0.05). On the Positive and Negative Syndrome Scale positive subscale, all treatments were superior to placebo with LOCF and MMRM; asenapine at 5 mg BID was superior to placebo on the negative subscale with MMRM and on the general psychopathology subscale with LOCF and MMRM. Treatment-related adverse events (AEs) occurred in 44% and 52%, 57%, and 41% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Extrapyramidal symptoms reported as AEs occurred in 15% and 18%, 34%, and 10% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Across all groups, no more than 5% of patients had clinically significant weight change. Post hoc analyses indicated that efficacy was similar with asenapine and haloperidol; greater contrasts were seen in AEs, especially extrapyramidal symptoms.", "entity": "Bipolar Disorder", "aliases": "Affective Psychosis Bipolar Depression Disorder Disorders Manic Mania Manias Depressive State States Manic-Depressive Psychoses", "definition": "A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence.\n    ", "id": "MESH:D001714"}
{"mention": "psychotic", "mention_text": "Asenapine is approved by the Food and Drugs Administration in adults for acute treatment of schizophrenia or of manic or mixed episodes associated with bipolar I disorder with or without psychotic features. In a double-blind 6-week trial, 458 patients with acute schizophrenia were randomly assigned to fixed-dose treatment with asenapine at 5 mg twice daily (BID), asenapine at 10 mg BID, placebo, or haloperidol at 4 mg BID (to verify assay sensitivity). With last observations carried forward (LOCF), mean Positive and Negative Syndrome Scale total score reductions from baseline to endpoint were significantly greater with asenapine at 5 mg BID (-16.2) and haloperidol (-15.4) than placebo (-10.7; both P < 0.05); using mixed model for repeated measures (MMRM), changes at day 42 were significantly greater with asenapine at 5 and 10 mg BID (-21.3 and -19.4, respectively) and haloperidol (-20.0) than placebo (-14.6; all P < 0.05). On the Positive and Negative Syndrome Scale positive subscale, all treatments were superior to placebo with LOCF and MMRM; asenapine at 5 mg BID was superior to placebo on the negative subscale with MMRM and on the general psychopathology subscale with LOCF and MMRM. Treatment-related adverse events (AEs) occurred in 44% and 52%, 57%, and 41% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Extrapyramidal symptoms reported as AEs occurred in 15% and 18%, 34%, and 10% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Across all groups, no more than 5% of patients had clinically significant weight change. Post hoc analyses indicated that efficacy was similar with asenapine and haloperidol; greater contrasts were seen in AEs, especially extrapyramidal symptoms.", "entity": "Psychotic Disorders", "aliases": "Brief Reactive Psychoses Psychosis Disorder Psychotic Schizoaffective Schizophreniform Disorders", "definition": "Disorders in which there is a loss of ego boundaries or a gross impairment in reality testing with delusions or prominent hallucinations. (From DSM-IV, 1994)\n    ", "id": "MESH:D011618"}
{"mention": "asenapine", "mention_text": "Asenapine is approved by the Food and Drugs Administration in adults for acute treatment of schizophrenia or of manic or mixed episodes associated with bipolar I disorder with or without psychotic features. In a double-blind 6-week trial, 458 patients with acute schizophrenia were randomly assigned to fixed-dose treatment with asenapine at 5 mg twice daily (BID), asenapine at 10 mg BID, placebo, or haloperidol at 4 mg BID (to verify assay sensitivity). With last observations carried forward (LOCF), mean Positive and Negative Syndrome Scale total score reductions from baseline to endpoint were significantly greater with asenapine at 5 mg BID (-16.2) and haloperidol (-15.4) than placebo (-10.7; both P < 0.05); using mixed model for repeated measures (MMRM), changes at day 42 were significantly greater with asenapine at 5 and 10 mg BID (-21.3 and -19.4, respectively) and haloperidol (-20.0) than placebo (-14.6; all P < 0.05). On the Positive and Negative Syndrome Scale positive subscale, all treatments were superior to placebo with LOCF and MMRM; asenapine at 5 mg BID was superior to placebo on the negative subscale with MMRM and on the general psychopathology subscale with LOCF and MMRM. Treatment-related adverse events (AEs) occurred in 44% and 52%, 57%, and 41% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Extrapyramidal symptoms reported as AEs occurred in 15% and 18%, 34%, and 10% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Across all groups, no more than 5% of patients had clinically significant weight change. Post hoc analyses indicated that efficacy was similar with asenapine and haloperidol; greater contrasts were seen in AEs, especially extrapyramidal symptoms.", "entity": "Asenapine", "aliases": "5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenz(2,3-6,7)oxepino(4,5-c)pyrrole Asenapine ORG 5222 ORG-5222 asenapine maleate saphris", "definition": "", "id": "MESH:C522667"}
{"mention": "haloperidol", "mention_text": "Asenapine is approved by the Food and Drugs Administration in adults for acute treatment of schizophrenia or of manic or mixed episodes associated with bipolar I disorder with or without psychotic features. In a double-blind 6-week trial, 458 patients with acute schizophrenia were randomly assigned to fixed-dose treatment with asenapine at 5 mg twice daily (BID), asenapine at 10 mg BID, placebo, or haloperidol at 4 mg BID (to verify assay sensitivity). With last observations carried forward (LOCF), mean Positive and Negative Syndrome Scale total score reductions from baseline to endpoint were significantly greater with asenapine at 5 mg BID (-16.2) and haloperidol (-15.4) than placebo (-10.7; both P < 0.05); using mixed model for repeated measures (MMRM), changes at day 42 were significantly greater with asenapine at 5 and 10 mg BID (-21.3 and -19.4, respectively) and haloperidol (-20.0) than placebo (-14.6; all P < 0.05). On the Positive and Negative Syndrome Scale positive subscale, all treatments were superior to placebo with LOCF and MMRM; asenapine at 5 mg BID was superior to placebo on the negative subscale with MMRM and on the general psychopathology subscale with LOCF and MMRM. Treatment-related adverse events (AEs) occurred in 44% and 52%, 57%, and 41% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Extrapyramidal symptoms reported as AEs occurred in 15% and 18%, 34%, and 10% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Across all groups, no more than 5% of patients had clinically significant weight change. Post hoc analyses indicated that efficacy was similar with asenapine and haloperidol; greater contrasts were seen in AEs, especially extrapyramidal symptoms.", "entity": "Haloperidol", "aliases": "Haldol Haloperidol", "definition": "A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)\n    ", "id": "MESH:D006220"}
{"mention": "Extrapyramidal symptoms", "mention_text": "Asenapine is approved by the Food and Drugs Administration in adults for acute treatment of schizophrenia or of manic or mixed episodes associated with bipolar I disorder with or without psychotic features. In a double-blind 6-week trial, 458 patients with acute schizophrenia were randomly assigned to fixed-dose treatment with asenapine at 5 mg twice daily (BID), asenapine at 10 mg BID, placebo, or haloperidol at 4 mg BID (to verify assay sensitivity). With last observations carried forward (LOCF), mean Positive and Negative Syndrome Scale total score reductions from baseline to endpoint were significantly greater with asenapine at 5 mg BID (-16.2) and haloperidol (-15.4) than placebo (-10.7; both P < 0.05); using mixed model for repeated measures (MMRM), changes at day 42 were significantly greater with asenapine at 5 and 10 mg BID (-21.3 and -19.4, respectively) and haloperidol (-20.0) than placebo (-14.6; all P < 0.05). On the Positive and Negative Syndrome Scale positive subscale, all treatments were superior to placebo with LOCF and MMRM; asenapine at 5 mg BID was superior to placebo on the negative subscale with MMRM and on the general psychopathology subscale with LOCF and MMRM. Treatment-related adverse events (AEs) occurred in 44% and 52%, 57%, and 41% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Extrapyramidal symptoms reported as AEs occurred in 15% and 18%, 34%, and 10% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Across all groups, no more than 5% of patients had clinically significant weight change. Post hoc analyses indicated that efficacy was similar with asenapine and haloperidol; greater contrasts were seen in AEs, especially extrapyramidal symptoms.", "entity": "Basal Ganglia Diseases", "aliases": "Basal Ganglia Disease Diseases Disorder Disorders Extrapyramidal Lenticulostriate", "definition": "Diseases of the BASAL GANGLIA including the PUTAMEN; GLOBUS PALLIDUS; claustrum; AMYGDALA; and CAUDATE NUCLEUS. DYSKINESIAS (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include CEREBROVASCULAR DISORDERS; NEURODEGENERATIVE DISEASES; and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D001480"}
{"mention": "extrapyramidal symptoms", "mention_text": "Asenapine is approved by the Food and Drugs Administration in adults for acute treatment of schizophrenia or of manic or mixed episodes associated with bipolar I disorder with or without psychotic features. In a double-blind 6-week trial, 458 patients with acute schizophrenia were randomly assigned to fixed-dose treatment with asenapine at 5 mg twice daily (BID), asenapine at 10 mg BID, placebo, or haloperidol at 4 mg BID (to verify assay sensitivity). With last observations carried forward (LOCF), mean Positive and Negative Syndrome Scale total score reductions from baseline to endpoint were significantly greater with asenapine at 5 mg BID (-16.2) and haloperidol (-15.4) than placebo (-10.7; both P < 0.05); using mixed model for repeated measures (MMRM), changes at day 42 were significantly greater with asenapine at 5 and 10 mg BID (-21.3 and -19.4, respectively) and haloperidol (-20.0) than placebo (-14.6; all P < 0.05). On the Positive and Negative Syndrome Scale positive subscale, all treatments were superior to placebo with LOCF and MMRM; asenapine at 5 mg BID was superior to placebo on the negative subscale with MMRM and on the general psychopathology subscale with LOCF and MMRM. Treatment-related adverse events (AEs) occurred in 44% and 52%, 57%, and 41% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Extrapyramidal symptoms reported as AEs occurred in 15% and 18%, 34%, and 10% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Across all groups, no more than 5% of patients had clinically significant weight change. Post hoc analyses indicated that efficacy was similar with asenapine and haloperidol; greater contrasts were seen in AEs, especially extrapyramidal symptoms.", "entity": "Basal Ganglia Diseases", "aliases": "Basal Ganglia Disease Diseases Disorder Disorders Extrapyramidal Lenticulostriate", "definition": "Diseases of the BASAL GANGLIA including the PUTAMEN; GLOBUS PALLIDUS; claustrum; AMYGDALA; and CAUDATE NUCLEUS. DYSKINESIAS (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include CEREBROVASCULAR DISORDERS; NEURODEGENERATIVE DISEASES; and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D001480"}
{"mention": "puromycin aminonucleoside", "mention_text": "Permeability, ultrastructural changes, and distribution of novel proteins in the glomerular barrier in early puromycin aminonucleoside nephrosis.", "entity": "Puromycin Aminonucleoside", "aliases": "3' Amino 3' deoxy N,N dimethyladenosine 3'-Amino-3'-deoxy-N,N-dimethyladenosine Aminonucleoside Puromycin", "definition": "PUROMYCIN derivative that lacks the methoxyphenylalanyl group on the amine of the sugar ring. It is an antibiotic with antineoplastic properties and can cause nephrosis.\n    ", "id": "MESH:D011692"}
{"mention": "nephrosis", "mention_text": "Permeability, ultrastructural changes, and distribution of novel proteins in the glomerular barrier in early puromycin aminonucleoside nephrosis.", "entity": "Nephrosis", "aliases": "Nephroses Nephrosis", "definition": "Pathological processes of the KIDNEY without inflammatory or neoplastic components. Nephrosis may be a primary disorder or secondary complication of other diseases. It is characterized by the NEPHROTIC SYNDROME indicating the presence of PROTEINURIA and HYPOALBUMINEMIA with accompanying EDEMA.\n    ", "id": "MESH:D009401"}
{"mention": "proteinuria", "mention_text": "BACKGROUND/AIMS: It is still unclear what happens in the glomerulus when proteinuria starts. Using puromycin aminonucleoside nephrosis (PAN) rats, we studied early ultrastructural and permeability changes in relation to the expression of the podocyte-associated molecules nephrin, a-actinin, dendrin, and plekhh2, the last two of which were only recently discovered in podocytes. METHODS: Using immune stainings, semiquantitative measurement was performed under the electron microscope. Permeability was assessed using isolated kidney perfusion with tracers. Possible effects of ACE inhibition were tested. RESULTS: By day 2, some patchy foot process effacement, but no proteinuria, appeared. The amount of nephrin was reduced in both diseased and normal areas. The other proteins showed few changes, which were limited to diseased areas. By day 4, foot process effacement was complete and proteinuria appeared in parallel with signs of size barrier damage. Nephrin decreased further, while dendrin and plekhh2 also decreased but a-actinin remained unchanged. ACE inhibition had no significant protective effect. CONCLUSIONS: PAN glomeruli already showed significant pathology by day 4, despite relatively mild proteinuria. This was preceded by altered nephrin expression, supporting its pivotal role in podocyte morphology. The novel proteins dendrin and plekhh2 were both reduced, suggesting roles in PAN, whereas a-actinin was unchanged.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "puromycin aminonucleoside", "mention_text": "BACKGROUND/AIMS: It is still unclear what happens in the glomerulus when proteinuria starts. Using puromycin aminonucleoside nephrosis (PAN) rats, we studied early ultrastructural and permeability changes in relation to the expression of the podocyte-associated molecules nephrin, a-actinin, dendrin, and plekhh2, the last two of which were only recently discovered in podocytes. METHODS: Using immune stainings, semiquantitative measurement was performed under the electron microscope. Permeability was assessed using isolated kidney perfusion with tracers. Possible effects of ACE inhibition were tested. RESULTS: By day 2, some patchy foot process effacement, but no proteinuria, appeared. The amount of nephrin was reduced in both diseased and normal areas. The other proteins showed few changes, which were limited to diseased areas. By day 4, foot process effacement was complete and proteinuria appeared in parallel with signs of size barrier damage. Nephrin decreased further, while dendrin and plekhh2 also decreased but a-actinin remained unchanged. ACE inhibition had no significant protective effect. CONCLUSIONS: PAN glomeruli already showed significant pathology by day 4, despite relatively mild proteinuria. This was preceded by altered nephrin expression, supporting its pivotal role in podocyte morphology. The novel proteins dendrin and plekhh2 were both reduced, suggesting roles in PAN, whereas a-actinin was unchanged.", "entity": "Puromycin Aminonucleoside", "aliases": "3' Amino 3' deoxy N,N dimethyladenosine 3'-Amino-3'-deoxy-N,N-dimethyladenosine Aminonucleoside Puromycin", "definition": "PUROMYCIN derivative that lacks the methoxyphenylalanyl group on the amine of the sugar ring. It is an antibiotic with antineoplastic properties and can cause nephrosis.\n    ", "id": "MESH:D011692"}
{"mention": "nephrosis", "mention_text": "BACKGROUND/AIMS: It is still unclear what happens in the glomerulus when proteinuria starts. Using puromycin aminonucleoside nephrosis (PAN) rats, we studied early ultrastructural and permeability changes in relation to the expression of the podocyte-associated molecules nephrin, a-actinin, dendrin, and plekhh2, the last two of which were only recently discovered in podocytes. METHODS: Using immune stainings, semiquantitative measurement was performed under the electron microscope. Permeability was assessed using isolated kidney perfusion with tracers. Possible effects of ACE inhibition were tested. RESULTS: By day 2, some patchy foot process effacement, but no proteinuria, appeared. The amount of nephrin was reduced in both diseased and normal areas. The other proteins showed few changes, which were limited to diseased areas. By day 4, foot process effacement was complete and proteinuria appeared in parallel with signs of size barrier damage. Nephrin decreased further, while dendrin and plekhh2 also decreased but a-actinin remained unchanged. ACE inhibition had no significant protective effect. CONCLUSIONS: PAN glomeruli already showed significant pathology by day 4, despite relatively mild proteinuria. This was preceded by altered nephrin expression, supporting its pivotal role in podocyte morphology. The novel proteins dendrin and plekhh2 were both reduced, suggesting roles in PAN, whereas a-actinin was unchanged.", "entity": "Nephrosis", "aliases": "Nephroses Nephrosis", "definition": "Pathological processes of the KIDNEY without inflammatory or neoplastic components. Nephrosis may be a primary disorder or secondary complication of other diseases. It is characterized by the NEPHROTIC SYNDROME indicating the presence of PROTEINURIA and HYPOALBUMINEMIA with accompanying EDEMA.\n    ", "id": "MESH:D009401"}
{"mention": "cardiac toxicity", "mention_text": "Twin preterm neonates with cardiac toxicity related to lopinavir/ritonavir therapy.", "entity": "Cardiotoxicity", "aliases": "Cardiac Toxicities Toxicity Cardiotoxicities Cardiotoxicity", "definition": "Damage to the heart or its function secondary to exposure to toxic substances such as drugs used in CHEMOTHERAPY; IMMUNOTHERAPY; or RADIATION.\n    ", "id": "MESH:D066126"}
{"mention": "lopinavir/ritonavir", "mention_text": "Twin preterm neonates with cardiac toxicity related to lopinavir/ritonavir therapy.", "entity": "lopinavir-ritonavir drug combination", "aliases": "Aluvia Kaletra Lopimune lopinavir-ritonavir drug combination", "definition": "", "id": "MESH:C558899"}
{"mention": "human immunodeficiency virus infection", "mention_text": "We report twin neonates who were born prematurely at 32 weeks of gestation to a mother with human immunodeficiency virus infection. One of the twins developed complete heart block and dilated cardiomyopathy related to lopinavir/ritonavir therapy, a boosted protease-inhibitor agent, while the other twin developed mild bradycardia. We recommend caution in the use of lopinavir/ritonavir in the immediate neonatal period.", "entity": "HIV Infections", "aliases": "HIV Infection Infections HTLV III LAV HTLV-III HTLV-III-LAV T Lymphotropic Virus Type Human T-Lymphotropic", "definition": "Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).\n    ", "id": "MESH:D015658"}
{"mention": "heart block", "mention_text": "We report twin neonates who were born prematurely at 32 weeks of gestation to a mother with human immunodeficiency virus infection. One of the twins developed complete heart block and dilated cardiomyopathy related to lopinavir/ritonavir therapy, a boosted protease-inhibitor agent, while the other twin developed mild bradycardia. We recommend caution in the use of lopinavir/ritonavir in the immediate neonatal period.", "entity": "Heart Block", "aliases": "A V Dissociation A-V Dissociations Atrioventricular Auriculo Ventricular Auriculo-Ventricular Block Heart Blocks", "definition": "Impaired conduction of cardiac impulse that can occur anywhere along the conduction pathway, such as between the SINOATRIAL NODE and the right atrium (SA block) or between atria and ventricles (AV block). Heart blocks can be classified by the duration, frequency, or completeness of conduction block. Reversibility depends on the degree of structural or functional defects.\n    ", "id": "MESH:D006327"}
{"mention": "dilated cardiomyopathy", "mention_text": "We report twin neonates who were born prematurely at 32 weeks of gestation to a mother with human immunodeficiency virus infection. One of the twins developed complete heart block and dilated cardiomyopathy related to lopinavir/ritonavir therapy, a boosted protease-inhibitor agent, while the other twin developed mild bradycardia. We recommend caution in the use of lopinavir/ritonavir in the immediate neonatal period.", "entity": "Cardiomyopathy, Dilated", "aliases": "1A Dilated cardiomyopathy 1As Cardiomyopathies Congestive Familial Idiopathic Cardiomyopathy 1a Autosomal Recessive CMD1A LMNA With Conduction Defect 1 with Deffect1", "definition": "A form of CARDIAC MUSCLE disease that is characterized by ventricular dilation, VENTRICULAR DYSFUNCTION, and HEART FAILURE. Risk factors include SMOKING; ALCOHOL DRINKING; HYPERTENSION; INFECTION; PREGNANCY; and mutations in the LMNA gene encoding LAMIN TYPE A, a NUCLEAR LAMINA protein.\n    ", "id": "MESH:D002311"}
{"mention": "lopinavir/ritonavir", "mention_text": "We report twin neonates who were born prematurely at 32 weeks of gestation to a mother with human immunodeficiency virus infection. One of the twins developed complete heart block and dilated cardiomyopathy related to lopinavir/ritonavir therapy, a boosted protease-inhibitor agent, while the other twin developed mild bradycardia. We recommend caution in the use of lopinavir/ritonavir in the immediate neonatal period.", "entity": "lopinavir-ritonavir drug combination", "aliases": "Aluvia Kaletra Lopimune lopinavir-ritonavir drug combination", "definition": "", "id": "MESH:C558899"}
{"mention": "bradycardia", "mention_text": "We report twin neonates who were born prematurely at 32 weeks of gestation to a mother with human immunodeficiency virus infection. One of the twins developed complete heart block and dilated cardiomyopathy related to lopinavir/ritonavir therapy, a boosted protease-inhibitor agent, while the other twin developed mild bradycardia. We recommend caution in the use of lopinavir/ritonavir in the immediate neonatal period.", "entity": "Bradycardia", "aliases": "Bradyarrhythmia Bradyarrhythmias Bradycardia Bradycardias", "definition": "Cardiac arrhythmias that are characterized by excessively slow HEART RATE, usually below 50 beats per minute in human adults. They can be classified broadly into SINOATRIAL NODE dysfunction and ATRIOVENTRICULAR BLOCK.\n    ", "id": "MESH:D001919"}
{"mention": "amnesia", "mention_text": "Learning of rats under amnesia caused by pentobarbital.", "entity": "Amnesia", "aliases": "Amnesia Memory Loss Dissociative Global Hysterical Tactile Temporary Amnesia-Memory Losses Amnesias Amnestic State States", "definition": "Pathologic partial or complete loss of the ability to recall past experiences (AMNESIA, RETROGRADE) or to form new memories (AMNESIA, ANTEROGRADE). This condition may be of organic or psychologic origin. Organic forms of amnesia are usually associated with dysfunction of the DIENCEPHALON or HIPPOCAMPUS. (From Adams et al., Principles of Neurology, 6th ed, pp426-7)\n    ", "id": "MESH:D000647"}
{"mention": "pentobarbital", "mention_text": "Learning of rats under amnesia caused by pentobarbital.", "entity": "Pentobarbital", "aliases": "Diabutal Etaminal Ethaminal Mebubarbital Mebumal Monosodium Salt Pentobarbital Nembutal Sodium Pentobarbitone Sagatal", "definition": "A short-acting barbiturate that is effective as a sedative and hypnotic (but not as an anti-anxiety) agent and is usually given orally. It is prescribed more frequently for sleep induction than for sedation but, like similar agents, may lose its effectiveness by the second week of continued administration. (From AMA Drug Evaluations Annual, 1994, p236)\n    ", "id": "MESH:D010424"}
{"mention": "amnesia", "mention_text": "Dissociated learning of rats in the normal state and the state of amnesia produced by pentobarbital (15 mg/kg, ip) was carried out. Rats were trained to approach a shelf where they received food reinforcement. In Group 1 the rats were trained under the influence of pentobarbital to run to the same shelf as in the normal state. In Group 2 the rats were trained to approach different shelves in different drug states. It was shown that memory dissociation occurred in both groups. Differences in the parameters of training under the influence of pentobarbital between Groups 1 and 2 were revealed. These findings show that the brain-dissociated state induced by pentobarbital is formed with the participation of the mechanisms of information perception.", "entity": "Amnesia", "aliases": "Amnesia Memory Loss Dissociative Global Hysterical Tactile Temporary Amnesia-Memory Losses Amnesias Amnestic State States", "definition": "Pathologic partial or complete loss of the ability to recall past experiences (AMNESIA, RETROGRADE) or to form new memories (AMNESIA, ANTEROGRADE). This condition may be of organic or psychologic origin. Organic forms of amnesia are usually associated with dysfunction of the DIENCEPHALON or HIPPOCAMPUS. (From Adams et al., Principles of Neurology, 6th ed, pp426-7)\n    ", "id": "MESH:D000647"}
{"mention": "pentobarbital", "mention_text": "Dissociated learning of rats in the normal state and the state of amnesia produced by pentobarbital (15 mg/kg, ip) was carried out. Rats were trained to approach a shelf where they received food reinforcement. In Group 1 the rats were trained under the influence of pentobarbital to run to the same shelf as in the normal state. In Group 2 the rats were trained to approach different shelves in different drug states. It was shown that memory dissociation occurred in both groups. Differences in the parameters of training under the influence of pentobarbital between Groups 1 and 2 were revealed. These findings show that the brain-dissociated state induced by pentobarbital is formed with the participation of the mechanisms of information perception.", "entity": "Pentobarbital", "aliases": "Diabutal Etaminal Ethaminal Mebubarbital Mebumal Monosodium Salt Pentobarbital Nembutal Sodium Pentobarbitone Sagatal", "definition": "A short-acting barbiturate that is effective as a sedative and hypnotic (but not as an anti-anxiety) agent and is usually given orally. It is prescribed more frequently for sleep induction than for sedation but, like similar agents, may lose its effectiveness by the second week of continued administration. (From AMA Drug Evaluations Annual, 1994, p236)\n    ", "id": "MESH:D010424"}
{"mention": "memory dissociation", "mention_text": "Dissociated learning of rats in the normal state and the state of amnesia produced by pentobarbital (15 mg/kg, ip) was carried out. Rats were trained to approach a shelf where they received food reinforcement. In Group 1 the rats were trained under the influence of pentobarbital to run to the same shelf as in the normal state. In Group 2 the rats were trained to approach different shelves in different drug states. It was shown that memory dissociation occurred in both groups. Differences in the parameters of training under the influence of pentobarbital between Groups 1 and 2 were revealed. These findings show that the brain-dissociated state induced by pentobarbital is formed with the participation of the mechanisms of information perception.", "entity": "Memory Disorders", "aliases": "Age Related Memory Disorders Age-Related Disorder Cognitive Retention Deficit Deficits Semantic Spatial Loss Losses", "definition": "Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions.\n    ", "id": "MESH:D008569"}
{"mention": "Angiosarcoma", "mention_text": "Angiosarcoma of the liver associated with diethylstilbestrol.", "entity": "Hemangiosarcoma", "aliases": "Angiosarcoma Angiosarcomas Hemangiosarcoma Hemangiosarcomas", "definition": "A rare malignant neoplasm characterized by rapidly proliferating, extensively infiltrating, anaplastic cells derived from blood vessels and lining irregular blood-filled or lumpy spaces. (Stedman, 25th ed)\n    ", "id": "MESH:D006394"}
{"mention": "Angiosarcoma of the liver", "mention_text": "Angiosarcoma of the liver associated with diethylstilbestrol.", "entity": "Liver Neoplasms", "aliases": "Cancer of Liver the Hepatic Hepatocellular Cancers Neoplasm Neoplasms", "definition": "Tumors or cancer of the LIVER.\n    ", "id": "MESH:D008113"}
{"mention": "diethylstilbestrol", "mention_text": "Angiosarcoma of the liver associated with diethylstilbestrol.", "entity": "Diethylstilbestrol", "aliases": "APS Brand of Diethylstilbestrol Agostilben Apstil Co Pharma Co-Pharma (Z)-Isomer Disodium Salt Distilbène Estrogen Stilbene Gerda Stilbestrol Tampovagan", "definition": "A synthetic nonsteroidal estrogen used in the treatment of menopausal and postmenopausal disorders. It was also used formerly as a growth promoter in animals. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), diethylstilbestrol has been listed as a known carcinogen. (Merck, 11th ed)\n    ", "id": "MESH:D004054"}
{"mention": "Angiosarcoma", "mention_text": "Angiosarcoma of the liver occurred in a 76-year-old man who had been treated for a well-differentiated adenocarcinoma of the liver with diethylstilbestrol for 13 years. Angiosarcoma was also present within pulmonary and renal arteries. The possibility that the intraarterial lesions might represent independent primary tumors is considered.", "entity": "Hemangiosarcoma", "aliases": "Angiosarcoma Angiosarcomas Hemangiosarcoma Hemangiosarcomas", "definition": "A rare malignant neoplasm characterized by rapidly proliferating, extensively infiltrating, anaplastic cells derived from blood vessels and lining irregular blood-filled or lumpy spaces. (Stedman, 25th ed)\n    ", "id": "MESH:D006394"}
{"mention": "Angiosarcoma of the liver", "mention_text": "Angiosarcoma of the liver occurred in a 76-year-old man who had been treated for a well-differentiated adenocarcinoma of the liver with diethylstilbestrol for 13 years. Angiosarcoma was also present within pulmonary and renal arteries. The possibility that the intraarterial lesions might represent independent primary tumors is considered.", "entity": "Liver Neoplasms", "aliases": "Cancer of Liver the Hepatic Hepatocellular Cancers Neoplasm Neoplasms", "definition": "Tumors or cancer of the LIVER.\n    ", "id": "MESH:D008113"}
{"mention": "adenocarcinoma", "mention_text": "Angiosarcoma of the liver occurred in a 76-year-old man who had been treated for a well-differentiated adenocarcinoma of the liver with diethylstilbestrol for 13 years. Angiosarcoma was also present within pulmonary and renal arteries. The possibility that the intraarterial lesions might represent independent primary tumors is considered.", "entity": "Adenocarcinoma", "aliases": "Adenocarcinoma Basal Cell Granular Oxyphilic Tubular Adenocarcinomas Adenoma Malignant Adenomas Carcinoma Cribriform Carcinomas", "definition": "A malignant epithelial tumor with a glandular organization.\n    ", "id": "MESH:D000230"}
{"mention": "adenocarcinoma of the liver", "mention_text": "Angiosarcoma of the liver occurred in a 76-year-old man who had been treated for a well-differentiated adenocarcinoma of the liver with diethylstilbestrol for 13 years. Angiosarcoma was also present within pulmonary and renal arteries. The possibility that the intraarterial lesions might represent independent primary tumors is considered.", "entity": "Liver Neoplasms", "aliases": "Cancer of Liver the Hepatic Hepatocellular Cancers Neoplasm Neoplasms", "definition": "Tumors or cancer of the LIVER.\n    ", "id": "MESH:D008113"}
{"mention": "diethylstilbestrol", "mention_text": "Angiosarcoma of the liver occurred in a 76-year-old man who had been treated for a well-differentiated adenocarcinoma of the liver with diethylstilbestrol for 13 years. Angiosarcoma was also present within pulmonary and renal arteries. The possibility that the intraarterial lesions might represent independent primary tumors is considered.", "entity": "Diethylstilbestrol", "aliases": "APS Brand of Diethylstilbestrol Agostilben Apstil Co Pharma Co-Pharma (Z)-Isomer Disodium Salt Distilbène Estrogen Stilbene Gerda Stilbestrol Tampovagan", "definition": "A synthetic nonsteroidal estrogen used in the treatment of menopausal and postmenopausal disorders. It was also used formerly as a growth promoter in animals. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), diethylstilbestrol has been listed as a known carcinogen. (Merck, 11th ed)\n    ", "id": "MESH:D004054"}
{"mention": "intraarterial lesions", "mention_text": "Angiosarcoma of the liver occurred in a 76-year-old man who had been treated for a well-differentiated adenocarcinoma of the liver with diethylstilbestrol for 13 years. Angiosarcoma was also present within pulmonary and renal arteries. The possibility that the intraarterial lesions might represent independent primary tumors is considered.", "entity": "Vascular Diseases", "aliases": "Disease Vascular Diseases", "definition": "Pathological processes involving any of the BLOOD VESSELS in the cardiac or peripheral circulation. They include diseases of ARTERIES; VEINS; and rest of the vasculature system in the body.\n    ", "id": "MESH:D014652"}
{"mention": "tumors", "mention_text": "Angiosarcoma of the liver occurred in a 76-year-old man who had been treated for a well-differentiated adenocarcinoma of the liver with diethylstilbestrol for 13 years. Angiosarcoma was also present within pulmonary and renal arteries. The possibility that the intraarterial lesions might represent independent primary tumors is considered.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "xanthine", "mention_text": "Role of xanthine oxidase in dexamethasone-induced hypertension in rats.", "entity": "Xanthine", "aliases": "Xanthine", "definition": "A purine base found in most body tissues and fluids, certain plants, and some urinary calculi. It is an intermediate in the degradation of adenosine monophosphate to uric acid, being formed by oxidation of hypoxanthine. The methylated xanthine compounds caffeine, theobromine, and theophylline and their derivatives are used in medicine for their bronchodilator effects. (Dorland, 28th ed)\n    ", "id": "MESH:D019820"}
{"mention": "dexamethasone", "mention_text": "Role of xanthine oxidase in dexamethasone-induced hypertension in rats.", "entity": "Dexamethasone", "aliases": "Alcon Brand of Dexamethasone Decaject L.A. Decaject-L.A. Decameth Decaspray Dexasone Dexpak ECR Foy Hexadecadrol Hexadrol ICN Maxidex Merck Merz 1 2 Methylfluorprednisolone Millicorten Oradexon", "definition": "An anti-inflammatory 9-fluoro-glucocorticoid.\n    ", "id": "MESH:D003907"}
{"mention": "hypertension", "mention_text": "Role of xanthine oxidase in dexamethasone-induced hypertension in rats.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "hypertension", "mention_text": "1. Glucocorticoid-induced hypertension (GC-HT) in the rat is associated with nitric oxide-redox imbalance. 2. We studied the role of xanthine oxidase (XO), which is implicated in the production of reactive oxygen species, in dexamethasone-induced hypertension (dex-HT). 3. Thirty male Sprague-Dawley rats were divided randomly into four treatment groups: saline, dexamethasone (dex), allopurinol plus saline, and allopurinol plus dex. 4. Systolic blood pressures (SBP) and bodyweights were recorded each alternate day. Thymus weight was used as a marker of glucocorticoid activity, and serum urate to assess XO inhibition. 5. Dex increased SBP (110 +/- 2-126 +/- 3 mmHg; P < 0.001) and decreased thymus (P < 0.001) and bodyweights (P\" < 0.01). Allopurinol decreased serum urate from 76 +/- 5 to 30 +/- 3 micromol/L (P < 0.001) in saline and from 84 +/- 13 to 28 +/- 2 micromol/L in dex-treated (P < 0.01) groups. 6. Allopurinol did not prevent dex-HT. This, together with our previous findings that allopurinol failed to prevent adrenocorticotrophic hormone induced hypertension, suggests that XO activity is not a major determinant of GC-HT in the rat.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "HT", "mention_text": "1. Glucocorticoid-induced hypertension (GC-HT) in the rat is associated with nitric oxide-redox imbalance. 2. We studied the role of xanthine oxidase (XO), which is implicated in the production of reactive oxygen species, in dexamethasone-induced hypertension (dex-HT). 3. Thirty male Sprague-Dawley rats were divided randomly into four treatment groups: saline, dexamethasone (dex), allopurinol plus saline, and allopurinol plus dex. 4. Systolic blood pressures (SBP) and bodyweights were recorded each alternate day. Thymus weight was used as a marker of glucocorticoid activity, and serum urate to assess XO inhibition. 5. Dex increased SBP (110 +/- 2-126 +/- 3 mmHg; P < 0.001) and decreased thymus (P < 0.001) and bodyweights (P\" < 0.01). Allopurinol decreased serum urate from 76 +/- 5 to 30 +/- 3 micromol/L (P < 0.001) in saline and from 84 +/- 13 to 28 +/- 2 micromol/L in dex-treated (P < 0.01) groups. 6. Allopurinol did not prevent dex-HT. This, together with our previous findings that allopurinol failed to prevent adrenocorticotrophic hormone induced hypertension, suggests that XO activity is not a major determinant of GC-HT in the rat.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "nitric oxide", "mention_text": "1. Glucocorticoid-induced hypertension (GC-HT) in the rat is associated with nitric oxide-redox imbalance. 2. We studied the role of xanthine oxidase (XO), which is implicated in the production of reactive oxygen species, in dexamethasone-induced hypertension (dex-HT). 3. Thirty male Sprague-Dawley rats were divided randomly into four treatment groups: saline, dexamethasone (dex), allopurinol plus saline, and allopurinol plus dex. 4. Systolic blood pressures (SBP) and bodyweights were recorded each alternate day. Thymus weight was used as a marker of glucocorticoid activity, and serum urate to assess XO inhibition. 5. Dex increased SBP (110 +/- 2-126 +/- 3 mmHg; P < 0.001) and decreased thymus (P < 0.001) and bodyweights (P\" < 0.01). Allopurinol decreased serum urate from 76 +/- 5 to 30 +/- 3 micromol/L (P < 0.001) in saline and from 84 +/- 13 to 28 +/- 2 micromol/L in dex-treated (P < 0.01) groups. 6. Allopurinol did not prevent dex-HT. This, together with our previous findings that allopurinol failed to prevent adrenocorticotrophic hormone induced hypertension, suggests that XO activity is not a major determinant of GC-HT in the rat.", "entity": "Nitric Oxide", "aliases": "Endogenous Nitrate Vasodilator Endothelium-Derived Nitric Oxide Mononitrogen Monoxide Nitrogen Endothelium Derived", "definition": "A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.\n    ", "id": "MESH:D009569"}
{"mention": "xanthine", "mention_text": "1. Glucocorticoid-induced hypertension (GC-HT) in the rat is associated with nitric oxide-redox imbalance. 2. We studied the role of xanthine oxidase (XO), which is implicated in the production of reactive oxygen species, in dexamethasone-induced hypertension (dex-HT). 3. Thirty male Sprague-Dawley rats were divided randomly into four treatment groups: saline, dexamethasone (dex), allopurinol plus saline, and allopurinol plus dex. 4. Systolic blood pressures (SBP) and bodyweights were recorded each alternate day. Thymus weight was used as a marker of glucocorticoid activity, and serum urate to assess XO inhibition. 5. Dex increased SBP (110 +/- 2-126 +/- 3 mmHg; P < 0.001) and decreased thymus (P < 0.001) and bodyweights (P\" < 0.01). Allopurinol decreased serum urate from 76 +/- 5 to 30 +/- 3 micromol/L (P < 0.001) in saline and from 84 +/- 13 to 28 +/- 2 micromol/L in dex-treated (P < 0.01) groups. 6. Allopurinol did not prevent dex-HT. This, together with our previous findings that allopurinol failed to prevent adrenocorticotrophic hormone induced hypertension, suggests that XO activity is not a major determinant of GC-HT in the rat.", "entity": "Xanthine", "aliases": "Xanthine", "definition": "A purine base found in most body tissues and fluids, certain plants, and some urinary calculi. It is an intermediate in the degradation of adenosine monophosphate to uric acid, being formed by oxidation of hypoxanthine. The methylated xanthine compounds caffeine, theobromine, and theophylline and their derivatives are used in medicine for their bronchodilator effects. (Dorland, 28th ed)\n    ", "id": "MESH:D019820"}
{"mention": "dexamethasone", "mention_text": "1. Glucocorticoid-induced hypertension (GC-HT) in the rat is associated with nitric oxide-redox imbalance. 2. We studied the role of xanthine oxidase (XO), which is implicated in the production of reactive oxygen species, in dexamethasone-induced hypertension (dex-HT). 3. Thirty male Sprague-Dawley rats were divided randomly into four treatment groups: saline, dexamethasone (dex), allopurinol plus saline, and allopurinol plus dex. 4. Systolic blood pressures (SBP) and bodyweights were recorded each alternate day. Thymus weight was used as a marker of glucocorticoid activity, and serum urate to assess XO inhibition. 5. Dex increased SBP (110 +/- 2-126 +/- 3 mmHg; P < 0.001) and decreased thymus (P < 0.001) and bodyweights (P\" < 0.01). Allopurinol decreased serum urate from 76 +/- 5 to 30 +/- 3 micromol/L (P < 0.001) in saline and from 84 +/- 13 to 28 +/- 2 micromol/L in dex-treated (P < 0.01) groups. 6. Allopurinol did not prevent dex-HT. This, together with our previous findings that allopurinol failed to prevent adrenocorticotrophic hormone induced hypertension, suggests that XO activity is not a major determinant of GC-HT in the rat.", "entity": "Dexamethasone", "aliases": "Alcon Brand of Dexamethasone Decaject L.A. Decaject-L.A. Decameth Decaspray Dexasone Dexpak ECR Foy Hexadecadrol Hexadrol ICN Maxidex Merck Merz 1 2 Methylfluorprednisolone Millicorten Oradexon", "definition": "An anti-inflammatory 9-fluoro-glucocorticoid.\n    ", "id": "MESH:D003907"}
{"mention": "dex", "mention_text": "1. Glucocorticoid-induced hypertension (GC-HT) in the rat is associated with nitric oxide-redox imbalance. 2. We studied the role of xanthine oxidase (XO), which is implicated in the production of reactive oxygen species, in dexamethasone-induced hypertension (dex-HT). 3. Thirty male Sprague-Dawley rats were divided randomly into four treatment groups: saline, dexamethasone (dex), allopurinol plus saline, and allopurinol plus dex. 4. Systolic blood pressures (SBP) and bodyweights were recorded each alternate day. Thymus weight was used as a marker of glucocorticoid activity, and serum urate to assess XO inhibition. 5. Dex increased SBP (110 +/- 2-126 +/- 3 mmHg; P < 0.001) and decreased thymus (P < 0.001) and bodyweights (P\" < 0.01). Allopurinol decreased serum urate from 76 +/- 5 to 30 +/- 3 micromol/L (P < 0.001) in saline and from 84 +/- 13 to 28 +/- 2 micromol/L in dex-treated (P < 0.01) groups. 6. Allopurinol did not prevent dex-HT. This, together with our previous findings that allopurinol failed to prevent adrenocorticotrophic hormone induced hypertension, suggests that XO activity is not a major determinant of GC-HT in the rat.", "entity": "Dexamethasone", "aliases": "Alcon Brand of Dexamethasone Decaject L.A. Decaject-L.A. Decameth Decaspray Dexasone Dexpak ECR Foy Hexadecadrol Hexadrol ICN Maxidex Merck Merz 1 2 Methylfluorprednisolone Millicorten Oradexon", "definition": "An anti-inflammatory 9-fluoro-glucocorticoid.\n    ", "id": "MESH:D003907"}
{"mention": "allopurinol", "mention_text": "1. Glucocorticoid-induced hypertension (GC-HT) in the rat is associated with nitric oxide-redox imbalance. 2. We studied the role of xanthine oxidase (XO), which is implicated in the production of reactive oxygen species, in dexamethasone-induced hypertension (dex-HT). 3. Thirty male Sprague-Dawley rats were divided randomly into four treatment groups: saline, dexamethasone (dex), allopurinol plus saline, and allopurinol plus dex. 4. Systolic blood pressures (SBP) and bodyweights were recorded each alternate day. Thymus weight was used as a marker of glucocorticoid activity, and serum urate to assess XO inhibition. 5. Dex increased SBP (110 +/- 2-126 +/- 3 mmHg; P < 0.001) and decreased thymus (P < 0.001) and bodyweights (P\" < 0.01). Allopurinol decreased serum urate from 76 +/- 5 to 30 +/- 3 micromol/L (P < 0.001) in saline and from 84 +/- 13 to 28 +/- 2 micromol/L in dex-treated (P < 0.01) groups. 6. Allopurinol did not prevent dex-HT. This, together with our previous findings that allopurinol failed to prevent adrenocorticotrophic hormone induced hypertension, suggests that XO activity is not a major determinant of GC-HT in the rat.", "entity": "Allopurinol", "aliases": "APS Brand of Allopurinol Allohexal Allohexan Alloprin Allopurin Alphapharm Amrad Ashbourne Azupharma BASF Bicther Boots Clonmel Dorsch Douglas Hennig Hexal Horner ICN Jenapharm Merckle Merz Multipharma Nicholas Novopharm Pharmafarm Pinewood Protea R.A.N. Rima Roche Rosen Rougier TAD Thiemann Wellcome gepepharm Allorin Allpargin Allural Apulonga Apurin Atisuril Bleminol Boehringer Mannheim Byk Gulden Caplenal Capurate Cellidrin Embarin Fawns & McAllan Foligan Glaxo Hamarin Henning Berlin Jenapuri", "definition": "A XANTHINE OXIDASE inhibitor that decreases URIC ACID production. It also acts as an antimetabolite on some simpler organisms.\n    ", "id": "MESH:D000493"}
{"mention": "urate", "mention_text": "1. Glucocorticoid-induced hypertension (GC-HT) in the rat is associated with nitric oxide-redox imbalance. 2. We studied the role of xanthine oxidase (XO), which is implicated in the production of reactive oxygen species, in dexamethasone-induced hypertension (dex-HT). 3. Thirty male Sprague-Dawley rats were divided randomly into four treatment groups: saline, dexamethasone (dex), allopurinol plus saline, and allopurinol plus dex. 4. Systolic blood pressures (SBP) and bodyweights were recorded each alternate day. Thymus weight was used as a marker of glucocorticoid activity, and serum urate to assess XO inhibition. 5. Dex increased SBP (110 +/- 2-126 +/- 3 mmHg; P < 0.001) and decreased thymus (P < 0.001) and bodyweights (P\" < 0.01). Allopurinol decreased serum urate from 76 +/- 5 to 30 +/- 3 micromol/L (P < 0.001) in saline and from 84 +/- 13 to 28 +/- 2 micromol/L in dex-treated (P < 0.01) groups. 6. Allopurinol did not prevent dex-HT. This, together with our previous findings that allopurinol failed to prevent adrenocorticotrophic hormone induced hypertension, suggests that XO activity is not a major determinant of GC-HT in the rat.", "entity": "Uric Acid", "aliases": "2,6,8-Trihydroxypurine Acid Urate Ammonium Sodium Uric Monohydrate Monosodium Potassium Trioxopurine", "definition": "An oxidation product, via XANTHINE OXIDASE, of oxypurines such as XANTHINE and HYPOXANTHINE. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals URATE OXIDASE further oxidizes it to ALLANTOIN.\n    ", "id": "MESH:D014527"}
{"mention": "Dex", "mention_text": "1. Glucocorticoid-induced hypertension (GC-HT) in the rat is associated with nitric oxide-redox imbalance. 2. We studied the role of xanthine oxidase (XO), which is implicated in the production of reactive oxygen species, in dexamethasone-induced hypertension (dex-HT). 3. Thirty male Sprague-Dawley rats were divided randomly into four treatment groups: saline, dexamethasone (dex), allopurinol plus saline, and allopurinol plus dex. 4. Systolic blood pressures (SBP) and bodyweights were recorded each alternate day. Thymus weight was used as a marker of glucocorticoid activity, and serum urate to assess XO inhibition. 5. Dex increased SBP (110 +/- 2-126 +/- 3 mmHg; P < 0.001) and decreased thymus (P < 0.001) and bodyweights (P\" < 0.01). Allopurinol decreased serum urate from 76 +/- 5 to 30 +/- 3 micromol/L (P < 0.001) in saline and from 84 +/- 13 to 28 +/- 2 micromol/L in dex-treated (P < 0.01) groups. 6. Allopurinol did not prevent dex-HT. This, together with our previous findings that allopurinol failed to prevent adrenocorticotrophic hormone induced hypertension, suggests that XO activity is not a major determinant of GC-HT in the rat.", "entity": "Dexamethasone", "aliases": "Alcon Brand of Dexamethasone Decaject L.A. Decaject-L.A. Decameth Decaspray Dexasone Dexpak ECR Foy Hexadecadrol Hexadrol ICN Maxidex Merck Merz 1 2 Methylfluorprednisolone Millicorten Oradexon", "definition": "An anti-inflammatory 9-fluoro-glucocorticoid.\n    ", "id": "MESH:D003907"}
{"mention": "increased SBP", "mention_text": "1. Glucocorticoid-induced hypertension (GC-HT) in the rat is associated with nitric oxide-redox imbalance. 2. We studied the role of xanthine oxidase (XO), which is implicated in the production of reactive oxygen species, in dexamethasone-induced hypertension (dex-HT). 3. Thirty male Sprague-Dawley rats were divided randomly into four treatment groups: saline, dexamethasone (dex), allopurinol plus saline, and allopurinol plus dex. 4. Systolic blood pressures (SBP) and bodyweights were recorded each alternate day. Thymus weight was used as a marker of glucocorticoid activity, and serum urate to assess XO inhibition. 5. Dex increased SBP (110 +/- 2-126 +/- 3 mmHg; P < 0.001) and decreased thymus (P < 0.001) and bodyweights (P\" < 0.01). Allopurinol decreased serum urate from 76 +/- 5 to 30 +/- 3 micromol/L (P < 0.001) in saline and from 84 +/- 13 to 28 +/- 2 micromol/L in dex-treated (P < 0.01) groups. 6. Allopurinol did not prevent dex-HT. This, together with our previous findings that allopurinol failed to prevent adrenocorticotrophic hormone induced hypertension, suggests that XO activity is not a major determinant of GC-HT in the rat.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "decreased thymus (P < 0.001) and bodyweights", "mention_text": "1. Glucocorticoid-induced hypertension (GC-HT) in the rat is associated with nitric oxide-redox imbalance. 2. We studied the role of xanthine oxidase (XO), which is implicated in the production of reactive oxygen species, in dexamethasone-induced hypertension (dex-HT). 3. Thirty male Sprague-Dawley rats were divided randomly into four treatment groups: saline, dexamethasone (dex), allopurinol plus saline, and allopurinol plus dex. 4. Systolic blood pressures (SBP) and bodyweights were recorded each alternate day. Thymus weight was used as a marker of glucocorticoid activity, and serum urate to assess XO inhibition. 5. Dex increased SBP (110 +/- 2-126 +/- 3 mmHg; P < 0.001) and decreased thymus (P < 0.001) and bodyweights (P\" < 0.01). Allopurinol decreased serum urate from 76 +/- 5 to 30 +/- 3 micromol/L (P < 0.001) in saline and from 84 +/- 13 to 28 +/- 2 micromol/L in dex-treated (P < 0.01) groups. 6. Allopurinol did not prevent dex-HT. This, together with our previous findings that allopurinol failed to prevent adrenocorticotrophic hormone induced hypertension, suggests that XO activity is not a major determinant of GC-HT in the rat.", "entity": "Weight Loss", "aliases": "Loss Weight Losses Reduction Reductions", "definition": "Decrease in existing BODY WEIGHT.\n    ", "id": "MESH:D015431"}
{"mention": "Allopurinol", "mention_text": "1. Glucocorticoid-induced hypertension (GC-HT) in the rat is associated with nitric oxide-redox imbalance. 2. We studied the role of xanthine oxidase (XO), which is implicated in the production of reactive oxygen species, in dexamethasone-induced hypertension (dex-HT). 3. Thirty male Sprague-Dawley rats were divided randomly into four treatment groups: saline, dexamethasone (dex), allopurinol plus saline, and allopurinol plus dex. 4. Systolic blood pressures (SBP) and bodyweights were recorded each alternate day. Thymus weight was used as a marker of glucocorticoid activity, and serum urate to assess XO inhibition. 5. Dex increased SBP (110 +/- 2-126 +/- 3 mmHg; P < 0.001) and decreased thymus (P < 0.001) and bodyweights (P\" < 0.01). Allopurinol decreased serum urate from 76 +/- 5 to 30 +/- 3 micromol/L (P < 0.001) in saline and from 84 +/- 13 to 28 +/- 2 micromol/L in dex-treated (P < 0.01) groups. 6. Allopurinol did not prevent dex-HT. This, together with our previous findings that allopurinol failed to prevent adrenocorticotrophic hormone induced hypertension, suggests that XO activity is not a major determinant of GC-HT in the rat.", "entity": "Allopurinol", "aliases": "APS Brand of Allopurinol Allohexal Allohexan Alloprin Allopurin Alphapharm Amrad Ashbourne Azupharma BASF Bicther Boots Clonmel Dorsch Douglas Hennig Hexal Horner ICN Jenapharm Merckle Merz Multipharma Nicholas Novopharm Pharmafarm Pinewood Protea R.A.N. Rima Roche Rosen Rougier TAD Thiemann Wellcome gepepharm Allorin Allpargin Allural Apulonga Apurin Atisuril Bleminol Boehringer Mannheim Byk Gulden Caplenal Capurate Cellidrin Embarin Fawns & McAllan Foligan Glaxo Hamarin Henning Berlin Jenapuri", "definition": "A XANTHINE OXIDASE inhibitor that decreases URIC ACID production. It also acts as an antimetabolite on some simpler organisms.\n    ", "id": "MESH:D000493"}
{"mention": "risperidone", "mention_text": "Extrapyramidal side effects with risperidone and haloperidol at comparable D2 receptor occupancy levels.", "entity": "Risperidone", "aliases": "Consta Risperdal R 64,766 64766 R-64,766 R-64766 R64,766 R64766 Risperidal Risperidone", "definition": "A selective blocker of DOPAMINE D2 RECEPTORS and SEROTONIN 5-HT2 RECEPTORS that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of SCHIZOPHRENIA.\n    ", "id": "MESH:D018967"}
{"mention": "haloperidol", "mention_text": "Extrapyramidal side effects with risperidone and haloperidol at comparable D2 receptor occupancy levels.", "entity": "Haloperidol", "aliases": "Haldol Haloperidol", "definition": "A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)\n    ", "id": "MESH:D006220"}
{"mention": "Risperidone", "mention_text": "Risperidone is an antipsychotic drug with high affinity at dopamine D2 and serotonin 5-HT2 receptors. Previous clinical studies have proposed that risperidone's pharmacologic profile may produce improved efficacy for negative psychotic symptoms and decreased propensity for extrapyramidal side effects; features shared by so-called 'atypical' neuroleptics. To determine if routine risperidone treatment is associated with a unique degree of D2 receptor occupancy and pattern of clinical effects, we used [123I]IBZM SPECT to determine D2 occupancy in subjects treated with routine clinical doses of risperidone (n = 12) or haloperidol (n = 7). Both risperidone and haloperidol produced D2 occupancy levels between approximately 60 and 90% at standard clinical doses. There was no significant difference between occupancy levels obtained with haloperidol or risperidone. Drug-induced parkinsonism was observed in subjects treated with risperidone (42%) and haloperidol (29%) and was observed at occupancy levels above 60%. Based on these observations, it is concluded that 5-HT2 blockade obtained with risperidone at D2 occupancy rates of 60% and above does not appear to protect against the risk for extrapyramidal side effects.", "entity": "Risperidone", "aliases": "Consta Risperdal R 64,766 64766 R-64,766 R-64766 R64,766 R64766 Risperidal Risperidone", "definition": "A selective blocker of DOPAMINE D2 RECEPTORS and SEROTONIN 5-HT2 RECEPTORS that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of SCHIZOPHRENIA.\n    ", "id": "MESH:D018967"}
{"mention": "dopamine", "mention_text": "Risperidone is an antipsychotic drug with high affinity at dopamine D2 and serotonin 5-HT2 receptors. Previous clinical studies have proposed that risperidone's pharmacologic profile may produce improved efficacy for negative psychotic symptoms and decreased propensity for extrapyramidal side effects; features shared by so-called 'atypical' neuroleptics. To determine if routine risperidone treatment is associated with a unique degree of D2 receptor occupancy and pattern of clinical effects, we used [123I]IBZM SPECT to determine D2 occupancy in subjects treated with routine clinical doses of risperidone (n = 12) or haloperidol (n = 7). Both risperidone and haloperidol produced D2 occupancy levels between approximately 60 and 90% at standard clinical doses. There was no significant difference between occupancy levels obtained with haloperidol or risperidone. Drug-induced parkinsonism was observed in subjects treated with risperidone (42%) and haloperidol (29%) and was observed at occupancy levels above 60%. Based on these observations, it is concluded that 5-HT2 blockade obtained with risperidone at D2 occupancy rates of 60% and above does not appear to protect against the risk for extrapyramidal side effects.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "serotonin 5-HT2", "mention_text": "Risperidone is an antipsychotic drug with high affinity at dopamine D2 and serotonin 5-HT2 receptors. Previous clinical studies have proposed that risperidone's pharmacologic profile may produce improved efficacy for negative psychotic symptoms and decreased propensity for extrapyramidal side effects; features shared by so-called 'atypical' neuroleptics. To determine if routine risperidone treatment is associated with a unique degree of D2 receptor occupancy and pattern of clinical effects, we used [123I]IBZM SPECT to determine D2 occupancy in subjects treated with routine clinical doses of risperidone (n = 12) or haloperidol (n = 7). Both risperidone and haloperidol produced D2 occupancy levels between approximately 60 and 90% at standard clinical doses. There was no significant difference between occupancy levels obtained with haloperidol or risperidone. Drug-induced parkinsonism was observed in subjects treated with risperidone (42%) and haloperidol (29%) and was observed at occupancy levels above 60%. Based on these observations, it is concluded that 5-HT2 blockade obtained with risperidone at D2 occupancy rates of 60% and above does not appear to protect against the risk for extrapyramidal side effects.", "entity": "Receptors, Serotonin, 5-HT2", "aliases": "5 HT 2 Receptors 5-HT-2 5-HT2 Serotonin S2 Serotonin-2 HT2", "definition": "A subclass of G-protein coupled SEROTONIN receptors that couple preferentially to the GQ-G11 G-PROTEINS resulting in increased intracellular levels of INOSITOL PHOSPHATES and free CALCIUM.\n    ", "id": "MESH:D044348"}
{"mention": "risperidone", "mention_text": "Risperidone is an antipsychotic drug with high affinity at dopamine D2 and serotonin 5-HT2 receptors. Previous clinical studies have proposed that risperidone's pharmacologic profile may produce improved efficacy for negative psychotic symptoms and decreased propensity for extrapyramidal side effects; features shared by so-called 'atypical' neuroleptics. To determine if routine risperidone treatment is associated with a unique degree of D2 receptor occupancy and pattern of clinical effects, we used [123I]IBZM SPECT to determine D2 occupancy in subjects treated with routine clinical doses of risperidone (n = 12) or haloperidol (n = 7). Both risperidone and haloperidol produced D2 occupancy levels between approximately 60 and 90% at standard clinical doses. There was no significant difference between occupancy levels obtained with haloperidol or risperidone. Drug-induced parkinsonism was observed in subjects treated with risperidone (42%) and haloperidol (29%) and was observed at occupancy levels above 60%. Based on these observations, it is concluded that 5-HT2 blockade obtained with risperidone at D2 occupancy rates of 60% and above does not appear to protect against the risk for extrapyramidal side effects.", "entity": "Risperidone", "aliases": "Consta Risperdal R 64,766 64766 R-64,766 R-64766 R64,766 R64766 Risperidal Risperidone", "definition": "A selective blocker of DOPAMINE D2 RECEPTORS and SEROTONIN 5-HT2 RECEPTORS that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of SCHIZOPHRENIA.\n    ", "id": "MESH:D018967"}
{"mention": "psychotic symptoms", "mention_text": "Risperidone is an antipsychotic drug with high affinity at dopamine D2 and serotonin 5-HT2 receptors. Previous clinical studies have proposed that risperidone's pharmacologic profile may produce improved efficacy for negative psychotic symptoms and decreased propensity for extrapyramidal side effects; features shared by so-called 'atypical' neuroleptics. To determine if routine risperidone treatment is associated with a unique degree of D2 receptor occupancy and pattern of clinical effects, we used [123I]IBZM SPECT to determine D2 occupancy in subjects treated with routine clinical doses of risperidone (n = 12) or haloperidol (n = 7). Both risperidone and haloperidol produced D2 occupancy levels between approximately 60 and 90% at standard clinical doses. There was no significant difference between occupancy levels obtained with haloperidol or risperidone. Drug-induced parkinsonism was observed in subjects treated with risperidone (42%) and haloperidol (29%) and was observed at occupancy levels above 60%. Based on these observations, it is concluded that 5-HT2 blockade obtained with risperidone at D2 occupancy rates of 60% and above does not appear to protect against the risk for extrapyramidal side effects.", "entity": "Psychotic Disorders", "aliases": "Brief Reactive Psychoses Psychosis Disorder Psychotic Schizoaffective Schizophreniform Disorders", "definition": "Disorders in which there is a loss of ego boundaries or a gross impairment in reality testing with delusions or prominent hallucinations. (From DSM-IV, 1994)\n    ", "id": "MESH:D011618"}
{"mention": "haloperidol", "mention_text": "Risperidone is an antipsychotic drug with high affinity at dopamine D2 and serotonin 5-HT2 receptors. Previous clinical studies have proposed that risperidone's pharmacologic profile may produce improved efficacy for negative psychotic symptoms and decreased propensity for extrapyramidal side effects; features shared by so-called 'atypical' neuroleptics. To determine if routine risperidone treatment is associated with a unique degree of D2 receptor occupancy and pattern of clinical effects, we used [123I]IBZM SPECT to determine D2 occupancy in subjects treated with routine clinical doses of risperidone (n = 12) or haloperidol (n = 7). Both risperidone and haloperidol produced D2 occupancy levels between approximately 60 and 90% at standard clinical doses. There was no significant difference between occupancy levels obtained with haloperidol or risperidone. Drug-induced parkinsonism was observed in subjects treated with risperidone (42%) and haloperidol (29%) and was observed at occupancy levels above 60%. Based on these observations, it is concluded that 5-HT2 blockade obtained with risperidone at D2 occupancy rates of 60% and above does not appear to protect against the risk for extrapyramidal side effects.", "entity": "Haloperidol", "aliases": "Haldol Haloperidol", "definition": "A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)\n    ", "id": "MESH:D006220"}
{"mention": "Drug-induced parkinsonism", "mention_text": "Risperidone is an antipsychotic drug with high affinity at dopamine D2 and serotonin 5-HT2 receptors. Previous clinical studies have proposed that risperidone's pharmacologic profile may produce improved efficacy for negative psychotic symptoms and decreased propensity for extrapyramidal side effects; features shared by so-called 'atypical' neuroleptics. To determine if routine risperidone treatment is associated with a unique degree of D2 receptor occupancy and pattern of clinical effects, we used [123I]IBZM SPECT to determine D2 occupancy in subjects treated with routine clinical doses of risperidone (n = 12) or haloperidol (n = 7). Both risperidone and haloperidol produced D2 occupancy levels between approximately 60 and 90% at standard clinical doses. There was no significant difference between occupancy levels obtained with haloperidol or risperidone. Drug-induced parkinsonism was observed in subjects treated with risperidone (42%) and haloperidol (29%) and was observed at occupancy levels above 60%. Based on these observations, it is concluded that 5-HT2 blockade obtained with risperidone at D2 occupancy rates of 60% and above does not appear to protect against the risk for extrapyramidal side effects.", "entity": "Parkinson Disease, Secondary", "aliases": "Atherosclerotic Parkinsonism Parkinson Disease Secondary Vascular Symptomatic", "definition": "Conditions which feature clinical manifestations resembling primary Parkinson disease that are caused by a known or suspected condition. Examples include parkinsonism caused by vascular injury, drugs, trauma, toxin exposure, neoplasms, infections and degenerative or hereditary conditions. Clinical features may include bradykinesia, rigidity, parkinsonian gait, and masked facies. In general, tremor is less prominent in secondary parkinsonism than in the primary form. (From Joynt, Clinical Neurology, 1998, Ch38, pp39-42)\n    ", "id": "MESH:D010302"}
{"mention": "Simvastatin-ezetimibe", "mention_text": "Simvastatin-ezetimibe-induced hepatic failure necessitating liver transplantation.", "entity": "ezetimibe, simvastatin drug combination", "aliases": "Inegy Vytorin ezetimibe simvastatin drug combination ezetimibe-simvastatin", "definition": "", "id": "MESH:C492458"}
{"mention": "hepatic failure", "mention_text": "Simvastatin-ezetimibe-induced hepatic failure necessitating liver transplantation.", "entity": "Liver Failure", "aliases": "Hepatic Failure Liver", "definition": "Severe inability of the LIVER to perform its normal metabolic functions, as evidenced by severe JAUNDICE and abnormal serum levels of AMMONIA; BILIRUBIN; ALKALINE PHOSPHATASE; ASPARTATE AMINOTRANSFERASE; LACTATE DEHYDROGENASES; and albumin/globulin ratio. (Blakiston's Gould Medical Dictionary, 4th ed)\n    ", "id": "MESH:D017093"}
{"mention": "statin", "mention_text": "Abstract Serum aminotransferase elevations are a commonly known adverse effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin-ezetimibe. We describe a 70-year-old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg/day to simvastatin 10 mg-ezetimibe 40 mg/day. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work-up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatinezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work-up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate-to-severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2-year follow-up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin-ezetimibe-induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatinezetimibe-induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin-ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.", "entity": "Simvastatin", "aliases": "MK 733 MK-733 MK733 Simvastatin Synvinolin Zocor", "definition": "A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL CHOLESTEROL.\n    ", "id": "MESH:D019821"}
{"mention": "hepatotoxic", "mention_text": "Abstract Serum aminotransferase elevations are a commonly known adverse effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin-ezetimibe. We describe a 70-year-old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg/day to simvastatin 10 mg-ezetimibe 40 mg/day. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work-up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatinezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work-up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate-to-severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2-year follow-up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin-ezetimibe-induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatinezetimibe-induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin-ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "ezetimibe", "mention_text": "Abstract Serum aminotransferase elevations are a commonly known adverse effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin-ezetimibe. We describe a 70-year-old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg/day to simvastatin 10 mg-ezetimibe 40 mg/day. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work-up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatinezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work-up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate-to-severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2-year follow-up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin-ezetimibe-induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatinezetimibe-induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin-ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.", "entity": "ezetimibe", "aliases": "(1-(4-fluorophenyl)-(3R)-(3-(4-fluorophenyl)-(3S)-hydroxypropyl)-(4S)-(4-hydroxyphenyl)-2-azetidinone) Essex brand of ezetimibe Ezetrol MSD Merck SCH 58235 SCH-58235 SCH58235 Schering-Plough Zetia ezetimib", "definition": "", "id": "MESH:C108606"}
{"mention": "simvastatin-ezetimibe", "mention_text": "Abstract Serum aminotransferase elevations are a commonly known adverse effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin-ezetimibe. We describe a 70-year-old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg/day to simvastatin 10 mg-ezetimibe 40 mg/day. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work-up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatinezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work-up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate-to-severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2-year follow-up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin-ezetimibe-induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatinezetimibe-induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin-ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.", "entity": "ezetimibe, simvastatin drug combination", "aliases": "Inegy Vytorin ezetimibe simvastatin drug combination ezetimibe-simvastatin", "definition": "", "id": "MESH:C492458"}
{"mention": "fulminant hepatic failure", "mention_text": "Abstract Serum aminotransferase elevations are a commonly known adverse effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin-ezetimibe. We describe a 70-year-old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg/day to simvastatin 10 mg-ezetimibe 40 mg/day. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work-up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatinezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work-up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate-to-severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2-year follow-up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin-ezetimibe-induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatinezetimibe-induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin-ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.", "entity": "Liver Failure, Acute", "aliases": "Acute Hepatic Failure Liver Fulminant Failures Fulminating", "definition": "A form of rapid-onset LIVER FAILURE, also known as fulminant hepatic failure, caused by severe liver injury or massive loss of HEPATOCYTES. It is characterized by sudden development of liver dysfunction and JAUNDICE. Acute liver failure may progress to exhibit cerebral dysfunction even HEPATIC COMA depending on the etiology that includes hepatic ISCHEMIA, drug toxicity, malignant infiltration, and viral hepatitis such as post-transfusion HEPATITIS B and HEPATITIS C.\n    ", "id": "MESH:D017114"}
{"mention": "simvastatin", "mention_text": "Abstract Serum aminotransferase elevations are a commonly known adverse effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin-ezetimibe. We describe a 70-year-old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg/day to simvastatin 10 mg-ezetimibe 40 mg/day. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work-up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatinezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work-up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate-to-severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2-year follow-up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin-ezetimibe-induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatinezetimibe-induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin-ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.", "entity": "Simvastatin", "aliases": "MK 733 MK-733 MK733 Simvastatin Synvinolin Zocor", "definition": "A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL CHOLESTEROL.\n    ", "id": "MESH:D019821"}
{"mention": "simvastatin 10 mg-ezetimibe 40 mg", "mention_text": "Abstract Serum aminotransferase elevations are a commonly known adverse effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin-ezetimibe. We describe a 70-year-old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg/day to simvastatin 10 mg-ezetimibe 40 mg/day. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work-up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatinezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work-up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate-to-severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2-year follow-up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin-ezetimibe-induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatinezetimibe-induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin-ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.", "entity": "ezetimibe, simvastatin drug combination", "aliases": "Inegy Vytorin ezetimibe simvastatin drug combination ezetimibe-simvastatin", "definition": "", "id": "MESH:C492458"}
{"mention": "hepatotoxicity", "mention_text": "Abstract Serum aminotransferase elevations are a commonly known adverse effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin-ezetimibe. We describe a 70-year-old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg/day to simvastatin 10 mg-ezetimibe 40 mg/day. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work-up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatinezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work-up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate-to-severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2-year follow-up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin-ezetimibe-induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatinezetimibe-induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin-ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "Simvastatinezetimibe", "mention_text": "Abstract Serum aminotransferase elevations are a commonly known adverse effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin-ezetimibe. We describe a 70-year-old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg/day to simvastatin 10 mg-ezetimibe 40 mg/day. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work-up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatinezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work-up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate-to-severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2-year follow-up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin-ezetimibe-induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatinezetimibe-induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin-ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.", "entity": "ezetimibe, simvastatin drug combination", "aliases": "Inegy Vytorin ezetimibe simvastatin drug combination ezetimibe-simvastatin", "definition": "", "id": "MESH:C492458"}
{"mention": "escitalopram", "mention_text": "Abstract Serum aminotransferase elevations are a commonly known adverse effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin-ezetimibe. We describe a 70-year-old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg/day to simvastatin 10 mg-ezetimibe 40 mg/day. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work-up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatinezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work-up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate-to-severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2-year follow-up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin-ezetimibe-induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatinezetimibe-induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin-ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.", "entity": "Citalopram", "aliases": "Citalopram Cytalopram Escitalopram Lexapro Lu-10-171 Lu10171", "definition": "A furancarbonitrile that is one of the SEROTONIN UPTAKE INHIBITORS used as an antidepressant. The drug is also effective in reducing ethanol uptake in alcoholics and is used in depressed patients who also suffer from tardive dyskinesia in preference to tricyclic antidepressants, which aggravate this condition.\n    ", "id": "MESH:D015283"}
{"mention": "depression", "mention_text": "Abstract Serum aminotransferase elevations are a commonly known adverse effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin-ezetimibe. We describe a 70-year-old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg/day to simvastatin 10 mg-ezetimibe 40 mg/day. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work-up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatinezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work-up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate-to-severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2-year follow-up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin-ezetimibe-induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatinezetimibe-induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin-ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "drug toxicity", "mention_text": "Abstract Serum aminotransferase elevations are a commonly known adverse effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin-ezetimibe. We describe a 70-year-old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg/day to simvastatin 10 mg-ezetimibe 40 mg/day. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work-up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatinezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work-up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate-to-severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2-year follow-up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin-ezetimibe-induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatinezetimibe-induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin-ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "Ezetimibe", "mention_text": "Abstract Serum aminotransferase elevations are a commonly known adverse effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin-ezetimibe. We describe a 70-year-old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg/day to simvastatin 10 mg-ezetimibe 40 mg/day. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work-up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatinezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work-up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate-to-severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2-year follow-up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin-ezetimibe-induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatinezetimibe-induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin-ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.", "entity": "ezetimibe", "aliases": "(1-(4-fluorophenyl)-(3R)-(3-(4-fluorophenyl)-(3S)-hydroxypropyl)-(4S)-(4-hydroxyphenyl)-2-azetidinone) Essex brand of ezetimibe Ezetrol MSD Merck SCH 58235 SCH-58235 SCH58235 Schering-Plough Zetia ezetimib", "definition": "", "id": "MESH:C108606"}
{"mention": "uridine diphosphate", "mention_text": "Abstract Serum aminotransferase elevations are a commonly known adverse effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin-ezetimibe. We describe a 70-year-old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg/day to simvastatin 10 mg-ezetimibe 40 mg/day. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work-up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatinezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work-up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate-to-severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2-year follow-up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin-ezetimibe-induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatinezetimibe-induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin-ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.", "entity": "Uridine Diphosphate", "aliases": "Diphosphate Uridine Pyrophosphate UDP", "definition": "A uracil nucleotide containing a pyrophosphate group esterified to C5 of the sugar moiety.\n    ", "id": "MESH:D014530"}
{"mention": "simvastatin hydroxy acid", "mention_text": "Abstract Serum aminotransferase elevations are a commonly known adverse effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin-ezetimibe. We describe a 70-year-old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg/day to simvastatin 10 mg-ezetimibe 40 mg/day. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work-up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatinezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work-up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate-to-severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2-year follow-up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin-ezetimibe-induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatinezetimibe-induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin-ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.", "entity": "simvastatin hydroxyacid", "aliases": "simvastatin hydroxyacid", "definition": "", "id": "MESH:C532833"}
{"mention": "liver failure", "mention_text": "Abstract Serum aminotransferase elevations are a commonly known adverse effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin-ezetimibe. We describe a 70-year-old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg/day to simvastatin 10 mg-ezetimibe 40 mg/day. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work-up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatinezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work-up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate-to-severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2-year follow-up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin-ezetimibe-induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatinezetimibe-induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin-ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.", "entity": "Liver Failure", "aliases": "Hepatic Failure Liver", "definition": "Severe inability of the LIVER to perform its normal metabolic functions, as evidenced by severe JAUNDICE and abnormal serum levels of AMMONIA; BILIRUBIN; ALKALINE PHOSPHATASE; ASPARTATE AMINOTRANSFERASE; LACTATE DEHYDROGENASES; and albumin/globulin ratio. (Blakiston's Gould Medical Dictionary, 4th ed)\n    ", "id": "MESH:D017093"}
{"mention": "simvastatinezetimibe", "mention_text": "Abstract Serum aminotransferase elevations are a commonly known adverse effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin-ezetimibe. We describe a 70-year-old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg/day to simvastatin 10 mg-ezetimibe 40 mg/day. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work-up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatinezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work-up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate-to-severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2-year follow-up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin-ezetimibe-induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatinezetimibe-induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin-ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.", "entity": "ezetimibe, simvastatin drug combination", "aliases": "Inegy Vytorin ezetimibe simvastatin drug combination ezetimibe-simvastatin", "definition": "", "id": "MESH:C492458"}
{"mention": "Methamphetamine", "mention_text": "AIM: The aim of the documentation of this clinical case is to make clinicians aware of \"meth mouth\" and the medical risks associated with this serious condition. BACKGROUND: Methamphetamine is a very addictive, powerful stimulant that increases wakefulness and physical activity and can produce other effects such as cardiac dysrhythmias, hypertension, hallucinations, and violent behavior. Dental patients abusing methamphetamine can present with poor oral hygiene, xerostomia, rampant caries (\"meth mouth\"), and excessive tooth wear. Oral rehabilitation of patients using methamphetamine can be challenging. CASE DESCRIPTION: A 30-year-old Caucasian woman presented with dental pain, bad breath, and self-reported poor esthetics. A comprehensive examination including her medical history, panoramic radiograph, and intraoral examination revealed 19 carious lesions, which is not very common for a healthy adult. She reported her use of methamphetamine for five years and had not experienced any major carious episodes before she started using the drug. SUMMARY: The patient's medical and dental histories along with radiographic and clinical findings lead to a diagnosis of \"meth mouth.\" Although three different dental treatment modalities (either conventional or implant-supported) have been offered to the patient since August 2007, the patient has yet to initiate any treatment. CLINICAL SIGNIFICANCE: This clinical case showing oral manifestations of meth mouth was presented to help dental practitioners recognize and manage patients who may be abusing methamphetamines. Dental practitioners also may be skeptical about the reliability of appointment keeping by these patients, as they frequently miss their appointments without reasonable justification.", "entity": "Methamphetamine", "aliases": "Abbott Brand of Methamphetamine Hydrochloride Deoxyephedrine Desoxyephedrine Desoxyn Langly Madrine Metamfetamine Methylamphetamine N N-Methylamphetamine", "definition": "A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.\n    ", "id": "MESH:D008694"}
{"mention": "cardiac dysrhythmias", "mention_text": "AIM: The aim of the documentation of this clinical case is to make clinicians aware of \"meth mouth\" and the medical risks associated with this serious condition. BACKGROUND: Methamphetamine is a very addictive, powerful stimulant that increases wakefulness and physical activity and can produce other effects such as cardiac dysrhythmias, hypertension, hallucinations, and violent behavior. Dental patients abusing methamphetamine can present with poor oral hygiene, xerostomia, rampant caries (\"meth mouth\"), and excessive tooth wear. Oral rehabilitation of patients using methamphetamine can be challenging. CASE DESCRIPTION: A 30-year-old Caucasian woman presented with dental pain, bad breath, and self-reported poor esthetics. A comprehensive examination including her medical history, panoramic radiograph, and intraoral examination revealed 19 carious lesions, which is not very common for a healthy adult. She reported her use of methamphetamine for five years and had not experienced any major carious episodes before she started using the drug. SUMMARY: The patient's medical and dental histories along with radiographic and clinical findings lead to a diagnosis of \"meth mouth.\" Although three different dental treatment modalities (either conventional or implant-supported) have been offered to the patient since August 2007, the patient has yet to initiate any treatment. CLINICAL SIGNIFICANCE: This clinical case showing oral manifestations of meth mouth was presented to help dental practitioners recognize and manage patients who may be abusing methamphetamines. Dental practitioners also may be skeptical about the reliability of appointment keeping by these patients, as they frequently miss their appointments without reasonable justification.", "entity": "Arrhythmias, Cardiac", "aliases": "Arrhythmia Cardiac Arrhythmias Arrythmia Dysrhythmia", "definition": "Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.\n    ", "id": "MESH:D001145"}
{"mention": "hypertension", "mention_text": "AIM: The aim of the documentation of this clinical case is to make clinicians aware of \"meth mouth\" and the medical risks associated with this serious condition. BACKGROUND: Methamphetamine is a very addictive, powerful stimulant that increases wakefulness and physical activity and can produce other effects such as cardiac dysrhythmias, hypertension, hallucinations, and violent behavior. Dental patients abusing methamphetamine can present with poor oral hygiene, xerostomia, rampant caries (\"meth mouth\"), and excessive tooth wear. Oral rehabilitation of patients using methamphetamine can be challenging. CASE DESCRIPTION: A 30-year-old Caucasian woman presented with dental pain, bad breath, and self-reported poor esthetics. A comprehensive examination including her medical history, panoramic radiograph, and intraoral examination revealed 19 carious lesions, which is not very common for a healthy adult. She reported her use of methamphetamine for five years and had not experienced any major carious episodes before she started using the drug. SUMMARY: The patient's medical and dental histories along with radiographic and clinical findings lead to a diagnosis of \"meth mouth.\" Although three different dental treatment modalities (either conventional or implant-supported) have been offered to the patient since August 2007, the patient has yet to initiate any treatment. CLINICAL SIGNIFICANCE: This clinical case showing oral manifestations of meth mouth was presented to help dental practitioners recognize and manage patients who may be abusing methamphetamines. Dental practitioners also may be skeptical about the reliability of appointment keeping by these patients, as they frequently miss their appointments without reasonable justification.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "hallucinations", "mention_text": "AIM: The aim of the documentation of this clinical case is to make clinicians aware of \"meth mouth\" and the medical risks associated with this serious condition. BACKGROUND: Methamphetamine is a very addictive, powerful stimulant that increases wakefulness and physical activity and can produce other effects such as cardiac dysrhythmias, hypertension, hallucinations, and violent behavior. Dental patients abusing methamphetamine can present with poor oral hygiene, xerostomia, rampant caries (\"meth mouth\"), and excessive tooth wear. Oral rehabilitation of patients using methamphetamine can be challenging. CASE DESCRIPTION: A 30-year-old Caucasian woman presented with dental pain, bad breath, and self-reported poor esthetics. A comprehensive examination including her medical history, panoramic radiograph, and intraoral examination revealed 19 carious lesions, which is not very common for a healthy adult. She reported her use of methamphetamine for five years and had not experienced any major carious episodes before she started using the drug. SUMMARY: The patient's medical and dental histories along with radiographic and clinical findings lead to a diagnosis of \"meth mouth.\" Although three different dental treatment modalities (either conventional or implant-supported) have been offered to the patient since August 2007, the patient has yet to initiate any treatment. CLINICAL SIGNIFICANCE: This clinical case showing oral manifestations of meth mouth was presented to help dental practitioners recognize and manage patients who may be abusing methamphetamines. Dental practitioners also may be skeptical about the reliability of appointment keeping by these patients, as they frequently miss their appointments without reasonable justification.", "entity": "Hallucinations", "aliases": "Auditory Hallucination Verbal Hallucinations Body Sensation Dissociative Elementary Gustatory of Hypnagogic Hypnapompic Kinesthetic Mood Congruent Incongruent Olfactory Organic Reflex Sensory Somatic Tactile Visual Formed People Internal Unformed", "definition": "Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with MENTAL DISORDERS.\n    ", "id": "MESH:D006212"}
{"mention": "violent behavior", "mention_text": "AIM: The aim of the documentation of this clinical case is to make clinicians aware of \"meth mouth\" and the medical risks associated with this serious condition. BACKGROUND: Methamphetamine is a very addictive, powerful stimulant that increases wakefulness and physical activity and can produce other effects such as cardiac dysrhythmias, hypertension, hallucinations, and violent behavior. Dental patients abusing methamphetamine can present with poor oral hygiene, xerostomia, rampant caries (\"meth mouth\"), and excessive tooth wear. Oral rehabilitation of patients using methamphetamine can be challenging. CASE DESCRIPTION: A 30-year-old Caucasian woman presented with dental pain, bad breath, and self-reported poor esthetics. A comprehensive examination including her medical history, panoramic radiograph, and intraoral examination revealed 19 carious lesions, which is not very common for a healthy adult. She reported her use of methamphetamine for five years and had not experienced any major carious episodes before she started using the drug. SUMMARY: The patient's medical and dental histories along with radiographic and clinical findings lead to a diagnosis of \"meth mouth.\" Although three different dental treatment modalities (either conventional or implant-supported) have been offered to the patient since August 2007, the patient has yet to initiate any treatment. CLINICAL SIGNIFICANCE: This clinical case showing oral manifestations of meth mouth was presented to help dental practitioners recognize and manage patients who may be abusing methamphetamines. Dental practitioners also may be skeptical about the reliability of appointment keeping by these patients, as they frequently miss their appointments without reasonable justification.", "entity": "Mental Disorders", "aliases": "Behavior Disorders Diagnosis Psychiatric Disorder Mental", "definition": "Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.\n    ", "id": "MESH:D001523"}
{"mention": "methamphetamine", "mention_text": "AIM: The aim of the documentation of this clinical case is to make clinicians aware of \"meth mouth\" and the medical risks associated with this serious condition. BACKGROUND: Methamphetamine is a very addictive, powerful stimulant that increases wakefulness and physical activity and can produce other effects such as cardiac dysrhythmias, hypertension, hallucinations, and violent behavior. Dental patients abusing methamphetamine can present with poor oral hygiene, xerostomia, rampant caries (\"meth mouth\"), and excessive tooth wear. Oral rehabilitation of patients using methamphetamine can be challenging. CASE DESCRIPTION: A 30-year-old Caucasian woman presented with dental pain, bad breath, and self-reported poor esthetics. A comprehensive examination including her medical history, panoramic radiograph, and intraoral examination revealed 19 carious lesions, which is not very common for a healthy adult. She reported her use of methamphetamine for five years and had not experienced any major carious episodes before she started using the drug. SUMMARY: The patient's medical and dental histories along with radiographic and clinical findings lead to a diagnosis of \"meth mouth.\" Although three different dental treatment modalities (either conventional or implant-supported) have been offered to the patient since August 2007, the patient has yet to initiate any treatment. CLINICAL SIGNIFICANCE: This clinical case showing oral manifestations of meth mouth was presented to help dental practitioners recognize and manage patients who may be abusing methamphetamines. Dental practitioners also may be skeptical about the reliability of appointment keeping by these patients, as they frequently miss their appointments without reasonable justification.", "entity": "Methamphetamine", "aliases": "Abbott Brand of Methamphetamine Hydrochloride Deoxyephedrine Desoxyephedrine Desoxyn Langly Madrine Metamfetamine Methylamphetamine N N-Methylamphetamine", "definition": "A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.\n    ", "id": "MESH:D008694"}
{"mention": "xerostomia", "mention_text": "AIM: The aim of the documentation of this clinical case is to make clinicians aware of \"meth mouth\" and the medical risks associated with this serious condition. BACKGROUND: Methamphetamine is a very addictive, powerful stimulant that increases wakefulness and physical activity and can produce other effects such as cardiac dysrhythmias, hypertension, hallucinations, and violent behavior. Dental patients abusing methamphetamine can present with poor oral hygiene, xerostomia, rampant caries (\"meth mouth\"), and excessive tooth wear. Oral rehabilitation of patients using methamphetamine can be challenging. CASE DESCRIPTION: A 30-year-old Caucasian woman presented with dental pain, bad breath, and self-reported poor esthetics. A comprehensive examination including her medical history, panoramic radiograph, and intraoral examination revealed 19 carious lesions, which is not very common for a healthy adult. She reported her use of methamphetamine for five years and had not experienced any major carious episodes before she started using the drug. SUMMARY: The patient's medical and dental histories along with radiographic and clinical findings lead to a diagnosis of \"meth mouth.\" Although three different dental treatment modalities (either conventional or implant-supported) have been offered to the patient since August 2007, the patient has yet to initiate any treatment. CLINICAL SIGNIFICANCE: This clinical case showing oral manifestations of meth mouth was presented to help dental practitioners recognize and manage patients who may be abusing methamphetamines. Dental practitioners also may be skeptical about the reliability of appointment keeping by these patients, as they frequently miss their appointments without reasonable justification.", "entity": "Xerostomia", "aliases": "Asialia Asialias Dryness Mouth Hyposalivation Hyposalivations Xerostomia Xerostomias", "definition": "Decreased salivary flow.\n    ", "id": "MESH:D014987"}
{"mention": "caries", "mention_text": "AIM: The aim of the documentation of this clinical case is to make clinicians aware of \"meth mouth\" and the medical risks associated with this serious condition. BACKGROUND: Methamphetamine is a very addictive, powerful stimulant that increases wakefulness and physical activity and can produce other effects such as cardiac dysrhythmias, hypertension, hallucinations, and violent behavior. Dental patients abusing methamphetamine can present with poor oral hygiene, xerostomia, rampant caries (\"meth mouth\"), and excessive tooth wear. Oral rehabilitation of patients using methamphetamine can be challenging. CASE DESCRIPTION: A 30-year-old Caucasian woman presented with dental pain, bad breath, and self-reported poor esthetics. A comprehensive examination including her medical history, panoramic radiograph, and intraoral examination revealed 19 carious lesions, which is not very common for a healthy adult. She reported her use of methamphetamine for five years and had not experienced any major carious episodes before she started using the drug. SUMMARY: The patient's medical and dental histories along with radiographic and clinical findings lead to a diagnosis of \"meth mouth.\" Although three different dental treatment modalities (either conventional or implant-supported) have been offered to the patient since August 2007, the patient has yet to initiate any treatment. CLINICAL SIGNIFICANCE: This clinical case showing oral manifestations of meth mouth was presented to help dental practitioners recognize and manage patients who may be abusing methamphetamines. Dental practitioners also may be skeptical about the reliability of appointment keeping by these patients, as they frequently miss their appointments without reasonable justification.", "entity": "Dental Caries", "aliases": "Caries Dental Carious Dentin Dentins Decay White Spot Spots", "definition": "Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp.\n    ", "id": "MESH:D003731"}
{"mention": "tooth wear", "mention_text": "AIM: The aim of the documentation of this clinical case is to make clinicians aware of \"meth mouth\" and the medical risks associated with this serious condition. BACKGROUND: Methamphetamine is a very addictive, powerful stimulant that increases wakefulness and physical activity and can produce other effects such as cardiac dysrhythmias, hypertension, hallucinations, and violent behavior. Dental patients abusing methamphetamine can present with poor oral hygiene, xerostomia, rampant caries (\"meth mouth\"), and excessive tooth wear. Oral rehabilitation of patients using methamphetamine can be challenging. CASE DESCRIPTION: A 30-year-old Caucasian woman presented with dental pain, bad breath, and self-reported poor esthetics. A comprehensive examination including her medical history, panoramic radiograph, and intraoral examination revealed 19 carious lesions, which is not very common for a healthy adult. She reported her use of methamphetamine for five years and had not experienced any major carious episodes before she started using the drug. SUMMARY: The patient's medical and dental histories along with radiographic and clinical findings lead to a diagnosis of \"meth mouth.\" Although three different dental treatment modalities (either conventional or implant-supported) have been offered to the patient since August 2007, the patient has yet to initiate any treatment. CLINICAL SIGNIFICANCE: This clinical case showing oral manifestations of meth mouth was presented to help dental practitioners recognize and manage patients who may be abusing methamphetamines. Dental practitioners also may be skeptical about the reliability of appointment keeping by these patients, as they frequently miss their appointments without reasonable justification.", "entity": "Tooth Wear", "aliases": "Dental Wear Wears Tooth", "definition": "Loss of the tooth substance by chemical or mechanical processes\n    ", "id": "MESH:D057085"}
{"mention": "pain", "mention_text": "AIM: The aim of the documentation of this clinical case is to make clinicians aware of \"meth mouth\" and the medical risks associated with this serious condition. BACKGROUND: Methamphetamine is a very addictive, powerful stimulant that increases wakefulness and physical activity and can produce other effects such as cardiac dysrhythmias, hypertension, hallucinations, and violent behavior. Dental patients abusing methamphetamine can present with poor oral hygiene, xerostomia, rampant caries (\"meth mouth\"), and excessive tooth wear. Oral rehabilitation of patients using methamphetamine can be challenging. CASE DESCRIPTION: A 30-year-old Caucasian woman presented with dental pain, bad breath, and self-reported poor esthetics. A comprehensive examination including her medical history, panoramic radiograph, and intraoral examination revealed 19 carious lesions, which is not very common for a healthy adult. She reported her use of methamphetamine for five years and had not experienced any major carious episodes before she started using the drug. SUMMARY: The patient's medical and dental histories along with radiographic and clinical findings lead to a diagnosis of \"meth mouth.\" Although three different dental treatment modalities (either conventional or implant-supported) have been offered to the patient since August 2007, the patient has yet to initiate any treatment. CLINICAL SIGNIFICANCE: This clinical case showing oral manifestations of meth mouth was presented to help dental practitioners recognize and manage patients who may be abusing methamphetamines. Dental practitioners also may be skeptical about the reliability of appointment keeping by these patients, as they frequently miss their appointments without reasonable justification.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "bad breath", "mention_text": "AIM: The aim of the documentation of this clinical case is to make clinicians aware of \"meth mouth\" and the medical risks associated with this serious condition. BACKGROUND: Methamphetamine is a very addictive, powerful stimulant that increases wakefulness and physical activity and can produce other effects such as cardiac dysrhythmias, hypertension, hallucinations, and violent behavior. Dental patients abusing methamphetamine can present with poor oral hygiene, xerostomia, rampant caries (\"meth mouth\"), and excessive tooth wear. Oral rehabilitation of patients using methamphetamine can be challenging. CASE DESCRIPTION: A 30-year-old Caucasian woman presented with dental pain, bad breath, and self-reported poor esthetics. A comprehensive examination including her medical history, panoramic radiograph, and intraoral examination revealed 19 carious lesions, which is not very common for a healthy adult. She reported her use of methamphetamine for five years and had not experienced any major carious episodes before she started using the drug. SUMMARY: The patient's medical and dental histories along with radiographic and clinical findings lead to a diagnosis of \"meth mouth.\" Although three different dental treatment modalities (either conventional or implant-supported) have been offered to the patient since August 2007, the patient has yet to initiate any treatment. CLINICAL SIGNIFICANCE: This clinical case showing oral manifestations of meth mouth was presented to help dental practitioners recognize and manage patients who may be abusing methamphetamines. Dental practitioners also may be skeptical about the reliability of appointment keeping by these patients, as they frequently miss their appointments without reasonable justification.", "entity": "Respiration Disorders", "aliases": "Disorder Respiration Disorders", "definition": "Diseases of the respiratory system in general or unspecified or for a specific respiratory disease not available.\n    ", "id": "MESH:D012120"}
{"mention": "carious lesions", "mention_text": "AIM: The aim of the documentation of this clinical case is to make clinicians aware of \"meth mouth\" and the medical risks associated with this serious condition. BACKGROUND: Methamphetamine is a very addictive, powerful stimulant that increases wakefulness and physical activity and can produce other effects such as cardiac dysrhythmias, hypertension, hallucinations, and violent behavior. Dental patients abusing methamphetamine can present with poor oral hygiene, xerostomia, rampant caries (\"meth mouth\"), and excessive tooth wear. Oral rehabilitation of patients using methamphetamine can be challenging. CASE DESCRIPTION: A 30-year-old Caucasian woman presented with dental pain, bad breath, and self-reported poor esthetics. A comprehensive examination including her medical history, panoramic radiograph, and intraoral examination revealed 19 carious lesions, which is not very common for a healthy adult. She reported her use of methamphetamine for five years and had not experienced any major carious episodes before she started using the drug. SUMMARY: The patient's medical and dental histories along with radiographic and clinical findings lead to a diagnosis of \"meth mouth.\" Although three different dental treatment modalities (either conventional or implant-supported) have been offered to the patient since August 2007, the patient has yet to initiate any treatment. CLINICAL SIGNIFICANCE: This clinical case showing oral manifestations of meth mouth was presented to help dental practitioners recognize and manage patients who may be abusing methamphetamines. Dental practitioners also may be skeptical about the reliability of appointment keeping by these patients, as they frequently miss their appointments without reasonable justification.", "entity": "Dental Caries", "aliases": "Caries Dental Carious Dentin Dentins Decay White Spot Spots", "definition": "Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp.\n    ", "id": "MESH:D003731"}
{"mention": "carious episodes", "mention_text": "AIM: The aim of the documentation of this clinical case is to make clinicians aware of \"meth mouth\" and the medical risks associated with this serious condition. BACKGROUND: Methamphetamine is a very addictive, powerful stimulant that increases wakefulness and physical activity and can produce other effects such as cardiac dysrhythmias, hypertension, hallucinations, and violent behavior. Dental patients abusing methamphetamine can present with poor oral hygiene, xerostomia, rampant caries (\"meth mouth\"), and excessive tooth wear. Oral rehabilitation of patients using methamphetamine can be challenging. CASE DESCRIPTION: A 30-year-old Caucasian woman presented with dental pain, bad breath, and self-reported poor esthetics. A comprehensive examination including her medical history, panoramic radiograph, and intraoral examination revealed 19 carious lesions, which is not very common for a healthy adult. She reported her use of methamphetamine for five years and had not experienced any major carious episodes before she started using the drug. SUMMARY: The patient's medical and dental histories along with radiographic and clinical findings lead to a diagnosis of \"meth mouth.\" Although three different dental treatment modalities (either conventional or implant-supported) have been offered to the patient since August 2007, the patient has yet to initiate any treatment. CLINICAL SIGNIFICANCE: This clinical case showing oral manifestations of meth mouth was presented to help dental practitioners recognize and manage patients who may be abusing methamphetamines. Dental practitioners also may be skeptical about the reliability of appointment keeping by these patients, as they frequently miss their appointments without reasonable justification.", "entity": "Dental Caries", "aliases": "Caries Dental Carious Dentin Dentins Decay White Spot Spots", "definition": "Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp.\n    ", "id": "MESH:D003731"}
{"mention": "methamphetamines", "mention_text": "AIM: The aim of the documentation of this clinical case is to make clinicians aware of \"meth mouth\" and the medical risks associated with this serious condition. BACKGROUND: Methamphetamine is a very addictive, powerful stimulant that increases wakefulness and physical activity and can produce other effects such as cardiac dysrhythmias, hypertension, hallucinations, and violent behavior. Dental patients abusing methamphetamine can present with poor oral hygiene, xerostomia, rampant caries (\"meth mouth\"), and excessive tooth wear. Oral rehabilitation of patients using methamphetamine can be challenging. CASE DESCRIPTION: A 30-year-old Caucasian woman presented with dental pain, bad breath, and self-reported poor esthetics. A comprehensive examination including her medical history, panoramic radiograph, and intraoral examination revealed 19 carious lesions, which is not very common for a healthy adult. She reported her use of methamphetamine for five years and had not experienced any major carious episodes before she started using the drug. SUMMARY: The patient's medical and dental histories along with radiographic and clinical findings lead to a diagnosis of \"meth mouth.\" Although three different dental treatment modalities (either conventional or implant-supported) have been offered to the patient since August 2007, the patient has yet to initiate any treatment. CLINICAL SIGNIFICANCE: This clinical case showing oral manifestations of meth mouth was presented to help dental practitioners recognize and manage patients who may be abusing methamphetamines. Dental practitioners also may be skeptical about the reliability of appointment keeping by these patients, as they frequently miss their appointments without reasonable justification.", "entity": "Methamphetamine", "aliases": "Abbott Brand of Methamphetamine Hydrochloride Deoxyephedrine Desoxyephedrine Desoxyn Langly Madrine Metamfetamine Methylamphetamine N N-Methylamphetamine", "definition": "A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.\n    ", "id": "MESH:D008694"}
{"mention": "Thyroxine", "mention_text": "Thyroxine abuse: an unusual case of thyrotoxicosis in pregnancy.", "entity": "Thyroxine", "aliases": "3,5,3',5'-Tetraiodothyronine Abbot Brand of Levothyroxine Sodium Allphar Aventis Berlin Chemie Berlin-Chemie Berlthyrox Byk Deladande Levothyroxin Delalande Dexnon Eferox Eltroxin Eltroxine Euthyrox Eutirox Forest Genpharm GlaxoSmithKline GlaxoWellcome Goldshield Henning Hexal 1 2 Kern L Thyrox Thyroxin beta Thyroxine Roche L-3,5,3',5'-Tetraiodothyronine L-Thyrox L-Thyroxin L-Thyroxine LThyroxin Leo Tiroxina Levo T Levo-T LevoT Levothroid Levothyroid Levoxine Levoxyl Lévothyrox Merck Lipha Santé", "definition": "The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (MONOIODOTYROSINE) and the coupling of iodotyrosines (DIIODOTYROSINE) in the THYROGLOBULIN. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form TRIIODOTHYRONINE which exerts a broad spectrum of stimulatory effects on cell metabolism.\n    ", "id": "MESH:D013974"}
{"mention": "thyrotoxicosis", "mention_text": "Thyroxine abuse: an unusual case of thyrotoxicosis in pregnancy.", "entity": "Thyrotoxicosis", "aliases": "Thyrotoxicoses Thyrotoxicosis", "definition": "A hypermetabolic syndrome caused by excess THYROID HORMONES which may come from endogenous or exogenous sources. The endogenous source of hormone may be thyroid HYPERPLASIA; THYROID NEOPLASMS; or hormone-producing extrathyroidal tissue. Thyrotoxicosis is characterized by NERVOUSNESS; TACHYCARDIA; FATIGUE; WEIGHT LOSS; heat intolerance; and excessive SWEATING.\n    ", "id": "MESH:D013971"}
{"mention": "Eating disorders", "mention_text": "Eating disorders and the associated behavioural problems and drug abuse are uncommon in pregnancy. When they do occur they are often unrecognized because of denial but when significant may pose a risk to both the mother and her fetus. This case illustrates a number of problems that may be encountered in women with eating disorders in pregnancy, including prolonged and recurrent metabolic disturbances and diuretic abuse. In particular it illustrates the derangements of thyroid function seen in pregnant women with eating disorders and reminds us that when a cause for thyrotoxicosis remains obscure, thyroxine abuse should be considered and explored.", "entity": "Eating Disorders", "aliases": "Appetite Disorder Disorders Eating", "definition": "A group of disorders characterized by physiological and psychological disturbances in appetite or food intake.\n    ", "id": "MESH:D001068"}
{"mention": "drug abuse", "mention_text": "Eating disorders and the associated behavioural problems and drug abuse are uncommon in pregnancy. When they do occur they are often unrecognized because of denial but when significant may pose a risk to both the mother and her fetus. This case illustrates a number of problems that may be encountered in women with eating disorders in pregnancy, including prolonged and recurrent metabolic disturbances and diuretic abuse. In particular it illustrates the derangements of thyroid function seen in pregnant women with eating disorders and reminds us that when a cause for thyrotoxicosis remains obscure, thyroxine abuse should be considered and explored.", "entity": "Substance-Related Disorders", "aliases": "Abuse Drug Substance Abuses Addiction Dependence Disorder Use Habituation Disorders Organic Mental Induced Substance-Induced Substance-Related", "definition": "Disorders related to substance abuse.\n    ", "id": "MESH:D019966"}
{"mention": "eating disorders", "mention_text": "Eating disorders and the associated behavioural problems and drug abuse are uncommon in pregnancy. When they do occur they are often unrecognized because of denial but when significant may pose a risk to both the mother and her fetus. This case illustrates a number of problems that may be encountered in women with eating disorders in pregnancy, including prolonged and recurrent metabolic disturbances and diuretic abuse. In particular it illustrates the derangements of thyroid function seen in pregnant women with eating disorders and reminds us that when a cause for thyrotoxicosis remains obscure, thyroxine abuse should be considered and explored.", "entity": "Eating Disorders", "aliases": "Appetite Disorder Disorders Eating", "definition": "A group of disorders characterized by physiological and psychological disturbances in appetite or food intake.\n    ", "id": "MESH:D001068"}
{"mention": "thyrotoxicosis", "mention_text": "Eating disorders and the associated behavioural problems and drug abuse are uncommon in pregnancy. When they do occur they are often unrecognized because of denial but when significant may pose a risk to both the mother and her fetus. This case illustrates a number of problems that may be encountered in women with eating disorders in pregnancy, including prolonged and recurrent metabolic disturbances and diuretic abuse. In particular it illustrates the derangements of thyroid function seen in pregnant women with eating disorders and reminds us that when a cause for thyrotoxicosis remains obscure, thyroxine abuse should be considered and explored.", "entity": "Thyrotoxicosis", "aliases": "Thyrotoxicoses Thyrotoxicosis", "definition": "A hypermetabolic syndrome caused by excess THYROID HORMONES which may come from endogenous or exogenous sources. The endogenous source of hormone may be thyroid HYPERPLASIA; THYROID NEOPLASMS; or hormone-producing extrathyroidal tissue. Thyrotoxicosis is characterized by NERVOUSNESS; TACHYCARDIA; FATIGUE; WEIGHT LOSS; heat intolerance; and excessive SWEATING.\n    ", "id": "MESH:D013971"}
{"mention": "thyroxine", "mention_text": "Eating disorders and the associated behavioural problems and drug abuse are uncommon in pregnancy. When they do occur they are often unrecognized because of denial but when significant may pose a risk to both the mother and her fetus. This case illustrates a number of problems that may be encountered in women with eating disorders in pregnancy, including prolonged and recurrent metabolic disturbances and diuretic abuse. In particular it illustrates the derangements of thyroid function seen in pregnant women with eating disorders and reminds us that when a cause for thyrotoxicosis remains obscure, thyroxine abuse should be considered and explored.", "entity": "Thyroxine", "aliases": "3,5,3',5'-Tetraiodothyronine Abbot Brand of Levothyroxine Sodium Allphar Aventis Berlin Chemie Berlin-Chemie Berlthyrox Byk Deladande Levothyroxin Delalande Dexnon Eferox Eltroxin Eltroxine Euthyrox Eutirox Forest Genpharm GlaxoSmithKline GlaxoWellcome Goldshield Henning Hexal 1 2 Kern L Thyrox Thyroxin beta Thyroxine Roche L-3,5,3',5'-Tetraiodothyronine L-Thyrox L-Thyroxin L-Thyroxine LThyroxin Leo Tiroxina Levo T Levo-T LevoT Levothroid Levothyroid Levoxine Levoxyl Lévothyrox Merck Lipha Santé", "definition": "The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (MONOIODOTYROSINE) and the coupling of iodotyrosines (DIIODOTYROSINE) in the THYROGLOBULIN. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form TRIIODOTHYRONINE which exerts a broad spectrum of stimulatory effects on cell metabolism.\n    ", "id": "MESH:D013974"}
{"mention": "methamphetamine", "mention_text": "Attenuation of methamphetamine-induced nigrostriatal dopaminergic neurotoxicity in mice by lipopolysaccharide pretreatment.", "entity": "Methamphetamine", "aliases": "Abbott Brand of Methamphetamine Hydrochloride Deoxyephedrine Desoxyephedrine Desoxyn Langly Madrine Metamfetamine Methylamphetamine N N-Methylamphetamine", "definition": "A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.\n    ", "id": "MESH:D008694"}
{"mention": "neurotoxicity", "mention_text": "Attenuation of methamphetamine-induced nigrostriatal dopaminergic neurotoxicity in mice by lipopolysaccharide pretreatment.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "lipopolysaccharide", "mention_text": "Attenuation of methamphetamine-induced nigrostriatal dopaminergic neurotoxicity in mice by lipopolysaccharide pretreatment.", "entity": "Lipopolysaccharides", "aliases": "Lipoglycans Lipopolysaccharides", "definition": "Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)\n    ", "id": "MESH:D008070"}
{"mention": "methamphetamine", "mention_text": "Immunological activation has been proposed to play a role in methamphetamine-induced dopaminergic terminal damage. In this study, we examined the roles of lipopolysaccharide, a pro-inflammatory and inflammatory factor, treatment in modulating the methamphetamine-induced nigrostriatal dopamine neurotoxicity. Lipopolysaccharide pretreatment did not affect the basal body temperature or methamphetamine-elicited hyperthermia three days later. Such systemic lipopolysaccharide treatment mitigated methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions in a dose-dependent manner. As the most potent dose (1 mg/kg) of lipopolysaccharide was administered two weeks, one day before or after the methamphetamine dosing regimen, methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions remained unaltered. Moreover, systemic lipopolysaccharide pretreatment (1 mg/kg) attenuated local methamphetamine infusion-produced dopamine and 3,4-dihydroxyphenylacetic acid depletions in the striatum, indicating that the protective effect of lipopolysaccharide is less likely due to interrupted peripheral distribution or metabolism of methamphetamine. We concluded a critical time window for systemic lipopolysaccharide pretreatment in exerting effective protection against methamphetamine-induced nigrostriatal dopamine neurotoxicity.", "entity": "Methamphetamine", "aliases": "Abbott Brand of Methamphetamine Hydrochloride Deoxyephedrine Desoxyephedrine Desoxyn Langly Madrine Metamfetamine Methylamphetamine N N-Methylamphetamine", "definition": "A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.\n    ", "id": "MESH:D008694"}
{"mention": "dopaminergic terminal damage", "mention_text": "Immunological activation has been proposed to play a role in methamphetamine-induced dopaminergic terminal damage. In this study, we examined the roles of lipopolysaccharide, a pro-inflammatory and inflammatory factor, treatment in modulating the methamphetamine-induced nigrostriatal dopamine neurotoxicity. Lipopolysaccharide pretreatment did not affect the basal body temperature or methamphetamine-elicited hyperthermia three days later. Such systemic lipopolysaccharide treatment mitigated methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions in a dose-dependent manner. As the most potent dose (1 mg/kg) of lipopolysaccharide was administered two weeks, one day before or after the methamphetamine dosing regimen, methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions remained unaltered. Moreover, systemic lipopolysaccharide pretreatment (1 mg/kg) attenuated local methamphetamine infusion-produced dopamine and 3,4-dihydroxyphenylacetic acid depletions in the striatum, indicating that the protective effect of lipopolysaccharide is less likely due to interrupted peripheral distribution or metabolism of methamphetamine. We concluded a critical time window for systemic lipopolysaccharide pretreatment in exerting effective protection against methamphetamine-induced nigrostriatal dopamine neurotoxicity.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "lipopolysaccharide", "mention_text": "Immunological activation has been proposed to play a role in methamphetamine-induced dopaminergic terminal damage. In this study, we examined the roles of lipopolysaccharide, a pro-inflammatory and inflammatory factor, treatment in modulating the methamphetamine-induced nigrostriatal dopamine neurotoxicity. Lipopolysaccharide pretreatment did not affect the basal body temperature or methamphetamine-elicited hyperthermia three days later. Such systemic lipopolysaccharide treatment mitigated methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions in a dose-dependent manner. As the most potent dose (1 mg/kg) of lipopolysaccharide was administered two weeks, one day before or after the methamphetamine dosing regimen, methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions remained unaltered. Moreover, systemic lipopolysaccharide pretreatment (1 mg/kg) attenuated local methamphetamine infusion-produced dopamine and 3,4-dihydroxyphenylacetic acid depletions in the striatum, indicating that the protective effect of lipopolysaccharide is less likely due to interrupted peripheral distribution or metabolism of methamphetamine. We concluded a critical time window for systemic lipopolysaccharide pretreatment in exerting effective protection against methamphetamine-induced nigrostriatal dopamine neurotoxicity.", "entity": "Lipopolysaccharides", "aliases": "Lipoglycans Lipopolysaccharides", "definition": "Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)\n    ", "id": "MESH:D008070"}
{"mention": "dopamine", "mention_text": "Immunological activation has been proposed to play a role in methamphetamine-induced dopaminergic terminal damage. In this study, we examined the roles of lipopolysaccharide, a pro-inflammatory and inflammatory factor, treatment in modulating the methamphetamine-induced nigrostriatal dopamine neurotoxicity. Lipopolysaccharide pretreatment did not affect the basal body temperature or methamphetamine-elicited hyperthermia three days later. Such systemic lipopolysaccharide treatment mitigated methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions in a dose-dependent manner. As the most potent dose (1 mg/kg) of lipopolysaccharide was administered two weeks, one day before or after the methamphetamine dosing regimen, methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions remained unaltered. Moreover, systemic lipopolysaccharide pretreatment (1 mg/kg) attenuated local methamphetamine infusion-produced dopamine and 3,4-dihydroxyphenylacetic acid depletions in the striatum, indicating that the protective effect of lipopolysaccharide is less likely due to interrupted peripheral distribution or metabolism of methamphetamine. We concluded a critical time window for systemic lipopolysaccharide pretreatment in exerting effective protection against methamphetamine-induced nigrostriatal dopamine neurotoxicity.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "neurotoxicity", "mention_text": "Immunological activation has been proposed to play a role in methamphetamine-induced dopaminergic terminal damage. In this study, we examined the roles of lipopolysaccharide, a pro-inflammatory and inflammatory factor, treatment in modulating the methamphetamine-induced nigrostriatal dopamine neurotoxicity. Lipopolysaccharide pretreatment did not affect the basal body temperature or methamphetamine-elicited hyperthermia three days later. Such systemic lipopolysaccharide treatment mitigated methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions in a dose-dependent manner. As the most potent dose (1 mg/kg) of lipopolysaccharide was administered two weeks, one day before or after the methamphetamine dosing regimen, methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions remained unaltered. Moreover, systemic lipopolysaccharide pretreatment (1 mg/kg) attenuated local methamphetamine infusion-produced dopamine and 3,4-dihydroxyphenylacetic acid depletions in the striatum, indicating that the protective effect of lipopolysaccharide is less likely due to interrupted peripheral distribution or metabolism of methamphetamine. We concluded a critical time window for systemic lipopolysaccharide pretreatment in exerting effective protection against methamphetamine-induced nigrostriatal dopamine neurotoxicity.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "Lipopolysaccharide", "mention_text": "Immunological activation has been proposed to play a role in methamphetamine-induced dopaminergic terminal damage. In this study, we examined the roles of lipopolysaccharide, a pro-inflammatory and inflammatory factor, treatment in modulating the methamphetamine-induced nigrostriatal dopamine neurotoxicity. Lipopolysaccharide pretreatment did not affect the basal body temperature or methamphetamine-elicited hyperthermia three days later. Such systemic lipopolysaccharide treatment mitigated methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions in a dose-dependent manner. As the most potent dose (1 mg/kg) of lipopolysaccharide was administered two weeks, one day before or after the methamphetamine dosing regimen, methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions remained unaltered. Moreover, systemic lipopolysaccharide pretreatment (1 mg/kg) attenuated local methamphetamine infusion-produced dopamine and 3,4-dihydroxyphenylacetic acid depletions in the striatum, indicating that the protective effect of lipopolysaccharide is less likely due to interrupted peripheral distribution or metabolism of methamphetamine. We concluded a critical time window for systemic lipopolysaccharide pretreatment in exerting effective protection against methamphetamine-induced nigrostriatal dopamine neurotoxicity.", "entity": "Lipopolysaccharides", "aliases": "Lipoglycans Lipopolysaccharides", "definition": "Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)\n    ", "id": "MESH:D008070"}
{"mention": "hyperthermia", "mention_text": "Immunological activation has been proposed to play a role in methamphetamine-induced dopaminergic terminal damage. In this study, we examined the roles of lipopolysaccharide, a pro-inflammatory and inflammatory factor, treatment in modulating the methamphetamine-induced nigrostriatal dopamine neurotoxicity. Lipopolysaccharide pretreatment did not affect the basal body temperature or methamphetamine-elicited hyperthermia three days later. Such systemic lipopolysaccharide treatment mitigated methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions in a dose-dependent manner. As the most potent dose (1 mg/kg) of lipopolysaccharide was administered two weeks, one day before or after the methamphetamine dosing regimen, methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions remained unaltered. Moreover, systemic lipopolysaccharide pretreatment (1 mg/kg) attenuated local methamphetamine infusion-produced dopamine and 3,4-dihydroxyphenylacetic acid depletions in the striatum, indicating that the protective effect of lipopolysaccharide is less likely due to interrupted peripheral distribution or metabolism of methamphetamine. We concluded a critical time window for systemic lipopolysaccharide pretreatment in exerting effective protection against methamphetamine-induced nigrostriatal dopamine neurotoxicity.", "entity": "Fever", "aliases": "Fever Fevers Hyperthermia Hyperthermias Pyrexia Pyrexias", "definition": "An abnormal elevation of body temperature, usually as a result of a pathologic process.\n    ", "id": "MESH:D005334"}
{"mention": "3,4-dihydroxyphenylacetic acid", "mention_text": "Immunological activation has been proposed to play a role in methamphetamine-induced dopaminergic terminal damage. In this study, we examined the roles of lipopolysaccharide, a pro-inflammatory and inflammatory factor, treatment in modulating the methamphetamine-induced nigrostriatal dopamine neurotoxicity. Lipopolysaccharide pretreatment did not affect the basal body temperature or methamphetamine-elicited hyperthermia three days later. Such systemic lipopolysaccharide treatment mitigated methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions in a dose-dependent manner. As the most potent dose (1 mg/kg) of lipopolysaccharide was administered two weeks, one day before or after the methamphetamine dosing regimen, methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions remained unaltered. Moreover, systemic lipopolysaccharide pretreatment (1 mg/kg) attenuated local methamphetamine infusion-produced dopamine and 3,4-dihydroxyphenylacetic acid depletions in the striatum, indicating that the protective effect of lipopolysaccharide is less likely due to interrupted peripheral distribution or metabolism of methamphetamine. We concluded a critical time window for systemic lipopolysaccharide pretreatment in exerting effective protection against methamphetamine-induced nigrostriatal dopamine neurotoxicity.", "entity": "3,4-Dihydroxyphenylacetic Acid", "aliases": "3,4 Dihydroxyphenylacetic Acid 3,4-Dihydroxyphenylacetic Monosodium Salt DOPAC Homoprotocatechuic", "definition": "A deaminated metabolite of LEVODOPA.\n    ", "id": "MESH:D015102"}
{"mention": "adriamycin", "mention_text": "Effect of converting enzyme inhibition on the course of adriamycin-induced nephropathy.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "nephropathy", "mention_text": "Effect of converting enzyme inhibition on the course of adriamycin-induced nephropathy.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "enalapril", "mention_text": "The effect of the converting enzyme inhibitor (CEI) enalapril was assessed in Munich-Wistar rats with established adriamycin nephrosis. Rats were given a single dose of adriamycin and one month later divided into four groups matched for albuminuria, blood pressure, and plasma albumin concentration. Groups 1 and 3 remained untreated while groups 2 and 4 received enalapril. Groups 1 and 2 underwent micropuncture studies after 10 days. These short-term studies showed that enalapril reduced arterial blood pressure (101 +/- 2 vs. 124 +/- 3 mm Hg, group 2 vs. 1, P less than 0.05) and glomerular capillary pressure (54 +/- 1 vs. 61 +/- 2 mm Hg, P less than 0.05) without reducing albuminuria (617 +/- 50 vs. 570 +/- 47 mg/day) or GFR (1.03 +/- 0.04 vs. 1.04 +/- 0.11 ml/min). Groups 3 and 4 were studied at four and at six months to assess the effect of enalapril on progression of renal injury in adriamycin nephrosis. Chronic enalapril treatment reduced blood pressure without reducing albuminuria in group 4. Untreated group 3 rats exhibited a progressive reduction in GFR (0.35 +/- 0.08 ml/min at 4 months, 0.27 +/- 0.07 ml/min at 6 months). Enalapril treatment blunted but did not prevent reduction in GFR in group 4 (0.86 +/- 0.15 ml/min at 4 months, 0.69 +/- 0.13 ml/min at 6 months, both P less than 0.05 vs. group 3). Reduction in GFR was associated with the development of glomerular sclerosis in both treated and untreated rats.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Enalapril", "aliases": "Enalapril Maleate MK 421 MK-421 MK421 Renitec Renitek", "definition": "One of the ANGIOTENSIN-CONVERTING ENZYME INHIBITORS that is used to treat hypertension.\n    ", "id": "MESH:D004656"}
{"mention": "adriamycin", "mention_text": "The effect of the converting enzyme inhibitor (CEI) enalapril was assessed in Munich-Wistar rats with established adriamycin nephrosis. Rats were given a single dose of adriamycin and one month later divided into four groups matched for albuminuria, blood pressure, and plasma albumin concentration. Groups 1 and 3 remained untreated while groups 2 and 4 received enalapril. Groups 1 and 2 underwent micropuncture studies after 10 days. These short-term studies showed that enalapril reduced arterial blood pressure (101 +/- 2 vs. 124 +/- 3 mm Hg, group 2 vs. 1, P less than 0.05) and glomerular capillary pressure (54 +/- 1 vs. 61 +/- 2 mm Hg, P less than 0.05) without reducing albuminuria (617 +/- 50 vs. 570 +/- 47 mg/day) or GFR (1.03 +/- 0.04 vs. 1.04 +/- 0.11 ml/min). Groups 3 and 4 were studied at four and at six months to assess the effect of enalapril on progression of renal injury in adriamycin nephrosis. Chronic enalapril treatment reduced blood pressure without reducing albuminuria in group 4. Untreated group 3 rats exhibited a progressive reduction in GFR (0.35 +/- 0.08 ml/min at 4 months, 0.27 +/- 0.07 ml/min at 6 months). Enalapril treatment blunted but did not prevent reduction in GFR in group 4 (0.86 +/- 0.15 ml/min at 4 months, 0.69 +/- 0.13 ml/min at 6 months, both P less than 0.05 vs. group 3). Reduction in GFR was associated with the development of glomerular sclerosis in both treated and untreated rats.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "nephrosis", "mention_text": "The effect of the converting enzyme inhibitor (CEI) enalapril was assessed in Munich-Wistar rats with established adriamycin nephrosis. Rats were given a single dose of adriamycin and one month later divided into four groups matched for albuminuria, blood pressure, and plasma albumin concentration. Groups 1 and 3 remained untreated while groups 2 and 4 received enalapril. Groups 1 and 2 underwent micropuncture studies after 10 days. These short-term studies showed that enalapril reduced arterial blood pressure (101 +/- 2 vs. 124 +/- 3 mm Hg, group 2 vs. 1, P less than 0.05) and glomerular capillary pressure (54 +/- 1 vs. 61 +/- 2 mm Hg, P less than 0.05) without reducing albuminuria (617 +/- 50 vs. 570 +/- 47 mg/day) or GFR (1.03 +/- 0.04 vs. 1.04 +/- 0.11 ml/min). Groups 3 and 4 were studied at four and at six months to assess the effect of enalapril on progression of renal injury in adriamycin nephrosis. Chronic enalapril treatment reduced blood pressure without reducing albuminuria in group 4. Untreated group 3 rats exhibited a progressive reduction in GFR (0.35 +/- 0.08 ml/min at 4 months, 0.27 +/- 0.07 ml/min at 6 months). Enalapril treatment blunted but did not prevent reduction in GFR in group 4 (0.86 +/- 0.15 ml/min at 4 months, 0.69 +/- 0.13 ml/min at 6 months, both P less than 0.05 vs. group 3). Reduction in GFR was associated with the development of glomerular sclerosis in both treated and untreated rats.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Nephrosis", "aliases": "Nephroses Nephrosis", "definition": "Pathological processes of the KIDNEY without inflammatory or neoplastic components. Nephrosis may be a primary disorder or secondary complication of other diseases. It is characterized by the NEPHROTIC SYNDROME indicating the presence of PROTEINURIA and HYPOALBUMINEMIA with accompanying EDEMA.\n    ", "id": "MESH:D009401"}
{"mention": "albuminuria", "mention_text": "The effect of the converting enzyme inhibitor (CEI) enalapril was assessed in Munich-Wistar rats with established adriamycin nephrosis. Rats were given a single dose of adriamycin and one month later divided into four groups matched for albuminuria, blood pressure, and plasma albumin concentration. Groups 1 and 3 remained untreated while groups 2 and 4 received enalapril. Groups 1 and 2 underwent micropuncture studies after 10 days. These short-term studies showed that enalapril reduced arterial blood pressure (101 +/- 2 vs. 124 +/- 3 mm Hg, group 2 vs. 1, P less than 0.05) and glomerular capillary pressure (54 +/- 1 vs. 61 +/- 2 mm Hg, P less than 0.05) without reducing albuminuria (617 +/- 50 vs. 570 +/- 47 mg/day) or GFR (1.03 +/- 0.04 vs. 1.04 +/- 0.11 ml/min). Groups 3 and 4 were studied at four and at six months to assess the effect of enalapril on progression of renal injury in adriamycin nephrosis. Chronic enalapril treatment reduced blood pressure without reducing albuminuria in group 4. Untreated group 3 rats exhibited a progressive reduction in GFR (0.35 +/- 0.08 ml/min at 4 months, 0.27 +/- 0.07 ml/min at 6 months). Enalapril treatment blunted but did not prevent reduction in GFR in group 4 (0.86 +/- 0.15 ml/min at 4 months, 0.69 +/- 0.13 ml/min at 6 months, both P less than 0.05 vs. group 3). Reduction in GFR was associated with the development of glomerular sclerosis in both treated and untreated rats.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Albuminuria", "aliases": "Albuminuria Albuminurias", "definition": "The presence of albumin in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D000419"}
{"mention": "renal injury", "mention_text": "The effect of the converting enzyme inhibitor (CEI) enalapril was assessed in Munich-Wistar rats with established adriamycin nephrosis. Rats were given a single dose of adriamycin and one month later divided into four groups matched for albuminuria, blood pressure, and plasma albumin concentration. Groups 1 and 3 remained untreated while groups 2 and 4 received enalapril. Groups 1 and 2 underwent micropuncture studies after 10 days. These short-term studies showed that enalapril reduced arterial blood pressure (101 +/- 2 vs. 124 +/- 3 mm Hg, group 2 vs. 1, P less than 0.05) and glomerular capillary pressure (54 +/- 1 vs. 61 +/- 2 mm Hg, P less than 0.05) without reducing albuminuria (617 +/- 50 vs. 570 +/- 47 mg/day) or GFR (1.03 +/- 0.04 vs. 1.04 +/- 0.11 ml/min). Groups 3 and 4 were studied at four and at six months to assess the effect of enalapril on progression of renal injury in adriamycin nephrosis. Chronic enalapril treatment reduced blood pressure without reducing albuminuria in group 4. Untreated group 3 rats exhibited a progressive reduction in GFR (0.35 +/- 0.08 ml/min at 4 months, 0.27 +/- 0.07 ml/min at 6 months). Enalapril treatment blunted but did not prevent reduction in GFR in group 4 (0.86 +/- 0.15 ml/min at 4 months, 0.69 +/- 0.13 ml/min at 6 months, both P less than 0.05 vs. group 3). Reduction in GFR was associated with the development of glomerular sclerosis in both treated and untreated rats.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "Enalapril", "mention_text": "The effect of the converting enzyme inhibitor (CEI) enalapril was assessed in Munich-Wistar rats with established adriamycin nephrosis. Rats were given a single dose of adriamycin and one month later divided into four groups matched for albuminuria, blood pressure, and plasma albumin concentration. Groups 1 and 3 remained untreated while groups 2 and 4 received enalapril. Groups 1 and 2 underwent micropuncture studies after 10 days. These short-term studies showed that enalapril reduced arterial blood pressure (101 +/- 2 vs. 124 +/- 3 mm Hg, group 2 vs. 1, P less than 0.05) and glomerular capillary pressure (54 +/- 1 vs. 61 +/- 2 mm Hg, P less than 0.05) without reducing albuminuria (617 +/- 50 vs. 570 +/- 47 mg/day) or GFR (1.03 +/- 0.04 vs. 1.04 +/- 0.11 ml/min). Groups 3 and 4 were studied at four and at six months to assess the effect of enalapril on progression of renal injury in adriamycin nephrosis. Chronic enalapril treatment reduced blood pressure without reducing albuminuria in group 4. Untreated group 3 rats exhibited a progressive reduction in GFR (0.35 +/- 0.08 ml/min at 4 months, 0.27 +/- 0.07 ml/min at 6 months). Enalapril treatment blunted but did not prevent reduction in GFR in group 4 (0.86 +/- 0.15 ml/min at 4 months, 0.69 +/- 0.13 ml/min at 6 months, both P less than 0.05 vs. group 3). Reduction in GFR was associated with the development of glomerular sclerosis in both treated and untreated rats.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Enalapril", "aliases": "Enalapril Maleate MK 421 MK-421 MK421 Renitec Renitek", "definition": "One of the ANGIOTENSIN-CONVERTING ENZYME INHIBITORS that is used to treat hypertension.\n    ", "id": "MESH:D004656"}
{"mention": "glomerular sclerosis", "mention_text": "The effect of the converting enzyme inhibitor (CEI) enalapril was assessed in Munich-Wistar rats with established adriamycin nephrosis. Rats were given a single dose of adriamycin and one month later divided into four groups matched for albuminuria, blood pressure, and plasma albumin concentration. Groups 1 and 3 remained untreated while groups 2 and 4 received enalapril. Groups 1 and 2 underwent micropuncture studies after 10 days. These short-term studies showed that enalapril reduced arterial blood pressure (101 +/- 2 vs. 124 +/- 3 mm Hg, group 2 vs. 1, P less than 0.05) and glomerular capillary pressure (54 +/- 1 vs. 61 +/- 2 mm Hg, P less than 0.05) without reducing albuminuria (617 +/- 50 vs. 570 +/- 47 mg/day) or GFR (1.03 +/- 0.04 vs. 1.04 +/- 0.11 ml/min). Groups 3 and 4 were studied at four and at six months to assess the effect of enalapril on progression of renal injury in adriamycin nephrosis. Chronic enalapril treatment reduced blood pressure without reducing albuminuria in group 4. Untreated group 3 rats exhibited a progressive reduction in GFR (0.35 +/- 0.08 ml/min at 4 months, 0.27 +/- 0.07 ml/min at 6 months). Enalapril treatment blunted but did not prevent reduction in GFR in group 4 (0.86 +/- 0.15 ml/min at 4 months, 0.69 +/- 0.13 ml/min at 6 months, both P less than 0.05 vs. group 3). Reduction in GFR was associated with the development of glomerular sclerosis in both treated and untreated rats.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "apnea", "mention_text": "Butyrylcholinesterase gene mutations in patients with prolonged apnea after succinylcholine for electroconvulsive therapy.", "entity": "Apnea", "aliases": "Apnea Apneas", "definition": "A transient absence of spontaneous respiration.\n    ", "id": "MESH:D001049"}
{"mention": "succinylcholine", "mention_text": "Butyrylcholinesterase gene mutations in patients with prolonged apnea after succinylcholine for electroconvulsive therapy.", "entity": "Succinylcholine", "aliases": "Anectine Bromide Suxamethonium Celocurine Dibromide Succinylcholine Dichloride Diiodide Diperchlorate Ditilin Listenon Lysthenon Myorelaxin Quelicin Succicuran Chloride Di H2O Di-H2O Iodide Succinyldicholine", "definition": "A quaternary skeletal muscle relaxant usually used in the form of its bromide, chloride, or iodide. It is a depolarizing relaxant, acting in about 30 seconds and with a duration of effect averaging three to five minutes. Succinylcholine is used in surgical, anesthetic, and other procedures in which a brief period of muscle relaxation is called for.\n    ", "id": "MESH:D013390"}
{"mention": "succinylcholine", "mention_text": "BACKGROUND: patients undergoing electroconvulsive therapy (ECT) often receive succinylcholine as part of the anesthetic procedure. The duration of action may be prolonged in patients with genetic variants of the butyrylcholinesterase enzyme (BChE), the most common being the K- and the A-variants. The aim of the study was to assess the clinical significance of genetic variants in butyrylcholinesterase gene (BCHE) in patients with a suspected prolonged duration of action of succinylcholine after ECT. METHODS: a total of 13 patients were referred to the Danish Cholinesterase Research Unit after ECT during 38 months. We determined the BChE activity and the BCHE genotype using molecular genetic methods, the duration of apnea, time to sufficient spontaneous ventilation and whether neuromuscular monitoring was used. The duration of apnea was compared with published data on normal subjects. RESULTS: in 11 patients, mutations were found in the BCHE gene, the K-variant being the most frequent. The duration of apnea was 5-15 min compared with 3-5.3 min from the literature. Severe distress was noted in the recovery phase in two patients. Neuromuscular monitoring was used in two patients. CONCLUSION: eleven of 13 patients with a prolonged duration of action of succinylcholine had mutations in BCHE, indicating that this is the possible reason for a prolonged period of apnea. We recommend objective neuromuscular monitoring during the first ECT.", "entity": "Succinylcholine", "aliases": "Anectine Bromide Suxamethonium Celocurine Dibromide Succinylcholine Dichloride Diiodide Diperchlorate Ditilin Listenon Lysthenon Myorelaxin Quelicin Succicuran Chloride Di H2O Di-H2O Iodide Succinyldicholine", "definition": "A quaternary skeletal muscle relaxant usually used in the form of its bromide, chloride, or iodide. It is a depolarizing relaxant, acting in about 30 seconds and with a duration of effect averaging three to five minutes. Succinylcholine is used in surgical, anesthetic, and other procedures in which a brief period of muscle relaxation is called for.\n    ", "id": "MESH:D013390"}
{"mention": "apnea", "mention_text": "BACKGROUND: patients undergoing electroconvulsive therapy (ECT) often receive succinylcholine as part of the anesthetic procedure. The duration of action may be prolonged in patients with genetic variants of the butyrylcholinesterase enzyme (BChE), the most common being the K- and the A-variants. The aim of the study was to assess the clinical significance of genetic variants in butyrylcholinesterase gene (BCHE) in patients with a suspected prolonged duration of action of succinylcholine after ECT. METHODS: a total of 13 patients were referred to the Danish Cholinesterase Research Unit after ECT during 38 months. We determined the BChE activity and the BCHE genotype using molecular genetic methods, the duration of apnea, time to sufficient spontaneous ventilation and whether neuromuscular monitoring was used. The duration of apnea was compared with published data on normal subjects. RESULTS: in 11 patients, mutations were found in the BCHE gene, the K-variant being the most frequent. The duration of apnea was 5-15 min compared with 3-5.3 min from the literature. Severe distress was noted in the recovery phase in two patients. Neuromuscular monitoring was used in two patients. CONCLUSION: eleven of 13 patients with a prolonged duration of action of succinylcholine had mutations in BCHE, indicating that this is the possible reason for a prolonged period of apnea. We recommend objective neuromuscular monitoring during the first ECT.", "entity": "Apnea", "aliases": "Apnea Apneas", "definition": "A transient absence of spontaneous respiration.\n    ", "id": "MESH:D001049"}
{"mention": "Ketamine", "mention_text": "Ketamine sedation for the reduction of children's fractures in the emergency department.", "entity": "Ketamine", "aliases": "2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone CI 581 CI-581 CI581 Calipsol Calypsol Kalipsol Ketalar Ketamine Hydrochloride Ketanest Ketaset", "definition": "A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors.\n    ", "id": "MESH:D007649"}
{"mention": "fractures", "mention_text": "Ketamine sedation for the reduction of children's fractures in the emergency department.", "entity": "Fractures, Bone", "aliases": "Bone Fracture Fractures Broken Bones", "definition": "Breaks in bones.\n    ", "id": "MESH:D050723"}
{"mention": "ketamine", "mention_text": "BACKGROUND: There recently has been a resurgence in the utilization of ketamine, a unique anesthetic, for emergency-department procedures requiring sedation. The purpose of the present study was to examine the safety and efficacy of ketamine for sedation in the treatment of children's fractures in the emergency department. METHODS: One hundred and fourteen children (average age, 5.3 years; range, twelve months to ten years and ten months) who underwent closed reduction of an isolated fracture or dislocation in the emergency department at a level-I trauma center were prospectively evaluated. Ketamine hydrochloride was administered intravenously (at a dose of two milligrams per kilogram of body weight) in ninety-nine of the patients and intramuscularly (at a dose of four milligrams per kilogram of body weight) in the other fifteen. A board-certified emergency physician skilled in airway management supervised administration of the anesthetic, and the patients were monitored by a registered nurse. Any pain during the reduction was rated by the orthopaedic surgeon treating the patient according to the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). RESULTS: The average time from intravenous administration of ketamine to manipulation of the fracture or dislocation was one minute and thirty-six seconds (range, twenty seconds to five minutes), and the average time from intramuscular administration to manipulation was four minutes and forty-two seconds (range, sixty seconds to fifteen minutes). The average score according to the Children's Hospital of Eastern Ontario Pain Scale was 6.4 points (range, 5 to 10 points), reflecting minimal or no pain during fracture reduction. Adequate fracture reduction was obtained in 111 of the children. Ninety-nine percent (sixty-eight) of the sixty-nine parents present during the reduction were pleased with the sedation and would allow it to be used again in a similar situation. Patency of the airway and independent respiration were maintained in all of the patients. Blood pressure and heart rate remained stable. Minor side effects included nausea (thirteen patients), emesis (eight of the thirteen patients with nausea), clumsiness (evident as ataxic movements in ten patients), and dysphoric reaction (one patient). No long-term sequelae were noted, and no patients had hallucinations or nightmares. CONCLUSIONS: Ketamine reliably, safely, and quickly provided adequate sedation to effectively facilitate the reduction of children's fractures in the emergency department at our institution. Ketamine should only be used in an environment such as the emergency department, where proper one-on-one monitoring is used and board-certified physicians skilled in airway management are directly involved in the care of the patient.", "entity": "Ketamine", "aliases": "2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone CI 581 CI-581 CI581 Calipsol Calypsol Kalipsol Ketalar Ketamine Hydrochloride Ketanest Ketaset", "definition": "A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors.\n    ", "id": "MESH:D007649"}
{"mention": "fractures", "mention_text": "BACKGROUND: There recently has been a resurgence in the utilization of ketamine, a unique anesthetic, for emergency-department procedures requiring sedation. The purpose of the present study was to examine the safety and efficacy of ketamine for sedation in the treatment of children's fractures in the emergency department. METHODS: One hundred and fourteen children (average age, 5.3 years; range, twelve months to ten years and ten months) who underwent closed reduction of an isolated fracture or dislocation in the emergency department at a level-I trauma center were prospectively evaluated. Ketamine hydrochloride was administered intravenously (at a dose of two milligrams per kilogram of body weight) in ninety-nine of the patients and intramuscularly (at a dose of four milligrams per kilogram of body weight) in the other fifteen. A board-certified emergency physician skilled in airway management supervised administration of the anesthetic, and the patients were monitored by a registered nurse. Any pain during the reduction was rated by the orthopaedic surgeon treating the patient according to the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). RESULTS: The average time from intravenous administration of ketamine to manipulation of the fracture or dislocation was one minute and thirty-six seconds (range, twenty seconds to five minutes), and the average time from intramuscular administration to manipulation was four minutes and forty-two seconds (range, sixty seconds to fifteen minutes). The average score according to the Children's Hospital of Eastern Ontario Pain Scale was 6.4 points (range, 5 to 10 points), reflecting minimal or no pain during fracture reduction. Adequate fracture reduction was obtained in 111 of the children. Ninety-nine percent (sixty-eight) of the sixty-nine parents present during the reduction were pleased with the sedation and would allow it to be used again in a similar situation. Patency of the airway and independent respiration were maintained in all of the patients. Blood pressure and heart rate remained stable. Minor side effects included nausea (thirteen patients), emesis (eight of the thirteen patients with nausea), clumsiness (evident as ataxic movements in ten patients), and dysphoric reaction (one patient). No long-term sequelae were noted, and no patients had hallucinations or nightmares. CONCLUSIONS: Ketamine reliably, safely, and quickly provided adequate sedation to effectively facilitate the reduction of children's fractures in the emergency department at our institution. Ketamine should only be used in an environment such as the emergency department, where proper one-on-one monitoring is used and board-certified physicians skilled in airway management are directly involved in the care of the patient.", "entity": "Fractures, Bone", "aliases": "Bone Fracture Fractures Broken Bones", "definition": "Breaks in bones.\n    ", "id": "MESH:D050723"}
{"mention": "fracture", "mention_text": "BACKGROUND: There recently has been a resurgence in the utilization of ketamine, a unique anesthetic, for emergency-department procedures requiring sedation. The purpose of the present study was to examine the safety and efficacy of ketamine for sedation in the treatment of children's fractures in the emergency department. METHODS: One hundred and fourteen children (average age, 5.3 years; range, twelve months to ten years and ten months) who underwent closed reduction of an isolated fracture or dislocation in the emergency department at a level-I trauma center were prospectively evaluated. Ketamine hydrochloride was administered intravenously (at a dose of two milligrams per kilogram of body weight) in ninety-nine of the patients and intramuscularly (at a dose of four milligrams per kilogram of body weight) in the other fifteen. A board-certified emergency physician skilled in airway management supervised administration of the anesthetic, and the patients were monitored by a registered nurse. Any pain during the reduction was rated by the orthopaedic surgeon treating the patient according to the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). RESULTS: The average time from intravenous administration of ketamine to manipulation of the fracture or dislocation was one minute and thirty-six seconds (range, twenty seconds to five minutes), and the average time from intramuscular administration to manipulation was four minutes and forty-two seconds (range, sixty seconds to fifteen minutes). The average score according to the Children's Hospital of Eastern Ontario Pain Scale was 6.4 points (range, 5 to 10 points), reflecting minimal or no pain during fracture reduction. Adequate fracture reduction was obtained in 111 of the children. Ninety-nine percent (sixty-eight) of the sixty-nine parents present during the reduction were pleased with the sedation and would allow it to be used again in a similar situation. Patency of the airway and independent respiration were maintained in all of the patients. Blood pressure and heart rate remained stable. Minor side effects included nausea (thirteen patients), emesis (eight of the thirteen patients with nausea), clumsiness (evident as ataxic movements in ten patients), and dysphoric reaction (one patient). No long-term sequelae were noted, and no patients had hallucinations or nightmares. CONCLUSIONS: Ketamine reliably, safely, and quickly provided adequate sedation to effectively facilitate the reduction of children's fractures in the emergency department at our institution. Ketamine should only be used in an environment such as the emergency department, where proper one-on-one monitoring is used and board-certified physicians skilled in airway management are directly involved in the care of the patient.", "entity": "Fractures, Bone", "aliases": "Bone Fracture Fractures Broken Bones", "definition": "Breaks in bones.\n    ", "id": "MESH:D050723"}
{"mention": "dislocation", "mention_text": "BACKGROUND: There recently has been a resurgence in the utilization of ketamine, a unique anesthetic, for emergency-department procedures requiring sedation. The purpose of the present study was to examine the safety and efficacy of ketamine for sedation in the treatment of children's fractures in the emergency department. METHODS: One hundred and fourteen children (average age, 5.3 years; range, twelve months to ten years and ten months) who underwent closed reduction of an isolated fracture or dislocation in the emergency department at a level-I trauma center were prospectively evaluated. Ketamine hydrochloride was administered intravenously (at a dose of two milligrams per kilogram of body weight) in ninety-nine of the patients and intramuscularly (at a dose of four milligrams per kilogram of body weight) in the other fifteen. A board-certified emergency physician skilled in airway management supervised administration of the anesthetic, and the patients were monitored by a registered nurse. Any pain during the reduction was rated by the orthopaedic surgeon treating the patient according to the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). RESULTS: The average time from intravenous administration of ketamine to manipulation of the fracture or dislocation was one minute and thirty-six seconds (range, twenty seconds to five minutes), and the average time from intramuscular administration to manipulation was four minutes and forty-two seconds (range, sixty seconds to fifteen minutes). The average score according to the Children's Hospital of Eastern Ontario Pain Scale was 6.4 points (range, 5 to 10 points), reflecting minimal or no pain during fracture reduction. Adequate fracture reduction was obtained in 111 of the children. Ninety-nine percent (sixty-eight) of the sixty-nine parents present during the reduction were pleased with the sedation and would allow it to be used again in a similar situation. Patency of the airway and independent respiration were maintained in all of the patients. Blood pressure and heart rate remained stable. Minor side effects included nausea (thirteen patients), emesis (eight of the thirteen patients with nausea), clumsiness (evident as ataxic movements in ten patients), and dysphoric reaction (one patient). No long-term sequelae were noted, and no patients had hallucinations or nightmares. CONCLUSIONS: Ketamine reliably, safely, and quickly provided adequate sedation to effectively facilitate the reduction of children's fractures in the emergency department at our institution. Ketamine should only be used in an environment such as the emergency department, where proper one-on-one monitoring is used and board-certified physicians skilled in airway management are directly involved in the care of the patient.", "entity": "Dislocations", "aliases": "Dislocation Dislocations", "definition": "", "id": "MESH:D004204"}
{"mention": "trauma", "mention_text": "BACKGROUND: There recently has been a resurgence in the utilization of ketamine, a unique anesthetic, for emergency-department procedures requiring sedation. The purpose of the present study was to examine the safety and efficacy of ketamine for sedation in the treatment of children's fractures in the emergency department. METHODS: One hundred and fourteen children (average age, 5.3 years; range, twelve months to ten years and ten months) who underwent closed reduction of an isolated fracture or dislocation in the emergency department at a level-I trauma center were prospectively evaluated. Ketamine hydrochloride was administered intravenously (at a dose of two milligrams per kilogram of body weight) in ninety-nine of the patients and intramuscularly (at a dose of four milligrams per kilogram of body weight) in the other fifteen. A board-certified emergency physician skilled in airway management supervised administration of the anesthetic, and the patients were monitored by a registered nurse. Any pain during the reduction was rated by the orthopaedic surgeon treating the patient according to the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). RESULTS: The average time from intravenous administration of ketamine to manipulation of the fracture or dislocation was one minute and thirty-six seconds (range, twenty seconds to five minutes), and the average time from intramuscular administration to manipulation was four minutes and forty-two seconds (range, sixty seconds to fifteen minutes). The average score according to the Children's Hospital of Eastern Ontario Pain Scale was 6.4 points (range, 5 to 10 points), reflecting minimal or no pain during fracture reduction. Adequate fracture reduction was obtained in 111 of the children. Ninety-nine percent (sixty-eight) of the sixty-nine parents present during the reduction were pleased with the sedation and would allow it to be used again in a similar situation. Patency of the airway and independent respiration were maintained in all of the patients. Blood pressure and heart rate remained stable. Minor side effects included nausea (thirteen patients), emesis (eight of the thirteen patients with nausea), clumsiness (evident as ataxic movements in ten patients), and dysphoric reaction (one patient). No long-term sequelae were noted, and no patients had hallucinations or nightmares. CONCLUSIONS: Ketamine reliably, safely, and quickly provided adequate sedation to effectively facilitate the reduction of children's fractures in the emergency department at our institution. Ketamine should only be used in an environment such as the emergency department, where proper one-on-one monitoring is used and board-certified physicians skilled in airway management are directly involved in the care of the patient.", "entity": "Wounds and Injuries", "aliases": "Injuries and Wounds Injury Trauma Traumas Wound", "definition": "Damage inflicted on the body as the direct or indirect result of an external force, with or without disruption of structural continuity.\n    ", "id": "MESH:D014947"}
{"mention": "Ketamine hydrochloride", "mention_text": "BACKGROUND: There recently has been a resurgence in the utilization of ketamine, a unique anesthetic, for emergency-department procedures requiring sedation. The purpose of the present study was to examine the safety and efficacy of ketamine for sedation in the treatment of children's fractures in the emergency department. METHODS: One hundred and fourteen children (average age, 5.3 years; range, twelve months to ten years and ten months) who underwent closed reduction of an isolated fracture or dislocation in the emergency department at a level-I trauma center were prospectively evaluated. Ketamine hydrochloride was administered intravenously (at a dose of two milligrams per kilogram of body weight) in ninety-nine of the patients and intramuscularly (at a dose of four milligrams per kilogram of body weight) in the other fifteen. A board-certified emergency physician skilled in airway management supervised administration of the anesthetic, and the patients were monitored by a registered nurse. Any pain during the reduction was rated by the orthopaedic surgeon treating the patient according to the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). RESULTS: The average time from intravenous administration of ketamine to manipulation of the fracture or dislocation was one minute and thirty-six seconds (range, twenty seconds to five minutes), and the average time from intramuscular administration to manipulation was four minutes and forty-two seconds (range, sixty seconds to fifteen minutes). The average score according to the Children's Hospital of Eastern Ontario Pain Scale was 6.4 points (range, 5 to 10 points), reflecting minimal or no pain during fracture reduction. Adequate fracture reduction was obtained in 111 of the children. Ninety-nine percent (sixty-eight) of the sixty-nine parents present during the reduction were pleased with the sedation and would allow it to be used again in a similar situation. Patency of the airway and independent respiration were maintained in all of the patients. Blood pressure and heart rate remained stable. Minor side effects included nausea (thirteen patients), emesis (eight of the thirteen patients with nausea), clumsiness (evident as ataxic movements in ten patients), and dysphoric reaction (one patient). No long-term sequelae were noted, and no patients had hallucinations or nightmares. CONCLUSIONS: Ketamine reliably, safely, and quickly provided adequate sedation to effectively facilitate the reduction of children's fractures in the emergency department at our institution. Ketamine should only be used in an environment such as the emergency department, where proper one-on-one monitoring is used and board-certified physicians skilled in airway management are directly involved in the care of the patient.", "entity": "Ketamine", "aliases": "2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone CI 581 CI-581 CI581 Calipsol Calypsol Kalipsol Ketalar Ketamine Hydrochloride Ketanest Ketaset", "definition": "A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors.\n    ", "id": "MESH:D007649"}
{"mention": "pain", "mention_text": "BACKGROUND: There recently has been a resurgence in the utilization of ketamine, a unique anesthetic, for emergency-department procedures requiring sedation. The purpose of the present study was to examine the safety and efficacy of ketamine for sedation in the treatment of children's fractures in the emergency department. METHODS: One hundred and fourteen children (average age, 5.3 years; range, twelve months to ten years and ten months) who underwent closed reduction of an isolated fracture or dislocation in the emergency department at a level-I trauma center were prospectively evaluated. Ketamine hydrochloride was administered intravenously (at a dose of two milligrams per kilogram of body weight) in ninety-nine of the patients and intramuscularly (at a dose of four milligrams per kilogram of body weight) in the other fifteen. A board-certified emergency physician skilled in airway management supervised administration of the anesthetic, and the patients were monitored by a registered nurse. Any pain during the reduction was rated by the orthopaedic surgeon treating the patient according to the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). RESULTS: The average time from intravenous administration of ketamine to manipulation of the fracture or dislocation was one minute and thirty-six seconds (range, twenty seconds to five minutes), and the average time from intramuscular administration to manipulation was four minutes and forty-two seconds (range, sixty seconds to fifteen minutes). The average score according to the Children's Hospital of Eastern Ontario Pain Scale was 6.4 points (range, 5 to 10 points), reflecting minimal or no pain during fracture reduction. Adequate fracture reduction was obtained in 111 of the children. Ninety-nine percent (sixty-eight) of the sixty-nine parents present during the reduction were pleased with the sedation and would allow it to be used again in a similar situation. Patency of the airway and independent respiration were maintained in all of the patients. Blood pressure and heart rate remained stable. Minor side effects included nausea (thirteen patients), emesis (eight of the thirteen patients with nausea), clumsiness (evident as ataxic movements in ten patients), and dysphoric reaction (one patient). No long-term sequelae were noted, and no patients had hallucinations or nightmares. CONCLUSIONS: Ketamine reliably, safely, and quickly provided adequate sedation to effectively facilitate the reduction of children's fractures in the emergency department at our institution. Ketamine should only be used in an environment such as the emergency department, where proper one-on-one monitoring is used and board-certified physicians skilled in airway management are directly involved in the care of the patient.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "Pain", "mention_text": "BACKGROUND: There recently has been a resurgence in the utilization of ketamine, a unique anesthetic, for emergency-department procedures requiring sedation. The purpose of the present study was to examine the safety and efficacy of ketamine for sedation in the treatment of children's fractures in the emergency department. METHODS: One hundred and fourteen children (average age, 5.3 years; range, twelve months to ten years and ten months) who underwent closed reduction of an isolated fracture or dislocation in the emergency department at a level-I trauma center were prospectively evaluated. Ketamine hydrochloride was administered intravenously (at a dose of two milligrams per kilogram of body weight) in ninety-nine of the patients and intramuscularly (at a dose of four milligrams per kilogram of body weight) in the other fifteen. A board-certified emergency physician skilled in airway management supervised administration of the anesthetic, and the patients were monitored by a registered nurse. Any pain during the reduction was rated by the orthopaedic surgeon treating the patient according to the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). RESULTS: The average time from intravenous administration of ketamine to manipulation of the fracture or dislocation was one minute and thirty-six seconds (range, twenty seconds to five minutes), and the average time from intramuscular administration to manipulation was four minutes and forty-two seconds (range, sixty seconds to fifteen minutes). The average score according to the Children's Hospital of Eastern Ontario Pain Scale was 6.4 points (range, 5 to 10 points), reflecting minimal or no pain during fracture reduction. Adequate fracture reduction was obtained in 111 of the children. Ninety-nine percent (sixty-eight) of the sixty-nine parents present during the reduction were pleased with the sedation and would allow it to be used again in a similar situation. Patency of the airway and independent respiration were maintained in all of the patients. Blood pressure and heart rate remained stable. Minor side effects included nausea (thirteen patients), emesis (eight of the thirteen patients with nausea), clumsiness (evident as ataxic movements in ten patients), and dysphoric reaction (one patient). No long-term sequelae were noted, and no patients had hallucinations or nightmares. CONCLUSIONS: Ketamine reliably, safely, and quickly provided adequate sedation to effectively facilitate the reduction of children's fractures in the emergency department at our institution. Ketamine should only be used in an environment such as the emergency department, where proper one-on-one monitoring is used and board-certified physicians skilled in airway management are directly involved in the care of the patient.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "nausea", "mention_text": "BACKGROUND: There recently has been a resurgence in the utilization of ketamine, a unique anesthetic, for emergency-department procedures requiring sedation. The purpose of the present study was to examine the safety and efficacy of ketamine for sedation in the treatment of children's fractures in the emergency department. METHODS: One hundred and fourteen children (average age, 5.3 years; range, twelve months to ten years and ten months) who underwent closed reduction of an isolated fracture or dislocation in the emergency department at a level-I trauma center were prospectively evaluated. Ketamine hydrochloride was administered intravenously (at a dose of two milligrams per kilogram of body weight) in ninety-nine of the patients and intramuscularly (at a dose of four milligrams per kilogram of body weight) in the other fifteen. A board-certified emergency physician skilled in airway management supervised administration of the anesthetic, and the patients were monitored by a registered nurse. Any pain during the reduction was rated by the orthopaedic surgeon treating the patient according to the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). RESULTS: The average time from intravenous administration of ketamine to manipulation of the fracture or dislocation was one minute and thirty-six seconds (range, twenty seconds to five minutes), and the average time from intramuscular administration to manipulation was four minutes and forty-two seconds (range, sixty seconds to fifteen minutes). The average score according to the Children's Hospital of Eastern Ontario Pain Scale was 6.4 points (range, 5 to 10 points), reflecting minimal or no pain during fracture reduction. Adequate fracture reduction was obtained in 111 of the children. Ninety-nine percent (sixty-eight) of the sixty-nine parents present during the reduction were pleased with the sedation and would allow it to be used again in a similar situation. Patency of the airway and independent respiration were maintained in all of the patients. Blood pressure and heart rate remained stable. Minor side effects included nausea (thirteen patients), emesis (eight of the thirteen patients with nausea), clumsiness (evident as ataxic movements in ten patients), and dysphoric reaction (one patient). No long-term sequelae were noted, and no patients had hallucinations or nightmares. CONCLUSIONS: Ketamine reliably, safely, and quickly provided adequate sedation to effectively facilitate the reduction of children's fractures in the emergency department at our institution. Ketamine should only be used in an environment such as the emergency department, where proper one-on-one monitoring is used and board-certified physicians skilled in airway management are directly involved in the care of the patient.", "entity": "Nausea", "aliases": "Nausea", "definition": "An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.\n    ", "id": "MESH:D009325"}
{"mention": "emesis", "mention_text": "BACKGROUND: There recently has been a resurgence in the utilization of ketamine, a unique anesthetic, for emergency-department procedures requiring sedation. The purpose of the present study was to examine the safety and efficacy of ketamine for sedation in the treatment of children's fractures in the emergency department. METHODS: One hundred and fourteen children (average age, 5.3 years; range, twelve months to ten years and ten months) who underwent closed reduction of an isolated fracture or dislocation in the emergency department at a level-I trauma center were prospectively evaluated. Ketamine hydrochloride was administered intravenously (at a dose of two milligrams per kilogram of body weight) in ninety-nine of the patients and intramuscularly (at a dose of four milligrams per kilogram of body weight) in the other fifteen. A board-certified emergency physician skilled in airway management supervised administration of the anesthetic, and the patients were monitored by a registered nurse. Any pain during the reduction was rated by the orthopaedic surgeon treating the patient according to the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). RESULTS: The average time from intravenous administration of ketamine to manipulation of the fracture or dislocation was one minute and thirty-six seconds (range, twenty seconds to five minutes), and the average time from intramuscular administration to manipulation was four minutes and forty-two seconds (range, sixty seconds to fifteen minutes). The average score according to the Children's Hospital of Eastern Ontario Pain Scale was 6.4 points (range, 5 to 10 points), reflecting minimal or no pain during fracture reduction. Adequate fracture reduction was obtained in 111 of the children. Ninety-nine percent (sixty-eight) of the sixty-nine parents present during the reduction were pleased with the sedation and would allow it to be used again in a similar situation. Patency of the airway and independent respiration were maintained in all of the patients. Blood pressure and heart rate remained stable. Minor side effects included nausea (thirteen patients), emesis (eight of the thirteen patients with nausea), clumsiness (evident as ataxic movements in ten patients), and dysphoric reaction (one patient). No long-term sequelae were noted, and no patients had hallucinations or nightmares. CONCLUSIONS: Ketamine reliably, safely, and quickly provided adequate sedation to effectively facilitate the reduction of children's fractures in the emergency department at our institution. Ketamine should only be used in an environment such as the emergency department, where proper one-on-one monitoring is used and board-certified physicians skilled in airway management are directly involved in the care of the patient.", "entity": "Vomiting", "aliases": "Emesis Vomiting", "definition": "The forcible expulsion of the contents of the STOMACH through the MOUTH.\n    ", "id": "MESH:D014839"}
{"mention": "clumsiness", "mention_text": "BACKGROUND: There recently has been a resurgence in the utilization of ketamine, a unique anesthetic, for emergency-department procedures requiring sedation. The purpose of the present study was to examine the safety and efficacy of ketamine for sedation in the treatment of children's fractures in the emergency department. METHODS: One hundred and fourteen children (average age, 5.3 years; range, twelve months to ten years and ten months) who underwent closed reduction of an isolated fracture or dislocation in the emergency department at a level-I trauma center were prospectively evaluated. Ketamine hydrochloride was administered intravenously (at a dose of two milligrams per kilogram of body weight) in ninety-nine of the patients and intramuscularly (at a dose of four milligrams per kilogram of body weight) in the other fifteen. A board-certified emergency physician skilled in airway management supervised administration of the anesthetic, and the patients were monitored by a registered nurse. Any pain during the reduction was rated by the orthopaedic surgeon treating the patient according to the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). RESULTS: The average time from intravenous administration of ketamine to manipulation of the fracture or dislocation was one minute and thirty-six seconds (range, twenty seconds to five minutes), and the average time from intramuscular administration to manipulation was four minutes and forty-two seconds (range, sixty seconds to fifteen minutes). The average score according to the Children's Hospital of Eastern Ontario Pain Scale was 6.4 points (range, 5 to 10 points), reflecting minimal or no pain during fracture reduction. Adequate fracture reduction was obtained in 111 of the children. Ninety-nine percent (sixty-eight) of the sixty-nine parents present during the reduction were pleased with the sedation and would allow it to be used again in a similar situation. Patency of the airway and independent respiration were maintained in all of the patients. Blood pressure and heart rate remained stable. Minor side effects included nausea (thirteen patients), emesis (eight of the thirteen patients with nausea), clumsiness (evident as ataxic movements in ten patients), and dysphoric reaction (one patient). No long-term sequelae were noted, and no patients had hallucinations or nightmares. CONCLUSIONS: Ketamine reliably, safely, and quickly provided adequate sedation to effectively facilitate the reduction of children's fractures in the emergency department at our institution. Ketamine should only be used in an environment such as the emergency department, where proper one-on-one monitoring is used and board-certified physicians skilled in airway management are directly involved in the care of the patient.", "entity": "Ataxia", "aliases": "Appendicular Ataxia Ataxias Limb Motor Sensory Truncal Ataxy Coordination Impairment Impairments Lack Dyscoordination Dyssynergia Incoordination Incoordinations of Rubral Tremor Tremors", "definition": "Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or PERIPHERAL NERVE DISEASES. Motor ataxia may be associated with CEREBELLAR DISEASES; CEREBRAL CORTEX diseases; THALAMIC DISEASES; BASAL GANGLIA DISEASES; injury to the RED NUCLEUS; and other conditions.\n    ", "id": "MESH:D001259"}
{"mention": "ataxic movements", "mention_text": "BACKGROUND: There recently has been a resurgence in the utilization of ketamine, a unique anesthetic, for emergency-department procedures requiring sedation. The purpose of the present study was to examine the safety and efficacy of ketamine for sedation in the treatment of children's fractures in the emergency department. METHODS: One hundred and fourteen children (average age, 5.3 years; range, twelve months to ten years and ten months) who underwent closed reduction of an isolated fracture or dislocation in the emergency department at a level-I trauma center were prospectively evaluated. Ketamine hydrochloride was administered intravenously (at a dose of two milligrams per kilogram of body weight) in ninety-nine of the patients and intramuscularly (at a dose of four milligrams per kilogram of body weight) in the other fifteen. A board-certified emergency physician skilled in airway management supervised administration of the anesthetic, and the patients were monitored by a registered nurse. Any pain during the reduction was rated by the orthopaedic surgeon treating the patient according to the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). RESULTS: The average time from intravenous administration of ketamine to manipulation of the fracture or dislocation was one minute and thirty-six seconds (range, twenty seconds to five minutes), and the average time from intramuscular administration to manipulation was four minutes and forty-two seconds (range, sixty seconds to fifteen minutes). The average score according to the Children's Hospital of Eastern Ontario Pain Scale was 6.4 points (range, 5 to 10 points), reflecting minimal or no pain during fracture reduction. Adequate fracture reduction was obtained in 111 of the children. Ninety-nine percent (sixty-eight) of the sixty-nine parents present during the reduction were pleased with the sedation and would allow it to be used again in a similar situation. Patency of the airway and independent respiration were maintained in all of the patients. Blood pressure and heart rate remained stable. Minor side effects included nausea (thirteen patients), emesis (eight of the thirteen patients with nausea), clumsiness (evident as ataxic movements in ten patients), and dysphoric reaction (one patient). No long-term sequelae were noted, and no patients had hallucinations or nightmares. CONCLUSIONS: Ketamine reliably, safely, and quickly provided adequate sedation to effectively facilitate the reduction of children's fractures in the emergency department at our institution. Ketamine should only be used in an environment such as the emergency department, where proper one-on-one monitoring is used and board-certified physicians skilled in airway management are directly involved in the care of the patient.", "entity": "Ataxia", "aliases": "Appendicular Ataxia Ataxias Limb Motor Sensory Truncal Ataxy Coordination Impairment Impairments Lack Dyscoordination Dyssynergia Incoordination Incoordinations of Rubral Tremor Tremors", "definition": "Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or PERIPHERAL NERVE DISEASES. Motor ataxia may be associated with CEREBELLAR DISEASES; CEREBRAL CORTEX diseases; THALAMIC DISEASES; BASAL GANGLIA DISEASES; injury to the RED NUCLEUS; and other conditions.\n    ", "id": "MESH:D001259"}
{"mention": "hallucinations", "mention_text": "BACKGROUND: There recently has been a resurgence in the utilization of ketamine, a unique anesthetic, for emergency-department procedures requiring sedation. The purpose of the present study was to examine the safety and efficacy of ketamine for sedation in the treatment of children's fractures in the emergency department. METHODS: One hundred and fourteen children (average age, 5.3 years; range, twelve months to ten years and ten months) who underwent closed reduction of an isolated fracture or dislocation in the emergency department at a level-I trauma center were prospectively evaluated. Ketamine hydrochloride was administered intravenously (at a dose of two milligrams per kilogram of body weight) in ninety-nine of the patients and intramuscularly (at a dose of four milligrams per kilogram of body weight) in the other fifteen. A board-certified emergency physician skilled in airway management supervised administration of the anesthetic, and the patients were monitored by a registered nurse. Any pain during the reduction was rated by the orthopaedic surgeon treating the patient according to the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). RESULTS: The average time from intravenous administration of ketamine to manipulation of the fracture or dislocation was one minute and thirty-six seconds (range, twenty seconds to five minutes), and the average time from intramuscular administration to manipulation was four minutes and forty-two seconds (range, sixty seconds to fifteen minutes). The average score according to the Children's Hospital of Eastern Ontario Pain Scale was 6.4 points (range, 5 to 10 points), reflecting minimal or no pain during fracture reduction. Adequate fracture reduction was obtained in 111 of the children. Ninety-nine percent (sixty-eight) of the sixty-nine parents present during the reduction were pleased with the sedation and would allow it to be used again in a similar situation. Patency of the airway and independent respiration were maintained in all of the patients. Blood pressure and heart rate remained stable. Minor side effects included nausea (thirteen patients), emesis (eight of the thirteen patients with nausea), clumsiness (evident as ataxic movements in ten patients), and dysphoric reaction (one patient). No long-term sequelae were noted, and no patients had hallucinations or nightmares. CONCLUSIONS: Ketamine reliably, safely, and quickly provided adequate sedation to effectively facilitate the reduction of children's fractures in the emergency department at our institution. Ketamine should only be used in an environment such as the emergency department, where proper one-on-one monitoring is used and board-certified physicians skilled in airway management are directly involved in the care of the patient.", "entity": "Hallucinations", "aliases": "Auditory Hallucination Verbal Hallucinations Body Sensation Dissociative Elementary Gustatory of Hypnagogic Hypnapompic Kinesthetic Mood Congruent Incongruent Olfactory Organic Reflex Sensory Somatic Tactile Visual Formed People Internal Unformed", "definition": "Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with MENTAL DISORDERS.\n    ", "id": "MESH:D006212"}
{"mention": "Ketamine", "mention_text": "BACKGROUND: There recently has been a resurgence in the utilization of ketamine, a unique anesthetic, for emergency-department procedures requiring sedation. The purpose of the present study was to examine the safety and efficacy of ketamine for sedation in the treatment of children's fractures in the emergency department. METHODS: One hundred and fourteen children (average age, 5.3 years; range, twelve months to ten years and ten months) who underwent closed reduction of an isolated fracture or dislocation in the emergency department at a level-I trauma center were prospectively evaluated. Ketamine hydrochloride was administered intravenously (at a dose of two milligrams per kilogram of body weight) in ninety-nine of the patients and intramuscularly (at a dose of four milligrams per kilogram of body weight) in the other fifteen. A board-certified emergency physician skilled in airway management supervised administration of the anesthetic, and the patients were monitored by a registered nurse. Any pain during the reduction was rated by the orthopaedic surgeon treating the patient according to the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). RESULTS: The average time from intravenous administration of ketamine to manipulation of the fracture or dislocation was one minute and thirty-six seconds (range, twenty seconds to five minutes), and the average time from intramuscular administration to manipulation was four minutes and forty-two seconds (range, sixty seconds to fifteen minutes). The average score according to the Children's Hospital of Eastern Ontario Pain Scale was 6.4 points (range, 5 to 10 points), reflecting minimal or no pain during fracture reduction. Adequate fracture reduction was obtained in 111 of the children. Ninety-nine percent (sixty-eight) of the sixty-nine parents present during the reduction were pleased with the sedation and would allow it to be used again in a similar situation. Patency of the airway and independent respiration were maintained in all of the patients. Blood pressure and heart rate remained stable. Minor side effects included nausea (thirteen patients), emesis (eight of the thirteen patients with nausea), clumsiness (evident as ataxic movements in ten patients), and dysphoric reaction (one patient). No long-term sequelae were noted, and no patients had hallucinations or nightmares. CONCLUSIONS: Ketamine reliably, safely, and quickly provided adequate sedation to effectively facilitate the reduction of children's fractures in the emergency department at our institution. Ketamine should only be used in an environment such as the emergency department, where proper one-on-one monitoring is used and board-certified physicians skilled in airway management are directly involved in the care of the patient.", "entity": "Ketamine", "aliases": "2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone CI 581 CI-581 CI581 Calipsol Calypsol Kalipsol Ketalar Ketamine Hydrochloride Ketanest Ketaset", "definition": "A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors.\n    ", "id": "MESH:D007649"}
{"mention": "lamivudine", "mention_text": "Prophylactic use of lamivudine with chronic immunosuppressive therapy for rheumatologic disorders.", "entity": "Lamivudine", "aliases": "2',3' Dideoxy 3' thiacytidine 2',3'-Dideoxy-3'-thiacytidine 3TC BCH 189 BCH-189 BCH189 Epivir GR-109714X GR109714X Lamivudine (2S-cis)-Isomer", "definition": "A reverse transcriptase inhibitor and ZALCITABINE analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease.\n    ", "id": "MESH:D019259"}
{"mention": "rheumatologic disorders", "mention_text": "Prophylactic use of lamivudine with chronic immunosuppressive therapy for rheumatologic disorders.", "entity": "Rheumatic Diseases", "aliases": "Disease Rheumatic Diseases Enthesopathies Enthesopathy Rheumatism", "definition": "Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement.\n    ", "id": "MESH:D012216"}
{"mention": "lamivudine", "mention_text": "The objective of this study was to report our experience concerning the effectiveness of the prophylactic administration of lamivudine in hepatitis B virus surface antigen (HBs Ag) positive patients with rheumatologic disease. From June 2004 to October 2006, 11 HBs Ag positive patients with rheumatologic diseases, who were on both immunosuppressive and prophylactic lamivudine therapies, were retrospectively assessed. Liver function tests, hepatitis B virus (HBV) serologic markers, and HBV DNA levels of the patients during follow-up were obtained from hospital file records. Eleven patients (six male) with median age 47 years (range 27-73), median disease duration 50 months (range 9-178) and median follow-up period of patients 13.8 months (range 5-27) were enrolled in this study. Lamivudine therapy was started 3-7 days prior to immunosuppressive therapy in all patients. Baseline, liver function tests were elevated in two patients (fourth patient: ALT:122 IU/l, AST:111 IU/l, tenth patient:ALT:294 IU/l, AST:274 IU/l, with minimal changes in the liver biopsy in both). Shortly after treatment their tests normalized and during follow-up period none of the patients had abnormal liver function tests. In four patients HBV DNA levels were higher than normal at baseline. Two of these normalized and the others increased later. In three additional patients, HBV DNA levels were increased during follow-up. None of the patients had significant clinical sings of HBV activation. Lamivudine was well tolerated and was continued in all patients. Prophylactic administration of lamivudine in patients who required immunosuppressive therapy seems to be safe, well tolerated and effective in preventing HBV reactivation.", "entity": "Lamivudine", "aliases": "2',3' Dideoxy 3' thiacytidine 2',3'-Dideoxy-3'-thiacytidine 3TC BCH 189 BCH-189 BCH189 Epivir GR-109714X GR109714X Lamivudine (2S-cis)-Isomer", "definition": "A reverse transcriptase inhibitor and ZALCITABINE analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease.\n    ", "id": "MESH:D019259"}
{"mention": "hepatitis B virus surface antigen", "mention_text": "The objective of this study was to report our experience concerning the effectiveness of the prophylactic administration of lamivudine in hepatitis B virus surface antigen (HBs Ag) positive patients with rheumatologic disease. From June 2004 to October 2006, 11 HBs Ag positive patients with rheumatologic diseases, who were on both immunosuppressive and prophylactic lamivudine therapies, were retrospectively assessed. Liver function tests, hepatitis B virus (HBV) serologic markers, and HBV DNA levels of the patients during follow-up were obtained from hospital file records. Eleven patients (six male) with median age 47 years (range 27-73), median disease duration 50 months (range 9-178) and median follow-up period of patients 13.8 months (range 5-27) were enrolled in this study. Lamivudine therapy was started 3-7 days prior to immunosuppressive therapy in all patients. Baseline, liver function tests were elevated in two patients (fourth patient: ALT:122 IU/l, AST:111 IU/l, tenth patient:ALT:294 IU/l, AST:274 IU/l, with minimal changes in the liver biopsy in both). Shortly after treatment their tests normalized and during follow-up period none of the patients had abnormal liver function tests. In four patients HBV DNA levels were higher than normal at baseline. Two of these normalized and the others increased later. In three additional patients, HBV DNA levels were increased during follow-up. None of the patients had significant clinical sings of HBV activation. Lamivudine was well tolerated and was continued in all patients. Prophylactic administration of lamivudine in patients who required immunosuppressive therapy seems to be safe, well tolerated and effective in preventing HBV reactivation.", "entity": "Hepatitis B Surface Antigens", "aliases": "Antigen Australia HBsAg Hepatitis B Surface Antigens", "definition": "Those hepatitis B antigens found on the surface of the Dane particle and on the 20 nm spherical and tubular particles. Several subspecificities of the surface antigen are known. These were formerly called the Australia antigen.\n    ", "id": "MESH:D006514"}
{"mention": "HBs Ag", "mention_text": "The objective of this study was to report our experience concerning the effectiveness of the prophylactic administration of lamivudine in hepatitis B virus surface antigen (HBs Ag) positive patients with rheumatologic disease. From June 2004 to October 2006, 11 HBs Ag positive patients with rheumatologic diseases, who were on both immunosuppressive and prophylactic lamivudine therapies, were retrospectively assessed. Liver function tests, hepatitis B virus (HBV) serologic markers, and HBV DNA levels of the patients during follow-up were obtained from hospital file records. Eleven patients (six male) with median age 47 years (range 27-73), median disease duration 50 months (range 9-178) and median follow-up period of patients 13.8 months (range 5-27) were enrolled in this study. Lamivudine therapy was started 3-7 days prior to immunosuppressive therapy in all patients. Baseline, liver function tests were elevated in two patients (fourth patient: ALT:122 IU/l, AST:111 IU/l, tenth patient:ALT:294 IU/l, AST:274 IU/l, with minimal changes in the liver biopsy in both). Shortly after treatment their tests normalized and during follow-up period none of the patients had abnormal liver function tests. In four patients HBV DNA levels were higher than normal at baseline. Two of these normalized and the others increased later. In three additional patients, HBV DNA levels were increased during follow-up. None of the patients had significant clinical sings of HBV activation. Lamivudine was well tolerated and was continued in all patients. Prophylactic administration of lamivudine in patients who required immunosuppressive therapy seems to be safe, well tolerated and effective in preventing HBV reactivation.", "entity": "Hepatitis B Surface Antigens", "aliases": "Antigen Australia HBsAg Hepatitis B Surface Antigens", "definition": "Those hepatitis B antigens found on the surface of the Dane particle and on the 20 nm spherical and tubular particles. Several subspecificities of the surface antigen are known. These were formerly called the Australia antigen.\n    ", "id": "MESH:D006514"}
{"mention": "rheumatologic disease", "mention_text": "The objective of this study was to report our experience concerning the effectiveness of the prophylactic administration of lamivudine in hepatitis B virus surface antigen (HBs Ag) positive patients with rheumatologic disease. From June 2004 to October 2006, 11 HBs Ag positive patients with rheumatologic diseases, who were on both immunosuppressive and prophylactic lamivudine therapies, were retrospectively assessed. Liver function tests, hepatitis B virus (HBV) serologic markers, and HBV DNA levels of the patients during follow-up were obtained from hospital file records. Eleven patients (six male) with median age 47 years (range 27-73), median disease duration 50 months (range 9-178) and median follow-up period of patients 13.8 months (range 5-27) were enrolled in this study. Lamivudine therapy was started 3-7 days prior to immunosuppressive therapy in all patients. Baseline, liver function tests were elevated in two patients (fourth patient: ALT:122 IU/l, AST:111 IU/l, tenth patient:ALT:294 IU/l, AST:274 IU/l, with minimal changes in the liver biopsy in both). Shortly after treatment their tests normalized and during follow-up period none of the patients had abnormal liver function tests. In four patients HBV DNA levels were higher than normal at baseline. Two of these normalized and the others increased later. In three additional patients, HBV DNA levels were increased during follow-up. None of the patients had significant clinical sings of HBV activation. Lamivudine was well tolerated and was continued in all patients. Prophylactic administration of lamivudine in patients who required immunosuppressive therapy seems to be safe, well tolerated and effective in preventing HBV reactivation.", "entity": "Rheumatic Diseases", "aliases": "Disease Rheumatic Diseases Enthesopathies Enthesopathy Rheumatism", "definition": "Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement.\n    ", "id": "MESH:D012216"}
{"mention": "rheumatologic diseases", "mention_text": "The objective of this study was to report our experience concerning the effectiveness of the prophylactic administration of lamivudine in hepatitis B virus surface antigen (HBs Ag) positive patients with rheumatologic disease. From June 2004 to October 2006, 11 HBs Ag positive patients with rheumatologic diseases, who were on both immunosuppressive and prophylactic lamivudine therapies, were retrospectively assessed. Liver function tests, hepatitis B virus (HBV) serologic markers, and HBV DNA levels of the patients during follow-up were obtained from hospital file records. Eleven patients (six male) with median age 47 years (range 27-73), median disease duration 50 months (range 9-178) and median follow-up period of patients 13.8 months (range 5-27) were enrolled in this study. Lamivudine therapy was started 3-7 days prior to immunosuppressive therapy in all patients. Baseline, liver function tests were elevated in two patients (fourth patient: ALT:122 IU/l, AST:111 IU/l, tenth patient:ALT:294 IU/l, AST:274 IU/l, with minimal changes in the liver biopsy in both). Shortly after treatment their tests normalized and during follow-up period none of the patients had abnormal liver function tests. In four patients HBV DNA levels were higher than normal at baseline. Two of these normalized and the others increased later. In three additional patients, HBV DNA levels were increased during follow-up. None of the patients had significant clinical sings of HBV activation. Lamivudine was well tolerated and was continued in all patients. Prophylactic administration of lamivudine in patients who required immunosuppressive therapy seems to be safe, well tolerated and effective in preventing HBV reactivation.", "entity": "Rheumatic Diseases", "aliases": "Disease Rheumatic Diseases Enthesopathies Enthesopathy Rheumatism", "definition": "Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement.\n    ", "id": "MESH:D012216"}
{"mention": "hepatitis B", "mention_text": "The objective of this study was to report our experience concerning the effectiveness of the prophylactic administration of lamivudine in hepatitis B virus surface antigen (HBs Ag) positive patients with rheumatologic disease. From June 2004 to October 2006, 11 HBs Ag positive patients with rheumatologic diseases, who were on both immunosuppressive and prophylactic lamivudine therapies, were retrospectively assessed. Liver function tests, hepatitis B virus (HBV) serologic markers, and HBV DNA levels of the patients during follow-up were obtained from hospital file records. Eleven patients (six male) with median age 47 years (range 27-73), median disease duration 50 months (range 9-178) and median follow-up period of patients 13.8 months (range 5-27) were enrolled in this study. Lamivudine therapy was started 3-7 days prior to immunosuppressive therapy in all patients. Baseline, liver function tests were elevated in two patients (fourth patient: ALT:122 IU/l, AST:111 IU/l, tenth patient:ALT:294 IU/l, AST:274 IU/l, with minimal changes in the liver biopsy in both). Shortly after treatment their tests normalized and during follow-up period none of the patients had abnormal liver function tests. In four patients HBV DNA levels were higher than normal at baseline. Two of these normalized and the others increased later. In three additional patients, HBV DNA levels were increased during follow-up. None of the patients had significant clinical sings of HBV activation. Lamivudine was well tolerated and was continued in all patients. Prophylactic administration of lamivudine in patients who required immunosuppressive therapy seems to be safe, well tolerated and effective in preventing HBV reactivation.", "entity": "Hepatitis B", "aliases": "Hepatitis B", "definition": "INFLAMMATION of the LIVER in humans caused by a member of the ORTHOHEPADNAVIRUS genus, HEPATITIS B VIRUS. It is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact.\n    ", "id": "MESH:D006509"}
{"mention": "Lamivudine", "mention_text": "The objective of this study was to report our experience concerning the effectiveness of the prophylactic administration of lamivudine in hepatitis B virus surface antigen (HBs Ag) positive patients with rheumatologic disease. From June 2004 to October 2006, 11 HBs Ag positive patients with rheumatologic diseases, who were on both immunosuppressive and prophylactic lamivudine therapies, were retrospectively assessed. Liver function tests, hepatitis B virus (HBV) serologic markers, and HBV DNA levels of the patients during follow-up were obtained from hospital file records. Eleven patients (six male) with median age 47 years (range 27-73), median disease duration 50 months (range 9-178) and median follow-up period of patients 13.8 months (range 5-27) were enrolled in this study. Lamivudine therapy was started 3-7 days prior to immunosuppressive therapy in all patients. Baseline, liver function tests were elevated in two patients (fourth patient: ALT:122 IU/l, AST:111 IU/l, tenth patient:ALT:294 IU/l, AST:274 IU/l, with minimal changes in the liver biopsy in both). Shortly after treatment their tests normalized and during follow-up period none of the patients had abnormal liver function tests. In four patients HBV DNA levels were higher than normal at baseline. Two of these normalized and the others increased later. In three additional patients, HBV DNA levels were increased during follow-up. None of the patients had significant clinical sings of HBV activation. Lamivudine was well tolerated and was continued in all patients. Prophylactic administration of lamivudine in patients who required immunosuppressive therapy seems to be safe, well tolerated and effective in preventing HBV reactivation.", "entity": "Lamivudine", "aliases": "2',3' Dideoxy 3' thiacytidine 2',3'-Dideoxy-3'-thiacytidine 3TC BCH 189 BCH-189 BCH189 Epivir GR-109714X GR109714X Lamivudine (2S-cis)-Isomer", "definition": "A reverse transcriptase inhibitor and ZALCITABINE analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease.\n    ", "id": "MESH:D019259"}
{"mention": "abnormal liver function", "mention_text": "The objective of this study was to report our experience concerning the effectiveness of the prophylactic administration of lamivudine in hepatitis B virus surface antigen (HBs Ag) positive patients with rheumatologic disease. From June 2004 to October 2006, 11 HBs Ag positive patients with rheumatologic diseases, who were on both immunosuppressive and prophylactic lamivudine therapies, were retrospectively assessed. Liver function tests, hepatitis B virus (HBV) serologic markers, and HBV DNA levels of the patients during follow-up were obtained from hospital file records. Eleven patients (six male) with median age 47 years (range 27-73), median disease duration 50 months (range 9-178) and median follow-up period of patients 13.8 months (range 5-27) were enrolled in this study. Lamivudine therapy was started 3-7 days prior to immunosuppressive therapy in all patients. Baseline, liver function tests were elevated in two patients (fourth patient: ALT:122 IU/l, AST:111 IU/l, tenth patient:ALT:294 IU/l, AST:274 IU/l, with minimal changes in the liver biopsy in both). Shortly after treatment their tests normalized and during follow-up period none of the patients had abnormal liver function tests. In four patients HBV DNA levels were higher than normal at baseline. Two of these normalized and the others increased later. In three additional patients, HBV DNA levels were increased during follow-up. None of the patients had significant clinical sings of HBV activation. Lamivudine was well tolerated and was continued in all patients. Prophylactic administration of lamivudine in patients who required immunosuppressive therapy seems to be safe, well tolerated and effective in preventing HBV reactivation.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "Midazolan", "mention_text": "BACKGROUND: TEE is a semi-invasive tool broadly used and its utilization associated to sedatives drugs might to affect the procedure safety. OBJECTIVE: to analyze aspects of TEE safety associated to the use of Midazolan (MZ) and Flumazenil (FL) and the influence of the clinical variables on the event rate. METHOD: prospective study with 137 patients that underwent TEE with MZ associated to moderate sedation. We analyzed the following events: complications related with the topical anesthesia, with MZ use and with the procedure. Uni- and multivariate analyses were used to test the influence of the clinical variables: age, sex, stroke, myocardiopathy (MP), duration of the test, mitral regurgitation (MR) and the MZ dose. RESULTS: All patients (65+/-16 yrs; 58% males) finished the examination. The mean doses of MZ and FL were 4.3+/-1.9 mg and 0.28+/-0.2 mg, respectively. The duration of the examination and the mean ejection fraction (EF) were 16.4+/-6.1 minutes and 60+/-9%, respectively. Mild hypoxia (SO2<90%) was the most common event (11 patients); 3 patients (2%) presented transient hypoxia due to upper airway obstruction by probe introduction and 8 (5.8%) due to hypoxia caused by MZ use. Transient hypotension (SAP<90mmHg) occurred in 1 patient (0.7%). The multivariate analysis showed that severe MR, MP (EF<45%) and high doses of MZ (>5mg) were associated with events (p<0.001). The EF was 40%, in the group with MP and 44% in the group with severe MR and it can be a factor associated with clinical events in the last group. CONCLUSION: TEE with sedation presents a low rate of events. There were no severe events and there was no need to interrupt the examinations.", "entity": "Midazolam", "aliases": "Dormicum Hydrochloride Midazolam Maleate Ro 21 3981 21-3981 213981 Versed", "definition": "A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH.\n    ", "id": "MESH:D008874"}
{"mention": "MZ", "mention_text": "BACKGROUND: TEE is a semi-invasive tool broadly used and its utilization associated to sedatives drugs might to affect the procedure safety. OBJECTIVE: to analyze aspects of TEE safety associated to the use of Midazolan (MZ) and Flumazenil (FL) and the influence of the clinical variables on the event rate. METHOD: prospective study with 137 patients that underwent TEE with MZ associated to moderate sedation. We analyzed the following events: complications related with the topical anesthesia, with MZ use and with the procedure. Uni- and multivariate analyses were used to test the influence of the clinical variables: age, sex, stroke, myocardiopathy (MP), duration of the test, mitral regurgitation (MR) and the MZ dose. RESULTS: All patients (65+/-16 yrs; 58% males) finished the examination. The mean doses of MZ and FL were 4.3+/-1.9 mg and 0.28+/-0.2 mg, respectively. The duration of the examination and the mean ejection fraction (EF) were 16.4+/-6.1 minutes and 60+/-9%, respectively. Mild hypoxia (SO2<90%) was the most common event (11 patients); 3 patients (2%) presented transient hypoxia due to upper airway obstruction by probe introduction and 8 (5.8%) due to hypoxia caused by MZ use. Transient hypotension (SAP<90mmHg) occurred in 1 patient (0.7%). The multivariate analysis showed that severe MR, MP (EF<45%) and high doses of MZ (>5mg) were associated with events (p<0.001). The EF was 40%, in the group with MP and 44% in the group with severe MR and it can be a factor associated with clinical events in the last group. CONCLUSION: TEE with sedation presents a low rate of events. There were no severe events and there was no need to interrupt the examinations.", "entity": "Midazolam", "aliases": "Dormicum Hydrochloride Midazolam Maleate Ro 21 3981 21-3981 213981 Versed", "definition": "A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH.\n    ", "id": "MESH:D008874"}
{"mention": "Flumazenil", "mention_text": "BACKGROUND: TEE is a semi-invasive tool broadly used and its utilization associated to sedatives drugs might to affect the procedure safety. OBJECTIVE: to analyze aspects of TEE safety associated to the use of Midazolan (MZ) and Flumazenil (FL) and the influence of the clinical variables on the event rate. METHOD: prospective study with 137 patients that underwent TEE with MZ associated to moderate sedation. We analyzed the following events: complications related with the topical anesthesia, with MZ use and with the procedure. Uni- and multivariate analyses were used to test the influence of the clinical variables: age, sex, stroke, myocardiopathy (MP), duration of the test, mitral regurgitation (MR) and the MZ dose. RESULTS: All patients (65+/-16 yrs; 58% males) finished the examination. The mean doses of MZ and FL were 4.3+/-1.9 mg and 0.28+/-0.2 mg, respectively. The duration of the examination and the mean ejection fraction (EF) were 16.4+/-6.1 minutes and 60+/-9%, respectively. Mild hypoxia (SO2<90%) was the most common event (11 patients); 3 patients (2%) presented transient hypoxia due to upper airway obstruction by probe introduction and 8 (5.8%) due to hypoxia caused by MZ use. Transient hypotension (SAP<90mmHg) occurred in 1 patient (0.7%). The multivariate analysis showed that severe MR, MP (EF<45%) and high doses of MZ (>5mg) were associated with events (p<0.001). The EF was 40%, in the group with MP and 44% in the group with severe MR and it can be a factor associated with clinical events in the last group. CONCLUSION: TEE with sedation presents a low rate of events. There were no severe events and there was no need to interrupt the examinations.", "entity": "Flumazenil", "aliases": "Anexate Flumazenil Flumazepil Hoffman La Roche Brand of Hoffman-La Lanexat Ro 15 1788 15-1788 151788 Romazicon", "definition": "A potent benzodiazepine receptor antagonist. Since it reverses the sedative and other actions of benzodiazepines, it has been suggested as an antidote to benzodiazepine overdoses.\n    ", "id": "MESH:D005442"}
{"mention": "FL", "mention_text": "BACKGROUND: TEE is a semi-invasive tool broadly used and its utilization associated to sedatives drugs might to affect the procedure safety. OBJECTIVE: to analyze aspects of TEE safety associated to the use of Midazolan (MZ) and Flumazenil (FL) and the influence of the clinical variables on the event rate. METHOD: prospective study with 137 patients that underwent TEE with MZ associated to moderate sedation. We analyzed the following events: complications related with the topical anesthesia, with MZ use and with the procedure. Uni- and multivariate analyses were used to test the influence of the clinical variables: age, sex, stroke, myocardiopathy (MP), duration of the test, mitral regurgitation (MR) and the MZ dose. RESULTS: All patients (65+/-16 yrs; 58% males) finished the examination. The mean doses of MZ and FL were 4.3+/-1.9 mg and 0.28+/-0.2 mg, respectively. The duration of the examination and the mean ejection fraction (EF) were 16.4+/-6.1 minutes and 60+/-9%, respectively. Mild hypoxia (SO2<90%) was the most common event (11 patients); 3 patients (2%) presented transient hypoxia due to upper airway obstruction by probe introduction and 8 (5.8%) due to hypoxia caused by MZ use. Transient hypotension (SAP<90mmHg) occurred in 1 patient (0.7%). The multivariate analysis showed that severe MR, MP (EF<45%) and high doses of MZ (>5mg) were associated with events (p<0.001). The EF was 40%, in the group with MP and 44% in the group with severe MR and it can be a factor associated with clinical events in the last group. CONCLUSION: TEE with sedation presents a low rate of events. There were no severe events and there was no need to interrupt the examinations.", "entity": "Flumazenil", "aliases": "Anexate Flumazenil Flumazepil Hoffman La Roche Brand of Hoffman-La Lanexat Ro 15 1788 15-1788 151788 Romazicon", "definition": "A potent benzodiazepine receptor antagonist. Since it reverses the sedative and other actions of benzodiazepines, it has been suggested as an antidote to benzodiazepine overdoses.\n    ", "id": "MESH:D005442"}
{"mention": "stroke", "mention_text": "BACKGROUND: TEE is a semi-invasive tool broadly used and its utilization associated to sedatives drugs might to affect the procedure safety. OBJECTIVE: to analyze aspects of TEE safety associated to the use of Midazolan (MZ) and Flumazenil (FL) and the influence of the clinical variables on the event rate. METHOD: prospective study with 137 patients that underwent TEE with MZ associated to moderate sedation. We analyzed the following events: complications related with the topical anesthesia, with MZ use and with the procedure. Uni- and multivariate analyses were used to test the influence of the clinical variables: age, sex, stroke, myocardiopathy (MP), duration of the test, mitral regurgitation (MR) and the MZ dose. RESULTS: All patients (65+/-16 yrs; 58% males) finished the examination. The mean doses of MZ and FL were 4.3+/-1.9 mg and 0.28+/-0.2 mg, respectively. The duration of the examination and the mean ejection fraction (EF) were 16.4+/-6.1 minutes and 60+/-9%, respectively. Mild hypoxia (SO2<90%) was the most common event (11 patients); 3 patients (2%) presented transient hypoxia due to upper airway obstruction by probe introduction and 8 (5.8%) due to hypoxia caused by MZ use. Transient hypotension (SAP<90mmHg) occurred in 1 patient (0.7%). The multivariate analysis showed that severe MR, MP (EF<45%) and high doses of MZ (>5mg) were associated with events (p<0.001). The EF was 40%, in the group with MP and 44% in the group with severe MR and it can be a factor associated with clinical events in the last group. CONCLUSION: TEE with sedation presents a low rate of events. There were no severe events and there was no need to interrupt the examinations.", "entity": "Stroke", "aliases": "Acute Cerebrovascular Accident Accidents Stroke Strokes Apoplexy Brain Vascular CVA (Cerebrovascular Accident) CVAs Cerebral", "definition": "A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)\n    ", "id": "MESH:D020521"}
{"mention": "myocardiopathy", "mention_text": "BACKGROUND: TEE is a semi-invasive tool broadly used and its utilization associated to sedatives drugs might to affect the procedure safety. OBJECTIVE: to analyze aspects of TEE safety associated to the use of Midazolan (MZ) and Flumazenil (FL) and the influence of the clinical variables on the event rate. METHOD: prospective study with 137 patients that underwent TEE with MZ associated to moderate sedation. We analyzed the following events: complications related with the topical anesthesia, with MZ use and with the procedure. Uni- and multivariate analyses were used to test the influence of the clinical variables: age, sex, stroke, myocardiopathy (MP), duration of the test, mitral regurgitation (MR) and the MZ dose. RESULTS: All patients (65+/-16 yrs; 58% males) finished the examination. The mean doses of MZ and FL were 4.3+/-1.9 mg and 0.28+/-0.2 mg, respectively. The duration of the examination and the mean ejection fraction (EF) were 16.4+/-6.1 minutes and 60+/-9%, respectively. Mild hypoxia (SO2<90%) was the most common event (11 patients); 3 patients (2%) presented transient hypoxia due to upper airway obstruction by probe introduction and 8 (5.8%) due to hypoxia caused by MZ use. Transient hypotension (SAP<90mmHg) occurred in 1 patient (0.7%). The multivariate analysis showed that severe MR, MP (EF<45%) and high doses of MZ (>5mg) were associated with events (p<0.001). The EF was 40%, in the group with MP and 44% in the group with severe MR and it can be a factor associated with clinical events in the last group. CONCLUSION: TEE with sedation presents a low rate of events. There were no severe events and there was no need to interrupt the examinations.", "entity": "Cardiomyopathies", "aliases": "Cardiomyopathies Primary Secondary Cardiomyopathy Disease Myocardial Diseases Myocardiopathies Myocardiopathy", "definition": "A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).\n    ", "id": "MESH:D009202"}
{"mention": "MP", "mention_text": "BACKGROUND: TEE is a semi-invasive tool broadly used and its utilization associated to sedatives drugs might to affect the procedure safety. OBJECTIVE: to analyze aspects of TEE safety associated to the use of Midazolan (MZ) and Flumazenil (FL) and the influence of the clinical variables on the event rate. METHOD: prospective study with 137 patients that underwent TEE with MZ associated to moderate sedation. We analyzed the following events: complications related with the topical anesthesia, with MZ use and with the procedure. Uni- and multivariate analyses were used to test the influence of the clinical variables: age, sex, stroke, myocardiopathy (MP), duration of the test, mitral regurgitation (MR) and the MZ dose. RESULTS: All patients (65+/-16 yrs; 58% males) finished the examination. The mean doses of MZ and FL were 4.3+/-1.9 mg and 0.28+/-0.2 mg, respectively. The duration of the examination and the mean ejection fraction (EF) were 16.4+/-6.1 minutes and 60+/-9%, respectively. Mild hypoxia (SO2<90%) was the most common event (11 patients); 3 patients (2%) presented transient hypoxia due to upper airway obstruction by probe introduction and 8 (5.8%) due to hypoxia caused by MZ use. Transient hypotension (SAP<90mmHg) occurred in 1 patient (0.7%). The multivariate analysis showed that severe MR, MP (EF<45%) and high doses of MZ (>5mg) were associated with events (p<0.001). The EF was 40%, in the group with MP and 44% in the group with severe MR and it can be a factor associated with clinical events in the last group. CONCLUSION: TEE with sedation presents a low rate of events. There were no severe events and there was no need to interrupt the examinations.", "entity": "Cardiomyopathies", "aliases": "Cardiomyopathies Primary Secondary Cardiomyopathy Disease Myocardial Diseases Myocardiopathies Myocardiopathy", "definition": "A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).\n    ", "id": "MESH:D009202"}
{"mention": "mitral regurgitation", "mention_text": "BACKGROUND: TEE is a semi-invasive tool broadly used and its utilization associated to sedatives drugs might to affect the procedure safety. OBJECTIVE: to analyze aspects of TEE safety associated to the use of Midazolan (MZ) and Flumazenil (FL) and the influence of the clinical variables on the event rate. METHOD: prospective study with 137 patients that underwent TEE with MZ associated to moderate sedation. We analyzed the following events: complications related with the topical anesthesia, with MZ use and with the procedure. Uni- and multivariate analyses were used to test the influence of the clinical variables: age, sex, stroke, myocardiopathy (MP), duration of the test, mitral regurgitation (MR) and the MZ dose. RESULTS: All patients (65+/-16 yrs; 58% males) finished the examination. The mean doses of MZ and FL were 4.3+/-1.9 mg and 0.28+/-0.2 mg, respectively. The duration of the examination and the mean ejection fraction (EF) were 16.4+/-6.1 minutes and 60+/-9%, respectively. Mild hypoxia (SO2<90%) was the most common event (11 patients); 3 patients (2%) presented transient hypoxia due to upper airway obstruction by probe introduction and 8 (5.8%) due to hypoxia caused by MZ use. Transient hypotension (SAP<90mmHg) occurred in 1 patient (0.7%). The multivariate analysis showed that severe MR, MP (EF<45%) and high doses of MZ (>5mg) were associated with events (p<0.001). The EF was 40%, in the group with MP and 44% in the group with severe MR and it can be a factor associated with clinical events in the last group. CONCLUSION: TEE with sedation presents a low rate of events. There were no severe events and there was no need to interrupt the examinations.", "entity": "Mitral Valve Insufficiency", "aliases": "Incompetence Mitral Valve Insufficiency Regurgitation", "definition": "Backflow of blood from the LEFT VENTRICLE into the LEFT ATRIUM due to imperfect closure of the MITRAL VALVE. This can lead to mitral valve regurgitation.\n    ", "id": "MESH:D008944"}
{"mention": "MR", "mention_text": "BACKGROUND: TEE is a semi-invasive tool broadly used and its utilization associated to sedatives drugs might to affect the procedure safety. OBJECTIVE: to analyze aspects of TEE safety associated to the use of Midazolan (MZ) and Flumazenil (FL) and the influence of the clinical variables on the event rate. METHOD: prospective study with 137 patients that underwent TEE with MZ associated to moderate sedation. We analyzed the following events: complications related with the topical anesthesia, with MZ use and with the procedure. Uni- and multivariate analyses were used to test the influence of the clinical variables: age, sex, stroke, myocardiopathy (MP), duration of the test, mitral regurgitation (MR) and the MZ dose. RESULTS: All patients (65+/-16 yrs; 58% males) finished the examination. The mean doses of MZ and FL were 4.3+/-1.9 mg and 0.28+/-0.2 mg, respectively. The duration of the examination and the mean ejection fraction (EF) were 16.4+/-6.1 minutes and 60+/-9%, respectively. Mild hypoxia (SO2<90%) was the most common event (11 patients); 3 patients (2%) presented transient hypoxia due to upper airway obstruction by probe introduction and 8 (5.8%) due to hypoxia caused by MZ use. Transient hypotension (SAP<90mmHg) occurred in 1 patient (0.7%). The multivariate analysis showed that severe MR, MP (EF<45%) and high doses of MZ (>5mg) were associated with events (p<0.001). The EF was 40%, in the group with MP and 44% in the group with severe MR and it can be a factor associated with clinical events in the last group. CONCLUSION: TEE with sedation presents a low rate of events. There were no severe events and there was no need to interrupt the examinations.", "entity": "Mitral Valve Insufficiency", "aliases": "Incompetence Mitral Valve Insufficiency Regurgitation", "definition": "Backflow of blood from the LEFT VENTRICLE into the LEFT ATRIUM due to imperfect closure of the MITRAL VALVE. This can lead to mitral valve regurgitation.\n    ", "id": "MESH:D008944"}
{"mention": "hypoxia", "mention_text": "BACKGROUND: TEE is a semi-invasive tool broadly used and its utilization associated to sedatives drugs might to affect the procedure safety. OBJECTIVE: to analyze aspects of TEE safety associated to the use of Midazolan (MZ) and Flumazenil (FL) and the influence of the clinical variables on the event rate. METHOD: prospective study with 137 patients that underwent TEE with MZ associated to moderate sedation. We analyzed the following events: complications related with the topical anesthesia, with MZ use and with the procedure. Uni- and multivariate analyses were used to test the influence of the clinical variables: age, sex, stroke, myocardiopathy (MP), duration of the test, mitral regurgitation (MR) and the MZ dose. RESULTS: All patients (65+/-16 yrs; 58% males) finished the examination. The mean doses of MZ and FL were 4.3+/-1.9 mg and 0.28+/-0.2 mg, respectively. The duration of the examination and the mean ejection fraction (EF) were 16.4+/-6.1 minutes and 60+/-9%, respectively. Mild hypoxia (SO2<90%) was the most common event (11 patients); 3 patients (2%) presented transient hypoxia due to upper airway obstruction by probe introduction and 8 (5.8%) due to hypoxia caused by MZ use. Transient hypotension (SAP<90mmHg) occurred in 1 patient (0.7%). The multivariate analysis showed that severe MR, MP (EF<45%) and high doses of MZ (>5mg) were associated with events (p<0.001). The EF was 40%, in the group with MP and 44% in the group with severe MR and it can be a factor associated with clinical events in the last group. CONCLUSION: TEE with sedation presents a low rate of events. There were no severe events and there was no need to interrupt the examinations.", "entity": "Anoxia", "aliases": "Anoxemia Anoxemias Anoxia Anoxias Deficiencies Oxygen Deficiency Hypoxemia Hypoxemias Hypoxia Hypoxias", "definition": "Relatively complete absence of oxygen in one or more tissues.\n    ", "id": "MESH:D000860"}
{"mention": "airway obstruction", "mention_text": "BACKGROUND: TEE is a semi-invasive tool broadly used and its utilization associated to sedatives drugs might to affect the procedure safety. OBJECTIVE: to analyze aspects of TEE safety associated to the use of Midazolan (MZ) and Flumazenil (FL) and the influence of the clinical variables on the event rate. METHOD: prospective study with 137 patients that underwent TEE with MZ associated to moderate sedation. We analyzed the following events: complications related with the topical anesthesia, with MZ use and with the procedure. Uni- and multivariate analyses were used to test the influence of the clinical variables: age, sex, stroke, myocardiopathy (MP), duration of the test, mitral regurgitation (MR) and the MZ dose. RESULTS: All patients (65+/-16 yrs; 58% males) finished the examination. The mean doses of MZ and FL were 4.3+/-1.9 mg and 0.28+/-0.2 mg, respectively. The duration of the examination and the mean ejection fraction (EF) were 16.4+/-6.1 minutes and 60+/-9%, respectively. Mild hypoxia (SO2<90%) was the most common event (11 patients); 3 patients (2%) presented transient hypoxia due to upper airway obstruction by probe introduction and 8 (5.8%) due to hypoxia caused by MZ use. Transient hypotension (SAP<90mmHg) occurred in 1 patient (0.7%). The multivariate analysis showed that severe MR, MP (EF<45%) and high doses of MZ (>5mg) were associated with events (p<0.001). The EF was 40%, in the group with MP and 44% in the group with severe MR and it can be a factor associated with clinical events in the last group. CONCLUSION: TEE with sedation presents a low rate of events. There were no severe events and there was no need to interrupt the examinations.", "entity": "Airway Obstruction", "aliases": "Airway Obstruction Obstructions Choking", "definition": "Any hindrance to the passage of air into and out of the lungs.\n    ", "id": "MESH:D000402"}
{"mention": "hypotension", "mention_text": "BACKGROUND: TEE is a semi-invasive tool broadly used and its utilization associated to sedatives drugs might to affect the procedure safety. OBJECTIVE: to analyze aspects of TEE safety associated to the use of Midazolan (MZ) and Flumazenil (FL) and the influence of the clinical variables on the event rate. METHOD: prospective study with 137 patients that underwent TEE with MZ associated to moderate sedation. We analyzed the following events: complications related with the topical anesthesia, with MZ use and with the procedure. Uni- and multivariate analyses were used to test the influence of the clinical variables: age, sex, stroke, myocardiopathy (MP), duration of the test, mitral regurgitation (MR) and the MZ dose. RESULTS: All patients (65+/-16 yrs; 58% males) finished the examination. The mean doses of MZ and FL were 4.3+/-1.9 mg and 0.28+/-0.2 mg, respectively. The duration of the examination and the mean ejection fraction (EF) were 16.4+/-6.1 minutes and 60+/-9%, respectively. Mild hypoxia (SO2<90%) was the most common event (11 patients); 3 patients (2%) presented transient hypoxia due to upper airway obstruction by probe introduction and 8 (5.8%) due to hypoxia caused by MZ use. Transient hypotension (SAP<90mmHg) occurred in 1 patient (0.7%). The multivariate analysis showed that severe MR, MP (EF<45%) and high doses of MZ (>5mg) were associated with events (p<0.001). The EF was 40%, in the group with MP and 44% in the group with severe MR and it can be a factor associated with clinical events in the last group. CONCLUSION: TEE with sedation presents a low rate of events. There were no severe events and there was no need to interrupt the examinations.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "calcium", "mention_text": "Effects of calcium channel blockers on bupivacaine-induced toxicity.", "entity": "Calcium", "aliases": "Blood Coagulation Factor IV Calcium", "definition": "A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.\n    ", "id": "MESH:D002118"}
{"mention": "bupivacaine", "mention_text": "Effects of calcium channel blockers on bupivacaine-induced toxicity.", "entity": "Bupivacaine", "aliases": "1-Butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide Abbott Brand of Bupivacaine Hydrochloride Anhydrous Astra AstraZeneca Aventis Braun Bupivacaina Bupivacain Janapharm RPR Bupivacain-RPR Carbonate Monohydrochloride Monohydrate Buvacaina Carbostesin Dolanaest Inibsa Jenapharm Marcain Marcaine Pisa Sensorcaine Strathmann Svedocain Sin Vasoconstr", "definition": "A widely used local anesthetic agent.\n    ", "id": "MESH:D002045"}
{"mention": "toxicity", "mention_text": "Effects of calcium channel blockers on bupivacaine-induced toxicity.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "calcium", "mention_text": "The purpose of this study was to investigate the influence of calcium channel blockers on bupivacaine-induced acute toxicity. For each of the three tested calcium channel blockers (diltiazem, verapamil and bepridil) 6 groups of mice were treated by two different doses, i.e. 2 and 10 mg/kg/i.p., or an equal volume of saline for the control group (n = 20); 15 minutes later, all the animals were injected with a single 50 mg/kg/i.p. dose of bupivacaine. The convulsant activity, the time of latency to convulse and the mortality rate were assessed in each group. The local anesthetic-induced mortality was significantly increased by the three different calcium channel blockers. The convulsant activity of bupivacaine was not significantly modified but calcium channel blockers decreased the time of latency to obtain bupivacaine-induced convulsions; this effect was less pronounced with bepridil.", "entity": "Calcium", "aliases": "Blood Coagulation Factor IV Calcium", "definition": "A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.\n    ", "id": "MESH:D002118"}
{"mention": "bupivacaine", "mention_text": "The purpose of this study was to investigate the influence of calcium channel blockers on bupivacaine-induced acute toxicity. For each of the three tested calcium channel blockers (diltiazem, verapamil and bepridil) 6 groups of mice were treated by two different doses, i.e. 2 and 10 mg/kg/i.p., or an equal volume of saline for the control group (n = 20); 15 minutes later, all the animals were injected with a single 50 mg/kg/i.p. dose of bupivacaine. The convulsant activity, the time of latency to convulse and the mortality rate were assessed in each group. The local anesthetic-induced mortality was significantly increased by the three different calcium channel blockers. The convulsant activity of bupivacaine was not significantly modified but calcium channel blockers decreased the time of latency to obtain bupivacaine-induced convulsions; this effect was less pronounced with bepridil.", "entity": "Bupivacaine", "aliases": "1-Butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide Abbott Brand of Bupivacaine Hydrochloride Anhydrous Astra AstraZeneca Aventis Braun Bupivacaina Bupivacain Janapharm RPR Bupivacain-RPR Carbonate Monohydrochloride Monohydrate Buvacaina Carbostesin Dolanaest Inibsa Jenapharm Marcain Marcaine Pisa Sensorcaine Strathmann Svedocain Sin Vasoconstr", "definition": "A widely used local anesthetic agent.\n    ", "id": "MESH:D002045"}
{"mention": "toxicity", "mention_text": "The purpose of this study was to investigate the influence of calcium channel blockers on bupivacaine-induced acute toxicity. For each of the three tested calcium channel blockers (diltiazem, verapamil and bepridil) 6 groups of mice were treated by two different doses, i.e. 2 and 10 mg/kg/i.p., or an equal volume of saline for the control group (n = 20); 15 minutes later, all the animals were injected with a single 50 mg/kg/i.p. dose of bupivacaine. The convulsant activity, the time of latency to convulse and the mortality rate were assessed in each group. The local anesthetic-induced mortality was significantly increased by the three different calcium channel blockers. The convulsant activity of bupivacaine was not significantly modified but calcium channel blockers decreased the time of latency to obtain bupivacaine-induced convulsions; this effect was less pronounced with bepridil.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "diltiazem", "mention_text": "The purpose of this study was to investigate the influence of calcium channel blockers on bupivacaine-induced acute toxicity. For each of the three tested calcium channel blockers (diltiazem, verapamil and bepridil) 6 groups of mice were treated by two different doses, i.e. 2 and 10 mg/kg/i.p., or an equal volume of saline for the control group (n = 20); 15 minutes later, all the animals were injected with a single 50 mg/kg/i.p. dose of bupivacaine. The convulsant activity, the time of latency to convulse and the mortality rate were assessed in each group. The local anesthetic-induced mortality was significantly increased by the three different calcium channel blockers. The convulsant activity of bupivacaine was not significantly modified but calcium channel blockers decreased the time of latency to obtain bupivacaine-induced convulsions; this effect was less pronounced with bepridil.", "entity": "Diltiazem", "aliases": "Aldizem Biovail Brand of Diltiazem Hydrochloride CRD 401 CRD-401 CRD401 Cardil Cardizem Dilacor XR Dilren Malate Dilzem Tiazac Watson Pharmaceuticals Diltazem", "definition": "A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of CALCIUM ion on membrane functions.\n    ", "id": "MESH:D004110"}
{"mention": "verapamil", "mention_text": "The purpose of this study was to investigate the influence of calcium channel blockers on bupivacaine-induced acute toxicity. For each of the three tested calcium channel blockers (diltiazem, verapamil and bepridil) 6 groups of mice were treated by two different doses, i.e. 2 and 10 mg/kg/i.p., or an equal volume of saline for the control group (n = 20); 15 minutes later, all the animals were injected with a single 50 mg/kg/i.p. dose of bupivacaine. The convulsant activity, the time of latency to convulse and the mortality rate were assessed in each group. The local anesthetic-induced mortality was significantly increased by the three different calcium channel blockers. The convulsant activity of bupivacaine was not significantly modified but calcium channel blockers decreased the time of latency to obtain bupivacaine-induced convulsions; this effect was less pronounced with bepridil.", "entity": "Verapamil", "aliases": "Calan Cordilox Dexverapamil Falicard Finoptin Hydrochloride Verapamil Iproveratril Isoptin Isoptine Izoptin Lekoptin Sandoz Brand of", "definition": "A calcium channel blocker that is a class IV anti-arrhythmia agent.\n    ", "id": "MESH:D014700"}
{"mention": "bepridil", "mention_text": "The purpose of this study was to investigate the influence of calcium channel blockers on bupivacaine-induced acute toxicity. For each of the three tested calcium channel blockers (diltiazem, verapamil and bepridil) 6 groups of mice were treated by two different doses, i.e. 2 and 10 mg/kg/i.p., or an equal volume of saline for the control group (n = 20); 15 minutes later, all the animals were injected with a single 50 mg/kg/i.p. dose of bupivacaine. The convulsant activity, the time of latency to convulse and the mortality rate were assessed in each group. The local anesthetic-induced mortality was significantly increased by the three different calcium channel blockers. The convulsant activity of bupivacaine was not significantly modified but calcium channel blockers decreased the time of latency to obtain bupivacaine-induced convulsions; this effect was less pronounced with bepridil.", "entity": "Bepridil", "aliases": "1978 CERM 1978-CERM 1978CERM Bedapin Bepadin Bepridil Monohydrochloride Monohydrate alpha Isomer alpha-Isomer (+)-Isomer (+-)-Isomer (-)-Isomer CERM-1978 CERM1978 Cordium Nourypharma Brand of Hydrochloride Riom Unicordium Vascor Wallace", "definition": "A long-acting calcium-blocking agent with significant anti-anginal activity. The drug produces significant coronary vasodilation and modest peripheral effects. It has antihypertensive and selective anti-arrhythmia activities and acts as a calmodulin antagonist.\n    ", "id": "MESH:D015764"}
{"mention": "convulsions", "mention_text": "The purpose of this study was to investigate the influence of calcium channel blockers on bupivacaine-induced acute toxicity. For each of the three tested calcium channel blockers (diltiazem, verapamil and bepridil) 6 groups of mice were treated by two different doses, i.e. 2 and 10 mg/kg/i.p., or an equal volume of saline for the control group (n = 20); 15 minutes later, all the animals were injected with a single 50 mg/kg/i.p. dose of bupivacaine. The convulsant activity, the time of latency to convulse and the mortality rate were assessed in each group. The local anesthetic-induced mortality was significantly increased by the three different calcium channel blockers. The convulsant activity of bupivacaine was not significantly modified but calcium channel blockers decreased the time of latency to obtain bupivacaine-induced convulsions; this effect was less pronounced with bepridil.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "Selegiline", "mention_text": "Selegiline-induced postural hypotension in Parkinson's disease: a longitudinal study on the effects of drug withdrawal.", "entity": "Selegiline", "aliases": "Bristol Myers Squibb Brand of Selegiline Bristol-Myers Deprenalin Deprenil Deprenyl E 250 E-250 E250 Eldepryl Emsam Humex Hydrochloride Jumex L-Deprenyl (R)-Isomer (R,S)-Isomer (S)-Isomer Valeant Selegyline Yumex Zelapar", "definition": "A selective, irreversible inhibitor of Type B monoamine oxidase. It is used in newly diagnosed patients with Parkinson's disease. It may slow progression of the clinical disease and delay the requirement for levodopa therapy. It also may be given with levodopa upon onset of disability. (From AMA Drug Evaluations Annual, 1994, p385) The compound without isomeric designation is Deprenyl.\n    ", "id": "MESH:D012642"}
{"mention": "postural hypotension", "mention_text": "Selegiline-induced postural hypotension in Parkinson's disease: a longitudinal study on the effects of drug withdrawal.", "entity": "Hypotension, Orthostatic", "aliases": "Hypotension Orthostatic Postural", "definition": "A significant drop in BLOOD PRESSURE after assuming a standing position. Orthostatic hypotension is a finding, and defined as a 20-mm Hg decrease in systolic pressure or a 10-mm Hg decrease in diastolic pressure 3 minutes after the person has risen from supine to standing. Symptoms generally include DIZZINESS, blurred vision, and SYNCOPE.\n    ", "id": "MESH:D007024"}
{"mention": "Parkinson's disease", "mention_text": "Selegiline-induced postural hypotension in Parkinson's disease: a longitudinal study on the effects of drug withdrawal.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "Parkinson's Disease", "mention_text": "OBJECTIVES: The United Kingdom Parkinson's Disease Research Group (UKPDRG) trial found an increased mortality in patients with Parkinson's disease (PD) randomized to receive 10 mg selegiline per day and L-dopa compared with those taking L-dopa alone. Recently, we found that therapy with selegiline and L-dopa was associated with selective systolic orthostatic hypotension which was abolished by withdrawal of selegiline. This unwanted effect on postural blood pressure was not the result of underlying autonomic failure. The aims of this study were to confirm our previous findings in a separate cohort of patients and to determine the time course of the cardiovascular consequences of stopping selegiline in the expectation that this might shed light on the mechanisms by which the drug causes orthostatic hypotension. METHODS: The cardiovascular responses to standing and head-up tilt were studied repeatedly in PD patients receiving selegiline and as the drug was withdrawn. RESULTS: Head-up tilt caused systolic orthostatic hypotension which was marked in six of 20 PD patients on selegiline, one of whom lost consciousness with unrecordable blood pressures. A lesser degree of orthostatic hypotension occurred with standing. Orthostatic hypotension was ameliorated 4 days after withdrawal of selegiline and totally abolished 7 days after discontinuation of the drug. Stopping selegiline also significantly reduced the supine systolic and diastolic blood pressures consistent with a previously undescribed supine pressor action. CONCLUSION: This study confirms our previous finding that selegiline in combination with L-dopa is associated with selective orthostatic hypotension. The possibilities that these cardiovascular findings might be the result of non-selective inhibition of monoamine oxidase or of amphetamine and metamphetamine are discussed.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "Parkinson's disease", "mention_text": "OBJECTIVES: The United Kingdom Parkinson's Disease Research Group (UKPDRG) trial found an increased mortality in patients with Parkinson's disease (PD) randomized to receive 10 mg selegiline per day and L-dopa compared with those taking L-dopa alone. Recently, we found that therapy with selegiline and L-dopa was associated with selective systolic orthostatic hypotension which was abolished by withdrawal of selegiline. This unwanted effect on postural blood pressure was not the result of underlying autonomic failure. The aims of this study were to confirm our previous findings in a separate cohort of patients and to determine the time course of the cardiovascular consequences of stopping selegiline in the expectation that this might shed light on the mechanisms by which the drug causes orthostatic hypotension. METHODS: The cardiovascular responses to standing and head-up tilt were studied repeatedly in PD patients receiving selegiline and as the drug was withdrawn. RESULTS: Head-up tilt caused systolic orthostatic hypotension which was marked in six of 20 PD patients on selegiline, one of whom lost consciousness with unrecordable blood pressures. A lesser degree of orthostatic hypotension occurred with standing. Orthostatic hypotension was ameliorated 4 days after withdrawal of selegiline and totally abolished 7 days after discontinuation of the drug. Stopping selegiline also significantly reduced the supine systolic and diastolic blood pressures consistent with a previously undescribed supine pressor action. CONCLUSION: This study confirms our previous finding that selegiline in combination with L-dopa is associated with selective orthostatic hypotension. The possibilities that these cardiovascular findings might be the result of non-selective inhibition of monoamine oxidase or of amphetamine and metamphetamine are discussed.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "PD", "mention_text": "OBJECTIVES: The United Kingdom Parkinson's Disease Research Group (UKPDRG) trial found an increased mortality in patients with Parkinson's disease (PD) randomized to receive 10 mg selegiline per day and L-dopa compared with those taking L-dopa alone. Recently, we found that therapy with selegiline and L-dopa was associated with selective systolic orthostatic hypotension which was abolished by withdrawal of selegiline. This unwanted effect on postural blood pressure was not the result of underlying autonomic failure. The aims of this study were to confirm our previous findings in a separate cohort of patients and to determine the time course of the cardiovascular consequences of stopping selegiline in the expectation that this might shed light on the mechanisms by which the drug causes orthostatic hypotension. METHODS: The cardiovascular responses to standing and head-up tilt were studied repeatedly in PD patients receiving selegiline and as the drug was withdrawn. RESULTS: Head-up tilt caused systolic orthostatic hypotension which was marked in six of 20 PD patients on selegiline, one of whom lost consciousness with unrecordable blood pressures. A lesser degree of orthostatic hypotension occurred with standing. Orthostatic hypotension was ameliorated 4 days after withdrawal of selegiline and totally abolished 7 days after discontinuation of the drug. Stopping selegiline also significantly reduced the supine systolic and diastolic blood pressures consistent with a previously undescribed supine pressor action. CONCLUSION: This study confirms our previous finding that selegiline in combination with L-dopa is associated with selective orthostatic hypotension. The possibilities that these cardiovascular findings might be the result of non-selective inhibition of monoamine oxidase or of amphetamine and metamphetamine are discussed.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "selegiline", "mention_text": "OBJECTIVES: The United Kingdom Parkinson's Disease Research Group (UKPDRG) trial found an increased mortality in patients with Parkinson's disease (PD) randomized to receive 10 mg selegiline per day and L-dopa compared with those taking L-dopa alone. Recently, we found that therapy with selegiline and L-dopa was associated with selective systolic orthostatic hypotension which was abolished by withdrawal of selegiline. This unwanted effect on postural blood pressure was not the result of underlying autonomic failure. The aims of this study were to confirm our previous findings in a separate cohort of patients and to determine the time course of the cardiovascular consequences of stopping selegiline in the expectation that this might shed light on the mechanisms by which the drug causes orthostatic hypotension. METHODS: The cardiovascular responses to standing and head-up tilt were studied repeatedly in PD patients receiving selegiline and as the drug was withdrawn. RESULTS: Head-up tilt caused systolic orthostatic hypotension which was marked in six of 20 PD patients on selegiline, one of whom lost consciousness with unrecordable blood pressures. A lesser degree of orthostatic hypotension occurred with standing. Orthostatic hypotension was ameliorated 4 days after withdrawal of selegiline and totally abolished 7 days after discontinuation of the drug. Stopping selegiline also significantly reduced the supine systolic and diastolic blood pressures consistent with a previously undescribed supine pressor action. CONCLUSION: This study confirms our previous finding that selegiline in combination with L-dopa is associated with selective orthostatic hypotension. The possibilities that these cardiovascular findings might be the result of non-selective inhibition of monoamine oxidase or of amphetamine and metamphetamine are discussed.", "entity": "Selegiline", "aliases": "Bristol Myers Squibb Brand of Selegiline Bristol-Myers Deprenalin Deprenil Deprenyl E 250 E-250 E250 Eldepryl Emsam Humex Hydrochloride Jumex L-Deprenyl (R)-Isomer (R,S)-Isomer (S)-Isomer Valeant Selegyline Yumex Zelapar", "definition": "A selective, irreversible inhibitor of Type B monoamine oxidase. It is used in newly diagnosed patients with Parkinson's disease. It may slow progression of the clinical disease and delay the requirement for levodopa therapy. It also may be given with levodopa upon onset of disability. (From AMA Drug Evaluations Annual, 1994, p385) The compound without isomeric designation is Deprenyl.\n    ", "id": "MESH:D012642"}
{"mention": "L-dopa", "mention_text": "OBJECTIVES: The United Kingdom Parkinson's Disease Research Group (UKPDRG) trial found an increased mortality in patients with Parkinson's disease (PD) randomized to receive 10 mg selegiline per day and L-dopa compared with those taking L-dopa alone. Recently, we found that therapy with selegiline and L-dopa was associated with selective systolic orthostatic hypotension which was abolished by withdrawal of selegiline. This unwanted effect on postural blood pressure was not the result of underlying autonomic failure. The aims of this study were to confirm our previous findings in a separate cohort of patients and to determine the time course of the cardiovascular consequences of stopping selegiline in the expectation that this might shed light on the mechanisms by which the drug causes orthostatic hypotension. METHODS: The cardiovascular responses to standing and head-up tilt were studied repeatedly in PD patients receiving selegiline and as the drug was withdrawn. RESULTS: Head-up tilt caused systolic orthostatic hypotension which was marked in six of 20 PD patients on selegiline, one of whom lost consciousness with unrecordable blood pressures. A lesser degree of orthostatic hypotension occurred with standing. Orthostatic hypotension was ameliorated 4 days after withdrawal of selegiline and totally abolished 7 days after discontinuation of the drug. Stopping selegiline also significantly reduced the supine systolic and diastolic blood pressures consistent with a previously undescribed supine pressor action. CONCLUSION: This study confirms our previous finding that selegiline in combination with L-dopa is associated with selective orthostatic hypotension. The possibilities that these cardiovascular findings might be the result of non-selective inhibition of monoamine oxidase or of amphetamine and metamphetamine are discussed.", "entity": "Levodopa", "aliases": "3 Hydroxy L tyrosine 3-Hydroxy-L-tyrosine Dopaflex Dopar 3,4 Dihydroxyphenylalanine Dopa L-3,4-Dihydroxyphenylalanine L-Dopa Larodopa Levodopa Levopa Medphano Brand of Roberts Roche", "definition": "The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.\n    ", "id": "MESH:D007980"}
{"mention": "systolic orthostatic hypotension", "mention_text": "OBJECTIVES: The United Kingdom Parkinson's Disease Research Group (UKPDRG) trial found an increased mortality in patients with Parkinson's disease (PD) randomized to receive 10 mg selegiline per day and L-dopa compared with those taking L-dopa alone. Recently, we found that therapy with selegiline and L-dopa was associated with selective systolic orthostatic hypotension which was abolished by withdrawal of selegiline. This unwanted effect on postural blood pressure was not the result of underlying autonomic failure. The aims of this study were to confirm our previous findings in a separate cohort of patients and to determine the time course of the cardiovascular consequences of stopping selegiline in the expectation that this might shed light on the mechanisms by which the drug causes orthostatic hypotension. METHODS: The cardiovascular responses to standing and head-up tilt were studied repeatedly in PD patients receiving selegiline and as the drug was withdrawn. RESULTS: Head-up tilt caused systolic orthostatic hypotension which was marked in six of 20 PD patients on selegiline, one of whom lost consciousness with unrecordable blood pressures. A lesser degree of orthostatic hypotension occurred with standing. Orthostatic hypotension was ameliorated 4 days after withdrawal of selegiline and totally abolished 7 days after discontinuation of the drug. Stopping selegiline also significantly reduced the supine systolic and diastolic blood pressures consistent with a previously undescribed supine pressor action. CONCLUSION: This study confirms our previous finding that selegiline in combination with L-dopa is associated with selective orthostatic hypotension. The possibilities that these cardiovascular findings might be the result of non-selective inhibition of monoamine oxidase or of amphetamine and metamphetamine are discussed.", "entity": "Hypotension, Orthostatic", "aliases": "Hypotension Orthostatic Postural", "definition": "A significant drop in BLOOD PRESSURE after assuming a standing position. Orthostatic hypotension is a finding, and defined as a 20-mm Hg decrease in systolic pressure or a 10-mm Hg decrease in diastolic pressure 3 minutes after the person has risen from supine to standing. Symptoms generally include DIZZINESS, blurred vision, and SYNCOPE.\n    ", "id": "MESH:D007024"}
{"mention": "orthostatic hypotension", "mention_text": "OBJECTIVES: The United Kingdom Parkinson's Disease Research Group (UKPDRG) trial found an increased mortality in patients with Parkinson's disease (PD) randomized to receive 10 mg selegiline per day and L-dopa compared with those taking L-dopa alone. Recently, we found that therapy with selegiline and L-dopa was associated with selective systolic orthostatic hypotension which was abolished by withdrawal of selegiline. This unwanted effect on postural blood pressure was not the result of underlying autonomic failure. The aims of this study were to confirm our previous findings in a separate cohort of patients and to determine the time course of the cardiovascular consequences of stopping selegiline in the expectation that this might shed light on the mechanisms by which the drug causes orthostatic hypotension. METHODS: The cardiovascular responses to standing and head-up tilt were studied repeatedly in PD patients receiving selegiline and as the drug was withdrawn. RESULTS: Head-up tilt caused systolic orthostatic hypotension which was marked in six of 20 PD patients on selegiline, one of whom lost consciousness with unrecordable blood pressures. A lesser degree of orthostatic hypotension occurred with standing. Orthostatic hypotension was ameliorated 4 days after withdrawal of selegiline and totally abolished 7 days after discontinuation of the drug. Stopping selegiline also significantly reduced the supine systolic and diastolic blood pressures consistent with a previously undescribed supine pressor action. CONCLUSION: This study confirms our previous finding that selegiline in combination with L-dopa is associated with selective orthostatic hypotension. The possibilities that these cardiovascular findings might be the result of non-selective inhibition of monoamine oxidase or of amphetamine and metamphetamine are discussed.", "entity": "Hypotension, Orthostatic", "aliases": "Hypotension Orthostatic Postural", "definition": "A significant drop in BLOOD PRESSURE after assuming a standing position. Orthostatic hypotension is a finding, and defined as a 20-mm Hg decrease in systolic pressure or a 10-mm Hg decrease in diastolic pressure 3 minutes after the person has risen from supine to standing. Symptoms generally include DIZZINESS, blurred vision, and SYNCOPE.\n    ", "id": "MESH:D007024"}
{"mention": "Orthostatic hypotension", "mention_text": "OBJECTIVES: The United Kingdom Parkinson's Disease Research Group (UKPDRG) trial found an increased mortality in patients with Parkinson's disease (PD) randomized to receive 10 mg selegiline per day and L-dopa compared with those taking L-dopa alone. Recently, we found that therapy with selegiline and L-dopa was associated with selective systolic orthostatic hypotension which was abolished by withdrawal of selegiline. This unwanted effect on postural blood pressure was not the result of underlying autonomic failure. The aims of this study were to confirm our previous findings in a separate cohort of patients and to determine the time course of the cardiovascular consequences of stopping selegiline in the expectation that this might shed light on the mechanisms by which the drug causes orthostatic hypotension. METHODS: The cardiovascular responses to standing and head-up tilt were studied repeatedly in PD patients receiving selegiline and as the drug was withdrawn. RESULTS: Head-up tilt caused systolic orthostatic hypotension which was marked in six of 20 PD patients on selegiline, one of whom lost consciousness with unrecordable blood pressures. A lesser degree of orthostatic hypotension occurred with standing. Orthostatic hypotension was ameliorated 4 days after withdrawal of selegiline and totally abolished 7 days after discontinuation of the drug. Stopping selegiline also significantly reduced the supine systolic and diastolic blood pressures consistent with a previously undescribed supine pressor action. CONCLUSION: This study confirms our previous finding that selegiline in combination with L-dopa is associated with selective orthostatic hypotension. The possibilities that these cardiovascular findings might be the result of non-selective inhibition of monoamine oxidase or of amphetamine and metamphetamine are discussed.", "entity": "Hypotension, Orthostatic", "aliases": "Hypotension Orthostatic Postural", "definition": "A significant drop in BLOOD PRESSURE after assuming a standing position. Orthostatic hypotension is a finding, and defined as a 20-mm Hg decrease in systolic pressure or a 10-mm Hg decrease in diastolic pressure 3 minutes after the person has risen from supine to standing. Symptoms generally include DIZZINESS, blurred vision, and SYNCOPE.\n    ", "id": "MESH:D007024"}
{"mention": "reduced the supine systolic and diastolic blood pressures", "mention_text": "OBJECTIVES: The United Kingdom Parkinson's Disease Research Group (UKPDRG) trial found an increased mortality in patients with Parkinson's disease (PD) randomized to receive 10 mg selegiline per day and L-dopa compared with those taking L-dopa alone. Recently, we found that therapy with selegiline and L-dopa was associated with selective systolic orthostatic hypotension which was abolished by withdrawal of selegiline. This unwanted effect on postural blood pressure was not the result of underlying autonomic failure. The aims of this study were to confirm our previous findings in a separate cohort of patients and to determine the time course of the cardiovascular consequences of stopping selegiline in the expectation that this might shed light on the mechanisms by which the drug causes orthostatic hypotension. METHODS: The cardiovascular responses to standing and head-up tilt were studied repeatedly in PD patients receiving selegiline and as the drug was withdrawn. RESULTS: Head-up tilt caused systolic orthostatic hypotension which was marked in six of 20 PD patients on selegiline, one of whom lost consciousness with unrecordable blood pressures. A lesser degree of orthostatic hypotension occurred with standing. Orthostatic hypotension was ameliorated 4 days after withdrawal of selegiline and totally abolished 7 days after discontinuation of the drug. Stopping selegiline also significantly reduced the supine systolic and diastolic blood pressures consistent with a previously undescribed supine pressor action. CONCLUSION: This study confirms our previous finding that selegiline in combination with L-dopa is associated with selective orthostatic hypotension. The possibilities that these cardiovascular findings might be the result of non-selective inhibition of monoamine oxidase or of amphetamine and metamphetamine are discussed.", "entity": "Hypotension, Orthostatic", "aliases": "Hypotension Orthostatic Postural", "definition": "A significant drop in BLOOD PRESSURE after assuming a standing position. Orthostatic hypotension is a finding, and defined as a 20-mm Hg decrease in systolic pressure or a 10-mm Hg decrease in diastolic pressure 3 minutes after the person has risen from supine to standing. Symptoms generally include DIZZINESS, blurred vision, and SYNCOPE.\n    ", "id": "MESH:D007024"}
{"mention": "amphetamine", "mention_text": "OBJECTIVES: The United Kingdom Parkinson's Disease Research Group (UKPDRG) trial found an increased mortality in patients with Parkinson's disease (PD) randomized to receive 10 mg selegiline per day and L-dopa compared with those taking L-dopa alone. Recently, we found that therapy with selegiline and L-dopa was associated with selective systolic orthostatic hypotension which was abolished by withdrawal of selegiline. This unwanted effect on postural blood pressure was not the result of underlying autonomic failure. The aims of this study were to confirm our previous findings in a separate cohort of patients and to determine the time course of the cardiovascular consequences of stopping selegiline in the expectation that this might shed light on the mechanisms by which the drug causes orthostatic hypotension. METHODS: The cardiovascular responses to standing and head-up tilt were studied repeatedly in PD patients receiving selegiline and as the drug was withdrawn. RESULTS: Head-up tilt caused systolic orthostatic hypotension which was marked in six of 20 PD patients on selegiline, one of whom lost consciousness with unrecordable blood pressures. A lesser degree of orthostatic hypotension occurred with standing. Orthostatic hypotension was ameliorated 4 days after withdrawal of selegiline and totally abolished 7 days after discontinuation of the drug. Stopping selegiline also significantly reduced the supine systolic and diastolic blood pressures consistent with a previously undescribed supine pressor action. CONCLUSION: This study confirms our previous finding that selegiline in combination with L-dopa is associated with selective orthostatic hypotension. The possibilities that these cardiovascular findings might be the result of non-selective inhibition of monoamine oxidase or of amphetamine and metamphetamine are discussed.", "entity": "Amphetamine", "aliases": "Amfetamine Amphetamine Sulfate (2:1) Centramina Desoxynorephedrin Fenamine Levoamphetamine Miquel Brand of Mydrial Phenamine Phenopromin Thyramine l l-Amphetamine levo levo-Amphetamine", "definition": "A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE.\n    ", "id": "MESH:D000661"}
{"mention": "metamphetamine", "mention_text": "OBJECTIVES: The United Kingdom Parkinson's Disease Research Group (UKPDRG) trial found an increased mortality in patients with Parkinson's disease (PD) randomized to receive 10 mg selegiline per day and L-dopa compared with those taking L-dopa alone. Recently, we found that therapy with selegiline and L-dopa was associated with selective systolic orthostatic hypotension which was abolished by withdrawal of selegiline. This unwanted effect on postural blood pressure was not the result of underlying autonomic failure. The aims of this study were to confirm our previous findings in a separate cohort of patients and to determine the time course of the cardiovascular consequences of stopping selegiline in the expectation that this might shed light on the mechanisms by which the drug causes orthostatic hypotension. METHODS: The cardiovascular responses to standing and head-up tilt were studied repeatedly in PD patients receiving selegiline and as the drug was withdrawn. RESULTS: Head-up tilt caused systolic orthostatic hypotension which was marked in six of 20 PD patients on selegiline, one of whom lost consciousness with unrecordable blood pressures. A lesser degree of orthostatic hypotension occurred with standing. Orthostatic hypotension was ameliorated 4 days after withdrawal of selegiline and totally abolished 7 days after discontinuation of the drug. Stopping selegiline also significantly reduced the supine systolic and diastolic blood pressures consistent with a previously undescribed supine pressor action. CONCLUSION: This study confirms our previous finding that selegiline in combination with L-dopa is associated with selective orthostatic hypotension. The possibilities that these cardiovascular findings might be the result of non-selective inhibition of monoamine oxidase or of amphetamine and metamphetamine are discussed.", "entity": "Methamphetamine", "aliases": "Abbott Brand of Methamphetamine Hydrochloride Deoxyephedrine Desoxyephedrine Desoxyn Langly Madrine Metamfetamine Methylamphetamine N N-Methylamphetamine", "definition": "A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.\n    ", "id": "MESH:D008694"}
{"mention": "capsaicin", "mention_text": "Explicit episodic memory for sensory-discriminative components of capsaicin-induced pain: immediate and delayed ratings.", "entity": "Capsaicin", "aliases": "8 Methyl N Vanillyl 6 Nonenamide 8-Methyl-N-Vanillyl-6-Nonenamide Alacan Brand of Capsaicin Antiphlogistine Rub A-535 Axsain Capsaicine Capsicum Farmaya Capsidol Capsin Capzasin Carter Horner Centrum Elan Flemming Gelcen Katrum Link Medicis NGX 4010 NGX-4010 NGX4010 Smaller Thompson Vinas Zacin Zostrix", "definition": "An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.\n    ", "id": "MESH:D002211"}
{"mention": "pain", "mention_text": "Explicit episodic memory for sensory-discriminative components of capsaicin-induced pain: immediate and delayed ratings.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "Pain", "mention_text": "Pain memory is thought to affect future pain sensitivity and thus contribute to clinical pain conditions. Systematic investigations of the human capacity to remember sensory features of experimental pain are sparse. In order to address long-term pain memory, nine healthy male volunteers received intradermal injections of three doses of capsaicin (0.05, 1 and 20 microg, separated by 15 min breaks), each given three times in a balanced design across three sessions at one week intervals. Pain rating was performed using a computerized visual analogue scale (0-100) digitized at 1/s, either immediately online or one hour or one day after injection. Subjects also recalled their pains one week later. Capsaicin injection reliably induced a dose-dependent flare (p<0.001) without any difference within or across sessions. The strong burning pain decayed exponentially within a few minutes. Subjects were able to reliably discriminate pain magnitude and duration across capsaicin doses (both p<0.001), regardless of whether first-time ratings were requested immediately, after one hour or after one day. Pain recall after one week was similarly precise (magnitude: p<0.01, duration: p<0.05). Correlation with rating recall after one week was best when first-time ratings were requested as late as one day after injection (R(2)=0.79) indicating that both rating retrievals utilized similar memory traces. These results indicate a reliable memory for magnitude and duration of experimentally induced pain. The data further suggest that the consolidation of this memory is an important interim stage, and may take up to one day.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "pain", "mention_text": "Pain memory is thought to affect future pain sensitivity and thus contribute to clinical pain conditions. Systematic investigations of the human capacity to remember sensory features of experimental pain are sparse. In order to address long-term pain memory, nine healthy male volunteers received intradermal injections of three doses of capsaicin (0.05, 1 and 20 microg, separated by 15 min breaks), each given three times in a balanced design across three sessions at one week intervals. Pain rating was performed using a computerized visual analogue scale (0-100) digitized at 1/s, either immediately online or one hour or one day after injection. Subjects also recalled their pains one week later. Capsaicin injection reliably induced a dose-dependent flare (p<0.001) without any difference within or across sessions. The strong burning pain decayed exponentially within a few minutes. Subjects were able to reliably discriminate pain magnitude and duration across capsaicin doses (both p<0.001), regardless of whether first-time ratings were requested immediately, after one hour or after one day. Pain recall after one week was similarly precise (magnitude: p<0.01, duration: p<0.05). Correlation with rating recall after one week was best when first-time ratings were requested as late as one day after injection (R(2)=0.79) indicating that both rating retrievals utilized similar memory traces. These results indicate a reliable memory for magnitude and duration of experimentally induced pain. The data further suggest that the consolidation of this memory is an important interim stage, and may take up to one day.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "capsaicin", "mention_text": "Pain memory is thought to affect future pain sensitivity and thus contribute to clinical pain conditions. Systematic investigations of the human capacity to remember sensory features of experimental pain are sparse. In order to address long-term pain memory, nine healthy male volunteers received intradermal injections of three doses of capsaicin (0.05, 1 and 20 microg, separated by 15 min breaks), each given three times in a balanced design across three sessions at one week intervals. Pain rating was performed using a computerized visual analogue scale (0-100) digitized at 1/s, either immediately online or one hour or one day after injection. Subjects also recalled their pains one week later. Capsaicin injection reliably induced a dose-dependent flare (p<0.001) without any difference within or across sessions. The strong burning pain decayed exponentially within a few minutes. Subjects were able to reliably discriminate pain magnitude and duration across capsaicin doses (both p<0.001), regardless of whether first-time ratings were requested immediately, after one hour or after one day. Pain recall after one week was similarly precise (magnitude: p<0.01, duration: p<0.05). Correlation with rating recall after one week was best when first-time ratings were requested as late as one day after injection (R(2)=0.79) indicating that both rating retrievals utilized similar memory traces. These results indicate a reliable memory for magnitude and duration of experimentally induced pain. The data further suggest that the consolidation of this memory is an important interim stage, and may take up to one day.", "entity": "Capsaicin", "aliases": "8 Methyl N Vanillyl 6 Nonenamide 8-Methyl-N-Vanillyl-6-Nonenamide Alacan Brand of Capsaicin Antiphlogistine Rub A-535 Axsain Capsaicine Capsicum Farmaya Capsidol Capsin Capzasin Carter Horner Centrum Elan Flemming Gelcen Katrum Link Medicis NGX 4010 NGX-4010 NGX4010 Smaller Thompson Vinas Zacin Zostrix", "definition": "An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.\n    ", "id": "MESH:D002211"}
{"mention": "pains", "mention_text": "Pain memory is thought to affect future pain sensitivity and thus contribute to clinical pain conditions. Systematic investigations of the human capacity to remember sensory features of experimental pain are sparse. In order to address long-term pain memory, nine healthy male volunteers received intradermal injections of three doses of capsaicin (0.05, 1 and 20 microg, separated by 15 min breaks), each given three times in a balanced design across three sessions at one week intervals. Pain rating was performed using a computerized visual analogue scale (0-100) digitized at 1/s, either immediately online or one hour or one day after injection. Subjects also recalled their pains one week later. Capsaicin injection reliably induced a dose-dependent flare (p<0.001) without any difference within or across sessions. The strong burning pain decayed exponentially within a few minutes. Subjects were able to reliably discriminate pain magnitude and duration across capsaicin doses (both p<0.001), regardless of whether first-time ratings were requested immediately, after one hour or after one day. Pain recall after one week was similarly precise (magnitude: p<0.01, duration: p<0.05). Correlation with rating recall after one week was best when first-time ratings were requested as late as one day after injection (R(2)=0.79) indicating that both rating retrievals utilized similar memory traces. These results indicate a reliable memory for magnitude and duration of experimentally induced pain. The data further suggest that the consolidation of this memory is an important interim stage, and may take up to one day.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "Capsaicin", "mention_text": "Pain memory is thought to affect future pain sensitivity and thus contribute to clinical pain conditions. Systematic investigations of the human capacity to remember sensory features of experimental pain are sparse. In order to address long-term pain memory, nine healthy male volunteers received intradermal injections of three doses of capsaicin (0.05, 1 and 20 microg, separated by 15 min breaks), each given three times in a balanced design across three sessions at one week intervals. Pain rating was performed using a computerized visual analogue scale (0-100) digitized at 1/s, either immediately online or one hour or one day after injection. Subjects also recalled their pains one week later. Capsaicin injection reliably induced a dose-dependent flare (p<0.001) without any difference within or across sessions. The strong burning pain decayed exponentially within a few minutes. Subjects were able to reliably discriminate pain magnitude and duration across capsaicin doses (both p<0.001), regardless of whether first-time ratings were requested immediately, after one hour or after one day. Pain recall after one week was similarly precise (magnitude: p<0.01, duration: p<0.05). Correlation with rating recall after one week was best when first-time ratings were requested as late as one day after injection (R(2)=0.79) indicating that both rating retrievals utilized similar memory traces. These results indicate a reliable memory for magnitude and duration of experimentally induced pain. The data further suggest that the consolidation of this memory is an important interim stage, and may take up to one day.", "entity": "Capsaicin", "aliases": "8 Methyl N Vanillyl 6 Nonenamide 8-Methyl-N-Vanillyl-6-Nonenamide Alacan Brand of Capsaicin Antiphlogistine Rub A-535 Axsain Capsaicine Capsicum Farmaya Capsidol Capsin Capzasin Carter Horner Centrum Elan Flemming Gelcen Katrum Link Medicis NGX 4010 NGX-4010 NGX4010 Smaller Thompson Vinas Zacin Zostrix", "definition": "An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.\n    ", "id": "MESH:D002211"}
{"mention": "captopril", "mention_text": "Reversibility of captopril-induced renal insufficiency after prolonged use in an unusual case of renovascular hypertension.", "entity": "Captopril", "aliases": "(S)-1-(3-Mercapto-2-methyl-1-oxopropyl)-L-proline Capoten Captopril Lopirin SQ 14,225 14,534 14225 14534 SQ-14,225 SQ-14,534 SQ-14225 SQ-14534 SQ14,225 SQ14,534 SQ14225 SQ14534", "definition": "A potent and specific inhibitor of PEPTIDYL-DIPEPTIDASE A. It blocks the conversion of ANGIOTENSIN I to ANGIOTENSIN II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the RENIN-ANGIOTENSIN SYSTEM and inhibits pressure responses to exogenous angiotensin.\n    ", "id": "MESH:D002216"}
{"mention": "renal insufficiency", "mention_text": "Reversibility of captopril-induced renal insufficiency after prolonged use in an unusual case of renovascular hypertension.", "entity": "Renal Insufficiency", "aliases": "Failure Kidney Renal Failures Insufficiency Insufficiencies", "definition": "Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.\n    ", "id": "MESH:D051437"}
{"mention": "renovascular hypertension", "mention_text": "Reversibility of captopril-induced renal insufficiency after prolonged use in an unusual case of renovascular hypertension.", "entity": "Hypertension, Renovascular", "aliases": "Goldblatt Hypertension Syndrome Renovascular", "definition": "Hypertension due to RENAL ARTERY OBSTRUCTION or compression.\n    ", "id": "MESH:D006978"}
{"mention": "hypertension", "mention_text": "We report a case of severe hypertension with an occluded renal artery to a solitary kidney, who developed sudden deterioration of renal function following treatment with captopril. His renal function remained impaired but stable during 2 years' treatment with captopril but returned to pre-treatment levels soon after cessation of the drug. This indicates reversibility in captopril-induced renal failure even after its prolonged use and suggests that no organic damage occurs to glomerular arterioles following chronic ACE inhibition.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "sudden deterioration of renal function", "mention_text": "We report a case of severe hypertension with an occluded renal artery to a solitary kidney, who developed sudden deterioration of renal function following treatment with captopril. His renal function remained impaired but stable during 2 years' treatment with captopril but returned to pre-treatment levels soon after cessation of the drug. This indicates reversibility in captopril-induced renal failure even after its prolonged use and suggests that no organic damage occurs to glomerular arterioles following chronic ACE inhibition.", "entity": "Acute Kidney Injury", "aliases": "Acute Kidney Failure Failures Injuries Injury Insufficiencies Insufficiency Renal", "definition": "Abrupt reduction in kidney function. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions.\n    ", "id": "MESH:D058186"}
{"mention": "captopril", "mention_text": "We report a case of severe hypertension with an occluded renal artery to a solitary kidney, who developed sudden deterioration of renal function following treatment with captopril. His renal function remained impaired but stable during 2 years' treatment with captopril but returned to pre-treatment levels soon after cessation of the drug. This indicates reversibility in captopril-induced renal failure even after its prolonged use and suggests that no organic damage occurs to glomerular arterioles following chronic ACE inhibition.", "entity": "Captopril", "aliases": "(S)-1-(3-Mercapto-2-methyl-1-oxopropyl)-L-proline Capoten Captopril Lopirin SQ 14,225 14,534 14225 14534 SQ-14,225 SQ-14,534 SQ-14225 SQ-14534 SQ14,225 SQ14,534 SQ14225 SQ14534", "definition": "A potent and specific inhibitor of PEPTIDYL-DIPEPTIDASE A. It blocks the conversion of ANGIOTENSIN I to ANGIOTENSIN II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the RENIN-ANGIOTENSIN SYSTEM and inhibits pressure responses to exogenous angiotensin.\n    ", "id": "MESH:D002216"}
{"mention": "renal failure", "mention_text": "We report a case of severe hypertension with an occluded renal artery to a solitary kidney, who developed sudden deterioration of renal function following treatment with captopril. His renal function remained impaired but stable during 2 years' treatment with captopril but returned to pre-treatment levels soon after cessation of the drug. This indicates reversibility in captopril-induced renal failure even after its prolonged use and suggests that no organic damage occurs to glomerular arterioles following chronic ACE inhibition.", "entity": "Renal Insufficiency", "aliases": "Failure Kidney Renal Failures Insufficiency Insufficiencies", "definition": "Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.\n    ", "id": "MESH:D051437"}
{"mention": "Liver disease", "mention_text": "Liver disease caused by propylthiouracil.", "entity": "Liver Diseases", "aliases": "Disease Liver Diseases Dysfunction Dysfunctions", "definition": "Pathological processes of the LIVER.\n    ", "id": "MESH:D008107"}
{"mention": "propylthiouracil", "mention_text": "Liver disease caused by propylthiouracil.", "entity": "Propylthiouracil", "aliases": "6 Propyl 2 Thiouracil 6-Propyl-2-Thiouracil Propylthiouracil", "definition": "A thiourea antithyroid agent. Propythiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of throxine to tri-iodothyronine. It is used in the treatment of hyperthyroidism. (From Martindale, The Extra Pharmacopeoia, 30th ed, p534)\n    ", "id": "MESH:D011441"}
{"mention": "chronic active (aggressive) hepatitis", "mention_text": "This report presents the clinical, laboratory, and light and electron microscopic observations on a patient with chronic active (aggressive) hepatitis caused by the administration of propylthiouracil. This is an addition to the list of drugs that must be considered in the evaluation of chronic liver disease.", "entity": "Hepatitis, Chronic", "aliases": "Chronic Active Hepatitis Cryptogenic Persistent Hepatitides", "definition": "INFLAMMATION of the LIVER with ongoing hepatocellular injury for 6 months or more, characterized by NECROSIS of HEPATOCYTES and inflammatory cell (LEUKOCYTES) infiltration. Chronic hepatitis can be caused by viruses, medications, autoimmune diseases, and other unknown factors.\n    ", "id": "MESH:D006521"}
{"mention": "propylthiouracil", "mention_text": "This report presents the clinical, laboratory, and light and electron microscopic observations on a patient with chronic active (aggressive) hepatitis caused by the administration of propylthiouracil. This is an addition to the list of drugs that must be considered in the evaluation of chronic liver disease.", "entity": "Propylthiouracil", "aliases": "6 Propyl 2 Thiouracil 6-Propyl-2-Thiouracil Propylthiouracil", "definition": "A thiourea antithyroid agent. Propythiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of throxine to tri-iodothyronine. It is used in the treatment of hyperthyroidism. (From Martindale, The Extra Pharmacopeoia, 30th ed, p534)\n    ", "id": "MESH:D011441"}
{"mention": "liver disease", "mention_text": "This report presents the clinical, laboratory, and light and electron microscopic observations on a patient with chronic active (aggressive) hepatitis caused by the administration of propylthiouracil. This is an addition to the list of drugs that must be considered in the evaluation of chronic liver disease.", "entity": "Liver Diseases", "aliases": "Disease Liver Diseases Dysfunction Dysfunctions", "definition": "Pathological processes of the LIVER.\n    ", "id": "MESH:D008107"}
{"mention": "Capsaicin", "mention_text": "Capsaicin-induced muscle pain alters the excitability of the human jaw-stretch reflex.", "entity": "Capsaicin", "aliases": "8 Methyl N Vanillyl 6 Nonenamide 8-Methyl-N-Vanillyl-6-Nonenamide Alacan Brand of Capsaicin Antiphlogistine Rub A-535 Axsain Capsaicine Capsicum Farmaya Capsidol Capsin Capzasin Carter Horner Centrum Elan Flemming Gelcen Katrum Link Medicis NGX 4010 NGX-4010 NGX4010 Smaller Thompson Vinas Zacin Zostrix", "definition": "An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.\n    ", "id": "MESH:D002211"}
{"mention": "muscle pain", "mention_text": "Capsaicin-induced muscle pain alters the excitability of the human jaw-stretch reflex.", "entity": "Myalgia", "aliases": "Muscle Pain Soreness Sorenesses Tenderness Myalgia Pains", "definition": "Painful sensation in the muscles.\n    ", "id": "MESH:D063806"}
{"mention": "temporomandibular disorders", "mention_text": "The pathophysiology of painful temporomandibular disorders is not fully understood, but evidence suggests that muscle pain modulates motor function in characteristic ways. This study tested the hypothesis that activation of nociceptive muscle afferent fibers would be linked to an increased excitability of the human jaw-stretch reflex and whether this process would be sensitive to length and velocity of the stretch. Capsaicin (10 micro g) was injected into the masseter muscle to induce pain in 11 healthy volunteers. Short-latency reflex responses were evoked in the masseter and temporalis muscles by a stretch device with different velocities and displacements before, during, and after the pain. The normalized reflex amplitude increased with an increase in velocity at a given displacement, but remained constant with different displacements at a given velocity. The normalized reflex amplitude was significantly higher during pain, but only at faster stretches in the painful muscle. Increased sensitivity of the fusimotor system during acute muscle pain could be one likely mechanism to explain the findings.", "entity": "Temporomandibular Joint Disorders", "aliases": "Disease TMJ Temporomandibular Joint Diseases Disorder Disorders", "definition": "A variety of conditions affecting the anatomic and functional characteristics of the temporomandibular joint. Factors contributing to the complexity of temporomandibular diseases are its relation to dentition and mastication and the symptomatic effects in other areas which account for referred pain to the joint and the difficulties in applying traditional diagnostic procedures to temporomandibular joint pathology where tissue is rarely obtained and x-rays are often inadequate or nonspecific. Common diseases are developmental abnormalities, trauma, subluxation, luxation, arthritis, and neoplasia. (From Thoma's Oral Pathology, 6th ed, pp577-600)\n    ", "id": "MESH:D013705"}
{"mention": "muscle pain", "mention_text": "The pathophysiology of painful temporomandibular disorders is not fully understood, but evidence suggests that muscle pain modulates motor function in characteristic ways. This study tested the hypothesis that activation of nociceptive muscle afferent fibers would be linked to an increased excitability of the human jaw-stretch reflex and whether this process would be sensitive to length and velocity of the stretch. Capsaicin (10 micro g) was injected into the masseter muscle to induce pain in 11 healthy volunteers. Short-latency reflex responses were evoked in the masseter and temporalis muscles by a stretch device with different velocities and displacements before, during, and after the pain. The normalized reflex amplitude increased with an increase in velocity at a given displacement, but remained constant with different displacements at a given velocity. The normalized reflex amplitude was significantly higher during pain, but only at faster stretches in the painful muscle. Increased sensitivity of the fusimotor system during acute muscle pain could be one likely mechanism to explain the findings.", "entity": "Myalgia", "aliases": "Muscle Pain Soreness Sorenesses Tenderness Myalgia Pains", "definition": "Painful sensation in the muscles.\n    ", "id": "MESH:D063806"}
{"mention": "nociceptive muscle", "mention_text": "The pathophysiology of painful temporomandibular disorders is not fully understood, but evidence suggests that muscle pain modulates motor function in characteristic ways. This study tested the hypothesis that activation of nociceptive muscle afferent fibers would be linked to an increased excitability of the human jaw-stretch reflex and whether this process would be sensitive to length and velocity of the stretch. Capsaicin (10 micro g) was injected into the masseter muscle to induce pain in 11 healthy volunteers. Short-latency reflex responses were evoked in the masseter and temporalis muscles by a stretch device with different velocities and displacements before, during, and after the pain. The normalized reflex amplitude increased with an increase in velocity at a given displacement, but remained constant with different displacements at a given velocity. The normalized reflex amplitude was significantly higher during pain, but only at faster stretches in the painful muscle. Increased sensitivity of the fusimotor system during acute muscle pain could be one likely mechanism to explain the findings.", "entity": "Myalgia", "aliases": "Muscle Pain Soreness Sorenesses Tenderness Myalgia Pains", "definition": "Painful sensation in the muscles.\n    ", "id": "MESH:D063806"}
{"mention": "Capsaicin", "mention_text": "The pathophysiology of painful temporomandibular disorders is not fully understood, but evidence suggests that muscle pain modulates motor function in characteristic ways. This study tested the hypothesis that activation of nociceptive muscle afferent fibers would be linked to an increased excitability of the human jaw-stretch reflex and whether this process would be sensitive to length and velocity of the stretch. Capsaicin (10 micro g) was injected into the masseter muscle to induce pain in 11 healthy volunteers. Short-latency reflex responses were evoked in the masseter and temporalis muscles by a stretch device with different velocities and displacements before, during, and after the pain. The normalized reflex amplitude increased with an increase in velocity at a given displacement, but remained constant with different displacements at a given velocity. The normalized reflex amplitude was significantly higher during pain, but only at faster stretches in the painful muscle. Increased sensitivity of the fusimotor system during acute muscle pain could be one likely mechanism to explain the findings.", "entity": "Capsaicin", "aliases": "8 Methyl N Vanillyl 6 Nonenamide 8-Methyl-N-Vanillyl-6-Nonenamide Alacan Brand of Capsaicin Antiphlogistine Rub A-535 Axsain Capsaicine Capsicum Farmaya Capsidol Capsin Capzasin Carter Horner Centrum Elan Flemming Gelcen Katrum Link Medicis NGX 4010 NGX-4010 NGX4010 Smaller Thompson Vinas Zacin Zostrix", "definition": "An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.\n    ", "id": "MESH:D002211"}
{"mention": "pain", "mention_text": "The pathophysiology of painful temporomandibular disorders is not fully understood, but evidence suggests that muscle pain modulates motor function in characteristic ways. This study tested the hypothesis that activation of nociceptive muscle afferent fibers would be linked to an increased excitability of the human jaw-stretch reflex and whether this process would be sensitive to length and velocity of the stretch. Capsaicin (10 micro g) was injected into the masseter muscle to induce pain in 11 healthy volunteers. Short-latency reflex responses were evoked in the masseter and temporalis muscles by a stretch device with different velocities and displacements before, during, and after the pain. The normalized reflex amplitude increased with an increase in velocity at a given displacement, but remained constant with different displacements at a given velocity. The normalized reflex amplitude was significantly higher during pain, but only at faster stretches in the painful muscle. Increased sensitivity of the fusimotor system during acute muscle pain could be one likely mechanism to explain the findings.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "painful muscle", "mention_text": "The pathophysiology of painful temporomandibular disorders is not fully understood, but evidence suggests that muscle pain modulates motor function in characteristic ways. This study tested the hypothesis that activation of nociceptive muscle afferent fibers would be linked to an increased excitability of the human jaw-stretch reflex and whether this process would be sensitive to length and velocity of the stretch. Capsaicin (10 micro g) was injected into the masseter muscle to induce pain in 11 healthy volunteers. Short-latency reflex responses were evoked in the masseter and temporalis muscles by a stretch device with different velocities and displacements before, during, and after the pain. The normalized reflex amplitude increased with an increase in velocity at a given displacement, but remained constant with different displacements at a given velocity. The normalized reflex amplitude was significantly higher during pain, but only at faster stretches in the painful muscle. Increased sensitivity of the fusimotor system during acute muscle pain could be one likely mechanism to explain the findings.", "entity": "Myalgia", "aliases": "Muscle Pain Soreness Sorenesses Tenderness Myalgia Pains", "definition": "Painful sensation in the muscles.\n    ", "id": "MESH:D063806"}
{"mention": "levodopa", "mention_text": "Repetitive transcranial magnetic stimulation for levodopa-induced dyskinesias in Parkinson's disease.", "entity": "Levodopa", "aliases": "3 Hydroxy L tyrosine 3-Hydroxy-L-tyrosine Dopaflex Dopar 3,4 Dihydroxyphenylalanine Dopa L-3,4-Dihydroxyphenylalanine L-Dopa Larodopa Levodopa Levopa Medphano Brand of Roberts Roche", "definition": "The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.\n    ", "id": "MESH:D007980"}
{"mention": "dyskinesias", "mention_text": "Repetitive transcranial magnetic stimulation for levodopa-induced dyskinesias in Parkinson's disease.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "Parkinson's disease", "mention_text": "Repetitive transcranial magnetic stimulation for levodopa-induced dyskinesias in Parkinson's disease.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "dyskinesias", "mention_text": "In a placebo-controlled, single-blinded, crossover study, we assessed the effect of \"real\" repetitive transcranial magnetic stimulation (rTMS) versus \"sham\" rTMS (placebo) on peak dose dyskinesias in patients with Parkinson's disease (PD). Ten patients with PD and prominent dyskinesias had rTMS (1,800 pulses; 1 Hz rate) delivered over the motor cortex for 4 consecutive days twice, once real stimuli and once sham stimulation were used; evaluations were done at the baseline and 1 day after the end of each of the treatment series. Direct comparison between sham and real rTMS effects showed no significant difference in clinician-assessed dyskinesia severity. However, comparison with the baseline showed small but significant reduction in dyskinesia severity following real rTMS but not placebo. The major effect was on dystonia subscore. Similarly, in patient diaries, although both treatments caused reduction in subjective dyskinesia scores during the days of intervention, the effect was sustained for 3 days after the intervention for the real rTMS only. Following rTMS, no side effects and no adverse effects on motor function and PD symptoms were noted. The results suggest the existence of residual beneficial clinical aftereffects of consecutive daily applications of low-frequency rTMS on dyskinesias in PD. The effects may be further exploited for potential therapeutic uses.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "Parkinson's disease", "mention_text": "In a placebo-controlled, single-blinded, crossover study, we assessed the effect of \"real\" repetitive transcranial magnetic stimulation (rTMS) versus \"sham\" rTMS (placebo) on peak dose dyskinesias in patients with Parkinson's disease (PD). Ten patients with PD and prominent dyskinesias had rTMS (1,800 pulses; 1 Hz rate) delivered over the motor cortex for 4 consecutive days twice, once real stimuli and once sham stimulation were used; evaluations were done at the baseline and 1 day after the end of each of the treatment series. Direct comparison between sham and real rTMS effects showed no significant difference in clinician-assessed dyskinesia severity. However, comparison with the baseline showed small but significant reduction in dyskinesia severity following real rTMS but not placebo. The major effect was on dystonia subscore. Similarly, in patient diaries, although both treatments caused reduction in subjective dyskinesia scores during the days of intervention, the effect was sustained for 3 days after the intervention for the real rTMS only. Following rTMS, no side effects and no adverse effects on motor function and PD symptoms were noted. The results suggest the existence of residual beneficial clinical aftereffects of consecutive daily applications of low-frequency rTMS on dyskinesias in PD. The effects may be further exploited for potential therapeutic uses.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "PD", "mention_text": "In a placebo-controlled, single-blinded, crossover study, we assessed the effect of \"real\" repetitive transcranial magnetic stimulation (rTMS) versus \"sham\" rTMS (placebo) on peak dose dyskinesias in patients with Parkinson's disease (PD). Ten patients with PD and prominent dyskinesias had rTMS (1,800 pulses; 1 Hz rate) delivered over the motor cortex for 4 consecutive days twice, once real stimuli and once sham stimulation were used; evaluations were done at the baseline and 1 day after the end of each of the treatment series. Direct comparison between sham and real rTMS effects showed no significant difference in clinician-assessed dyskinesia severity. However, comparison with the baseline showed small but significant reduction in dyskinesia severity following real rTMS but not placebo. The major effect was on dystonia subscore. Similarly, in patient diaries, although both treatments caused reduction in subjective dyskinesia scores during the days of intervention, the effect was sustained for 3 days after the intervention for the real rTMS only. Following rTMS, no side effects and no adverse effects on motor function and PD symptoms were noted. The results suggest the existence of residual beneficial clinical aftereffects of consecutive daily applications of low-frequency rTMS on dyskinesias in PD. The effects may be further exploited for potential therapeutic uses.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "dyskinesia", "mention_text": "In a placebo-controlled, single-blinded, crossover study, we assessed the effect of \"real\" repetitive transcranial magnetic stimulation (rTMS) versus \"sham\" rTMS (placebo) on peak dose dyskinesias in patients with Parkinson's disease (PD). Ten patients with PD and prominent dyskinesias had rTMS (1,800 pulses; 1 Hz rate) delivered over the motor cortex for 4 consecutive days twice, once real stimuli and once sham stimulation were used; evaluations were done at the baseline and 1 day after the end of each of the treatment series. Direct comparison between sham and real rTMS effects showed no significant difference in clinician-assessed dyskinesia severity. However, comparison with the baseline showed small but significant reduction in dyskinesia severity following real rTMS but not placebo. The major effect was on dystonia subscore. Similarly, in patient diaries, although both treatments caused reduction in subjective dyskinesia scores during the days of intervention, the effect was sustained for 3 days after the intervention for the real rTMS only. Following rTMS, no side effects and no adverse effects on motor function and PD symptoms were noted. The results suggest the existence of residual beneficial clinical aftereffects of consecutive daily applications of low-frequency rTMS on dyskinesias in PD. The effects may be further exploited for potential therapeutic uses.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "dystonia", "mention_text": "In a placebo-controlled, single-blinded, crossover study, we assessed the effect of \"real\" repetitive transcranial magnetic stimulation (rTMS) versus \"sham\" rTMS (placebo) on peak dose dyskinesias in patients with Parkinson's disease (PD). Ten patients with PD and prominent dyskinesias had rTMS (1,800 pulses; 1 Hz rate) delivered over the motor cortex for 4 consecutive days twice, once real stimuli and once sham stimulation were used; evaluations were done at the baseline and 1 day after the end of each of the treatment series. Direct comparison between sham and real rTMS effects showed no significant difference in clinician-assessed dyskinesia severity. However, comparison with the baseline showed small but significant reduction in dyskinesia severity following real rTMS but not placebo. The major effect was on dystonia subscore. Similarly, in patient diaries, although both treatments caused reduction in subjective dyskinesia scores during the days of intervention, the effect was sustained for 3 days after the intervention for the real rTMS only. Following rTMS, no side effects and no adverse effects on motor function and PD symptoms were noted. The results suggest the existence of residual beneficial clinical aftereffects of consecutive daily applications of low-frequency rTMS on dyskinesias in PD. The effects may be further exploited for potential therapeutic uses.", "entity": "Dystonia", "aliases": "Diurnal Dystonia Limb Muscle Paroxysmal", "definition": "An attitude or posture due to the co-contraction of agonists and antagonist muscles in one region of the body. It most often affects the large axial muscles of the trunk and limb girdles. Conditions which feature persistent or recurrent episodes of dystonia as a primary manifestation of disease are referred to as DYSTONIC DISORDERS. (Adams et al., Principles of Neurology, 6th ed, p77)\n    ", "id": "MESH:D004421"}
{"mention": "Disulfiram", "mention_text": "Disulfiram-like syndrome after hydrogen cyanamide professional skin exposure: two case reports in France.", "entity": "Disulfiram", "aliases": "Alcophobin Allphar Brand of Disulfiram Altana Pharma Antabus Antabuse Anticol Bis(diethylthiocarbamoyl) Disulfide Bohm Dicupral Tetraethylthiuram Dumex Esperal Odyssey Orphan Sanofi Synthelabo Tetraethylthioperoxydicarbonic Diamide ((H2N)C(S))2S2 Teturam", "definition": "A carbamate derivative used as an alcohol deterrent. It is a relatively nontoxic substance when administered alone, but markedly alters the intermediary metabolism of alcohol. When alcohol is ingested after administration of disulfiram, blood acetaldehyde concentrations are increased, followed by flushing, systemic vasodilation, respiratory difficulties, nausea, hypotension, and other symptoms (acetaldehyde syndrome). It acts by inhibiting aldehyde dehydrogenase.\n    ", "id": "MESH:D004221"}
{"mention": "hydrogen cyanamide", "mention_text": "Disulfiram-like syndrome after hydrogen cyanamide professional skin exposure: two case reports in France.", "entity": "Cyanamide", "aliases": "Abstem Calcium Carbimide Cyanamide Citrated Salt Colme (1:1) (2:1) Ipsen Brand of Temposil", "definition": "A cyanide compound which has been used as a fertilizer, defoliant and in many manufacturing processes. It often occurs as the calcium salt, sometimes also referred to as cyanamide. The citrated calcium salt is used in the treatment of alcoholism.\n    ", "id": "MESH:D003484"}
{"mention": "Hydrogen cyanamide", "mention_text": "Hydrogen cyanamide is a plant growth regulator used in agriculture to induce bud break in fruit trees. Contact with the skin can result in percutaneous absorption of the substance that inhibits aldehyde dehydrogenase and can induce acetaldehyde syndrome in case of alcohol use. The purpose of this report is to describe two cases of a disulfiram-like syndrome following occupational exposure to hydrogen cyanamide. The first case involved a 59-year-old man who used Dormex, which contains hydrogen cyanamide, without protection after consuming a large amount of alcohol during a meal. In less than 1 hour after the ingestion of alcohol, he developed malaise with flushing of the face, tachycardia, and dyspnea. Manifestations regressed spontaneously under surveillance in the hospital. The second case occurred in a 55-year-old farmer following cutaneous contact with Dormex. Five hours after exposure, he developed disulfiram-like syndrome with flushing, tachycardia, and arterial hypotension after consuming three glasses of wine. The patient recovered spontaneously in 3 hours under surveillance in the hospital. These cases confirm the necessity of avoiding alcohol consumption as recommended in the instructions for use of Dormex and of preventing cutaneous contact during use.", "entity": "Cyanamide", "aliases": "Abstem Calcium Carbimide Cyanamide Citrated Salt Colme (1:1) (2:1) Ipsen Brand of Temposil", "definition": "A cyanide compound which has been used as a fertilizer, defoliant and in many manufacturing processes. It often occurs as the calcium salt, sometimes also referred to as cyanamide. The citrated calcium salt is used in the treatment of alcoholism.\n    ", "id": "MESH:D003484"}
{"mention": "aldehyde", "mention_text": "Hydrogen cyanamide is a plant growth regulator used in agriculture to induce bud break in fruit trees. Contact with the skin can result in percutaneous absorption of the substance that inhibits aldehyde dehydrogenase and can induce acetaldehyde syndrome in case of alcohol use. The purpose of this report is to describe two cases of a disulfiram-like syndrome following occupational exposure to hydrogen cyanamide. The first case involved a 59-year-old man who used Dormex, which contains hydrogen cyanamide, without protection after consuming a large amount of alcohol during a meal. In less than 1 hour after the ingestion of alcohol, he developed malaise with flushing of the face, tachycardia, and dyspnea. Manifestations regressed spontaneously under surveillance in the hospital. The second case occurred in a 55-year-old farmer following cutaneous contact with Dormex. Five hours after exposure, he developed disulfiram-like syndrome with flushing, tachycardia, and arterial hypotension after consuming three glasses of wine. The patient recovered spontaneously in 3 hours under surveillance in the hospital. These cases confirm the necessity of avoiding alcohol consumption as recommended in the instructions for use of Dormex and of preventing cutaneous contact during use.", "entity": "Acetaldehyde", "aliases": "Acetaldehyde Ethanal", "definition": "A colorless, flammable liquid used in the manufacture of acetic acid, perfumes, and flavors. It is also an intermediate in the metabolism of alcohol. It has a general narcotic action and also causes irritation of mucous membranes. Large doses may cause death from respiratory paralysis.\n    ", "id": "MESH:D000079"}
{"mention": "acetaldehyde", "mention_text": "Hydrogen cyanamide is a plant growth regulator used in agriculture to induce bud break in fruit trees. Contact with the skin can result in percutaneous absorption of the substance that inhibits aldehyde dehydrogenase and can induce acetaldehyde syndrome in case of alcohol use. The purpose of this report is to describe two cases of a disulfiram-like syndrome following occupational exposure to hydrogen cyanamide. The first case involved a 59-year-old man who used Dormex, which contains hydrogen cyanamide, without protection after consuming a large amount of alcohol during a meal. In less than 1 hour after the ingestion of alcohol, he developed malaise with flushing of the face, tachycardia, and dyspnea. Manifestations regressed spontaneously under surveillance in the hospital. The second case occurred in a 55-year-old farmer following cutaneous contact with Dormex. Five hours after exposure, he developed disulfiram-like syndrome with flushing, tachycardia, and arterial hypotension after consuming three glasses of wine. The patient recovered spontaneously in 3 hours under surveillance in the hospital. These cases confirm the necessity of avoiding alcohol consumption as recommended in the instructions for use of Dormex and of preventing cutaneous contact during use.", "entity": "Acetaldehyde", "aliases": "Acetaldehyde Ethanal", "definition": "A colorless, flammable liquid used in the manufacture of acetic acid, perfumes, and flavors. It is also an intermediate in the metabolism of alcohol. It has a general narcotic action and also causes irritation of mucous membranes. Large doses may cause death from respiratory paralysis.\n    ", "id": "MESH:D000079"}
{"mention": "alcohol", "mention_text": "Hydrogen cyanamide is a plant growth regulator used in agriculture to induce bud break in fruit trees. Contact with the skin can result in percutaneous absorption of the substance that inhibits aldehyde dehydrogenase and can induce acetaldehyde syndrome in case of alcohol use. The purpose of this report is to describe two cases of a disulfiram-like syndrome following occupational exposure to hydrogen cyanamide. The first case involved a 59-year-old man who used Dormex, which contains hydrogen cyanamide, without protection after consuming a large amount of alcohol during a meal. In less than 1 hour after the ingestion of alcohol, he developed malaise with flushing of the face, tachycardia, and dyspnea. Manifestations regressed spontaneously under surveillance in the hospital. The second case occurred in a 55-year-old farmer following cutaneous contact with Dormex. Five hours after exposure, he developed disulfiram-like syndrome with flushing, tachycardia, and arterial hypotension after consuming three glasses of wine. The patient recovered spontaneously in 3 hours under surveillance in the hospital. These cases confirm the necessity of avoiding alcohol consumption as recommended in the instructions for use of Dormex and of preventing cutaneous contact during use.", "entity": "Ethanol", "aliases": "Absolute Alcohol Ethyl Grain Ethanol", "definition": "A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.\n    ", "id": "MESH:D000431"}
{"mention": "disulfiram", "mention_text": "Hydrogen cyanamide is a plant growth regulator used in agriculture to induce bud break in fruit trees. Contact with the skin can result in percutaneous absorption of the substance that inhibits aldehyde dehydrogenase and can induce acetaldehyde syndrome in case of alcohol use. The purpose of this report is to describe two cases of a disulfiram-like syndrome following occupational exposure to hydrogen cyanamide. The first case involved a 59-year-old man who used Dormex, which contains hydrogen cyanamide, without protection after consuming a large amount of alcohol during a meal. In less than 1 hour after the ingestion of alcohol, he developed malaise with flushing of the face, tachycardia, and dyspnea. Manifestations regressed spontaneously under surveillance in the hospital. The second case occurred in a 55-year-old farmer following cutaneous contact with Dormex. Five hours after exposure, he developed disulfiram-like syndrome with flushing, tachycardia, and arterial hypotension after consuming three glasses of wine. The patient recovered spontaneously in 3 hours under surveillance in the hospital. These cases confirm the necessity of avoiding alcohol consumption as recommended in the instructions for use of Dormex and of preventing cutaneous contact during use.", "entity": "Disulfiram", "aliases": "Alcophobin Allphar Brand of Disulfiram Altana Pharma Antabus Antabuse Anticol Bis(diethylthiocarbamoyl) Disulfide Bohm Dicupral Tetraethylthiuram Dumex Esperal Odyssey Orphan Sanofi Synthelabo Tetraethylthioperoxydicarbonic Diamide ((H2N)C(S))2S2 Teturam", "definition": "A carbamate derivative used as an alcohol deterrent. It is a relatively nontoxic substance when administered alone, but markedly alters the intermediary metabolism of alcohol. When alcohol is ingested after administration of disulfiram, blood acetaldehyde concentrations are increased, followed by flushing, systemic vasodilation, respiratory difficulties, nausea, hypotension, and other symptoms (acetaldehyde syndrome). It acts by inhibiting aldehyde dehydrogenase.\n    ", "id": "MESH:D004221"}
{"mention": "hydrogen cyanamide", "mention_text": "Hydrogen cyanamide is a plant growth regulator used in agriculture to induce bud break in fruit trees. Contact with the skin can result in percutaneous absorption of the substance that inhibits aldehyde dehydrogenase and can induce acetaldehyde syndrome in case of alcohol use. The purpose of this report is to describe two cases of a disulfiram-like syndrome following occupational exposure to hydrogen cyanamide. The first case involved a 59-year-old man who used Dormex, which contains hydrogen cyanamide, without protection after consuming a large amount of alcohol during a meal. In less than 1 hour after the ingestion of alcohol, he developed malaise with flushing of the face, tachycardia, and dyspnea. Manifestations regressed spontaneously under surveillance in the hospital. The second case occurred in a 55-year-old farmer following cutaneous contact with Dormex. Five hours after exposure, he developed disulfiram-like syndrome with flushing, tachycardia, and arterial hypotension after consuming three glasses of wine. The patient recovered spontaneously in 3 hours under surveillance in the hospital. These cases confirm the necessity of avoiding alcohol consumption as recommended in the instructions for use of Dormex and of preventing cutaneous contact during use.", "entity": "Cyanamide", "aliases": "Abstem Calcium Carbimide Cyanamide Citrated Salt Colme (1:1) (2:1) Ipsen Brand of Temposil", "definition": "A cyanide compound which has been used as a fertilizer, defoliant and in many manufacturing processes. It often occurs as the calcium salt, sometimes also referred to as cyanamide. The citrated calcium salt is used in the treatment of alcoholism.\n    ", "id": "MESH:D003484"}
{"mention": "Dormex", "mention_text": "Hydrogen cyanamide is a plant growth regulator used in agriculture to induce bud break in fruit trees. Contact with the skin can result in percutaneous absorption of the substance that inhibits aldehyde dehydrogenase and can induce acetaldehyde syndrome in case of alcohol use. The purpose of this report is to describe two cases of a disulfiram-like syndrome following occupational exposure to hydrogen cyanamide. The first case involved a 59-year-old man who used Dormex, which contains hydrogen cyanamide, without protection after consuming a large amount of alcohol during a meal. In less than 1 hour after the ingestion of alcohol, he developed malaise with flushing of the face, tachycardia, and dyspnea. Manifestations regressed spontaneously under surveillance in the hospital. The second case occurred in a 55-year-old farmer following cutaneous contact with Dormex. Five hours after exposure, he developed disulfiram-like syndrome with flushing, tachycardia, and arterial hypotension after consuming three glasses of wine. The patient recovered spontaneously in 3 hours under surveillance in the hospital. These cases confirm the necessity of avoiding alcohol consumption as recommended in the instructions for use of Dormex and of preventing cutaneous contact during use.", "entity": "Cyanamide", "aliases": "Abstem Calcium Carbimide Cyanamide Citrated Salt Colme (1:1) (2:1) Ipsen Brand of Temposil", "definition": "A cyanide compound which has been used as a fertilizer, defoliant and in many manufacturing processes. It often occurs as the calcium salt, sometimes also referred to as cyanamide. The citrated calcium salt is used in the treatment of alcoholism.\n    ", "id": "MESH:D003484"}
{"mention": "flushing of the face", "mention_text": "Hydrogen cyanamide is a plant growth regulator used in agriculture to induce bud break in fruit trees. Contact with the skin can result in percutaneous absorption of the substance that inhibits aldehyde dehydrogenase and can induce acetaldehyde syndrome in case of alcohol use. The purpose of this report is to describe two cases of a disulfiram-like syndrome following occupational exposure to hydrogen cyanamide. The first case involved a 59-year-old man who used Dormex, which contains hydrogen cyanamide, without protection after consuming a large amount of alcohol during a meal. In less than 1 hour after the ingestion of alcohol, he developed malaise with flushing of the face, tachycardia, and dyspnea. Manifestations regressed spontaneously under surveillance in the hospital. The second case occurred in a 55-year-old farmer following cutaneous contact with Dormex. Five hours after exposure, he developed disulfiram-like syndrome with flushing, tachycardia, and arterial hypotension after consuming three glasses of wine. The patient recovered spontaneously in 3 hours under surveillance in the hospital. These cases confirm the necessity of avoiding alcohol consumption as recommended in the instructions for use of Dormex and of preventing cutaneous contact during use.", "entity": "Flushing", "aliases": "Flushing Flushings", "definition": "A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process.\n    ", "id": "MESH:D005483"}
{"mention": "tachycardia", "mention_text": "Hydrogen cyanamide is a plant growth regulator used in agriculture to induce bud break in fruit trees. Contact with the skin can result in percutaneous absorption of the substance that inhibits aldehyde dehydrogenase and can induce acetaldehyde syndrome in case of alcohol use. The purpose of this report is to describe two cases of a disulfiram-like syndrome following occupational exposure to hydrogen cyanamide. The first case involved a 59-year-old man who used Dormex, which contains hydrogen cyanamide, without protection after consuming a large amount of alcohol during a meal. In less than 1 hour after the ingestion of alcohol, he developed malaise with flushing of the face, tachycardia, and dyspnea. Manifestations regressed spontaneously under surveillance in the hospital. The second case occurred in a 55-year-old farmer following cutaneous contact with Dormex. Five hours after exposure, he developed disulfiram-like syndrome with flushing, tachycardia, and arterial hypotension after consuming three glasses of wine. The patient recovered spontaneously in 3 hours under surveillance in the hospital. These cases confirm the necessity of avoiding alcohol consumption as recommended in the instructions for use of Dormex and of preventing cutaneous contact during use.", "entity": "Tachycardia", "aliases": "Tachyarrhythmia Tachyarrhythmias Tachycardia Tachycardias", "definition": "Abnormally rapid heartbeat, usually with a HEART RATE above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia.\n    ", "id": "MESH:D013610"}
{"mention": "dyspnea", "mention_text": "Hydrogen cyanamide is a plant growth regulator used in agriculture to induce bud break in fruit trees. Contact with the skin can result in percutaneous absorption of the substance that inhibits aldehyde dehydrogenase and can induce acetaldehyde syndrome in case of alcohol use. The purpose of this report is to describe two cases of a disulfiram-like syndrome following occupational exposure to hydrogen cyanamide. The first case involved a 59-year-old man who used Dormex, which contains hydrogen cyanamide, without protection after consuming a large amount of alcohol during a meal. In less than 1 hour after the ingestion of alcohol, he developed malaise with flushing of the face, tachycardia, and dyspnea. Manifestations regressed spontaneously under surveillance in the hospital. The second case occurred in a 55-year-old farmer following cutaneous contact with Dormex. Five hours after exposure, he developed disulfiram-like syndrome with flushing, tachycardia, and arterial hypotension after consuming three glasses of wine. The patient recovered spontaneously in 3 hours under surveillance in the hospital. These cases confirm the necessity of avoiding alcohol consumption as recommended in the instructions for use of Dormex and of preventing cutaneous contact during use.", "entity": "Dyspnea", "aliases": "Breath Shortness Shortnesses Breathlessness Breathlessnesses Dyspnea Dyspneas of", "definition": "Difficult or labored breathing.\n    ", "id": "MESH:D004417"}
{"mention": "flushing", "mention_text": "Hydrogen cyanamide is a plant growth regulator used in agriculture to induce bud break in fruit trees. Contact with the skin can result in percutaneous absorption of the substance that inhibits aldehyde dehydrogenase and can induce acetaldehyde syndrome in case of alcohol use. The purpose of this report is to describe two cases of a disulfiram-like syndrome following occupational exposure to hydrogen cyanamide. The first case involved a 59-year-old man who used Dormex, which contains hydrogen cyanamide, without protection after consuming a large amount of alcohol during a meal. In less than 1 hour after the ingestion of alcohol, he developed malaise with flushing of the face, tachycardia, and dyspnea. Manifestations regressed spontaneously under surveillance in the hospital. The second case occurred in a 55-year-old farmer following cutaneous contact with Dormex. Five hours after exposure, he developed disulfiram-like syndrome with flushing, tachycardia, and arterial hypotension after consuming three glasses of wine. The patient recovered spontaneously in 3 hours under surveillance in the hospital. These cases confirm the necessity of avoiding alcohol consumption as recommended in the instructions for use of Dormex and of preventing cutaneous contact during use.", "entity": "Flushing", "aliases": "Flushing Flushings", "definition": "A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process.\n    ", "id": "MESH:D005483"}
{"mention": "arterial hypotension", "mention_text": "Hydrogen cyanamide is a plant growth regulator used in agriculture to induce bud break in fruit trees. Contact with the skin can result in percutaneous absorption of the substance that inhibits aldehyde dehydrogenase and can induce acetaldehyde syndrome in case of alcohol use. The purpose of this report is to describe two cases of a disulfiram-like syndrome following occupational exposure to hydrogen cyanamide. The first case involved a 59-year-old man who used Dormex, which contains hydrogen cyanamide, without protection after consuming a large amount of alcohol during a meal. In less than 1 hour after the ingestion of alcohol, he developed malaise with flushing of the face, tachycardia, and dyspnea. Manifestations regressed spontaneously under surveillance in the hospital. The second case occurred in a 55-year-old farmer following cutaneous contact with Dormex. Five hours after exposure, he developed disulfiram-like syndrome with flushing, tachycardia, and arterial hypotension after consuming three glasses of wine. The patient recovered spontaneously in 3 hours under surveillance in the hospital. These cases confirm the necessity of avoiding alcohol consumption as recommended in the instructions for use of Dormex and of preventing cutaneous contact during use.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "trimipramine", "mention_text": "Repeated trimipramine induces dopamine D2/D3 and alpha1-adrenergic up-regulation.", "entity": "Trimipramine", "aliases": "10,11 Dihydro-N,N,beta-trimethyl-5H-dibenz(b,f)azepine-5-propanamine AWD.pharma Brand of Trimipramine Maleate Apo Trimip Apo-Trimip ApoTrimip Apotex Aventis Azupharma Eldoral Herphonal Hexal Merck dura Neuro Novo Tripramine Novo-Tripramine NovoTripramine Novopharm Nu Pharm Nu-Pharm Nu-Trimipramine NuTrimipramine Odyssey Rhodiapharm Rhone Poulenc Rorer Rhone-Poulenc Rhotrimine Stadapharm Stangyl Surmontil Temmler Trimeprimine Trimidura Trimineurin Trimipramin AZU Stada beta neurazpharm Trimiprami", "definition": "Tricyclic antidepressant similar to IMIPRAMINE, but with more antihistaminic and sedative properties.\n    ", "id": "MESH:D014299"}
{"mention": "dopamine", "mention_text": "Repeated trimipramine induces dopamine D2/D3 and alpha1-adrenergic up-regulation.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "Trimipramine", "mention_text": "Trimipramine (TRI), which shows a clinical antidepressant activity, is chemically related to imipramine but does not inhibit the reuptake of noradrenaline and 5-hydroxytryptamine, nor does it induce beta-adrenergic down-regulation. The mechanism of its antidepressant activity is still unknown. The aim of the present study was to find out whether TRI given repeatedly was able to induce adaptive changes in the dopaminergic and alpha1-adrenergic systems, demonstrated by us previously for various antidepressants. TRI was given to male Wistar rats and male Albino Swiss mice perorally twice daily for 14 days. In the acute experiment TRI (given i.p.) does not antagonize the reserpine hypothermia in mice and does not potentiate the 5-hydroxytryptophan head twitches in rats. TRI given repeatedly to rats increases the locomotor hyperactivity induced by d-amphetamine, quinpirole and (+)-7-hydroxy-dipropyloaminotetralin (dopamine D2 and D3 effects). The stereotypies induced by d-amphetamine or apomorphine are not potentiated by TRI. It increases the behaviour stimulation evoked by phenylephrine (given intraventricularly) in rats, evaluated in the open field test as well as the aggressiveness evoked by clonidine in mice, both these effects being mediated by an alpha1-adrenergic receptor. It may be concluded that, like other tricyclic antidepressants studied previously, TRI given repeatedly increases the responsiveness of brain dopamine D2 and D3 (locomotor activity but not stereotypy) as well as alpha1-adrenergic receptors to their agonists. A question arises whether the reuptake inhibition is of any importance to the adaptive changes induced by repeated antidepressants, suggested to be responsible for the antidepressant activity.", "entity": "Trimipramine", "aliases": "10,11 Dihydro-N,N,beta-trimethyl-5H-dibenz(b,f)azepine-5-propanamine AWD.pharma Brand of Trimipramine Maleate Apo Trimip Apo-Trimip ApoTrimip Apotex Aventis Azupharma Eldoral Herphonal Hexal Merck dura Neuro Novo Tripramine Novo-Tripramine NovoTripramine Novopharm Nu Pharm Nu-Pharm Nu-Trimipramine NuTrimipramine Odyssey Rhodiapharm Rhone Poulenc Rorer Rhone-Poulenc Rhotrimine Stadapharm Stangyl Surmontil Temmler Trimeprimine Trimidura Trimineurin Trimipramin AZU Stada beta neurazpharm Trimiprami", "definition": "Tricyclic antidepressant similar to IMIPRAMINE, but with more antihistaminic and sedative properties.\n    ", "id": "MESH:D014299"}
{"mention": "TRI", "mention_text": "Trimipramine (TRI), which shows a clinical antidepressant activity, is chemically related to imipramine but does not inhibit the reuptake of noradrenaline and 5-hydroxytryptamine, nor does it induce beta-adrenergic down-regulation. The mechanism of its antidepressant activity is still unknown. The aim of the present study was to find out whether TRI given repeatedly was able to induce adaptive changes in the dopaminergic and alpha1-adrenergic systems, demonstrated by us previously for various antidepressants. TRI was given to male Wistar rats and male Albino Swiss mice perorally twice daily for 14 days. In the acute experiment TRI (given i.p.) does not antagonize the reserpine hypothermia in mice and does not potentiate the 5-hydroxytryptophan head twitches in rats. TRI given repeatedly to rats increases the locomotor hyperactivity induced by d-amphetamine, quinpirole and (+)-7-hydroxy-dipropyloaminotetralin (dopamine D2 and D3 effects). The stereotypies induced by d-amphetamine or apomorphine are not potentiated by TRI. It increases the behaviour stimulation evoked by phenylephrine (given intraventricularly) in rats, evaluated in the open field test as well as the aggressiveness evoked by clonidine in mice, both these effects being mediated by an alpha1-adrenergic receptor. It may be concluded that, like other tricyclic antidepressants studied previously, TRI given repeatedly increases the responsiveness of brain dopamine D2 and D3 (locomotor activity but not stereotypy) as well as alpha1-adrenergic receptors to their agonists. A question arises whether the reuptake inhibition is of any importance to the adaptive changes induced by repeated antidepressants, suggested to be responsible for the antidepressant activity.", "entity": "Trimipramine", "aliases": "10,11 Dihydro-N,N,beta-trimethyl-5H-dibenz(b,f)azepine-5-propanamine AWD.pharma Brand of Trimipramine Maleate Apo Trimip Apo-Trimip ApoTrimip Apotex Aventis Azupharma Eldoral Herphonal Hexal Merck dura Neuro Novo Tripramine Novo-Tripramine NovoTripramine Novopharm Nu Pharm Nu-Pharm Nu-Trimipramine NuTrimipramine Odyssey Rhodiapharm Rhone Poulenc Rorer Rhone-Poulenc Rhotrimine Stadapharm Stangyl Surmontil Temmler Trimeprimine Trimidura Trimineurin Trimipramin AZU Stada beta neurazpharm Trimiprami", "definition": "Tricyclic antidepressant similar to IMIPRAMINE, but with more antihistaminic and sedative properties.\n    ", "id": "MESH:D014299"}
{"mention": "antidepressant", "mention_text": "Trimipramine (TRI), which shows a clinical antidepressant activity, is chemically related to imipramine but does not inhibit the reuptake of noradrenaline and 5-hydroxytryptamine, nor does it induce beta-adrenergic down-regulation. The mechanism of its antidepressant activity is still unknown. The aim of the present study was to find out whether TRI given repeatedly was able to induce adaptive changes in the dopaminergic and alpha1-adrenergic systems, demonstrated by us previously for various antidepressants. TRI was given to male Wistar rats and male Albino Swiss mice perorally twice daily for 14 days. In the acute experiment TRI (given i.p.) does not antagonize the reserpine hypothermia in mice and does not potentiate the 5-hydroxytryptophan head twitches in rats. TRI given repeatedly to rats increases the locomotor hyperactivity induced by d-amphetamine, quinpirole and (+)-7-hydroxy-dipropyloaminotetralin (dopamine D2 and D3 effects). The stereotypies induced by d-amphetamine or apomorphine are not potentiated by TRI. It increases the behaviour stimulation evoked by phenylephrine (given intraventricularly) in rats, evaluated in the open field test as well as the aggressiveness evoked by clonidine in mice, both these effects being mediated by an alpha1-adrenergic receptor. It may be concluded that, like other tricyclic antidepressants studied previously, TRI given repeatedly increases the responsiveness of brain dopamine D2 and D3 (locomotor activity but not stereotypy) as well as alpha1-adrenergic receptors to their agonists. A question arises whether the reuptake inhibition is of any importance to the adaptive changes induced by repeated antidepressants, suggested to be responsible for the antidepressant activity.", "entity": "Antidepressive Agents", "aliases": "Agents Antidepressive Antidepressant Drugs Antidepressants Thymoanaleptics Thymoleptics", "definition": "Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.\n    ", "id": "MESH:D000928"}
{"mention": "imipramine", "mention_text": "Trimipramine (TRI), which shows a clinical antidepressant activity, is chemically related to imipramine but does not inhibit the reuptake of noradrenaline and 5-hydroxytryptamine, nor does it induce beta-adrenergic down-regulation. The mechanism of its antidepressant activity is still unknown. The aim of the present study was to find out whether TRI given repeatedly was able to induce adaptive changes in the dopaminergic and alpha1-adrenergic systems, demonstrated by us previously for various antidepressants. TRI was given to male Wistar rats and male Albino Swiss mice perorally twice daily for 14 days. In the acute experiment TRI (given i.p.) does not antagonize the reserpine hypothermia in mice and does not potentiate the 5-hydroxytryptophan head twitches in rats. TRI given repeatedly to rats increases the locomotor hyperactivity induced by d-amphetamine, quinpirole and (+)-7-hydroxy-dipropyloaminotetralin (dopamine D2 and D3 effects). The stereotypies induced by d-amphetamine or apomorphine are not potentiated by TRI. It increases the behaviour stimulation evoked by phenylephrine (given intraventricularly) in rats, evaluated in the open field test as well as the aggressiveness evoked by clonidine in mice, both these effects being mediated by an alpha1-adrenergic receptor. It may be concluded that, like other tricyclic antidepressants studied previously, TRI given repeatedly increases the responsiveness of brain dopamine D2 and D3 (locomotor activity but not stereotypy) as well as alpha1-adrenergic receptors to their agonists. A question arises whether the reuptake inhibition is of any importance to the adaptive changes induced by repeated antidepressants, suggested to be responsible for the antidepressant activity.", "entity": "Imipramine", "aliases": "Imidobenzyle Imipramine Hydrochloride Monohydrochloride Imizin Janimine Melipramine Norchlorimipramine Pryleugan Tofranil", "definition": "The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group.\n    ", "id": "MESH:D007099"}
{"mention": "noradrenaline", "mention_text": "Trimipramine (TRI), which shows a clinical antidepressant activity, is chemically related to imipramine but does not inhibit the reuptake of noradrenaline and 5-hydroxytryptamine, nor does it induce beta-adrenergic down-regulation. The mechanism of its antidepressant activity is still unknown. The aim of the present study was to find out whether TRI given repeatedly was able to induce adaptive changes in the dopaminergic and alpha1-adrenergic systems, demonstrated by us previously for various antidepressants. TRI was given to male Wistar rats and male Albino Swiss mice perorally twice daily for 14 days. In the acute experiment TRI (given i.p.) does not antagonize the reserpine hypothermia in mice and does not potentiate the 5-hydroxytryptophan head twitches in rats. TRI given repeatedly to rats increases the locomotor hyperactivity induced by d-amphetamine, quinpirole and (+)-7-hydroxy-dipropyloaminotetralin (dopamine D2 and D3 effects). The stereotypies induced by d-amphetamine or apomorphine are not potentiated by TRI. It increases the behaviour stimulation evoked by phenylephrine (given intraventricularly) in rats, evaluated in the open field test as well as the aggressiveness evoked by clonidine in mice, both these effects being mediated by an alpha1-adrenergic receptor. It may be concluded that, like other tricyclic antidepressants studied previously, TRI given repeatedly increases the responsiveness of brain dopamine D2 and D3 (locomotor activity but not stereotypy) as well as alpha1-adrenergic receptors to their agonists. A question arises whether the reuptake inhibition is of any importance to the adaptive changes induced by repeated antidepressants, suggested to be responsible for the antidepressant activity.", "entity": "Norepinephrine", "aliases": "Abbott Brand of Levophed Bitartrate Arterenol Aventis Norepinephrine Hydrochloride Noradrenaline Levarterenol Levonor Levonorepinephrine Noradrénaline tartrate renaudin Norepinephrin d-Tartrate (1:1) (+)-Isomer (+,-)-Isomer l-Tartrate Monohydrate (1:2) Renaudin", "definition": "Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.\n    ", "id": "MESH:D009638"}
{"mention": "5-hydroxytryptamine", "mention_text": "Trimipramine (TRI), which shows a clinical antidepressant activity, is chemically related to imipramine but does not inhibit the reuptake of noradrenaline and 5-hydroxytryptamine, nor does it induce beta-adrenergic down-regulation. The mechanism of its antidepressant activity is still unknown. The aim of the present study was to find out whether TRI given repeatedly was able to induce adaptive changes in the dopaminergic and alpha1-adrenergic systems, demonstrated by us previously for various antidepressants. TRI was given to male Wistar rats and male Albino Swiss mice perorally twice daily for 14 days. In the acute experiment TRI (given i.p.) does not antagonize the reserpine hypothermia in mice and does not potentiate the 5-hydroxytryptophan head twitches in rats. TRI given repeatedly to rats increases the locomotor hyperactivity induced by d-amphetamine, quinpirole and (+)-7-hydroxy-dipropyloaminotetralin (dopamine D2 and D3 effects). The stereotypies induced by d-amphetamine or apomorphine are not potentiated by TRI. It increases the behaviour stimulation evoked by phenylephrine (given intraventricularly) in rats, evaluated in the open field test as well as the aggressiveness evoked by clonidine in mice, both these effects being mediated by an alpha1-adrenergic receptor. It may be concluded that, like other tricyclic antidepressants studied previously, TRI given repeatedly increases the responsiveness of brain dopamine D2 and D3 (locomotor activity but not stereotypy) as well as alpha1-adrenergic receptors to their agonists. A question arises whether the reuptake inhibition is of any importance to the adaptive changes induced by repeated antidepressants, suggested to be responsible for the antidepressant activity.", "entity": "Serotonin", "aliases": "3-(2-Aminoethyl)-1H-indol-5-ol 5 Hydroxytryptamine 5-HT 5-Hydroxytryptamine Enteramine Hippophaine Serotonin", "definition": "A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.\n    ", "id": "MESH:D012701"}
{"mention": "antidepressants", "mention_text": "Trimipramine (TRI), which shows a clinical antidepressant activity, is chemically related to imipramine but does not inhibit the reuptake of noradrenaline and 5-hydroxytryptamine, nor does it induce beta-adrenergic down-regulation. The mechanism of its antidepressant activity is still unknown. The aim of the present study was to find out whether TRI given repeatedly was able to induce adaptive changes in the dopaminergic and alpha1-adrenergic systems, demonstrated by us previously for various antidepressants. TRI was given to male Wistar rats and male Albino Swiss mice perorally twice daily for 14 days. In the acute experiment TRI (given i.p.) does not antagonize the reserpine hypothermia in mice and does not potentiate the 5-hydroxytryptophan head twitches in rats. TRI given repeatedly to rats increases the locomotor hyperactivity induced by d-amphetamine, quinpirole and (+)-7-hydroxy-dipropyloaminotetralin (dopamine D2 and D3 effects). The stereotypies induced by d-amphetamine or apomorphine are not potentiated by TRI. It increases the behaviour stimulation evoked by phenylephrine (given intraventricularly) in rats, evaluated in the open field test as well as the aggressiveness evoked by clonidine in mice, both these effects being mediated by an alpha1-adrenergic receptor. It may be concluded that, like other tricyclic antidepressants studied previously, TRI given repeatedly increases the responsiveness of brain dopamine D2 and D3 (locomotor activity but not stereotypy) as well as alpha1-adrenergic receptors to their agonists. A question arises whether the reuptake inhibition is of any importance to the adaptive changes induced by repeated antidepressants, suggested to be responsible for the antidepressant activity.", "entity": "Antidepressive Agents", "aliases": "Agents Antidepressive Antidepressant Drugs Antidepressants Thymoanaleptics Thymoleptics", "definition": "Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.\n    ", "id": "MESH:D000928"}
{"mention": "reserpine", "mention_text": "Trimipramine (TRI), which shows a clinical antidepressant activity, is chemically related to imipramine but does not inhibit the reuptake of noradrenaline and 5-hydroxytryptamine, nor does it induce beta-adrenergic down-regulation. The mechanism of its antidepressant activity is still unknown. The aim of the present study was to find out whether TRI given repeatedly was able to induce adaptive changes in the dopaminergic and alpha1-adrenergic systems, demonstrated by us previously for various antidepressants. TRI was given to male Wistar rats and male Albino Swiss mice perorally twice daily for 14 days. In the acute experiment TRI (given i.p.) does not antagonize the reserpine hypothermia in mice and does not potentiate the 5-hydroxytryptophan head twitches in rats. TRI given repeatedly to rats increases the locomotor hyperactivity induced by d-amphetamine, quinpirole and (+)-7-hydroxy-dipropyloaminotetralin (dopamine D2 and D3 effects). The stereotypies induced by d-amphetamine or apomorphine are not potentiated by TRI. It increases the behaviour stimulation evoked by phenylephrine (given intraventricularly) in rats, evaluated in the open field test as well as the aggressiveness evoked by clonidine in mice, both these effects being mediated by an alpha1-adrenergic receptor. It may be concluded that, like other tricyclic antidepressants studied previously, TRI given repeatedly increases the responsiveness of brain dopamine D2 and D3 (locomotor activity but not stereotypy) as well as alpha1-adrenergic receptors to their agonists. A question arises whether the reuptake inhibition is of any importance to the adaptive changes induced by repeated antidepressants, suggested to be responsible for the antidepressant activity.", "entity": "Reserpine", "aliases": "Raunervil Raupasil Rausedil Rausedyl Reserpine Serpasil Serpivite V Serp V-Serp Vangarde Brand of Vitarine", "definition": "An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use.\n    ", "id": "MESH:D012110"}
{"mention": "hypothermia", "mention_text": "Trimipramine (TRI), which shows a clinical antidepressant activity, is chemically related to imipramine but does not inhibit the reuptake of noradrenaline and 5-hydroxytryptamine, nor does it induce beta-adrenergic down-regulation. The mechanism of its antidepressant activity is still unknown. The aim of the present study was to find out whether TRI given repeatedly was able to induce adaptive changes in the dopaminergic and alpha1-adrenergic systems, demonstrated by us previously for various antidepressants. TRI was given to male Wistar rats and male Albino Swiss mice perorally twice daily for 14 days. In the acute experiment TRI (given i.p.) does not antagonize the reserpine hypothermia in mice and does not potentiate the 5-hydroxytryptophan head twitches in rats. TRI given repeatedly to rats increases the locomotor hyperactivity induced by d-amphetamine, quinpirole and (+)-7-hydroxy-dipropyloaminotetralin (dopamine D2 and D3 effects). The stereotypies induced by d-amphetamine or apomorphine are not potentiated by TRI. It increases the behaviour stimulation evoked by phenylephrine (given intraventricularly) in rats, evaluated in the open field test as well as the aggressiveness evoked by clonidine in mice, both these effects being mediated by an alpha1-adrenergic receptor. It may be concluded that, like other tricyclic antidepressants studied previously, TRI given repeatedly increases the responsiveness of brain dopamine D2 and D3 (locomotor activity but not stereotypy) as well as alpha1-adrenergic receptors to their agonists. A question arises whether the reuptake inhibition is of any importance to the adaptive changes induced by repeated antidepressants, suggested to be responsible for the antidepressant activity.", "entity": "Hypothermia", "aliases": "Accidental Hypothermia Hypothermias", "definition": "Lower than normal body temperature, especially in warm-blooded animals.\n    ", "id": "MESH:D007035"}
{"mention": "5-hydroxytryptophan", "mention_text": "Trimipramine (TRI), which shows a clinical antidepressant activity, is chemically related to imipramine but does not inhibit the reuptake of noradrenaline and 5-hydroxytryptamine, nor does it induce beta-adrenergic down-regulation. The mechanism of its antidepressant activity is still unknown. The aim of the present study was to find out whether TRI given repeatedly was able to induce adaptive changes in the dopaminergic and alpha1-adrenergic systems, demonstrated by us previously for various antidepressants. TRI was given to male Wistar rats and male Albino Swiss mice perorally twice daily for 14 days. In the acute experiment TRI (given i.p.) does not antagonize the reserpine hypothermia in mice and does not potentiate the 5-hydroxytryptophan head twitches in rats. TRI given repeatedly to rats increases the locomotor hyperactivity induced by d-amphetamine, quinpirole and (+)-7-hydroxy-dipropyloaminotetralin (dopamine D2 and D3 effects). The stereotypies induced by d-amphetamine or apomorphine are not potentiated by TRI. It increases the behaviour stimulation evoked by phenylephrine (given intraventricularly) in rats, evaluated in the open field test as well as the aggressiveness evoked by clonidine in mice, both these effects being mediated by an alpha1-adrenergic receptor. It may be concluded that, like other tricyclic antidepressants studied previously, TRI given repeatedly increases the responsiveness of brain dopamine D2 and D3 (locomotor activity but not stereotypy) as well as alpha1-adrenergic receptors to their agonists. A question arises whether the reuptake inhibition is of any importance to the adaptive changes induced by repeated antidepressants, suggested to be responsible for the antidepressant activity.", "entity": "5-Hydroxytryptophan", "aliases": "5 Hydroxytryptophan 5-HTP 5-Hydroxy- Tryptophan 5-Hydroxytryptophan Oxitriptan Oxytryptophan Hydroxy", "definition": "The immediate precursor in the biosynthesis of SEROTONIN from tryptophan. It is used as an antiepileptic and antidepressant.\n    ", "id": "MESH:D006916"}
{"mention": "hyperactivity", "mention_text": "Trimipramine (TRI), which shows a clinical antidepressant activity, is chemically related to imipramine but does not inhibit the reuptake of noradrenaline and 5-hydroxytryptamine, nor does it induce beta-adrenergic down-regulation. The mechanism of its antidepressant activity is still unknown. The aim of the present study was to find out whether TRI given repeatedly was able to induce adaptive changes in the dopaminergic and alpha1-adrenergic systems, demonstrated by us previously for various antidepressants. TRI was given to male Wistar rats and male Albino Swiss mice perorally twice daily for 14 days. In the acute experiment TRI (given i.p.) does not antagonize the reserpine hypothermia in mice and does not potentiate the 5-hydroxytryptophan head twitches in rats. TRI given repeatedly to rats increases the locomotor hyperactivity induced by d-amphetamine, quinpirole and (+)-7-hydroxy-dipropyloaminotetralin (dopamine D2 and D3 effects). The stereotypies induced by d-amphetamine or apomorphine are not potentiated by TRI. It increases the behaviour stimulation evoked by phenylephrine (given intraventricularly) in rats, evaluated in the open field test as well as the aggressiveness evoked by clonidine in mice, both these effects being mediated by an alpha1-adrenergic receptor. It may be concluded that, like other tricyclic antidepressants studied previously, TRI given repeatedly increases the responsiveness of brain dopamine D2 and D3 (locomotor activity but not stereotypy) as well as alpha1-adrenergic receptors to their agonists. A question arises whether the reuptake inhibition is of any importance to the adaptive changes induced by repeated antidepressants, suggested to be responsible for the antidepressant activity.", "entity": "Hyperkinesis", "aliases": "Generalized Hyperkinesia Hyperkinesias Hyperactivity Motor Hyperkinesis Hyperkinetic Movement Movements", "definition": "Excessive movement of muscles of the body as a whole, which may be associated with organic or psychological disorders.\n    ", "id": "MESH:D006948"}
{"mention": "d-amphetamine", "mention_text": "Trimipramine (TRI), which shows a clinical antidepressant activity, is chemically related to imipramine but does not inhibit the reuptake of noradrenaline and 5-hydroxytryptamine, nor does it induce beta-adrenergic down-regulation. The mechanism of its antidepressant activity is still unknown. The aim of the present study was to find out whether TRI given repeatedly was able to induce adaptive changes in the dopaminergic and alpha1-adrenergic systems, demonstrated by us previously for various antidepressants. TRI was given to male Wistar rats and male Albino Swiss mice perorally twice daily for 14 days. In the acute experiment TRI (given i.p.) does not antagonize the reserpine hypothermia in mice and does not potentiate the 5-hydroxytryptophan head twitches in rats. TRI given repeatedly to rats increases the locomotor hyperactivity induced by d-amphetamine, quinpirole and (+)-7-hydroxy-dipropyloaminotetralin (dopamine D2 and D3 effects). The stereotypies induced by d-amphetamine or apomorphine are not potentiated by TRI. It increases the behaviour stimulation evoked by phenylephrine (given intraventricularly) in rats, evaluated in the open field test as well as the aggressiveness evoked by clonidine in mice, both these effects being mediated by an alpha1-adrenergic receptor. It may be concluded that, like other tricyclic antidepressants studied previously, TRI given repeatedly increases the responsiveness of brain dopamine D2 and D3 (locomotor activity but not stereotypy) as well as alpha1-adrenergic receptors to their agonists. A question arises whether the reuptake inhibition is of any importance to the adaptive changes induced by repeated antidepressants, suggested to be responsible for the antidepressant activity.", "entity": "Dextroamphetamine", "aliases": "Celltech Brand of Dextroamphetamine Sulfate Curban Dexamfetamine Dexamphetamine Dexedrine Dextro Amphetamine Dextro-Amphetamine DextroStat GlaxoSmithKline Mallinckrodt Oxydess Pasadena Shire Vortech d d-Amphetamine dextro dextro-Amphetamine", "definition": "The d-form of AMPHETAMINE. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic.\n    ", "id": "MESH:D003913"}
{"mention": "quinpirole", "mention_text": "Trimipramine (TRI), which shows a clinical antidepressant activity, is chemically related to imipramine but does not inhibit the reuptake of noradrenaline and 5-hydroxytryptamine, nor does it induce beta-adrenergic down-regulation. The mechanism of its antidepressant activity is still unknown. The aim of the present study was to find out whether TRI given repeatedly was able to induce adaptive changes in the dopaminergic and alpha1-adrenergic systems, demonstrated by us previously for various antidepressants. TRI was given to male Wistar rats and male Albino Swiss mice perorally twice daily for 14 days. In the acute experiment TRI (given i.p.) does not antagonize the reserpine hypothermia in mice and does not potentiate the 5-hydroxytryptophan head twitches in rats. TRI given repeatedly to rats increases the locomotor hyperactivity induced by d-amphetamine, quinpirole and (+)-7-hydroxy-dipropyloaminotetralin (dopamine D2 and D3 effects). The stereotypies induced by d-amphetamine or apomorphine are not potentiated by TRI. It increases the behaviour stimulation evoked by phenylephrine (given intraventricularly) in rats, evaluated in the open field test as well as the aggressiveness evoked by clonidine in mice, both these effects being mediated by an alpha1-adrenergic receptor. It may be concluded that, like other tricyclic antidepressants studied previously, TRI given repeatedly increases the responsiveness of brain dopamine D2 and D3 (locomotor activity but not stereotypy) as well as alpha1-adrenergic receptors to their agonists. A question arises whether the reuptake inhibition is of any importance to the adaptive changes induced by repeated antidepressants, suggested to be responsible for the antidepressant activity.", "entity": "Quinpirole", "aliases": "Quinpirole Hydrochloride Monohydrochloride", "definition": "A dopamine D2/D3 receptor agonist.\n    ", "id": "MESH:D019257"}
{"mention": "dopamine", "mention_text": "Trimipramine (TRI), which shows a clinical antidepressant activity, is chemically related to imipramine but does not inhibit the reuptake of noradrenaline and 5-hydroxytryptamine, nor does it induce beta-adrenergic down-regulation. The mechanism of its antidepressant activity is still unknown. The aim of the present study was to find out whether TRI given repeatedly was able to induce adaptive changes in the dopaminergic and alpha1-adrenergic systems, demonstrated by us previously for various antidepressants. TRI was given to male Wistar rats and male Albino Swiss mice perorally twice daily for 14 days. In the acute experiment TRI (given i.p.) does not antagonize the reserpine hypothermia in mice and does not potentiate the 5-hydroxytryptophan head twitches in rats. TRI given repeatedly to rats increases the locomotor hyperactivity induced by d-amphetamine, quinpirole and (+)-7-hydroxy-dipropyloaminotetralin (dopamine D2 and D3 effects). The stereotypies induced by d-amphetamine or apomorphine are not potentiated by TRI. It increases the behaviour stimulation evoked by phenylephrine (given intraventricularly) in rats, evaluated in the open field test as well as the aggressiveness evoked by clonidine in mice, both these effects being mediated by an alpha1-adrenergic receptor. It may be concluded that, like other tricyclic antidepressants studied previously, TRI given repeatedly increases the responsiveness of brain dopamine D2 and D3 (locomotor activity but not stereotypy) as well as alpha1-adrenergic receptors to their agonists. A question arises whether the reuptake inhibition is of any importance to the adaptive changes induced by repeated antidepressants, suggested to be responsible for the antidepressant activity.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "apomorphine", "mention_text": "Trimipramine (TRI), which shows a clinical antidepressant activity, is chemically related to imipramine but does not inhibit the reuptake of noradrenaline and 5-hydroxytryptamine, nor does it induce beta-adrenergic down-regulation. The mechanism of its antidepressant activity is still unknown. The aim of the present study was to find out whether TRI given repeatedly was able to induce adaptive changes in the dopaminergic and alpha1-adrenergic systems, demonstrated by us previously for various antidepressants. TRI was given to male Wistar rats and male Albino Swiss mice perorally twice daily for 14 days. In the acute experiment TRI (given i.p.) does not antagonize the reserpine hypothermia in mice and does not potentiate the 5-hydroxytryptophan head twitches in rats. TRI given repeatedly to rats increases the locomotor hyperactivity induced by d-amphetamine, quinpirole and (+)-7-hydroxy-dipropyloaminotetralin (dopamine D2 and D3 effects). The stereotypies induced by d-amphetamine or apomorphine are not potentiated by TRI. It increases the behaviour stimulation evoked by phenylephrine (given intraventricularly) in rats, evaluated in the open field test as well as the aggressiveness evoked by clonidine in mice, both these effects being mediated by an alpha1-adrenergic receptor. It may be concluded that, like other tricyclic antidepressants studied previously, TRI given repeatedly increases the responsiveness of brain dopamine D2 and D3 (locomotor activity but not stereotypy) as well as alpha1-adrenergic receptors to their agonists. A question arises whether the reuptake inhibition is of any importance to the adaptive changes induced by repeated antidepressants, suggested to be responsible for the antidepressant activity.", "entity": "Apomorphine", "aliases": "Aguettant Brand of Apomorphine Hydrochloride Anhydrous Apokinon Apomorphin Teclapharm Apomorphin-Teclapharm ApomorphinTeclapharm Chloride Hemihydrate Britaject Britannia", "definition": "A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use.\n    ", "id": "MESH:D001058"}
{"mention": "phenylephrine", "mention_text": "Trimipramine (TRI), which shows a clinical antidepressant activity, is chemically related to imipramine but does not inhibit the reuptake of noradrenaline and 5-hydroxytryptamine, nor does it induce beta-adrenergic down-regulation. The mechanism of its antidepressant activity is still unknown. The aim of the present study was to find out whether TRI given repeatedly was able to induce adaptive changes in the dopaminergic and alpha1-adrenergic systems, demonstrated by us previously for various antidepressants. TRI was given to male Wistar rats and male Albino Swiss mice perorally twice daily for 14 days. In the acute experiment TRI (given i.p.) does not antagonize the reserpine hypothermia in mice and does not potentiate the 5-hydroxytryptophan head twitches in rats. TRI given repeatedly to rats increases the locomotor hyperactivity induced by d-amphetamine, quinpirole and (+)-7-hydroxy-dipropyloaminotetralin (dopamine D2 and D3 effects). The stereotypies induced by d-amphetamine or apomorphine are not potentiated by TRI. It increases the behaviour stimulation evoked by phenylephrine (given intraventricularly) in rats, evaluated in the open field test as well as the aggressiveness evoked by clonidine in mice, both these effects being mediated by an alpha1-adrenergic receptor. It may be concluded that, like other tricyclic antidepressants studied previously, TRI given repeatedly increases the responsiveness of brain dopamine D2 and D3 (locomotor activity but not stereotypy) as well as alpha1-adrenergic receptors to their agonists. A question arises whether the reuptake inhibition is of any importance to the adaptive changes induced by repeated antidepressants, suggested to be responsible for the antidepressant activity.", "entity": "Phenylephrine", "aliases": "(R)-3-Hydroxy-alpha-((methylamino)methyl)benzenemethanol Metaoxedrin Metasympatol Mezaton Neo Synephrine Neo-Synephrine Neosynephrine Phenylephrine Hydrochloride Tannate", "definition": "An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.\n    ", "id": "MESH:D010656"}
{"mention": "aggressiveness", "mention_text": "Trimipramine (TRI), which shows a clinical antidepressant activity, is chemically related to imipramine but does not inhibit the reuptake of noradrenaline and 5-hydroxytryptamine, nor does it induce beta-adrenergic down-regulation. The mechanism of its antidepressant activity is still unknown. The aim of the present study was to find out whether TRI given repeatedly was able to induce adaptive changes in the dopaminergic and alpha1-adrenergic systems, demonstrated by us previously for various antidepressants. TRI was given to male Wistar rats and male Albino Swiss mice perorally twice daily for 14 days. In the acute experiment TRI (given i.p.) does not antagonize the reserpine hypothermia in mice and does not potentiate the 5-hydroxytryptophan head twitches in rats. TRI given repeatedly to rats increases the locomotor hyperactivity induced by d-amphetamine, quinpirole and (+)-7-hydroxy-dipropyloaminotetralin (dopamine D2 and D3 effects). The stereotypies induced by d-amphetamine or apomorphine are not potentiated by TRI. It increases the behaviour stimulation evoked by phenylephrine (given intraventricularly) in rats, evaluated in the open field test as well as the aggressiveness evoked by clonidine in mice, both these effects being mediated by an alpha1-adrenergic receptor. It may be concluded that, like other tricyclic antidepressants studied previously, TRI given repeatedly increases the responsiveness of brain dopamine D2 and D3 (locomotor activity but not stereotypy) as well as alpha1-adrenergic receptors to their agonists. A question arises whether the reuptake inhibition is of any importance to the adaptive changes induced by repeated antidepressants, suggested to be responsible for the antidepressant activity.", "entity": "Personality Disorders", "aliases": "As If Personality Avoidant Disorder Disorders Impulse Ridden Impulse-Ridden Inadequate Narcissistic", "definition": "A major deviation from normal patterns of behavior.\n    ", "id": "MESH:D010554"}
{"mention": "clonidine", "mention_text": "Trimipramine (TRI), which shows a clinical antidepressant activity, is chemically related to imipramine but does not inhibit the reuptake of noradrenaline and 5-hydroxytryptamine, nor does it induce beta-adrenergic down-regulation. The mechanism of its antidepressant activity is still unknown. The aim of the present study was to find out whether TRI given repeatedly was able to induce adaptive changes in the dopaminergic and alpha1-adrenergic systems, demonstrated by us previously for various antidepressants. TRI was given to male Wistar rats and male Albino Swiss mice perorally twice daily for 14 days. In the acute experiment TRI (given i.p.) does not antagonize the reserpine hypothermia in mice and does not potentiate the 5-hydroxytryptophan head twitches in rats. TRI given repeatedly to rats increases the locomotor hyperactivity induced by d-amphetamine, quinpirole and (+)-7-hydroxy-dipropyloaminotetralin (dopamine D2 and D3 effects). The stereotypies induced by d-amphetamine or apomorphine are not potentiated by TRI. It increases the behaviour stimulation evoked by phenylephrine (given intraventricularly) in rats, evaluated in the open field test as well as the aggressiveness evoked by clonidine in mice, both these effects being mediated by an alpha1-adrenergic receptor. It may be concluded that, like other tricyclic antidepressants studied previously, TRI given repeatedly increases the responsiveness of brain dopamine D2 and D3 (locomotor activity but not stereotypy) as well as alpha1-adrenergic receptors to their agonists. A question arises whether the reuptake inhibition is of any importance to the adaptive changes induced by repeated antidepressants, suggested to be responsible for the antidepressant activity.", "entity": "Clonidine", "aliases": "Boehringer Ingelheim Brand of Clonidine Hydrochloride Catapres Catapresan Catapressan Chlophazolin Clofelin Clofenil Dihydrochloride Monohydrobromide Monohydrochloride Clopheline Dixarit Gemiton Hemiton Isoglaucon Klofelin Klofenil M 5041T M-5041T M5041T ST 155 ST-155 ST155", "definition": "An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.\n    ", "id": "MESH:D003000"}
{"mention": "Ranitidine", "mention_text": "Ranitidine-induced acute interstitial nephritis in a cadaveric renal allograft.", "entity": "Ranitidine", "aliases": "AH 19065 AH-19065 AH19065 Biotidin Hydrochloride Ranitidine N (2-(((5-((Dimethylamino)methyl)-2-furanyl)methyl)thio)ethyl)-N'-methyl-2-nitro-1,1-ethenediamine Ranisen Ranitidin Sostril Zantac Zantic", "definition": "A non-imidazole blocker of those histamine receptors that mediate gastric secretion (H2 receptors). It is used to treat gastrointestinal ulcers.\n    ", "id": "MESH:D011899"}
{"mention": "interstitial nephritis", "mention_text": "Ranitidine-induced acute interstitial nephritis in a cadaveric renal allograft.", "entity": "Nephritis, Interstitial", "aliases": "Interstitial Nephritides Nephritis Tubulointerstitial", "definition": "Inflammation of the interstitial tissue of the kidney. This term is generally used for primary inflammation of KIDNEY TUBULES and/or surrounding interstitium. For primary inflammation of glomerular interstitium, see GLOMERULONEPHRITIS. Infiltration of the inflammatory cells into the interstitial compartment results in EDEMA, increased spaces between the tubules, and tubular renal dysfunction.\n    ", "id": "MESH:D009395"}
{"mention": "Ranitidine", "mention_text": "Ranitidine frequently is used for preventing peptic ulceration after renal transplantation. This drug occasionally has been associated with acute interstitial nephritis in native kidneys. There are no similar reports with renal transplantation. We report a case of ranitidine-induced acute interstitial nephritis in a recipient of a cadaveric renal allograft presenting with acute allograft dysfunction within 48 hours of exposure to the drug. The biopsy specimen showed pathognomonic features, including eosinophilic infiltration of the interstitial compartment. Allograft function improved rapidly and returned to baseline after stopping the drug.", "entity": "Ranitidine", "aliases": "AH 19065 AH-19065 AH19065 Biotidin Hydrochloride Ranitidine N (2-(((5-((Dimethylamino)methyl)-2-furanyl)methyl)thio)ethyl)-N'-methyl-2-nitro-1,1-ethenediamine Ranisen Ranitidin Sostril Zantac Zantic", "definition": "A non-imidazole blocker of those histamine receptors that mediate gastric secretion (H2 receptors). It is used to treat gastrointestinal ulcers.\n    ", "id": "MESH:D011899"}
{"mention": "interstitial nephritis", "mention_text": "Ranitidine frequently is used for preventing peptic ulceration after renal transplantation. This drug occasionally has been associated with acute interstitial nephritis in native kidneys. There are no similar reports with renal transplantation. We report a case of ranitidine-induced acute interstitial nephritis in a recipient of a cadaveric renal allograft presenting with acute allograft dysfunction within 48 hours of exposure to the drug. The biopsy specimen showed pathognomonic features, including eosinophilic infiltration of the interstitial compartment. Allograft function improved rapidly and returned to baseline after stopping the drug.", "entity": "Nephritis, Interstitial", "aliases": "Interstitial Nephritides Nephritis Tubulointerstitial", "definition": "Inflammation of the interstitial tissue of the kidney. This term is generally used for primary inflammation of KIDNEY TUBULES and/or surrounding interstitium. For primary inflammation of glomerular interstitium, see GLOMERULONEPHRITIS. Infiltration of the inflammatory cells into the interstitial compartment results in EDEMA, increased spaces between the tubules, and tubular renal dysfunction.\n    ", "id": "MESH:D009395"}
{"mention": "ranitidine", "mention_text": "Ranitidine frequently is used for preventing peptic ulceration after renal transplantation. This drug occasionally has been associated with acute interstitial nephritis in native kidneys. There are no similar reports with renal transplantation. We report a case of ranitidine-induced acute interstitial nephritis in a recipient of a cadaveric renal allograft presenting with acute allograft dysfunction within 48 hours of exposure to the drug. The biopsy specimen showed pathognomonic features, including eosinophilic infiltration of the interstitial compartment. Allograft function improved rapidly and returned to baseline after stopping the drug.", "entity": "Ranitidine", "aliases": "AH 19065 AH-19065 AH19065 Biotidin Hydrochloride Ranitidine N (2-(((5-((Dimethylamino)methyl)-2-furanyl)methyl)thio)ethyl)-N'-methyl-2-nitro-1,1-ethenediamine Ranisen Ranitidin Sostril Zantac Zantic", "definition": "A non-imidazole blocker of those histamine receptors that mediate gastric secretion (H2 receptors). It is used to treat gastrointestinal ulcers.\n    ", "id": "MESH:D011899"}
{"mention": "doxorubicin", "mention_text": "Late, late doxorubicin cardiotoxicity.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "cardiotoxicity", "mention_text": "Late, late doxorubicin cardiotoxicity.", "entity": "Cardiotoxicity", "aliases": "Cardiac Toxicities Toxicity Cardiotoxicities Cardiotoxicity", "definition": "Damage to the heart or its function secondary to exposure to toxic substances such as drugs used in CHEMOTHERAPY; IMMUNOTHERAPY; or RADIATION.\n    ", "id": "MESH:D066126"}
{"mention": "Cardiac toxicity", "mention_text": "Cardiac toxicity is a major complication which limits the use of adriamycin as a chemotherapeutic agent. Cardiomyopathy is frequent when the total dose exceeds 600 mg/m2 and occurs within one to six months after cessation of therapy. A patient is reported who developed progressive cardiomyopathy two and one-half years after receiving 580 mg/m2 which apparently represents late, late cardiotoxicity.", "entity": "Cardiotoxicity", "aliases": "Cardiac Toxicities Toxicity Cardiotoxicities Cardiotoxicity", "definition": "Damage to the heart or its function secondary to exposure to toxic substances such as drugs used in CHEMOTHERAPY; IMMUNOTHERAPY; or RADIATION.\n    ", "id": "MESH:D066126"}
{"mention": "adriamycin", "mention_text": "Cardiac toxicity is a major complication which limits the use of adriamycin as a chemotherapeutic agent. Cardiomyopathy is frequent when the total dose exceeds 600 mg/m2 and occurs within one to six months after cessation of therapy. A patient is reported who developed progressive cardiomyopathy two and one-half years after receiving 580 mg/m2 which apparently represents late, late cardiotoxicity.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "Cardiomyopathy", "mention_text": "Cardiac toxicity is a major complication which limits the use of adriamycin as a chemotherapeutic agent. Cardiomyopathy is frequent when the total dose exceeds 600 mg/m2 and occurs within one to six months after cessation of therapy. A patient is reported who developed progressive cardiomyopathy two and one-half years after receiving 580 mg/m2 which apparently represents late, late cardiotoxicity.", "entity": "Cardiomyopathies", "aliases": "Cardiomyopathies Primary Secondary Cardiomyopathy Disease Myocardial Diseases Myocardiopathies Myocardiopathy", "definition": "A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).\n    ", "id": "MESH:D009202"}
{"mention": "cardiomyopathy", "mention_text": "Cardiac toxicity is a major complication which limits the use of adriamycin as a chemotherapeutic agent. Cardiomyopathy is frequent when the total dose exceeds 600 mg/m2 and occurs within one to six months after cessation of therapy. A patient is reported who developed progressive cardiomyopathy two and one-half years after receiving 580 mg/m2 which apparently represents late, late cardiotoxicity.", "entity": "Cardiomyopathies", "aliases": "Cardiomyopathies Primary Secondary Cardiomyopathy Disease Myocardial Diseases Myocardiopathies Myocardiopathy", "definition": "A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).\n    ", "id": "MESH:D009202"}
{"mention": "cardiotoxicity", "mention_text": "Cardiac toxicity is a major complication which limits the use of adriamycin as a chemotherapeutic agent. Cardiomyopathy is frequent when the total dose exceeds 600 mg/m2 and occurs within one to six months after cessation of therapy. A patient is reported who developed progressive cardiomyopathy two and one-half years after receiving 580 mg/m2 which apparently represents late, late cardiotoxicity.", "entity": "Cardiotoxicity", "aliases": "Cardiac Toxicities Toxicity Cardiotoxicities Cardiotoxicity", "definition": "Damage to the heart or its function secondary to exposure to toxic substances such as drugs used in CHEMOTHERAPY; IMMUNOTHERAPY; or RADIATION.\n    ", "id": "MESH:D066126"}
{"mention": "Acetazolamide", "mention_text": "Acetazolamide-induced nephrolithiasis: implications for treatment of neuromuscular disorders.", "entity": "Acetazolamide", "aliases": "Acetadiazol Acetazolam Acetazolamide Apotex Brand Chiesi Dioptic Grin ICN Jumer Llorens Medphano Novopharm Orion Sodium (Sterile) Wassermann Monosodium Salt Ak Zol Ak-Zol AkZol Apo Apo-Acetazolamide ApoAcetazolamide of Ciba Vision Cyanamid Preparation Diacarb Diamox Diuramide Défiltran Edemox Glauconox Glaupax Huma Zolamide Huma-Zolamide HumaZolamide Lederle Storz Théraplix Whelehan Wyeth", "definition": "One of the CARBONIC ANHYDRASE INHIBITORS that is sometimes effective against absence seizures. It is sometimes useful also as an adjunct in the treatment of tonic-clonic, myoclonic, and atonic seizures, particularly in women whose seizures occur or are exacerbated at specific times in the menstrual cycle. However, its usefulness is transient often because of rapid development of tolerance. Its antiepileptic effect may be due to its inhibitory effect on brain carbonic anhydrase, which leads to an increased transneuronal chloride gradient, increased chloride current, and increased inhibition. (From Smith and Reynard, Textbook of Pharmacology, 1991, p337)\n    ", "id": "MESH:D000086"}
{"mention": "nephrolithiasis", "mention_text": "Acetazolamide-induced nephrolithiasis: implications for treatment of neuromuscular disorders.", "entity": "Nephrolithiasis", "aliases": "Nephrolithiasis", "definition": "Formation of stones in the KIDNEY.\n    ", "id": "MESH:D053040"}
{"mention": "neuromuscular disorders", "mention_text": "Acetazolamide-induced nephrolithiasis: implications for treatment of neuromuscular disorders.", "entity": "Neuromuscular Diseases", "aliases": "Amyotonia Congenita Benign Fasciculation-Cramp Syndrome Syndromes Cramp Fasciculation Cramp-Fasciculation Foley Denny Brown Foley-Denny-Brown Neuromuscular Disease Diseases Oppenheim Oppenheim's Oppenheims", "definition": "A general term encompassing lower MOTOR NEURON DISEASE; PERIPHERAL NERVOUS SYSTEM DISEASES; and certain MUSCULAR DISEASES. Manifestations include MUSCLE WEAKNESS; FASCICULATION; muscle ATROPHY; SPASM; MYOKYMIA; MUSCLE HYPERTONIA, myalgias, and MUSCLE HYPOTONIA.\n    ", "id": "MESH:D009468"}
{"mention": "nephrolithiasis", "mention_text": "Carbonic anhydrase inhibitors can cause nephrolithiasis. We studied 20 patients receiving long-term carbonic anhydrase inhibitor treatment for periodic paralysis and myotonia. Three patients on acetazolamide (15%) developed renal calculi. Extracorporeal lithotripsy successfully removed a renal calculus in one patient and surgery removed a staghorn calculus in another, permitting continued treatment. Renal function remained normal in all patients. Nephrolithiasis is a complication of acetazolamide but does not preclude its use.", "entity": "Nephrolithiasis", "aliases": "Nephrolithiasis", "definition": "Formation of stones in the KIDNEY.\n    ", "id": "MESH:D053040"}
{"mention": "paralysis", "mention_text": "Carbonic anhydrase inhibitors can cause nephrolithiasis. We studied 20 patients receiving long-term carbonic anhydrase inhibitor treatment for periodic paralysis and myotonia. Three patients on acetazolamide (15%) developed renal calculi. Extracorporeal lithotripsy successfully removed a renal calculus in one patient and surgery removed a staghorn calculus in another, permitting continued treatment. Renal function remained normal in all patients. Nephrolithiasis is a complication of acetazolamide but does not preclude its use.", "entity": "Paralysis", "aliases": "Palsies Palsy Paralyses Paralysis Todd Todd's Plegia Plegias Todds", "definition": "A general term most often used to describe severe or complete loss of muscle strength due to motor system disease from the level of the cerebral cortex to the muscle fiber. This term may also occasionally refer to a loss of sensory function. (From Adams et al., Principles of Neurology, 6th ed, p45)\n    ", "id": "MESH:D010243"}
{"mention": "myotonia", "mention_text": "Carbonic anhydrase inhibitors can cause nephrolithiasis. We studied 20 patients receiving long-term carbonic anhydrase inhibitor treatment for periodic paralysis and myotonia. Three patients on acetazolamide (15%) developed renal calculi. Extracorporeal lithotripsy successfully removed a renal calculus in one patient and surgery removed a staghorn calculus in another, permitting continued treatment. Renal function remained normal in all patients. Nephrolithiasis is a complication of acetazolamide but does not preclude its use.", "entity": "Myotonia", "aliases": "Myotonia Percussion Myotonias Myotonic Phenomenon Phenomenons", "definition": "Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of MYOTONIC DISORDERS.\n    ", "id": "MESH:D009222"}
{"mention": "acetazolamide", "mention_text": "Carbonic anhydrase inhibitors can cause nephrolithiasis. We studied 20 patients receiving long-term carbonic anhydrase inhibitor treatment for periodic paralysis and myotonia. Three patients on acetazolamide (15%) developed renal calculi. Extracorporeal lithotripsy successfully removed a renal calculus in one patient and surgery removed a staghorn calculus in another, permitting continued treatment. Renal function remained normal in all patients. Nephrolithiasis is a complication of acetazolamide but does not preclude its use.", "entity": "Acetazolamide", "aliases": "Acetadiazol Acetazolam Acetazolamide Apotex Brand Chiesi Dioptic Grin ICN Jumer Llorens Medphano Novopharm Orion Sodium (Sterile) Wassermann Monosodium Salt Ak Zol Ak-Zol AkZol Apo Apo-Acetazolamide ApoAcetazolamide of Ciba Vision Cyanamid Preparation Diacarb Diamox Diuramide Défiltran Edemox Glauconox Glaupax Huma Zolamide Huma-Zolamide HumaZolamide Lederle Storz Théraplix Whelehan Wyeth", "definition": "One of the CARBONIC ANHYDRASE INHIBITORS that is sometimes effective against absence seizures. It is sometimes useful also as an adjunct in the treatment of tonic-clonic, myoclonic, and atonic seizures, particularly in women whose seizures occur or are exacerbated at specific times in the menstrual cycle. However, its usefulness is transient often because of rapid development of tolerance. Its antiepileptic effect may be due to its inhibitory effect on brain carbonic anhydrase, which leads to an increased transneuronal chloride gradient, increased chloride current, and increased inhibition. (From Smith and Reynard, Textbook of Pharmacology, 1991, p337)\n    ", "id": "MESH:D000086"}
{"mention": "renal calculi", "mention_text": "Carbonic anhydrase inhibitors can cause nephrolithiasis. We studied 20 patients receiving long-term carbonic anhydrase inhibitor treatment for periodic paralysis and myotonia. Three patients on acetazolamide (15%) developed renal calculi. Extracorporeal lithotripsy successfully removed a renal calculus in one patient and surgery removed a staghorn calculus in another, permitting continued treatment. Renal function remained normal in all patients. Nephrolithiasis is a complication of acetazolamide but does not preclude its use.", "entity": "Kidney Calculi", "aliases": "Calculi Kidney Renal Calculus Stone Stones Nephrolith", "definition": "Stones in the KIDNEY, usually formed in the urine-collecting area of the kidney (KIDNEY PELVIS). Their sizes vary and most contains CALCIUM OXALATE.\n    ", "id": "MESH:D007669"}
{"mention": "renal calculus", "mention_text": "Carbonic anhydrase inhibitors can cause nephrolithiasis. We studied 20 patients receiving long-term carbonic anhydrase inhibitor treatment for periodic paralysis and myotonia. Three patients on acetazolamide (15%) developed renal calculi. Extracorporeal lithotripsy successfully removed a renal calculus in one patient and surgery removed a staghorn calculus in another, permitting continued treatment. Renal function remained normal in all patients. Nephrolithiasis is a complication of acetazolamide but does not preclude its use.", "entity": "Kidney Calculi", "aliases": "Calculi Kidney Renal Calculus Stone Stones Nephrolith", "definition": "Stones in the KIDNEY, usually formed in the urine-collecting area of the kidney (KIDNEY PELVIS). Their sizes vary and most contains CALCIUM OXALATE.\n    ", "id": "MESH:D007669"}
{"mention": "calculus", "mention_text": "Carbonic anhydrase inhibitors can cause nephrolithiasis. We studied 20 patients receiving long-term carbonic anhydrase inhibitor treatment for periodic paralysis and myotonia. Three patients on acetazolamide (15%) developed renal calculi. Extracorporeal lithotripsy successfully removed a renal calculus in one patient and surgery removed a staghorn calculus in another, permitting continued treatment. Renal function remained normal in all patients. Nephrolithiasis is a complication of acetazolamide but does not preclude its use.", "entity": "Calculi", "aliases": "Biliary or Urinary Stones Calculi Calculus", "definition": "An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones.\n    ", "id": "MESH:D002137"}
{"mention": "Nephrolithiasis", "mention_text": "Carbonic anhydrase inhibitors can cause nephrolithiasis. We studied 20 patients receiving long-term carbonic anhydrase inhibitor treatment for periodic paralysis and myotonia. Three patients on acetazolamide (15%) developed renal calculi. Extracorporeal lithotripsy successfully removed a renal calculus in one patient and surgery removed a staghorn calculus in another, permitting continued treatment. Renal function remained normal in all patients. Nephrolithiasis is a complication of acetazolamide but does not preclude its use.", "entity": "Nephrolithiasis", "aliases": "Nephrolithiasis", "definition": "Formation of stones in the KIDNEY.\n    ", "id": "MESH:D053040"}
{"mention": "scabies", "mention_text": "Is the treatment of scabies hazardous?", "entity": "Scabies", "aliases": "Mange Sarcoptic Scabies", "definition": "A contagious cutaneous inflammation caused by the bite of the mite SARCOPTES SCABIEI. It is characterized by pruritic papular eruptions and burrows and affects primarily the axillae, elbows, wrists, and genitalia, although it can spread to cover the entire body.\n    ", "id": "MESH:D012532"}
{"mention": "scabies", "mention_text": "Treatment for scabies is usually initiated by general practitioners; most consider lindane (gamma benzene hexachloride) the treatment of choice. Lindane is also widely used as an agricultural and industrial pesticide, and as a result the toxic profile of this insecticide is well understood. Evidence is accumulating that lindane can be toxic to the central nervous system and may be associated with aplastic anaemia. Preparations containing lindane continue to be sold over the counter and may represent a hazard to poorly informed patients. This literature review suggests that general practitioners should prescribe scabicides with increased caution for certain at-risk groups, and give adequate warnings regarding potential toxicity.", "entity": "Scabies", "aliases": "Mange Sarcoptic Scabies", "definition": "A contagious cutaneous inflammation caused by the bite of the mite SARCOPTES SCABIEI. It is characterized by pruritic papular eruptions and burrows and affects primarily the axillae, elbows, wrists, and genitalia, although it can spread to cover the entire body.\n    ", "id": "MESH:D012532"}
{"mention": "lindane", "mention_text": "Treatment for scabies is usually initiated by general practitioners; most consider lindane (gamma benzene hexachloride) the treatment of choice. Lindane is also widely used as an agricultural and industrial pesticide, and as a result the toxic profile of this insecticide is well understood. Evidence is accumulating that lindane can be toxic to the central nervous system and may be associated with aplastic anaemia. Preparations containing lindane continue to be sold over the counter and may represent a hazard to poorly informed patients. This literature review suggests that general practitioners should prescribe scabicides with increased caution for certain at-risk groups, and give adequate warnings regarding potential toxicity.", "entity": "Lindane", "aliases": "BHC Insecticide Benzene Hexachloride Chinoin Brand of Lindane Delitex Gamma 666 Gamma-666 Gamma666 Gammexane Hexachlorane gamma-Benzene Hexachlorocyclohexane Infectopharm Jacutin Kwell PMS PMS-Lindane PMSLindane Pharmascience Scabecid Scabene Scabisan Stiefel Tetocid gamma gamma-Hexachlorocyclohexane", "definition": "An organochlorine insecticide that has been used as a pediculicide and a scabicide. It has been shown to cause cancer.\n    ", "id": "MESH:D001556"}
{"mention": "gamma benzene hexachloride", "mention_text": "Treatment for scabies is usually initiated by general practitioners; most consider lindane (gamma benzene hexachloride) the treatment of choice. Lindane is also widely used as an agricultural and industrial pesticide, and as a result the toxic profile of this insecticide is well understood. Evidence is accumulating that lindane can be toxic to the central nervous system and may be associated with aplastic anaemia. Preparations containing lindane continue to be sold over the counter and may represent a hazard to poorly informed patients. This literature review suggests that general practitioners should prescribe scabicides with increased caution for certain at-risk groups, and give adequate warnings regarding potential toxicity.", "entity": "Lindane", "aliases": "BHC Insecticide Benzene Hexachloride Chinoin Brand of Lindane Delitex Gamma 666 Gamma-666 Gamma666 Gammexane Hexachlorane gamma-Benzene Hexachlorocyclohexane Infectopharm Jacutin Kwell PMS PMS-Lindane PMSLindane Pharmascience Scabecid Scabene Scabisan Stiefel Tetocid gamma gamma-Hexachlorocyclohexane", "definition": "An organochlorine insecticide that has been used as a pediculicide and a scabicide. It has been shown to cause cancer.\n    ", "id": "MESH:D001556"}
{"mention": "Lindane", "mention_text": "Treatment for scabies is usually initiated by general practitioners; most consider lindane (gamma benzene hexachloride) the treatment of choice. Lindane is also widely used as an agricultural and industrial pesticide, and as a result the toxic profile of this insecticide is well understood. Evidence is accumulating that lindane can be toxic to the central nervous system and may be associated with aplastic anaemia. Preparations containing lindane continue to be sold over the counter and may represent a hazard to poorly informed patients. This literature review suggests that general practitioners should prescribe scabicides with increased caution for certain at-risk groups, and give adequate warnings regarding potential toxicity.", "entity": "Lindane", "aliases": "BHC Insecticide Benzene Hexachloride Chinoin Brand of Lindane Delitex Gamma 666 Gamma-666 Gamma666 Gammexane Hexachlorane gamma-Benzene Hexachlorocyclohexane Infectopharm Jacutin Kwell PMS PMS-Lindane PMSLindane Pharmascience Scabecid Scabene Scabisan Stiefel Tetocid gamma gamma-Hexachlorocyclohexane", "definition": "An organochlorine insecticide that has been used as a pediculicide and a scabicide. It has been shown to cause cancer.\n    ", "id": "MESH:D001556"}
{"mention": "toxic to the central nervous system", "mention_text": "Treatment for scabies is usually initiated by general practitioners; most consider lindane (gamma benzene hexachloride) the treatment of choice. Lindane is also widely used as an agricultural and industrial pesticide, and as a result the toxic profile of this insecticide is well understood. Evidence is accumulating that lindane can be toxic to the central nervous system and may be associated with aplastic anaemia. Preparations containing lindane continue to be sold over the counter and may represent a hazard to poorly informed patients. This literature review suggests that general practitioners should prescribe scabicides with increased caution for certain at-risk groups, and give adequate warnings regarding potential toxicity.", "entity": "Central Nervous System Diseases", "aliases": "CNS Disease Diseases Central Nervous System Disorders", "definition": "Diseases of any component of the brain (including the cerebral hemispheres, diencephalon, brain stem, and cerebellum) or the spinal cord.\n    ", "id": "MESH:D002493"}
{"mention": "aplastic anaemia", "mention_text": "Treatment for scabies is usually initiated by general practitioners; most consider lindane (gamma benzene hexachloride) the treatment of choice. Lindane is also widely used as an agricultural and industrial pesticide, and as a result the toxic profile of this insecticide is well understood. Evidence is accumulating that lindane can be toxic to the central nervous system and may be associated with aplastic anaemia. Preparations containing lindane continue to be sold over the counter and may represent a hazard to poorly informed patients. This literature review suggests that general practitioners should prescribe scabicides with increased caution for certain at-risk groups, and give adequate warnings regarding potential toxicity.", "entity": "Anemia, Aplastic", "aliases": "Anemia Aplastic Hypoplastic Anemias", "definition": "A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements.\n    ", "id": "MESH:D000741"}
{"mention": "toxicity", "mention_text": "Treatment for scabies is usually initiated by general practitioners; most consider lindane (gamma benzene hexachloride) the treatment of choice. Lindane is also widely used as an agricultural and industrial pesticide, and as a result the toxic profile of this insecticide is well understood. Evidence is accumulating that lindane can be toxic to the central nervous system and may be associated with aplastic anaemia. Preparations containing lindane continue to be sold over the counter and may represent a hazard to poorly informed patients. This literature review suggests that general practitioners should prescribe scabicides with increased caution for certain at-risk groups, and give adequate warnings regarding potential toxicity.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "masseter spasm", "mention_text": "Anaesthetists' nightmare: masseter spasm after induction in an undiagnosed case of myotonia congenita.", "entity": "Trismus", "aliases": "Lock Jaw Lockjaw Masseter Muscle Spasm Spasms Trismus", "definition": "Spasmodic contraction of the masseter muscle resulting in forceful jaw closure. This may be seen with a variety of diseases, including TETANUS, as a complication of radiation therapy, trauma, or in association with neoplastic conditions.\n    ", "id": "MESH:D014313"}
{"mention": "myotonia congenita", "mention_text": "Anaesthetists' nightmare: masseter spasm after induction in an undiagnosed case of myotonia congenita.", "entity": "Myotonia Congenita", "aliases": "Batten Turner Congenital Myopathy Batten-Turner Becker Disease Generalized Myotonia Thomsen Thomsen's Thomsens of Myotonias Congenita Autosomal Dominant Recessive Levior", "definition": "Inherited myotonic disorders with early childhood onset MYOTONIA. Muscular hypertrophy is common and myotonia may impair ambulation and other movements. It is classified as Thomsen (autosomal dominant) or Becker (autosomal recessive) generalized myotonia mainly based on the inheritance pattern. Becker type is also clinically more severe. An autosomal dominant variant with milder symptoms and later onset is known as myotonia levior. Mutations in the voltage-dependent skeletal muscle chloride channel are associated with the disorders.\n    ", "id": "MESH:D009224"}
{"mention": "myotonia congenita", "mention_text": "We report an undiagnosed case of myotonia congenita in a 24-year-old previously healthy primigravida, who developed life threatening masseter spasm following a standard dose of intravenous suxamethonium for induction of anaesthesia. Neither the patient nor the anaesthetist was aware of the diagnosis before this potentially lethal complication occurred.", "entity": "Myotonia Congenita", "aliases": "Batten Turner Congenital Myopathy Batten-Turner Becker Disease Generalized Myotonia Thomsen Thomsen's Thomsens of Myotonias Congenita Autosomal Dominant Recessive Levior", "definition": "Inherited myotonic disorders with early childhood onset MYOTONIA. Muscular hypertrophy is common and myotonia may impair ambulation and other movements. It is classified as Thomsen (autosomal dominant) or Becker (autosomal recessive) generalized myotonia mainly based on the inheritance pattern. Becker type is also clinically more severe. An autosomal dominant variant with milder symptoms and later onset is known as myotonia levior. Mutations in the voltage-dependent skeletal muscle chloride channel are associated with the disorders.\n    ", "id": "MESH:D009224"}
{"mention": "masseter spasm", "mention_text": "We report an undiagnosed case of myotonia congenita in a 24-year-old previously healthy primigravida, who developed life threatening masseter spasm following a standard dose of intravenous suxamethonium for induction of anaesthesia. Neither the patient nor the anaesthetist was aware of the diagnosis before this potentially lethal complication occurred.", "entity": "Trismus", "aliases": "Lock Jaw Lockjaw Masseter Muscle Spasm Spasms Trismus", "definition": "Spasmodic contraction of the masseter muscle resulting in forceful jaw closure. This may be seen with a variety of diseases, including TETANUS, as a complication of radiation therapy, trauma, or in association with neoplastic conditions.\n    ", "id": "MESH:D014313"}
{"mention": "suxamethonium", "mention_text": "We report an undiagnosed case of myotonia congenita in a 24-year-old previously healthy primigravida, who developed life threatening masseter spasm following a standard dose of intravenous suxamethonium for induction of anaesthesia. Neither the patient nor the anaesthetist was aware of the diagnosis before this potentially lethal complication occurred.", "entity": "Succinylcholine", "aliases": "Anectine Bromide Suxamethonium Celocurine Dibromide Succinylcholine Dichloride Diiodide Diperchlorate Ditilin Listenon Lysthenon Myorelaxin Quelicin Succicuran Chloride Di H2O Di-H2O Iodide Succinyldicholine", "definition": "A quaternary skeletal muscle relaxant usually used in the form of its bromide, chloride, or iodide. It is a depolarizing relaxant, acting in about 30 seconds and with a duration of effect averaging three to five minutes. Succinylcholine is used in surgical, anesthetic, and other procedures in which a brief period of muscle relaxation is called for.\n    ", "id": "MESH:D013390"}
{"mention": "Toxicity", "mention_text": "Toxicity in rhesus monkeys following administration of the 8-aminoquinoline 8-[(4-amino-l-methylbutyl)amino]- 5-(l-hexyloxy)-6-methoxy-4-methylquinoline (WR242511).", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "8-aminoquinoline", "mention_text": "Toxicity in rhesus monkeys following administration of the 8-aminoquinoline 8-[(4-amino-l-methylbutyl)amino]- 5-(l-hexyloxy)-6-methoxy-4-methylquinoline (WR242511).", "entity": "8-aminoquinoline", "aliases": "8-((6-(diethylamino)hexyl)amino)-6-methoxy-4-methylquinoline 8-(6-diethylaminohexylamino)-6-methoxy-4-methylquinoline dihydrochloride 8-aminoquinoline 8-quinolinamine N,N-diethyl-N'-(6-methoxy-4-methyl-8-quinolinyl)-1,6- hexanediamine WR 006026 6026 WR-006026 WR-6026 WR006026 WR6026 sitamaquine", "definition": "", "id": "MESH:C080436"}
{"mention": "8-[(4-amino-l-methylbutyl)amino]- 5-(l-hexyloxy)-6-methoxy-4-methylquinoline", "mention_text": "Toxicity in rhesus monkeys following administration of the 8-aminoquinoline 8-[(4-amino-l-methylbutyl)amino]- 5-(l-hexyloxy)-6-methoxy-4-methylquinoline (WR242511).", "entity": "WR 242511", "aliases": "WR 242511 phosphate (1:2) salt WR-242511 WR242511", "definition": "", "id": "MESH:C068820"}
{"mention": "WR242511", "mention_text": "Toxicity in rhesus monkeys following administration of the 8-aminoquinoline 8-[(4-amino-l-methylbutyl)amino]- 5-(l-hexyloxy)-6-methoxy-4-methylquinoline (WR242511).", "entity": "WR 242511", "aliases": "WR 242511 phosphate (1:2) salt WR-242511 WR242511", "definition": "", "id": "MESH:C068820"}
{"mention": "toxicity", "mention_text": "INTRODUCTION: Many substances that form methemoglobin (MHb) effectively counter cyanide (CN) toxicity. Although MHb formers are generally applied as treatments for CN poisoning, it has been proposed that a stable, long-acting MHb former could serve as a CN pretreatment. Using this rationale, the 8-aminoquinoline WR242511, a potent long-lasting MHb former in rodents and beagle dogs, was studied in the rhesus monkey for advanced development as a potential CN pretreatment. METHODS: In this study, WR242511 was administered intravenously (IV) in 2 female and 4 male rhesus monkeys in doses of 3.5 and/or 7.0 mg/kg; a single male also received WR242511 orally (PO) at 7.0 mg/kg. Health status and MHb levels were monitored following exposure. RESULTS: The selected doses of WR242511, which produced significant methemoglobinemia in beagle dogs in earlier studies conducted elsewhere, produced very little MHb (mean < 2.0%) in the rhesus monkey. Furthermore, transient hemoglobinuria was noted approximately 60 minutes postinjection of WR242511 (3.5 or 7.0 mg/kg), and 2 lethalities occurred (one IV and one PO) following the 7.0 mg/kg dose. Myoglobinuria was also observed following the 7.0 mg/kg dose. Histopathology analyses in the 2 animals that died revealed liver and kidney toxicity, with greater severity in the orally-treated animal. CONCLUSIONS: These data demonstrate direct and/or indirect drug-induced toxicity. It is concluded that WR242511 should not be pursued as a pretreatment for CN poisoning unless the anti-CN characteristics of this compound can be successfully dissociated from those producing undesirable toxicity.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "poisoning", "mention_text": "INTRODUCTION: Many substances that form methemoglobin (MHb) effectively counter cyanide (CN) toxicity. Although MHb formers are generally applied as treatments for CN poisoning, it has been proposed that a stable, long-acting MHb former could serve as a CN pretreatment. Using this rationale, the 8-aminoquinoline WR242511, a potent long-lasting MHb former in rodents and beagle dogs, was studied in the rhesus monkey for advanced development as a potential CN pretreatment. METHODS: In this study, WR242511 was administered intravenously (IV) in 2 female and 4 male rhesus monkeys in doses of 3.5 and/or 7.0 mg/kg; a single male also received WR242511 orally (PO) at 7.0 mg/kg. Health status and MHb levels were monitored following exposure. RESULTS: The selected doses of WR242511, which produced significant methemoglobinemia in beagle dogs in earlier studies conducted elsewhere, produced very little MHb (mean < 2.0%) in the rhesus monkey. Furthermore, transient hemoglobinuria was noted approximately 60 minutes postinjection of WR242511 (3.5 or 7.0 mg/kg), and 2 lethalities occurred (one IV and one PO) following the 7.0 mg/kg dose. Myoglobinuria was also observed following the 7.0 mg/kg dose. Histopathology analyses in the 2 animals that died revealed liver and kidney toxicity, with greater severity in the orally-treated animal. CONCLUSIONS: These data demonstrate direct and/or indirect drug-induced toxicity. It is concluded that WR242511 should not be pursued as a pretreatment for CN poisoning unless the anti-CN characteristics of this compound can be successfully dissociated from those producing undesirable toxicity.", "entity": "Poisoning", "aliases": "Poisoning Poisonings", "definition": "A condition or physical state produced by the ingestion, injection, inhalation of or exposure to a deleterious agent.\n    ", "id": "MESH:D011041"}
{"mention": "8-aminoquinoline", "mention_text": "INTRODUCTION: Many substances that form methemoglobin (MHb) effectively counter cyanide (CN) toxicity. Although MHb formers are generally applied as treatments for CN poisoning, it has been proposed that a stable, long-acting MHb former could serve as a CN pretreatment. Using this rationale, the 8-aminoquinoline WR242511, a potent long-lasting MHb former in rodents and beagle dogs, was studied in the rhesus monkey for advanced development as a potential CN pretreatment. METHODS: In this study, WR242511 was administered intravenously (IV) in 2 female and 4 male rhesus monkeys in doses of 3.5 and/or 7.0 mg/kg; a single male also received WR242511 orally (PO) at 7.0 mg/kg. Health status and MHb levels were monitored following exposure. RESULTS: The selected doses of WR242511, which produced significant methemoglobinemia in beagle dogs in earlier studies conducted elsewhere, produced very little MHb (mean < 2.0%) in the rhesus monkey. Furthermore, transient hemoglobinuria was noted approximately 60 minutes postinjection of WR242511 (3.5 or 7.0 mg/kg), and 2 lethalities occurred (one IV and one PO) following the 7.0 mg/kg dose. Myoglobinuria was also observed following the 7.0 mg/kg dose. Histopathology analyses in the 2 animals that died revealed liver and kidney toxicity, with greater severity in the orally-treated animal. CONCLUSIONS: These data demonstrate direct and/or indirect drug-induced toxicity. It is concluded that WR242511 should not be pursued as a pretreatment for CN poisoning unless the anti-CN characteristics of this compound can be successfully dissociated from those producing undesirable toxicity.", "entity": "8-aminoquinoline", "aliases": "8-((6-(diethylamino)hexyl)amino)-6-methoxy-4-methylquinoline 8-(6-diethylaminohexylamino)-6-methoxy-4-methylquinoline dihydrochloride 8-aminoquinoline 8-quinolinamine N,N-diethyl-N'-(6-methoxy-4-methyl-8-quinolinyl)-1,6- hexanediamine WR 006026 6026 WR-006026 WR-6026 WR006026 WR6026 sitamaquine", "definition": "", "id": "MESH:C080436"}
{"mention": "WR242511", "mention_text": "INTRODUCTION: Many substances that form methemoglobin (MHb) effectively counter cyanide (CN) toxicity. Although MHb formers are generally applied as treatments for CN poisoning, it has been proposed that a stable, long-acting MHb former could serve as a CN pretreatment. Using this rationale, the 8-aminoquinoline WR242511, a potent long-lasting MHb former in rodents and beagle dogs, was studied in the rhesus monkey for advanced development as a potential CN pretreatment. METHODS: In this study, WR242511 was administered intravenously (IV) in 2 female and 4 male rhesus monkeys in doses of 3.5 and/or 7.0 mg/kg; a single male also received WR242511 orally (PO) at 7.0 mg/kg. Health status and MHb levels were monitored following exposure. RESULTS: The selected doses of WR242511, which produced significant methemoglobinemia in beagle dogs in earlier studies conducted elsewhere, produced very little MHb (mean < 2.0%) in the rhesus monkey. Furthermore, transient hemoglobinuria was noted approximately 60 minutes postinjection of WR242511 (3.5 or 7.0 mg/kg), and 2 lethalities occurred (one IV and one PO) following the 7.0 mg/kg dose. Myoglobinuria was also observed following the 7.0 mg/kg dose. Histopathology analyses in the 2 animals that died revealed liver and kidney toxicity, with greater severity in the orally-treated animal. CONCLUSIONS: These data demonstrate direct and/or indirect drug-induced toxicity. It is concluded that WR242511 should not be pursued as a pretreatment for CN poisoning unless the anti-CN characteristics of this compound can be successfully dissociated from those producing undesirable toxicity.", "entity": "WR 242511", "aliases": "WR 242511 phosphate (1:2) salt WR-242511 WR242511", "definition": "", "id": "MESH:C068820"}
{"mention": "methemoglobinemia", "mention_text": "INTRODUCTION: Many substances that form methemoglobin (MHb) effectively counter cyanide (CN) toxicity. Although MHb formers are generally applied as treatments for CN poisoning, it has been proposed that a stable, long-acting MHb former could serve as a CN pretreatment. Using this rationale, the 8-aminoquinoline WR242511, a potent long-lasting MHb former in rodents and beagle dogs, was studied in the rhesus monkey for advanced development as a potential CN pretreatment. METHODS: In this study, WR242511 was administered intravenously (IV) in 2 female and 4 male rhesus monkeys in doses of 3.5 and/or 7.0 mg/kg; a single male also received WR242511 orally (PO) at 7.0 mg/kg. Health status and MHb levels were monitored following exposure. RESULTS: The selected doses of WR242511, which produced significant methemoglobinemia in beagle dogs in earlier studies conducted elsewhere, produced very little MHb (mean < 2.0%) in the rhesus monkey. Furthermore, transient hemoglobinuria was noted approximately 60 minutes postinjection of WR242511 (3.5 or 7.0 mg/kg), and 2 lethalities occurred (one IV and one PO) following the 7.0 mg/kg dose. Myoglobinuria was also observed following the 7.0 mg/kg dose. Histopathology analyses in the 2 animals that died revealed liver and kidney toxicity, with greater severity in the orally-treated animal. CONCLUSIONS: These data demonstrate direct and/or indirect drug-induced toxicity. It is concluded that WR242511 should not be pursued as a pretreatment for CN poisoning unless the anti-CN characteristics of this compound can be successfully dissociated from those producing undesirable toxicity.", "entity": "Methemoglobinemia", "aliases": "Methemoglobinemia Methemoglobinemias", "definition": "The presence of methemoglobin in the blood, resulting in cyanosis. A small amount of methemoglobin is present in the blood normally, but injury or toxic agents convert a larger proportion of hemoglobin into methemoglobin, which does not function reversibly as an oxygen carrier. Methemoglobinemia may be due to a defect in the enzyme NADH methemoglobin reductase (an autosomal recessive trait) or to an abnormality in hemoglobin M (an autosomal dominant trait). (Dorland, 27th ed)\n    ", "id": "MESH:D008708"}
{"mention": "hemoglobinuria", "mention_text": "INTRODUCTION: Many substances that form methemoglobin (MHb) effectively counter cyanide (CN) toxicity. Although MHb formers are generally applied as treatments for CN poisoning, it has been proposed that a stable, long-acting MHb former could serve as a CN pretreatment. Using this rationale, the 8-aminoquinoline WR242511, a potent long-lasting MHb former in rodents and beagle dogs, was studied in the rhesus monkey for advanced development as a potential CN pretreatment. METHODS: In this study, WR242511 was administered intravenously (IV) in 2 female and 4 male rhesus monkeys in doses of 3.5 and/or 7.0 mg/kg; a single male also received WR242511 orally (PO) at 7.0 mg/kg. Health status and MHb levels were monitored following exposure. RESULTS: The selected doses of WR242511, which produced significant methemoglobinemia in beagle dogs in earlier studies conducted elsewhere, produced very little MHb (mean < 2.0%) in the rhesus monkey. Furthermore, transient hemoglobinuria was noted approximately 60 minutes postinjection of WR242511 (3.5 or 7.0 mg/kg), and 2 lethalities occurred (one IV and one PO) following the 7.0 mg/kg dose. Myoglobinuria was also observed following the 7.0 mg/kg dose. Histopathology analyses in the 2 animals that died revealed liver and kidney toxicity, with greater severity in the orally-treated animal. CONCLUSIONS: These data demonstrate direct and/or indirect drug-induced toxicity. It is concluded that WR242511 should not be pursued as a pretreatment for CN poisoning unless the anti-CN characteristics of this compound can be successfully dissociated from those producing undesirable toxicity.", "entity": "Hemoglobinuria", "aliases": "Hemoglobinuria", "definition": "The presence of free HEMOGLOBIN in the URINE, indicating hemolysis of ERYTHROCYTES within the vascular system. After saturating the hemoglobin-binding proteins (HAPTOGLOBINS), free hemoglobin begins to appear in the urine.\n    ", "id": "MESH:D006456"}
{"mention": "Myoglobinuria", "mention_text": "INTRODUCTION: Many substances that form methemoglobin (MHb) effectively counter cyanide (CN) toxicity. Although MHb formers are generally applied as treatments for CN poisoning, it has been proposed that a stable, long-acting MHb former could serve as a CN pretreatment. Using this rationale, the 8-aminoquinoline WR242511, a potent long-lasting MHb former in rodents and beagle dogs, was studied in the rhesus monkey for advanced development as a potential CN pretreatment. METHODS: In this study, WR242511 was administered intravenously (IV) in 2 female and 4 male rhesus monkeys in doses of 3.5 and/or 7.0 mg/kg; a single male also received WR242511 orally (PO) at 7.0 mg/kg. Health status and MHb levels were monitored following exposure. RESULTS: The selected doses of WR242511, which produced significant methemoglobinemia in beagle dogs in earlier studies conducted elsewhere, produced very little MHb (mean < 2.0%) in the rhesus monkey. Furthermore, transient hemoglobinuria was noted approximately 60 minutes postinjection of WR242511 (3.5 or 7.0 mg/kg), and 2 lethalities occurred (one IV and one PO) following the 7.0 mg/kg dose. Myoglobinuria was also observed following the 7.0 mg/kg dose. Histopathology analyses in the 2 animals that died revealed liver and kidney toxicity, with greater severity in the orally-treated animal. CONCLUSIONS: These data demonstrate direct and/or indirect drug-induced toxicity. It is concluded that WR242511 should not be pursued as a pretreatment for CN poisoning unless the anti-CN characteristics of this compound can be successfully dissociated from those producing undesirable toxicity.", "entity": "Myoglobinuria", "aliases": "Myoglobinuria Myoglobinurias", "definition": "", "id": "MESH:D009212"}
{"mention": "kidney toxicity", "mention_text": "INTRODUCTION: Many substances that form methemoglobin (MHb) effectively counter cyanide (CN) toxicity. Although MHb formers are generally applied as treatments for CN poisoning, it has been proposed that a stable, long-acting MHb former could serve as a CN pretreatment. Using this rationale, the 8-aminoquinoline WR242511, a potent long-lasting MHb former in rodents and beagle dogs, was studied in the rhesus monkey for advanced development as a potential CN pretreatment. METHODS: In this study, WR242511 was administered intravenously (IV) in 2 female and 4 male rhesus monkeys in doses of 3.5 and/or 7.0 mg/kg; a single male also received WR242511 orally (PO) at 7.0 mg/kg. Health status and MHb levels were monitored following exposure. RESULTS: The selected doses of WR242511, which produced significant methemoglobinemia in beagle dogs in earlier studies conducted elsewhere, produced very little MHb (mean < 2.0%) in the rhesus monkey. Furthermore, transient hemoglobinuria was noted approximately 60 minutes postinjection of WR242511 (3.5 or 7.0 mg/kg), and 2 lethalities occurred (one IV and one PO) following the 7.0 mg/kg dose. Myoglobinuria was also observed following the 7.0 mg/kg dose. Histopathology analyses in the 2 animals that died revealed liver and kidney toxicity, with greater severity in the orally-treated animal. CONCLUSIONS: These data demonstrate direct and/or indirect drug-induced toxicity. It is concluded that WR242511 should not be pursued as a pretreatment for CN poisoning unless the anti-CN characteristics of this compound can be successfully dissociated from those producing undesirable toxicity.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "hearing loss", "mention_text": "Neuroplasticity of the adult primate auditory cortex following cochlear hearing loss.", "entity": "Hearing Loss", "aliases": "Hearing Impairment Loss Hypoacuses Hypoacusis", "definition": "A general term for the complete or partial loss of the ability to hear from one or both ears.\n    ", "id": "MESH:D034381"}
{"mention": "hearing loss", "mention_text": "Tonotopic organization is an essential feature of the primary auditory area (A1) of primate cortex. In A1 of macaque monkeys, low frequencies are represented rostrolaterally and high frequencies are represented caudomedially. The purpose of this study was to determine if changes occur in this tonotopic organization following cochlear hearing loss. Under anesthesia, the superior temporal gyrus of adult macaque monkeys was exposed, and the tonotopic organization of A1 was mapped using conventional microelectrode recording techniques. Following recovery, the monkeys were selectively deafened for high frequencies using kanamycin and furosemide. The actual frequencies deafened were determined by the loss of tone-burst elicited auditory brainstem responses. Three months after deafening, A1 was remapped. Postmortem cytoarchitectural features identifying A1 were correlated with the electrophysiologic data. The results indicate that the deprived area of A1 undergoes extensive reorganization and becomes responsive to intact cochlear frequencies. The region of cortex that represents the low frequencies was not obviously affected by the cochlear hearing loss.", "entity": "Hearing Loss", "aliases": "Hearing Impairment Loss Hypoacuses Hypoacusis", "definition": "A general term for the complete or partial loss of the ability to hear from one or both ears.\n    ", "id": "MESH:D034381"}
{"mention": "kanamycin", "mention_text": "Tonotopic organization is an essential feature of the primary auditory area (A1) of primate cortex. In A1 of macaque monkeys, low frequencies are represented rostrolaterally and high frequencies are represented caudomedially. The purpose of this study was to determine if changes occur in this tonotopic organization following cochlear hearing loss. Under anesthesia, the superior temporal gyrus of adult macaque monkeys was exposed, and the tonotopic organization of A1 was mapped using conventional microelectrode recording techniques. Following recovery, the monkeys were selectively deafened for high frequencies using kanamycin and furosemide. The actual frequencies deafened were determined by the loss of tone-burst elicited auditory brainstem responses. Three months after deafening, A1 was remapped. Postmortem cytoarchitectural features identifying A1 were correlated with the electrophysiologic data. The results indicate that the deprived area of A1 undergoes extensive reorganization and becomes responsive to intact cochlear frequencies. The region of cortex that represents the low frequencies was not obviously affected by the cochlear hearing loss.", "entity": "Kanamycin", "aliases": "Kanamycin A Sulfate Kantrex", "definition": "Antibiotic complex produced by Streptomyces kanamyceticus from Japanese soil. Comprises 3 components: kanamycin A, the major component, and kanamycins B and C, the minor components.\n    ", "id": "MESH:D007612"}
{"mention": "furosemide", "mention_text": "Tonotopic organization is an essential feature of the primary auditory area (A1) of primate cortex. In A1 of macaque monkeys, low frequencies are represented rostrolaterally and high frequencies are represented caudomedially. The purpose of this study was to determine if changes occur in this tonotopic organization following cochlear hearing loss. Under anesthesia, the superior temporal gyrus of adult macaque monkeys was exposed, and the tonotopic organization of A1 was mapped using conventional microelectrode recording techniques. Following recovery, the monkeys were selectively deafened for high frequencies using kanamycin and furosemide. The actual frequencies deafened were determined by the loss of tone-burst elicited auditory brainstem responses. Three months after deafening, A1 was remapped. Postmortem cytoarchitectural features identifying A1 were correlated with the electrophysiologic data. The results indicate that the deprived area of A1 undergoes extensive reorganization and becomes responsive to intact cochlear frequencies. The region of cortex that represents the low frequencies was not obviously affected by the cochlear hearing loss.", "entity": "Furosemide", "aliases": "Errolon Frusemid Frusemide Furanthril Furantral Furosemide Monohydrochloride Monosodium Salt Fursemide Fusid Lasix Salix (brand of furosemide)", "definition": "A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for EDEMA and chronic RENAL INSUFFICIENCY.\n    ", "id": "MESH:D005665"}
{"mention": "sumatriptan", "mention_text": "The site of common side effects of sumatriptan.", "entity": "Sumatriptan", "aliases": "3-(2-(Dimethylamino)ethyl)-N-methyl-1H-indole-5-methanesulfonamide GR 43175 GR-43175 GR43175 GSK Brand of Sumatriptan Glaxo Wellcome Imigran Succinate", "definition": "A serotonin agonist that acts selectively at 5HT1 receptors. It is used in the treatment of MIGRAINE DISORDERS.\n    ", "id": "MESH:D018170"}
{"mention": "Atypical sensations", "mention_text": "Atypical sensations following the use of subcutaneous sumatriptan are common, but of uncertain origin. They are almost always benign, but can be mistaken for a serious adverse event by the patient. Two patients are presented with tingling or burning sensations limited to areas of heat exposure or sunburn. In these individuals, side effects are most likely generated superficially in the skin.", "entity": "Paresthesia", "aliases": "Distal Paresthesia Paresthesias Dysesthesia Dysesthesias Formication Formications Painful", "definition": "Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation.\n    ", "id": "MESH:D010292"}
{"mention": "sumatriptan", "mention_text": "Atypical sensations following the use of subcutaneous sumatriptan are common, but of uncertain origin. They are almost always benign, but can be mistaken for a serious adverse event by the patient. Two patients are presented with tingling or burning sensations limited to areas of heat exposure or sunburn. In these individuals, side effects are most likely generated superficially in the skin.", "entity": "Sumatriptan", "aliases": "3-(2-(Dimethylamino)ethyl)-N-methyl-1H-indole-5-methanesulfonamide GR 43175 GR-43175 GR43175 GSK Brand of Sumatriptan Glaxo Wellcome Imigran Succinate", "definition": "A serotonin agonist that acts selectively at 5HT1 receptors. It is used in the treatment of MIGRAINE DISORDERS.\n    ", "id": "MESH:D018170"}
{"mention": "tingling or burning sensations", "mention_text": "Atypical sensations following the use of subcutaneous sumatriptan are common, but of uncertain origin. They are almost always benign, but can be mistaken for a serious adverse event by the patient. Two patients are presented with tingling or burning sensations limited to areas of heat exposure or sunburn. In these individuals, side effects are most likely generated superficially in the skin.", "entity": "Paresthesia", "aliases": "Distal Paresthesia Paresthesias Dysesthesia Dysesthesias Formication Formications Painful", "definition": "Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation.\n    ", "id": "MESH:D010292"}
{"mention": "sunburn", "mention_text": "Atypical sensations following the use of subcutaneous sumatriptan are common, but of uncertain origin. They are almost always benign, but can be mistaken for a serious adverse event by the patient. Two patients are presented with tingling or burning sensations limited to areas of heat exposure or sunburn. In these individuals, side effects are most likely generated superficially in the skin.", "entity": "Sunburn", "aliases": "Sunburn Sunburns", "definition": "An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight.\n    ", "id": "MESH:D013471"}
{"mention": "Tremor", "mention_text": "Tremor side effects of salbutamol, quantified by a laser pointer technique.", "entity": "Tremor", "aliases": "Action Tremor Tremors Coarse Continuous Darkness Fine Intention Intermittent Involuntary Quiver Quivers Limb Massive Muscle Neonatal Nerve Passive Perioral Persistent Pill Rolling Rest Resting Saturnine Semirhythmic Senile Static", "definition": "Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of CEREBELLAR DISEASES, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of PARKINSON DISEASE.\n    ", "id": "MESH:D014202"}
{"mention": "salbutamol", "mention_text": "Tremor side effects of salbutamol, quantified by a laser pointer technique.", "entity": "Albuterol", "aliases": "2-t-Butylamino-1-(4-hydroxy-3-hydroxy-3-hydroxymethyl)phenylethanol Albuterol Sulfate Proventil Salbutamol Sultanol Ventolin", "definition": "A short-acting beta-2 adrenergic agonist that is primarily used as a bronchodilator agent to treat ASTHMA. Albuterol is prepared as a racemic mixture of R(-) and S(+) stereoisomers. The stereospecific preparation of R(-) isomer of albuterol is referred to as levalbuterol.\n    ", "id": "MESH:D000420"}
{"mention": "tremor", "mention_text": "OBJECTIVE: To study tremor side effects of salbutamol an easily applicable, quick and low-priced method is needed. A new method using a commercially available, pen-shaped laser pointer was developed. Aim of the study was to determine sensitivity, reproducibility, reference values and the agreement with a questionnaire. METHODS: Tremor was measured using a laser pointer technique. To determine sensitivity we assessed tremor in 44 patients with obstructive lung disease after administration of cumulative doses of salbutamol. Subjects were asked to aim at the centre of a target, subdivided in concentric circles, from 5 m distance. The circle in which the participant succeeded to aim was recorded in millimetres radius. In another series of measurements, reproducibility and reference values of the tremor was assessed in 65 healthy subjects in three sessions, at 9 a.m., 4 p.m. and 9 a.m., respectively, 1 week later. Postural tremor was measured with the arm horizontally outstretched rest tremor with the arm supported by an armrest and finally tremor was measured after holding a 2-kg weight until exhaustion. Inter-observer variability was measured in a series of 10 healthy subjects. Tremor was measured simultaneously by two independent observers. RESULTS: Salbutamol significantly increased tremor severity in patients in a dose-dependent way. Within healthy adults no age-dependency could be found (b = 0.262 mm/year; P = 0.72). There was no agreement between the questionnaire and tremor severity (r = 0.093; P = 0.53). Postural tremor showed no significant difference between the first and third session (P = 0.07). Support of the arm decreased tremor severity, exhaustion increased tremor severity significantly. A good agreement was found between two independent observers (interclass correlation coefficient 0.72). DISCUSSION: Quantifying tremor by using an inexpensive laser pointer is, with the exception of children (<12 years) a sensitive and reproducible method.", "entity": "Tremor", "aliases": "Action Tremor Tremors Coarse Continuous Darkness Fine Intention Intermittent Involuntary Quiver Quivers Limb Massive Muscle Neonatal Nerve Passive Perioral Persistent Pill Rolling Rest Resting Saturnine Semirhythmic Senile Static", "definition": "Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of CEREBELLAR DISEASES, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of PARKINSON DISEASE.\n    ", "id": "MESH:D014202"}
{"mention": "salbutamol", "mention_text": "OBJECTIVE: To study tremor side effects of salbutamol an easily applicable, quick and low-priced method is needed. A new method using a commercially available, pen-shaped laser pointer was developed. Aim of the study was to determine sensitivity, reproducibility, reference values and the agreement with a questionnaire. METHODS: Tremor was measured using a laser pointer technique. To determine sensitivity we assessed tremor in 44 patients with obstructive lung disease after administration of cumulative doses of salbutamol. Subjects were asked to aim at the centre of a target, subdivided in concentric circles, from 5 m distance. The circle in which the participant succeeded to aim was recorded in millimetres radius. In another series of measurements, reproducibility and reference values of the tremor was assessed in 65 healthy subjects in three sessions, at 9 a.m., 4 p.m. and 9 a.m., respectively, 1 week later. Postural tremor was measured with the arm horizontally outstretched rest tremor with the arm supported by an armrest and finally tremor was measured after holding a 2-kg weight until exhaustion. Inter-observer variability was measured in a series of 10 healthy subjects. Tremor was measured simultaneously by two independent observers. RESULTS: Salbutamol significantly increased tremor severity in patients in a dose-dependent way. Within healthy adults no age-dependency could be found (b = 0.262 mm/year; P = 0.72). There was no agreement between the questionnaire and tremor severity (r = 0.093; P = 0.53). Postural tremor showed no significant difference between the first and third session (P = 0.07). Support of the arm decreased tremor severity, exhaustion increased tremor severity significantly. A good agreement was found between two independent observers (interclass correlation coefficient 0.72). DISCUSSION: Quantifying tremor by using an inexpensive laser pointer is, with the exception of children (<12 years) a sensitive and reproducible method.", "entity": "Albuterol", "aliases": "2-t-Butylamino-1-(4-hydroxy-3-hydroxy-3-hydroxymethyl)phenylethanol Albuterol Sulfate Proventil Salbutamol Sultanol Ventolin", "definition": "A short-acting beta-2 adrenergic agonist that is primarily used as a bronchodilator agent to treat ASTHMA. Albuterol is prepared as a racemic mixture of R(-) and S(+) stereoisomers. The stereospecific preparation of R(-) isomer of albuterol is referred to as levalbuterol.\n    ", "id": "MESH:D000420"}
{"mention": "Tremor", "mention_text": "OBJECTIVE: To study tremor side effects of salbutamol an easily applicable, quick and low-priced method is needed. A new method using a commercially available, pen-shaped laser pointer was developed. Aim of the study was to determine sensitivity, reproducibility, reference values and the agreement with a questionnaire. METHODS: Tremor was measured using a laser pointer technique. To determine sensitivity we assessed tremor in 44 patients with obstructive lung disease after administration of cumulative doses of salbutamol. Subjects were asked to aim at the centre of a target, subdivided in concentric circles, from 5 m distance. The circle in which the participant succeeded to aim was recorded in millimetres radius. In another series of measurements, reproducibility and reference values of the tremor was assessed in 65 healthy subjects in three sessions, at 9 a.m., 4 p.m. and 9 a.m., respectively, 1 week later. Postural tremor was measured with the arm horizontally outstretched rest tremor with the arm supported by an armrest and finally tremor was measured after holding a 2-kg weight until exhaustion. Inter-observer variability was measured in a series of 10 healthy subjects. Tremor was measured simultaneously by two independent observers. RESULTS: Salbutamol significantly increased tremor severity in patients in a dose-dependent way. Within healthy adults no age-dependency could be found (b = 0.262 mm/year; P = 0.72). There was no agreement between the questionnaire and tremor severity (r = 0.093; P = 0.53). Postural tremor showed no significant difference between the first and third session (P = 0.07). Support of the arm decreased tremor severity, exhaustion increased tremor severity significantly. A good agreement was found between two independent observers (interclass correlation coefficient 0.72). DISCUSSION: Quantifying tremor by using an inexpensive laser pointer is, with the exception of children (<12 years) a sensitive and reproducible method.", "entity": "Tremor", "aliases": "Action Tremor Tremors Coarse Continuous Darkness Fine Intention Intermittent Involuntary Quiver Quivers Limb Massive Muscle Neonatal Nerve Passive Perioral Persistent Pill Rolling Rest Resting Saturnine Semirhythmic Senile Static", "definition": "Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of CEREBELLAR DISEASES, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of PARKINSON DISEASE.\n    ", "id": "MESH:D014202"}
{"mention": "obstructive lung disease", "mention_text": "OBJECTIVE: To study tremor side effects of salbutamol an easily applicable, quick and low-priced method is needed. A new method using a commercially available, pen-shaped laser pointer was developed. Aim of the study was to determine sensitivity, reproducibility, reference values and the agreement with a questionnaire. METHODS: Tremor was measured using a laser pointer technique. To determine sensitivity we assessed tremor in 44 patients with obstructive lung disease after administration of cumulative doses of salbutamol. Subjects were asked to aim at the centre of a target, subdivided in concentric circles, from 5 m distance. The circle in which the participant succeeded to aim was recorded in millimetres radius. In another series of measurements, reproducibility and reference values of the tremor was assessed in 65 healthy subjects in three sessions, at 9 a.m., 4 p.m. and 9 a.m., respectively, 1 week later. Postural tremor was measured with the arm horizontally outstretched rest tremor with the arm supported by an armrest and finally tremor was measured after holding a 2-kg weight until exhaustion. Inter-observer variability was measured in a series of 10 healthy subjects. Tremor was measured simultaneously by two independent observers. RESULTS: Salbutamol significantly increased tremor severity in patients in a dose-dependent way. Within healthy adults no age-dependency could be found (b = 0.262 mm/year; P = 0.72). There was no agreement between the questionnaire and tremor severity (r = 0.093; P = 0.53). Postural tremor showed no significant difference between the first and third session (P = 0.07). Support of the arm decreased tremor severity, exhaustion increased tremor severity significantly. A good agreement was found between two independent observers (interclass correlation coefficient 0.72). DISCUSSION: Quantifying tremor by using an inexpensive laser pointer is, with the exception of children (<12 years) a sensitive and reproducible method.", "entity": "Lung Diseases, Obstructive", "aliases": "Lung Disease Obstructive Diseases Pulmonary", "definition": "Any disorder marked by obstruction of conducting airways of the lung. AIRWAY OBSTRUCTION may be acute, chronic, intermittent, or persistent.\n    ", "id": "MESH:D008173"}
{"mention": "Salbutamol", "mention_text": "OBJECTIVE: To study tremor side effects of salbutamol an easily applicable, quick and low-priced method is needed. A new method using a commercially available, pen-shaped laser pointer was developed. Aim of the study was to determine sensitivity, reproducibility, reference values and the agreement with a questionnaire. METHODS: Tremor was measured using a laser pointer technique. To determine sensitivity we assessed tremor in 44 patients with obstructive lung disease after administration of cumulative doses of salbutamol. Subjects were asked to aim at the centre of a target, subdivided in concentric circles, from 5 m distance. The circle in which the participant succeeded to aim was recorded in millimetres radius. In another series of measurements, reproducibility and reference values of the tremor was assessed in 65 healthy subjects in three sessions, at 9 a.m., 4 p.m. and 9 a.m., respectively, 1 week later. Postural tremor was measured with the arm horizontally outstretched rest tremor with the arm supported by an armrest and finally tremor was measured after holding a 2-kg weight until exhaustion. Inter-observer variability was measured in a series of 10 healthy subjects. Tremor was measured simultaneously by two independent observers. RESULTS: Salbutamol significantly increased tremor severity in patients in a dose-dependent way. Within healthy adults no age-dependency could be found (b = 0.262 mm/year; P = 0.72). There was no agreement between the questionnaire and tremor severity (r = 0.093; P = 0.53). Postural tremor showed no significant difference between the first and third session (P = 0.07). Support of the arm decreased tremor severity, exhaustion increased tremor severity significantly. A good agreement was found between two independent observers (interclass correlation coefficient 0.72). DISCUSSION: Quantifying tremor by using an inexpensive laser pointer is, with the exception of children (<12 years) a sensitive and reproducible method.", "entity": "Albuterol", "aliases": "2-t-Butylamino-1-(4-hydroxy-3-hydroxy-3-hydroxymethyl)phenylethanol Albuterol Sulfate Proventil Salbutamol Sultanol Ventolin", "definition": "A short-acting beta-2 adrenergic agonist that is primarily used as a bronchodilator agent to treat ASTHMA. Albuterol is prepared as a racemic mixture of R(-) and S(+) stereoisomers. The stereospecific preparation of R(-) isomer of albuterol is referred to as levalbuterol.\n    ", "id": "MESH:D000420"}
{"mention": "venous thromboembolism", "mention_text": "Increased frequency of venous thromboembolism with the combination of docetaxel and thalidomide in patients with metastatic androgen-independent prostate cancer.", "entity": "Venous Thromboembolism", "aliases": "Thromboembolism Venous", "definition": "Obstruction of a vein or VEINS (embolism) by a blood clot (THROMBUS) in the blood stream.\n    ", "id": "MESH:D054556"}
{"mention": "docetaxel", "mention_text": "Increased frequency of venous thromboembolism with the combination of docetaxel and thalidomide in patients with metastatic androgen-independent prostate cancer.", "entity": "docetaxel", "aliases": "N-debenzoyl-N-tert-butoxycarbonyl-10-deacetyltaxol NSC 628503 RP 56976 RP-56976 Taxoltere metro Taxotere docetaxel anhydrous hydrate trihydrate docetaxol", "definition": "", "id": "MESH:C067311"}
{"mention": "thalidomide", "mention_text": "Increased frequency of venous thromboembolism with the combination of docetaxel and thalidomide in patients with metastatic androgen-independent prostate cancer.", "entity": "Thalidomide", "aliases": "Celgene Brand of Thalidomide Sedoval Thalomid", "definition": "A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.\n    ", "id": "MESH:D013792"}
{"mention": "prostate cancer", "mention_text": "Increased frequency of venous thromboembolism with the combination of docetaxel and thalidomide in patients with metastatic androgen-independent prostate cancer.", "entity": "Prostatic Neoplasms", "aliases": "Cancer of Prostate the Prostatic Cancers Neoplasm Neoplasms", "definition": "Tumors or cancer of the PROSTATE.\n    ", "id": "MESH:D011471"}
{"mention": "venous thromboembolism", "mention_text": "STUDY OBJECTIVE: To evaluate the frequency of venous thromboembolism (VTE) in patients with advanced androgen-independent prostate cancer who were treated with docetaxel alone or in combination with thalidomide. DESIGN: Retrospective analysis of a randomized phase II trial. SETTING: National Institutes of Health clinical research center. PATIENTS: Seventy men, aged 50-80 years, with advanced androgen-independent prostate cancer. INTERVENTION: Each patient received either intravenous docetaxel 30 mg/m2/week for 3 consecutive weeks, followed by 1 week off, or the combination of continuous oral thalidomide 200 mg every evening plus the same docetaxel regimen. This 4-week cycle was repeated until there was evidence of excessive toxicity or disease progression. MEASUREMENTS AND MAIN RESULTS: None of 23 patients who received docetaxel alone developed VTE, whereas 9 of 47 patients (19%) who received docetaxel plus thalidomide developed VTE (p=0.025). CONCLUSION: The addition of thalidomide to docetaxel in the treatment of prostate cancer significantly increases the frequency of VTE. Clinicians should be aware of this potential complication when adding thalidomide to chemotherapeutic regimens.", "entity": "Venous Thromboembolism", "aliases": "Thromboembolism Venous", "definition": "Obstruction of a vein or VEINS (embolism) by a blood clot (THROMBUS) in the blood stream.\n    ", "id": "MESH:D054556"}
{"mention": "VTE", "mention_text": "STUDY OBJECTIVE: To evaluate the frequency of venous thromboembolism (VTE) in patients with advanced androgen-independent prostate cancer who were treated with docetaxel alone or in combination with thalidomide. DESIGN: Retrospective analysis of a randomized phase II trial. SETTING: National Institutes of Health clinical research center. PATIENTS: Seventy men, aged 50-80 years, with advanced androgen-independent prostate cancer. INTERVENTION: Each patient received either intravenous docetaxel 30 mg/m2/week for 3 consecutive weeks, followed by 1 week off, or the combination of continuous oral thalidomide 200 mg every evening plus the same docetaxel regimen. This 4-week cycle was repeated until there was evidence of excessive toxicity or disease progression. MEASUREMENTS AND MAIN RESULTS: None of 23 patients who received docetaxel alone developed VTE, whereas 9 of 47 patients (19%) who received docetaxel plus thalidomide developed VTE (p=0.025). CONCLUSION: The addition of thalidomide to docetaxel in the treatment of prostate cancer significantly increases the frequency of VTE. Clinicians should be aware of this potential complication when adding thalidomide to chemotherapeutic regimens.", "entity": "Venous Thromboembolism", "aliases": "Thromboembolism Venous", "definition": "Obstruction of a vein or VEINS (embolism) by a blood clot (THROMBUS) in the blood stream.\n    ", "id": "MESH:D054556"}
{"mention": "prostate cancer", "mention_text": "STUDY OBJECTIVE: To evaluate the frequency of venous thromboembolism (VTE) in patients with advanced androgen-independent prostate cancer who were treated with docetaxel alone or in combination with thalidomide. DESIGN: Retrospective analysis of a randomized phase II trial. SETTING: National Institutes of Health clinical research center. PATIENTS: Seventy men, aged 50-80 years, with advanced androgen-independent prostate cancer. INTERVENTION: Each patient received either intravenous docetaxel 30 mg/m2/week for 3 consecutive weeks, followed by 1 week off, or the combination of continuous oral thalidomide 200 mg every evening plus the same docetaxel regimen. This 4-week cycle was repeated until there was evidence of excessive toxicity or disease progression. MEASUREMENTS AND MAIN RESULTS: None of 23 patients who received docetaxel alone developed VTE, whereas 9 of 47 patients (19%) who received docetaxel plus thalidomide developed VTE (p=0.025). CONCLUSION: The addition of thalidomide to docetaxel in the treatment of prostate cancer significantly increases the frequency of VTE. Clinicians should be aware of this potential complication when adding thalidomide to chemotherapeutic regimens.", "entity": "Prostatic Neoplasms", "aliases": "Cancer of Prostate the Prostatic Cancers Neoplasm Neoplasms", "definition": "Tumors or cancer of the PROSTATE.\n    ", "id": "MESH:D011471"}
{"mention": "docetaxel", "mention_text": "STUDY OBJECTIVE: To evaluate the frequency of venous thromboembolism (VTE) in patients with advanced androgen-independent prostate cancer who were treated with docetaxel alone or in combination with thalidomide. DESIGN: Retrospective analysis of a randomized phase II trial. SETTING: National Institutes of Health clinical research center. PATIENTS: Seventy men, aged 50-80 years, with advanced androgen-independent prostate cancer. INTERVENTION: Each patient received either intravenous docetaxel 30 mg/m2/week for 3 consecutive weeks, followed by 1 week off, or the combination of continuous oral thalidomide 200 mg every evening plus the same docetaxel regimen. This 4-week cycle was repeated until there was evidence of excessive toxicity or disease progression. MEASUREMENTS AND MAIN RESULTS: None of 23 patients who received docetaxel alone developed VTE, whereas 9 of 47 patients (19%) who received docetaxel plus thalidomide developed VTE (p=0.025). CONCLUSION: The addition of thalidomide to docetaxel in the treatment of prostate cancer significantly increases the frequency of VTE. Clinicians should be aware of this potential complication when adding thalidomide to chemotherapeutic regimens.", "entity": "docetaxel", "aliases": "N-debenzoyl-N-tert-butoxycarbonyl-10-deacetyltaxol NSC 628503 RP 56976 RP-56976 Taxoltere metro Taxotere docetaxel anhydrous hydrate trihydrate docetaxol", "definition": "", "id": "MESH:C067311"}
{"mention": "thalidomide", "mention_text": "STUDY OBJECTIVE: To evaluate the frequency of venous thromboembolism (VTE) in patients with advanced androgen-independent prostate cancer who were treated with docetaxel alone or in combination with thalidomide. DESIGN: Retrospective analysis of a randomized phase II trial. SETTING: National Institutes of Health clinical research center. PATIENTS: Seventy men, aged 50-80 years, with advanced androgen-independent prostate cancer. INTERVENTION: Each patient received either intravenous docetaxel 30 mg/m2/week for 3 consecutive weeks, followed by 1 week off, or the combination of continuous oral thalidomide 200 mg every evening plus the same docetaxel regimen. This 4-week cycle was repeated until there was evidence of excessive toxicity or disease progression. MEASUREMENTS AND MAIN RESULTS: None of 23 patients who received docetaxel alone developed VTE, whereas 9 of 47 patients (19%) who received docetaxel plus thalidomide developed VTE (p=0.025). CONCLUSION: The addition of thalidomide to docetaxel in the treatment of prostate cancer significantly increases the frequency of VTE. Clinicians should be aware of this potential complication when adding thalidomide to chemotherapeutic regimens.", "entity": "Thalidomide", "aliases": "Celgene Brand of Thalidomide Sedoval Thalomid", "definition": "A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.\n    ", "id": "MESH:D013792"}
{"mention": "toxicity", "mention_text": "STUDY OBJECTIVE: To evaluate the frequency of venous thromboembolism (VTE) in patients with advanced androgen-independent prostate cancer who were treated with docetaxel alone or in combination with thalidomide. DESIGN: Retrospective analysis of a randomized phase II trial. SETTING: National Institutes of Health clinical research center. PATIENTS: Seventy men, aged 50-80 years, with advanced androgen-independent prostate cancer. INTERVENTION: Each patient received either intravenous docetaxel 30 mg/m2/week for 3 consecutive weeks, followed by 1 week off, or the combination of continuous oral thalidomide 200 mg every evening plus the same docetaxel regimen. This 4-week cycle was repeated until there was evidence of excessive toxicity or disease progression. MEASUREMENTS AND MAIN RESULTS: None of 23 patients who received docetaxel alone developed VTE, whereas 9 of 47 patients (19%) who received docetaxel plus thalidomide developed VTE (p=0.025). CONCLUSION: The addition of thalidomide to docetaxel in the treatment of prostate cancer significantly increases the frequency of VTE. Clinicians should be aware of this potential complication when adding thalidomide to chemotherapeutic regimens.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "quaternary ammonium", "mention_text": "Sublingual absorption of the quaternary ammonium antiarrhythmic agent, UM-272.", "entity": "Quaternary Ammonium Compounds", "aliases": "Ammonium Compounds Quaternary", "definition": "Derivatives of ammonium compounds, NH4+ Y-, in which all four of the hydrogens bonded to nitrogen have been replaced with hydrocarbyl groups. These are distinguished from IMINES which are RN=CR2.\n    ", "id": "MESH:D000644"}
{"mention": "UM-272", "mention_text": "Sublingual absorption of the quaternary ammonium antiarrhythmic agent, UM-272.", "entity": "pranolium", "aliases": "N,N-dimethyl-1-isopropylamino-3-(1-naphthyloxy)propan-2-ol N,N-dimethylpropranolol SC 27761 UM 272 UM-272 dimethylpropranolol pranolium chloride iodide (+-)-isomer", "definition": "", "id": "MESH:C002616"}
{"mention": "UM-272", "mention_text": "UM-272 (N,N-dimethylpropranolol), a quaternary antiarrhythmic agent, was administered sublingually to dogs with ouabain-induced ventricular tachycardias. Both anti-arrhythmic efficacy and bioavailability were compared to oral drug. Sublingual UM-272 converted ventricular tachycardia to sinus rhythm in all 5 dogs. The area under the plasma concentration time curve at 90 min was 4-12 times greater than for oral drug, suggesting the existence of an absorption-limiting process in the intestine, and providing an alternate form of administration for quaternary drugs.", "entity": "pranolium", "aliases": "N,N-dimethyl-1-isopropylamino-3-(1-naphthyloxy)propan-2-ol N,N-dimethylpropranolol SC 27761 UM 272 UM-272 dimethylpropranolol pranolium chloride iodide (+-)-isomer", "definition": "", "id": "MESH:C002616"}
{"mention": "N,N-dimethylpropranolol", "mention_text": "UM-272 (N,N-dimethylpropranolol), a quaternary antiarrhythmic agent, was administered sublingually to dogs with ouabain-induced ventricular tachycardias. Both anti-arrhythmic efficacy and bioavailability were compared to oral drug. Sublingual UM-272 converted ventricular tachycardia to sinus rhythm in all 5 dogs. The area under the plasma concentration time curve at 90 min was 4-12 times greater than for oral drug, suggesting the existence of an absorption-limiting process in the intestine, and providing an alternate form of administration for quaternary drugs.", "entity": "pranolium", "aliases": "N,N-dimethyl-1-isopropylamino-3-(1-naphthyloxy)propan-2-ol N,N-dimethylpropranolol SC 27761 UM 272 UM-272 dimethylpropranolol pranolium chloride iodide (+-)-isomer", "definition": "", "id": "MESH:C002616"}
{"mention": "ouabain", "mention_text": "UM-272 (N,N-dimethylpropranolol), a quaternary antiarrhythmic agent, was administered sublingually to dogs with ouabain-induced ventricular tachycardias. Both anti-arrhythmic efficacy and bioavailability were compared to oral drug. Sublingual UM-272 converted ventricular tachycardia to sinus rhythm in all 5 dogs. The area under the plasma concentration time curve at 90 min was 4-12 times greater than for oral drug, suggesting the existence of an absorption-limiting process in the intestine, and providing an alternate form of administration for quaternary drugs.", "entity": "Ouabain", "aliases": "Acocantherin Acolongifloroside K G Strophanthin G-Strophanthin Ouabain", "definition": "A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like DIGITALIS. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-EXCHANGING ATPASE.\n    ", "id": "MESH:D010042"}
{"mention": "ventricular tachycardias", "mention_text": "UM-272 (N,N-dimethylpropranolol), a quaternary antiarrhythmic agent, was administered sublingually to dogs with ouabain-induced ventricular tachycardias. Both anti-arrhythmic efficacy and bioavailability were compared to oral drug. Sublingual UM-272 converted ventricular tachycardia to sinus rhythm in all 5 dogs. The area under the plasma concentration time curve at 90 min was 4-12 times greater than for oral drug, suggesting the existence of an absorption-limiting process in the intestine, and providing an alternate form of administration for quaternary drugs.", "entity": "Tachycardia, Ventricular", "aliases": "Tachycardia Ventricular Tachycardias", "definition": "An abnormally rapid ventricular rhythm usually in excess of 150 beats per minute. It is generated within the ventricle below the BUNDLE OF HIS, either as autonomic impulse formation or reentrant impulse conduction. Depending on the etiology, onset of ventricular tachycardia can be paroxysmal (sudden) or nonparoxysmal, its wide QRS complexes can be uniform or polymorphic, and the ventricular beating may be independent of the atrial beating (AV dissociation).\n    ", "id": "MESH:D017180"}
{"mention": "ventricular tachycardia", "mention_text": "UM-272 (N,N-dimethylpropranolol), a quaternary antiarrhythmic agent, was administered sublingually to dogs with ouabain-induced ventricular tachycardias. Both anti-arrhythmic efficacy and bioavailability were compared to oral drug. Sublingual UM-272 converted ventricular tachycardia to sinus rhythm in all 5 dogs. The area under the plasma concentration time curve at 90 min was 4-12 times greater than for oral drug, suggesting the existence of an absorption-limiting process in the intestine, and providing an alternate form of administration for quaternary drugs.", "entity": "Tachycardia, Ventricular", "aliases": "Tachycardia Ventricular Tachycardias", "definition": "An abnormally rapid ventricular rhythm usually in excess of 150 beats per minute. It is generated within the ventricle below the BUNDLE OF HIS, either as autonomic impulse formation or reentrant impulse conduction. Depending on the etiology, onset of ventricular tachycardia can be paroxysmal (sudden) or nonparoxysmal, its wide QRS complexes can be uniform or polymorphic, and the ventricular beating may be independent of the atrial beating (AV dissociation).\n    ", "id": "MESH:D017180"}
{"mention": "thrombocytopenia", "mention_text": "Severe thrombocytopenia and haemolytic anaemia associated with ciprofloxacin: a case report with fatal outcome.", "entity": "Thrombocytopenia", "aliases": "Thrombocytopenia Thrombocytopenias Thrombopenia Thrombopenias", "definition": "A subnormal level of BLOOD PLATELETS.\n    ", "id": "MESH:D013921"}
{"mention": "haemolytic anaemia", "mention_text": "Severe thrombocytopenia and haemolytic anaemia associated with ciprofloxacin: a case report with fatal outcome.", "entity": "Anemia, Hemolytic", "aliases": "Acquired Hemolytic Anemia Microangiopathic", "definition": "A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES).\n    ", "id": "MESH:D000743"}
{"mention": "ciprofloxacin", "mention_text": "Severe thrombocytopenia and haemolytic anaemia associated with ciprofloxacin: a case report with fatal outcome.", "entity": "Ciprofloxacin", "aliases": "Anhydrous Ciprofloxacin Hydrochloride Bay 09867 Bay-09867 Bay09867 Ciprinol Cipro Monohydrochloride Monohydrate", "definition": "A broad-spectrum antimicrobial carboxyfluoroquinoline.\n    ", "id": "MESH:D002939"}
{"mention": "ciprofloxacin", "mention_text": "Haematological adverse reactions associated with fatal outcome are rare during treatment with ciprofloxacin. A 30-year old Caucasian man reported with abdominal pain and jaundice after 3-day administration of oral ciprofloxacin for a suspect of urinary tract infection. Clinical evaluations suggested an initial diagnosis of severe thrombocytopenia and haemolysis. The patient progressively developed petechiae and purpura on thorax and lower limbs. Despite pharmacological and supportive interventions, laboratory parameters worsened and the patient died 17 hours after admission. An accurate autopsy revealed most organs with diffuse petechial haemorrhages. No signs of bone marrow depression were found. No thrombi or signs of microangiopathies were observed in arterial vessels. Blood and urine cultures did not show any bacterial growth. This case report shows that ciprofloxacin may precipitate life-threatening thrombocytopenia and haemolytic anaemia, even in the early phases of treatment and without apparent previous exposures.", "entity": "Ciprofloxacin", "aliases": "Anhydrous Ciprofloxacin Hydrochloride Bay 09867 Bay-09867 Bay09867 Ciprinol Cipro Monohydrochloride Monohydrate", "definition": "A broad-spectrum antimicrobial carboxyfluoroquinoline.\n    ", "id": "MESH:D002939"}
{"mention": "abdominal pain", "mention_text": "Haematological adverse reactions associated with fatal outcome are rare during treatment with ciprofloxacin. A 30-year old Caucasian man reported with abdominal pain and jaundice after 3-day administration of oral ciprofloxacin for a suspect of urinary tract infection. Clinical evaluations suggested an initial diagnosis of severe thrombocytopenia and haemolysis. The patient progressively developed petechiae and purpura on thorax and lower limbs. Despite pharmacological and supportive interventions, laboratory parameters worsened and the patient died 17 hours after admission. An accurate autopsy revealed most organs with diffuse petechial haemorrhages. No signs of bone marrow depression were found. No thrombi or signs of microangiopathies were observed in arterial vessels. Blood and urine cultures did not show any bacterial growth. This case report shows that ciprofloxacin may precipitate life-threatening thrombocytopenia and haemolytic anaemia, even in the early phases of treatment and without apparent previous exposures.", "entity": "Abdominal Pain", "aliases": "Abdominal Pain Pains", "definition": "Sensation of discomfort, distress, or agony in the abdominal region; generally associated with functional disorders, tissue injuries, or diseases.\n    ", "id": "MESH:D015746"}
{"mention": "jaundice", "mention_text": "Haematological adverse reactions associated with fatal outcome are rare during treatment with ciprofloxacin. A 30-year old Caucasian man reported with abdominal pain and jaundice after 3-day administration of oral ciprofloxacin for a suspect of urinary tract infection. Clinical evaluations suggested an initial diagnosis of severe thrombocytopenia and haemolysis. The patient progressively developed petechiae and purpura on thorax and lower limbs. Despite pharmacological and supportive interventions, laboratory parameters worsened and the patient died 17 hours after admission. An accurate autopsy revealed most organs with diffuse petechial haemorrhages. No signs of bone marrow depression were found. No thrombi or signs of microangiopathies were observed in arterial vessels. Blood and urine cultures did not show any bacterial growth. This case report shows that ciprofloxacin may precipitate life-threatening thrombocytopenia and haemolytic anaemia, even in the early phases of treatment and without apparent previous exposures.", "entity": "Jaundice", "aliases": "Hemolytic Jaundice Jaundices Icterus", "definition": "A clinical manifestation of HYPERBILIRUBINEMIA, characterized by the yellowish staining of the SKIN; MUCOUS MEMBRANE; and SCLERA. Clinical jaundice usually is a sign of LIVER dysfunction.\n    ", "id": "MESH:D007565"}
{"mention": "urinary tract infection", "mention_text": "Haematological adverse reactions associated with fatal outcome are rare during treatment with ciprofloxacin. A 30-year old Caucasian man reported with abdominal pain and jaundice after 3-day administration of oral ciprofloxacin for a suspect of urinary tract infection. Clinical evaluations suggested an initial diagnosis of severe thrombocytopenia and haemolysis. The patient progressively developed petechiae and purpura on thorax and lower limbs. Despite pharmacological and supportive interventions, laboratory parameters worsened and the patient died 17 hours after admission. An accurate autopsy revealed most organs with diffuse petechial haemorrhages. No signs of bone marrow depression were found. No thrombi or signs of microangiopathies were observed in arterial vessels. Blood and urine cultures did not show any bacterial growth. This case report shows that ciprofloxacin may precipitate life-threatening thrombocytopenia and haemolytic anaemia, even in the early phases of treatment and without apparent previous exposures.", "entity": "Urinary Tract Infections", "aliases": "Infection Urinary Tract Infections", "definition": "Inflammatory responses of the epithelium of the URINARY TRACT to microbial invasions. They are often bacterial infections with associated BACTERIURIA and PYURIA.\n    ", "id": "MESH:D014552"}
{"mention": "thrombocytopenia", "mention_text": "Haematological adverse reactions associated with fatal outcome are rare during treatment with ciprofloxacin. A 30-year old Caucasian man reported with abdominal pain and jaundice after 3-day administration of oral ciprofloxacin for a suspect of urinary tract infection. Clinical evaluations suggested an initial diagnosis of severe thrombocytopenia and haemolysis. The patient progressively developed petechiae and purpura on thorax and lower limbs. Despite pharmacological and supportive interventions, laboratory parameters worsened and the patient died 17 hours after admission. An accurate autopsy revealed most organs with diffuse petechial haemorrhages. No signs of bone marrow depression were found. No thrombi or signs of microangiopathies were observed in arterial vessels. Blood and urine cultures did not show any bacterial growth. This case report shows that ciprofloxacin may precipitate life-threatening thrombocytopenia and haemolytic anaemia, even in the early phases of treatment and without apparent previous exposures.", "entity": "Thrombocytopenia", "aliases": "Thrombocytopenia Thrombocytopenias Thrombopenia Thrombopenias", "definition": "A subnormal level of BLOOD PLATELETS.\n    ", "id": "MESH:D013921"}
{"mention": "haemolysis", "mention_text": "Haematological adverse reactions associated with fatal outcome are rare during treatment with ciprofloxacin. A 30-year old Caucasian man reported with abdominal pain and jaundice after 3-day administration of oral ciprofloxacin for a suspect of urinary tract infection. Clinical evaluations suggested an initial diagnosis of severe thrombocytopenia and haemolysis. The patient progressively developed petechiae and purpura on thorax and lower limbs. Despite pharmacological and supportive interventions, laboratory parameters worsened and the patient died 17 hours after admission. An accurate autopsy revealed most organs with diffuse petechial haemorrhages. No signs of bone marrow depression were found. No thrombi or signs of microangiopathies were observed in arterial vessels. Blood and urine cultures did not show any bacterial growth. This case report shows that ciprofloxacin may precipitate life-threatening thrombocytopenia and haemolytic anaemia, even in the early phases of treatment and without apparent previous exposures.", "entity": "Hemolysis", "aliases": "Hemolysis", "definition": "The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.\n    ", "id": "MESH:D006461"}
{"mention": "petechiae", "mention_text": "Haematological adverse reactions associated with fatal outcome are rare during treatment with ciprofloxacin. A 30-year old Caucasian man reported with abdominal pain and jaundice after 3-day administration of oral ciprofloxacin for a suspect of urinary tract infection. Clinical evaluations suggested an initial diagnosis of severe thrombocytopenia and haemolysis. The patient progressively developed petechiae and purpura on thorax and lower limbs. Despite pharmacological and supportive interventions, laboratory parameters worsened and the patient died 17 hours after admission. An accurate autopsy revealed most organs with diffuse petechial haemorrhages. No signs of bone marrow depression were found. No thrombi or signs of microangiopathies were observed in arterial vessels. Blood and urine cultures did not show any bacterial growth. This case report shows that ciprofloxacin may precipitate life-threatening thrombocytopenia and haemolytic anaemia, even in the early phases of treatment and without apparent previous exposures.", "entity": "Purpura", "aliases": "Petechiae Purpura Purpuras", "definition": "Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. When the size of the discolorization is >2-3 cm it is generally called Ecchymoses (ECCHYMOSIS).\n    ", "id": "MESH:D011693"}
{"mention": "purpura", "mention_text": "Haematological adverse reactions associated with fatal outcome are rare during treatment with ciprofloxacin. A 30-year old Caucasian man reported with abdominal pain and jaundice after 3-day administration of oral ciprofloxacin for a suspect of urinary tract infection. Clinical evaluations suggested an initial diagnosis of severe thrombocytopenia and haemolysis. The patient progressively developed petechiae and purpura on thorax and lower limbs. Despite pharmacological and supportive interventions, laboratory parameters worsened and the patient died 17 hours after admission. An accurate autopsy revealed most organs with diffuse petechial haemorrhages. No signs of bone marrow depression were found. No thrombi or signs of microangiopathies were observed in arterial vessels. Blood and urine cultures did not show any bacterial growth. This case report shows that ciprofloxacin may precipitate life-threatening thrombocytopenia and haemolytic anaemia, even in the early phases of treatment and without apparent previous exposures.", "entity": "Purpura", "aliases": "Petechiae Purpura Purpuras", "definition": "Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. When the size of the discolorization is >2-3 cm it is generally called Ecchymoses (ECCHYMOSIS).\n    ", "id": "MESH:D011693"}
{"mention": "haemorrhages", "mention_text": "Haematological adverse reactions associated with fatal outcome are rare during treatment with ciprofloxacin. A 30-year old Caucasian man reported with abdominal pain and jaundice after 3-day administration of oral ciprofloxacin for a suspect of urinary tract infection. Clinical evaluations suggested an initial diagnosis of severe thrombocytopenia and haemolysis. The patient progressively developed petechiae and purpura on thorax and lower limbs. Despite pharmacological and supportive interventions, laboratory parameters worsened and the patient died 17 hours after admission. An accurate autopsy revealed most organs with diffuse petechial haemorrhages. No signs of bone marrow depression were found. No thrombi or signs of microangiopathies were observed in arterial vessels. Blood and urine cultures did not show any bacterial growth. This case report shows that ciprofloxacin may precipitate life-threatening thrombocytopenia and haemolytic anaemia, even in the early phases of treatment and without apparent previous exposures.", "entity": "Hemorrhage", "aliases": "Bleeding Hemorrhage Hemorrhages", "definition": "Bleeding or escape of blood from a vessel.\n    ", "id": "MESH:D006470"}
{"mention": "bone marrow depression", "mention_text": "Haematological adverse reactions associated with fatal outcome are rare during treatment with ciprofloxacin. A 30-year old Caucasian man reported with abdominal pain and jaundice after 3-day administration of oral ciprofloxacin for a suspect of urinary tract infection. Clinical evaluations suggested an initial diagnosis of severe thrombocytopenia and haemolysis. The patient progressively developed petechiae and purpura on thorax and lower limbs. Despite pharmacological and supportive interventions, laboratory parameters worsened and the patient died 17 hours after admission. An accurate autopsy revealed most organs with diffuse petechial haemorrhages. No signs of bone marrow depression were found. No thrombi or signs of microangiopathies were observed in arterial vessels. Blood and urine cultures did not show any bacterial growth. This case report shows that ciprofloxacin may precipitate life-threatening thrombocytopenia and haemolytic anaemia, even in the early phases of treatment and without apparent previous exposures.", "entity": "Bone Marrow Diseases", "aliases": "Bone Marrow Disease Diseases", "definition": "", "id": "MESH:D001855"}
{"mention": "thrombi", "mention_text": "Haematological adverse reactions associated with fatal outcome are rare during treatment with ciprofloxacin. A 30-year old Caucasian man reported with abdominal pain and jaundice after 3-day administration of oral ciprofloxacin for a suspect of urinary tract infection. Clinical evaluations suggested an initial diagnosis of severe thrombocytopenia and haemolysis. The patient progressively developed petechiae and purpura on thorax and lower limbs. Despite pharmacological and supportive interventions, laboratory parameters worsened and the patient died 17 hours after admission. An accurate autopsy revealed most organs with diffuse petechial haemorrhages. No signs of bone marrow depression were found. No thrombi or signs of microangiopathies were observed in arterial vessels. Blood and urine cultures did not show any bacterial growth. This case report shows that ciprofloxacin may precipitate life-threatening thrombocytopenia and haemolytic anaemia, even in the early phases of treatment and without apparent previous exposures.", "entity": "Thrombosis", "aliases": "Thromboses Thrombosis Thrombus", "definition": "Formation and development of a thrombus or blood clot in the blood vessel.\n    ", "id": "MESH:D013927"}
{"mention": "microangiopathies", "mention_text": "Haematological adverse reactions associated with fatal outcome are rare during treatment with ciprofloxacin. A 30-year old Caucasian man reported with abdominal pain and jaundice after 3-day administration of oral ciprofloxacin for a suspect of urinary tract infection. Clinical evaluations suggested an initial diagnosis of severe thrombocytopenia and haemolysis. The patient progressively developed petechiae and purpura on thorax and lower limbs. Despite pharmacological and supportive interventions, laboratory parameters worsened and the patient died 17 hours after admission. An accurate autopsy revealed most organs with diffuse petechial haemorrhages. No signs of bone marrow depression were found. No thrombi or signs of microangiopathies were observed in arterial vessels. Blood and urine cultures did not show any bacterial growth. This case report shows that ciprofloxacin may precipitate life-threatening thrombocytopenia and haemolytic anaemia, even in the early phases of treatment and without apparent previous exposures.", "entity": "Vascular Diseases", "aliases": "Disease Vascular Diseases", "definition": "Pathological processes involving any of the BLOOD VESSELS in the cardiac or peripheral circulation. They include diseases of ARTERIES; VEINS; and rest of the vasculature system in the body.\n    ", "id": "MESH:D014652"}
{"mention": "haemolytic anaemia", "mention_text": "Haematological adverse reactions associated with fatal outcome are rare during treatment with ciprofloxacin. A 30-year old Caucasian man reported with abdominal pain and jaundice after 3-day administration of oral ciprofloxacin for a suspect of urinary tract infection. Clinical evaluations suggested an initial diagnosis of severe thrombocytopenia and haemolysis. The patient progressively developed petechiae and purpura on thorax and lower limbs. Despite pharmacological and supportive interventions, laboratory parameters worsened and the patient died 17 hours after admission. An accurate autopsy revealed most organs with diffuse petechial haemorrhages. No signs of bone marrow depression were found. No thrombi or signs of microangiopathies were observed in arterial vessels. Blood and urine cultures did not show any bacterial growth. This case report shows that ciprofloxacin may precipitate life-threatening thrombocytopenia and haemolytic anaemia, even in the early phases of treatment and without apparent previous exposures.", "entity": "Anemia, Hemolytic", "aliases": "Acquired Hemolytic Anemia Microangiopathic", "definition": "A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES).\n    ", "id": "MESH:D000743"}
{"mention": "Simvastatin", "mention_text": "Simvastatin-induced bilateral leg compartment syndrome and myonecrosis associated with hypothyroidism.", "entity": "Simvastatin", "aliases": "MK 733 MK-733 MK733 Simvastatin Synvinolin Zocor", "definition": "A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL CHOLESTEROL.\n    ", "id": "MESH:D019821"}
{"mention": "compartment syndrome", "mention_text": "Simvastatin-induced bilateral leg compartment syndrome and myonecrosis associated with hypothyroidism.", "entity": "Compartment Syndromes", "aliases": "Compartment Syndrome Syndromes", "definition": "Conditions in which increased pressure within a limited space compromises the BLOOD CIRCULATION and function of tissue within that space. Some of the causes of increased pressure are TRAUMA, tight dressings, HEMORRHAGE, and exercise. Sequelae include nerve compression (NERVE COMPRESSION SYNDROMES); PARALYSIS; and ISCHEMIC CONTRACTURE.\n    ", "id": "MESH:D003161"}
{"mention": "myonecrosis", "mention_text": "Simvastatin-induced bilateral leg compartment syndrome and myonecrosis associated with hypothyroidism.", "entity": "Muscular Diseases", "aliases": "Muscle Disorder Disorders Muscular Disease Diseases Myopathic Condition Conditions Myopathies Myopathy", "definition": "Acquired, familial, and congenital disorders of SKELETAL MUSCLE and SMOOTH MUSCLE.\n    ", "id": "MESH:D009135"}
{"mention": "hypothyroidism", "mention_text": "Simvastatin-induced bilateral leg compartment syndrome and myonecrosis associated with hypothyroidism.", "entity": "Hypothyroidism", "aliases": "Hypothyroidism Hypothyroidisms", "definition": "A syndrome that results from abnormally low secretion of THYROID HORMONES from the THYROID GLAND, leading to a decrease in BASAL METABOLIC RATE. In its most severe form, there is accumulation of MUCOPOLYSACCHARIDES in the SKIN and EDEMA, known as MYXEDEMA.\n    ", "id": "MESH:D007037"}
{"mention": "hypothyroid", "mention_text": "A 54-year-old hypothyroid male taking thyroxine and simvastatin presented with bilateral leg compartment syndrome and myonecrosis. Urgent fasciotomies were performed and the patient made an uneventful recovery with the withdrawal of simvastatin. It is likely that this complication will be seen more often with the increased worldwide use of this drug and its approval for all arteriopathic patients.", "entity": "Hypothyroidism", "aliases": "Hypothyroidism Hypothyroidisms", "definition": "A syndrome that results from abnormally low secretion of THYROID HORMONES from the THYROID GLAND, leading to a decrease in BASAL METABOLIC RATE. In its most severe form, there is accumulation of MUCOPOLYSACCHARIDES in the SKIN and EDEMA, known as MYXEDEMA.\n    ", "id": "MESH:D007037"}
{"mention": "thyroxine", "mention_text": "A 54-year-old hypothyroid male taking thyroxine and simvastatin presented with bilateral leg compartment syndrome and myonecrosis. Urgent fasciotomies were performed and the patient made an uneventful recovery with the withdrawal of simvastatin. It is likely that this complication will be seen more often with the increased worldwide use of this drug and its approval for all arteriopathic patients.", "entity": "Thyroxine", "aliases": "3,5,3',5'-Tetraiodothyronine Abbot Brand of Levothyroxine Sodium Allphar Aventis Berlin Chemie Berlin-Chemie Berlthyrox Byk Deladande Levothyroxin Delalande Dexnon Eferox Eltroxin Eltroxine Euthyrox Eutirox Forest Genpharm GlaxoSmithKline GlaxoWellcome Goldshield Henning Hexal 1 2 Kern L Thyrox Thyroxin beta Thyroxine Roche L-3,5,3',5'-Tetraiodothyronine L-Thyrox L-Thyroxin L-Thyroxine LThyroxin Leo Tiroxina Levo T Levo-T LevoT Levothroid Levothyroid Levoxine Levoxyl Lévothyrox Merck Lipha Santé", "definition": "The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (MONOIODOTYROSINE) and the coupling of iodotyrosines (DIIODOTYROSINE) in the THYROGLOBULIN. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form TRIIODOTHYRONINE which exerts a broad spectrum of stimulatory effects on cell metabolism.\n    ", "id": "MESH:D013974"}
{"mention": "simvastatin", "mention_text": "A 54-year-old hypothyroid male taking thyroxine and simvastatin presented with bilateral leg compartment syndrome and myonecrosis. Urgent fasciotomies were performed and the patient made an uneventful recovery with the withdrawal of simvastatin. It is likely that this complication will be seen more often with the increased worldwide use of this drug and its approval for all arteriopathic patients.", "entity": "Simvastatin", "aliases": "MK 733 MK-733 MK733 Simvastatin Synvinolin Zocor", "definition": "A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL CHOLESTEROL.\n    ", "id": "MESH:D019821"}
{"mention": "compartment syndrome", "mention_text": "A 54-year-old hypothyroid male taking thyroxine and simvastatin presented with bilateral leg compartment syndrome and myonecrosis. Urgent fasciotomies were performed and the patient made an uneventful recovery with the withdrawal of simvastatin. It is likely that this complication will be seen more often with the increased worldwide use of this drug and its approval for all arteriopathic patients.", "entity": "Compartment Syndromes", "aliases": "Compartment Syndrome Syndromes", "definition": "Conditions in which increased pressure within a limited space compromises the BLOOD CIRCULATION and function of tissue within that space. Some of the causes of increased pressure are TRAUMA, tight dressings, HEMORRHAGE, and exercise. Sequelae include nerve compression (NERVE COMPRESSION SYNDROMES); PARALYSIS; and ISCHEMIC CONTRACTURE.\n    ", "id": "MESH:D003161"}
{"mention": "myonecrosis", "mention_text": "A 54-year-old hypothyroid male taking thyroxine and simvastatin presented with bilateral leg compartment syndrome and myonecrosis. Urgent fasciotomies were performed and the patient made an uneventful recovery with the withdrawal of simvastatin. It is likely that this complication will be seen more often with the increased worldwide use of this drug and its approval for all arteriopathic patients.", "entity": "Muscular Diseases", "aliases": "Muscle Disorder Disorders Muscular Disease Diseases Myopathic Condition Conditions Myopathies Myopathy", "definition": "Acquired, familial, and congenital disorders of SKELETAL MUSCLE and SMOOTH MUSCLE.\n    ", "id": "MESH:D009135"}
{"mention": "arteriopathic", "mention_text": "A 54-year-old hypothyroid male taking thyroxine and simvastatin presented with bilateral leg compartment syndrome and myonecrosis. Urgent fasciotomies were performed and the patient made an uneventful recovery with the withdrawal of simvastatin. It is likely that this complication will be seen more often with the increased worldwide use of this drug and its approval for all arteriopathic patients.", "entity": "Vascular Diseases", "aliases": "Disease Vascular Diseases", "definition": "Pathological processes involving any of the BLOOD VESSELS in the cardiac or peripheral circulation. They include diseases of ARTERIES; VEINS; and rest of the vasculature system in the body.\n    ", "id": "MESH:D014652"}
{"mention": "Bile duct hamartoma", "mention_text": "Bile duct hamartoma occurring in association with long-term treatment with danazol.", "entity": "Bile Duct Neoplasms", "aliases": "Bile Duct Cancer Cancers Neoplasm Neoplasms of the", "definition": "Tumors or cancer of the BILE DUCTS.\n    ", "id": "MESH:D001650"}
{"mention": "hamartoma", "mention_text": "Bile duct hamartoma occurring in association with long-term treatment with danazol.", "entity": "Hamartoma", "aliases": "Hamartoma Hamartomas", "definition": "A focal malformation resembling a neoplasm, composed of an overgrowth of mature cells and tissues that normally occur in the affected area.\n    ", "id": "MESH:D006222"}
{"mention": "danazol", "mention_text": "Bile duct hamartoma occurring in association with long-term treatment with danazol.", "entity": "Danazol", "aliases": "Alphapharm Brand of Danazol Antigen Azol Cyclomen Danatrol Danazant Danazol-ratiopharm Danocrine Danol Danoval Kendrick Ladogal Norciden Panacrine Sanofi Synthelabo Winthrop ratiopharm", "definition": "A synthetic steroid with antigonadotropic and anti-estrogenic activities that acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. It possesses some androgenic properties. Danazol has been used in the treatment of endometriosis and some benign breast disorders.\n    ", "id": "MESH:D003613"}
{"mention": "bile duct hamartoma", "mention_text": "We report a case of bile duct hamartoma which developed in a patient who had been on long-term danazol treatment. Such patients should be under close follow-up, preferably with periodic ultrasound examination of the liver. If the patient develops a liver mass, because of non-specific clinical features and imaging appearances, biopsy may be the only way to achieve a definitive diagnosis.", "entity": "Bile Duct Neoplasms", "aliases": "Bile Duct Cancer Cancers Neoplasm Neoplasms of the", "definition": "Tumors or cancer of the BILE DUCTS.\n    ", "id": "MESH:D001650"}
{"mention": "hamartoma", "mention_text": "We report a case of bile duct hamartoma which developed in a patient who had been on long-term danazol treatment. Such patients should be under close follow-up, preferably with periodic ultrasound examination of the liver. If the patient develops a liver mass, because of non-specific clinical features and imaging appearances, biopsy may be the only way to achieve a definitive diagnosis.", "entity": "Hamartoma", "aliases": "Hamartoma Hamartomas", "definition": "A focal malformation resembling a neoplasm, composed of an overgrowth of mature cells and tissues that normally occur in the affected area.\n    ", "id": "MESH:D006222"}
{"mention": "danazol", "mention_text": "We report a case of bile duct hamartoma which developed in a patient who had been on long-term danazol treatment. Such patients should be under close follow-up, preferably with periodic ultrasound examination of the liver. If the patient develops a liver mass, because of non-specific clinical features and imaging appearances, biopsy may be the only way to achieve a definitive diagnosis.", "entity": "Danazol", "aliases": "Alphapharm Brand of Danazol Antigen Azol Cyclomen Danatrol Danazant Danazol-ratiopharm Danocrine Danol Danoval Kendrick Ladogal Norciden Panacrine Sanofi Synthelabo Winthrop ratiopharm", "definition": "A synthetic steroid with antigonadotropic and anti-estrogenic activities that acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. It possesses some androgenic properties. Danazol has been used in the treatment of endometriosis and some benign breast disorders.\n    ", "id": "MESH:D003613"}
{"mention": "liver mass", "mention_text": "We report a case of bile duct hamartoma which developed in a patient who had been on long-term danazol treatment. Such patients should be under close follow-up, preferably with periodic ultrasound examination of the liver. If the patient develops a liver mass, because of non-specific clinical features and imaging appearances, biopsy may be the only way to achieve a definitive diagnosis.", "entity": "Liver Diseases", "aliases": "Disease Liver Diseases Dysfunction Dysfunctions", "definition": "Pathological processes of the LIVER.\n    ", "id": "MESH:D008107"}
{"mention": "Granulomatous", "mention_text": "Granulomatous hepatitis due to combination of amoxicillin and clavulanic acid.", "entity": "Granuloma", "aliases": "Granuloma Granulomas", "definition": "A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents.\n    ", "id": "MESH:D006099"}
{"mention": "hepatitis", "mention_text": "Granulomatous hepatitis due to combination of amoxicillin and clavulanic acid.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "combination of amoxicillin and clavulanic acid", "mention_text": "Granulomatous hepatitis due to combination of amoxicillin and clavulanic acid.", "entity": "Amoxicillin-Potassium Clavulanate Combination", "aliases": "Amox clav Amox-clav Amoxi Clavulanate Amoxi-Clavulanate Amoxicillin Clavulanic Acid Potassium Combination Amoxicillin-Clavulanic Amoxicillin-Potassium Amoxycillin Potentiated Amoxycillin-Clavulanic Augmentin BRL 25000 BRL-25000 BRL25000 Clavulanate-Amoxicillin Clavulin Co amoxiclav Co-amoxiclav Coamoxiclav Spektramox Synulox", "definition": "A fixed-ratio combination of amoxicillin trihydrate and potassium clavulanate.\n    ", "id": "MESH:D019980"}
{"mention": "amoxicillin-clavulanic acid", "mention_text": "We report the case of a patient with amoxicillin-clavulanic acid-induced hepatitis with histologic multiple granulomas. This type of lesion broadens the spectrum of liver injury due to this drug combination, mainly represented by a benign cholestatic syndrome. The association of granulomas and eosinophilia favor an immunoallergic mechanism. As penicillin derivatives and amoxicillin alone are known to induce such types of lesions, the amoxicillin component, with or without a potentiating effect of clavulanic acid, might have a major role.", "entity": "Amoxicillin-Potassium Clavulanate Combination", "aliases": "Amox clav Amox-clav Amoxi Clavulanate Amoxi-Clavulanate Amoxicillin Clavulanic Acid Potassium Combination Amoxicillin-Clavulanic Amoxicillin-Potassium Amoxycillin Potentiated Amoxycillin-Clavulanic Augmentin BRL 25000 BRL-25000 BRL25000 Clavulanate-Amoxicillin Clavulin Co amoxiclav Co-amoxiclav Coamoxiclav Spektramox Synulox", "definition": "A fixed-ratio combination of amoxicillin trihydrate and potassium clavulanate.\n    ", "id": "MESH:D019980"}
{"mention": "hepatitis", "mention_text": "We report the case of a patient with amoxicillin-clavulanic acid-induced hepatitis with histologic multiple granulomas. This type of lesion broadens the spectrum of liver injury due to this drug combination, mainly represented by a benign cholestatic syndrome. The association of granulomas and eosinophilia favor an immunoallergic mechanism. As penicillin derivatives and amoxicillin alone are known to induce such types of lesions, the amoxicillin component, with or without a potentiating effect of clavulanic acid, might have a major role.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "granulomas", "mention_text": "We report the case of a patient with amoxicillin-clavulanic acid-induced hepatitis with histologic multiple granulomas. This type of lesion broadens the spectrum of liver injury due to this drug combination, mainly represented by a benign cholestatic syndrome. The association of granulomas and eosinophilia favor an immunoallergic mechanism. As penicillin derivatives and amoxicillin alone are known to induce such types of lesions, the amoxicillin component, with or without a potentiating effect of clavulanic acid, might have a major role.", "entity": "Granuloma", "aliases": "Granuloma Granulomas", "definition": "A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents.\n    ", "id": "MESH:D006099"}
{"mention": "liver injury", "mention_text": "We report the case of a patient with amoxicillin-clavulanic acid-induced hepatitis with histologic multiple granulomas. This type of lesion broadens the spectrum of liver injury due to this drug combination, mainly represented by a benign cholestatic syndrome. The association of granulomas and eosinophilia favor an immunoallergic mechanism. As penicillin derivatives and amoxicillin alone are known to induce such types of lesions, the amoxicillin component, with or without a potentiating effect of clavulanic acid, might have a major role.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "cholestatic syndrome", "mention_text": "We report the case of a patient with amoxicillin-clavulanic acid-induced hepatitis with histologic multiple granulomas. This type of lesion broadens the spectrum of liver injury due to this drug combination, mainly represented by a benign cholestatic syndrome. The association of granulomas and eosinophilia favor an immunoallergic mechanism. As penicillin derivatives and amoxicillin alone are known to induce such types of lesions, the amoxicillin component, with or without a potentiating effect of clavulanic acid, might have a major role.", "entity": "Cholestasis", "aliases": "Bile Duct Obstruction Obstructions Biliary Stases Stasis Cholestases Cholestasis", "definition": "Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).\n    ", "id": "MESH:D002779"}
{"mention": "eosinophilia", "mention_text": "We report the case of a patient with amoxicillin-clavulanic acid-induced hepatitis with histologic multiple granulomas. This type of lesion broadens the spectrum of liver injury due to this drug combination, mainly represented by a benign cholestatic syndrome. The association of granulomas and eosinophilia favor an immunoallergic mechanism. As penicillin derivatives and amoxicillin alone are known to induce such types of lesions, the amoxicillin component, with or without a potentiating effect of clavulanic acid, might have a major role.", "entity": "Eosinophilia", "aliases": "Eosinophilia Tropical Eosinophilias", "definition": "Abnormal increase of EOSINOPHILS in the blood, tissues or organs.\n    ", "id": "MESH:D004802"}
{"mention": "penicillin", "mention_text": "We report the case of a patient with amoxicillin-clavulanic acid-induced hepatitis with histologic multiple granulomas. This type of lesion broadens the spectrum of liver injury due to this drug combination, mainly represented by a benign cholestatic syndrome. The association of granulomas and eosinophilia favor an immunoallergic mechanism. As penicillin derivatives and amoxicillin alone are known to induce such types of lesions, the amoxicillin component, with or without a potentiating effect of clavulanic acid, might have a major role.", "entity": "Penicillins", "aliases": "Antibiotics Penicillin Penicillins", "definition": "A group of antibiotics that contain 6-aminopenicillanic acid with a side chain attached to the 6-amino group. The penicillin nucleus is the chief structural requirement for biological activity. The side-chain structure determines many of the antibacterial and pharmacological characteristics. (Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1065)\n    ", "id": "MESH:D010406"}
{"mention": "amoxicillin", "mention_text": "We report the case of a patient with amoxicillin-clavulanic acid-induced hepatitis with histologic multiple granulomas. This type of lesion broadens the spectrum of liver injury due to this drug combination, mainly represented by a benign cholestatic syndrome. The association of granulomas and eosinophilia favor an immunoallergic mechanism. As penicillin derivatives and amoxicillin alone are known to induce such types of lesions, the amoxicillin component, with or without a potentiating effect of clavulanic acid, might have a major role.", "entity": "Amoxicillin", "aliases": "Actimoxi Amoxicillin Anhydrous Clariana Brand Monopotassium Salt Monosodium Sodium Trihydrate (R*)-Isomer Amoxicilline Amoxil Amoxycillin BRL 2333 BRL-2333 BRL2333 Clamoxyl G.A. parenteral of Hydroxyampicillin Penamox Pfizer Polymox SmithKline Beecham Trimox Wymox", "definition": "A broad-spectrum semisynthetic antibiotic similar to AMPICILLIN except that its resistance to gastric acid permits higher serum levels with oral administration.\n    ", "id": "MESH:D000658"}
{"mention": "clavulanic acid", "mention_text": "We report the case of a patient with amoxicillin-clavulanic acid-induced hepatitis with histologic multiple granulomas. This type of lesion broadens the spectrum of liver injury due to this drug combination, mainly represented by a benign cholestatic syndrome. The association of granulomas and eosinophilia favor an immunoallergic mechanism. As penicillin derivatives and amoxicillin alone are known to induce such types of lesions, the amoxicillin component, with or without a potentiating effect of clavulanic acid, might have a major role.", "entity": "Clavulanic Acid", "aliases": "BRL 14151 BRL-14151 BRL14151 Clavulanate Potassium Sodium Clavulanic Acid Monopotassium Salt Monosodium MM MM-14151 MM14151", "definition": "Clavulanic acid and its salts and esters. The acid is a suicide inhibitor of bacterial beta-lactamase enzymes from Streptomyces clavuligerus. Administered alone, it has only weak antibacterial activity against most organisms, but given in combination with other beta-lactam antibiotics it prevents antibiotic inactivation by microbial lactamase.\n    ", "id": "MESH:D019818"}
{"mention": "Intracranial aneurysms", "mention_text": "Intracranial aneurysms and cocaine abuse: analysis of prognostic indicators.", "entity": "Intracranial Aneurysm", "aliases": "Aneurysm Anterior Cerebral Artery Communicating Basilar Berry Brain Giant Intracranial Mycotic Middle Posterior Aneurysms", "definition": "Abnormal outpouching in the wall of intracranial blood vessels. Most common are the saccular (berry) aneurysms located at branch points in CIRCLE OF WILLIS at the base of the brain. Vessel rupture results in SUBARACHNOID HEMORRHAGE or INTRACRANIAL HEMORRHAGES. Giant aneurysms (>2.5 cm in diameter) may compress adjacent structures, including the OCULOMOTOR NERVE. (From Adams et al., Principles of Neurology, 6th ed, p841)\n    ", "id": "MESH:D002532"}
{"mention": "cocaine abuse", "mention_text": "Intracranial aneurysms and cocaine abuse: analysis of prognostic indicators.", "entity": "Cocaine-Related Disorders", "aliases": "Abuse Cocaine Addiction Dependence Related Disorders Cocaine-Related Disorder Dependences", "definition": "Disorders related or resulting from use of cocaine.\n    ", "id": "MESH:D019970"}
{"mention": "subarachnoid hemorrhage", "mention_text": "OBJECTIVE: The outcome of subarachnoid hemorrhage associated with cocaine abuse is reportedly poor. However, no study in the literature has reported the use of a statistical model to analyze the variables that influence outcome. METHODS: A review of admissions during a 6-year period revealed 14 patients with cocaine-related aneurysms. This group was compared with a control group of 135 patients with ruptured aneurysms and no history of cocaine abuse. Age at presentation, time of ictus after intoxication, Hunt and Hess grade of subarachnoid hemorrhage, size of the aneurysm, location of the aneurysm, and the Glasgow Outcome Scale score were assessed and compared. RESULTS: The patients in the study group were significantly younger than the patients in the control group (P < 0.002). In patients in the study group, all aneurysms were located in the anterior circulation. The majority of these aneurysms were smaller than those of the control group (8 +/- 6.08 mm versus 11 +/- 5.4 mm; P = 0.05). The differences in mortality and morbidity between the two groups were not significant. Hunt and Hess grade (P < 0.005) and age (P < 0.007) were significant predictors of outcome for the patients with cocaine-related aneurysms. CONCLUSION: Cocaine use predisposed aneurysmal rupture at a significantly earlier age and in much smaller aneurysms. Contrary to the published literature, this group did reasonably well with aggressive management.", "entity": "Subarachnoid Hemorrhage", "aliases": "Aneurysmal Subarachnoid Hemorrhage Hemorrhages Intracranial Perinatal Spontaneous SAH (Subarachnoid Hemorrhage) SAHs", "definition": "Bleeding into the intracranial or spinal SUBARACHNOID SPACE, most resulting from INTRACRANIAL ANEURYSM rupture. It can occur after traumatic injuries (SUBARACHNOID HEMORRHAGE, TRAUMATIC). Clinical features include HEADACHE; NAUSEA; VOMITING, nuchal rigidity, variable neurological deficits and reduced mental status.\n    ", "id": "MESH:D013345"}
{"mention": "cocaine abuse", "mention_text": "OBJECTIVE: The outcome of subarachnoid hemorrhage associated with cocaine abuse is reportedly poor. However, no study in the literature has reported the use of a statistical model to analyze the variables that influence outcome. METHODS: A review of admissions during a 6-year period revealed 14 patients with cocaine-related aneurysms. This group was compared with a control group of 135 patients with ruptured aneurysms and no history of cocaine abuse. Age at presentation, time of ictus after intoxication, Hunt and Hess grade of subarachnoid hemorrhage, size of the aneurysm, location of the aneurysm, and the Glasgow Outcome Scale score were assessed and compared. RESULTS: The patients in the study group were significantly younger than the patients in the control group (P < 0.002). In patients in the study group, all aneurysms were located in the anterior circulation. The majority of these aneurysms were smaller than those of the control group (8 +/- 6.08 mm versus 11 +/- 5.4 mm; P = 0.05). The differences in mortality and morbidity between the two groups were not significant. Hunt and Hess grade (P < 0.005) and age (P < 0.007) were significant predictors of outcome for the patients with cocaine-related aneurysms. CONCLUSION: Cocaine use predisposed aneurysmal rupture at a significantly earlier age and in much smaller aneurysms. Contrary to the published literature, this group did reasonably well with aggressive management.", "entity": "Cocaine-Related Disorders", "aliases": "Abuse Cocaine Addiction Dependence Related Disorders Cocaine-Related Disorder Dependences", "definition": "Disorders related or resulting from use of cocaine.\n    ", "id": "MESH:D019970"}
{"mention": "cocaine", "mention_text": "OBJECTIVE: The outcome of subarachnoid hemorrhage associated with cocaine abuse is reportedly poor. However, no study in the literature has reported the use of a statistical model to analyze the variables that influence outcome. METHODS: A review of admissions during a 6-year period revealed 14 patients with cocaine-related aneurysms. This group was compared with a control group of 135 patients with ruptured aneurysms and no history of cocaine abuse. Age at presentation, time of ictus after intoxication, Hunt and Hess grade of subarachnoid hemorrhage, size of the aneurysm, location of the aneurysm, and the Glasgow Outcome Scale score were assessed and compared. RESULTS: The patients in the study group were significantly younger than the patients in the control group (P < 0.002). In patients in the study group, all aneurysms were located in the anterior circulation. The majority of these aneurysms were smaller than those of the control group (8 +/- 6.08 mm versus 11 +/- 5.4 mm; P = 0.05). The differences in mortality and morbidity between the two groups were not significant. Hunt and Hess grade (P < 0.005) and age (P < 0.007) were significant predictors of outcome for the patients with cocaine-related aneurysms. CONCLUSION: Cocaine use predisposed aneurysmal rupture at a significantly earlier age and in much smaller aneurysms. Contrary to the published literature, this group did reasonably well with aggressive management.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "aneurysms", "mention_text": "OBJECTIVE: The outcome of subarachnoid hemorrhage associated with cocaine abuse is reportedly poor. However, no study in the literature has reported the use of a statistical model to analyze the variables that influence outcome. METHODS: A review of admissions during a 6-year period revealed 14 patients with cocaine-related aneurysms. This group was compared with a control group of 135 patients with ruptured aneurysms and no history of cocaine abuse. Age at presentation, time of ictus after intoxication, Hunt and Hess grade of subarachnoid hemorrhage, size of the aneurysm, location of the aneurysm, and the Glasgow Outcome Scale score were assessed and compared. RESULTS: The patients in the study group were significantly younger than the patients in the control group (P < 0.002). In patients in the study group, all aneurysms were located in the anterior circulation. The majority of these aneurysms were smaller than those of the control group (8 +/- 6.08 mm versus 11 +/- 5.4 mm; P = 0.05). The differences in mortality and morbidity between the two groups were not significant. Hunt and Hess grade (P < 0.005) and age (P < 0.007) were significant predictors of outcome for the patients with cocaine-related aneurysms. CONCLUSION: Cocaine use predisposed aneurysmal rupture at a significantly earlier age and in much smaller aneurysms. Contrary to the published literature, this group did reasonably well with aggressive management.", "entity": "Aneurysm", "aliases": "Aneurysm Fusiform Aneurysms Saccular", "definition": "Pathological outpouching or sac-like dilatation in the wall of any blood vessel (ARTERIES or VEINS) or the heart (HEART ANEURYSM). It indicates a thin and weakened area in the wall which may later rupture. Aneurysms are classified by location, etiology, or other characteristics.\n    ", "id": "MESH:D000783"}
{"mention": "ruptured aneurysms", "mention_text": "OBJECTIVE: The outcome of subarachnoid hemorrhage associated with cocaine abuse is reportedly poor. However, no study in the literature has reported the use of a statistical model to analyze the variables that influence outcome. METHODS: A review of admissions during a 6-year period revealed 14 patients with cocaine-related aneurysms. This group was compared with a control group of 135 patients with ruptured aneurysms and no history of cocaine abuse. Age at presentation, time of ictus after intoxication, Hunt and Hess grade of subarachnoid hemorrhage, size of the aneurysm, location of the aneurysm, and the Glasgow Outcome Scale score were assessed and compared. RESULTS: The patients in the study group were significantly younger than the patients in the control group (P < 0.002). In patients in the study group, all aneurysms were located in the anterior circulation. The majority of these aneurysms were smaller than those of the control group (8 +/- 6.08 mm versus 11 +/- 5.4 mm; P = 0.05). The differences in mortality and morbidity between the two groups were not significant. Hunt and Hess grade (P < 0.005) and age (P < 0.007) were significant predictors of outcome for the patients with cocaine-related aneurysms. CONCLUSION: Cocaine use predisposed aneurysmal rupture at a significantly earlier age and in much smaller aneurysms. Contrary to the published literature, this group did reasonably well with aggressive management.", "entity": "Aneurysm, Ruptured", "aliases": "Aneurysm Ruptured Aneurysms", "definition": "The tearing or bursting of the weakened wall of the aneurysmal sac, usually heralded by sudden worsening pain. The great danger of a ruptured aneurysm is the large amount of blood spilling into the surrounding tissues and cavities, causing HEMORRHAGIC SHOCK.\n    ", "id": "MESH:D017542"}
{"mention": "aneurysm", "mention_text": "OBJECTIVE: The outcome of subarachnoid hemorrhage associated with cocaine abuse is reportedly poor. However, no study in the literature has reported the use of a statistical model to analyze the variables that influence outcome. METHODS: A review of admissions during a 6-year period revealed 14 patients with cocaine-related aneurysms. This group was compared with a control group of 135 patients with ruptured aneurysms and no history of cocaine abuse. Age at presentation, time of ictus after intoxication, Hunt and Hess grade of subarachnoid hemorrhage, size of the aneurysm, location of the aneurysm, and the Glasgow Outcome Scale score were assessed and compared. RESULTS: The patients in the study group were significantly younger than the patients in the control group (P < 0.002). In patients in the study group, all aneurysms were located in the anterior circulation. The majority of these aneurysms were smaller than those of the control group (8 +/- 6.08 mm versus 11 +/- 5.4 mm; P = 0.05). The differences in mortality and morbidity between the two groups were not significant. Hunt and Hess grade (P < 0.005) and age (P < 0.007) were significant predictors of outcome for the patients with cocaine-related aneurysms. CONCLUSION: Cocaine use predisposed aneurysmal rupture at a significantly earlier age and in much smaller aneurysms. Contrary to the published literature, this group did reasonably well with aggressive management.", "entity": "Aneurysm", "aliases": "Aneurysm Fusiform Aneurysms Saccular", "definition": "Pathological outpouching or sac-like dilatation in the wall of any blood vessel (ARTERIES or VEINS) or the heart (HEART ANEURYSM). It indicates a thin and weakened area in the wall which may later rupture. Aneurysms are classified by location, etiology, or other characteristics.\n    ", "id": "MESH:D000783"}
{"mention": "Cocaine", "mention_text": "OBJECTIVE: The outcome of subarachnoid hemorrhage associated with cocaine abuse is reportedly poor. However, no study in the literature has reported the use of a statistical model to analyze the variables that influence outcome. METHODS: A review of admissions during a 6-year period revealed 14 patients with cocaine-related aneurysms. This group was compared with a control group of 135 patients with ruptured aneurysms and no history of cocaine abuse. Age at presentation, time of ictus after intoxication, Hunt and Hess grade of subarachnoid hemorrhage, size of the aneurysm, location of the aneurysm, and the Glasgow Outcome Scale score were assessed and compared. RESULTS: The patients in the study group were significantly younger than the patients in the control group (P < 0.002). In patients in the study group, all aneurysms were located in the anterior circulation. The majority of these aneurysms were smaller than those of the control group (8 +/- 6.08 mm versus 11 +/- 5.4 mm; P = 0.05). The differences in mortality and morbidity between the two groups were not significant. Hunt and Hess grade (P < 0.005) and age (P < 0.007) were significant predictors of outcome for the patients with cocaine-related aneurysms. CONCLUSION: Cocaine use predisposed aneurysmal rupture at a significantly earlier age and in much smaller aneurysms. Contrary to the published literature, this group did reasonably well with aggressive management.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "aneurysmal rupture", "mention_text": "OBJECTIVE: The outcome of subarachnoid hemorrhage associated with cocaine abuse is reportedly poor. However, no study in the literature has reported the use of a statistical model to analyze the variables that influence outcome. METHODS: A review of admissions during a 6-year period revealed 14 patients with cocaine-related aneurysms. This group was compared with a control group of 135 patients with ruptured aneurysms and no history of cocaine abuse. Age at presentation, time of ictus after intoxication, Hunt and Hess grade of subarachnoid hemorrhage, size of the aneurysm, location of the aneurysm, and the Glasgow Outcome Scale score were assessed and compared. RESULTS: The patients in the study group were significantly younger than the patients in the control group (P < 0.002). In patients in the study group, all aneurysms were located in the anterior circulation. The majority of these aneurysms were smaller than those of the control group (8 +/- 6.08 mm versus 11 +/- 5.4 mm; P = 0.05). The differences in mortality and morbidity between the two groups were not significant. Hunt and Hess grade (P < 0.005) and age (P < 0.007) were significant predictors of outcome for the patients with cocaine-related aneurysms. CONCLUSION: Cocaine use predisposed aneurysmal rupture at a significantly earlier age and in much smaller aneurysms. Contrary to the published literature, this group did reasonably well with aggressive management.", "entity": "Aneurysm, Ruptured", "aliases": "Aneurysm Ruptured Aneurysms", "definition": "The tearing or bursting of the weakened wall of the aneurysmal sac, usually heralded by sudden worsening pain. The great danger of a ruptured aneurysm is the large amount of blood spilling into the surrounding tissues and cavities, causing HEMORRHAGIC SHOCK.\n    ", "id": "MESH:D017542"}
{"mention": "epileptic", "mention_text": "Anti-epileptic drugs-induced de novo absence seizures.", "entity": "Epilepsy", "aliases": "Aura Auras Awakening Epilepsy Cryptogenic Epilepsies Epileptic Seizure Seizures Disorder Disorders Single", "definition": "A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313)\n    ", "id": "MESH:D004827"}
{"mention": "absence seizures", "mention_text": "Anti-epileptic drugs-induced de novo absence seizures.", "entity": "Epilepsy, Absence", "aliases": "Absence Epilepsies Childhood Juvenile Epilepsy Seizure Disorder Disorders Atonic Seizures Akinetic Petit Mal Convulsion Absences Atypical Minor Pykno Pykno-Epilepsies Pykno-Epilepsy Pyknolepsies Pyknolepsy", "definition": "A childhood seizure disorder characterized by rhythmic electrical brain discharges of generalized onset. Clinical features include a sudden cessation of ongoing activity usually without loss of postural tone. Rhythmic blinking of the eyelids or lip smacking frequently accompanies the SEIZURES. The usual duration is 5-10 seconds, and multiple episodes may occur daily. Juvenile absence epilepsy is characterized by the juvenile onset of absence seizures and an increased incidence of myoclonus and tonic-clonic seizures. (Menkes, Textbook of Child Neurology, 5th ed, p736)\n    ", "id": "MESH:D004832"}
{"mention": "absence epilepsy", "mention_text": "The authors present three patients with de novo absence epilepsy after administration of carbamazepine and vigabatrin. Despite the underlying diseases, the prognosis for drug-induced de novo absence seizure is good because it subsides rapidly after discontinuing the use of the offending drugs. The gamma-aminobutyric acid-transmitted thalamocortical circuitry accounts for a major part of the underlying neurophysiology of the absence epilepsy. Because drug-induced de novo absence seizure is rare, pro-absence drugs can only be considered a promoting factor. The underlying epileptogenecity of the patients or the synergistic effects of the accompanying drugs is required to trigger the de novo absence seizure. The possibility of drug-induced aggravation should be considered whenever an unexpected increase in seizure frequency and/or new seizure types appear following a change in drug treatment. By understanding the underlying mechanism of absence epilepsy, we can avoid the inappropriate use of anticonvulsants in children with epilepsy and prevent drug-induced absence seizures.", "entity": "Epilepsy, Absence", "aliases": "Absence Epilepsies Childhood Juvenile Epilepsy Seizure Disorder Disorders Atonic Seizures Akinetic Petit Mal Convulsion Absences Atypical Minor Pykno Pykno-Epilepsies Pykno-Epilepsy Pyknolepsies Pyknolepsy", "definition": "A childhood seizure disorder characterized by rhythmic electrical brain discharges of generalized onset. Clinical features include a sudden cessation of ongoing activity usually without loss of postural tone. Rhythmic blinking of the eyelids or lip smacking frequently accompanies the SEIZURES. The usual duration is 5-10 seconds, and multiple episodes may occur daily. Juvenile absence epilepsy is characterized by the juvenile onset of absence seizures and an increased incidence of myoclonus and tonic-clonic seizures. (Menkes, Textbook of Child Neurology, 5th ed, p736)\n    ", "id": "MESH:D004832"}
{"mention": "carbamazepine", "mention_text": "The authors present three patients with de novo absence epilepsy after administration of carbamazepine and vigabatrin. Despite the underlying diseases, the prognosis for drug-induced de novo absence seizure is good because it subsides rapidly after discontinuing the use of the offending drugs. The gamma-aminobutyric acid-transmitted thalamocortical circuitry accounts for a major part of the underlying neurophysiology of the absence epilepsy. Because drug-induced de novo absence seizure is rare, pro-absence drugs can only be considered a promoting factor. The underlying epileptogenecity of the patients or the synergistic effects of the accompanying drugs is required to trigger the de novo absence seizure. The possibility of drug-induced aggravation should be considered whenever an unexpected increase in seizure frequency and/or new seizure types appear following a change in drug treatment. By understanding the underlying mechanism of absence epilepsy, we can avoid the inappropriate use of anticonvulsants in children with epilepsy and prevent drug-induced absence seizures.", "entity": "Carbamazepine", "aliases": "Amizepine Carbamazepine Acetate Anhydrous Dihydrate Hydrochloride L-Tartrate (4:1) Phosphate Sulfate (2:1) Carbazepin Epitol Finlepsin Neurotol Tegretol", "definition": "An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of PHENYTOIN; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar.\n    ", "id": "MESH:D002220"}
{"mention": "vigabatrin", "mention_text": "The authors present three patients with de novo absence epilepsy after administration of carbamazepine and vigabatrin. Despite the underlying diseases, the prognosis for drug-induced de novo absence seizure is good because it subsides rapidly after discontinuing the use of the offending drugs. The gamma-aminobutyric acid-transmitted thalamocortical circuitry accounts for a major part of the underlying neurophysiology of the absence epilepsy. Because drug-induced de novo absence seizure is rare, pro-absence drugs can only be considered a promoting factor. The underlying epileptogenecity of the patients or the synergistic effects of the accompanying drugs is required to trigger the de novo absence seizure. The possibility of drug-induced aggravation should be considered whenever an unexpected increase in seizure frequency and/or new seizure types appear following a change in drug treatment. By understanding the underlying mechanism of absence epilepsy, we can avoid the inappropriate use of anticonvulsants in children with epilepsy and prevent drug-induced absence seizures.", "entity": "Vigabatrin", "aliases": "Acid gamma-Vinyl-gamma-Aminobutyric Aventis Brand of Vigabatrin Hoechst Sabril Sabrilex Yamanouchi gamma Vinyl GABA Aminobutyric gamma-Vinyl-GABA", "definition": "An analogue of GAMMA-AMINOBUTYRIC ACID. It is an irreversible inhibitor of 4-AMINOBUTYRATE TRANSAMINASE, the enzyme responsible for the catabolism of GAMMA-AMINOBUTYRIC ACID. (From Martindale The Extra Pharmacopoeia, 31st ed)\n    ", "id": "MESH:D020888"}
{"mention": "absence seizure", "mention_text": "The authors present three patients with de novo absence epilepsy after administration of carbamazepine and vigabatrin. Despite the underlying diseases, the prognosis for drug-induced de novo absence seizure is good because it subsides rapidly after discontinuing the use of the offending drugs. The gamma-aminobutyric acid-transmitted thalamocortical circuitry accounts for a major part of the underlying neurophysiology of the absence epilepsy. Because drug-induced de novo absence seizure is rare, pro-absence drugs can only be considered a promoting factor. The underlying epileptogenecity of the patients or the synergistic effects of the accompanying drugs is required to trigger the de novo absence seizure. The possibility of drug-induced aggravation should be considered whenever an unexpected increase in seizure frequency and/or new seizure types appear following a change in drug treatment. By understanding the underlying mechanism of absence epilepsy, we can avoid the inappropriate use of anticonvulsants in children with epilepsy and prevent drug-induced absence seizures.", "entity": "Epilepsy, Absence", "aliases": "Absence Epilepsies Childhood Juvenile Epilepsy Seizure Disorder Disorders Atonic Seizures Akinetic Petit Mal Convulsion Absences Atypical Minor Pykno Pykno-Epilepsies Pykno-Epilepsy Pyknolepsies Pyknolepsy", "definition": "A childhood seizure disorder characterized by rhythmic electrical brain discharges of generalized onset. Clinical features include a sudden cessation of ongoing activity usually without loss of postural tone. Rhythmic blinking of the eyelids or lip smacking frequently accompanies the SEIZURES. The usual duration is 5-10 seconds, and multiple episodes may occur daily. Juvenile absence epilepsy is characterized by the juvenile onset of absence seizures and an increased incidence of myoclonus and tonic-clonic seizures. (Menkes, Textbook of Child Neurology, 5th ed, p736)\n    ", "id": "MESH:D004832"}
{"mention": "gamma-aminobutyric acid", "mention_text": "The authors present three patients with de novo absence epilepsy after administration of carbamazepine and vigabatrin. Despite the underlying diseases, the prognosis for drug-induced de novo absence seizure is good because it subsides rapidly after discontinuing the use of the offending drugs. The gamma-aminobutyric acid-transmitted thalamocortical circuitry accounts for a major part of the underlying neurophysiology of the absence epilepsy. Because drug-induced de novo absence seizure is rare, pro-absence drugs can only be considered a promoting factor. The underlying epileptogenecity of the patients or the synergistic effects of the accompanying drugs is required to trigger the de novo absence seizure. The possibility of drug-induced aggravation should be considered whenever an unexpected increase in seizure frequency and/or new seizure types appear following a change in drug treatment. By understanding the underlying mechanism of absence epilepsy, we can avoid the inappropriate use of anticonvulsants in children with epilepsy and prevent drug-induced absence seizures.", "entity": "gamma-Aminobutyric Acid", "aliases": "4 Aminobutanoic Acid Aminobutyric 4-Aminobutanoic 4-Aminobutyric Hydrochloride gamma-Aminobutyric Aminalon Aminalone GABA Lithium Gammalon gamma Monolithium Salt Monosodium Calcium (2:1) Zinc", "definition": "The most common inhibitory neurotransmitter in the central nervous system.\n    ", "id": "MESH:D005680"}
{"mention": "seizure", "mention_text": "The authors present three patients with de novo absence epilepsy after administration of carbamazepine and vigabatrin. Despite the underlying diseases, the prognosis for drug-induced de novo absence seizure is good because it subsides rapidly after discontinuing the use of the offending drugs. The gamma-aminobutyric acid-transmitted thalamocortical circuitry accounts for a major part of the underlying neurophysiology of the absence epilepsy. Because drug-induced de novo absence seizure is rare, pro-absence drugs can only be considered a promoting factor. The underlying epileptogenecity of the patients or the synergistic effects of the accompanying drugs is required to trigger the de novo absence seizure. The possibility of drug-induced aggravation should be considered whenever an unexpected increase in seizure frequency and/or new seizure types appear following a change in drug treatment. By understanding the underlying mechanism of absence epilepsy, we can avoid the inappropriate use of anticonvulsants in children with epilepsy and prevent drug-induced absence seizures.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "epilepsy", "mention_text": "The authors present three patients with de novo absence epilepsy after administration of carbamazepine and vigabatrin. Despite the underlying diseases, the prognosis for drug-induced de novo absence seizure is good because it subsides rapidly after discontinuing the use of the offending drugs. The gamma-aminobutyric acid-transmitted thalamocortical circuitry accounts for a major part of the underlying neurophysiology of the absence epilepsy. Because drug-induced de novo absence seizure is rare, pro-absence drugs can only be considered a promoting factor. The underlying epileptogenecity of the patients or the synergistic effects of the accompanying drugs is required to trigger the de novo absence seizure. The possibility of drug-induced aggravation should be considered whenever an unexpected increase in seizure frequency and/or new seizure types appear following a change in drug treatment. By understanding the underlying mechanism of absence epilepsy, we can avoid the inappropriate use of anticonvulsants in children with epilepsy and prevent drug-induced absence seizures.", "entity": "Epilepsy", "aliases": "Aura Auras Awakening Epilepsy Cryptogenic Epilepsies Epileptic Seizure Seizures Disorder Disorders Single", "definition": "A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313)\n    ", "id": "MESH:D004827"}
{"mention": "absence seizures", "mention_text": "The authors present three patients with de novo absence epilepsy after administration of carbamazepine and vigabatrin. Despite the underlying diseases, the prognosis for drug-induced de novo absence seizure is good because it subsides rapidly after discontinuing the use of the offending drugs. The gamma-aminobutyric acid-transmitted thalamocortical circuitry accounts for a major part of the underlying neurophysiology of the absence epilepsy. Because drug-induced de novo absence seizure is rare, pro-absence drugs can only be considered a promoting factor. The underlying epileptogenecity of the patients or the synergistic effects of the accompanying drugs is required to trigger the de novo absence seizure. The possibility of drug-induced aggravation should be considered whenever an unexpected increase in seizure frequency and/or new seizure types appear following a change in drug treatment. By understanding the underlying mechanism of absence epilepsy, we can avoid the inappropriate use of anticonvulsants in children with epilepsy and prevent drug-induced absence seizures.", "entity": "Epilepsy, Absence", "aliases": "Absence Epilepsies Childhood Juvenile Epilepsy Seizure Disorder Disorders Atonic Seizures Akinetic Petit Mal Convulsion Absences Atypical Minor Pykno Pykno-Epilepsies Pykno-Epilepsy Pyknolepsies Pyknolepsy", "definition": "A childhood seizure disorder characterized by rhythmic electrical brain discharges of generalized onset. Clinical features include a sudden cessation of ongoing activity usually without loss of postural tone. Rhythmic blinking of the eyelids or lip smacking frequently accompanies the SEIZURES. The usual duration is 5-10 seconds, and multiple episodes may occur daily. Juvenile absence epilepsy is characterized by the juvenile onset of absence seizures and an increased incidence of myoclonus and tonic-clonic seizures. (Menkes, Textbook of Child Neurology, 5th ed, p736)\n    ", "id": "MESH:D004832"}
{"mention": "Procainamide", "mention_text": "Procainamide-induced polymorphous ventricular tachycardia.", "entity": "Procainamide", "aliases": "Amide Procaine Apo-Procainamide Apotex Brand of Procainamide Hydrochloride Apothecon Biocoryl Bristol-Myers Squibb Monarch Novocainamide Novocamid Parke Davis Pfizer Procamide Procan SR Procanbid Pronestyl Rhythmin Sidmark Uriach", "definition": "A class Ia antiarrhythmic drug that is structurally-related to PROCAINE.\n    ", "id": "MESH:D011342"}
{"mention": "ventricular tachycardia", "mention_text": "Procainamide-induced polymorphous ventricular tachycardia.", "entity": "Tachycardia, Ventricular", "aliases": "Tachycardia Ventricular Tachycardias", "definition": "An abnormally rapid ventricular rhythm usually in excess of 150 beats per minute. It is generated within the ventricle below the BUNDLE OF HIS, either as autonomic impulse formation or reentrant impulse conduction. Depending on the etiology, onset of ventricular tachycardia can be paroxysmal (sudden) or nonparoxysmal, its wide QRS complexes can be uniform or polymorphic, and the ventricular beating may be independent of the atrial beating (AV dissociation).\n    ", "id": "MESH:D017180"}
{"mention": "procainamide", "mention_text": "Seven cases of procainamide-induced polymorphous ventricular tachycardia are presented. In four patients, polymorphous ventricular tachycardia appeared after intravenous administration of 200 to 400 mg of procainamide for the treatment of sustained ventricular tachycardia. In the remaining three patients, procainamide was administered orally for treatment of chronic premature ventricular contractions or atrial flutter. These patients had Q-T prolongation and recurrent syncope due to polymorphous ventricular tachycardia. In four patients, the arrhythmia was rapidly diagnosed and treated with disappearance of further episodes of the arrhythmia. In two patients, the arrhythmia degenerated into irreversible ventricular fibrillation and both patients died. In the seventh patient, a permanent ventricular pacemaker was inserted and, despite continuation of procainamide therapy, polymorphous ventricular tachycardia did not reoccur. These seven cases demonstrate that procainamide can produce an acquired prolonged Q-T syndrome with polymorphous ventricular tachycardia.", "entity": "Procainamide", "aliases": "Amide Procaine Apo-Procainamide Apotex Brand of Procainamide Hydrochloride Apothecon Biocoryl Bristol-Myers Squibb Monarch Novocainamide Novocamid Parke Davis Pfizer Procamide Procan SR Procanbid Pronestyl Rhythmin Sidmark Uriach", "definition": "A class Ia antiarrhythmic drug that is structurally-related to PROCAINE.\n    ", "id": "MESH:D011342"}
{"mention": "ventricular tachycardia", "mention_text": "Seven cases of procainamide-induced polymorphous ventricular tachycardia are presented. In four patients, polymorphous ventricular tachycardia appeared after intravenous administration of 200 to 400 mg of procainamide for the treatment of sustained ventricular tachycardia. In the remaining three patients, procainamide was administered orally for treatment of chronic premature ventricular contractions or atrial flutter. These patients had Q-T prolongation and recurrent syncope due to polymorphous ventricular tachycardia. In four patients, the arrhythmia was rapidly diagnosed and treated with disappearance of further episodes of the arrhythmia. In two patients, the arrhythmia degenerated into irreversible ventricular fibrillation and both patients died. In the seventh patient, a permanent ventricular pacemaker was inserted and, despite continuation of procainamide therapy, polymorphous ventricular tachycardia did not reoccur. These seven cases demonstrate that procainamide can produce an acquired prolonged Q-T syndrome with polymorphous ventricular tachycardia.", "entity": "Tachycardia, Ventricular", "aliases": "Tachycardia Ventricular Tachycardias", "definition": "An abnormally rapid ventricular rhythm usually in excess of 150 beats per minute. It is generated within the ventricle below the BUNDLE OF HIS, either as autonomic impulse formation or reentrant impulse conduction. Depending on the etiology, onset of ventricular tachycardia can be paroxysmal (sudden) or nonparoxysmal, its wide QRS complexes can be uniform or polymorphic, and the ventricular beating may be independent of the atrial beating (AV dissociation).\n    ", "id": "MESH:D017180"}
{"mention": "premature ventricular contractions", "mention_text": "Seven cases of procainamide-induced polymorphous ventricular tachycardia are presented. In four patients, polymorphous ventricular tachycardia appeared after intravenous administration of 200 to 400 mg of procainamide for the treatment of sustained ventricular tachycardia. In the remaining three patients, procainamide was administered orally for treatment of chronic premature ventricular contractions or atrial flutter. These patients had Q-T prolongation and recurrent syncope due to polymorphous ventricular tachycardia. In four patients, the arrhythmia was rapidly diagnosed and treated with disappearance of further episodes of the arrhythmia. In two patients, the arrhythmia degenerated into irreversible ventricular fibrillation and both patients died. In the seventh patient, a permanent ventricular pacemaker was inserted and, despite continuation of procainamide therapy, polymorphous ventricular tachycardia did not reoccur. These seven cases demonstrate that procainamide can produce an acquired prolonged Q-T syndrome with polymorphous ventricular tachycardia.", "entity": "Ventricular Premature Complexes", "aliases": "Ectopic Beat Ventricular Beats Extrasystole Premature Complex Contraction Contractions Extrasystoles Complexes", "definition": "A type of cardiac arrhythmia with premature contractions of the HEART VENTRICLES. It is characterized by the premature QRS complex on ECG that is of abnormal shape and great duration (generally >129 msec). It is the most common form of all cardiac arrhythmias. Premature ventricular complexes have no clinical significance except in concurrence with heart diseases.\n    ", "id": "MESH:D018879"}
{"mention": "atrial flutter", "mention_text": "Seven cases of procainamide-induced polymorphous ventricular tachycardia are presented. In four patients, polymorphous ventricular tachycardia appeared after intravenous administration of 200 to 400 mg of procainamide for the treatment of sustained ventricular tachycardia. In the remaining three patients, procainamide was administered orally for treatment of chronic premature ventricular contractions or atrial flutter. These patients had Q-T prolongation and recurrent syncope due to polymorphous ventricular tachycardia. In four patients, the arrhythmia was rapidly diagnosed and treated with disappearance of further episodes of the arrhythmia. In two patients, the arrhythmia degenerated into irreversible ventricular fibrillation and both patients died. In the seventh patient, a permanent ventricular pacemaker was inserted and, despite continuation of procainamide therapy, polymorphous ventricular tachycardia did not reoccur. These seven cases demonstrate that procainamide can produce an acquired prolonged Q-T syndrome with polymorphous ventricular tachycardia.", "entity": "Atrial Flutter", "aliases": "Atrial Flutter Flutters Auricular", "definition": "Rapid, irregular atrial contractions caused by a block of electrical impulse conduction in the right atrium and a reentrant wave front traveling up the inter-atrial septum and down the right atrial free wall or vice versa. Unlike ATRIAL FIBRILLATION which is caused by abnormal impulse generation, typical atrial flutter is caused by abnormal impulse conduction. As in atrial fibrillation, patients with atrial flutter cannot effectively pump blood into the lower chambers of the heart (HEART VENTRICLES).\n    ", "id": "MESH:D001282"}
{"mention": "Q-T prolongation", "mention_text": "Seven cases of procainamide-induced polymorphous ventricular tachycardia are presented. In four patients, polymorphous ventricular tachycardia appeared after intravenous administration of 200 to 400 mg of procainamide for the treatment of sustained ventricular tachycardia. In the remaining three patients, procainamide was administered orally for treatment of chronic premature ventricular contractions or atrial flutter. These patients had Q-T prolongation and recurrent syncope due to polymorphous ventricular tachycardia. In four patients, the arrhythmia was rapidly diagnosed and treated with disappearance of further episodes of the arrhythmia. In two patients, the arrhythmia degenerated into irreversible ventricular fibrillation and both patients died. In the seventh patient, a permanent ventricular pacemaker was inserted and, despite continuation of procainamide therapy, polymorphous ventricular tachycardia did not reoccur. These seven cases demonstrate that procainamide can produce an acquired prolonged Q-T syndrome with polymorphous ventricular tachycardia.", "entity": "Long QT Syndrome", "aliases": "Long QT Syndrome", "definition": "A condition that is characterized by episodes of fainting (SYNCOPE) and varying degree of ventricular arrhythmia as indicated by the prolonged QT interval. The inherited forms are caused by mutation of genes encoding cardiac ion channel proteins. The two major forms are ROMANO-WARD SYNDROME and JERVELL-LANGE NIELSEN SYNDROME.\n    ", "id": "MESH:D008133"}
{"mention": "syncope", "mention_text": "Seven cases of procainamide-induced polymorphous ventricular tachycardia are presented. In four patients, polymorphous ventricular tachycardia appeared after intravenous administration of 200 to 400 mg of procainamide for the treatment of sustained ventricular tachycardia. In the remaining three patients, procainamide was administered orally for treatment of chronic premature ventricular contractions or atrial flutter. These patients had Q-T prolongation and recurrent syncope due to polymorphous ventricular tachycardia. In four patients, the arrhythmia was rapidly diagnosed and treated with disappearance of further episodes of the arrhythmia. In two patients, the arrhythmia degenerated into irreversible ventricular fibrillation and both patients died. In the seventh patient, a permanent ventricular pacemaker was inserted and, despite continuation of procainamide therapy, polymorphous ventricular tachycardia did not reoccur. These seven cases demonstrate that procainamide can produce an acquired prolonged Q-T syndrome with polymorphous ventricular tachycardia.", "entity": "Syncope", "aliases": "Attack Drop Cardiogenic Syncope Syncopes Carotid Sinus Convulsive Deglutitional Attacks Effort Episode Syncopal Fainting Hyperventilation Micturition Postural Presyncope Presyncopes Situational Stokes-Adams Episodes Vertigo Stokes Adams Tussive Vertigos", "definition": "A transient loss of consciousness and postural tone caused by diminished blood flow to the brain (i.e., BRAIN ISCHEMIA). Presyncope refers to the sensation of lightheadedness and loss of strength that precedes a syncopal event or accompanies an incomplete syncope. (From Adams et al., Principles of Neurology, 6th ed, pp367-9)\n    ", "id": "MESH:D013575"}
{"mention": "arrhythmia", "mention_text": "Seven cases of procainamide-induced polymorphous ventricular tachycardia are presented. In four patients, polymorphous ventricular tachycardia appeared after intravenous administration of 200 to 400 mg of procainamide for the treatment of sustained ventricular tachycardia. In the remaining three patients, procainamide was administered orally for treatment of chronic premature ventricular contractions or atrial flutter. These patients had Q-T prolongation and recurrent syncope due to polymorphous ventricular tachycardia. In four patients, the arrhythmia was rapidly diagnosed and treated with disappearance of further episodes of the arrhythmia. In two patients, the arrhythmia degenerated into irreversible ventricular fibrillation and both patients died. In the seventh patient, a permanent ventricular pacemaker was inserted and, despite continuation of procainamide therapy, polymorphous ventricular tachycardia did not reoccur. These seven cases demonstrate that procainamide can produce an acquired prolonged Q-T syndrome with polymorphous ventricular tachycardia.", "entity": "Arrhythmias, Cardiac", "aliases": "Arrhythmia Cardiac Arrhythmias Arrythmia Dysrhythmia", "definition": "Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.\n    ", "id": "MESH:D001145"}
{"mention": "ventricular fibrillation", "mention_text": "Seven cases of procainamide-induced polymorphous ventricular tachycardia are presented. In four patients, polymorphous ventricular tachycardia appeared after intravenous administration of 200 to 400 mg of procainamide for the treatment of sustained ventricular tachycardia. In the remaining three patients, procainamide was administered orally for treatment of chronic premature ventricular contractions or atrial flutter. These patients had Q-T prolongation and recurrent syncope due to polymorphous ventricular tachycardia. In four patients, the arrhythmia was rapidly diagnosed and treated with disappearance of further episodes of the arrhythmia. In two patients, the arrhythmia degenerated into irreversible ventricular fibrillation and both patients died. In the seventh patient, a permanent ventricular pacemaker was inserted and, despite continuation of procainamide therapy, polymorphous ventricular tachycardia did not reoccur. These seven cases demonstrate that procainamide can produce an acquired prolonged Q-T syndrome with polymorphous ventricular tachycardia.", "entity": "Ventricular Fibrillation", "aliases": "Fibrillation Ventricular Fibrillations", "definition": "A potentially lethal cardiac arrhythmia that is characterized by uncoordinated extremely rapid firing of electrical impulses (400-600/min) in HEART VENTRICLES. Such asynchronous ventricular quivering or fibrillation prevents any effective cardiac output and results in unconsciousness (SYNCOPE). It is one of the major electrocardiographic patterns seen with CARDIAC ARREST.\n    ", "id": "MESH:D014693"}
{"mention": "prolonged Q-T syndrome", "mention_text": "Seven cases of procainamide-induced polymorphous ventricular tachycardia are presented. In four patients, polymorphous ventricular tachycardia appeared after intravenous administration of 200 to 400 mg of procainamide for the treatment of sustained ventricular tachycardia. In the remaining three patients, procainamide was administered orally for treatment of chronic premature ventricular contractions or atrial flutter. These patients had Q-T prolongation and recurrent syncope due to polymorphous ventricular tachycardia. In four patients, the arrhythmia was rapidly diagnosed and treated with disappearance of further episodes of the arrhythmia. In two patients, the arrhythmia degenerated into irreversible ventricular fibrillation and both patients died. In the seventh patient, a permanent ventricular pacemaker was inserted and, despite continuation of procainamide therapy, polymorphous ventricular tachycardia did not reoccur. These seven cases demonstrate that procainamide can produce an acquired prolonged Q-T syndrome with polymorphous ventricular tachycardia.", "entity": "Long QT Syndrome", "aliases": "Long QT Syndrome", "definition": "A condition that is characterized by episodes of fainting (SYNCOPE) and varying degree of ventricular arrhythmia as indicated by the prolonged QT interval. The inherited forms are caused by mutation of genes encoding cardiac ion channel proteins. The two major forms are ROMANO-WARD SYNDROME and JERVELL-LANGE NIELSEN SYNDROME.\n    ", "id": "MESH:D008133"}
{"mention": "bradykinin", "mention_text": "Role of activation of bradykinin B2 receptors in disruption of the blood-brain barrier during acute hypertension.", "entity": "Bradykinin", "aliases": "Arg Pro Pro Gly Phe Ser Pro Phe Arg Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg Bradykinin Acetate (9-D-Arg)-Isomer Diacetate Hydrochloride Triacetate (1-D-Arg)-Isomer (2-D-Pro)-Isomer (2-D-Pro-3-D-Pro-7-D-Pro)-Isomer (2-D-Pro-7-D-Pro)-Isomer (3-D-Pro)-Isomer (3-D-Pro-7-D-Pro)-Isomer (5-D-Phe)-Isomer (5-D-Phe-8-D-Phe)-Isomer (6-D-Ser)-Isomer (7-D-Pro)-Isomer (8-D-Phe)-Isomer", "definition": "A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.\n    ", "id": "MESH:D001920"}
{"mention": "hypertension", "mention_text": "Role of activation of bradykinin B2 receptors in disruption of the blood-brain barrier during acute hypertension.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "hypertension", "mention_text": "Cellular mechanisms which account for disruption the blood-brain barrier during acute hypertension are not clear. The goal of this study was to determine the role of synthesis/release of bradykinin to activate B2 receptors in disruption of the blood-brain barrier during acute hypertension. Permeability of the blood-brain barrier was quantitated by clearance of fluorescent-labeled dextran before and during phenylephrine-induced acute hypertension in rats treated with vehicle and Hoe-140 (0.1 microM). Phenylephrine infusion increased arterial pressure, arteriolar diameter and clearance of fluorescent dextran by a similar magnitude in both groups. These findings suggest that disruption of the blood-brain barrier during acute hypertension is not related to the synthesis/release of bradykinin to activate B2 receptors.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "bradykinin", "mention_text": "Cellular mechanisms which account for disruption the blood-brain barrier during acute hypertension are not clear. The goal of this study was to determine the role of synthesis/release of bradykinin to activate B2 receptors in disruption of the blood-brain barrier during acute hypertension. Permeability of the blood-brain barrier was quantitated by clearance of fluorescent-labeled dextran before and during phenylephrine-induced acute hypertension in rats treated with vehicle and Hoe-140 (0.1 microM). Phenylephrine infusion increased arterial pressure, arteriolar diameter and clearance of fluorescent dextran by a similar magnitude in both groups. These findings suggest that disruption of the blood-brain barrier during acute hypertension is not related to the synthesis/release of bradykinin to activate B2 receptors.", "entity": "Bradykinin", "aliases": "Arg Pro Pro Gly Phe Ser Pro Phe Arg Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg Bradykinin Acetate (9-D-Arg)-Isomer Diacetate Hydrochloride Triacetate (1-D-Arg)-Isomer (2-D-Pro)-Isomer (2-D-Pro-3-D-Pro-7-D-Pro)-Isomer (2-D-Pro-7-D-Pro)-Isomer (3-D-Pro)-Isomer (3-D-Pro-7-D-Pro)-Isomer (5-D-Phe)-Isomer (5-D-Phe-8-D-Phe)-Isomer (6-D-Ser)-Isomer (7-D-Pro)-Isomer (8-D-Phe)-Isomer", "definition": "A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.\n    ", "id": "MESH:D001920"}
{"mention": "dextran", "mention_text": "Cellular mechanisms which account for disruption the blood-brain barrier during acute hypertension are not clear. The goal of this study was to determine the role of synthesis/release of bradykinin to activate B2 receptors in disruption of the blood-brain barrier during acute hypertension. Permeability of the blood-brain barrier was quantitated by clearance of fluorescent-labeled dextran before and during phenylephrine-induced acute hypertension in rats treated with vehicle and Hoe-140 (0.1 microM). Phenylephrine infusion increased arterial pressure, arteriolar diameter and clearance of fluorescent dextran by a similar magnitude in both groups. These findings suggest that disruption of the blood-brain barrier during acute hypertension is not related to the synthesis/release of bradykinin to activate B2 receptors.", "entity": "Dextrans", "aliases": "Dextran 40 40000 70 75 80 B 1355 S B-1355 B-1355-S B1355 B512 Derivatives M T 500 T-40 T-500 Dextrans Hemodex Hyskon Infukoll Macrodex Polyglucin Promit Rheodextran Rheoisodex Rheomacrodex Rheopolyglucin Rondex Saviosol", "definition": "A group of glucose polymers made by certain bacteria. Dextrans are used therapeutically as plasma volume expanders and anticoagulants. They are also commonly used in biological experimentation and in industry for a wide variety of purposes.\n    ", "id": "MESH:D003911"}
{"mention": "phenylephrine", "mention_text": "Cellular mechanisms which account for disruption the blood-brain barrier during acute hypertension are not clear. The goal of this study was to determine the role of synthesis/release of bradykinin to activate B2 receptors in disruption of the blood-brain barrier during acute hypertension. Permeability of the blood-brain barrier was quantitated by clearance of fluorescent-labeled dextran before and during phenylephrine-induced acute hypertension in rats treated with vehicle and Hoe-140 (0.1 microM). Phenylephrine infusion increased arterial pressure, arteriolar diameter and clearance of fluorescent dextran by a similar magnitude in both groups. These findings suggest that disruption of the blood-brain barrier during acute hypertension is not related to the synthesis/release of bradykinin to activate B2 receptors.", "entity": "Phenylephrine", "aliases": "(R)-3-Hydroxy-alpha-((methylamino)methyl)benzenemethanol Metaoxedrin Metasympatol Mezaton Neo Synephrine Neo-Synephrine Neosynephrine Phenylephrine Hydrochloride Tannate", "definition": "An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.\n    ", "id": "MESH:D010656"}
{"mention": "Hoe-140", "mention_text": "Cellular mechanisms which account for disruption the blood-brain barrier during acute hypertension are not clear. The goal of this study was to determine the role of synthesis/release of bradykinin to activate B2 receptors in disruption of the blood-brain barrier during acute hypertension. Permeability of the blood-brain barrier was quantitated by clearance of fluorescent-labeled dextran before and during phenylephrine-induced acute hypertension in rats treated with vehicle and Hoe-140 (0.1 microM). Phenylephrine infusion increased arterial pressure, arteriolar diameter and clearance of fluorescent dextran by a similar magnitude in both groups. These findings suggest that disruption of the blood-brain barrier during acute hypertension is not related to the synthesis/release of bradykinin to activate B2 receptors.", "entity": "icatibant", "aliases": "D-Arg(Hyp(3)-Thi(5)-D-Tic(7)-Oic(8))BK HOE 140 HOE-140 HOE140 Hoechst Hoechst-140 JE 049 JE-049 WIN 65365 WIN-65365 icatibant acetate", "definition": "", "id": "MESH:C065679"}
{"mention": "Phenylephrine", "mention_text": "Cellular mechanisms which account for disruption the blood-brain barrier during acute hypertension are not clear. The goal of this study was to determine the role of synthesis/release of bradykinin to activate B2 receptors in disruption of the blood-brain barrier during acute hypertension. Permeability of the blood-brain barrier was quantitated by clearance of fluorescent-labeled dextran before and during phenylephrine-induced acute hypertension in rats treated with vehicle and Hoe-140 (0.1 microM). Phenylephrine infusion increased arterial pressure, arteriolar diameter and clearance of fluorescent dextran by a similar magnitude in both groups. These findings suggest that disruption of the blood-brain barrier during acute hypertension is not related to the synthesis/release of bradykinin to activate B2 receptors.", "entity": "Phenylephrine", "aliases": "(R)-3-Hydroxy-alpha-((methylamino)methyl)benzenemethanol Metaoxedrin Metasympatol Mezaton Neo Synephrine Neo-Synephrine Neosynephrine Phenylephrine Hydrochloride Tannate", "definition": "An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.\n    ", "id": "MESH:D010656"}
{"mention": "5-azacytidine", "mention_text": "5-azacytidine potentiates initiation induced by carcinogens in rat liver.", "entity": "Azacitidine", "aliases": "5 Azacytidine 5-Azacytidine Azacitidine NSC 102816 NSC-102816 NSC102816 Pharmion Brand of Vidaza", "definition": "A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.\n    ", "id": "MESH:D001374"}
{"mention": "initiation induced by carcinogens", "mention_text": "5-azacytidine potentiates initiation induced by carcinogens in rat liver.", "entity": "Precancerous Conditions", "aliases": "Condition Precancerous Preneoplastic Conditions", "definition": "Pathological processes that tend eventually to become malignant. (From Dorland, 27th ed)\n    ", "id": "MESH:D011230"}
{"mention": "initiation of carcinogenic process", "mention_text": "To test the validity of the hypothesis that hypomethylation of DNA plays an important role in the initiation of carcinogenic process, 5-azacytidine (5-AzC) (10 mg/kg), an inhibitor of DNA methylation, was given to rats during the phase of repair synthesis induced by the three carcinogens, benzo[a]-pyrene (200 mg/kg), N-methyl-N-nitrosourea (60 mg/kg) and 1,2-dimethylhydrazine (1,2-DMH) (100 mg/kg). The initiated hepatocytes in the liver were assayed as the gamma-glutamyltransferase (gamma-GT) positive foci formed following a 2-week selection regimen consisting of dietary 0.02% 2-acetylaminofluorene coupled with a necrogenic dose of CCl4. The results obtained indicate that with all three carcinogens, administration of 5-AzC during repair synthesis increased the incidence of initiated hepatocytes, for example 10-20 foci/cm2 in 5-AzC and carcinogen-treated rats compared with 3-5 foci/cm2 in rats treated with carcinogen only. Administration of [3H]-5-azadeoxycytidine during the repair synthesis induced by 1,2-DMH further showed that 0.019 mol % of cytosine residues in DNA were substituted by the analogue, indicating that incorporation of 5-AzC occurs during repair synthesis. In the absence of the carcinogen, 5-AzC given after a two thirds partial hepatectomy, when its incorporation should be maximum, failed to induce any gamma-GT positive foci. The results suggest that hypomethylation of DNA per se may not be sufficient for initiation. Perhaps two events might be necessary for initiation, the first caused by the carcinogen and a second involving hypomethylation of DNA.", "entity": "Precancerous Conditions", "aliases": "Condition Precancerous Preneoplastic Conditions", "definition": "Pathological processes that tend eventually to become malignant. (From Dorland, 27th ed)\n    ", "id": "MESH:D011230"}
{"mention": "5-azacytidine", "mention_text": "To test the validity of the hypothesis that hypomethylation of DNA plays an important role in the initiation of carcinogenic process, 5-azacytidine (5-AzC) (10 mg/kg), an inhibitor of DNA methylation, was given to rats during the phase of repair synthesis induced by the three carcinogens, benzo[a]-pyrene (200 mg/kg), N-methyl-N-nitrosourea (60 mg/kg) and 1,2-dimethylhydrazine (1,2-DMH) (100 mg/kg). The initiated hepatocytes in the liver were assayed as the gamma-glutamyltransferase (gamma-GT) positive foci formed following a 2-week selection regimen consisting of dietary 0.02% 2-acetylaminofluorene coupled with a necrogenic dose of CCl4. The results obtained indicate that with all three carcinogens, administration of 5-AzC during repair synthesis increased the incidence of initiated hepatocytes, for example 10-20 foci/cm2 in 5-AzC and carcinogen-treated rats compared with 3-5 foci/cm2 in rats treated with carcinogen only. Administration of [3H]-5-azadeoxycytidine during the repair synthesis induced by 1,2-DMH further showed that 0.019 mol % of cytosine residues in DNA were substituted by the analogue, indicating that incorporation of 5-AzC occurs during repair synthesis. In the absence of the carcinogen, 5-AzC given after a two thirds partial hepatectomy, when its incorporation should be maximum, failed to induce any gamma-GT positive foci. The results suggest that hypomethylation of DNA per se may not be sufficient for initiation. Perhaps two events might be necessary for initiation, the first caused by the carcinogen and a second involving hypomethylation of DNA.", "entity": "Azacitidine", "aliases": "5 Azacytidine 5-Azacytidine Azacitidine NSC 102816 NSC-102816 NSC102816 Pharmion Brand of Vidaza", "definition": "A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.\n    ", "id": "MESH:D001374"}
{"mention": "5-AzC", "mention_text": "To test the validity of the hypothesis that hypomethylation of DNA plays an important role in the initiation of carcinogenic process, 5-azacytidine (5-AzC) (10 mg/kg), an inhibitor of DNA methylation, was given to rats during the phase of repair synthesis induced by the three carcinogens, benzo[a]-pyrene (200 mg/kg), N-methyl-N-nitrosourea (60 mg/kg) and 1,2-dimethylhydrazine (1,2-DMH) (100 mg/kg). The initiated hepatocytes in the liver were assayed as the gamma-glutamyltransferase (gamma-GT) positive foci formed following a 2-week selection regimen consisting of dietary 0.02% 2-acetylaminofluorene coupled with a necrogenic dose of CCl4. The results obtained indicate that with all three carcinogens, administration of 5-AzC during repair synthesis increased the incidence of initiated hepatocytes, for example 10-20 foci/cm2 in 5-AzC and carcinogen-treated rats compared with 3-5 foci/cm2 in rats treated with carcinogen only. Administration of [3H]-5-azadeoxycytidine during the repair synthesis induced by 1,2-DMH further showed that 0.019 mol % of cytosine residues in DNA were substituted by the analogue, indicating that incorporation of 5-AzC occurs during repair synthesis. In the absence of the carcinogen, 5-AzC given after a two thirds partial hepatectomy, when its incorporation should be maximum, failed to induce any gamma-GT positive foci. The results suggest that hypomethylation of DNA per se may not be sufficient for initiation. Perhaps two events might be necessary for initiation, the first caused by the carcinogen and a second involving hypomethylation of DNA.", "entity": "Azacitidine", "aliases": "5 Azacytidine 5-Azacytidine Azacitidine NSC 102816 NSC-102816 NSC102816 Pharmion Brand of Vidaza", "definition": "A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.\n    ", "id": "MESH:D001374"}
{"mention": "benzo[a]-pyrene", "mention_text": "To test the validity of the hypothesis that hypomethylation of DNA plays an important role in the initiation of carcinogenic process, 5-azacytidine (5-AzC) (10 mg/kg), an inhibitor of DNA methylation, was given to rats during the phase of repair synthesis induced by the three carcinogens, benzo[a]-pyrene (200 mg/kg), N-methyl-N-nitrosourea (60 mg/kg) and 1,2-dimethylhydrazine (1,2-DMH) (100 mg/kg). The initiated hepatocytes in the liver were assayed as the gamma-glutamyltransferase (gamma-GT) positive foci formed following a 2-week selection regimen consisting of dietary 0.02% 2-acetylaminofluorene coupled with a necrogenic dose of CCl4. The results obtained indicate that with all three carcinogens, administration of 5-AzC during repair synthesis increased the incidence of initiated hepatocytes, for example 10-20 foci/cm2 in 5-AzC and carcinogen-treated rats compared with 3-5 foci/cm2 in rats treated with carcinogen only. Administration of [3H]-5-azadeoxycytidine during the repair synthesis induced by 1,2-DMH further showed that 0.019 mol % of cytosine residues in DNA were substituted by the analogue, indicating that incorporation of 5-AzC occurs during repair synthesis. In the absence of the carcinogen, 5-AzC given after a two thirds partial hepatectomy, when its incorporation should be maximum, failed to induce any gamma-GT positive foci. The results suggest that hypomethylation of DNA per se may not be sufficient for initiation. Perhaps two events might be necessary for initiation, the first caused by the carcinogen and a second involving hypomethylation of DNA.", "entity": "Benzo(a)pyrene", "aliases": "3,4 Benzopyrene Benzpyrene 3,4-Benzopyrene 3,4-Benzpyrene Benzo(a)pyrene", "definition": "A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke.\n    ", "id": "MESH:D001564"}
{"mention": "N-methyl-N-nitrosourea", "mention_text": "To test the validity of the hypothesis that hypomethylation of DNA plays an important role in the initiation of carcinogenic process, 5-azacytidine (5-AzC) (10 mg/kg), an inhibitor of DNA methylation, was given to rats during the phase of repair synthesis induced by the three carcinogens, benzo[a]-pyrene (200 mg/kg), N-methyl-N-nitrosourea (60 mg/kg) and 1,2-dimethylhydrazine (1,2-DMH) (100 mg/kg). The initiated hepatocytes in the liver were assayed as the gamma-glutamyltransferase (gamma-GT) positive foci formed following a 2-week selection regimen consisting of dietary 0.02% 2-acetylaminofluorene coupled with a necrogenic dose of CCl4. The results obtained indicate that with all three carcinogens, administration of 5-AzC during repair synthesis increased the incidence of initiated hepatocytes, for example 10-20 foci/cm2 in 5-AzC and carcinogen-treated rats compared with 3-5 foci/cm2 in rats treated with carcinogen only. Administration of [3H]-5-azadeoxycytidine during the repair synthesis induced by 1,2-DMH further showed that 0.019 mol % of cytosine residues in DNA were substituted by the analogue, indicating that incorporation of 5-AzC occurs during repair synthesis. In the absence of the carcinogen, 5-AzC given after a two thirds partial hepatectomy, when its incorporation should be maximum, failed to induce any gamma-GT positive foci. The results suggest that hypomethylation of DNA per se may not be sufficient for initiation. Perhaps two events might be necessary for initiation, the first caused by the carcinogen and a second involving hypomethylation of DNA.", "entity": "Methylnitrosourea", "aliases": "Methylnitrosourea N Methyl N nitrosourea N-Methyl-N-nitrosourea NSC 23909 NSC-23909 NSC23909 Nitrosomethylurea", "definition": "A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties.\n    ", "id": "MESH:D008770"}
{"mention": "1,2-dimethylhydrazine", "mention_text": "To test the validity of the hypothesis that hypomethylation of DNA plays an important role in the initiation of carcinogenic process, 5-azacytidine (5-AzC) (10 mg/kg), an inhibitor of DNA methylation, was given to rats during the phase of repair synthesis induced by the three carcinogens, benzo[a]-pyrene (200 mg/kg), N-methyl-N-nitrosourea (60 mg/kg) and 1,2-dimethylhydrazine (1,2-DMH) (100 mg/kg). The initiated hepatocytes in the liver were assayed as the gamma-glutamyltransferase (gamma-GT) positive foci formed following a 2-week selection regimen consisting of dietary 0.02% 2-acetylaminofluorene coupled with a necrogenic dose of CCl4. The results obtained indicate that with all three carcinogens, administration of 5-AzC during repair synthesis increased the incidence of initiated hepatocytes, for example 10-20 foci/cm2 in 5-AzC and carcinogen-treated rats compared with 3-5 foci/cm2 in rats treated with carcinogen only. Administration of [3H]-5-azadeoxycytidine during the repair synthesis induced by 1,2-DMH further showed that 0.019 mol % of cytosine residues in DNA were substituted by the analogue, indicating that incorporation of 5-AzC occurs during repair synthesis. In the absence of the carcinogen, 5-AzC given after a two thirds partial hepatectomy, when its incorporation should be maximum, failed to induce any gamma-GT positive foci. The results suggest that hypomethylation of DNA per se may not be sufficient for initiation. Perhaps two events might be necessary for initiation, the first caused by the carcinogen and a second involving hypomethylation of DNA.", "entity": "1,2-Dimethylhydrazine", "aliases": "1,2 Dimethyl hydrazine Dimethylhydrazine 1,2-Dimethyl-hydrazine 1,2-Dimethylhydrazine N,N' N,N'-Dimethylhydrazine SDMH sym sym-Dimethylhydrazine", "definition": "A DNA alkylating agent that has been shown to be a potent carcinogen and is widely used to induce colon tumors in experimental animals.\n    ", "id": "MESH:D019813"}
{"mention": "1,2-DMH", "mention_text": "To test the validity of the hypothesis that hypomethylation of DNA plays an important role in the initiation of carcinogenic process, 5-azacytidine (5-AzC) (10 mg/kg), an inhibitor of DNA methylation, was given to rats during the phase of repair synthesis induced by the three carcinogens, benzo[a]-pyrene (200 mg/kg), N-methyl-N-nitrosourea (60 mg/kg) and 1,2-dimethylhydrazine (1,2-DMH) (100 mg/kg). The initiated hepatocytes in the liver were assayed as the gamma-glutamyltransferase (gamma-GT) positive foci formed following a 2-week selection regimen consisting of dietary 0.02% 2-acetylaminofluorene coupled with a necrogenic dose of CCl4. The results obtained indicate that with all three carcinogens, administration of 5-AzC during repair synthesis increased the incidence of initiated hepatocytes, for example 10-20 foci/cm2 in 5-AzC and carcinogen-treated rats compared with 3-5 foci/cm2 in rats treated with carcinogen only. Administration of [3H]-5-azadeoxycytidine during the repair synthesis induced by 1,2-DMH further showed that 0.019 mol % of cytosine residues in DNA were substituted by the analogue, indicating that incorporation of 5-AzC occurs during repair synthesis. In the absence of the carcinogen, 5-AzC given after a two thirds partial hepatectomy, when its incorporation should be maximum, failed to induce any gamma-GT positive foci. The results suggest that hypomethylation of DNA per se may not be sufficient for initiation. Perhaps two events might be necessary for initiation, the first caused by the carcinogen and a second involving hypomethylation of DNA.", "entity": "1,2-Dimethylhydrazine", "aliases": "1,2 Dimethyl hydrazine Dimethylhydrazine 1,2-Dimethyl-hydrazine 1,2-Dimethylhydrazine N,N' N,N'-Dimethylhydrazine SDMH sym sym-Dimethylhydrazine", "definition": "A DNA alkylating agent that has been shown to be a potent carcinogen and is widely used to induce colon tumors in experimental animals.\n    ", "id": "MESH:D019813"}
{"mention": "2-acetylaminofluorene", "mention_text": "To test the validity of the hypothesis that hypomethylation of DNA plays an important role in the initiation of carcinogenic process, 5-azacytidine (5-AzC) (10 mg/kg), an inhibitor of DNA methylation, was given to rats during the phase of repair synthesis induced by the three carcinogens, benzo[a]-pyrene (200 mg/kg), N-methyl-N-nitrosourea (60 mg/kg) and 1,2-dimethylhydrazine (1,2-DMH) (100 mg/kg). The initiated hepatocytes in the liver were assayed as the gamma-glutamyltransferase (gamma-GT) positive foci formed following a 2-week selection regimen consisting of dietary 0.02% 2-acetylaminofluorene coupled with a necrogenic dose of CCl4. The results obtained indicate that with all three carcinogens, administration of 5-AzC during repair synthesis increased the incidence of initiated hepatocytes, for example 10-20 foci/cm2 in 5-AzC and carcinogen-treated rats compared with 3-5 foci/cm2 in rats treated with carcinogen only. Administration of [3H]-5-azadeoxycytidine during the repair synthesis induced by 1,2-DMH further showed that 0.019 mol % of cytosine residues in DNA were substituted by the analogue, indicating that incorporation of 5-AzC occurs during repair synthesis. In the absence of the carcinogen, 5-AzC given after a two thirds partial hepatectomy, when its incorporation should be maximum, failed to induce any gamma-GT positive foci. The results suggest that hypomethylation of DNA per se may not be sufficient for initiation. Perhaps two events might be necessary for initiation, the first caused by the carcinogen and a second involving hypomethylation of DNA.", "entity": "2-Acetylaminofluorene", "aliases": "2 Acetamidofluorene Acetylaminofluorene Fluorenylacetamide 2-AAF 2-Acetamidofluorene 2-Acetylaminofluorene 2-Fluorenylacetamide AAF Aminofluorene Fluoren ylacetamide Fluoren-2-ylacetamide N Acetyl N-2-Fluorenylacetamide N-Acetyl-2-Aminofluorene", "definition": "A hepatic carcinogen whose mechanism of activation involves N-hydroxylation to the aryl hydroxamic acid followed by enzymatic sulfonation to sulfoxyfluorenylacetamide. It is used to study the carcinogenicity and mutagenicity of aromatic amines.\n    ", "id": "MESH:D015073"}
{"mention": "CCl4", "mention_text": "To test the validity of the hypothesis that hypomethylation of DNA plays an important role in the initiation of carcinogenic process, 5-azacytidine (5-AzC) (10 mg/kg), an inhibitor of DNA methylation, was given to rats during the phase of repair synthesis induced by the three carcinogens, benzo[a]-pyrene (200 mg/kg), N-methyl-N-nitrosourea (60 mg/kg) and 1,2-dimethylhydrazine (1,2-DMH) (100 mg/kg). The initiated hepatocytes in the liver were assayed as the gamma-glutamyltransferase (gamma-GT) positive foci formed following a 2-week selection regimen consisting of dietary 0.02% 2-acetylaminofluorene coupled with a necrogenic dose of CCl4. The results obtained indicate that with all three carcinogens, administration of 5-AzC during repair synthesis increased the incidence of initiated hepatocytes, for example 10-20 foci/cm2 in 5-AzC and carcinogen-treated rats compared with 3-5 foci/cm2 in rats treated with carcinogen only. Administration of [3H]-5-azadeoxycytidine during the repair synthesis induced by 1,2-DMH further showed that 0.019 mol % of cytosine residues in DNA were substituted by the analogue, indicating that incorporation of 5-AzC occurs during repair synthesis. In the absence of the carcinogen, 5-AzC given after a two thirds partial hepatectomy, when its incorporation should be maximum, failed to induce any gamma-GT positive foci. The results suggest that hypomethylation of DNA per se may not be sufficient for initiation. Perhaps two events might be necessary for initiation, the first caused by the carcinogen and a second involving hypomethylation of DNA.", "entity": "Carbon Tetrachloride", "aliases": "Carbon Tetrachloride Tetrachloromethane", "definition": "A solvent for oils, fats, lacquers, varnishes, rubber waxes, and resins, and a starting material in the manufacturing of organic compounds. Poisoning by inhalation, ingestion or skin absorption is possible and may be fatal. (Merck Index, 11th ed)\n    ", "id": "MESH:D002251"}
{"mention": "[3H]-5-azadeoxycytidine", "mention_text": "To test the validity of the hypothesis that hypomethylation of DNA plays an important role in the initiation of carcinogenic process, 5-azacytidine (5-AzC) (10 mg/kg), an inhibitor of DNA methylation, was given to rats during the phase of repair synthesis induced by the three carcinogens, benzo[a]-pyrene (200 mg/kg), N-methyl-N-nitrosourea (60 mg/kg) and 1,2-dimethylhydrazine (1,2-DMH) (100 mg/kg). The initiated hepatocytes in the liver were assayed as the gamma-glutamyltransferase (gamma-GT) positive foci formed following a 2-week selection regimen consisting of dietary 0.02% 2-acetylaminofluorene coupled with a necrogenic dose of CCl4. The results obtained indicate that with all three carcinogens, administration of 5-AzC during repair synthesis increased the incidence of initiated hepatocytes, for example 10-20 foci/cm2 in 5-AzC and carcinogen-treated rats compared with 3-5 foci/cm2 in rats treated with carcinogen only. Administration of [3H]-5-azadeoxycytidine during the repair synthesis induced by 1,2-DMH further showed that 0.019 mol % of cytosine residues in DNA were substituted by the analogue, indicating that incorporation of 5-AzC occurs during repair synthesis. In the absence of the carcinogen, 5-AzC given after a two thirds partial hepatectomy, when its incorporation should be maximum, failed to induce any gamma-GT positive foci. The results suggest that hypomethylation of DNA per se may not be sufficient for initiation. Perhaps two events might be necessary for initiation, the first caused by the carcinogen and a second involving hypomethylation of DNA.", "entity": "decitabine", "aliases": "2'-deoxy-5-azacytidine 5-aza-2'-deoxycytidine 5-azadeoxycytidine 5-deoxyazacytidine AzadC compound Dacogen NSC 127716 NSC-127716 decitabine mesylate", "definition": "", "id": "MESH:C014347"}
{"mention": "cytosine", "mention_text": "To test the validity of the hypothesis that hypomethylation of DNA plays an important role in the initiation of carcinogenic process, 5-azacytidine (5-AzC) (10 mg/kg), an inhibitor of DNA methylation, was given to rats during the phase of repair synthesis induced by the three carcinogens, benzo[a]-pyrene (200 mg/kg), N-methyl-N-nitrosourea (60 mg/kg) and 1,2-dimethylhydrazine (1,2-DMH) (100 mg/kg). The initiated hepatocytes in the liver were assayed as the gamma-glutamyltransferase (gamma-GT) positive foci formed following a 2-week selection regimen consisting of dietary 0.02% 2-acetylaminofluorene coupled with a necrogenic dose of CCl4. The results obtained indicate that with all three carcinogens, administration of 5-AzC during repair synthesis increased the incidence of initiated hepatocytes, for example 10-20 foci/cm2 in 5-AzC and carcinogen-treated rats compared with 3-5 foci/cm2 in rats treated with carcinogen only. Administration of [3H]-5-azadeoxycytidine during the repair synthesis induced by 1,2-DMH further showed that 0.019 mol % of cytosine residues in DNA were substituted by the analogue, indicating that incorporation of 5-AzC occurs during repair synthesis. In the absence of the carcinogen, 5-AzC given after a two thirds partial hepatectomy, when its incorporation should be maximum, failed to induce any gamma-GT positive foci. The results suggest that hypomethylation of DNA per se may not be sufficient for initiation. Perhaps two events might be necessary for initiation, the first caused by the carcinogen and a second involving hypomethylation of DNA.", "entity": "Cytosine", "aliases": "Cytosine", "definition": "A pyrimidine base that is a fundamental unit of nucleic acids.\n    ", "id": "MESH:D003596"}
{"mention": "emergent rabbit syndrome", "mention_text": "Withdrawal-emergent rabbit syndrome during dose reduction of risperidone.", "entity": "Basal Ganglia Diseases", "aliases": "Basal Ganglia Disease Diseases Disorder Disorders Extrapyramidal Lenticulostriate", "definition": "Diseases of the BASAL GANGLIA including the PUTAMEN; GLOBUS PALLIDUS; claustrum; AMYGDALA; and CAUDATE NUCLEUS. DYSKINESIAS (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include CEREBROVASCULAR DISORDERS; NEURODEGENERATIVE DISEASES; and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D001480"}
{"mention": "risperidone", "mention_text": "Withdrawal-emergent rabbit syndrome during dose reduction of risperidone.", "entity": "Risperidone", "aliases": "Consta Risperdal R 64,766 64766 R-64,766 R-64766 R64,766 R64766 Risperidal Risperidone", "definition": "A selective blocker of DOPAMINE D2 RECEPTORS and SEROTONIN 5-HT2 RECEPTORS that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of SCHIZOPHRENIA.\n    ", "id": "MESH:D018967"}
{"mention": "Rabbit syndrome", "mention_text": "Rabbit syndrome (RS) is a rare extrapyramidal side effect caused by prolonged neuroleptic medication. Here we present a case of withdrawal-emergent RS, which is the first of its kind to be reported. The patient developed RS during dose reduction of risperidone. The symptom was treated successfully with trihexyphenidyl anticholinergic therapy. The underlying mechanism of withdrawal-emergent RS in the present case may have been related to the pharmacological profile of risperidone, a serotonin-dopamine antagonist, suggesting the pathophysiologic influence of the serotonin system in the development of RS.", "entity": "Basal Ganglia Diseases", "aliases": "Basal Ganglia Disease Diseases Disorder Disorders Extrapyramidal Lenticulostriate", "definition": "Diseases of the BASAL GANGLIA including the PUTAMEN; GLOBUS PALLIDUS; claustrum; AMYGDALA; and CAUDATE NUCLEUS. DYSKINESIAS (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include CEREBROVASCULAR DISORDERS; NEURODEGENERATIVE DISEASES; and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D001480"}
{"mention": "RS", "mention_text": "Rabbit syndrome (RS) is a rare extrapyramidal side effect caused by prolonged neuroleptic medication. Here we present a case of withdrawal-emergent RS, which is the first of its kind to be reported. The patient developed RS during dose reduction of risperidone. The symptom was treated successfully with trihexyphenidyl anticholinergic therapy. The underlying mechanism of withdrawal-emergent RS in the present case may have been related to the pharmacological profile of risperidone, a serotonin-dopamine antagonist, suggesting the pathophysiologic influence of the serotonin system in the development of RS.", "entity": "Basal Ganglia Diseases", "aliases": "Basal Ganglia Disease Diseases Disorder Disorders Extrapyramidal Lenticulostriate", "definition": "Diseases of the BASAL GANGLIA including the PUTAMEN; GLOBUS PALLIDUS; claustrum; AMYGDALA; and CAUDATE NUCLEUS. DYSKINESIAS (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include CEREBROVASCULAR DISORDERS; NEURODEGENERATIVE DISEASES; and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D001480"}
{"mention": "emergent RS", "mention_text": "Rabbit syndrome (RS) is a rare extrapyramidal side effect caused by prolonged neuroleptic medication. Here we present a case of withdrawal-emergent RS, which is the first of its kind to be reported. The patient developed RS during dose reduction of risperidone. The symptom was treated successfully with trihexyphenidyl anticholinergic therapy. The underlying mechanism of withdrawal-emergent RS in the present case may have been related to the pharmacological profile of risperidone, a serotonin-dopamine antagonist, suggesting the pathophysiologic influence of the serotonin system in the development of RS.", "entity": "Basal Ganglia Diseases", "aliases": "Basal Ganglia Disease Diseases Disorder Disorders Extrapyramidal Lenticulostriate", "definition": "Diseases of the BASAL GANGLIA including the PUTAMEN; GLOBUS PALLIDUS; claustrum; AMYGDALA; and CAUDATE NUCLEUS. DYSKINESIAS (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include CEREBROVASCULAR DISORDERS; NEURODEGENERATIVE DISEASES; and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D001480"}
{"mention": "risperidone", "mention_text": "Rabbit syndrome (RS) is a rare extrapyramidal side effect caused by prolonged neuroleptic medication. Here we present a case of withdrawal-emergent RS, which is the first of its kind to be reported. The patient developed RS during dose reduction of risperidone. The symptom was treated successfully with trihexyphenidyl anticholinergic therapy. The underlying mechanism of withdrawal-emergent RS in the present case may have been related to the pharmacological profile of risperidone, a serotonin-dopamine antagonist, suggesting the pathophysiologic influence of the serotonin system in the development of RS.", "entity": "Risperidone", "aliases": "Consta Risperdal R 64,766 64766 R-64,766 R-64766 R64,766 R64766 Risperidal Risperidone", "definition": "A selective blocker of DOPAMINE D2 RECEPTORS and SEROTONIN 5-HT2 RECEPTORS that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of SCHIZOPHRENIA.\n    ", "id": "MESH:D018967"}
{"mention": "trihexyphenidyl", "mention_text": "Rabbit syndrome (RS) is a rare extrapyramidal side effect caused by prolonged neuroleptic medication. Here we present a case of withdrawal-emergent RS, which is the first of its kind to be reported. The patient developed RS during dose reduction of risperidone. The symptom was treated successfully with trihexyphenidyl anticholinergic therapy. The underlying mechanism of withdrawal-emergent RS in the present case may have been related to the pharmacological profile of risperidone, a serotonin-dopamine antagonist, suggesting the pathophysiologic influence of the serotonin system in the development of RS.", "entity": "Trihexyphenidyl", "aliases": "AHP Brand of Trihexyphenidyl Hydrochloride Apo Trihex Apo-Trihex ApoTrihex Apotex Artane Aventis Benzhexol Cyclodol Cypress Eisai Hexal Hipokinon Lederle Liquipharm Parkinane Parkopan Pharmaceutical Associates Psicofarma Rugby Schrein Trihexane Trihexidyl Elixir Wyeth", "definition": "One of the centrally acting MUSCARINIC ANTAGONISTS used for treatment of PARKINSONIAN DISORDERS and drug-induced extrapyramidal movement disorders and as an antispasmodic.\n    ", "id": "MESH:D014282"}
{"mention": "serotonin", "mention_text": "Rabbit syndrome (RS) is a rare extrapyramidal side effect caused by prolonged neuroleptic medication. Here we present a case of withdrawal-emergent RS, which is the first of its kind to be reported. The patient developed RS during dose reduction of risperidone. The symptom was treated successfully with trihexyphenidyl anticholinergic therapy. The underlying mechanism of withdrawal-emergent RS in the present case may have been related to the pharmacological profile of risperidone, a serotonin-dopamine antagonist, suggesting the pathophysiologic influence of the serotonin system in the development of RS.", "entity": "Serotonin", "aliases": "3-(2-Aminoethyl)-1H-indol-5-ol 5 Hydroxytryptamine 5-HT 5-Hydroxytryptamine Enteramine Hippophaine Serotonin", "definition": "A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.\n    ", "id": "MESH:D012701"}
{"mention": "dopamine", "mention_text": "Rabbit syndrome (RS) is a rare extrapyramidal side effect caused by prolonged neuroleptic medication. Here we present a case of withdrawal-emergent RS, which is the first of its kind to be reported. The patient developed RS during dose reduction of risperidone. The symptom was treated successfully with trihexyphenidyl anticholinergic therapy. The underlying mechanism of withdrawal-emergent RS in the present case may have been related to the pharmacological profile of risperidone, a serotonin-dopamine antagonist, suggesting the pathophysiologic influence of the serotonin system in the development of RS.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "Verapamil", "mention_text": "Verapamil withdrawal as a possible cause of myocardial infarction in a hypertensive woman with a normal coronary angiogram.", "entity": "Verapamil", "aliases": "Calan Cordilox Dexverapamil Falicard Finoptin Hydrochloride Verapamil Iproveratril Isoptin Isoptine Izoptin Lekoptin Sandoz Brand of", "definition": "A calcium channel blocker that is a class IV anti-arrhythmia agent.\n    ", "id": "MESH:D014700"}
{"mention": "myocardial infarction", "mention_text": "Verapamil withdrawal as a possible cause of myocardial infarction in a hypertensive woman with a normal coronary angiogram.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "hypertensive", "mention_text": "Verapamil withdrawal as a possible cause of myocardial infarction in a hypertensive woman with a normal coronary angiogram.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "Verapamil", "mention_text": "Verapamil is an effective and relatively-safe antihypertensive drug. Serious adverse effects are uncommon and mainly have been related to the depression of cardiac contractility and conduction, especially when the drug is combined with beta-blocking agents. We report a case in which myocardial infarction coincided with the introduction of captopril and the withdrawal of verapamil in a previously asymptomatic woman with severe hypertension. Possible mechanisms that involve a verapamil-related increase in platelet and/or vascular alpha 2-adrenoreceptor affinity for catecholamines are discussed.", "entity": "Verapamil", "aliases": "Calan Cordilox Dexverapamil Falicard Finoptin Hydrochloride Verapamil Iproveratril Isoptin Isoptine Izoptin Lekoptin Sandoz Brand of", "definition": "A calcium channel blocker that is a class IV anti-arrhythmia agent.\n    ", "id": "MESH:D014700"}
{"mention": "depression", "mention_text": "Verapamil is an effective and relatively-safe antihypertensive drug. Serious adverse effects are uncommon and mainly have been related to the depression of cardiac contractility and conduction, especially when the drug is combined with beta-blocking agents. We report a case in which myocardial infarction coincided with the introduction of captopril and the withdrawal of verapamil in a previously asymptomatic woman with severe hypertension. Possible mechanisms that involve a verapamil-related increase in platelet and/or vascular alpha 2-adrenoreceptor affinity for catecholamines are discussed.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "myocardial infarction", "mention_text": "Verapamil is an effective and relatively-safe antihypertensive drug. Serious adverse effects are uncommon and mainly have been related to the depression of cardiac contractility and conduction, especially when the drug is combined with beta-blocking agents. We report a case in which myocardial infarction coincided with the introduction of captopril and the withdrawal of verapamil in a previously asymptomatic woman with severe hypertension. Possible mechanisms that involve a verapamil-related increase in platelet and/or vascular alpha 2-adrenoreceptor affinity for catecholamines are discussed.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "captopril", "mention_text": "Verapamil is an effective and relatively-safe antihypertensive drug. Serious adverse effects are uncommon and mainly have been related to the depression of cardiac contractility and conduction, especially when the drug is combined with beta-blocking agents. We report a case in which myocardial infarction coincided with the introduction of captopril and the withdrawal of verapamil in a previously asymptomatic woman with severe hypertension. Possible mechanisms that involve a verapamil-related increase in platelet and/or vascular alpha 2-adrenoreceptor affinity for catecholamines are discussed.", "entity": "Captopril", "aliases": "(S)-1-(3-Mercapto-2-methyl-1-oxopropyl)-L-proline Capoten Captopril Lopirin SQ 14,225 14,534 14225 14534 SQ-14,225 SQ-14,534 SQ-14225 SQ-14534 SQ14,225 SQ14,534 SQ14225 SQ14534", "definition": "A potent and specific inhibitor of PEPTIDYL-DIPEPTIDASE A. It blocks the conversion of ANGIOTENSIN I to ANGIOTENSIN II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the RENIN-ANGIOTENSIN SYSTEM and inhibits pressure responses to exogenous angiotensin.\n    ", "id": "MESH:D002216"}
{"mention": "verapamil", "mention_text": "Verapamil is an effective and relatively-safe antihypertensive drug. Serious adverse effects are uncommon and mainly have been related to the depression of cardiac contractility and conduction, especially when the drug is combined with beta-blocking agents. We report a case in which myocardial infarction coincided with the introduction of captopril and the withdrawal of verapamil in a previously asymptomatic woman with severe hypertension. Possible mechanisms that involve a verapamil-related increase in platelet and/or vascular alpha 2-adrenoreceptor affinity for catecholamines are discussed.", "entity": "Verapamil", "aliases": "Calan Cordilox Dexverapamil Falicard Finoptin Hydrochloride Verapamil Iproveratril Isoptin Isoptine Izoptin Lekoptin Sandoz Brand of", "definition": "A calcium channel blocker that is a class IV anti-arrhythmia agent.\n    ", "id": "MESH:D014700"}
{"mention": "hypertension", "mention_text": "Verapamil is an effective and relatively-safe antihypertensive drug. Serious adverse effects are uncommon and mainly have been related to the depression of cardiac contractility and conduction, especially when the drug is combined with beta-blocking agents. We report a case in which myocardial infarction coincided with the introduction of captopril and the withdrawal of verapamil in a previously asymptomatic woman with severe hypertension. Possible mechanisms that involve a verapamil-related increase in platelet and/or vascular alpha 2-adrenoreceptor affinity for catecholamines are discussed.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "catecholamines", "mention_text": "Verapamil is an effective and relatively-safe antihypertensive drug. Serious adverse effects are uncommon and mainly have been related to the depression of cardiac contractility and conduction, especially when the drug is combined with beta-blocking agents. We report a case in which myocardial infarction coincided with the introduction of captopril and the withdrawal of verapamil in a previously asymptomatic woman with severe hypertension. Possible mechanisms that involve a verapamil-related increase in platelet and/or vascular alpha 2-adrenoreceptor affinity for catecholamines are discussed.", "entity": "Catecholamines", "aliases": "Catecholamines Sympathins", "definition": "A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine.\n    ", "id": "MESH:D002395"}
{"mention": "meningeal leukemia", "mention_text": "Remission induction of meningeal leukemia with high-dose intravenous methotrexate.", "entity": "Meningeal Neoplasms", "aliases": "Benign Meningeal Neoplasm Neoplasms Cancer Cancers Intracranial Leptomeningeal Malignant Spinal Tumor Tumors", "definition": "Benign and malignant neoplastic processes that arise from or secondarily involve the meningeal coverings of the brain and spinal cord.\n    ", "id": "MESH:D008577"}
{"mention": "methotrexate", "mention_text": "Remission induction of meningeal leukemia with high-dose intravenous methotrexate.", "entity": "Methotrexate", "aliases": "Amethopterin Dicesium Salt Methotrexate Hydrate Sodium (D)-Isomer (DL)-Isomer Disodium Mexate", "definition": "An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.\n    ", "id": "MESH:D008727"}
{"mention": "acute lymphoblastic leukemia", "mention_text": "Twenty children with acute lymphoblastic leukemia who developed meningeal disease were treated with a high-dose intravenous methotrexate regimen that was designed to achieve and maintain CSF methotrexate concentrations of 10(-5) mol/L without the need for concomitant intrathecal dosing. The methotrexate was administered as a loading dose of 6,000 mg/m2 for a period of one hour followed by an infusion of 1,200 mg/m2/h for 23 hours. Leucovorin rescue was initiated 12 hours after the end of the infusion with a loading dose of 200 mg/m2 followed by 12 mg/m2 every three hours for six doses and then every six hours until the plasma methotrexate level decreased to less than 1 X 10(-7) mol/L. The mean steady-state plasma and CSF methotrexate concentrations achieved were 1.1 X 10(-3) mol/L and 3.6 X 10(-5) mol/L, respectively. All 20 patients responded to this regimen, 16/20 (80%) achieved a complete remission, and 20% obtained a partial remission. The most common toxicities encountered were transient serum transaminase and bilirubin elevations, neutropenia, and mucositis. One patient had focal seizures and transient hemiparesis but recovered completely. High-dose intravenous methotrexate is an effective treatment for the induction of remission after meningeal relapse in acute lymphoblastic leukemia.", "entity": "Precursor Cell Lymphoblastic Leukemia-Lymphoma", "aliases": "ALL Childhood Acute Lymphoblastic Leukemia Lymphocytic Lymphoid L1 L2 Philadelphia-Positive Adult Lymphoma Precursor Cell Leukemia-Lymphoma", "definition": "A neoplasm characterized by abnormalities of the lymphoid cell precursors leading to excessive lymphoblasts in the marrow and other organs. It is the most common cancer in children and accounts for the vast majority of all childhood leukemias.\n    ", "id": "MESH:D054198"}
{"mention": "meningeal disease", "mention_text": "Twenty children with acute lymphoblastic leukemia who developed meningeal disease were treated with a high-dose intravenous methotrexate regimen that was designed to achieve and maintain CSF methotrexate concentrations of 10(-5) mol/L without the need for concomitant intrathecal dosing. The methotrexate was administered as a loading dose of 6,000 mg/m2 for a period of one hour followed by an infusion of 1,200 mg/m2/h for 23 hours. Leucovorin rescue was initiated 12 hours after the end of the infusion with a loading dose of 200 mg/m2 followed by 12 mg/m2 every three hours for six doses and then every six hours until the plasma methotrexate level decreased to less than 1 X 10(-7) mol/L. The mean steady-state plasma and CSF methotrexate concentrations achieved were 1.1 X 10(-3) mol/L and 3.6 X 10(-5) mol/L, respectively. All 20 patients responded to this regimen, 16/20 (80%) achieved a complete remission, and 20% obtained a partial remission. The most common toxicities encountered were transient serum transaminase and bilirubin elevations, neutropenia, and mucositis. One patient had focal seizures and transient hemiparesis but recovered completely. High-dose intravenous methotrexate is an effective treatment for the induction of remission after meningeal relapse in acute lymphoblastic leukemia.", "entity": "Central Nervous System Diseases", "aliases": "CNS Disease Diseases Central Nervous System Disorders", "definition": "Diseases of any component of the brain (including the cerebral hemispheres, diencephalon, brain stem, and cerebellum) or the spinal cord.\n    ", "id": "MESH:D002493"}
{"mention": "methotrexate", "mention_text": "Twenty children with acute lymphoblastic leukemia who developed meningeal disease were treated with a high-dose intravenous methotrexate regimen that was designed to achieve and maintain CSF methotrexate concentrations of 10(-5) mol/L without the need for concomitant intrathecal dosing. The methotrexate was administered as a loading dose of 6,000 mg/m2 for a period of one hour followed by an infusion of 1,200 mg/m2/h for 23 hours. Leucovorin rescue was initiated 12 hours after the end of the infusion with a loading dose of 200 mg/m2 followed by 12 mg/m2 every three hours for six doses and then every six hours until the plasma methotrexate level decreased to less than 1 X 10(-7) mol/L. The mean steady-state plasma and CSF methotrexate concentrations achieved were 1.1 X 10(-3) mol/L and 3.6 X 10(-5) mol/L, respectively. All 20 patients responded to this regimen, 16/20 (80%) achieved a complete remission, and 20% obtained a partial remission. The most common toxicities encountered were transient serum transaminase and bilirubin elevations, neutropenia, and mucositis. One patient had focal seizures and transient hemiparesis but recovered completely. High-dose intravenous methotrexate is an effective treatment for the induction of remission after meningeal relapse in acute lymphoblastic leukemia.", "entity": "Methotrexate", "aliases": "Amethopterin Dicesium Salt Methotrexate Hydrate Sodium (D)-Isomer (DL)-Isomer Disodium Mexate", "definition": "An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.\n    ", "id": "MESH:D008727"}
{"mention": "Leucovorin", "mention_text": "Twenty children with acute lymphoblastic leukemia who developed meningeal disease were treated with a high-dose intravenous methotrexate regimen that was designed to achieve and maintain CSF methotrexate concentrations of 10(-5) mol/L without the need for concomitant intrathecal dosing. The methotrexate was administered as a loading dose of 6,000 mg/m2 for a period of one hour followed by an infusion of 1,200 mg/m2/h for 23 hours. Leucovorin rescue was initiated 12 hours after the end of the infusion with a loading dose of 200 mg/m2 followed by 12 mg/m2 every three hours for six doses and then every six hours until the plasma methotrexate level decreased to less than 1 X 10(-7) mol/L. The mean steady-state plasma and CSF methotrexate concentrations achieved were 1.1 X 10(-3) mol/L and 3.6 X 10(-5) mol/L, respectively. All 20 patients responded to this regimen, 16/20 (80%) achieved a complete remission, and 20% obtained a partial remission. The most common toxicities encountered were transient serum transaminase and bilirubin elevations, neutropenia, and mucositis. One patient had focal seizures and transient hemiparesis but recovered completely. High-dose intravenous methotrexate is an effective treatment for the induction of remission after meningeal relapse in acute lymphoblastic leukemia.", "entity": "Leucovorin", "aliases": "5 Formyltetrahydrofolate Formyltetrahydropteroylglutamate 5-Formyltetrahydrofolate 5-Formyltetrahydropteroylglutamate Acid Folinic Calcium Folinate Leucovorin Citrovorum Factor SF Acid-SF (D)-Isomer (DL)-Isomer (R)-Isomer (1:1) Salt Pentahydrate Monosodium Leukovorin Leukovorum N(5)-Formyltetrahydrofolate Wellcovorin", "definition": "The active metabolite of FOLIC ACID. Leucovorin is used principally as its calcium salt as an antidote to folic acid antagonists which block the conversion of folic acid to folinic acid.\n    ", "id": "MESH:D002955"}
{"mention": "toxicities", "mention_text": "Twenty children with acute lymphoblastic leukemia who developed meningeal disease were treated with a high-dose intravenous methotrexate regimen that was designed to achieve and maintain CSF methotrexate concentrations of 10(-5) mol/L without the need for concomitant intrathecal dosing. The methotrexate was administered as a loading dose of 6,000 mg/m2 for a period of one hour followed by an infusion of 1,200 mg/m2/h for 23 hours. Leucovorin rescue was initiated 12 hours after the end of the infusion with a loading dose of 200 mg/m2 followed by 12 mg/m2 every three hours for six doses and then every six hours until the plasma methotrexate level decreased to less than 1 X 10(-7) mol/L. The mean steady-state plasma and CSF methotrexate concentrations achieved were 1.1 X 10(-3) mol/L and 3.6 X 10(-5) mol/L, respectively. All 20 patients responded to this regimen, 16/20 (80%) achieved a complete remission, and 20% obtained a partial remission. The most common toxicities encountered were transient serum transaminase and bilirubin elevations, neutropenia, and mucositis. One patient had focal seizures and transient hemiparesis but recovered completely. High-dose intravenous methotrexate is an effective treatment for the induction of remission after meningeal relapse in acute lymphoblastic leukemia.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "bilirubin", "mention_text": "Twenty children with acute lymphoblastic leukemia who developed meningeal disease were treated with a high-dose intravenous methotrexate regimen that was designed to achieve and maintain CSF methotrexate concentrations of 10(-5) mol/L without the need for concomitant intrathecal dosing. The methotrexate was administered as a loading dose of 6,000 mg/m2 for a period of one hour followed by an infusion of 1,200 mg/m2/h for 23 hours. Leucovorin rescue was initiated 12 hours after the end of the infusion with a loading dose of 200 mg/m2 followed by 12 mg/m2 every three hours for six doses and then every six hours until the plasma methotrexate level decreased to less than 1 X 10(-7) mol/L. The mean steady-state plasma and CSF methotrexate concentrations achieved were 1.1 X 10(-3) mol/L and 3.6 X 10(-5) mol/L, respectively. All 20 patients responded to this regimen, 16/20 (80%) achieved a complete remission, and 20% obtained a partial remission. The most common toxicities encountered were transient serum transaminase and bilirubin elevations, neutropenia, and mucositis. One patient had focal seizures and transient hemiparesis but recovered completely. High-dose intravenous methotrexate is an effective treatment for the induction of remission after meningeal relapse in acute lymphoblastic leukemia.", "entity": "Bilirubin", "aliases": "Bilirubin IX alpha (15E)-Isomer (4E)-Isomer (4E,15E)-Isomer Calcium Salt Disodium Monosodium Bilirubinate Hematoidin delta delta-Bilirubin", "definition": "A bile pigment that is a degradation product of HEME.\n    ", "id": "MESH:D001663"}
{"mention": "neutropenia", "mention_text": "Twenty children with acute lymphoblastic leukemia who developed meningeal disease were treated with a high-dose intravenous methotrexate regimen that was designed to achieve and maintain CSF methotrexate concentrations of 10(-5) mol/L without the need for concomitant intrathecal dosing. The methotrexate was administered as a loading dose of 6,000 mg/m2 for a period of one hour followed by an infusion of 1,200 mg/m2/h for 23 hours. Leucovorin rescue was initiated 12 hours after the end of the infusion with a loading dose of 200 mg/m2 followed by 12 mg/m2 every three hours for six doses and then every six hours until the plasma methotrexate level decreased to less than 1 X 10(-7) mol/L. The mean steady-state plasma and CSF methotrexate concentrations achieved were 1.1 X 10(-3) mol/L and 3.6 X 10(-5) mol/L, respectively. All 20 patients responded to this regimen, 16/20 (80%) achieved a complete remission, and 20% obtained a partial remission. The most common toxicities encountered were transient serum transaminase and bilirubin elevations, neutropenia, and mucositis. One patient had focal seizures and transient hemiparesis but recovered completely. High-dose intravenous methotrexate is an effective treatment for the induction of remission after meningeal relapse in acute lymphoblastic leukemia.", "entity": "Neutropenia", "aliases": "Neutropenia Neutropenias", "definition": "A decrease in the number of NEUTROPHILS found in the blood.\n    ", "id": "MESH:D009503"}
{"mention": "mucositis", "mention_text": "Twenty children with acute lymphoblastic leukemia who developed meningeal disease were treated with a high-dose intravenous methotrexate regimen that was designed to achieve and maintain CSF methotrexate concentrations of 10(-5) mol/L without the need for concomitant intrathecal dosing. The methotrexate was administered as a loading dose of 6,000 mg/m2 for a period of one hour followed by an infusion of 1,200 mg/m2/h for 23 hours. Leucovorin rescue was initiated 12 hours after the end of the infusion with a loading dose of 200 mg/m2 followed by 12 mg/m2 every three hours for six doses and then every six hours until the plasma methotrexate level decreased to less than 1 X 10(-7) mol/L. The mean steady-state plasma and CSF methotrexate concentrations achieved were 1.1 X 10(-3) mol/L and 3.6 X 10(-5) mol/L, respectively. All 20 patients responded to this regimen, 16/20 (80%) achieved a complete remission, and 20% obtained a partial remission. The most common toxicities encountered were transient serum transaminase and bilirubin elevations, neutropenia, and mucositis. One patient had focal seizures and transient hemiparesis but recovered completely. High-dose intravenous methotrexate is an effective treatment for the induction of remission after meningeal relapse in acute lymphoblastic leukemia.", "entity": "Mucositis", "aliases": "Mucositides Mucositis", "definition": "An INFLAMMATION of the MUCOSA with burning or tingling sensation. It is characterized by atrophy of the squamous EPITHELIUM, vascular damage, inflammatory infiltration, and ulceration. It usually occurs at the mucous lining of the MOUTH, the GASTROINTESTINAL TRACT or the airway due to chemical irritations, CHEMOTHERAPY, or radiation therapy (RADIOTHERAPY).\n    ", "id": "MESH:D052016"}
{"mention": "seizures", "mention_text": "Twenty children with acute lymphoblastic leukemia who developed meningeal disease were treated with a high-dose intravenous methotrexate regimen that was designed to achieve and maintain CSF methotrexate concentrations of 10(-5) mol/L without the need for concomitant intrathecal dosing. The methotrexate was administered as a loading dose of 6,000 mg/m2 for a period of one hour followed by an infusion of 1,200 mg/m2/h for 23 hours. Leucovorin rescue was initiated 12 hours after the end of the infusion with a loading dose of 200 mg/m2 followed by 12 mg/m2 every three hours for six doses and then every six hours until the plasma methotrexate level decreased to less than 1 X 10(-7) mol/L. The mean steady-state plasma and CSF methotrexate concentrations achieved were 1.1 X 10(-3) mol/L and 3.6 X 10(-5) mol/L, respectively. All 20 patients responded to this regimen, 16/20 (80%) achieved a complete remission, and 20% obtained a partial remission. The most common toxicities encountered were transient serum transaminase and bilirubin elevations, neutropenia, and mucositis. One patient had focal seizures and transient hemiparesis but recovered completely. High-dose intravenous methotrexate is an effective treatment for the induction of remission after meningeal relapse in acute lymphoblastic leukemia.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "transient hemiparesis", "mention_text": "Twenty children with acute lymphoblastic leukemia who developed meningeal disease were treated with a high-dose intravenous methotrexate regimen that was designed to achieve and maintain CSF methotrexate concentrations of 10(-5) mol/L without the need for concomitant intrathecal dosing. The methotrexate was administered as a loading dose of 6,000 mg/m2 for a period of one hour followed by an infusion of 1,200 mg/m2/h for 23 hours. Leucovorin rescue was initiated 12 hours after the end of the infusion with a loading dose of 200 mg/m2 followed by 12 mg/m2 every three hours for six doses and then every six hours until the plasma methotrexate level decreased to less than 1 X 10(-7) mol/L. The mean steady-state plasma and CSF methotrexate concentrations achieved were 1.1 X 10(-3) mol/L and 3.6 X 10(-5) mol/L, respectively. All 20 patients responded to this regimen, 16/20 (80%) achieved a complete remission, and 20% obtained a partial remission. The most common toxicities encountered were transient serum transaminase and bilirubin elevations, neutropenia, and mucositis. One patient had focal seizures and transient hemiparesis but recovered completely. High-dose intravenous methotrexate is an effective treatment for the induction of remission after meningeal relapse in acute lymphoblastic leukemia.", "entity": "Paresis", "aliases": "Brachial Pareses Paresis Crural Extremity Lower Upper Hemipareses Hemiparesis Monopareses Monoparesis Muscle Muscular", "definition": "A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for PARALYSIS (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis (see NEUROSYPHILIS). \"General paresis\" and \"general paralysis\" may still carry that connotation. Bilateral lower extremity paresis is referred to as PARAPARESIS.\n    ", "id": "MESH:D010291"}
{"mention": "Hypersensitivity", "mention_text": "Hypersensitivity to carbamazepine presenting with a leukemoid reaction, eosinophilia, erythroderma, and renal failure.", "entity": "Drug Hypersensitivity", "aliases": "Allergies Drug Allergy Hypersensitivities Hypersensitivity", "definition": "Immunologically mediated adverse reactions to medicinal substances used legally or illegally.\n    ", "id": "MESH:D004342"}
{"mention": "carbamazepine", "mention_text": "Hypersensitivity to carbamazepine presenting with a leukemoid reaction, eosinophilia, erythroderma, and renal failure.", "entity": "Carbamazepine", "aliases": "Amizepine Carbamazepine Acetate Anhydrous Dihydrate Hydrochloride L-Tartrate (4:1) Phosphate Sulfate (2:1) Carbazepin Epitol Finlepsin Neurotol Tegretol", "definition": "An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of PHENYTOIN; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar.\n    ", "id": "MESH:D002220"}
{"mention": "leukemoid reaction", "mention_text": "Hypersensitivity to carbamazepine presenting with a leukemoid reaction, eosinophilia, erythroderma, and renal failure.", "entity": "Leukemoid Reaction", "aliases": "Leukemoid Reaction Reactions", "definition": "A peripheral blood picture resembling that of leukemia or indistinguishable from it on the basis of morphologic appearance alone. (Dorland, 27th ed)\n    ", "id": "MESH:D007955"}
{"mention": "eosinophilia", "mention_text": "Hypersensitivity to carbamazepine presenting with a leukemoid reaction, eosinophilia, erythroderma, and renal failure.", "entity": "Eosinophilia", "aliases": "Eosinophilia Tropical Eosinophilias", "definition": "Abnormal increase of EOSINOPHILS in the blood, tissues or organs.\n    ", "id": "MESH:D004802"}
{"mention": "erythroderma", "mention_text": "Hypersensitivity to carbamazepine presenting with a leukemoid reaction, eosinophilia, erythroderma, and renal failure.", "entity": "Dermatitis, Exfoliative", "aliases": "Dermatitides Exfoliative Dermatitis Exfoliativa Erythroderma Erythrodermas", "definition": "The widespread involvement of the skin by a scaly, erythematous dermatitis occurring either as a secondary or reactive process to an underlying cutaneous disorder (e.g., atopic dermatitis, psoriasis, etc.), or as a primary or idiopathic disease. It is often associated with the loss of hair and nails, hyperkeratosis of the palms and soles, and pruritus. (From Dorland, 27th ed)\n    ", "id": "MESH:D003873"}
{"mention": "renal failure", "mention_text": "Hypersensitivity to carbamazepine presenting with a leukemoid reaction, eosinophilia, erythroderma, and renal failure.", "entity": "Renal Insufficiency", "aliases": "Failure Kidney Renal Failures Insufficiency Insufficiencies", "definition": "Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.\n    ", "id": "MESH:D051437"}
{"mention": "hypersensitivity", "mention_text": "We report a patient in whom hypersensitivity to carbamazepine presented with generalized erythroderma, a severe leukemoid reaction, eosinophilia, hyponatremia, and renal failure. This is the first report of such an unusual reaction to carbamazepine.", "entity": "Drug Hypersensitivity", "aliases": "Allergies Drug Allergy Hypersensitivities Hypersensitivity", "definition": "Immunologically mediated adverse reactions to medicinal substances used legally or illegally.\n    ", "id": "MESH:D004342"}
{"mention": "carbamazepine", "mention_text": "We report a patient in whom hypersensitivity to carbamazepine presented with generalized erythroderma, a severe leukemoid reaction, eosinophilia, hyponatremia, and renal failure. This is the first report of such an unusual reaction to carbamazepine.", "entity": "Carbamazepine", "aliases": "Amizepine Carbamazepine Acetate Anhydrous Dihydrate Hydrochloride L-Tartrate (4:1) Phosphate Sulfate (2:1) Carbazepin Epitol Finlepsin Neurotol Tegretol", "definition": "An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of PHENYTOIN; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar.\n    ", "id": "MESH:D002220"}
{"mention": "erythroderma", "mention_text": "We report a patient in whom hypersensitivity to carbamazepine presented with generalized erythroderma, a severe leukemoid reaction, eosinophilia, hyponatremia, and renal failure. This is the first report of such an unusual reaction to carbamazepine.", "entity": "Dermatitis, Exfoliative", "aliases": "Dermatitides Exfoliative Dermatitis Exfoliativa Erythroderma Erythrodermas", "definition": "The widespread involvement of the skin by a scaly, erythematous dermatitis occurring either as a secondary or reactive process to an underlying cutaneous disorder (e.g., atopic dermatitis, psoriasis, etc.), or as a primary or idiopathic disease. It is often associated with the loss of hair and nails, hyperkeratosis of the palms and soles, and pruritus. (From Dorland, 27th ed)\n    ", "id": "MESH:D003873"}
{"mention": "leukemoid reaction", "mention_text": "We report a patient in whom hypersensitivity to carbamazepine presented with generalized erythroderma, a severe leukemoid reaction, eosinophilia, hyponatremia, and renal failure. This is the first report of such an unusual reaction to carbamazepine.", "entity": "Leukemoid Reaction", "aliases": "Leukemoid Reaction Reactions", "definition": "A peripheral blood picture resembling that of leukemia or indistinguishable from it on the basis of morphologic appearance alone. (Dorland, 27th ed)\n    ", "id": "MESH:D007955"}
{"mention": "eosinophilia", "mention_text": "We report a patient in whom hypersensitivity to carbamazepine presented with generalized erythroderma, a severe leukemoid reaction, eosinophilia, hyponatremia, and renal failure. This is the first report of such an unusual reaction to carbamazepine.", "entity": "Eosinophilia", "aliases": "Eosinophilia Tropical Eosinophilias", "definition": "Abnormal increase of EOSINOPHILS in the blood, tissues or organs.\n    ", "id": "MESH:D004802"}
{"mention": "hyponatremia", "mention_text": "We report a patient in whom hypersensitivity to carbamazepine presented with generalized erythroderma, a severe leukemoid reaction, eosinophilia, hyponatremia, and renal failure. This is the first report of such an unusual reaction to carbamazepine.", "entity": "Hyponatremia", "aliases": "Hyponatremia Hyponatremias", "definition": "Deficiency of sodium in the blood; salt depletion. (Dorland, 27th ed)\n    ", "id": "MESH:D007010"}
{"mention": "renal failure", "mention_text": "We report a patient in whom hypersensitivity to carbamazepine presented with generalized erythroderma, a severe leukemoid reaction, eosinophilia, hyponatremia, and renal failure. This is the first report of such an unusual reaction to carbamazepine.", "entity": "Renal Insufficiency", "aliases": "Failure Kidney Renal Failures Insufficiency Insufficiencies", "definition": "Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.\n    ", "id": "MESH:D051437"}
{"mention": "nicotine", "mention_text": "The interpeduncular nucleus regulates nicotine's effects on free-field activity.", "entity": "Nicotine", "aliases": "Bitartrate Nicotine Tartrate", "definition": "Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.\n    ", "id": "MESH:D009538"}
{"mention": "kainic acid", "mention_text": "Partial lesions were made with kainic acid in the interpeduncular nucleus of the ventral midbrain of the rat. Compared with sham-operated controls, lesions significantly (p < 0.25) blunted the early (<60 min) free-field locomotor hypoactivity caused by nicotine (0.5 mg kg(-1), i.m.), enhanced the later (60-120 min) nicotine-induced hyperactivity, and raised spontaneous nocturnal activity. Lesions reduced the extent of immunohistological staining for choline acetyltransferase in the interpeduncular nucleus (p <0.025), but not for tyrosine hydroxylase in the surrounding catecholaminergic A10 region. We conclude that the interpeduncular nucleus mediates nicotinic depression of locomotor activity and dampens nicotinic arousal mechanisms located elsewhere in the brain.", "entity": "Kainic Acid", "aliases": "Acid Digenic Kainic Kainate", "definition": "(2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose.\n    ", "id": "MESH:D007608"}
{"mention": "locomotor hypoactivity", "mention_text": "Partial lesions were made with kainic acid in the interpeduncular nucleus of the ventral midbrain of the rat. Compared with sham-operated controls, lesions significantly (p < 0.25) blunted the early (<60 min) free-field locomotor hypoactivity caused by nicotine (0.5 mg kg(-1), i.m.), enhanced the later (60-120 min) nicotine-induced hyperactivity, and raised spontaneous nocturnal activity. Lesions reduced the extent of immunohistological staining for choline acetyltransferase in the interpeduncular nucleus (p <0.025), but not for tyrosine hydroxylase in the surrounding catecholaminergic A10 region. We conclude that the interpeduncular nucleus mediates nicotinic depression of locomotor activity and dampens nicotinic arousal mechanisms located elsewhere in the brain.", "entity": "Movement Disorders", "aliases": "Dyskinesia Syndrome Syndromes Lingual-Facial-Buccal Linguofacial Oral Oral-facial Orofacial Tardive Dyskinesias Dystonia Dystonias Etat Marbre Lingual Facial Buccal Movement Disorder Disorders facial Status Marmoratus", "definition": "Syndromes which feature DYSKINESIAS as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions.\n    ", "id": "MESH:D009069"}
{"mention": "nicotine", "mention_text": "Partial lesions were made with kainic acid in the interpeduncular nucleus of the ventral midbrain of the rat. Compared with sham-operated controls, lesions significantly (p < 0.25) blunted the early (<60 min) free-field locomotor hypoactivity caused by nicotine (0.5 mg kg(-1), i.m.), enhanced the later (60-120 min) nicotine-induced hyperactivity, and raised spontaneous nocturnal activity. Lesions reduced the extent of immunohistological staining for choline acetyltransferase in the interpeduncular nucleus (p <0.025), but not for tyrosine hydroxylase in the surrounding catecholaminergic A10 region. We conclude that the interpeduncular nucleus mediates nicotinic depression of locomotor activity and dampens nicotinic arousal mechanisms located elsewhere in the brain.", "entity": "Nicotine", "aliases": "Bitartrate Nicotine Tartrate", "definition": "Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.\n    ", "id": "MESH:D009538"}
{"mention": "hyperactivity", "mention_text": "Partial lesions were made with kainic acid in the interpeduncular nucleus of the ventral midbrain of the rat. Compared with sham-operated controls, lesions significantly (p < 0.25) blunted the early (<60 min) free-field locomotor hypoactivity caused by nicotine (0.5 mg kg(-1), i.m.), enhanced the later (60-120 min) nicotine-induced hyperactivity, and raised spontaneous nocturnal activity. Lesions reduced the extent of immunohistological staining for choline acetyltransferase in the interpeduncular nucleus (p <0.025), but not for tyrosine hydroxylase in the surrounding catecholaminergic A10 region. We conclude that the interpeduncular nucleus mediates nicotinic depression of locomotor activity and dampens nicotinic arousal mechanisms located elsewhere in the brain.", "entity": "Hyperkinesis", "aliases": "Generalized Hyperkinesia Hyperkinesias Hyperactivity Motor Hyperkinesis Hyperkinetic Movement Movements", "definition": "Excessive movement of muscles of the body as a whole, which may be associated with organic or psychological disorders.\n    ", "id": "MESH:D006948"}
{"mention": "choline", "mention_text": "Partial lesions were made with kainic acid in the interpeduncular nucleus of the ventral midbrain of the rat. Compared with sham-operated controls, lesions significantly (p < 0.25) blunted the early (<60 min) free-field locomotor hypoactivity caused by nicotine (0.5 mg kg(-1), i.m.), enhanced the later (60-120 min) nicotine-induced hyperactivity, and raised spontaneous nocturnal activity. Lesions reduced the extent of immunohistological staining for choline acetyltransferase in the interpeduncular nucleus (p <0.025), but not for tyrosine hydroxylase in the surrounding catecholaminergic A10 region. We conclude that the interpeduncular nucleus mediates nicotinic depression of locomotor activity and dampens nicotinic arousal mechanisms located elsewhere in the brain.", "entity": "Choline", "aliases": "2-Hydroxy-N,N,N-trimethylethanaminium Bitartrate Choline Bursine Chloride Citrate Hydroxide O Sulfate O-Sulfate Fagine Vidine", "definition": "A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism.\n    ", "id": "MESH:D002794"}
{"mention": "tyrosine", "mention_text": "Partial lesions were made with kainic acid in the interpeduncular nucleus of the ventral midbrain of the rat. Compared with sham-operated controls, lesions significantly (p < 0.25) blunted the early (<60 min) free-field locomotor hypoactivity caused by nicotine (0.5 mg kg(-1), i.m.), enhanced the later (60-120 min) nicotine-induced hyperactivity, and raised spontaneous nocturnal activity. Lesions reduced the extent of immunohistological staining for choline acetyltransferase in the interpeduncular nucleus (p <0.025), but not for tyrosine hydroxylase in the surrounding catecholaminergic A10 region. We conclude that the interpeduncular nucleus mediates nicotinic depression of locomotor activity and dampens nicotinic arousal mechanisms located elsewhere in the brain.", "entity": "Tyrosine", "aliases": "L Tyrosine L-Tyrosine isomer L-isomer para para-Tyrosine", "definition": "A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.\n    ", "id": "MESH:D014443"}
{"mention": "depression", "mention_text": "Partial lesions were made with kainic acid in the interpeduncular nucleus of the ventral midbrain of the rat. Compared with sham-operated controls, lesions significantly (p < 0.25) blunted the early (<60 min) free-field locomotor hypoactivity caused by nicotine (0.5 mg kg(-1), i.m.), enhanced the later (60-120 min) nicotine-induced hyperactivity, and raised spontaneous nocturnal activity. Lesions reduced the extent of immunohistological staining for choline acetyltransferase in the interpeduncular nucleus (p <0.025), but not for tyrosine hydroxylase in the surrounding catecholaminergic A10 region. We conclude that the interpeduncular nucleus mediates nicotinic depression of locomotor activity and dampens nicotinic arousal mechanisms located elsewhere in the brain.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "dobutamine", "mention_text": "Assessment of a new non-invasive index of cardiac performance for detection of dobutamine-induced myocardial ischemia.", "entity": "Dobutamine", "aliases": "Boehringer Ingelheim Brand of Dobutamine Hydrochloride Dobucor Dobuject Dobutamin Fresenius Hexal Solvay ratiopharm Dobutamin-ratiopharm Dobutamina Inibsa Rovi (+)-Isomer Hydrobromide Lactobionate Phosphate (1:1) Salt (-)-Isomer Tartrate (R-(R*,R*))-Isomer (S-(R*,R*))-Isomer Dobutrex Eli Lilly Irisfarma Juste Kendrick 81929 Oxiken Pisa Posiject", "definition": "A catecholamine derivative with specificity for BETA-1 ADRENERGIC RECEPTORS. It is commonly used as a cardiotonic agent after CARDIAC SURGERY and during DOBUTAMINE STRESS ECHOCARDIOGRAPHY.\n    ", "id": "MESH:D004280"}
{"mention": "myocardial ischemia", "mention_text": "Assessment of a new non-invasive index of cardiac performance for detection of dobutamine-induced myocardial ischemia.", "entity": "Myocardial Ischemia", "aliases": "Disease Ischemic Heart Diseases Ischemia Myocardial Ischemias", "definition": "A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).\n    ", "id": "MESH:D017202"}
{"mention": "dobutamine", "mention_text": "BACKGROUND: Electrocardiography has a very low sensitivity in detecting dobutamine-induced myocardial ischemia. OBJECTIVES: To assess the added diagnostic value of a new cardiac performance index (dP/dtejc) measurement, based on brachial artery flow changes, as compared to standard 12-lead ECG, for detecting dobutamine-induced myocardial ischemia, using Tc99m-Sestamibi single-photon emission computed tomography as the gold standard of comparison to assess the presence or absence of ischemia. METHODS: The study group comprised 40 patients undergoing Sestamibi-SPECT/dobutamine stress test. Simultaneous measurements of ECG and brachial artery dP/dtejc were performed at each dobutamine level. In 19 of the 40 patients perfusion defects compatible with ischemia were detected on SPECT. The increase in dP/dtejc during infusion of dobutamine in this group was severely impaired as compared to the non-ischemic group. dP/dtejc outcome was combined with the ECG results, giving an ECG-enhanced value, and compared to ECG alone. RESULTS: The sensitivity improved dramatically from 16% to 79%, positive predictive value increased from 60% to 68% and negative predictive value from 54% to 78%, and specificity decreased from 90% to 67%. CONCLUSIONS: If ECG alone is used for specificity, the combination with dP/dtejc improved the sensitivity of the test and could be a cost-savings alternative to cardiac imaging or perfusion studies to detect myocardial ischemia, especially in patients unable to exercise.", "entity": "Dobutamine", "aliases": "Boehringer Ingelheim Brand of Dobutamine Hydrochloride Dobucor Dobuject Dobutamin Fresenius Hexal Solvay ratiopharm Dobutamin-ratiopharm Dobutamina Inibsa Rovi (+)-Isomer Hydrobromide Lactobionate Phosphate (1:1) Salt (-)-Isomer Tartrate (R-(R*,R*))-Isomer (S-(R*,R*))-Isomer Dobutrex Eli Lilly Irisfarma Juste Kendrick 81929 Oxiken Pisa Posiject", "definition": "A catecholamine derivative with specificity for BETA-1 ADRENERGIC RECEPTORS. It is commonly used as a cardiotonic agent after CARDIAC SURGERY and during DOBUTAMINE STRESS ECHOCARDIOGRAPHY.\n    ", "id": "MESH:D004280"}
{"mention": "myocardial ischemia", "mention_text": "BACKGROUND: Electrocardiography has a very low sensitivity in detecting dobutamine-induced myocardial ischemia. OBJECTIVES: To assess the added diagnostic value of a new cardiac performance index (dP/dtejc) measurement, based on brachial artery flow changes, as compared to standard 12-lead ECG, for detecting dobutamine-induced myocardial ischemia, using Tc99m-Sestamibi single-photon emission computed tomography as the gold standard of comparison to assess the presence or absence of ischemia. METHODS: The study group comprised 40 patients undergoing Sestamibi-SPECT/dobutamine stress test. Simultaneous measurements of ECG and brachial artery dP/dtejc were performed at each dobutamine level. In 19 of the 40 patients perfusion defects compatible with ischemia were detected on SPECT. The increase in dP/dtejc during infusion of dobutamine in this group was severely impaired as compared to the non-ischemic group. dP/dtejc outcome was combined with the ECG results, giving an ECG-enhanced value, and compared to ECG alone. RESULTS: The sensitivity improved dramatically from 16% to 79%, positive predictive value increased from 60% to 68% and negative predictive value from 54% to 78%, and specificity decreased from 90% to 67%. CONCLUSIONS: If ECG alone is used for specificity, the combination with dP/dtejc improved the sensitivity of the test and could be a cost-savings alternative to cardiac imaging or perfusion studies to detect myocardial ischemia, especially in patients unable to exercise.", "entity": "Myocardial Ischemia", "aliases": "Disease Ischemic Heart Diseases Ischemia Myocardial Ischemias", "definition": "A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).\n    ", "id": "MESH:D017202"}
{"mention": "Tc99m-Sestamibi", "mention_text": "BACKGROUND: Electrocardiography has a very low sensitivity in detecting dobutamine-induced myocardial ischemia. OBJECTIVES: To assess the added diagnostic value of a new cardiac performance index (dP/dtejc) measurement, based on brachial artery flow changes, as compared to standard 12-lead ECG, for detecting dobutamine-induced myocardial ischemia, using Tc99m-Sestamibi single-photon emission computed tomography as the gold standard of comparison to assess the presence or absence of ischemia. METHODS: The study group comprised 40 patients undergoing Sestamibi-SPECT/dobutamine stress test. Simultaneous measurements of ECG and brachial artery dP/dtejc were performed at each dobutamine level. In 19 of the 40 patients perfusion defects compatible with ischemia were detected on SPECT. The increase in dP/dtejc during infusion of dobutamine in this group was severely impaired as compared to the non-ischemic group. dP/dtejc outcome was combined with the ECG results, giving an ECG-enhanced value, and compared to ECG alone. RESULTS: The sensitivity improved dramatically from 16% to 79%, positive predictive value increased from 60% to 68% and negative predictive value from 54% to 78%, and specificity decreased from 90% to 67%. CONCLUSIONS: If ECG alone is used for specificity, the combination with dP/dtejc improved the sensitivity of the test and could be a cost-savings alternative to cardiac imaging or perfusion studies to detect myocardial ischemia, especially in patients unable to exercise.", "entity": "Technetium Tc 99m Sestamibi", "aliases": "99mTc Hexamibi Sestamibi 99mTc-Hexamibi 99mTc-Sestamibi Cardiolite Du Pont Brand of Technetium Tc 99m Methoxy 2 isobutylisonitrile MIBI Tc-99m-Methoxy-2-isobutylisonitrile methylpropylisonitrile 2-Methoxy-2-methylpropylisonitrile Chloride Technetium-99m-Hexamibi Technetium-99m-Sestamibi", "definition": "A technetium imaging agent used to reveal blood-starved cardiac tissue during a heart attack.\n    ", "id": "MESH:D017256"}
{"mention": "ischemia", "mention_text": "BACKGROUND: Electrocardiography has a very low sensitivity in detecting dobutamine-induced myocardial ischemia. OBJECTIVES: To assess the added diagnostic value of a new cardiac performance index (dP/dtejc) measurement, based on brachial artery flow changes, as compared to standard 12-lead ECG, for detecting dobutamine-induced myocardial ischemia, using Tc99m-Sestamibi single-photon emission computed tomography as the gold standard of comparison to assess the presence or absence of ischemia. METHODS: The study group comprised 40 patients undergoing Sestamibi-SPECT/dobutamine stress test. Simultaneous measurements of ECG and brachial artery dP/dtejc were performed at each dobutamine level. In 19 of the 40 patients perfusion defects compatible with ischemia were detected on SPECT. The increase in dP/dtejc during infusion of dobutamine in this group was severely impaired as compared to the non-ischemic group. dP/dtejc outcome was combined with the ECG results, giving an ECG-enhanced value, and compared to ECG alone. RESULTS: The sensitivity improved dramatically from 16% to 79%, positive predictive value increased from 60% to 68% and negative predictive value from 54% to 78%, and specificity decreased from 90% to 67%. CONCLUSIONS: If ECG alone is used for specificity, the combination with dP/dtejc improved the sensitivity of the test and could be a cost-savings alternative to cardiac imaging or perfusion studies to detect myocardial ischemia, especially in patients unable to exercise.", "entity": "Ischemia", "aliases": "Ischemia Ischemias", "definition": "A hypoperfusion of the BLOOD through an organ or tissue caused by a PATHOLOGIC CONSTRICTION or obstruction of its BLOOD VESSELS, or an absence of BLOOD CIRCULATION.\n    ", "id": "MESH:D007511"}
{"mention": "Sestamibi", "mention_text": "BACKGROUND: Electrocardiography has a very low sensitivity in detecting dobutamine-induced myocardial ischemia. OBJECTIVES: To assess the added diagnostic value of a new cardiac performance index (dP/dtejc) measurement, based on brachial artery flow changes, as compared to standard 12-lead ECG, for detecting dobutamine-induced myocardial ischemia, using Tc99m-Sestamibi single-photon emission computed tomography as the gold standard of comparison to assess the presence or absence of ischemia. METHODS: The study group comprised 40 patients undergoing Sestamibi-SPECT/dobutamine stress test. Simultaneous measurements of ECG and brachial artery dP/dtejc were performed at each dobutamine level. In 19 of the 40 patients perfusion defects compatible with ischemia were detected on SPECT. The increase in dP/dtejc during infusion of dobutamine in this group was severely impaired as compared to the non-ischemic group. dP/dtejc outcome was combined with the ECG results, giving an ECG-enhanced value, and compared to ECG alone. RESULTS: The sensitivity improved dramatically from 16% to 79%, positive predictive value increased from 60% to 68% and negative predictive value from 54% to 78%, and specificity decreased from 90% to 67%. CONCLUSIONS: If ECG alone is used for specificity, the combination with dP/dtejc improved the sensitivity of the test and could be a cost-savings alternative to cardiac imaging or perfusion studies to detect myocardial ischemia, especially in patients unable to exercise.", "entity": "Technetium Tc 99m Sestamibi", "aliases": "99mTc Hexamibi Sestamibi 99mTc-Hexamibi 99mTc-Sestamibi Cardiolite Du Pont Brand of Technetium Tc 99m Methoxy 2 isobutylisonitrile MIBI Tc-99m-Methoxy-2-isobutylisonitrile methylpropylisonitrile 2-Methoxy-2-methylpropylisonitrile Chloride Technetium-99m-Hexamibi Technetium-99m-Sestamibi", "definition": "A technetium imaging agent used to reveal blood-starved cardiac tissue during a heart attack.\n    ", "id": "MESH:D017256"}
{"mention": "Acute liver failure", "mention_text": "Acute liver failure in two patients with regular alcohol consumption ingesting paracetamol at therapeutic dosage.", "entity": "Liver Failure, Acute", "aliases": "Acute Hepatic Failure Liver Fulminant Failures Fulminating", "definition": "A form of rapid-onset LIVER FAILURE, also known as fulminant hepatic failure, caused by severe liver injury or massive loss of HEPATOCYTES. It is characterized by sudden development of liver dysfunction and JAUNDICE. Acute liver failure may progress to exhibit cerebral dysfunction even HEPATIC COMA depending on the etiology that includes hepatic ISCHEMIA, drug toxicity, malignant infiltration, and viral hepatitis such as post-transfusion HEPATITIS B and HEPATITIS C.\n    ", "id": "MESH:D017114"}
{"mention": "alcohol", "mention_text": "Acute liver failure in two patients with regular alcohol consumption ingesting paracetamol at therapeutic dosage.", "entity": "Ethanol", "aliases": "Absolute Alcohol Ethyl Grain Ethanol", "definition": "A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.\n    ", "id": "MESH:D000431"}
{"mention": "paracetamol", "mention_text": "Acute liver failure in two patients with regular alcohol consumption ingesting paracetamol at therapeutic dosage.", "entity": "Acetaminophen", "aliases": "APAP Acamol Acephen Acetaco Acetamidophenol Acetaminophen Acetominophen Algotropyl Anacin 3 Anacin-3 Anacin3 Datril Hydroxyacetanilide N-(4-Hydroxyphenyl)acetanilide N-Acetyl-p-aminophenol Panadol Paracetamol Tylenol p-Acetamidophenol p-Hydroxyacetanilide", "definition": "Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.\n    ", "id": "MESH:D000082"}
{"mention": "alcohol", "mention_text": "BACKGROUND: The possible role of alcohol in the development of hepatotoxicity associated with therapeutic doses of paracetamol (acetaminophen) is currently debated. CASE REPORT: We describe 2 patients who were regular consumers of alcohol and who developed liver failure within 3-5 days after hospitalization and stopping alcohol consumption while being treated with 4 g paracetamol/day. A paracetamol serum level obtained in one of these patients was not in the toxic range. Possible risk factors for the development of hepatotoxicity in patients treated with therapeutic doses of paracetamol are discussed. CONCLUSION: In patients with risk factors, e.g. regular consumption of alcohol, liver failure is possible when therapeutic doses are ingested. We propose that the paracetamol dose should not exceed 2 g/day in such patients and that their liver function should be monitored closely while being treated with paracetamol.", "entity": "Ethanol", "aliases": "Absolute Alcohol Ethyl Grain Ethanol", "definition": "A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.\n    ", "id": "MESH:D000431"}
{"mention": "hepatotoxicity", "mention_text": "BACKGROUND: The possible role of alcohol in the development of hepatotoxicity associated with therapeutic doses of paracetamol (acetaminophen) is currently debated. CASE REPORT: We describe 2 patients who were regular consumers of alcohol and who developed liver failure within 3-5 days after hospitalization and stopping alcohol consumption while being treated with 4 g paracetamol/day. A paracetamol serum level obtained in one of these patients was not in the toxic range. Possible risk factors for the development of hepatotoxicity in patients treated with therapeutic doses of paracetamol are discussed. CONCLUSION: In patients with risk factors, e.g. regular consumption of alcohol, liver failure is possible when therapeutic doses are ingested. We propose that the paracetamol dose should not exceed 2 g/day in such patients and that their liver function should be monitored closely while being treated with paracetamol.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "paracetamol", "mention_text": "BACKGROUND: The possible role of alcohol in the development of hepatotoxicity associated with therapeutic doses of paracetamol (acetaminophen) is currently debated. CASE REPORT: We describe 2 patients who were regular consumers of alcohol and who developed liver failure within 3-5 days after hospitalization and stopping alcohol consumption while being treated with 4 g paracetamol/day. A paracetamol serum level obtained in one of these patients was not in the toxic range. Possible risk factors for the development of hepatotoxicity in patients treated with therapeutic doses of paracetamol are discussed. CONCLUSION: In patients with risk factors, e.g. regular consumption of alcohol, liver failure is possible when therapeutic doses are ingested. We propose that the paracetamol dose should not exceed 2 g/day in such patients and that their liver function should be monitored closely while being treated with paracetamol.", "entity": "Acetaminophen", "aliases": "APAP Acamol Acephen Acetaco Acetamidophenol Acetaminophen Acetominophen Algotropyl Anacin 3 Anacin-3 Anacin3 Datril Hydroxyacetanilide N-(4-Hydroxyphenyl)acetanilide N-Acetyl-p-aminophenol Panadol Paracetamol Tylenol p-Acetamidophenol p-Hydroxyacetanilide", "definition": "Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.\n    ", "id": "MESH:D000082"}
{"mention": "acetaminophen", "mention_text": "BACKGROUND: The possible role of alcohol in the development of hepatotoxicity associated with therapeutic doses of paracetamol (acetaminophen) is currently debated. CASE REPORT: We describe 2 patients who were regular consumers of alcohol and who developed liver failure within 3-5 days after hospitalization and stopping alcohol consumption while being treated with 4 g paracetamol/day. A paracetamol serum level obtained in one of these patients was not in the toxic range. Possible risk factors for the development of hepatotoxicity in patients treated with therapeutic doses of paracetamol are discussed. CONCLUSION: In patients with risk factors, e.g. regular consumption of alcohol, liver failure is possible when therapeutic doses are ingested. We propose that the paracetamol dose should not exceed 2 g/day in such patients and that their liver function should be monitored closely while being treated with paracetamol.", "entity": "Acetaminophen", "aliases": "APAP Acamol Acephen Acetaco Acetamidophenol Acetaminophen Acetominophen Algotropyl Anacin 3 Anacin-3 Anacin3 Datril Hydroxyacetanilide N-(4-Hydroxyphenyl)acetanilide N-Acetyl-p-aminophenol Panadol Paracetamol Tylenol p-Acetamidophenol p-Hydroxyacetanilide", "definition": "Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.\n    ", "id": "MESH:D000082"}
{"mention": "liver failure", "mention_text": "BACKGROUND: The possible role of alcohol in the development of hepatotoxicity associated with therapeutic doses of paracetamol (acetaminophen) is currently debated. CASE REPORT: We describe 2 patients who were regular consumers of alcohol and who developed liver failure within 3-5 days after hospitalization and stopping alcohol consumption while being treated with 4 g paracetamol/day. A paracetamol serum level obtained in one of these patients was not in the toxic range. Possible risk factors for the development of hepatotoxicity in patients treated with therapeutic doses of paracetamol are discussed. CONCLUSION: In patients with risk factors, e.g. regular consumption of alcohol, liver failure is possible when therapeutic doses are ingested. We propose that the paracetamol dose should not exceed 2 g/day in such patients and that their liver function should be monitored closely while being treated with paracetamol.", "entity": "Liver Failure", "aliases": "Hepatic Failure Liver", "definition": "Severe inability of the LIVER to perform its normal metabolic functions, as evidenced by severe JAUNDICE and abnormal serum levels of AMMONIA; BILIRUBIN; ALKALINE PHOSPHATASE; ASPARTATE AMINOTRANSFERASE; LACTATE DEHYDROGENASES; and albumin/globulin ratio. (Blakiston's Gould Medical Dictionary, 4th ed)\n    ", "id": "MESH:D017093"}
{"mention": "Cocaine", "mention_text": "Cocaine related chest pain: are we seeing the tip of an iceberg?", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "chest pain", "mention_text": "Cocaine related chest pain: are we seeing the tip of an iceberg?", "entity": "Chest Pain", "aliases": "Chest Pain Pains", "definition": "Pressure, burning, or numbness in the chest.\n    ", "id": "MESH:D002637"}
{"mention": "cocaine", "mention_text": "The recreational use of cocaine is on the increase. The emergency nurse ought to be familiar with some of the cardiovascular consequences of cocaine use. In particular, the tendency of cocaine to produce chest pain ought to be in the mind of the emergency nurse when faced with a young victim of chest pain who is otherwise at low risk. The mechanism of chest pain related to cocaine use is discussed and treatment dilemmas are discussed. Finally, moral issues relating to the testing of potential cocaine users will be addressed.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "chest pain", "mention_text": "The recreational use of cocaine is on the increase. The emergency nurse ought to be familiar with some of the cardiovascular consequences of cocaine use. In particular, the tendency of cocaine to produce chest pain ought to be in the mind of the emergency nurse when faced with a young victim of chest pain who is otherwise at low risk. The mechanism of chest pain related to cocaine use is discussed and treatment dilemmas are discussed. Finally, moral issues relating to the testing of potential cocaine users will be addressed.", "entity": "Chest Pain", "aliases": "Chest Pain Pains", "definition": "Pressure, burning, or numbness in the chest.\n    ", "id": "MESH:D002637"}
{"mention": "rhabdomyolysis", "mention_text": "Severe rhabdomyolysis and acute renal failure secondary to concomitant use of simvastatin, amiodarone, and atazanavir.", "entity": "Rhabdomyolysis", "aliases": "Rhabdomyolyses Rhabdomyolysis", "definition": "Necrosis or disintegration of skeletal muscle often followed by myoglobinuria.\n    ", "id": "MESH:D012206"}
{"mention": "acute renal failure", "mention_text": "Severe rhabdomyolysis and acute renal failure secondary to concomitant use of simvastatin, amiodarone, and atazanavir.", "entity": "Acute Kidney Injury", "aliases": "Acute Kidney Failure Failures Injuries Injury Insufficiencies Insufficiency Renal", "definition": "Abrupt reduction in kidney function. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions.\n    ", "id": "MESH:D058186"}
{"mention": "simvastatin", "mention_text": "Severe rhabdomyolysis and acute renal failure secondary to concomitant use of simvastatin, amiodarone, and atazanavir.", "entity": "Simvastatin", "aliases": "MK 733 MK-733 MK733 Simvastatin Synvinolin Zocor", "definition": "A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL CHOLESTEROL.\n    ", "id": "MESH:D019821"}
{"mention": "amiodarone", "mention_text": "Severe rhabdomyolysis and acute renal failure secondary to concomitant use of simvastatin, amiodarone, and atazanavir.", "entity": "Amiodarone", "aliases": "ASTA Medica Brand of Amiodarone Hydrochloride Alphapharm Amiobeta Amiodarex Amiodarona Amiohexal Aratac Armstrong Berenguer Infale Betapharm Braxan Corbionax Cordarex Cordarone G Gam Hexal Kordaron L 3428 L-3428 L3428 Leurquin Ortacrone Pharma Investi Rytmarone SKF 33134 A 33134-A 33134A Sanofi Winthrop Tachydaron Trangorex Wyeth", "definition": "An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.\n    ", "id": "MESH:D000638"}
{"mention": "atazanavir", "mention_text": "Severe rhabdomyolysis and acute renal failure secondary to concomitant use of simvastatin, amiodarone, and atazanavir.", "entity": "atazanavir", "aliases": "3,12-bis(1,1-dimethylethyl)-8-hydroxy-4,11-dioxo-9-(phenylmethyl)-6-((4-(2-pyridinyl)phenyl)methyl)-2,5,6,10,13-pentaazatetradecanedioic acid dimethyl ester BMS 232632 BMS-232632 BMS-232632-05 BMS232632 CGP 73547 75136 75176 75355 CGP-73547 CGP-75136 CGP-75176 CGP-75355 CGP75136 CGP75176 CGP75355 Reyataz atazanavir sulfate", "definition": "", "id": "MESH:C413408"}
{"mention": "simvastatin", "mention_text": "OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.", "entity": "Simvastatin", "aliases": "MK 733 MK-733 MK733 Simvastatin Synvinolin Zocor", "definition": "A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL CHOLESTEROL.\n    ", "id": "MESH:D019821"}
{"mention": "amiodarone", "mention_text": "OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.", "entity": "Amiodarone", "aliases": "ASTA Medica Brand of Amiodarone Hydrochloride Alphapharm Amiobeta Amiodarex Amiodarona Amiohexal Aratac Armstrong Berenguer Infale Betapharm Braxan Corbionax Cordarex Cordarone G Gam Hexal Kordaron L 3428 L-3428 L3428 Leurquin Ortacrone Pharma Investi Rytmarone SKF 33134 A 33134-A 33134A Sanofi Winthrop Tachydaron Trangorex Wyeth", "definition": "An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.\n    ", "id": "MESH:D000638"}
{"mention": "atazanavir", "mention_text": "OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.", "entity": "atazanavir", "aliases": "3,12-bis(1,1-dimethylethyl)-8-hydroxy-4,11-dioxo-9-(phenylmethyl)-6-((4-(2-pyridinyl)phenyl)methyl)-2,5,6,10,13-pentaazatetradecanedioic acid dimethyl ester BMS 232632 BMS-232632 BMS-232632-05 BMS232632 CGP 73547 75136 75176 75355 CGP-73547 CGP-75136 CGP-75176 CGP-75355 CGP75136 CGP75176 CGP75355 Reyataz atazanavir sulfate", "definition": "", "id": "MESH:C413408"}
{"mention": "rhabdomyolysis", "mention_text": "OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.", "entity": "Rhabdomyolysis", "aliases": "Rhabdomyolyses Rhabdomyolysis", "definition": "Necrosis or disintegration of skeletal muscle often followed by myoglobinuria.\n    ", "id": "MESH:D012206"}
{"mention": "acute renal failure", "mention_text": "OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.", "entity": "Acute Kidney Injury", "aliases": "Acute Kidney Failure Failures Injuries Injury Insufficiencies Insufficiency Renal", "definition": "Abrupt reduction in kidney function. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions.\n    ", "id": "MESH:D058186"}
{"mention": "human immunodeficiency virus", "mention_text": "OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.", "entity": "HIV Infections", "aliases": "HIV Infection Infections HTLV III LAV HTLV-III HTLV-III-LAV T Lymphotropic Virus Type Human T-Lymphotropic", "definition": "Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).\n    ", "id": "MESH:D015658"}
{"mention": "atrial fibrillation", "mention_text": "OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.", "entity": "Atrial Fibrillation", "aliases": "Atrial Fibrillation Fibrillations Auricular Familial", "definition": "Abnormal cardiac rhythm that is characterized by rapid, uncoordinated firing of electrical impulses in the upper chambers of the heart (HEART ATRIA). In such case, blood cannot be effectively pumped into the lower chambers of the heart (HEART VENTRICLES). It is caused by abnormal impulse generation.\n    ", "id": "MESH:D001281"}
{"mention": "coronary artery disease", "mention_text": "OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.", "entity": "Coronary Artery Disease", "aliases": "Arterioscleroses Coronary Arteriosclerosis Artery Disease Diseases Atheroscleroses Atherosclerosis", "definition": "Pathological processes of CORONARY ARTERIES that may derive from a congenital abnormality, atherosclerotic, or non-atherosclerotic cause.\n    ", "id": "MESH:D003324"}
{"mention": "hyperlipidemia", "mention_text": "OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.", "entity": "Hyperlipidemias", "aliases": "Hyperlipemia Hyperlipemias Hyperlipidemia Hyperlipidemias Lipemia Lipemias Lipidemia Lipidemias", "definition": "Conditions with excess LIPIDS in the blood.\n    ", "id": "MESH:D006949"}
{"mention": "pain", "mention_text": "OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "fatigue", "mention_text": "OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.", "entity": "Fatigue", "aliases": "Fatigue Lassitude", "definition": "The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.\n    ", "id": "MESH:D005221"}
{"mention": "creatine", "mention_text": "OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.", "entity": "Creatine", "aliases": "Creatine", "definition": "An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as CREATININE in the urine.\n    ", "id": "MESH:D003401"}
{"mention": "blood urea nitrogen", "mention_text": "OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.", "entity": "Blood Urea Nitrogen", "aliases": "BUN Blood Urea Nitrogen", "definition": "The urea concentration of the blood stated in terms of nitrogen content. Serum (plasma) urea nitrogen is approximately 12% higher than blood urea nitrogen concentration because of the greater protein content of red blood cells. Increases in blood or serum urea nitrogen are referred to as azotemia and may have prerenal, renal, or postrenal causes. (From Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984)\n    ", "id": "MESH:D001806"}
{"mention": "creatinine", "mention_text": "OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.", "entity": "Creatinine", "aliases": "Creatinine Sulfate Salt Krebiozen", "definition": "", "id": "MESH:D003404"}
{"mention": "aspartate", "mention_text": "OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.", "entity": "Aspartic Acid", "aliases": "(+-)-Aspartic Acid (R,S)-Aspartic Ammonium Aspartate Magnesium Hydrochloride Calcium Dipotassium Disodium Monopotassium Monosodium Potassium Sodium Aspartic Salt Hydrobromide (1:1) Trihydrate (2:1) Magnesium-Potassium (2:1:2) L L-Aspartate L-Aspartic Magnesiocard Mg 5 Longoral Mg-5-Longoral Mg5Longoral", "definition": "One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.\n    ", "id": "MESH:D001224"}
{"mention": "alanine", "mention_text": "OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.", "entity": "Alanine", "aliases": "Abufène Alanine Doms-Adrian Brand L Isomer L-Isomer Doms Adrian of L-Alanine", "definition": "A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases IMMUNITY, and provides energy for muscle tissue, BRAIN, and the CENTRAL NERVOUS SYSTEM.\n    ", "id": "MESH:D000409"}
{"mention": "Simvastatin", "mention_text": "OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.", "entity": "Simvastatin", "aliases": "MK 733 MK-733 MK733 Simvastatin Synvinolin Zocor", "definition": "A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL CHOLESTEROL.\n    ", "id": "MESH:D019821"}
{"mention": "Amiodarone", "mention_text": "OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.", "entity": "Amiodarone", "aliases": "ASTA Medica Brand of Amiodarone Hydrochloride Alphapharm Amiobeta Amiodarex Amiodarona Amiohexal Aratac Armstrong Berenguer Infale Betapharm Braxan Corbionax Cordarex Cordarone G Gam Hexal Kordaron L 3428 L-3428 L3428 Leurquin Ortacrone Pharma Investi Rytmarone SKF 33134 A 33134-A 33134A Sanofi Winthrop Tachydaron Trangorex Wyeth", "definition": "An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.\n    ", "id": "MESH:D000638"}
{"mention": "statins", "mention_text": "OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.", "entity": "Simvastatin", "aliases": "MK 733 MK-733 MK733 Simvastatin Synvinolin Zocor", "definition": "A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL CHOLESTEROL.\n    ", "id": "MESH:D019821"}
{"mention": "pravastatin", "mention_text": "OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.", "entity": "Pravastatin", "aliases": "Apo Pravastatin Apo-Pravastatin Apotex Brand of Sodium Aventis Bristacol Bristol-Myers Squibb CS 514 CS-514 CS514 Elisor Eptastatin Esteve Juste Lin Lin-Pravastatin Linson Pharma Lipemol Liplat Lipostat Mevalotin Nu Nu-Pharma Nu-Pravastatin Prareduct Pravachol Pravacol Pravasin Monosodium Salt (6 beta)-Isomer tert Octylamine tert-Octylamine RMS 431 RMS-431 RMS431 SQ 31,000 31000 SQ-31,000 SQ-31000 SQ31,000 SQ31000 Sankyo Selektine Vasten", "definition": "An antilipemic fungal metabolite isolated from cultures of Nocardia autotrophica. It acts as a competitive inhibitor of HMG CoA reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES).\n    ", "id": "MESH:D017035"}
{"mention": "fluvastatin", "mention_text": "OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.", "entity": "fluvastatin", "aliases": "7-(3-(4-fluorophenyl)-1-(1-methylethyl)-1H-indol-2-yl)-3,5-dihydroxy-6-heptenoate Lescol XU 62-320 62320 XU-62320 fluindostatin fluvastatin sodium salt", "definition": "", "id": "MESH:C065180"}
{"mention": "rosuvastatin", "mention_text": "OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.", "entity": "rosuvastatin", "aliases": "Crestor ZD 4522 ZD4522 rosuvastatin calcium", "definition": "", "id": "MESH:C422923"}
{"mention": "atorvastatin", "mention_text": "OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.", "entity": "atorvastatin", "aliases": "CI 981 CI-981 Lipitor atorvastatin calcium anhydrous hydrate trihydrate salt liptonorm", "definition": "", "id": "MESH:C065179"}
{"mention": "lovastatin", "mention_text": "OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.", "entity": "Lovastatin", "aliases": "1 alpha-Isomer Lovastatin 6 Methylcompactin 6-Methylcompactin (1 alpha(S*))-Isomer alpha Isomer MK 803 MK-803 MK803 Mevacor Mevinolin Monacolin K", "definition": "A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver.\n    ", "id": "MESH:D008148"}
{"mention": "vinorelbine", "mention_text": "Phase II trial of vinorelbine in metastatic squamous cell esophageal carcinoma. European Organization for Research and Treatment of Cancer Gastrointestinal Treat Cancer Cooperative Group.", "entity": "vinorelbine", "aliases": "5'-nor-anhydrovinblastine KW 2307 KW-2307 Navelbine vinorelbine tartrate", "definition": "", "id": "MESH:C030852"}
{"mention": "squamous cell esophageal carcinoma", "mention_text": "Phase II trial of vinorelbine in metastatic squamous cell esophageal carcinoma. European Organization for Research and Treatment of Cancer Gastrointestinal Treat Cancer Cooperative Group.", "entity": "Esophageal Squamous Cell Carcinoma", "aliases": "Esophageal Squamous Cell Carcinoma", "definition": "", "id": "MESH:C562729"}
{"mention": "Cancer", "mention_text": "Phase II trial of vinorelbine in metastatic squamous cell esophageal carcinoma. European Organization for Research and Treatment of Cancer Gastrointestinal Treat Cancer Cooperative Group.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "vinorelbine", "mention_text": "PURPOSE: To evaluate the response rate and toxic effects of vinorelbine (VNB) administered as a single agent in metastatic squamous cell esophageal carcinoma. PATIENTS AND METHODS: Forty-six eligible patients with measurable lesions were included and were stratified according to previous chemotherapy. Thirty patients without prior chemotherapy and 16 pretreated with cisplatin-based chemotherapy were assessable for toxicity and response. VNB was administered weekly as a 25-mg/m2 short intravenous (i.v.) infusion. RESULTS: Six of 30 patients (20%) without prior chemotherapy achieved a partial response (PR) (95% confidence interval [CI], 8% to 39%). The median duration of response was 21 weeks (range, 17 to 28). One of 16 patients (6%) with prior chemotherapy had a complete response (CR) of 31 weeks' duration (95% CI, 0% to 30%). The overall response rate (World Health Organization [WHO] criteria) was 15% (CR, 2%; PR 13%; 95% CI, 6% to 29%). The median dose-intensity (DI) was 20 mg/m2/wk. VNB was well tolerated and zero instances of WHO grade 4 nonhematologic toxicity occurred. At least one episode of grade 3 or 4 granulocytopenia was seen in 59% of patients. A grade 2 or 3 infection occurred in 16% of patients, but no toxic deaths occurred. Other side effects were rare, and peripheral neurotoxicity has been minor (26% grade 1). CONCLUSION: These data indicate that VNB is an active agent in metastatic esophageal squamous cell carcinoma. Given its excellent tolerance profile and low toxicity, further evaluation of VNB in combination therapy is warranted.", "entity": "vinorelbine", "aliases": "5'-nor-anhydrovinblastine KW 2307 KW-2307 Navelbine vinorelbine tartrate", "definition": "", "id": "MESH:C030852"}
{"mention": "VNB", "mention_text": "PURPOSE: To evaluate the response rate and toxic effects of vinorelbine (VNB) administered as a single agent in metastatic squamous cell esophageal carcinoma. PATIENTS AND METHODS: Forty-six eligible patients with measurable lesions were included and were stratified according to previous chemotherapy. Thirty patients without prior chemotherapy and 16 pretreated with cisplatin-based chemotherapy were assessable for toxicity and response. VNB was administered weekly as a 25-mg/m2 short intravenous (i.v.) infusion. RESULTS: Six of 30 patients (20%) without prior chemotherapy achieved a partial response (PR) (95% confidence interval [CI], 8% to 39%). The median duration of response was 21 weeks (range, 17 to 28). One of 16 patients (6%) with prior chemotherapy had a complete response (CR) of 31 weeks' duration (95% CI, 0% to 30%). The overall response rate (World Health Organization [WHO] criteria) was 15% (CR, 2%; PR 13%; 95% CI, 6% to 29%). The median dose-intensity (DI) was 20 mg/m2/wk. VNB was well tolerated and zero instances of WHO grade 4 nonhematologic toxicity occurred. At least one episode of grade 3 or 4 granulocytopenia was seen in 59% of patients. A grade 2 or 3 infection occurred in 16% of patients, but no toxic deaths occurred. Other side effects were rare, and peripheral neurotoxicity has been minor (26% grade 1). CONCLUSION: These data indicate that VNB is an active agent in metastatic esophageal squamous cell carcinoma. Given its excellent tolerance profile and low toxicity, further evaluation of VNB in combination therapy is warranted.", "entity": "vinorelbine", "aliases": "5'-nor-anhydrovinblastine KW 2307 KW-2307 Navelbine vinorelbine tartrate", "definition": "", "id": "MESH:C030852"}
{"mention": "squamous cell esophageal carcinoma", "mention_text": "PURPOSE: To evaluate the response rate and toxic effects of vinorelbine (VNB) administered as a single agent in metastatic squamous cell esophageal carcinoma. PATIENTS AND METHODS: Forty-six eligible patients with measurable lesions were included and were stratified according to previous chemotherapy. Thirty patients without prior chemotherapy and 16 pretreated with cisplatin-based chemotherapy were assessable for toxicity and response. VNB was administered weekly as a 25-mg/m2 short intravenous (i.v.) infusion. RESULTS: Six of 30 patients (20%) without prior chemotherapy achieved a partial response (PR) (95% confidence interval [CI], 8% to 39%). The median duration of response was 21 weeks (range, 17 to 28). One of 16 patients (6%) with prior chemotherapy had a complete response (CR) of 31 weeks' duration (95% CI, 0% to 30%). The overall response rate (World Health Organization [WHO] criteria) was 15% (CR, 2%; PR 13%; 95% CI, 6% to 29%). The median dose-intensity (DI) was 20 mg/m2/wk. VNB was well tolerated and zero instances of WHO grade 4 nonhematologic toxicity occurred. At least one episode of grade 3 or 4 granulocytopenia was seen in 59% of patients. A grade 2 or 3 infection occurred in 16% of patients, but no toxic deaths occurred. Other side effects were rare, and peripheral neurotoxicity has been minor (26% grade 1). CONCLUSION: These data indicate that VNB is an active agent in metastatic esophageal squamous cell carcinoma. Given its excellent tolerance profile and low toxicity, further evaluation of VNB in combination therapy is warranted.", "entity": "Esophageal Squamous Cell Carcinoma", "aliases": "Esophageal Squamous Cell Carcinoma", "definition": "", "id": "MESH:C562729"}
{"mention": "cisplatin", "mention_text": "PURPOSE: To evaluate the response rate and toxic effects of vinorelbine (VNB) administered as a single agent in metastatic squamous cell esophageal carcinoma. PATIENTS AND METHODS: Forty-six eligible patients with measurable lesions were included and were stratified according to previous chemotherapy. Thirty patients without prior chemotherapy and 16 pretreated with cisplatin-based chemotherapy were assessable for toxicity and response. VNB was administered weekly as a 25-mg/m2 short intravenous (i.v.) infusion. RESULTS: Six of 30 patients (20%) without prior chemotherapy achieved a partial response (PR) (95% confidence interval [CI], 8% to 39%). The median duration of response was 21 weeks (range, 17 to 28). One of 16 patients (6%) with prior chemotherapy had a complete response (CR) of 31 weeks' duration (95% CI, 0% to 30%). The overall response rate (World Health Organization [WHO] criteria) was 15% (CR, 2%; PR 13%; 95% CI, 6% to 29%). The median dose-intensity (DI) was 20 mg/m2/wk. VNB was well tolerated and zero instances of WHO grade 4 nonhematologic toxicity occurred. At least one episode of grade 3 or 4 granulocytopenia was seen in 59% of patients. A grade 2 or 3 infection occurred in 16% of patients, but no toxic deaths occurred. Other side effects were rare, and peripheral neurotoxicity has been minor (26% grade 1). CONCLUSION: These data indicate that VNB is an active agent in metastatic esophageal squamous cell carcinoma. Given its excellent tolerance profile and low toxicity, further evaluation of VNB in combination therapy is warranted.", "entity": "Cisplatin", "aliases": "Biocisplatinum Cisplatin Diamminodichloride Platinum Dichlorodiammineplatinum NSC-119875 Platidiam Platino Platinol cis Diamminedichloroplatinum cis-Diamminedichloroplatinum cis-Diamminedichloroplatinum(II) cis-Dichlorodiammineplatinum(II) cis-Platinum", "definition": "An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.\n    ", "id": "MESH:D002945"}
{"mention": "toxicity", "mention_text": "PURPOSE: To evaluate the response rate and toxic effects of vinorelbine (VNB) administered as a single agent in metastatic squamous cell esophageal carcinoma. PATIENTS AND METHODS: Forty-six eligible patients with measurable lesions were included and were stratified according to previous chemotherapy. Thirty patients without prior chemotherapy and 16 pretreated with cisplatin-based chemotherapy were assessable for toxicity and response. VNB was administered weekly as a 25-mg/m2 short intravenous (i.v.) infusion. RESULTS: Six of 30 patients (20%) without prior chemotherapy achieved a partial response (PR) (95% confidence interval [CI], 8% to 39%). The median duration of response was 21 weeks (range, 17 to 28). One of 16 patients (6%) with prior chemotherapy had a complete response (CR) of 31 weeks' duration (95% CI, 0% to 30%). The overall response rate (World Health Organization [WHO] criteria) was 15% (CR, 2%; PR 13%; 95% CI, 6% to 29%). The median dose-intensity (DI) was 20 mg/m2/wk. VNB was well tolerated and zero instances of WHO grade 4 nonhematologic toxicity occurred. At least one episode of grade 3 or 4 granulocytopenia was seen in 59% of patients. A grade 2 or 3 infection occurred in 16% of patients, but no toxic deaths occurred. Other side effects were rare, and peripheral neurotoxicity has been minor (26% grade 1). CONCLUSION: These data indicate that VNB is an active agent in metastatic esophageal squamous cell carcinoma. Given its excellent tolerance profile and low toxicity, further evaluation of VNB in combination therapy is warranted.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "granulocytopenia", "mention_text": "PURPOSE: To evaluate the response rate and toxic effects of vinorelbine (VNB) administered as a single agent in metastatic squamous cell esophageal carcinoma. PATIENTS AND METHODS: Forty-six eligible patients with measurable lesions were included and were stratified according to previous chemotherapy. Thirty patients without prior chemotherapy and 16 pretreated with cisplatin-based chemotherapy were assessable for toxicity and response. VNB was administered weekly as a 25-mg/m2 short intravenous (i.v.) infusion. RESULTS: Six of 30 patients (20%) without prior chemotherapy achieved a partial response (PR) (95% confidence interval [CI], 8% to 39%). The median duration of response was 21 weeks (range, 17 to 28). One of 16 patients (6%) with prior chemotherapy had a complete response (CR) of 31 weeks' duration (95% CI, 0% to 30%). The overall response rate (World Health Organization [WHO] criteria) was 15% (CR, 2%; PR 13%; 95% CI, 6% to 29%). The median dose-intensity (DI) was 20 mg/m2/wk. VNB was well tolerated and zero instances of WHO grade 4 nonhematologic toxicity occurred. At least one episode of grade 3 or 4 granulocytopenia was seen in 59% of patients. A grade 2 or 3 infection occurred in 16% of patients, but no toxic deaths occurred. Other side effects were rare, and peripheral neurotoxicity has been minor (26% grade 1). CONCLUSION: These data indicate that VNB is an active agent in metastatic esophageal squamous cell carcinoma. Given its excellent tolerance profile and low toxicity, further evaluation of VNB in combination therapy is warranted.", "entity": "Agranulocytosis", "aliases": "Agranulocytoses Agranulocytosis Granulocytopenia Granulocytopenias", "definition": "A decrease in the number of GRANULOCYTES; (BASOPHILS; EOSINOPHILS; and NEUTROPHILS).\n    ", "id": "MESH:D000380"}
{"mention": "infection", "mention_text": "PURPOSE: To evaluate the response rate and toxic effects of vinorelbine (VNB) administered as a single agent in metastatic squamous cell esophageal carcinoma. PATIENTS AND METHODS: Forty-six eligible patients with measurable lesions were included and were stratified according to previous chemotherapy. Thirty patients without prior chemotherapy and 16 pretreated with cisplatin-based chemotherapy were assessable for toxicity and response. VNB was administered weekly as a 25-mg/m2 short intravenous (i.v.) infusion. RESULTS: Six of 30 patients (20%) without prior chemotherapy achieved a partial response (PR) (95% confidence interval [CI], 8% to 39%). The median duration of response was 21 weeks (range, 17 to 28). One of 16 patients (6%) with prior chemotherapy had a complete response (CR) of 31 weeks' duration (95% CI, 0% to 30%). The overall response rate (World Health Organization [WHO] criteria) was 15% (CR, 2%; PR 13%; 95% CI, 6% to 29%). The median dose-intensity (DI) was 20 mg/m2/wk. VNB was well tolerated and zero instances of WHO grade 4 nonhematologic toxicity occurred. At least one episode of grade 3 or 4 granulocytopenia was seen in 59% of patients. A grade 2 or 3 infection occurred in 16% of patients, but no toxic deaths occurred. Other side effects were rare, and peripheral neurotoxicity has been minor (26% grade 1). CONCLUSION: These data indicate that VNB is an active agent in metastatic esophageal squamous cell carcinoma. Given its excellent tolerance profile and low toxicity, further evaluation of VNB in combination therapy is warranted.", "entity": "Infection", "aliases": "Infection Infections", "definition": "Invasion of the host organism by microorganisms that can cause pathological conditions or diseases.\n    ", "id": "MESH:D007239"}
{"mention": "deaths", "mention_text": "PURPOSE: To evaluate the response rate and toxic effects of vinorelbine (VNB) administered as a single agent in metastatic squamous cell esophageal carcinoma. PATIENTS AND METHODS: Forty-six eligible patients with measurable lesions were included and were stratified according to previous chemotherapy. Thirty patients without prior chemotherapy and 16 pretreated with cisplatin-based chemotherapy were assessable for toxicity and response. VNB was administered weekly as a 25-mg/m2 short intravenous (i.v.) infusion. RESULTS: Six of 30 patients (20%) without prior chemotherapy achieved a partial response (PR) (95% confidence interval [CI], 8% to 39%). The median duration of response was 21 weeks (range, 17 to 28). One of 16 patients (6%) with prior chemotherapy had a complete response (CR) of 31 weeks' duration (95% CI, 0% to 30%). The overall response rate (World Health Organization [WHO] criteria) was 15% (CR, 2%; PR 13%; 95% CI, 6% to 29%). The median dose-intensity (DI) was 20 mg/m2/wk. VNB was well tolerated and zero instances of WHO grade 4 nonhematologic toxicity occurred. At least one episode of grade 3 or 4 granulocytopenia was seen in 59% of patients. A grade 2 or 3 infection occurred in 16% of patients, but no toxic deaths occurred. Other side effects were rare, and peripheral neurotoxicity has been minor (26% grade 1). CONCLUSION: These data indicate that VNB is an active agent in metastatic esophageal squamous cell carcinoma. Given its excellent tolerance profile and low toxicity, further evaluation of VNB in combination therapy is warranted.", "entity": "Death", "aliases": "Cardiac Death Determination of Near-Death Experience", "definition": "Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.\n    ", "id": "MESH:D003643"}
{"mention": "peripheral neurotoxicity", "mention_text": "PURPOSE: To evaluate the response rate and toxic effects of vinorelbine (VNB) administered as a single agent in metastatic squamous cell esophageal carcinoma. PATIENTS AND METHODS: Forty-six eligible patients with measurable lesions were included and were stratified according to previous chemotherapy. Thirty patients without prior chemotherapy and 16 pretreated with cisplatin-based chemotherapy were assessable for toxicity and response. VNB was administered weekly as a 25-mg/m2 short intravenous (i.v.) infusion. RESULTS: Six of 30 patients (20%) without prior chemotherapy achieved a partial response (PR) (95% confidence interval [CI], 8% to 39%). The median duration of response was 21 weeks (range, 17 to 28). One of 16 patients (6%) with prior chemotherapy had a complete response (CR) of 31 weeks' duration (95% CI, 0% to 30%). The overall response rate (World Health Organization [WHO] criteria) was 15% (CR, 2%; PR 13%; 95% CI, 6% to 29%). The median dose-intensity (DI) was 20 mg/m2/wk. VNB was well tolerated and zero instances of WHO grade 4 nonhematologic toxicity occurred. At least one episode of grade 3 or 4 granulocytopenia was seen in 59% of patients. A grade 2 or 3 infection occurred in 16% of patients, but no toxic deaths occurred. Other side effects were rare, and peripheral neurotoxicity has been minor (26% grade 1). CONCLUSION: These data indicate that VNB is an active agent in metastatic esophageal squamous cell carcinoma. Given its excellent tolerance profile and low toxicity, further evaluation of VNB in combination therapy is warranted.", "entity": "Peripheral Nervous System Diseases", "aliases": "Nerve Disease Peripheral Diseases Neuropathy PNS (Peripheral Nervous System) System Disorders Neuropathies", "definition": "Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.\n    ", "id": "MESH:D010523"}
{"mention": "esophageal squamous cell carcinoma", "mention_text": "PURPOSE: To evaluate the response rate and toxic effects of vinorelbine (VNB) administered as a single agent in metastatic squamous cell esophageal carcinoma. PATIENTS AND METHODS: Forty-six eligible patients with measurable lesions were included and were stratified according to previous chemotherapy. Thirty patients without prior chemotherapy and 16 pretreated with cisplatin-based chemotherapy were assessable for toxicity and response. VNB was administered weekly as a 25-mg/m2 short intravenous (i.v.) infusion. RESULTS: Six of 30 patients (20%) without prior chemotherapy achieved a partial response (PR) (95% confidence interval [CI], 8% to 39%). The median duration of response was 21 weeks (range, 17 to 28). One of 16 patients (6%) with prior chemotherapy had a complete response (CR) of 31 weeks' duration (95% CI, 0% to 30%). The overall response rate (World Health Organization [WHO] criteria) was 15% (CR, 2%; PR 13%; 95% CI, 6% to 29%). The median dose-intensity (DI) was 20 mg/m2/wk. VNB was well tolerated and zero instances of WHO grade 4 nonhematologic toxicity occurred. At least one episode of grade 3 or 4 granulocytopenia was seen in 59% of patients. A grade 2 or 3 infection occurred in 16% of patients, but no toxic deaths occurred. Other side effects were rare, and peripheral neurotoxicity has been minor (26% grade 1). CONCLUSION: These data indicate that VNB is an active agent in metastatic esophageal squamous cell carcinoma. Given its excellent tolerance profile and low toxicity, further evaluation of VNB in combination therapy is warranted.", "entity": "Esophageal Squamous Cell Carcinoma", "aliases": "Esophageal Squamous Cell Carcinoma", "definition": "", "id": "MESH:C562729"}
{"mention": "Paclitaxel", "mention_text": "Paclitaxel, cisplatin, and gemcitabine combination chemotherapy within a multidisciplinary therapeutic approach in metastatic nonsmall cell lung carcinoma.", "entity": "Paclitaxel", "aliases": "7 epi Taxol 7-epi-Taxol Anzatax Bris Bristol-Myers Brand of Paclitaxel Squibb Bull Ivax Lemery NSC 125973 NSC-125973 NSC125973 Onxol (4 alpha)-Isomer Paxene Praxel A", "definition": "A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.\n    ", "id": "MESH:D017239"}
{"mention": "cisplatin", "mention_text": "Paclitaxel, cisplatin, and gemcitabine combination chemotherapy within a multidisciplinary therapeutic approach in metastatic nonsmall cell lung carcinoma.", "entity": "Cisplatin", "aliases": "Biocisplatinum Cisplatin Diamminodichloride Platinum Dichlorodiammineplatinum NSC-119875 Platidiam Platino Platinol cis Diamminedichloroplatinum cis-Diamminedichloroplatinum cis-Diamminedichloroplatinum(II) cis-Dichlorodiammineplatinum(II) cis-Platinum", "definition": "An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.\n    ", "id": "MESH:D002945"}
{"mention": "gemcitabine", "mention_text": "Paclitaxel, cisplatin, and gemcitabine combination chemotherapy within a multidisciplinary therapeutic approach in metastatic nonsmall cell lung carcinoma.", "entity": "gemcitabine", "aliases": "2',2'-DFDC 2',2'-difluoro-2'-deoxycytidine 2',2'-difluorodeoxycytidine 2'-deoxy-2',2''-difluorocytidine-5'-O-monophosphate 2'-deoxy-2'-difluorocytidine Gemzar LY 188011 LY-188011 dFdCyd gemcitabine hydrochloride (D-threo-pentafuranosyl)-isomer (alpha-D-threo-pentofuranosyl)-isomer (beta-D-threo-pentafuranosyl)-isomer", "definition": "", "id": "MESH:C056507"}
{"mention": "nonsmall cell lung carcinoma", "mention_text": "Paclitaxel, cisplatin, and gemcitabine combination chemotherapy within a multidisciplinary therapeutic approach in metastatic nonsmall cell lung carcinoma.", "entity": "Carcinoma, Non-Small-Cell Lung", "aliases": "Carcinoma Non Small Cell Lung Non-Small Non-Small-Cell Carcinomas Cancer Nonsmall", "definition": "A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.\n    ", "id": "MESH:D002289"}
{"mention": "Cisplatin", "mention_text": "BACKGROUND: Cisplatin-based chemotherapy combinations improve quality of life and survival in advanced nonsmall cell lung carcinoma (NSCLC). The emergence of new active drugs might translate into more effective regimens for the treatment of this disease. METHODS: The objective of this study was to determine the feasibility, response rate, and toxicity of a paclitaxel, cisplatin, and gemcitabine combination to treat metastatic NSCLC. Thirty-five consecutive chemotherapy-naive patients with Stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0-2 were treated with a combination of paclitaxel (135 mg/m(2) given intravenously in 3 hours) on Day 1, cisplatin (120 mg/m(2) given intravenously in 6 hours) on Day 1, and gemcitabine (800 mg/m(2) given intravenously in 30 minutes) on Days 1 and 8, every 4 weeks. Although responding patients were scheduled to receive consolidation radiotherapy and 24 patients received preplanned second-line chemotherapy after disease progression, the response and toxicity rates reported refer only to the chemotherapy regimen given. RESULTS: All the patients were examined for toxicity; 34 were examinable for response. An objective response was observed in 73.5% of the patients (95% confidence interval [CI], 55.6-87.1%), including 4 complete responses (11.7%). According to intention-to-treat, the overall response rate was 71.4% (95% CI, 53. 7-85.4%). After 154 courses of therapy, the median dose intensity was 131 mg/m(2) for paclitaxel (97.3%), 117 mg/m(2) for cisplatin (97.3%), and 1378 mg/m(2) for gemcitabine (86.2%). World Health Organization Grade 3-4 neutropenia and thrombocytopenia occurred in 39.9% and 11.4% of patients, respectively. There was one treatment-related death. Nonhematologic toxicities were mild. After a median follow-up of 22 months, the median progression free survival rate was 7 months, and the median survival time was 16 months. CONCLUSIONS: The combination of paclitaxel, cisplatin, and gemcitabine is well tolerated and shows high activity in metastatic NSCLC. This treatment merits further comparison with other cisplatin-based regimens.", "entity": "Cisplatin", "aliases": "Biocisplatinum Cisplatin Diamminodichloride Platinum Dichlorodiammineplatinum NSC-119875 Platidiam Platino Platinol cis Diamminedichloroplatinum cis-Diamminedichloroplatinum cis-Diamminedichloroplatinum(II) cis-Dichlorodiammineplatinum(II) cis-Platinum", "definition": "An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.\n    ", "id": "MESH:D002945"}
{"mention": "nonsmall cell lung carcinoma", "mention_text": "BACKGROUND: Cisplatin-based chemotherapy combinations improve quality of life and survival in advanced nonsmall cell lung carcinoma (NSCLC). The emergence of new active drugs might translate into more effective regimens for the treatment of this disease. METHODS: The objective of this study was to determine the feasibility, response rate, and toxicity of a paclitaxel, cisplatin, and gemcitabine combination to treat metastatic NSCLC. Thirty-five consecutive chemotherapy-naive patients with Stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0-2 were treated with a combination of paclitaxel (135 mg/m(2) given intravenously in 3 hours) on Day 1, cisplatin (120 mg/m(2) given intravenously in 6 hours) on Day 1, and gemcitabine (800 mg/m(2) given intravenously in 30 minutes) on Days 1 and 8, every 4 weeks. Although responding patients were scheduled to receive consolidation radiotherapy and 24 patients received preplanned second-line chemotherapy after disease progression, the response and toxicity rates reported refer only to the chemotherapy regimen given. RESULTS: All the patients were examined for toxicity; 34 were examinable for response. An objective response was observed in 73.5% of the patients (95% confidence interval [CI], 55.6-87.1%), including 4 complete responses (11.7%). According to intention-to-treat, the overall response rate was 71.4% (95% CI, 53. 7-85.4%). After 154 courses of therapy, the median dose intensity was 131 mg/m(2) for paclitaxel (97.3%), 117 mg/m(2) for cisplatin (97.3%), and 1378 mg/m(2) for gemcitabine (86.2%). World Health Organization Grade 3-4 neutropenia and thrombocytopenia occurred in 39.9% and 11.4% of patients, respectively. There was one treatment-related death. Nonhematologic toxicities were mild. After a median follow-up of 22 months, the median progression free survival rate was 7 months, and the median survival time was 16 months. CONCLUSIONS: The combination of paclitaxel, cisplatin, and gemcitabine is well tolerated and shows high activity in metastatic NSCLC. This treatment merits further comparison with other cisplatin-based regimens.", "entity": "Carcinoma, Non-Small-Cell Lung", "aliases": "Carcinoma Non Small Cell Lung Non-Small Non-Small-Cell Carcinomas Cancer Nonsmall", "definition": "A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.\n    ", "id": "MESH:D002289"}
{"mention": "NSCLC", "mention_text": "BACKGROUND: Cisplatin-based chemotherapy combinations improve quality of life and survival in advanced nonsmall cell lung carcinoma (NSCLC). The emergence of new active drugs might translate into more effective regimens for the treatment of this disease. METHODS: The objective of this study was to determine the feasibility, response rate, and toxicity of a paclitaxel, cisplatin, and gemcitabine combination to treat metastatic NSCLC. Thirty-five consecutive chemotherapy-naive patients with Stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0-2 were treated with a combination of paclitaxel (135 mg/m(2) given intravenously in 3 hours) on Day 1, cisplatin (120 mg/m(2) given intravenously in 6 hours) on Day 1, and gemcitabine (800 mg/m(2) given intravenously in 30 minutes) on Days 1 and 8, every 4 weeks. Although responding patients were scheduled to receive consolidation radiotherapy and 24 patients received preplanned second-line chemotherapy after disease progression, the response and toxicity rates reported refer only to the chemotherapy regimen given. RESULTS: All the patients were examined for toxicity; 34 were examinable for response. An objective response was observed in 73.5% of the patients (95% confidence interval [CI], 55.6-87.1%), including 4 complete responses (11.7%). According to intention-to-treat, the overall response rate was 71.4% (95% CI, 53. 7-85.4%). After 154 courses of therapy, the median dose intensity was 131 mg/m(2) for paclitaxel (97.3%), 117 mg/m(2) for cisplatin (97.3%), and 1378 mg/m(2) for gemcitabine (86.2%). World Health Organization Grade 3-4 neutropenia and thrombocytopenia occurred in 39.9% and 11.4% of patients, respectively. There was one treatment-related death. Nonhematologic toxicities were mild. After a median follow-up of 22 months, the median progression free survival rate was 7 months, and the median survival time was 16 months. CONCLUSIONS: The combination of paclitaxel, cisplatin, and gemcitabine is well tolerated and shows high activity in metastatic NSCLC. This treatment merits further comparison with other cisplatin-based regimens.", "entity": "Carcinoma, Non-Small-Cell Lung", "aliases": "Carcinoma Non Small Cell Lung Non-Small Non-Small-Cell Carcinomas Cancer Nonsmall", "definition": "A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.\n    ", "id": "MESH:D002289"}
{"mention": "toxicity", "mention_text": "BACKGROUND: Cisplatin-based chemotherapy combinations improve quality of life and survival in advanced nonsmall cell lung carcinoma (NSCLC). The emergence of new active drugs might translate into more effective regimens for the treatment of this disease. METHODS: The objective of this study was to determine the feasibility, response rate, and toxicity of a paclitaxel, cisplatin, and gemcitabine combination to treat metastatic NSCLC. Thirty-five consecutive chemotherapy-naive patients with Stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0-2 were treated with a combination of paclitaxel (135 mg/m(2) given intravenously in 3 hours) on Day 1, cisplatin (120 mg/m(2) given intravenously in 6 hours) on Day 1, and gemcitabine (800 mg/m(2) given intravenously in 30 minutes) on Days 1 and 8, every 4 weeks. Although responding patients were scheduled to receive consolidation radiotherapy and 24 patients received preplanned second-line chemotherapy after disease progression, the response and toxicity rates reported refer only to the chemotherapy regimen given. RESULTS: All the patients were examined for toxicity; 34 were examinable for response. An objective response was observed in 73.5% of the patients (95% confidence interval [CI], 55.6-87.1%), including 4 complete responses (11.7%). According to intention-to-treat, the overall response rate was 71.4% (95% CI, 53. 7-85.4%). After 154 courses of therapy, the median dose intensity was 131 mg/m(2) for paclitaxel (97.3%), 117 mg/m(2) for cisplatin (97.3%), and 1378 mg/m(2) for gemcitabine (86.2%). World Health Organization Grade 3-4 neutropenia and thrombocytopenia occurred in 39.9% and 11.4% of patients, respectively. There was one treatment-related death. Nonhematologic toxicities were mild. After a median follow-up of 22 months, the median progression free survival rate was 7 months, and the median survival time was 16 months. CONCLUSIONS: The combination of paclitaxel, cisplatin, and gemcitabine is well tolerated and shows high activity in metastatic NSCLC. This treatment merits further comparison with other cisplatin-based regimens.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "paclitaxel", "mention_text": "BACKGROUND: Cisplatin-based chemotherapy combinations improve quality of life and survival in advanced nonsmall cell lung carcinoma (NSCLC). The emergence of new active drugs might translate into more effective regimens for the treatment of this disease. METHODS: The objective of this study was to determine the feasibility, response rate, and toxicity of a paclitaxel, cisplatin, and gemcitabine combination to treat metastatic NSCLC. Thirty-five consecutive chemotherapy-naive patients with Stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0-2 were treated with a combination of paclitaxel (135 mg/m(2) given intravenously in 3 hours) on Day 1, cisplatin (120 mg/m(2) given intravenously in 6 hours) on Day 1, and gemcitabine (800 mg/m(2) given intravenously in 30 minutes) on Days 1 and 8, every 4 weeks. Although responding patients were scheduled to receive consolidation radiotherapy and 24 patients received preplanned second-line chemotherapy after disease progression, the response and toxicity rates reported refer only to the chemotherapy regimen given. RESULTS: All the patients were examined for toxicity; 34 were examinable for response. An objective response was observed in 73.5% of the patients (95% confidence interval [CI], 55.6-87.1%), including 4 complete responses (11.7%). According to intention-to-treat, the overall response rate was 71.4% (95% CI, 53. 7-85.4%). After 154 courses of therapy, the median dose intensity was 131 mg/m(2) for paclitaxel (97.3%), 117 mg/m(2) for cisplatin (97.3%), and 1378 mg/m(2) for gemcitabine (86.2%). World Health Organization Grade 3-4 neutropenia and thrombocytopenia occurred in 39.9% and 11.4% of patients, respectively. There was one treatment-related death. Nonhematologic toxicities were mild. After a median follow-up of 22 months, the median progression free survival rate was 7 months, and the median survival time was 16 months. CONCLUSIONS: The combination of paclitaxel, cisplatin, and gemcitabine is well tolerated and shows high activity in metastatic NSCLC. This treatment merits further comparison with other cisplatin-based regimens.", "entity": "Paclitaxel", "aliases": "7 epi Taxol 7-epi-Taxol Anzatax Bris Bristol-Myers Brand of Paclitaxel Squibb Bull Ivax Lemery NSC 125973 NSC-125973 NSC125973 Onxol (4 alpha)-Isomer Paxene Praxel A", "definition": "A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.\n    ", "id": "MESH:D017239"}
{"mention": "cisplatin", "mention_text": "BACKGROUND: Cisplatin-based chemotherapy combinations improve quality of life and survival in advanced nonsmall cell lung carcinoma (NSCLC). The emergence of new active drugs might translate into more effective regimens for the treatment of this disease. METHODS: The objective of this study was to determine the feasibility, response rate, and toxicity of a paclitaxel, cisplatin, and gemcitabine combination to treat metastatic NSCLC. Thirty-five consecutive chemotherapy-naive patients with Stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0-2 were treated with a combination of paclitaxel (135 mg/m(2) given intravenously in 3 hours) on Day 1, cisplatin (120 mg/m(2) given intravenously in 6 hours) on Day 1, and gemcitabine (800 mg/m(2) given intravenously in 30 minutes) on Days 1 and 8, every 4 weeks. Although responding patients were scheduled to receive consolidation radiotherapy and 24 patients received preplanned second-line chemotherapy after disease progression, the response and toxicity rates reported refer only to the chemotherapy regimen given. RESULTS: All the patients were examined for toxicity; 34 were examinable for response. An objective response was observed in 73.5% of the patients (95% confidence interval [CI], 55.6-87.1%), including 4 complete responses (11.7%). According to intention-to-treat, the overall response rate was 71.4% (95% CI, 53. 7-85.4%). After 154 courses of therapy, the median dose intensity was 131 mg/m(2) for paclitaxel (97.3%), 117 mg/m(2) for cisplatin (97.3%), and 1378 mg/m(2) for gemcitabine (86.2%). World Health Organization Grade 3-4 neutropenia and thrombocytopenia occurred in 39.9% and 11.4% of patients, respectively. There was one treatment-related death. Nonhematologic toxicities were mild. After a median follow-up of 22 months, the median progression free survival rate was 7 months, and the median survival time was 16 months. CONCLUSIONS: The combination of paclitaxel, cisplatin, and gemcitabine is well tolerated and shows high activity in metastatic NSCLC. This treatment merits further comparison with other cisplatin-based regimens.", "entity": "Cisplatin", "aliases": "Biocisplatinum Cisplatin Diamminodichloride Platinum Dichlorodiammineplatinum NSC-119875 Platidiam Platino Platinol cis Diamminedichloroplatinum cis-Diamminedichloroplatinum cis-Diamminedichloroplatinum(II) cis-Dichlorodiammineplatinum(II) cis-Platinum", "definition": "An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.\n    ", "id": "MESH:D002945"}
{"mention": "gemcitabine", "mention_text": "BACKGROUND: Cisplatin-based chemotherapy combinations improve quality of life and survival in advanced nonsmall cell lung carcinoma (NSCLC). The emergence of new active drugs might translate into more effective regimens for the treatment of this disease. METHODS: The objective of this study was to determine the feasibility, response rate, and toxicity of a paclitaxel, cisplatin, and gemcitabine combination to treat metastatic NSCLC. Thirty-five consecutive chemotherapy-naive patients with Stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0-2 were treated with a combination of paclitaxel (135 mg/m(2) given intravenously in 3 hours) on Day 1, cisplatin (120 mg/m(2) given intravenously in 6 hours) on Day 1, and gemcitabine (800 mg/m(2) given intravenously in 30 minutes) on Days 1 and 8, every 4 weeks. Although responding patients were scheduled to receive consolidation radiotherapy and 24 patients received preplanned second-line chemotherapy after disease progression, the response and toxicity rates reported refer only to the chemotherapy regimen given. RESULTS: All the patients were examined for toxicity; 34 were examinable for response. An objective response was observed in 73.5% of the patients (95% confidence interval [CI], 55.6-87.1%), including 4 complete responses (11.7%). According to intention-to-treat, the overall response rate was 71.4% (95% CI, 53. 7-85.4%). After 154 courses of therapy, the median dose intensity was 131 mg/m(2) for paclitaxel (97.3%), 117 mg/m(2) for cisplatin (97.3%), and 1378 mg/m(2) for gemcitabine (86.2%). World Health Organization Grade 3-4 neutropenia and thrombocytopenia occurred in 39.9% and 11.4% of patients, respectively. There was one treatment-related death. Nonhematologic toxicities were mild. After a median follow-up of 22 months, the median progression free survival rate was 7 months, and the median survival time was 16 months. CONCLUSIONS: The combination of paclitaxel, cisplatin, and gemcitabine is well tolerated and shows high activity in metastatic NSCLC. This treatment merits further comparison with other cisplatin-based regimens.", "entity": "gemcitabine", "aliases": "2',2'-DFDC 2',2'-difluoro-2'-deoxycytidine 2',2'-difluorodeoxycytidine 2'-deoxy-2',2''-difluorocytidine-5'-O-monophosphate 2'-deoxy-2'-difluorocytidine Gemzar LY 188011 LY-188011 dFdCyd gemcitabine hydrochloride (D-threo-pentafuranosyl)-isomer (alpha-D-threo-pentofuranosyl)-isomer (beta-D-threo-pentafuranosyl)-isomer", "definition": "", "id": "MESH:C056507"}
{"mention": "neutropenia", "mention_text": "BACKGROUND: Cisplatin-based chemotherapy combinations improve quality of life and survival in advanced nonsmall cell lung carcinoma (NSCLC). The emergence of new active drugs might translate into more effective regimens for the treatment of this disease. METHODS: The objective of this study was to determine the feasibility, response rate, and toxicity of a paclitaxel, cisplatin, and gemcitabine combination to treat metastatic NSCLC. Thirty-five consecutive chemotherapy-naive patients with Stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0-2 were treated with a combination of paclitaxel (135 mg/m(2) given intravenously in 3 hours) on Day 1, cisplatin (120 mg/m(2) given intravenously in 6 hours) on Day 1, and gemcitabine (800 mg/m(2) given intravenously in 30 minutes) on Days 1 and 8, every 4 weeks. Although responding patients were scheduled to receive consolidation radiotherapy and 24 patients received preplanned second-line chemotherapy after disease progression, the response and toxicity rates reported refer only to the chemotherapy regimen given. RESULTS: All the patients were examined for toxicity; 34 were examinable for response. An objective response was observed in 73.5% of the patients (95% confidence interval [CI], 55.6-87.1%), including 4 complete responses (11.7%). According to intention-to-treat, the overall response rate was 71.4% (95% CI, 53. 7-85.4%). After 154 courses of therapy, the median dose intensity was 131 mg/m(2) for paclitaxel (97.3%), 117 mg/m(2) for cisplatin (97.3%), and 1378 mg/m(2) for gemcitabine (86.2%). World Health Organization Grade 3-4 neutropenia and thrombocytopenia occurred in 39.9% and 11.4% of patients, respectively. There was one treatment-related death. Nonhematologic toxicities were mild. After a median follow-up of 22 months, the median progression free survival rate was 7 months, and the median survival time was 16 months. CONCLUSIONS: The combination of paclitaxel, cisplatin, and gemcitabine is well tolerated and shows high activity in metastatic NSCLC. This treatment merits further comparison with other cisplatin-based regimens.", "entity": "Neutropenia", "aliases": "Neutropenia Neutropenias", "definition": "A decrease in the number of NEUTROPHILS found in the blood.\n    ", "id": "MESH:D009503"}
{"mention": "thrombocytopenia", "mention_text": "BACKGROUND: Cisplatin-based chemotherapy combinations improve quality of life and survival in advanced nonsmall cell lung carcinoma (NSCLC). The emergence of new active drugs might translate into more effective regimens for the treatment of this disease. METHODS: The objective of this study was to determine the feasibility, response rate, and toxicity of a paclitaxel, cisplatin, and gemcitabine combination to treat metastatic NSCLC. Thirty-five consecutive chemotherapy-naive patients with Stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0-2 were treated with a combination of paclitaxel (135 mg/m(2) given intravenously in 3 hours) on Day 1, cisplatin (120 mg/m(2) given intravenously in 6 hours) on Day 1, and gemcitabine (800 mg/m(2) given intravenously in 30 minutes) on Days 1 and 8, every 4 weeks. Although responding patients were scheduled to receive consolidation radiotherapy and 24 patients received preplanned second-line chemotherapy after disease progression, the response and toxicity rates reported refer only to the chemotherapy regimen given. RESULTS: All the patients were examined for toxicity; 34 were examinable for response. An objective response was observed in 73.5% of the patients (95% confidence interval [CI], 55.6-87.1%), including 4 complete responses (11.7%). According to intention-to-treat, the overall response rate was 71.4% (95% CI, 53. 7-85.4%). After 154 courses of therapy, the median dose intensity was 131 mg/m(2) for paclitaxel (97.3%), 117 mg/m(2) for cisplatin (97.3%), and 1378 mg/m(2) for gemcitabine (86.2%). World Health Organization Grade 3-4 neutropenia and thrombocytopenia occurred in 39.9% and 11.4% of patients, respectively. There was one treatment-related death. Nonhematologic toxicities were mild. After a median follow-up of 22 months, the median progression free survival rate was 7 months, and the median survival time was 16 months. CONCLUSIONS: The combination of paclitaxel, cisplatin, and gemcitabine is well tolerated and shows high activity in metastatic NSCLC. This treatment merits further comparison with other cisplatin-based regimens.", "entity": "Thrombocytopenia", "aliases": "Thrombocytopenia Thrombocytopenias Thrombopenia Thrombopenias", "definition": "A subnormal level of BLOOD PLATELETS.\n    ", "id": "MESH:D013921"}
{"mention": "death", "mention_text": "BACKGROUND: Cisplatin-based chemotherapy combinations improve quality of life and survival in advanced nonsmall cell lung carcinoma (NSCLC). The emergence of new active drugs might translate into more effective regimens for the treatment of this disease. METHODS: The objective of this study was to determine the feasibility, response rate, and toxicity of a paclitaxel, cisplatin, and gemcitabine combination to treat metastatic NSCLC. Thirty-five consecutive chemotherapy-naive patients with Stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0-2 were treated with a combination of paclitaxel (135 mg/m(2) given intravenously in 3 hours) on Day 1, cisplatin (120 mg/m(2) given intravenously in 6 hours) on Day 1, and gemcitabine (800 mg/m(2) given intravenously in 30 minutes) on Days 1 and 8, every 4 weeks. Although responding patients were scheduled to receive consolidation radiotherapy and 24 patients received preplanned second-line chemotherapy after disease progression, the response and toxicity rates reported refer only to the chemotherapy regimen given. RESULTS: All the patients were examined for toxicity; 34 were examinable for response. An objective response was observed in 73.5% of the patients (95% confidence interval [CI], 55.6-87.1%), including 4 complete responses (11.7%). According to intention-to-treat, the overall response rate was 71.4% (95% CI, 53. 7-85.4%). After 154 courses of therapy, the median dose intensity was 131 mg/m(2) for paclitaxel (97.3%), 117 mg/m(2) for cisplatin (97.3%), and 1378 mg/m(2) for gemcitabine (86.2%). World Health Organization Grade 3-4 neutropenia and thrombocytopenia occurred in 39.9% and 11.4% of patients, respectively. There was one treatment-related death. Nonhematologic toxicities were mild. After a median follow-up of 22 months, the median progression free survival rate was 7 months, and the median survival time was 16 months. CONCLUSIONS: The combination of paclitaxel, cisplatin, and gemcitabine is well tolerated and shows high activity in metastatic NSCLC. This treatment merits further comparison with other cisplatin-based regimens.", "entity": "Death", "aliases": "Cardiac Death Determination of Near-Death Experience", "definition": "Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.\n    ", "id": "MESH:D003643"}
{"mention": "toxicities", "mention_text": "BACKGROUND: Cisplatin-based chemotherapy combinations improve quality of life and survival in advanced nonsmall cell lung carcinoma (NSCLC). The emergence of new active drugs might translate into more effective regimens for the treatment of this disease. METHODS: The objective of this study was to determine the feasibility, response rate, and toxicity of a paclitaxel, cisplatin, and gemcitabine combination to treat metastatic NSCLC. Thirty-five consecutive chemotherapy-naive patients with Stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0-2 were treated with a combination of paclitaxel (135 mg/m(2) given intravenously in 3 hours) on Day 1, cisplatin (120 mg/m(2) given intravenously in 6 hours) on Day 1, and gemcitabine (800 mg/m(2) given intravenously in 30 minutes) on Days 1 and 8, every 4 weeks. Although responding patients were scheduled to receive consolidation radiotherapy and 24 patients received preplanned second-line chemotherapy after disease progression, the response and toxicity rates reported refer only to the chemotherapy regimen given. RESULTS: All the patients were examined for toxicity; 34 were examinable for response. An objective response was observed in 73.5% of the patients (95% confidence interval [CI], 55.6-87.1%), including 4 complete responses (11.7%). According to intention-to-treat, the overall response rate was 71.4% (95% CI, 53. 7-85.4%). After 154 courses of therapy, the median dose intensity was 131 mg/m(2) for paclitaxel (97.3%), 117 mg/m(2) for cisplatin (97.3%), and 1378 mg/m(2) for gemcitabine (86.2%). World Health Organization Grade 3-4 neutropenia and thrombocytopenia occurred in 39.9% and 11.4% of patients, respectively. There was one treatment-related death. Nonhematologic toxicities were mild. After a median follow-up of 22 months, the median progression free survival rate was 7 months, and the median survival time was 16 months. CONCLUSIONS: The combination of paclitaxel, cisplatin, and gemcitabine is well tolerated and shows high activity in metastatic NSCLC. This treatment merits further comparison with other cisplatin-based regimens.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "aponidine hydrochloride", "mention_text": "Evaluation of adverse reactions of aponidine hydrochloride ophthalmic solution.", "entity": "apraclonidine", "aliases": "2-(4-amino-2,6-dichloro)phenyliminoimidazolidine 4-aminoclonidine ALO 2145 ALO-2145 Iopidine Iopimax apraclonidine hydrochloride p-aminoclonidine para-aminoclonidine", "definition": "", "id": "MESH:C016986"}
{"mention": "apraclonidine", "mention_text": "We prospectively evaluated the adverse reactions of apraclonidine in 20 normal volunteers by instilling a single drop of 1% apraclonidine in their right eyes. Examinations, including blood pressure, pulse rate, conjunctiva and cornea, intraocular pressure (IOP), pupil diameter, basal tear secretion and margin reflex distance of both upper and lower eyelids, were performed prior to entry and at 1, 3, 5 and 7 hours after instillation. The ocular hypotensive effects were statistically significant for apraclonidine-treated eyes throughout the study and also statistically significant for contralateral eyes from three hours after topical administration of 1% apraclonidine. Decreases in systolic blood pressure were statistically, but not clinically, significant. No significant changes in diastolic blood pressure, pulse rate and basal tear secretion were noted. Conjunctival blanching and mydriasis were commonly found. Upper lid retraction was frequently noted. While the elevations of the upper lid margin in most subjects were not more than 2 mm and did not cause noticeable change in appearance, one subject suffered from mechanical entropion and marked corneal abrasion 3 hours after instillation of the medication. This may well be a particularly notable finding in Asian people.", "entity": "apraclonidine", "aliases": "2-(4-amino-2,6-dichloro)phenyliminoimidazolidine 4-aminoclonidine ALO 2145 ALO-2145 Iopidine Iopimax apraclonidine hydrochloride p-aminoclonidine para-aminoclonidine", "definition": "", "id": "MESH:C016986"}
{"mention": "ocular hypotensive", "mention_text": "We prospectively evaluated the adverse reactions of apraclonidine in 20 normal volunteers by instilling a single drop of 1% apraclonidine in their right eyes. Examinations, including blood pressure, pulse rate, conjunctiva and cornea, intraocular pressure (IOP), pupil diameter, basal tear secretion and margin reflex distance of both upper and lower eyelids, were performed prior to entry and at 1, 3, 5 and 7 hours after instillation. The ocular hypotensive effects were statistically significant for apraclonidine-treated eyes throughout the study and also statistically significant for contralateral eyes from three hours after topical administration of 1% apraclonidine. Decreases in systolic blood pressure were statistically, but not clinically, significant. No significant changes in diastolic blood pressure, pulse rate and basal tear secretion were noted. Conjunctival blanching and mydriasis were commonly found. Upper lid retraction was frequently noted. While the elevations of the upper lid margin in most subjects were not more than 2 mm and did not cause noticeable change in appearance, one subject suffered from mechanical entropion and marked corneal abrasion 3 hours after instillation of the medication. This may well be a particularly notable finding in Asian people.", "entity": "Ocular Hypotension", "aliases": "Hypotension Ocular Hypotony", "definition": "Abnormally low intraocular pressure often related to chronic inflammation (uveitis).\n    ", "id": "MESH:D015814"}
{"mention": "Decreases in systolic blood pressure", "mention_text": "We prospectively evaluated the adverse reactions of apraclonidine in 20 normal volunteers by instilling a single drop of 1% apraclonidine in their right eyes. Examinations, including blood pressure, pulse rate, conjunctiva and cornea, intraocular pressure (IOP), pupil diameter, basal tear secretion and margin reflex distance of both upper and lower eyelids, were performed prior to entry and at 1, 3, 5 and 7 hours after instillation. The ocular hypotensive effects were statistically significant for apraclonidine-treated eyes throughout the study and also statistically significant for contralateral eyes from three hours after topical administration of 1% apraclonidine. Decreases in systolic blood pressure were statistically, but not clinically, significant. No significant changes in diastolic blood pressure, pulse rate and basal tear secretion were noted. Conjunctival blanching and mydriasis were commonly found. Upper lid retraction was frequently noted. While the elevations of the upper lid margin in most subjects were not more than 2 mm and did not cause noticeable change in appearance, one subject suffered from mechanical entropion and marked corneal abrasion 3 hours after instillation of the medication. This may well be a particularly notable finding in Asian people.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "Conjunctival blanching", "mention_text": "We prospectively evaluated the adverse reactions of apraclonidine in 20 normal volunteers by instilling a single drop of 1% apraclonidine in their right eyes. Examinations, including blood pressure, pulse rate, conjunctiva and cornea, intraocular pressure (IOP), pupil diameter, basal tear secretion and margin reflex distance of both upper and lower eyelids, were performed prior to entry and at 1, 3, 5 and 7 hours after instillation. The ocular hypotensive effects were statistically significant for apraclonidine-treated eyes throughout the study and also statistically significant for contralateral eyes from three hours after topical administration of 1% apraclonidine. Decreases in systolic blood pressure were statistically, but not clinically, significant. No significant changes in diastolic blood pressure, pulse rate and basal tear secretion were noted. Conjunctival blanching and mydriasis were commonly found. Upper lid retraction was frequently noted. While the elevations of the upper lid margin in most subjects were not more than 2 mm and did not cause noticeable change in appearance, one subject suffered from mechanical entropion and marked corneal abrasion 3 hours after instillation of the medication. This may well be a particularly notable finding in Asian people.", "entity": "Conjunctival Diseases", "aliases": "Conjunctival Disease Diseases", "definition": "", "id": "MESH:D003229"}
{"mention": "mydriasis", "mention_text": "We prospectively evaluated the adverse reactions of apraclonidine in 20 normal volunteers by instilling a single drop of 1% apraclonidine in their right eyes. Examinations, including blood pressure, pulse rate, conjunctiva and cornea, intraocular pressure (IOP), pupil diameter, basal tear secretion and margin reflex distance of both upper and lower eyelids, were performed prior to entry and at 1, 3, 5 and 7 hours after instillation. The ocular hypotensive effects were statistically significant for apraclonidine-treated eyes throughout the study and also statistically significant for contralateral eyes from three hours after topical administration of 1% apraclonidine. Decreases in systolic blood pressure were statistically, but not clinically, significant. No significant changes in diastolic blood pressure, pulse rate and basal tear secretion were noted. Conjunctival blanching and mydriasis were commonly found. Upper lid retraction was frequently noted. While the elevations of the upper lid margin in most subjects were not more than 2 mm and did not cause noticeable change in appearance, one subject suffered from mechanical entropion and marked corneal abrasion 3 hours after instillation of the medication. This may well be a particularly notable finding in Asian people.", "entity": "Mydriasis", "aliases": "Mydriasis", "definition": "Dilation of pupils to greater than 6 mm combined with failure of the pupils to constrict when stimulated with light. This condition may occur due to injury of the pupillary fibers in the oculomotor nerve, in acute angle-closure glaucoma, and in ADIE SYNDROME.\n    ", "id": "MESH:D015878"}
{"mention": "entropion", "mention_text": "We prospectively evaluated the adverse reactions of apraclonidine in 20 normal volunteers by instilling a single drop of 1% apraclonidine in their right eyes. Examinations, including blood pressure, pulse rate, conjunctiva and cornea, intraocular pressure (IOP), pupil diameter, basal tear secretion and margin reflex distance of both upper and lower eyelids, were performed prior to entry and at 1, 3, 5 and 7 hours after instillation. The ocular hypotensive effects were statistically significant for apraclonidine-treated eyes throughout the study and also statistically significant for contralateral eyes from three hours after topical administration of 1% apraclonidine. Decreases in systolic blood pressure were statistically, but not clinically, significant. No significant changes in diastolic blood pressure, pulse rate and basal tear secretion were noted. Conjunctival blanching and mydriasis were commonly found. Upper lid retraction was frequently noted. While the elevations of the upper lid margin in most subjects were not more than 2 mm and did not cause noticeable change in appearance, one subject suffered from mechanical entropion and marked corneal abrasion 3 hours after instillation of the medication. This may well be a particularly notable finding in Asian people.", "entity": "Entropion", "aliases": "Entropion Entropions", "definition": "The turning inward (inversion) of the edge of the eyelid, with the tarsal cartilage turned inward toward the eyeball. (Dorland, 27th ed)\n    ", "id": "MESH:D004774"}
{"mention": "corneal abrasion", "mention_text": "We prospectively evaluated the adverse reactions of apraclonidine in 20 normal volunteers by instilling a single drop of 1% apraclonidine in their right eyes. Examinations, including blood pressure, pulse rate, conjunctiva and cornea, intraocular pressure (IOP), pupil diameter, basal tear secretion and margin reflex distance of both upper and lower eyelids, were performed prior to entry and at 1, 3, 5 and 7 hours after instillation. The ocular hypotensive effects were statistically significant for apraclonidine-treated eyes throughout the study and also statistically significant for contralateral eyes from three hours after topical administration of 1% apraclonidine. Decreases in systolic blood pressure were statistically, but not clinically, significant. No significant changes in diastolic blood pressure, pulse rate and basal tear secretion were noted. Conjunctival blanching and mydriasis were commonly found. Upper lid retraction was frequently noted. While the elevations of the upper lid margin in most subjects were not more than 2 mm and did not cause noticeable change in appearance, one subject suffered from mechanical entropion and marked corneal abrasion 3 hours after instillation of the medication. This may well be a particularly notable finding in Asian people.", "entity": "Corneal Diseases", "aliases": "Corneal Disease Diseases", "definition": "Diseases of the cornea.\n    ", "id": "MESH:D003316"}
{"mention": "Carmofur", "mention_text": "Carmofur-induced organic mental disorders.", "entity": "1-hexylcarbamoyl-5-fluorouracil", "aliases": "1-hexylcarbamoyl-5-fluorouracil HCFU Mifurol N-hexylcarbamoyl-5-fluorouracil carmofur", "definition": "", "id": "MESH:C017367"}
{"mention": "organic mental disorders", "mention_text": "Carmofur-induced organic mental disorders.", "entity": "Delirium, Dementia, Amnestic, Cognitive Disorders", "aliases": "Clerambault Syndrome Delirium Dementia Amnestic Cognitive Disorders Organic Mental Kandinsky Disorder Nonpsychotic Brain Psychotic Psychoses Traumatic", "definition": "Cognitive disorders including delirium, dementia, and other cognitive disorders. These may be the result of substance use, trauma, or other causes.\n    ", "id": "MESH:D019965"}
{"mention": "Organic mental disorder", "mention_text": "Organic mental disorder was observed in a 29-year-old female in the prognostic period after the onset of carmofur-induced leukoencephalopathy. Symptoms such as euphoria, emotional lability and puerile attitude noted in the patient were diagnosed as organic personality syndrome according to the criteria defined in the DSM-III-R. It is referred to as a frontal lobe syndrome. Brain CT revealed a periventricular low density area in the frontal white matter and moderate dilatation of the lateral ventricles especially at the bilateral anterior horns. Consequently, carmofur-induced leukoencephalopathy may uncommonly result in organic personality syndrome in the residual state. It may be attributed to the structural damage to the frontal lobe.", "entity": "Delirium, Dementia, Amnestic, Cognitive Disorders", "aliases": "Clerambault Syndrome Delirium Dementia Amnestic Cognitive Disorders Organic Mental Kandinsky Disorder Nonpsychotic Brain Psychotic Psychoses Traumatic", "definition": "Cognitive disorders including delirium, dementia, and other cognitive disorders. These may be the result of substance use, trauma, or other causes.\n    ", "id": "MESH:D019965"}
{"mention": "carmofur", "mention_text": "Organic mental disorder was observed in a 29-year-old female in the prognostic period after the onset of carmofur-induced leukoencephalopathy. Symptoms such as euphoria, emotional lability and puerile attitude noted in the patient were diagnosed as organic personality syndrome according to the criteria defined in the DSM-III-R. It is referred to as a frontal lobe syndrome. Brain CT revealed a periventricular low density area in the frontal white matter and moderate dilatation of the lateral ventricles especially at the bilateral anterior horns. Consequently, carmofur-induced leukoencephalopathy may uncommonly result in organic personality syndrome in the residual state. It may be attributed to the structural damage to the frontal lobe.", "entity": "1-hexylcarbamoyl-5-fluorouracil", "aliases": "1-hexylcarbamoyl-5-fluorouracil HCFU Mifurol N-hexylcarbamoyl-5-fluorouracil carmofur", "definition": "", "id": "MESH:C017367"}
{"mention": "leukoencephalopathy", "mention_text": "Organic mental disorder was observed in a 29-year-old female in the prognostic period after the onset of carmofur-induced leukoencephalopathy. Symptoms such as euphoria, emotional lability and puerile attitude noted in the patient were diagnosed as organic personality syndrome according to the criteria defined in the DSM-III-R. It is referred to as a frontal lobe syndrome. Brain CT revealed a periventricular low density area in the frontal white matter and moderate dilatation of the lateral ventricles especially at the bilateral anterior horns. Consequently, carmofur-induced leukoencephalopathy may uncommonly result in organic personality syndrome in the residual state. It may be attributed to the structural damage to the frontal lobe.", "entity": "Leukoencephalopathies", "aliases": "CACH Syndrome Syndromes CACH/VWM Centralis Diffusa Myelinosis Diffusas Childhood Ataxia with Central Nervous System Hypomyelination Hypomyelinization Diffuse Cree Leukoencephalopathies Leukoencephalopathy Disease White Matter Diseases Vanishing Leukodystrophy", "definition": "Any of various diseases affecting the white matter of the central nervous system.\n    ", "id": "MESH:D056784"}
{"mention": "organic personality syndrome", "mention_text": "Organic mental disorder was observed in a 29-year-old female in the prognostic period after the onset of carmofur-induced leukoencephalopathy. Symptoms such as euphoria, emotional lability and puerile attitude noted in the patient were diagnosed as organic personality syndrome according to the criteria defined in the DSM-III-R. It is referred to as a frontal lobe syndrome. Brain CT revealed a periventricular low density area in the frontal white matter and moderate dilatation of the lateral ventricles especially at the bilateral anterior horns. Consequently, carmofur-induced leukoencephalopathy may uncommonly result in organic personality syndrome in the residual state. It may be attributed to the structural damage to the frontal lobe.", "entity": "Personality Disorders", "aliases": "As If Personality Avoidant Disorder Disorders Impulse Ridden Impulse-Ridden Inadequate Narcissistic", "definition": "A major deviation from normal patterns of behavior.\n    ", "id": "MESH:D010554"}
{"mention": "frontal lobe syndrome", "mention_text": "Organic mental disorder was observed in a 29-year-old female in the prognostic period after the onset of carmofur-induced leukoencephalopathy. Symptoms such as euphoria, emotional lability and puerile attitude noted in the patient were diagnosed as organic personality syndrome according to the criteria defined in the DSM-III-R. It is referred to as a frontal lobe syndrome. Brain CT revealed a periventricular low density area in the frontal white matter and moderate dilatation of the lateral ventricles especially at the bilateral anterior horns. Consequently, carmofur-induced leukoencephalopathy may uncommonly result in organic personality syndrome in the residual state. It may be attributed to the structural damage to the frontal lobe.", "entity": "Brain Diseases", "aliases": "Brain Disease Diseases Disorder Disorders CNS Intracranial Central Nervous System Encephalon", "definition": "Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.\n    ", "id": "MESH:D001927"}
{"mention": "structural damage to the frontal lobe", "mention_text": "Organic mental disorder was observed in a 29-year-old female in the prognostic period after the onset of carmofur-induced leukoencephalopathy. Symptoms such as euphoria, emotional lability and puerile attitude noted in the patient were diagnosed as organic personality syndrome according to the criteria defined in the DSM-III-R. It is referred to as a frontal lobe syndrome. Brain CT revealed a periventricular low density area in the frontal white matter and moderate dilatation of the lateral ventricles especially at the bilateral anterior horns. Consequently, carmofur-induced leukoencephalopathy may uncommonly result in organic personality syndrome in the residual state. It may be attributed to the structural damage to the frontal lobe.", "entity": "Brain Diseases", "aliases": "Brain Disease Diseases Disorder Disorders CNS Intracranial Central Nervous System Encephalon", "definition": "Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.\n    ", "id": "MESH:D001927"}
{"mention": "mexiletine", "mention_text": "International mexiletine and placebo antiarrhythmic coronary trial: I. Report on arrhythmia and other findings. Impact Research Group.", "entity": "Mexiletine", "aliases": "Boehringer Ingelheim Brand of Mexiletine Hydrochloride KO 1173 KO-1173 KO1173 KOE KOE-1173 KOE1173 Mexiletene Mexitil PL Mexityl Novo Novo-Mexiletine Novopharm", "definition": "Antiarrhythmic agent pharmacologically similar to LIDOCAINE. It may have some anticonvulsant properties.\n    ", "id": "MESH:D008801"}
{"mention": "arrhythmia", "mention_text": "International mexiletine and placebo antiarrhythmic coronary trial: I. Report on arrhythmia and other findings. Impact Research Group.", "entity": "Arrhythmias, Cardiac", "aliases": "Arrhythmia Cardiac Arrhythmias Arrythmia Dysrhythmia", "definition": "Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.\n    ", "id": "MESH:D001145"}
{"mention": "mexiletine", "mention_text": "The antiarrhythmic effects of the sustained release form of mexiletine (Mexitil-Perlongets) were evaluated in a double-blind placebo trial in 630 patients with recent documented myocardial infarction. The primary response variable was based on central reading of 24 hour ambulatory electrocardiographic recordings and was defined as the occurrence of 30 or more single premature ventricular complexes in any two consecutive 30 minute blocks or one or more runs of two or more premature ventricular complexes in the entire 24 hour electrocardiographic recording. Large differences, regarded as statistically significant, between the mexiletine and placebo groups were noted in that end point at months 1 and 4, but only trends were observed at month 12. These differences were observed even though the serum mexiletine levels obtained in this study were generally lower than those observed in studies that have used the regular form of the drug. There were more deaths in the mexiletine group (7.6%) than in the placebo group (4.8%); the difference was not statistically significant. The incidence of coronary events was similar in both groups. Previously recognized side effects, particularly tremor and gastrointestinal problems, were more frequent in the mexiletine group than in the placebo group.", "entity": "Mexiletine", "aliases": "Boehringer Ingelheim Brand of Mexiletine Hydrochloride KO 1173 KO-1173 KO1173 KOE KOE-1173 KOE1173 Mexiletene Mexitil PL Mexityl Novo Novo-Mexiletine Novopharm", "definition": "Antiarrhythmic agent pharmacologically similar to LIDOCAINE. It may have some anticonvulsant properties.\n    ", "id": "MESH:D008801"}
{"mention": "Mexitil-Perlongets", "mention_text": "The antiarrhythmic effects of the sustained release form of mexiletine (Mexitil-Perlongets) were evaluated in a double-blind placebo trial in 630 patients with recent documented myocardial infarction. The primary response variable was based on central reading of 24 hour ambulatory electrocardiographic recordings and was defined as the occurrence of 30 or more single premature ventricular complexes in any two consecutive 30 minute blocks or one or more runs of two or more premature ventricular complexes in the entire 24 hour electrocardiographic recording. Large differences, regarded as statistically significant, between the mexiletine and placebo groups were noted in that end point at months 1 and 4, but only trends were observed at month 12. These differences were observed even though the serum mexiletine levels obtained in this study were generally lower than those observed in studies that have used the regular form of the drug. There were more deaths in the mexiletine group (7.6%) than in the placebo group (4.8%); the difference was not statistically significant. The incidence of coronary events was similar in both groups. Previously recognized side effects, particularly tremor and gastrointestinal problems, were more frequent in the mexiletine group than in the placebo group.", "entity": "Mexiletine", "aliases": "Boehringer Ingelheim Brand of Mexiletine Hydrochloride KO 1173 KO-1173 KO1173 KOE KOE-1173 KOE1173 Mexiletene Mexitil PL Mexityl Novo Novo-Mexiletine Novopharm", "definition": "Antiarrhythmic agent pharmacologically similar to LIDOCAINE. It may have some anticonvulsant properties.\n    ", "id": "MESH:D008801"}
{"mention": "myocardial infarction", "mention_text": "The antiarrhythmic effects of the sustained release form of mexiletine (Mexitil-Perlongets) were evaluated in a double-blind placebo trial in 630 patients with recent documented myocardial infarction. The primary response variable was based on central reading of 24 hour ambulatory electrocardiographic recordings and was defined as the occurrence of 30 or more single premature ventricular complexes in any two consecutive 30 minute blocks or one or more runs of two or more premature ventricular complexes in the entire 24 hour electrocardiographic recording. Large differences, regarded as statistically significant, between the mexiletine and placebo groups were noted in that end point at months 1 and 4, but only trends were observed at month 12. These differences were observed even though the serum mexiletine levels obtained in this study were generally lower than those observed in studies that have used the regular form of the drug. There were more deaths in the mexiletine group (7.6%) than in the placebo group (4.8%); the difference was not statistically significant. The incidence of coronary events was similar in both groups. Previously recognized side effects, particularly tremor and gastrointestinal problems, were more frequent in the mexiletine group than in the placebo group.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "deaths", "mention_text": "The antiarrhythmic effects of the sustained release form of mexiletine (Mexitil-Perlongets) were evaluated in a double-blind placebo trial in 630 patients with recent documented myocardial infarction. The primary response variable was based on central reading of 24 hour ambulatory electrocardiographic recordings and was defined as the occurrence of 30 or more single premature ventricular complexes in any two consecutive 30 minute blocks or one or more runs of two or more premature ventricular complexes in the entire 24 hour electrocardiographic recording. Large differences, regarded as statistically significant, between the mexiletine and placebo groups were noted in that end point at months 1 and 4, but only trends were observed at month 12. These differences were observed even though the serum mexiletine levels obtained in this study were generally lower than those observed in studies that have used the regular form of the drug. There were more deaths in the mexiletine group (7.6%) than in the placebo group (4.8%); the difference was not statistically significant. The incidence of coronary events was similar in both groups. Previously recognized side effects, particularly tremor and gastrointestinal problems, were more frequent in the mexiletine group than in the placebo group.", "entity": "Death", "aliases": "Cardiac Death Determination of Near-Death Experience", "definition": "Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.\n    ", "id": "MESH:D003643"}
{"mention": "tremor", "mention_text": "The antiarrhythmic effects of the sustained release form of mexiletine (Mexitil-Perlongets) were evaluated in a double-blind placebo trial in 630 patients with recent documented myocardial infarction. The primary response variable was based on central reading of 24 hour ambulatory electrocardiographic recordings and was defined as the occurrence of 30 or more single premature ventricular complexes in any two consecutive 30 minute blocks or one or more runs of two or more premature ventricular complexes in the entire 24 hour electrocardiographic recording. Large differences, regarded as statistically significant, between the mexiletine and placebo groups were noted in that end point at months 1 and 4, but only trends were observed at month 12. These differences were observed even though the serum mexiletine levels obtained in this study were generally lower than those observed in studies that have used the regular form of the drug. There were more deaths in the mexiletine group (7.6%) than in the placebo group (4.8%); the difference was not statistically significant. The incidence of coronary events was similar in both groups. Previously recognized side effects, particularly tremor and gastrointestinal problems, were more frequent in the mexiletine group than in the placebo group.", "entity": "Tremor", "aliases": "Action Tremor Tremors Coarse Continuous Darkness Fine Intention Intermittent Involuntary Quiver Quivers Limb Massive Muscle Neonatal Nerve Passive Perioral Persistent Pill Rolling Rest Resting Saturnine Semirhythmic Senile Static", "definition": "Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of CEREBELLAR DISEASES, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of PARKINSON DISEASE.\n    ", "id": "MESH:D014202"}
{"mention": "gastrointestinal problems", "mention_text": "The antiarrhythmic effects of the sustained release form of mexiletine (Mexitil-Perlongets) were evaluated in a double-blind placebo trial in 630 patients with recent documented myocardial infarction. The primary response variable was based on central reading of 24 hour ambulatory electrocardiographic recordings and was defined as the occurrence of 30 or more single premature ventricular complexes in any two consecutive 30 minute blocks or one or more runs of two or more premature ventricular complexes in the entire 24 hour electrocardiographic recording. Large differences, regarded as statistically significant, between the mexiletine and placebo groups were noted in that end point at months 1 and 4, but only trends were observed at month 12. These differences were observed even though the serum mexiletine levels obtained in this study were generally lower than those observed in studies that have used the regular form of the drug. There were more deaths in the mexiletine group (7.6%) than in the placebo group (4.8%); the difference was not statistically significant. The incidence of coronary events was similar in both groups. Previously recognized side effects, particularly tremor and gastrointestinal problems, were more frequent in the mexiletine group than in the placebo group.", "entity": "Signs and Symptoms, Digestive", "aliases": "Signs and Symptoms Digestive", "definition": "Digestive system manifestations of diseases of the gastrointestinal system or of other organs.\n    ", "id": "MESH:D012817"}
{"mention": "amphetamine", "mention_text": "Regional localization of the antagonism of amphetamine-induced hyperactivity by intracerebral calcitonin injections.", "entity": "Amphetamine", "aliases": "Amfetamine Amphetamine Sulfate (2:1) Centramina Desoxynorephedrin Fenamine Levoamphetamine Miquel Brand of Mydrial Phenamine Phenopromin Thyramine l l-Amphetamine levo levo-Amphetamine", "definition": "A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE.\n    ", "id": "MESH:D000661"}
{"mention": "hyperactivity", "mention_text": "Regional localization of the antagonism of amphetamine-induced hyperactivity by intracerebral calcitonin injections.", "entity": "Hyperkinesis", "aliases": "Generalized Hyperkinesia Hyperkinesias Hyperactivity Motor Hyperkinesis Hyperkinetic Movement Movements", "definition": "Excessive movement of muscles of the body as a whole, which may be associated with organic or psychological disorders.\n    ", "id": "MESH:D006948"}
{"mention": "calcitonin", "mention_text": "Regional localization of the antagonism of amphetamine-induced hyperactivity by intracerebral calcitonin injections.", "entity": "Calcitonin", "aliases": "Calcitonin Calcitonin(1-32) Eel Calcitrin Ciba 47175 BA 47175-BA 47175BA Thyrocalcitonin", "definition": "A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults.\n    ", "id": "MESH:D002116"}
{"mention": "Calcitonin", "mention_text": "Calcitonin receptors are found in the brain, and intracerebral infusions of calcitonin can produce behavioral effects. Among these behavioral effects are decreases in food intake and decreases in amphetamine-induced locomotor activity. In previous experiments we found that decreases in food intake were induced by local administration of calcitonin into several hypothalamic sites and into the nucleus accumbens. In the present experiment calcitonin decreased locomotor activity when locally injected into the same sites where it decreases food intake. The areas where calcitonin is most effective in decreasing locomotor activity are located in the hypothalamus and nucleus accumbens, suggesting that these areas are the major sites of action of calcitonin in inhibiting amphetamine-induced locomotor activity.", "entity": "Calcitonin", "aliases": "Calcitonin Calcitonin(1-32) Eel Calcitrin Ciba 47175 BA 47175-BA 47175BA Thyrocalcitonin", "definition": "A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults.\n    ", "id": "MESH:D002116"}
{"mention": "calcitonin", "mention_text": "Calcitonin receptors are found in the brain, and intracerebral infusions of calcitonin can produce behavioral effects. Among these behavioral effects are decreases in food intake and decreases in amphetamine-induced locomotor activity. In previous experiments we found that decreases in food intake were induced by local administration of calcitonin into several hypothalamic sites and into the nucleus accumbens. In the present experiment calcitonin decreased locomotor activity when locally injected into the same sites where it decreases food intake. The areas where calcitonin is most effective in decreasing locomotor activity are located in the hypothalamus and nucleus accumbens, suggesting that these areas are the major sites of action of calcitonin in inhibiting amphetamine-induced locomotor activity.", "entity": "Calcitonin", "aliases": "Calcitonin Calcitonin(1-32) Eel Calcitrin Ciba 47175 BA 47175-BA 47175BA Thyrocalcitonin", "definition": "A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults.\n    ", "id": "MESH:D002116"}
{"mention": "amphetamine", "mention_text": "Calcitonin receptors are found in the brain, and intracerebral infusions of calcitonin can produce behavioral effects. Among these behavioral effects are decreases in food intake and decreases in amphetamine-induced locomotor activity. In previous experiments we found that decreases in food intake were induced by local administration of calcitonin into several hypothalamic sites and into the nucleus accumbens. In the present experiment calcitonin decreased locomotor activity when locally injected into the same sites where it decreases food intake. The areas where calcitonin is most effective in decreasing locomotor activity are located in the hypothalamus and nucleus accumbens, suggesting that these areas are the major sites of action of calcitonin in inhibiting amphetamine-induced locomotor activity.", "entity": "Amphetamine", "aliases": "Amfetamine Amphetamine Sulfate (2:1) Centramina Desoxynorephedrin Fenamine Levoamphetamine Miquel Brand of Mydrial Phenamine Phenopromin Thyramine l l-Amphetamine levo levo-Amphetamine", "definition": "A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE.\n    ", "id": "MESH:D000661"}
{"mention": "intracranial bleeding", "mention_text": "Fatal intracranial bleeding associated with prehospital use of epinephrine.", "entity": "Subarachnoid Hemorrhage", "aliases": "Aneurysmal Subarachnoid Hemorrhage Hemorrhages Intracranial Perinatal Spontaneous SAH (Subarachnoid Hemorrhage) SAHs", "definition": "Bleeding into the intracranial or spinal SUBARACHNOID SPACE, most resulting from INTRACRANIAL ANEURYSM rupture. It can occur after traumatic injuries (SUBARACHNOID HEMORRHAGE, TRAUMATIC). Clinical features include HEADACHE; NAUSEA; VOMITING, nuchal rigidity, variable neurological deficits and reduced mental status.\n    ", "id": "MESH:D013345"}
{"mention": "epinephrine", "mention_text": "Fatal intracranial bleeding associated with prehospital use of epinephrine.", "entity": "Epinephrine", "aliases": "4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-benzenediol Acetate Epinephrine Adrenaline Acid Tartrate Bitartrate Hydrochloride Allergan Brand of Epifrin Hydrogen Epitrate Lyophrin Medihaler-Epi", "definition": "The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.\n    ", "id": "MESH:D004837"}
{"mention": "allergic reaction", "mention_text": "We present a case of paramedic misjudgment in the execution of a protocol for the treatment of allergic reaction in a case of pulmonary edema with wheezing. The sudden onset of respiratory distress, rash, and a history of a new medicine led the two paramedics on the scene to administer subcutaneous epinephrine. Subsequently, acute cardiac arrest and fatal subarachnoid hemorrhage occurred. Epinephrine has a proven role in cardiac arrest in prehospital care; however, use by paramedics in patients with suspected allergic reaction and severe hypertension should be viewed with caution.", "entity": "Drug Hypersensitivity", "aliases": "Allergies Drug Allergy Hypersensitivities Hypersensitivity", "definition": "Immunologically mediated adverse reactions to medicinal substances used legally or illegally.\n    ", "id": "MESH:D004342"}
{"mention": "pulmonary edema", "mention_text": "We present a case of paramedic misjudgment in the execution of a protocol for the treatment of allergic reaction in a case of pulmonary edema with wheezing. The sudden onset of respiratory distress, rash, and a history of a new medicine led the two paramedics on the scene to administer subcutaneous epinephrine. Subsequently, acute cardiac arrest and fatal subarachnoid hemorrhage occurred. Epinephrine has a proven role in cardiac arrest in prehospital care; however, use by paramedics in patients with suspected allergic reaction and severe hypertension should be viewed with caution.", "entity": "Pulmonary Edema", "aliases": "Edema Pulmonary Edemas Lung Wet Lungs", "definition": "Excessive accumulation of extravascular fluid in the lung, an indication of a serious underlying disease or disorder. Pulmonary edema prevents efficient PULMONARY GAS EXCHANGE in the PULMONARY ALVEOLI, and can be life-threatening.\n    ", "id": "MESH:D011654"}
{"mention": "wheezing", "mention_text": "We present a case of paramedic misjudgment in the execution of a protocol for the treatment of allergic reaction in a case of pulmonary edema with wheezing. The sudden onset of respiratory distress, rash, and a history of a new medicine led the two paramedics on the scene to administer subcutaneous epinephrine. Subsequently, acute cardiac arrest and fatal subarachnoid hemorrhage occurred. Epinephrine has a proven role in cardiac arrest in prehospital care; however, use by paramedics in patients with suspected allergic reaction and severe hypertension should be viewed with caution.", "entity": "Respiratory Sounds", "aliases": "Breathing Sound Sounds Crackle Crackles Lung Pleural Rub Rubs Rale Rales Respiratory Rhonchi Rhonchus Stridor Stridors Wheezing Wheezings", "definition": "Noises, normal and abnormal, heard on auscultation over any part of the RESPIRATORY TRACT.\n    ", "id": "MESH:D012135"}
{"mention": "respiratory distress", "mention_text": "We present a case of paramedic misjudgment in the execution of a protocol for the treatment of allergic reaction in a case of pulmonary edema with wheezing. The sudden onset of respiratory distress, rash, and a history of a new medicine led the two paramedics on the scene to administer subcutaneous epinephrine. Subsequently, acute cardiac arrest and fatal subarachnoid hemorrhage occurred. Epinephrine has a proven role in cardiac arrest in prehospital care; however, use by paramedics in patients with suspected allergic reaction and severe hypertension should be viewed with caution.", "entity": "Respiratory Distress Syndrome, Adult", "aliases": "ARDS Human ARDSs Acute Respiratory Distress Syndrome Adult Lung Shock", "definition": "A syndrome characterized by progressive life-threatening RESPIRATORY INSUFFICIENCY in the absence of known LUNG DISEASES, usually following a systemic insult such as surgery or major TRAUMA.\n    ", "id": "MESH:D012128"}
{"mention": "rash", "mention_text": "We present a case of paramedic misjudgment in the execution of a protocol for the treatment of allergic reaction in a case of pulmonary edema with wheezing. The sudden onset of respiratory distress, rash, and a history of a new medicine led the two paramedics on the scene to administer subcutaneous epinephrine. Subsequently, acute cardiac arrest and fatal subarachnoid hemorrhage occurred. Epinephrine has a proven role in cardiac arrest in prehospital care; however, use by paramedics in patients with suspected allergic reaction and severe hypertension should be viewed with caution.", "entity": "Exanthema", "aliases": "Exanthem Exanthema Rash Skin", "definition": "Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke's disease), fifth (ERYTHEMA INFECTIOSUM), and sixth (EXANTHEMA SUBITUM) numeric designations survive as occasional synonyms in current terminology.\n    ", "id": "MESH:D005076"}
{"mention": "epinephrine", "mention_text": "We present a case of paramedic misjudgment in the execution of a protocol for the treatment of allergic reaction in a case of pulmonary edema with wheezing. The sudden onset of respiratory distress, rash, and a history of a new medicine led the two paramedics on the scene to administer subcutaneous epinephrine. Subsequently, acute cardiac arrest and fatal subarachnoid hemorrhage occurred. Epinephrine has a proven role in cardiac arrest in prehospital care; however, use by paramedics in patients with suspected allergic reaction and severe hypertension should be viewed with caution.", "entity": "Epinephrine", "aliases": "4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-benzenediol Acetate Epinephrine Adrenaline Acid Tartrate Bitartrate Hydrochloride Allergan Brand of Epifrin Hydrogen Epitrate Lyophrin Medihaler-Epi", "definition": "The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.\n    ", "id": "MESH:D004837"}
{"mention": "cardiac arrest", "mention_text": "We present a case of paramedic misjudgment in the execution of a protocol for the treatment of allergic reaction in a case of pulmonary edema with wheezing. The sudden onset of respiratory distress, rash, and a history of a new medicine led the two paramedics on the scene to administer subcutaneous epinephrine. Subsequently, acute cardiac arrest and fatal subarachnoid hemorrhage occurred. Epinephrine has a proven role in cardiac arrest in prehospital care; however, use by paramedics in patients with suspected allergic reaction and severe hypertension should be viewed with caution.", "entity": "Heart Arrest", "aliases": "Arrest Cardiac Cardiopulmonary Heart Asystole Asystoles", "definition": "Cessation of heart beat or MYOCARDIAL CONTRACTION. If it is treated within a few minutes, heart arrest can be reversed in most cases to normal cardiac rhythm and effective circulation.\n    ", "id": "MESH:D006323"}
{"mention": "subarachnoid hemorrhage", "mention_text": "We present a case of paramedic misjudgment in the execution of a protocol for the treatment of allergic reaction in a case of pulmonary edema with wheezing. The sudden onset of respiratory distress, rash, and a history of a new medicine led the two paramedics on the scene to administer subcutaneous epinephrine. Subsequently, acute cardiac arrest and fatal subarachnoid hemorrhage occurred. Epinephrine has a proven role in cardiac arrest in prehospital care; however, use by paramedics in patients with suspected allergic reaction and severe hypertension should be viewed with caution.", "entity": "Subarachnoid Hemorrhage", "aliases": "Aneurysmal Subarachnoid Hemorrhage Hemorrhages Intracranial Perinatal Spontaneous SAH (Subarachnoid Hemorrhage) SAHs", "definition": "Bleeding into the intracranial or spinal SUBARACHNOID SPACE, most resulting from INTRACRANIAL ANEURYSM rupture. It can occur after traumatic injuries (SUBARACHNOID HEMORRHAGE, TRAUMATIC). Clinical features include HEADACHE; NAUSEA; VOMITING, nuchal rigidity, variable neurological deficits and reduced mental status.\n    ", "id": "MESH:D013345"}
{"mention": "Epinephrine", "mention_text": "We present a case of paramedic misjudgment in the execution of a protocol for the treatment of allergic reaction in a case of pulmonary edema with wheezing. The sudden onset of respiratory distress, rash, and a history of a new medicine led the two paramedics on the scene to administer subcutaneous epinephrine. Subsequently, acute cardiac arrest and fatal subarachnoid hemorrhage occurred. Epinephrine has a proven role in cardiac arrest in prehospital care; however, use by paramedics in patients with suspected allergic reaction and severe hypertension should be viewed with caution.", "entity": "Epinephrine", "aliases": "4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-benzenediol Acetate Epinephrine Adrenaline Acid Tartrate Bitartrate Hydrochloride Allergan Brand of Epifrin Hydrogen Epitrate Lyophrin Medihaler-Epi", "definition": "The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.\n    ", "id": "MESH:D004837"}
{"mention": "hypertension", "mention_text": "We present a case of paramedic misjudgment in the execution of a protocol for the treatment of allergic reaction in a case of pulmonary edema with wheezing. The sudden onset of respiratory distress, rash, and a history of a new medicine led the two paramedics on the scene to administer subcutaneous epinephrine. Subsequently, acute cardiac arrest and fatal subarachnoid hemorrhage occurred. Epinephrine has a proven role in cardiac arrest in prehospital care; however, use by paramedics in patients with suspected allergic reaction and severe hypertension should be viewed with caution.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "rhabdomyolysis", "mention_text": "A case of massive rhabdomyolysis following molindone administration.", "entity": "Rhabdomyolysis", "aliases": "Rhabdomyolyses Rhabdomyolysis", "definition": "Necrosis or disintegration of skeletal muscle often followed by myoglobinuria.\n    ", "id": "MESH:D012206"}
{"mention": "molindone", "mention_text": "A case of massive rhabdomyolysis following molindone administration.", "entity": "Molindone", "aliases": "Endo Brand of Molindone Hydrochloride Moban Monohydrochloride", "definition": "An indole derivative effective in schizophrenia and other psychoses and possibly useful in the treatment of the aggressive type of undersocialized conduct disorder. Molindone has much lower affinity for D2 receptors than most antipsychotic agents and has a relatively low affinity for D1 receptors. It has only low to moderate affinity for cholinergic and alpha-adrenergic receptors. Some electrophysiologic data from animals indicate that molindone has certain characteristics that resemble those of CLOZAPINE. (From AMA Drug Evaluations Annual, 1994, p283)\n    ", "id": "MESH:D008972"}
{"mention": "Rhabdomyolysis", "mention_text": "Rhabdomyolysis is a potentially lethal syndrome that psychiatric patients seem predisposed to develop. The clinical signs and symptoms, typical laboratory features, and complications of rhabdomyolysis are presented. The case of a schizophrenic patient is reported to illustrate massive rhabdomyolysis and subsequent acute renal failure following molindone administration. Physicians who prescribe molindone should be aware of this reaction.", "entity": "Rhabdomyolysis", "aliases": "Rhabdomyolyses Rhabdomyolysis", "definition": "Necrosis or disintegration of skeletal muscle often followed by myoglobinuria.\n    ", "id": "MESH:D012206"}
{"mention": "psychiatric", "mention_text": "Rhabdomyolysis is a potentially lethal syndrome that psychiatric patients seem predisposed to develop. The clinical signs and symptoms, typical laboratory features, and complications of rhabdomyolysis are presented. The case of a schizophrenic patient is reported to illustrate massive rhabdomyolysis and subsequent acute renal failure following molindone administration. Physicians who prescribe molindone should be aware of this reaction.", "entity": "Mental Disorders", "aliases": "Behavior Disorders Diagnosis Psychiatric Disorder Mental", "definition": "Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.\n    ", "id": "MESH:D001523"}
{"mention": "rhabdomyolysis", "mention_text": "Rhabdomyolysis is a potentially lethal syndrome that psychiatric patients seem predisposed to develop. The clinical signs and symptoms, typical laboratory features, and complications of rhabdomyolysis are presented. The case of a schizophrenic patient is reported to illustrate massive rhabdomyolysis and subsequent acute renal failure following molindone administration. Physicians who prescribe molindone should be aware of this reaction.", "entity": "Rhabdomyolysis", "aliases": "Rhabdomyolyses Rhabdomyolysis", "definition": "Necrosis or disintegration of skeletal muscle often followed by myoglobinuria.\n    ", "id": "MESH:D012206"}
{"mention": "schizophrenic", "mention_text": "Rhabdomyolysis is a potentially lethal syndrome that psychiatric patients seem predisposed to develop. The clinical signs and symptoms, typical laboratory features, and complications of rhabdomyolysis are presented. The case of a schizophrenic patient is reported to illustrate massive rhabdomyolysis and subsequent acute renal failure following molindone administration. Physicians who prescribe molindone should be aware of this reaction.", "entity": "Schizophrenia", "aliases": "Dementia Praecox Disorder Schizophrenic Disorders Schizophrenia Schizophrenias", "definition": "A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior.\n    ", "id": "MESH:D012559"}
{"mention": "acute renal failure", "mention_text": "Rhabdomyolysis is a potentially lethal syndrome that psychiatric patients seem predisposed to develop. The clinical signs and symptoms, typical laboratory features, and complications of rhabdomyolysis are presented. The case of a schizophrenic patient is reported to illustrate massive rhabdomyolysis and subsequent acute renal failure following molindone administration. Physicians who prescribe molindone should be aware of this reaction.", "entity": "Acute Kidney Injury", "aliases": "Acute Kidney Failure Failures Injuries Injury Insufficiencies Insufficiency Renal", "definition": "Abrupt reduction in kidney function. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions.\n    ", "id": "MESH:D058186"}
{"mention": "molindone", "mention_text": "Rhabdomyolysis is a potentially lethal syndrome that psychiatric patients seem predisposed to develop. The clinical signs and symptoms, typical laboratory features, and complications of rhabdomyolysis are presented. The case of a schizophrenic patient is reported to illustrate massive rhabdomyolysis and subsequent acute renal failure following molindone administration. Physicians who prescribe molindone should be aware of this reaction.", "entity": "Molindone", "aliases": "Endo Brand of Molindone Hydrochloride Moban Monohydrochloride", "definition": "An indole derivative effective in schizophrenia and other psychoses and possibly useful in the treatment of the aggressive type of undersocialized conduct disorder. Molindone has much lower affinity for D2 receptors than most antipsychotic agents and has a relatively low affinity for D1 receptors. It has only low to moderate affinity for cholinergic and alpha-adrenergic receptors. Some electrophysiologic data from animals indicate that molindone has certain characteristics that resemble those of CLOZAPINE. (From AMA Drug Evaluations Annual, 1994, p283)\n    ", "id": "MESH:D008972"}
{"mention": "Cardiovascular alterations", "mention_text": "Cardiovascular alterations in rat fetuses exposed to calcium channel blockers.", "entity": "Cardiovascular Abnormalities", "aliases": "Abnormalities Cardiovascular Abnormality", "definition": "Congenital, inherited, or acquired anomalies of the CARDIOVASCULAR SYSTEM, including the HEART and BLOOD VESSELS.\n    ", "id": "MESH:D018376"}
{"mention": "calcium", "mention_text": "Cardiovascular alterations in rat fetuses exposed to calcium channel blockers.", "entity": "Calcium", "aliases": "Blood Coagulation Factor IV Calcium", "definition": "A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.\n    ", "id": "MESH:D002118"}
{"mention": "calcium", "mention_text": "Preclinical toxicologic investigation suggested that a new calcium channel blocker, Ro 40-5967, induced cardiovascular alterations in rat fetuses exposed to this agent during organogenesis. The present study was designed to investigate the hypothesis that calcium channel blockers in general induce cardiovascular malformations indicating a pharmacologic class effect. We studied three calcium channel blockers of different structure, nifedipine, diltiazem, and verapamil, along with the new agent. Pregnant rats were administered one of these calcium channel blockers during the period of cardiac morphogenesis and the offspring examined on day 20 of gestation for cardiovascular malformations. A low incidence of cardiovascular malformations was observed after exposure to each of the four calcium channel blockers, but this incidence was statistically significant only for verapamil and nifedipine. All four agents were associated with aortic arch branching variants, although significantly increased only for Ro 40-5967 and verapamil.", "entity": "Calcium", "aliases": "Blood Coagulation Factor IV Calcium", "definition": "A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.\n    ", "id": "MESH:D002118"}
{"mention": "Ro 40-5967", "mention_text": "Preclinical toxicologic investigation suggested that a new calcium channel blocker, Ro 40-5967, induced cardiovascular alterations in rat fetuses exposed to this agent during organogenesis. The present study was designed to investigate the hypothesis that calcium channel blockers in general induce cardiovascular malformations indicating a pharmacologic class effect. We studied three calcium channel blockers of different structure, nifedipine, diltiazem, and verapamil, along with the new agent. Pregnant rats were administered one of these calcium channel blockers during the period of cardiac morphogenesis and the offspring examined on day 20 of gestation for cardiovascular malformations. A low incidence of cardiovascular malformations was observed after exposure to each of the four calcium channel blockers, but this incidence was statistically significant only for verapamil and nifedipine. All four agents were associated with aortic arch branching variants, although significantly increased only for Ro 40-5967 and verapamil.", "entity": "Mibefradil", "aliases": "Mibefradil Dihydrochloride Posicor Ro 40 5967 40-5967 405967 Roche Brand of", "definition": "A benzimidazoyl-substituted tetraline that selectively binds and inhibits CALCIUM CHANNELS, T-TYPE.\n    ", "id": "MESH:D020748"}
{"mention": "cardiovascular alterations", "mention_text": "Preclinical toxicologic investigation suggested that a new calcium channel blocker, Ro 40-5967, induced cardiovascular alterations in rat fetuses exposed to this agent during organogenesis. The present study was designed to investigate the hypothesis that calcium channel blockers in general induce cardiovascular malformations indicating a pharmacologic class effect. We studied three calcium channel blockers of different structure, nifedipine, diltiazem, and verapamil, along with the new agent. Pregnant rats were administered one of these calcium channel blockers during the period of cardiac morphogenesis and the offspring examined on day 20 of gestation for cardiovascular malformations. A low incidence of cardiovascular malformations was observed after exposure to each of the four calcium channel blockers, but this incidence was statistically significant only for verapamil and nifedipine. All four agents were associated with aortic arch branching variants, although significantly increased only for Ro 40-5967 and verapamil.", "entity": "Cardiovascular Abnormalities", "aliases": "Abnormalities Cardiovascular Abnormality", "definition": "Congenital, inherited, or acquired anomalies of the CARDIOVASCULAR SYSTEM, including the HEART and BLOOD VESSELS.\n    ", "id": "MESH:D018376"}
{"mention": "cardiovascular malformations", "mention_text": "Preclinical toxicologic investigation suggested that a new calcium channel blocker, Ro 40-5967, induced cardiovascular alterations in rat fetuses exposed to this agent during organogenesis. The present study was designed to investigate the hypothesis that calcium channel blockers in general induce cardiovascular malformations indicating a pharmacologic class effect. We studied three calcium channel blockers of different structure, nifedipine, diltiazem, and verapamil, along with the new agent. Pregnant rats were administered one of these calcium channel blockers during the period of cardiac morphogenesis and the offspring examined on day 20 of gestation for cardiovascular malformations. A low incidence of cardiovascular malformations was observed after exposure to each of the four calcium channel blockers, but this incidence was statistically significant only for verapamil and nifedipine. All four agents were associated with aortic arch branching variants, although significantly increased only for Ro 40-5967 and verapamil.", "entity": "Cardiovascular Abnormalities", "aliases": "Abnormalities Cardiovascular Abnormality", "definition": "Congenital, inherited, or acquired anomalies of the CARDIOVASCULAR SYSTEM, including the HEART and BLOOD VESSELS.\n    ", "id": "MESH:D018376"}
{"mention": "nifedipine", "mention_text": "Preclinical toxicologic investigation suggested that a new calcium channel blocker, Ro 40-5967, induced cardiovascular alterations in rat fetuses exposed to this agent during organogenesis. The present study was designed to investigate the hypothesis that calcium channel blockers in general induce cardiovascular malformations indicating a pharmacologic class effect. We studied three calcium channel blockers of different structure, nifedipine, diltiazem, and verapamil, along with the new agent. Pregnant rats were administered one of these calcium channel blockers during the period of cardiac morphogenesis and the offspring examined on day 20 of gestation for cardiovascular malformations. A low incidence of cardiovascular malformations was observed after exposure to each of the four calcium channel blockers, but this incidence was statistically significant only for verapamil and nifedipine. All four agents were associated with aortic arch branching variants, although significantly increased only for Ro 40-5967 and verapamil.", "entity": "Nifedipine", "aliases": "AWD Pharma Brand of Nifedipine Adalat Adcock Ingram BAY a 1040 BAY-a-1040 BAYa1040 Bay Bay-1040 Bay1040 Bayer Cordipin Cordipine Corinfar Fenigidin KRKA Korinfar Monohydrochloride Nifangin GTIS Orion Pfizer Nifedipine-GTIS Procardia XL Vascard", "definition": "A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.\n    ", "id": "MESH:D009543"}
{"mention": "diltiazem", "mention_text": "Preclinical toxicologic investigation suggested that a new calcium channel blocker, Ro 40-5967, induced cardiovascular alterations in rat fetuses exposed to this agent during organogenesis. The present study was designed to investigate the hypothesis that calcium channel blockers in general induce cardiovascular malformations indicating a pharmacologic class effect. We studied three calcium channel blockers of different structure, nifedipine, diltiazem, and verapamil, along with the new agent. Pregnant rats were administered one of these calcium channel blockers during the period of cardiac morphogenesis and the offspring examined on day 20 of gestation for cardiovascular malformations. A low incidence of cardiovascular malformations was observed after exposure to each of the four calcium channel blockers, but this incidence was statistically significant only for verapamil and nifedipine. All four agents were associated with aortic arch branching variants, although significantly increased only for Ro 40-5967 and verapamil.", "entity": "Diltiazem", "aliases": "Aldizem Biovail Brand of Diltiazem Hydrochloride CRD 401 CRD-401 CRD401 Cardil Cardizem Dilacor XR Dilren Malate Dilzem Tiazac Watson Pharmaceuticals Diltazem", "definition": "A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of CALCIUM ion on membrane functions.\n    ", "id": "MESH:D004110"}
{"mention": "verapamil", "mention_text": "Preclinical toxicologic investigation suggested that a new calcium channel blocker, Ro 40-5967, induced cardiovascular alterations in rat fetuses exposed to this agent during organogenesis. The present study was designed to investigate the hypothesis that calcium channel blockers in general induce cardiovascular malformations indicating a pharmacologic class effect. We studied three calcium channel blockers of different structure, nifedipine, diltiazem, and verapamil, along with the new agent. Pregnant rats were administered one of these calcium channel blockers during the period of cardiac morphogenesis and the offspring examined on day 20 of gestation for cardiovascular malformations. A low incidence of cardiovascular malformations was observed after exposure to each of the four calcium channel blockers, but this incidence was statistically significant only for verapamil and nifedipine. All four agents were associated with aortic arch branching variants, although significantly increased only for Ro 40-5967 and verapamil.", "entity": "Verapamil", "aliases": "Calan Cordilox Dexverapamil Falicard Finoptin Hydrochloride Verapamil Iproveratril Isoptin Isoptine Izoptin Lekoptin Sandoz Brand of", "definition": "A calcium channel blocker that is a class IV anti-arrhythmia agent.\n    ", "id": "MESH:D014700"}
{"mention": "lamivudine", "mention_text": "Differential impact of immune escape mutations G145R and P120T on the replication of lamivudine-resistant hepatitis B virus e antigen-positive and -negative strains.", "entity": "Lamivudine", "aliases": "2',3' Dideoxy 3' thiacytidine 2',3'-Dideoxy-3'-thiacytidine 3TC BCH 189 BCH-189 BCH189 Epivir GR-109714X GR109714X Lamivudine (2S-cis)-Isomer", "definition": "A reverse transcriptase inhibitor and ZALCITABINE analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease.\n    ", "id": "MESH:D019259"}
{"mention": "hepatitis B virus e antigen", "mention_text": "Differential impact of immune escape mutations G145R and P120T on the replication of lamivudine-resistant hepatitis B virus e antigen-positive and -negative strains.", "entity": "Hepatitis B e Antigens", "aliases": "Antigens Hepatitis Be e HBe Ag-1 Ag-2 HBeAg B", "definition": "A closely related group of antigens found in the plasma only during the infective phase of hepatitis B or in virulent chronic hepatitis B, probably indicating active virus replication; there are three subtypes which may exist in a complex with immunoglobulins G.\n    ", "id": "MESH:D006513"}
{"mention": "hepatitis B", "mention_text": "Immune escape variants of the hepatitis B virus (HBV) represent an emerging clinical challenge, because they can be associated with vaccine escape, HBV reactivation, and failure of diagnostic tests. Recent data suggest a preferential selection of immune escape mutants in distinct peripheral blood leukocyte compartments of infected individuals. We therefore systematically analyzed the functional impact of the most prevalent immune escape variants, the sG145R and sP120T mutants, on the viral replication efficacy and antiviral drug susceptibility of common treatment-associated mutants with resistance to lamivudine (LAM) and/or HBeAg negativity. Replication-competent HBV strains with sG145R or sP120T and LAM resistance (rtM204I or rtL180M/rtM204V) were generated on an HBeAg-positive and an HBeAg-negative background with precore (PC) and basal core promoter (BCP) mutants. The sG145R mutation strongly reduced HBsAg levels and was able to fully restore the impaired replication of LAM-resistant HBV mutants to the levels of wild-type HBV, and PC or BCP mutations further enhanced viral replication. Although the sP120T substitution also impaired HBsAg secretion, it did not enhance the replication of LAM-resistant clones. However, the concomitant occurrence of HBeAg negativity (PC/BCP), sP120T, and LAM resistance resulted in the restoration of replication to levels of wild-type HBV. In all clones with combined immune escape and LAM resistance mutations, the nucleotide analogues adefovir and tenofovir remained effective in suppressing viral replication in vitro. These findings reveal the differential impact of immune escape variants on the replication and drug susceptibility of complex HBV mutants, supporting the need of close surveillance and treatment adjustment in response to the selection of distinct mutational patterns.", "entity": "Hepatitis B", "aliases": "Hepatitis B", "definition": "INFLAMMATION of the LIVER in humans caused by a member of the ORTHOHEPADNAVIRUS genus, HEPATITIS B VIRUS. It is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact.\n    ", "id": "MESH:D006509"}
{"mention": "lamivudine", "mention_text": "Immune escape variants of the hepatitis B virus (HBV) represent an emerging clinical challenge, because they can be associated with vaccine escape, HBV reactivation, and failure of diagnostic tests. Recent data suggest a preferential selection of immune escape mutants in distinct peripheral blood leukocyte compartments of infected individuals. We therefore systematically analyzed the functional impact of the most prevalent immune escape variants, the sG145R and sP120T mutants, on the viral replication efficacy and antiviral drug susceptibility of common treatment-associated mutants with resistance to lamivudine (LAM) and/or HBeAg negativity. Replication-competent HBV strains with sG145R or sP120T and LAM resistance (rtM204I or rtL180M/rtM204V) were generated on an HBeAg-positive and an HBeAg-negative background with precore (PC) and basal core promoter (BCP) mutants. The sG145R mutation strongly reduced HBsAg levels and was able to fully restore the impaired replication of LAM-resistant HBV mutants to the levels of wild-type HBV, and PC or BCP mutations further enhanced viral replication. Although the sP120T substitution also impaired HBsAg secretion, it did not enhance the replication of LAM-resistant clones. However, the concomitant occurrence of HBeAg negativity (PC/BCP), sP120T, and LAM resistance resulted in the restoration of replication to levels of wild-type HBV. In all clones with combined immune escape and LAM resistance mutations, the nucleotide analogues adefovir and tenofovir remained effective in suppressing viral replication in vitro. These findings reveal the differential impact of immune escape variants on the replication and drug susceptibility of complex HBV mutants, supporting the need of close surveillance and treatment adjustment in response to the selection of distinct mutational patterns.", "entity": "Lamivudine", "aliases": "2',3' Dideoxy 3' thiacytidine 2',3'-Dideoxy-3'-thiacytidine 3TC BCH 189 BCH-189 BCH189 Epivir GR-109714X GR109714X Lamivudine (2S-cis)-Isomer", "definition": "A reverse transcriptase inhibitor and ZALCITABINE analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease.\n    ", "id": "MESH:D019259"}
{"mention": "LAM", "mention_text": "Immune escape variants of the hepatitis B virus (HBV) represent an emerging clinical challenge, because they can be associated with vaccine escape, HBV reactivation, and failure of diagnostic tests. Recent data suggest a preferential selection of immune escape mutants in distinct peripheral blood leukocyte compartments of infected individuals. We therefore systematically analyzed the functional impact of the most prevalent immune escape variants, the sG145R and sP120T mutants, on the viral replication efficacy and antiviral drug susceptibility of common treatment-associated mutants with resistance to lamivudine (LAM) and/or HBeAg negativity. Replication-competent HBV strains with sG145R or sP120T and LAM resistance (rtM204I or rtL180M/rtM204V) were generated on an HBeAg-positive and an HBeAg-negative background with precore (PC) and basal core promoter (BCP) mutants. The sG145R mutation strongly reduced HBsAg levels and was able to fully restore the impaired replication of LAM-resistant HBV mutants to the levels of wild-type HBV, and PC or BCP mutations further enhanced viral replication. Although the sP120T substitution also impaired HBsAg secretion, it did not enhance the replication of LAM-resistant clones. However, the concomitant occurrence of HBeAg negativity (PC/BCP), sP120T, and LAM resistance resulted in the restoration of replication to levels of wild-type HBV. In all clones with combined immune escape and LAM resistance mutations, the nucleotide analogues adefovir and tenofovir remained effective in suppressing viral replication in vitro. These findings reveal the differential impact of immune escape variants on the replication and drug susceptibility of complex HBV mutants, supporting the need of close surveillance and treatment adjustment in response to the selection of distinct mutational patterns.", "entity": "Lamivudine", "aliases": "2',3' Dideoxy 3' thiacytidine 2',3'-Dideoxy-3'-thiacytidine 3TC BCH 189 BCH-189 BCH189 Epivir GR-109714X GR109714X Lamivudine (2S-cis)-Isomer", "definition": "A reverse transcriptase inhibitor and ZALCITABINE analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease.\n    ", "id": "MESH:D019259"}
{"mention": "HBeAg", "mention_text": "Immune escape variants of the hepatitis B virus (HBV) represent an emerging clinical challenge, because they can be associated with vaccine escape, HBV reactivation, and failure of diagnostic tests. Recent data suggest a preferential selection of immune escape mutants in distinct peripheral blood leukocyte compartments of infected individuals. We therefore systematically analyzed the functional impact of the most prevalent immune escape variants, the sG145R and sP120T mutants, on the viral replication efficacy and antiviral drug susceptibility of common treatment-associated mutants with resistance to lamivudine (LAM) and/or HBeAg negativity. Replication-competent HBV strains with sG145R or sP120T and LAM resistance (rtM204I or rtL180M/rtM204V) were generated on an HBeAg-positive and an HBeAg-negative background with precore (PC) and basal core promoter (BCP) mutants. The sG145R mutation strongly reduced HBsAg levels and was able to fully restore the impaired replication of LAM-resistant HBV mutants to the levels of wild-type HBV, and PC or BCP mutations further enhanced viral replication. Although the sP120T substitution also impaired HBsAg secretion, it did not enhance the replication of LAM-resistant clones. However, the concomitant occurrence of HBeAg negativity (PC/BCP), sP120T, and LAM resistance resulted in the restoration of replication to levels of wild-type HBV. In all clones with combined immune escape and LAM resistance mutations, the nucleotide analogues adefovir and tenofovir remained effective in suppressing viral replication in vitro. These findings reveal the differential impact of immune escape variants on the replication and drug susceptibility of complex HBV mutants, supporting the need of close surveillance and treatment adjustment in response to the selection of distinct mutational patterns.", "entity": "Hepatitis B e Antigens", "aliases": "Antigens Hepatitis Be e HBe Ag-1 Ag-2 HBeAg B", "definition": "A closely related group of antigens found in the plasma only during the infective phase of hepatitis B or in virulent chronic hepatitis B, probably indicating active virus replication; there are three subtypes which may exist in a complex with immunoglobulins G.\n    ", "id": "MESH:D006513"}
{"mention": "HBsAg", "mention_text": "Immune escape variants of the hepatitis B virus (HBV) represent an emerging clinical challenge, because they can be associated with vaccine escape, HBV reactivation, and failure of diagnostic tests. Recent data suggest a preferential selection of immune escape mutants in distinct peripheral blood leukocyte compartments of infected individuals. We therefore systematically analyzed the functional impact of the most prevalent immune escape variants, the sG145R and sP120T mutants, on the viral replication efficacy and antiviral drug susceptibility of common treatment-associated mutants with resistance to lamivudine (LAM) and/or HBeAg negativity. Replication-competent HBV strains with sG145R or sP120T and LAM resistance (rtM204I or rtL180M/rtM204V) were generated on an HBeAg-positive and an HBeAg-negative background with precore (PC) and basal core promoter (BCP) mutants. The sG145R mutation strongly reduced HBsAg levels and was able to fully restore the impaired replication of LAM-resistant HBV mutants to the levels of wild-type HBV, and PC or BCP mutations further enhanced viral replication. Although the sP120T substitution also impaired HBsAg secretion, it did not enhance the replication of LAM-resistant clones. However, the concomitant occurrence of HBeAg negativity (PC/BCP), sP120T, and LAM resistance resulted in the restoration of replication to levels of wild-type HBV. In all clones with combined immune escape and LAM resistance mutations, the nucleotide analogues adefovir and tenofovir remained effective in suppressing viral replication in vitro. These findings reveal the differential impact of immune escape variants on the replication and drug susceptibility of complex HBV mutants, supporting the need of close surveillance and treatment adjustment in response to the selection of distinct mutational patterns.", "entity": "Hepatitis B Surface Antigens", "aliases": "Antigen Australia HBsAg Hepatitis B Surface Antigens", "definition": "Those hepatitis B antigens found on the surface of the Dane particle and on the 20 nm spherical and tubular particles. Several subspecificities of the surface antigen are known. These were formerly called the Australia antigen.\n    ", "id": "MESH:D006514"}
{"mention": "nucleotide", "mention_text": "Immune escape variants of the hepatitis B virus (HBV) represent an emerging clinical challenge, because they can be associated with vaccine escape, HBV reactivation, and failure of diagnostic tests. Recent data suggest a preferential selection of immune escape mutants in distinct peripheral blood leukocyte compartments of infected individuals. We therefore systematically analyzed the functional impact of the most prevalent immune escape variants, the sG145R and sP120T mutants, on the viral replication efficacy and antiviral drug susceptibility of common treatment-associated mutants with resistance to lamivudine (LAM) and/or HBeAg negativity. Replication-competent HBV strains with sG145R or sP120T and LAM resistance (rtM204I or rtL180M/rtM204V) were generated on an HBeAg-positive and an HBeAg-negative background with precore (PC) and basal core promoter (BCP) mutants. The sG145R mutation strongly reduced HBsAg levels and was able to fully restore the impaired replication of LAM-resistant HBV mutants to the levels of wild-type HBV, and PC or BCP mutations further enhanced viral replication. Although the sP120T substitution also impaired HBsAg secretion, it did not enhance the replication of LAM-resistant clones. However, the concomitant occurrence of HBeAg negativity (PC/BCP), sP120T, and LAM resistance resulted in the restoration of replication to levels of wild-type HBV. In all clones with combined immune escape and LAM resistance mutations, the nucleotide analogues adefovir and tenofovir remained effective in suppressing viral replication in vitro. These findings reveal the differential impact of immune escape variants on the replication and drug susceptibility of complex HBV mutants, supporting the need of close surveillance and treatment adjustment in response to the selection of distinct mutational patterns.", "entity": "Nucleotides", "aliases": "Nucleotides", "definition": "The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)\n    ", "id": "MESH:D009711"}
{"mention": "adefovir", "mention_text": "Immune escape variants of the hepatitis B virus (HBV) represent an emerging clinical challenge, because they can be associated with vaccine escape, HBV reactivation, and failure of diagnostic tests. Recent data suggest a preferential selection of immune escape mutants in distinct peripheral blood leukocyte compartments of infected individuals. We therefore systematically analyzed the functional impact of the most prevalent immune escape variants, the sG145R and sP120T mutants, on the viral replication efficacy and antiviral drug susceptibility of common treatment-associated mutants with resistance to lamivudine (LAM) and/or HBeAg negativity. Replication-competent HBV strains with sG145R or sP120T and LAM resistance (rtM204I or rtL180M/rtM204V) were generated on an HBeAg-positive and an HBeAg-negative background with precore (PC) and basal core promoter (BCP) mutants. The sG145R mutation strongly reduced HBsAg levels and was able to fully restore the impaired replication of LAM-resistant HBV mutants to the levels of wild-type HBV, and PC or BCP mutations further enhanced viral replication. Although the sP120T substitution also impaired HBsAg secretion, it did not enhance the replication of LAM-resistant clones. However, the concomitant occurrence of HBeAg negativity (PC/BCP), sP120T, and LAM resistance resulted in the restoration of replication to levels of wild-type HBV. In all clones with combined immune escape and LAM resistance mutations, the nucleotide analogues adefovir and tenofovir remained effective in suppressing viral replication in vitro. These findings reveal the differential impact of immune escape variants on the replication and drug susceptibility of complex HBV mutants, supporting the need of close surveillance and treatment adjustment in response to the selection of distinct mutational patterns.", "entity": "adefovir", "aliases": "9-(2-phosphonomethoxyethyl)adenine 9-(2-phosphonylmethoxyethyl)adenine 9-PMEA adefovir", "definition": "", "id": "MESH:C053001"}
{"mention": "tenofovir", "mention_text": "Immune escape variants of the hepatitis B virus (HBV) represent an emerging clinical challenge, because they can be associated with vaccine escape, HBV reactivation, and failure of diagnostic tests. Recent data suggest a preferential selection of immune escape mutants in distinct peripheral blood leukocyte compartments of infected individuals. We therefore systematically analyzed the functional impact of the most prevalent immune escape variants, the sG145R and sP120T mutants, on the viral replication efficacy and antiviral drug susceptibility of common treatment-associated mutants with resistance to lamivudine (LAM) and/or HBeAg negativity. Replication-competent HBV strains with sG145R or sP120T and LAM resistance (rtM204I or rtL180M/rtM204V) were generated on an HBeAg-positive and an HBeAg-negative background with precore (PC) and basal core promoter (BCP) mutants. The sG145R mutation strongly reduced HBsAg levels and was able to fully restore the impaired replication of LAM-resistant HBV mutants to the levels of wild-type HBV, and PC or BCP mutations further enhanced viral replication. Although the sP120T substitution also impaired HBsAg secretion, it did not enhance the replication of LAM-resistant clones. However, the concomitant occurrence of HBeAg negativity (PC/BCP), sP120T, and LAM resistance resulted in the restoration of replication to levels of wild-type HBV. In all clones with combined immune escape and LAM resistance mutations, the nucleotide analogues adefovir and tenofovir remained effective in suppressing viral replication in vitro. These findings reveal the differential impact of immune escape variants on the replication and drug susceptibility of complex HBV mutants, supporting the need of close surveillance and treatment adjustment in response to the selection of distinct mutational patterns.", "entity": "tenofovir", "aliases": "(R)-9-(2-phosphonylmethoxypropyl)adenine 9-(2-phosphonomethoxypropyl)adenine 9-(2-phosphonylmethoxypropyl)adenine (+-)-isomer (R)-isomer (S)-isomer 9-PMPA (tenofovir) tenofovir", "definition": "", "id": "MESH:C096918"}
{"mention": "sevoflurane", "mention_text": "The effects of sevoflurane on lidocaine-induced convulsions.", "entity": "sevoflurane", "aliases": "BAX 3084 Ultane fluoromethyl hexafluoroisopropyl ether fluoromethyl-2,2,2-trifluoro-1-(trifluoromethyl)ethyl sevoflurane sevorane", "definition": "", "id": "MESH:C009250"}
{"mention": "lidocaine", "mention_text": "The effects of sevoflurane on lidocaine-induced convulsions.", "entity": "Lidocaine", "aliases": "2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide 2-2EtN-2MePhAcN Astrazeneca Brand of Lidocaine Dalcaine Jenapharm Lidocanine Hydrochloride Carbonate (2:1) Hydrocarbonate Monoacetate Monohydrochloride Monohydrate Sulfate (1:1) Lignocaine Novocol Octocaine Strathmann Xylesthesin Xylocaine Xylocitin Xyloneural", "definition": "A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.\n    ", "id": "MESH:D008012"}
{"mention": "convulsions", "mention_text": "The effects of sevoflurane on lidocaine-induced convulsions.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "sevoflurane", "mention_text": "The influence of sevoflurane on lidocaine-induced convulsions was studied in cats. The convulsive threshold (mean +/- SD) was 41.4 +/- 6.5 mg. l(-1) with lidocaine infusion (6 mg.kg(-1).min(-1)), increasing significantly to 66.6 +/- 10.9 mg. l(-1) when the end-tidal concentration of sevoflurane was 0.8%. However, the threshold (61.6 +/- 8.7 mg. l(-1)) during 1.6% sevoflurane was not significant from that during 0.8% sevoflurane, indicating a celling effect. There was no significant difference in the convulsive threshold between sevoflurane and enflurane. The rise in blood pressure became less marked when higher concentrations of sevoflurane or enflurane were administered and the blood pressure at convulsions decreased significantly in 1.6% sevoflurane, and in 0.8% and 1.6% enflurane. However, there was no significant difference in the lidocaine concentrations measured when the systolic blood pressure became 70 mmHg. Apamin, a selective blocker of calcium-dependent potassium channels, was administered intracerebroventricularly in rats anesthetized with 0.8% sevoflurane to investigate the mechanism of the anticonvulsive effects. Apamin (10 ng) had a tendency to decrease the convulsive threshold (21.6 +/- 2.2 to 19.9 +/- 2.5 mg. l(-1)) but this was not statistically significant. It is suggested that sevoflurane reduces the convulsive effect of lidocaine toxicity but carries some risk due to circulatory depression.", "entity": "sevoflurane", "aliases": "BAX 3084 Ultane fluoromethyl hexafluoroisopropyl ether fluoromethyl-2,2,2-trifluoro-1-(trifluoromethyl)ethyl sevoflurane sevorane", "definition": "", "id": "MESH:C009250"}
{"mention": "lidocaine", "mention_text": "The influence of sevoflurane on lidocaine-induced convulsions was studied in cats. The convulsive threshold (mean +/- SD) was 41.4 +/- 6.5 mg. l(-1) with lidocaine infusion (6 mg.kg(-1).min(-1)), increasing significantly to 66.6 +/- 10.9 mg. l(-1) when the end-tidal concentration of sevoflurane was 0.8%. However, the threshold (61.6 +/- 8.7 mg. l(-1)) during 1.6% sevoflurane was not significant from that during 0.8% sevoflurane, indicating a celling effect. There was no significant difference in the convulsive threshold between sevoflurane and enflurane. The rise in blood pressure became less marked when higher concentrations of sevoflurane or enflurane were administered and the blood pressure at convulsions decreased significantly in 1.6% sevoflurane, and in 0.8% and 1.6% enflurane. However, there was no significant difference in the lidocaine concentrations measured when the systolic blood pressure became 70 mmHg. Apamin, a selective blocker of calcium-dependent potassium channels, was administered intracerebroventricularly in rats anesthetized with 0.8% sevoflurane to investigate the mechanism of the anticonvulsive effects. Apamin (10 ng) had a tendency to decrease the convulsive threshold (21.6 +/- 2.2 to 19.9 +/- 2.5 mg. l(-1)) but this was not statistically significant. It is suggested that sevoflurane reduces the convulsive effect of lidocaine toxicity but carries some risk due to circulatory depression.", "entity": "Lidocaine", "aliases": "2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide 2-2EtN-2MePhAcN Astrazeneca Brand of Lidocaine Dalcaine Jenapharm Lidocanine Hydrochloride Carbonate (2:1) Hydrocarbonate Monoacetate Monohydrochloride Monohydrate Sulfate (1:1) Lignocaine Novocol Octocaine Strathmann Xylesthesin Xylocaine Xylocitin Xyloneural", "definition": "A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.\n    ", "id": "MESH:D008012"}
{"mention": "convulsions", "mention_text": "The influence of sevoflurane on lidocaine-induced convulsions was studied in cats. The convulsive threshold (mean +/- SD) was 41.4 +/- 6.5 mg. l(-1) with lidocaine infusion (6 mg.kg(-1).min(-1)), increasing significantly to 66.6 +/- 10.9 mg. l(-1) when the end-tidal concentration of sevoflurane was 0.8%. However, the threshold (61.6 +/- 8.7 mg. l(-1)) during 1.6% sevoflurane was not significant from that during 0.8% sevoflurane, indicating a celling effect. There was no significant difference in the convulsive threshold between sevoflurane and enflurane. The rise in blood pressure became less marked when higher concentrations of sevoflurane or enflurane were administered and the blood pressure at convulsions decreased significantly in 1.6% sevoflurane, and in 0.8% and 1.6% enflurane. However, there was no significant difference in the lidocaine concentrations measured when the systolic blood pressure became 70 mmHg. Apamin, a selective blocker of calcium-dependent potassium channels, was administered intracerebroventricularly in rats anesthetized with 0.8% sevoflurane to investigate the mechanism of the anticonvulsive effects. Apamin (10 ng) had a tendency to decrease the convulsive threshold (21.6 +/- 2.2 to 19.9 +/- 2.5 mg. l(-1)) but this was not statistically significant. It is suggested that sevoflurane reduces the convulsive effect of lidocaine toxicity but carries some risk due to circulatory depression.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "convulsive", "mention_text": "The influence of sevoflurane on lidocaine-induced convulsions was studied in cats. The convulsive threshold (mean +/- SD) was 41.4 +/- 6.5 mg. l(-1) with lidocaine infusion (6 mg.kg(-1).min(-1)), increasing significantly to 66.6 +/- 10.9 mg. l(-1) when the end-tidal concentration of sevoflurane was 0.8%. However, the threshold (61.6 +/- 8.7 mg. l(-1)) during 1.6% sevoflurane was not significant from that during 0.8% sevoflurane, indicating a celling effect. There was no significant difference in the convulsive threshold between sevoflurane and enflurane. The rise in blood pressure became less marked when higher concentrations of sevoflurane or enflurane were administered and the blood pressure at convulsions decreased significantly in 1.6% sevoflurane, and in 0.8% and 1.6% enflurane. However, there was no significant difference in the lidocaine concentrations measured when the systolic blood pressure became 70 mmHg. Apamin, a selective blocker of calcium-dependent potassium channels, was administered intracerebroventricularly in rats anesthetized with 0.8% sevoflurane to investigate the mechanism of the anticonvulsive effects. Apamin (10 ng) had a tendency to decrease the convulsive threshold (21.6 +/- 2.2 to 19.9 +/- 2.5 mg. l(-1)) but this was not statistically significant. It is suggested that sevoflurane reduces the convulsive effect of lidocaine toxicity but carries some risk due to circulatory depression.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "enflurane", "mention_text": "The influence of sevoflurane on lidocaine-induced convulsions was studied in cats. The convulsive threshold (mean +/- SD) was 41.4 +/- 6.5 mg. l(-1) with lidocaine infusion (6 mg.kg(-1).min(-1)), increasing significantly to 66.6 +/- 10.9 mg. l(-1) when the end-tidal concentration of sevoflurane was 0.8%. However, the threshold (61.6 +/- 8.7 mg. l(-1)) during 1.6% sevoflurane was not significant from that during 0.8% sevoflurane, indicating a celling effect. There was no significant difference in the convulsive threshold between sevoflurane and enflurane. The rise in blood pressure became less marked when higher concentrations of sevoflurane or enflurane were administered and the blood pressure at convulsions decreased significantly in 1.6% sevoflurane, and in 0.8% and 1.6% enflurane. However, there was no significant difference in the lidocaine concentrations measured when the systolic blood pressure became 70 mmHg. Apamin, a selective blocker of calcium-dependent potassium channels, was administered intracerebroventricularly in rats anesthetized with 0.8% sevoflurane to investigate the mechanism of the anticonvulsive effects. Apamin (10 ng) had a tendency to decrease the convulsive threshold (21.6 +/- 2.2 to 19.9 +/- 2.5 mg. l(-1)) but this was not statistically significant. It is suggested that sevoflurane reduces the convulsive effect of lidocaine toxicity but carries some risk due to circulatory depression.", "entity": "Enflurane", "aliases": "Abbott Brand of Enflurane Alyrane AstraZeneca Baxter Anaesthesia Enfran Enlirane Ethrane Etran Pisa Zeneca", "definition": "An extremely stable inhalation anesthetic that allows rapid adjustments of anesthesia depth with little change in pulse or respiratory rate.\n    ", "id": "MESH:D004737"}
{"mention": "Apamin", "mention_text": "The influence of sevoflurane on lidocaine-induced convulsions was studied in cats. The convulsive threshold (mean +/- SD) was 41.4 +/- 6.5 mg. l(-1) with lidocaine infusion (6 mg.kg(-1).min(-1)), increasing significantly to 66.6 +/- 10.9 mg. l(-1) when the end-tidal concentration of sevoflurane was 0.8%. However, the threshold (61.6 +/- 8.7 mg. l(-1)) during 1.6% sevoflurane was not significant from that during 0.8% sevoflurane, indicating a celling effect. There was no significant difference in the convulsive threshold between sevoflurane and enflurane. The rise in blood pressure became less marked when higher concentrations of sevoflurane or enflurane were administered and the blood pressure at convulsions decreased significantly in 1.6% sevoflurane, and in 0.8% and 1.6% enflurane. However, there was no significant difference in the lidocaine concentrations measured when the systolic blood pressure became 70 mmHg. Apamin, a selective blocker of calcium-dependent potassium channels, was administered intracerebroventricularly in rats anesthetized with 0.8% sevoflurane to investigate the mechanism of the anticonvulsive effects. Apamin (10 ng) had a tendency to decrease the convulsive threshold (21.6 +/- 2.2 to 19.9 +/- 2.5 mg. l(-1)) but this was not statistically significant. It is suggested that sevoflurane reduces the convulsive effect of lidocaine toxicity but carries some risk due to circulatory depression.", "entity": "Apamin", "aliases": "Apamin", "definition": "A highly neurotoxic polypeptide from the venom of the honey bee (Apis mellifera). It consists of 18 amino acids with two disulfide bridges and causes hyperexcitability resulting in convulsions and respiratory paralysis.\n    ", "id": "MESH:D001030"}
{"mention": "calcium", "mention_text": "The influence of sevoflurane on lidocaine-induced convulsions was studied in cats. The convulsive threshold (mean +/- SD) was 41.4 +/- 6.5 mg. l(-1) with lidocaine infusion (6 mg.kg(-1).min(-1)), increasing significantly to 66.6 +/- 10.9 mg. l(-1) when the end-tidal concentration of sevoflurane was 0.8%. However, the threshold (61.6 +/- 8.7 mg. l(-1)) during 1.6% sevoflurane was not significant from that during 0.8% sevoflurane, indicating a celling effect. There was no significant difference in the convulsive threshold between sevoflurane and enflurane. The rise in blood pressure became less marked when higher concentrations of sevoflurane or enflurane were administered and the blood pressure at convulsions decreased significantly in 1.6% sevoflurane, and in 0.8% and 1.6% enflurane. However, there was no significant difference in the lidocaine concentrations measured when the systolic blood pressure became 70 mmHg. Apamin, a selective blocker of calcium-dependent potassium channels, was administered intracerebroventricularly in rats anesthetized with 0.8% sevoflurane to investigate the mechanism of the anticonvulsive effects. Apamin (10 ng) had a tendency to decrease the convulsive threshold (21.6 +/- 2.2 to 19.9 +/- 2.5 mg. l(-1)) but this was not statistically significant. It is suggested that sevoflurane reduces the convulsive effect of lidocaine toxicity but carries some risk due to circulatory depression.", "entity": "Calcium", "aliases": "Blood Coagulation Factor IV Calcium", "definition": "A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.\n    ", "id": "MESH:D002118"}
{"mention": "potassium", "mention_text": "The influence of sevoflurane on lidocaine-induced convulsions was studied in cats. The convulsive threshold (mean +/- SD) was 41.4 +/- 6.5 mg. l(-1) with lidocaine infusion (6 mg.kg(-1).min(-1)), increasing significantly to 66.6 +/- 10.9 mg. l(-1) when the end-tidal concentration of sevoflurane was 0.8%. However, the threshold (61.6 +/- 8.7 mg. l(-1)) during 1.6% sevoflurane was not significant from that during 0.8% sevoflurane, indicating a celling effect. There was no significant difference in the convulsive threshold between sevoflurane and enflurane. The rise in blood pressure became less marked when higher concentrations of sevoflurane or enflurane were administered and the blood pressure at convulsions decreased significantly in 1.6% sevoflurane, and in 0.8% and 1.6% enflurane. However, there was no significant difference in the lidocaine concentrations measured when the systolic blood pressure became 70 mmHg. Apamin, a selective blocker of calcium-dependent potassium channels, was administered intracerebroventricularly in rats anesthetized with 0.8% sevoflurane to investigate the mechanism of the anticonvulsive effects. Apamin (10 ng) had a tendency to decrease the convulsive threshold (21.6 +/- 2.2 to 19.9 +/- 2.5 mg. l(-1)) but this was not statistically significant. It is suggested that sevoflurane reduces the convulsive effect of lidocaine toxicity but carries some risk due to circulatory depression.", "entity": "Potassium", "aliases": "Potassium", "definition": "An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.\n    ", "id": "MESH:D011188"}
{"mention": "toxicity", "mention_text": "The influence of sevoflurane on lidocaine-induced convulsions was studied in cats. The convulsive threshold (mean +/- SD) was 41.4 +/- 6.5 mg. l(-1) with lidocaine infusion (6 mg.kg(-1).min(-1)), increasing significantly to 66.6 +/- 10.9 mg. l(-1) when the end-tidal concentration of sevoflurane was 0.8%. However, the threshold (61.6 +/- 8.7 mg. l(-1)) during 1.6% sevoflurane was not significant from that during 0.8% sevoflurane, indicating a celling effect. There was no significant difference in the convulsive threshold between sevoflurane and enflurane. The rise in blood pressure became less marked when higher concentrations of sevoflurane or enflurane were administered and the blood pressure at convulsions decreased significantly in 1.6% sevoflurane, and in 0.8% and 1.6% enflurane. However, there was no significant difference in the lidocaine concentrations measured when the systolic blood pressure became 70 mmHg. Apamin, a selective blocker of calcium-dependent potassium channels, was administered intracerebroventricularly in rats anesthetized with 0.8% sevoflurane to investigate the mechanism of the anticonvulsive effects. Apamin (10 ng) had a tendency to decrease the convulsive threshold (21.6 +/- 2.2 to 19.9 +/- 2.5 mg. l(-1)) but this was not statistically significant. It is suggested that sevoflurane reduces the convulsive effect of lidocaine toxicity but carries some risk due to circulatory depression.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "depression", "mention_text": "The influence of sevoflurane on lidocaine-induced convulsions was studied in cats. The convulsive threshold (mean +/- SD) was 41.4 +/- 6.5 mg. l(-1) with lidocaine infusion (6 mg.kg(-1).min(-1)), increasing significantly to 66.6 +/- 10.9 mg. l(-1) when the end-tidal concentration of sevoflurane was 0.8%. However, the threshold (61.6 +/- 8.7 mg. l(-1)) during 1.6% sevoflurane was not significant from that during 0.8% sevoflurane, indicating a celling effect. There was no significant difference in the convulsive threshold between sevoflurane and enflurane. The rise in blood pressure became less marked when higher concentrations of sevoflurane or enflurane were administered and the blood pressure at convulsions decreased significantly in 1.6% sevoflurane, and in 0.8% and 1.6% enflurane. However, there was no significant difference in the lidocaine concentrations measured when the systolic blood pressure became 70 mmHg. Apamin, a selective blocker of calcium-dependent potassium channels, was administered intracerebroventricularly in rats anesthetized with 0.8% sevoflurane to investigate the mechanism of the anticonvulsive effects. Apamin (10 ng) had a tendency to decrease the convulsive threshold (21.6 +/- 2.2 to 19.9 +/- 2.5 mg. l(-1)) but this was not statistically significant. It is suggested that sevoflurane reduces the convulsive effect of lidocaine toxicity but carries some risk due to circulatory depression.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "atorvastatin", "mention_text": "Anti-oxidant effects of atorvastatin in dexamethasone-induced hypertension in the rat.", "entity": "atorvastatin", "aliases": "CI 981 CI-981 Lipitor atorvastatin calcium anhydrous hydrate trihydrate salt liptonorm", "definition": "", "id": "MESH:C065179"}
{"mention": "dexamethasone", "mention_text": "Anti-oxidant effects of atorvastatin in dexamethasone-induced hypertension in the rat.", "entity": "Dexamethasone", "aliases": "Alcon Brand of Dexamethasone Decaject L.A. Decaject-L.A. Decameth Decaspray Dexasone Dexpak ECR Foy Hexadecadrol Hexadrol ICN Maxidex Merck Merz 1 2 Methylfluorprednisolone Millicorten Oradexon", "definition": "An anti-inflammatory 9-fluoro-glucocorticoid.\n    ", "id": "MESH:D003907"}
{"mention": "hypertension", "mention_text": "Anti-oxidant effects of atorvastatin in dexamethasone-induced hypertension in the rat.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "Dexamethasone", "mention_text": "1. Dexamethasone (Dex)-induced hypertension is characterized by endothelial dysfunction associated with nitric oxide (NO) deficiency and increased superoxide (O2-) production. Atorvastatin (Ato) possesses pleiotropic properties that have been reported to improve endothelial function through increased availability of NO and reduced O2- production in various forms of hypertension. In the present study, we investigated whether 50 mg/kg per day, p.o., Ato could prevent endothelial NO synthase (eNOS) downregulation and the increase in O2- in Sprague-Dawley (SD) rats, thereby reducing blood pressure. 2. Male SD rats (n = 30) were treated with Ato (50 mg/kg per day in drinking water) or tap water for 15 days. Dexamethasone (10 microg/kg per day, s.c.) or saline was started after 4 days in Ato-treated and non-treated rats and continued for 11-13 days. Systolic blood pressure (SBP) was measured on alternate days using the tail-cuff method. Endothelial function was assessed by acetylcholine-induced vasorelaxation and phenylephrine-induced vasoconstriction in aortic segments. Vascular eNOS mRNA was assessed by semi-quantitative reverse transcription-polymerase chain reaction. 3. In rats treated with Dex alone, SBP was increased from 109 +/- 2 to 133 +/- 2 mmHg on Days 4 and Day 14, respectively (P < 0.001). In the Ato + Dex group, SBP was increased from 113 +/- 2 to 119 +/- 2 mmHg on Days 4 to 14, respectively (P < 0.001), but was significantly lower than SBP in the group treated with Dex alone (P < 0.05). Endothelial-dependent relaxation and eNOS mRNA expression were greater in the Dex + Ato group than in the Dex only group (P < 0.05 and P < 0.0001, respectively). Aortic superoxide production was lower in the Dex + Ato group compared with the group treated with Dex alone (P < 0.0001). 4. Treatment with Ato improved endothelial function, reduced superoxide production and reduced SBP in Dex-treated SD rats.", "entity": "Dexamethasone", "aliases": "Alcon Brand of Dexamethasone Decaject L.A. Decaject-L.A. Decameth Decaspray Dexasone Dexpak ECR Foy Hexadecadrol Hexadrol ICN Maxidex Merck Merz 1 2 Methylfluorprednisolone Millicorten Oradexon", "definition": "An anti-inflammatory 9-fluoro-glucocorticoid.\n    ", "id": "MESH:D003907"}
{"mention": "Dex", "mention_text": "1. Dexamethasone (Dex)-induced hypertension is characterized by endothelial dysfunction associated with nitric oxide (NO) deficiency and increased superoxide (O2-) production. Atorvastatin (Ato) possesses pleiotropic properties that have been reported to improve endothelial function through increased availability of NO and reduced O2- production in various forms of hypertension. In the present study, we investigated whether 50 mg/kg per day, p.o., Ato could prevent endothelial NO synthase (eNOS) downregulation and the increase in O2- in Sprague-Dawley (SD) rats, thereby reducing blood pressure. 2. Male SD rats (n = 30) were treated with Ato (50 mg/kg per day in drinking water) or tap water for 15 days. Dexamethasone (10 microg/kg per day, s.c.) or saline was started after 4 days in Ato-treated and non-treated rats and continued for 11-13 days. Systolic blood pressure (SBP) was measured on alternate days using the tail-cuff method. Endothelial function was assessed by acetylcholine-induced vasorelaxation and phenylephrine-induced vasoconstriction in aortic segments. Vascular eNOS mRNA was assessed by semi-quantitative reverse transcription-polymerase chain reaction. 3. In rats treated with Dex alone, SBP was increased from 109 +/- 2 to 133 +/- 2 mmHg on Days 4 and Day 14, respectively (P < 0.001). In the Ato + Dex group, SBP was increased from 113 +/- 2 to 119 +/- 2 mmHg on Days 4 to 14, respectively (P < 0.001), but was significantly lower than SBP in the group treated with Dex alone (P < 0.05). Endothelial-dependent relaxation and eNOS mRNA expression were greater in the Dex + Ato group than in the Dex only group (P < 0.05 and P < 0.0001, respectively). Aortic superoxide production was lower in the Dex + Ato group compared with the group treated with Dex alone (P < 0.0001). 4. Treatment with Ato improved endothelial function, reduced superoxide production and reduced SBP in Dex-treated SD rats.", "entity": "Dexamethasone", "aliases": "Alcon Brand of Dexamethasone Decaject L.A. Decaject-L.A. Decameth Decaspray Dexasone Dexpak ECR Foy Hexadecadrol Hexadrol ICN Maxidex Merck Merz 1 2 Methylfluorprednisolone Millicorten Oradexon", "definition": "An anti-inflammatory 9-fluoro-glucocorticoid.\n    ", "id": "MESH:D003907"}
{"mention": "hypertension", "mention_text": "1. Dexamethasone (Dex)-induced hypertension is characterized by endothelial dysfunction associated with nitric oxide (NO) deficiency and increased superoxide (O2-) production. Atorvastatin (Ato) possesses pleiotropic properties that have been reported to improve endothelial function through increased availability of NO and reduced O2- production in various forms of hypertension. In the present study, we investigated whether 50 mg/kg per day, p.o., Ato could prevent endothelial NO synthase (eNOS) downregulation and the increase in O2- in Sprague-Dawley (SD) rats, thereby reducing blood pressure. 2. Male SD rats (n = 30) were treated with Ato (50 mg/kg per day in drinking water) or tap water for 15 days. Dexamethasone (10 microg/kg per day, s.c.) or saline was started after 4 days in Ato-treated and non-treated rats and continued for 11-13 days. Systolic blood pressure (SBP) was measured on alternate days using the tail-cuff method. Endothelial function was assessed by acetylcholine-induced vasorelaxation and phenylephrine-induced vasoconstriction in aortic segments. Vascular eNOS mRNA was assessed by semi-quantitative reverse transcription-polymerase chain reaction. 3. In rats treated with Dex alone, SBP was increased from 109 +/- 2 to 133 +/- 2 mmHg on Days 4 and Day 14, respectively (P < 0.001). In the Ato + Dex group, SBP was increased from 113 +/- 2 to 119 +/- 2 mmHg on Days 4 to 14, respectively (P < 0.001), but was significantly lower than SBP in the group treated with Dex alone (P < 0.05). Endothelial-dependent relaxation and eNOS mRNA expression were greater in the Dex + Ato group than in the Dex only group (P < 0.05 and P < 0.0001, respectively). Aortic superoxide production was lower in the Dex + Ato group compared with the group treated with Dex alone (P < 0.0001). 4. Treatment with Ato improved endothelial function, reduced superoxide production and reduced SBP in Dex-treated SD rats.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "nitric oxide", "mention_text": "1. Dexamethasone (Dex)-induced hypertension is characterized by endothelial dysfunction associated with nitric oxide (NO) deficiency and increased superoxide (O2-) production. Atorvastatin (Ato) possesses pleiotropic properties that have been reported to improve endothelial function through increased availability of NO and reduced O2- production in various forms of hypertension. In the present study, we investigated whether 50 mg/kg per day, p.o., Ato could prevent endothelial NO synthase (eNOS) downregulation and the increase in O2- in Sprague-Dawley (SD) rats, thereby reducing blood pressure. 2. Male SD rats (n = 30) were treated with Ato (50 mg/kg per day in drinking water) or tap water for 15 days. Dexamethasone (10 microg/kg per day, s.c.) or saline was started after 4 days in Ato-treated and non-treated rats and continued for 11-13 days. Systolic blood pressure (SBP) was measured on alternate days using the tail-cuff method. Endothelial function was assessed by acetylcholine-induced vasorelaxation and phenylephrine-induced vasoconstriction in aortic segments. Vascular eNOS mRNA was assessed by semi-quantitative reverse transcription-polymerase chain reaction. 3. In rats treated with Dex alone, SBP was increased from 109 +/- 2 to 133 +/- 2 mmHg on Days 4 and Day 14, respectively (P < 0.001). In the Ato + Dex group, SBP was increased from 113 +/- 2 to 119 +/- 2 mmHg on Days 4 to 14, respectively (P < 0.001), but was significantly lower than SBP in the group treated with Dex alone (P < 0.05). Endothelial-dependent relaxation and eNOS mRNA expression were greater in the Dex + Ato group than in the Dex only group (P < 0.05 and P < 0.0001, respectively). Aortic superoxide production was lower in the Dex + Ato group compared with the group treated with Dex alone (P < 0.0001). 4. Treatment with Ato improved endothelial function, reduced superoxide production and reduced SBP in Dex-treated SD rats.", "entity": "Nitric Oxide", "aliases": "Endogenous Nitrate Vasodilator Endothelium-Derived Nitric Oxide Mononitrogen Monoxide Nitrogen Endothelium Derived", "definition": "A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.\n    ", "id": "MESH:D009569"}
{"mention": "NO", "mention_text": "1. Dexamethasone (Dex)-induced hypertension is characterized by endothelial dysfunction associated with nitric oxide (NO) deficiency and increased superoxide (O2-) production. Atorvastatin (Ato) possesses pleiotropic properties that have been reported to improve endothelial function through increased availability of NO and reduced O2- production in various forms of hypertension. In the present study, we investigated whether 50 mg/kg per day, p.o., Ato could prevent endothelial NO synthase (eNOS) downregulation and the increase in O2- in Sprague-Dawley (SD) rats, thereby reducing blood pressure. 2. Male SD rats (n = 30) were treated with Ato (50 mg/kg per day in drinking water) or tap water for 15 days. Dexamethasone (10 microg/kg per day, s.c.) or saline was started after 4 days in Ato-treated and non-treated rats and continued for 11-13 days. Systolic blood pressure (SBP) was measured on alternate days using the tail-cuff method. Endothelial function was assessed by acetylcholine-induced vasorelaxation and phenylephrine-induced vasoconstriction in aortic segments. Vascular eNOS mRNA was assessed by semi-quantitative reverse transcription-polymerase chain reaction. 3. In rats treated with Dex alone, SBP was increased from 109 +/- 2 to 133 +/- 2 mmHg on Days 4 and Day 14, respectively (P < 0.001). In the Ato + Dex group, SBP was increased from 113 +/- 2 to 119 +/- 2 mmHg on Days 4 to 14, respectively (P < 0.001), but was significantly lower than SBP in the group treated with Dex alone (P < 0.05). Endothelial-dependent relaxation and eNOS mRNA expression were greater in the Dex + Ato group than in the Dex only group (P < 0.05 and P < 0.0001, respectively). Aortic superoxide production was lower in the Dex + Ato group compared with the group treated with Dex alone (P < 0.0001). 4. Treatment with Ato improved endothelial function, reduced superoxide production and reduced SBP in Dex-treated SD rats.", "entity": "Nitric Oxide", "aliases": "Endogenous Nitrate Vasodilator Endothelium-Derived Nitric Oxide Mononitrogen Monoxide Nitrogen Endothelium Derived", "definition": "A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.\n    ", "id": "MESH:D009569"}
{"mention": "superoxide", "mention_text": "1. Dexamethasone (Dex)-induced hypertension is characterized by endothelial dysfunction associated with nitric oxide (NO) deficiency and increased superoxide (O2-) production. Atorvastatin (Ato) possesses pleiotropic properties that have been reported to improve endothelial function through increased availability of NO and reduced O2- production in various forms of hypertension. In the present study, we investigated whether 50 mg/kg per day, p.o., Ato could prevent endothelial NO synthase (eNOS) downregulation and the increase in O2- in Sprague-Dawley (SD) rats, thereby reducing blood pressure. 2. Male SD rats (n = 30) were treated with Ato (50 mg/kg per day in drinking water) or tap water for 15 days. Dexamethasone (10 microg/kg per day, s.c.) or saline was started after 4 days in Ato-treated and non-treated rats and continued for 11-13 days. Systolic blood pressure (SBP) was measured on alternate days using the tail-cuff method. Endothelial function was assessed by acetylcholine-induced vasorelaxation and phenylephrine-induced vasoconstriction in aortic segments. Vascular eNOS mRNA was assessed by semi-quantitative reverse transcription-polymerase chain reaction. 3. In rats treated with Dex alone, SBP was increased from 109 +/- 2 to 133 +/- 2 mmHg on Days 4 and Day 14, respectively (P < 0.001). In the Ato + Dex group, SBP was increased from 113 +/- 2 to 119 +/- 2 mmHg on Days 4 to 14, respectively (P < 0.001), but was significantly lower than SBP in the group treated with Dex alone (P < 0.05). Endothelial-dependent relaxation and eNOS mRNA expression were greater in the Dex + Ato group than in the Dex only group (P < 0.05 and P < 0.0001, respectively). Aortic superoxide production was lower in the Dex + Ato group compared with the group treated with Dex alone (P < 0.0001). 4. Treatment with Ato improved endothelial function, reduced superoxide production and reduced SBP in Dex-treated SD rats.", "entity": "Superoxides", "aliases": "Superoxide Anion Radical Superoxides", "definition": "Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides.\n    ", "id": "MESH:D013481"}
{"mention": "O2-", "mention_text": "1. Dexamethasone (Dex)-induced hypertension is characterized by endothelial dysfunction associated with nitric oxide (NO) deficiency and increased superoxide (O2-) production. Atorvastatin (Ato) possesses pleiotropic properties that have been reported to improve endothelial function through increased availability of NO and reduced O2- production in various forms of hypertension. In the present study, we investigated whether 50 mg/kg per day, p.o., Ato could prevent endothelial NO synthase (eNOS) downregulation and the increase in O2- in Sprague-Dawley (SD) rats, thereby reducing blood pressure. 2. Male SD rats (n = 30) were treated with Ato (50 mg/kg per day in drinking water) or tap water for 15 days. Dexamethasone (10 microg/kg per day, s.c.) or saline was started after 4 days in Ato-treated and non-treated rats and continued for 11-13 days. Systolic blood pressure (SBP) was measured on alternate days using the tail-cuff method. Endothelial function was assessed by acetylcholine-induced vasorelaxation and phenylephrine-induced vasoconstriction in aortic segments. Vascular eNOS mRNA was assessed by semi-quantitative reverse transcription-polymerase chain reaction. 3. In rats treated with Dex alone, SBP was increased from 109 +/- 2 to 133 +/- 2 mmHg on Days 4 and Day 14, respectively (P < 0.001). In the Ato + Dex group, SBP was increased from 113 +/- 2 to 119 +/- 2 mmHg on Days 4 to 14, respectively (P < 0.001), but was significantly lower than SBP in the group treated with Dex alone (P < 0.05). Endothelial-dependent relaxation and eNOS mRNA expression were greater in the Dex + Ato group than in the Dex only group (P < 0.05 and P < 0.0001, respectively). Aortic superoxide production was lower in the Dex + Ato group compared with the group treated with Dex alone (P < 0.0001). 4. Treatment with Ato improved endothelial function, reduced superoxide production and reduced SBP in Dex-treated SD rats.", "entity": "Superoxides", "aliases": "Superoxide Anion Radical Superoxides", "definition": "Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides.\n    ", "id": "MESH:D013481"}
{"mention": "Atorvastatin", "mention_text": "1. Dexamethasone (Dex)-induced hypertension is characterized by endothelial dysfunction associated with nitric oxide (NO) deficiency and increased superoxide (O2-) production. Atorvastatin (Ato) possesses pleiotropic properties that have been reported to improve endothelial function through increased availability of NO and reduced O2- production in various forms of hypertension. In the present study, we investigated whether 50 mg/kg per day, p.o., Ato could prevent endothelial NO synthase (eNOS) downregulation and the increase in O2- in Sprague-Dawley (SD) rats, thereby reducing blood pressure. 2. Male SD rats (n = 30) were treated with Ato (50 mg/kg per day in drinking water) or tap water for 15 days. Dexamethasone (10 microg/kg per day, s.c.) or saline was started after 4 days in Ato-treated and non-treated rats and continued for 11-13 days. Systolic blood pressure (SBP) was measured on alternate days using the tail-cuff method. Endothelial function was assessed by acetylcholine-induced vasorelaxation and phenylephrine-induced vasoconstriction in aortic segments. Vascular eNOS mRNA was assessed by semi-quantitative reverse transcription-polymerase chain reaction. 3. In rats treated with Dex alone, SBP was increased from 109 +/- 2 to 133 +/- 2 mmHg on Days 4 and Day 14, respectively (P < 0.001). In the Ato + Dex group, SBP was increased from 113 +/- 2 to 119 +/- 2 mmHg on Days 4 to 14, respectively (P < 0.001), but was significantly lower than SBP in the group treated with Dex alone (P < 0.05). Endothelial-dependent relaxation and eNOS mRNA expression were greater in the Dex + Ato group than in the Dex only group (P < 0.05 and P < 0.0001, respectively). Aortic superoxide production was lower in the Dex + Ato group compared with the group treated with Dex alone (P < 0.0001). 4. Treatment with Ato improved endothelial function, reduced superoxide production and reduced SBP in Dex-treated SD rats.", "entity": "atorvastatin", "aliases": "CI 981 CI-981 Lipitor atorvastatin calcium anhydrous hydrate trihydrate salt liptonorm", "definition": "", "id": "MESH:C065179"}
{"mention": "Ato", "mention_text": "1. Dexamethasone (Dex)-induced hypertension is characterized by endothelial dysfunction associated with nitric oxide (NO) deficiency and increased superoxide (O2-) production. Atorvastatin (Ato) possesses pleiotropic properties that have been reported to improve endothelial function through increased availability of NO and reduced O2- production in various forms of hypertension. In the present study, we investigated whether 50 mg/kg per day, p.o., Ato could prevent endothelial NO synthase (eNOS) downregulation and the increase in O2- in Sprague-Dawley (SD) rats, thereby reducing blood pressure. 2. Male SD rats (n = 30) were treated with Ato (50 mg/kg per day in drinking water) or tap water for 15 days. Dexamethasone (10 microg/kg per day, s.c.) or saline was started after 4 days in Ato-treated and non-treated rats and continued for 11-13 days. Systolic blood pressure (SBP) was measured on alternate days using the tail-cuff method. Endothelial function was assessed by acetylcholine-induced vasorelaxation and phenylephrine-induced vasoconstriction in aortic segments. Vascular eNOS mRNA was assessed by semi-quantitative reverse transcription-polymerase chain reaction. 3. In rats treated with Dex alone, SBP was increased from 109 +/- 2 to 133 +/- 2 mmHg on Days 4 and Day 14, respectively (P < 0.001). In the Ato + Dex group, SBP was increased from 113 +/- 2 to 119 +/- 2 mmHg on Days 4 to 14, respectively (P < 0.001), but was significantly lower than SBP in the group treated with Dex alone (P < 0.05). Endothelial-dependent relaxation and eNOS mRNA expression were greater in the Dex + Ato group than in the Dex only group (P < 0.05 and P < 0.0001, respectively). Aortic superoxide production was lower in the Dex + Ato group compared with the group treated with Dex alone (P < 0.0001). 4. Treatment with Ato improved endothelial function, reduced superoxide production and reduced SBP in Dex-treated SD rats.", "entity": "atorvastatin", "aliases": "CI 981 CI-981 Lipitor atorvastatin calcium anhydrous hydrate trihydrate salt liptonorm", "definition": "", "id": "MESH:C065179"}
{"mention": "acetylcholine", "mention_text": "1. Dexamethasone (Dex)-induced hypertension is characterized by endothelial dysfunction associated with nitric oxide (NO) deficiency and increased superoxide (O2-) production. Atorvastatin (Ato) possesses pleiotropic properties that have been reported to improve endothelial function through increased availability of NO and reduced O2- production in various forms of hypertension. In the present study, we investigated whether 50 mg/kg per day, p.o., Ato could prevent endothelial NO synthase (eNOS) downregulation and the increase in O2- in Sprague-Dawley (SD) rats, thereby reducing blood pressure. 2. Male SD rats (n = 30) were treated with Ato (50 mg/kg per day in drinking water) or tap water for 15 days. Dexamethasone (10 microg/kg per day, s.c.) or saline was started after 4 days in Ato-treated and non-treated rats and continued for 11-13 days. Systolic blood pressure (SBP) was measured on alternate days using the tail-cuff method. Endothelial function was assessed by acetylcholine-induced vasorelaxation and phenylephrine-induced vasoconstriction in aortic segments. Vascular eNOS mRNA was assessed by semi-quantitative reverse transcription-polymerase chain reaction. 3. In rats treated with Dex alone, SBP was increased from 109 +/- 2 to 133 +/- 2 mmHg on Days 4 and Day 14, respectively (P < 0.001). In the Ato + Dex group, SBP was increased from 113 +/- 2 to 119 +/- 2 mmHg on Days 4 to 14, respectively (P < 0.001), but was significantly lower than SBP in the group treated with Dex alone (P < 0.05). Endothelial-dependent relaxation and eNOS mRNA expression were greater in the Dex + Ato group than in the Dex only group (P < 0.05 and P < 0.0001, respectively). Aortic superoxide production was lower in the Dex + Ato group compared with the group treated with Dex alone (P < 0.0001). 4. Treatment with Ato improved endothelial function, reduced superoxide production and reduced SBP in Dex-treated SD rats.", "entity": "Acetylcholine", "aliases": "2-(Acetyloxy)-N,N,N-trimethylethanaminium Acetilcolina Cusi Acetylcholine Bromide Chloride Fluoride Hydroxide Iodide L Tartrate L-Tartrate Perchlorate Picrate (1:1) Sulfate Alcon Brand of Bournonville Bromoacetylcholine Chloroacetylcholine Ciba Vision Iolab Miochol", "definition": "A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.\n    ", "id": "MESH:D000109"}
{"mention": "phenylephrine", "mention_text": "1. Dexamethasone (Dex)-induced hypertension is characterized by endothelial dysfunction associated with nitric oxide (NO) deficiency and increased superoxide (O2-) production. Atorvastatin (Ato) possesses pleiotropic properties that have been reported to improve endothelial function through increased availability of NO and reduced O2- production in various forms of hypertension. In the present study, we investigated whether 50 mg/kg per day, p.o., Ato could prevent endothelial NO synthase (eNOS) downregulation and the increase in O2- in Sprague-Dawley (SD) rats, thereby reducing blood pressure. 2. Male SD rats (n = 30) were treated with Ato (50 mg/kg per day in drinking water) or tap water for 15 days. Dexamethasone (10 microg/kg per day, s.c.) or saline was started after 4 days in Ato-treated and non-treated rats and continued for 11-13 days. Systolic blood pressure (SBP) was measured on alternate days using the tail-cuff method. Endothelial function was assessed by acetylcholine-induced vasorelaxation and phenylephrine-induced vasoconstriction in aortic segments. Vascular eNOS mRNA was assessed by semi-quantitative reverse transcription-polymerase chain reaction. 3. In rats treated with Dex alone, SBP was increased from 109 +/- 2 to 133 +/- 2 mmHg on Days 4 and Day 14, respectively (P < 0.001). In the Ato + Dex group, SBP was increased from 113 +/- 2 to 119 +/- 2 mmHg on Days 4 to 14, respectively (P < 0.001), but was significantly lower than SBP in the group treated with Dex alone (P < 0.05). Endothelial-dependent relaxation and eNOS mRNA expression were greater in the Dex + Ato group than in the Dex only group (P < 0.05 and P < 0.0001, respectively). Aortic superoxide production was lower in the Dex + Ato group compared with the group treated with Dex alone (P < 0.0001). 4. Treatment with Ato improved endothelial function, reduced superoxide production and reduced SBP in Dex-treated SD rats.", "entity": "Phenylephrine", "aliases": "(R)-3-Hydroxy-alpha-((methylamino)methyl)benzenemethanol Metaoxedrin Metasympatol Mezaton Neo Synephrine Neo-Synephrine Neosynephrine Phenylephrine Hydrochloride Tannate", "definition": "An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.\n    ", "id": "MESH:D010656"}
{"mention": "99mTc-glucarate", "mention_text": "99mTc-glucarate for detection of isoproterenol-induced myocardial infarction in rats.", "entity": "technetium Tc 99m glucarate", "aliases": "99mTc glucarate Tc-99m-glucarate technetium Tc 99m", "definition": "", "id": "MESH:C067171"}
{"mention": "isoproterenol", "mention_text": "99mTc-glucarate for detection of isoproterenol-induced myocardial infarction in rats.", "entity": "Isoproterenol", "aliases": "4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol Euspiran Hydrochloride Isoproterenol Isadrin Isadrine Isoprenaline Isopropyl Noradrenaline Isopropylarterenol Isopropylnoradrenaline Isopropylnorepinephrine Sulfate Isuprel Izadrin Norisodrine Novodrin", "definition": "Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.\n    ", "id": "MESH:D007545"}
{"mention": "myocardial infarction", "mention_text": "99mTc-glucarate for detection of isoproterenol-induced myocardial infarction in rats.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "Infarct", "mention_text": "Infarct-avid radiopharmaceuticals are necessary for rapid and timely diagnosis of acute myocardial infarction. The animal model used to produce infarction implies artery ligation but chemical induction can be easily obtained with isoproterenol. A new infarct-avid radiopharmaceutical based on glucaric acid was prepared in the hospital radiopharmacy of the INCMNSZ. 99mTc-glucarate was easy to prepare, stable for 96 h and was used to study its biodistribution in rats with isoproterenol-induced acute myocardial infarction. Histological studies demonstrated that the rats developed an infarct 18 h after isoproterenol administration. The rat biodistribution studies showed a rapid blood clearance via the kidneys. Thirty minutes after 99mTc-glucarate administration the standardised heart uptake value S(h)UV was 4.7 in infarcted rat heart which is six times more than in normal rats. ROIs drawn over the gamma camera images showed a ratio of 4.4. The high image quality suggests that high contrast images can be obtained in humans and the 96 h stability makes it an ideal agent to detect, in patients, early cardiac infarction.", "entity": "Infarction", "aliases": "Infarction Infarctions", "definition": "Formation of an infarct, which is NECROSIS in tissue due to local ISCHEMIA resulting from obstruction of BLOOD CIRCULATION, most commonly by a THROMBUS or EMBOLUS.\n    ", "id": "MESH:D007238"}
{"mention": "myocardial infarction", "mention_text": "Infarct-avid radiopharmaceuticals are necessary for rapid and timely diagnosis of acute myocardial infarction. The animal model used to produce infarction implies artery ligation but chemical induction can be easily obtained with isoproterenol. A new infarct-avid radiopharmaceutical based on glucaric acid was prepared in the hospital radiopharmacy of the INCMNSZ. 99mTc-glucarate was easy to prepare, stable for 96 h and was used to study its biodistribution in rats with isoproterenol-induced acute myocardial infarction. Histological studies demonstrated that the rats developed an infarct 18 h after isoproterenol administration. The rat biodistribution studies showed a rapid blood clearance via the kidneys. Thirty minutes after 99mTc-glucarate administration the standardised heart uptake value S(h)UV was 4.7 in infarcted rat heart which is six times more than in normal rats. ROIs drawn over the gamma camera images showed a ratio of 4.4. The high image quality suggests that high contrast images can be obtained in humans and the 96 h stability makes it an ideal agent to detect, in patients, early cardiac infarction.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "infarction", "mention_text": "Infarct-avid radiopharmaceuticals are necessary for rapid and timely diagnosis of acute myocardial infarction. The animal model used to produce infarction implies artery ligation but chemical induction can be easily obtained with isoproterenol. A new infarct-avid radiopharmaceutical based on glucaric acid was prepared in the hospital radiopharmacy of the INCMNSZ. 99mTc-glucarate was easy to prepare, stable for 96 h and was used to study its biodistribution in rats with isoproterenol-induced acute myocardial infarction. Histological studies demonstrated that the rats developed an infarct 18 h after isoproterenol administration. The rat biodistribution studies showed a rapid blood clearance via the kidneys. Thirty minutes after 99mTc-glucarate administration the standardised heart uptake value S(h)UV was 4.7 in infarcted rat heart which is six times more than in normal rats. ROIs drawn over the gamma camera images showed a ratio of 4.4. The high image quality suggests that high contrast images can be obtained in humans and the 96 h stability makes it an ideal agent to detect, in patients, early cardiac infarction.", "entity": "Infarction", "aliases": "Infarction Infarctions", "definition": "Formation of an infarct, which is NECROSIS in tissue due to local ISCHEMIA resulting from obstruction of BLOOD CIRCULATION, most commonly by a THROMBUS or EMBOLUS.\n    ", "id": "MESH:D007238"}
{"mention": "isoproterenol", "mention_text": "Infarct-avid radiopharmaceuticals are necessary for rapid and timely diagnosis of acute myocardial infarction. The animal model used to produce infarction implies artery ligation but chemical induction can be easily obtained with isoproterenol. A new infarct-avid radiopharmaceutical based on glucaric acid was prepared in the hospital radiopharmacy of the INCMNSZ. 99mTc-glucarate was easy to prepare, stable for 96 h and was used to study its biodistribution in rats with isoproterenol-induced acute myocardial infarction. Histological studies demonstrated that the rats developed an infarct 18 h after isoproterenol administration. The rat biodistribution studies showed a rapid blood clearance via the kidneys. Thirty minutes after 99mTc-glucarate administration the standardised heart uptake value S(h)UV was 4.7 in infarcted rat heart which is six times more than in normal rats. ROIs drawn over the gamma camera images showed a ratio of 4.4. The high image quality suggests that high contrast images can be obtained in humans and the 96 h stability makes it an ideal agent to detect, in patients, early cardiac infarction.", "entity": "Isoproterenol", "aliases": "4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol Euspiran Hydrochloride Isoproterenol Isadrin Isadrine Isoprenaline Isopropyl Noradrenaline Isopropylarterenol Isopropylnoradrenaline Isopropylnorepinephrine Sulfate Isuprel Izadrin Norisodrine Novodrin", "definition": "Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.\n    ", "id": "MESH:D007545"}
{"mention": "infarct", "mention_text": "Infarct-avid radiopharmaceuticals are necessary for rapid and timely diagnosis of acute myocardial infarction. The animal model used to produce infarction implies artery ligation but chemical induction can be easily obtained with isoproterenol. A new infarct-avid radiopharmaceutical based on glucaric acid was prepared in the hospital radiopharmacy of the INCMNSZ. 99mTc-glucarate was easy to prepare, stable for 96 h and was used to study its biodistribution in rats with isoproterenol-induced acute myocardial infarction. Histological studies demonstrated that the rats developed an infarct 18 h after isoproterenol administration. The rat biodistribution studies showed a rapid blood clearance via the kidneys. Thirty minutes after 99mTc-glucarate administration the standardised heart uptake value S(h)UV was 4.7 in infarcted rat heart which is six times more than in normal rats. ROIs drawn over the gamma camera images showed a ratio of 4.4. The high image quality suggests that high contrast images can be obtained in humans and the 96 h stability makes it an ideal agent to detect, in patients, early cardiac infarction.", "entity": "Infarction", "aliases": "Infarction Infarctions", "definition": "Formation of an infarct, which is NECROSIS in tissue due to local ISCHEMIA resulting from obstruction of BLOOD CIRCULATION, most commonly by a THROMBUS or EMBOLUS.\n    ", "id": "MESH:D007238"}
{"mention": "glucaric acid", "mention_text": "Infarct-avid radiopharmaceuticals are necessary for rapid and timely diagnosis of acute myocardial infarction. The animal model used to produce infarction implies artery ligation but chemical induction can be easily obtained with isoproterenol. A new infarct-avid radiopharmaceutical based on glucaric acid was prepared in the hospital radiopharmacy of the INCMNSZ. 99mTc-glucarate was easy to prepare, stable for 96 h and was used to study its biodistribution in rats with isoproterenol-induced acute myocardial infarction. Histological studies demonstrated that the rats developed an infarct 18 h after isoproterenol administration. The rat biodistribution studies showed a rapid blood clearance via the kidneys. Thirty minutes after 99mTc-glucarate administration the standardised heart uptake value S(h)UV was 4.7 in infarcted rat heart which is six times more than in normal rats. ROIs drawn over the gamma camera images showed a ratio of 4.4. The high image quality suggests that high contrast images can be obtained in humans and the 96 h stability makes it an ideal agent to detect, in patients, early cardiac infarction.", "entity": "Glucaric Acid", "aliases": "Acid Saccharic Anhydrous Calcium Glucarate Saccharate Tetrahydrate D Glucaric D-Glucaric D-Saccharic Glucosaccharic L Gularic L-Gularic Levo Levo-Gularic Tetrahydroxyadipic", "definition": "A sugar acid derived from D-glucose in which both the aldehydic carbon atom and the carbon atom bearing the primary hydroxyl group are oxidized to carboxylic acid groups.\n    ", "id": "MESH:D005937"}
{"mention": "99mTc-glucarate", "mention_text": "Infarct-avid radiopharmaceuticals are necessary for rapid and timely diagnosis of acute myocardial infarction. The animal model used to produce infarction implies artery ligation but chemical induction can be easily obtained with isoproterenol. A new infarct-avid radiopharmaceutical based on glucaric acid was prepared in the hospital radiopharmacy of the INCMNSZ. 99mTc-glucarate was easy to prepare, stable for 96 h and was used to study its biodistribution in rats with isoproterenol-induced acute myocardial infarction. Histological studies demonstrated that the rats developed an infarct 18 h after isoproterenol administration. The rat biodistribution studies showed a rapid blood clearance via the kidneys. Thirty minutes after 99mTc-glucarate administration the standardised heart uptake value S(h)UV was 4.7 in infarcted rat heart which is six times more than in normal rats. ROIs drawn over the gamma camera images showed a ratio of 4.4. The high image quality suggests that high contrast images can be obtained in humans and the 96 h stability makes it an ideal agent to detect, in patients, early cardiac infarction.", "entity": "technetium Tc 99m glucarate", "aliases": "99mTc glucarate Tc-99m-glucarate technetium Tc 99m", "definition": "", "id": "MESH:C067171"}
{"mention": "cardiac infarction", "mention_text": "Infarct-avid radiopharmaceuticals are necessary for rapid and timely diagnosis of acute myocardial infarction. The animal model used to produce infarction implies artery ligation but chemical induction can be easily obtained with isoproterenol. A new infarct-avid radiopharmaceutical based on glucaric acid was prepared in the hospital radiopharmacy of the INCMNSZ. 99mTc-glucarate was easy to prepare, stable for 96 h and was used to study its biodistribution in rats with isoproterenol-induced acute myocardial infarction. Histological studies demonstrated that the rats developed an infarct 18 h after isoproterenol administration. The rat biodistribution studies showed a rapid blood clearance via the kidneys. Thirty minutes after 99mTc-glucarate administration the standardised heart uptake value S(h)UV was 4.7 in infarcted rat heart which is six times more than in normal rats. ROIs drawn over the gamma camera images showed a ratio of 4.4. The high image quality suggests that high contrast images can be obtained in humans and the 96 h stability makes it an ideal agent to detect, in patients, early cardiac infarction.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "haloperidol", "mention_text": "A randomized, placebo-controlled dose-comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer's disease.", "entity": "Haloperidol", "aliases": "Haldol Haloperidol", "definition": "A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)\n    ", "id": "MESH:D006220"}
{"mention": "psychosis", "mention_text": "A randomized, placebo-controlled dose-comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer's disease.", "entity": "Psychotic Disorders", "aliases": "Brief Reactive Psychoses Psychosis Disorder Psychotic Schizoaffective Schizophreniform Disorders", "definition": "Disorders in which there is a loss of ego boundaries or a gross impairment in reality testing with delusions or prominent hallucinations. (From DSM-IV, 1994)\n    ", "id": "MESH:D011618"}
{"mention": "disruptive behaviors", "mention_text": "A randomized, placebo-controlled dose-comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer's disease.", "entity": "Attention Deficit and Disruptive Behavior Disorders", "aliases": "Attention Deficit and Disruptive Behavior Disorders Disorder Defiant Oppositional", "definition": "", "id": "MESH:D019958"}
{"mention": "Alzheimer's disease", "mention_text": "A randomized, placebo-controlled dose-comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer's disease.", "entity": "Alzheimer Disease", "aliases": "Acute Confusional Senile Dementia Alzheimer (AD) Disease Early Onset Late Sclerosis Syndrome Type (ATD) Alzheimer's Focal Alzheimer-Type Presenile Primary Degenerative Familial (FAD)", "definition": "A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)\n    ", "id": "MESH:D000544"}
{"mention": "haloperidol", "mention_text": "OBJECTIVE: The goal of this study was to compare the efficacy and side effects of two doses of haloperidol and placebo in the treatment of psychosis and disruptive behaviors in patients with Alzheimer's disease. METHOD: In a 6-week random-assignment, double-blind, placebo-controlled trial (phase A), haloperidol, 2-3 mg/day (standard dose), and haloperidol, 0.50-0.75 mg/day (low dose), were compared in 71 outpatients with Alzheimer's disease. For the subsequent 6-week double-blind crossover phase (phase B), patients taking standard- or low-dose haloperidol were switched to placebo, and patients taking placebo were randomly assigned to standard- or low-dose haloperidol. RESULTS: For the 60 patients who completed phase A, standard-dose haloperidol was efficacious and superior to both low-dose haloperidol and placebo for scores on the Brief Psychiatric Rating Scale psychosis factor and on psychomotor agitation. Response rates according to three sets of criteria were greater with the standard dose (55%-60%) than the low dose (25%-35%) and placebo (25%-30%). The advantage of standard dose over low dose was replicated in phase B. In phase A, extrapyramidal signs tended to be greater with the standard dose than in the other two conditions, primarily because of a subgroup (20%) who developed moderate to severe signs. Low-dose haloperidol did not differ from placebo on any measure of efficacy or side effects. CONCLUSIONS: The results indicated a favorable therapeutic profile for haloperidol in doses of 2-3 mg/day, although a subgroup developed moderate to severe extrapyramidal signs. A starting dose of 1 mg/day with gradual, upward dose titration is recommended. The narrow therapeutic window observed with haloperidol may also apply to other neuroleptics used in Alzheimer's disease patients with psychosis and disruptive behaviors.", "entity": "Haloperidol", "aliases": "Haldol Haloperidol", "definition": "A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)\n    ", "id": "MESH:D006220"}
{"mention": "psychosis", "mention_text": "OBJECTIVE: The goal of this study was to compare the efficacy and side effects of two doses of haloperidol and placebo in the treatment of psychosis and disruptive behaviors in patients with Alzheimer's disease. METHOD: In a 6-week random-assignment, double-blind, placebo-controlled trial (phase A), haloperidol, 2-3 mg/day (standard dose), and haloperidol, 0.50-0.75 mg/day (low dose), were compared in 71 outpatients with Alzheimer's disease. For the subsequent 6-week double-blind crossover phase (phase B), patients taking standard- or low-dose haloperidol were switched to placebo, and patients taking placebo were randomly assigned to standard- or low-dose haloperidol. RESULTS: For the 60 patients who completed phase A, standard-dose haloperidol was efficacious and superior to both low-dose haloperidol and placebo for scores on the Brief Psychiatric Rating Scale psychosis factor and on psychomotor agitation. Response rates according to three sets of criteria were greater with the standard dose (55%-60%) than the low dose (25%-35%) and placebo (25%-30%). The advantage of standard dose over low dose was replicated in phase B. In phase A, extrapyramidal signs tended to be greater with the standard dose than in the other two conditions, primarily because of a subgroup (20%) who developed moderate to severe signs. Low-dose haloperidol did not differ from placebo on any measure of efficacy or side effects. CONCLUSIONS: The results indicated a favorable therapeutic profile for haloperidol in doses of 2-3 mg/day, although a subgroup developed moderate to severe extrapyramidal signs. A starting dose of 1 mg/day with gradual, upward dose titration is recommended. The narrow therapeutic window observed with haloperidol may also apply to other neuroleptics used in Alzheimer's disease patients with psychosis and disruptive behaviors.", "entity": "Psychotic Disorders", "aliases": "Brief Reactive Psychoses Psychosis Disorder Psychotic Schizoaffective Schizophreniform Disorders", "definition": "Disorders in which there is a loss of ego boundaries or a gross impairment in reality testing with delusions or prominent hallucinations. (From DSM-IV, 1994)\n    ", "id": "MESH:D011618"}
{"mention": "disruptive behaviors", "mention_text": "OBJECTIVE: The goal of this study was to compare the efficacy and side effects of two doses of haloperidol and placebo in the treatment of psychosis and disruptive behaviors in patients with Alzheimer's disease. METHOD: In a 6-week random-assignment, double-blind, placebo-controlled trial (phase A), haloperidol, 2-3 mg/day (standard dose), and haloperidol, 0.50-0.75 mg/day (low dose), were compared in 71 outpatients with Alzheimer's disease. For the subsequent 6-week double-blind crossover phase (phase B), patients taking standard- or low-dose haloperidol were switched to placebo, and patients taking placebo were randomly assigned to standard- or low-dose haloperidol. RESULTS: For the 60 patients who completed phase A, standard-dose haloperidol was efficacious and superior to both low-dose haloperidol and placebo for scores on the Brief Psychiatric Rating Scale psychosis factor and on psychomotor agitation. Response rates according to three sets of criteria were greater with the standard dose (55%-60%) than the low dose (25%-35%) and placebo (25%-30%). The advantage of standard dose over low dose was replicated in phase B. In phase A, extrapyramidal signs tended to be greater with the standard dose than in the other two conditions, primarily because of a subgroup (20%) who developed moderate to severe signs. Low-dose haloperidol did not differ from placebo on any measure of efficacy or side effects. CONCLUSIONS: The results indicated a favorable therapeutic profile for haloperidol in doses of 2-3 mg/day, although a subgroup developed moderate to severe extrapyramidal signs. A starting dose of 1 mg/day with gradual, upward dose titration is recommended. The narrow therapeutic window observed with haloperidol may also apply to other neuroleptics used in Alzheimer's disease patients with psychosis and disruptive behaviors.", "entity": "Attention Deficit and Disruptive Behavior Disorders", "aliases": "Attention Deficit and Disruptive Behavior Disorders Disorder Defiant Oppositional", "definition": "", "id": "MESH:D019958"}
{"mention": "Alzheimer's disease", "mention_text": "OBJECTIVE: The goal of this study was to compare the efficacy and side effects of two doses of haloperidol and placebo in the treatment of psychosis and disruptive behaviors in patients with Alzheimer's disease. METHOD: In a 6-week random-assignment, double-blind, placebo-controlled trial (phase A), haloperidol, 2-3 mg/day (standard dose), and haloperidol, 0.50-0.75 mg/day (low dose), were compared in 71 outpatients with Alzheimer's disease. For the subsequent 6-week double-blind crossover phase (phase B), patients taking standard- or low-dose haloperidol were switched to placebo, and patients taking placebo were randomly assigned to standard- or low-dose haloperidol. RESULTS: For the 60 patients who completed phase A, standard-dose haloperidol was efficacious and superior to both low-dose haloperidol and placebo for scores on the Brief Psychiatric Rating Scale psychosis factor and on psychomotor agitation. Response rates according to three sets of criteria were greater with the standard dose (55%-60%) than the low dose (25%-35%) and placebo (25%-30%). The advantage of standard dose over low dose was replicated in phase B. In phase A, extrapyramidal signs tended to be greater with the standard dose than in the other two conditions, primarily because of a subgroup (20%) who developed moderate to severe signs. Low-dose haloperidol did not differ from placebo on any measure of efficacy or side effects. CONCLUSIONS: The results indicated a favorable therapeutic profile for haloperidol in doses of 2-3 mg/day, although a subgroup developed moderate to severe extrapyramidal signs. A starting dose of 1 mg/day with gradual, upward dose titration is recommended. The narrow therapeutic window observed with haloperidol may also apply to other neuroleptics used in Alzheimer's disease patients with psychosis and disruptive behaviors.", "entity": "Alzheimer Disease", "aliases": "Acute Confusional Senile Dementia Alzheimer (AD) Disease Early Onset Late Sclerosis Syndrome Type (ATD) Alzheimer's Focal Alzheimer-Type Presenile Primary Degenerative Familial (FAD)", "definition": "A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)\n    ", "id": "MESH:D000544"}
{"mention": "psychomotor agitation", "mention_text": "OBJECTIVE: The goal of this study was to compare the efficacy and side effects of two doses of haloperidol and placebo in the treatment of psychosis and disruptive behaviors in patients with Alzheimer's disease. METHOD: In a 6-week random-assignment, double-blind, placebo-controlled trial (phase A), haloperidol, 2-3 mg/day (standard dose), and haloperidol, 0.50-0.75 mg/day (low dose), were compared in 71 outpatients with Alzheimer's disease. For the subsequent 6-week double-blind crossover phase (phase B), patients taking standard- or low-dose haloperidol were switched to placebo, and patients taking placebo were randomly assigned to standard- or low-dose haloperidol. RESULTS: For the 60 patients who completed phase A, standard-dose haloperidol was efficacious and superior to both low-dose haloperidol and placebo for scores on the Brief Psychiatric Rating Scale psychosis factor and on psychomotor agitation. Response rates according to three sets of criteria were greater with the standard dose (55%-60%) than the low dose (25%-35%) and placebo (25%-30%). The advantage of standard dose over low dose was replicated in phase B. In phase A, extrapyramidal signs tended to be greater with the standard dose than in the other two conditions, primarily because of a subgroup (20%) who developed moderate to severe signs. Low-dose haloperidol did not differ from placebo on any measure of efficacy or side effects. CONCLUSIONS: The results indicated a favorable therapeutic profile for haloperidol in doses of 2-3 mg/day, although a subgroup developed moderate to severe extrapyramidal signs. A starting dose of 1 mg/day with gradual, upward dose titration is recommended. The narrow therapeutic window observed with haloperidol may also apply to other neuroleptics used in Alzheimer's disease patients with psychosis and disruptive behaviors.", "entity": "Psychomotor Agitation", "aliases": "Agitation Psychomotor Akathisia Excitement Hyperactivity Restlessness", "definition": "A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions.\n    ", "id": "MESH:D011595"}
{"mention": "extrapyramidal signs", "mention_text": "OBJECTIVE: The goal of this study was to compare the efficacy and side effects of two doses of haloperidol and placebo in the treatment of psychosis and disruptive behaviors in patients with Alzheimer's disease. METHOD: In a 6-week random-assignment, double-blind, placebo-controlled trial (phase A), haloperidol, 2-3 mg/day (standard dose), and haloperidol, 0.50-0.75 mg/day (low dose), were compared in 71 outpatients with Alzheimer's disease. For the subsequent 6-week double-blind crossover phase (phase B), patients taking standard- or low-dose haloperidol were switched to placebo, and patients taking placebo were randomly assigned to standard- or low-dose haloperidol. RESULTS: For the 60 patients who completed phase A, standard-dose haloperidol was efficacious and superior to both low-dose haloperidol and placebo for scores on the Brief Psychiatric Rating Scale psychosis factor and on psychomotor agitation. Response rates according to three sets of criteria were greater with the standard dose (55%-60%) than the low dose (25%-35%) and placebo (25%-30%). The advantage of standard dose over low dose was replicated in phase B. In phase A, extrapyramidal signs tended to be greater with the standard dose than in the other two conditions, primarily because of a subgroup (20%) who developed moderate to severe signs. Low-dose haloperidol did not differ from placebo on any measure of efficacy or side effects. CONCLUSIONS: The results indicated a favorable therapeutic profile for haloperidol in doses of 2-3 mg/day, although a subgroup developed moderate to severe extrapyramidal signs. A starting dose of 1 mg/day with gradual, upward dose titration is recommended. The narrow therapeutic window observed with haloperidol may also apply to other neuroleptics used in Alzheimer's disease patients with psychosis and disruptive behaviors.", "entity": "Basal Ganglia Diseases", "aliases": "Basal Ganglia Disease Diseases Disorder Disorders Extrapyramidal Lenticulostriate", "definition": "Diseases of the BASAL GANGLIA including the PUTAMEN; GLOBUS PALLIDUS; claustrum; AMYGDALA; and CAUDATE NUCLEUS. DYSKINESIAS (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include CEREBROVASCULAR DISORDERS; NEURODEGENERATIVE DISEASES; and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D001480"}
{"mention": "adriamycin", "mention_text": "Individual differences in renal ACE activity in healthy rats predict susceptibility to adriamycin-induced renal damage.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "renal damage", "mention_text": "Individual differences in renal ACE activity in healthy rats predict susceptibility to adriamycin-induced renal damage.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "angiotensin", "mention_text": "BACKGROUND: In man, differences in angiotensin-converting enzyme (ACE) levels, related to ACE (I/D) genotype, are associated with renal prognosis. This raises the hypothesis that individual differences in renal ACE activity are involved in renal susceptibility to inflicted damage. Therefore, we studied the predictive effect of renal ACE activity for the severity of renal damage induced by a single injection of adriamycin in rats. METHODS: Renal ACE activity (Hip-His-Leu cleavage by cortical homogenates) was determined by renal biopsy in 27 adult male Wistar rats. After 1 week of recovery, proteinuria was induced by adriamycin [1.5 mg/kg intravenously (i.v.) n = 18; controls, saline i.v. n = 9]. Proteinuria was measured every 2 weeks. After 12 weeks, rats were sacrificed and their kidneys harvested. RESULTS: As anticipated, adriamycin elicited nephrotic range proteinuria, renal interstitial damage and mild focal glomerulosclerosis. Baseline renal ACE positively correlated with the relative rise in proteinuria after adriamycin (r = 0.62, P<0.01), renal interstitial alpha-smooth muscle actin (r = 0.49, P<0.05), interstitial macrophage influx (r = 0.56, P<0.05), interstitial collagen III (r = 0.53, P<0.05), glomerular alpha-smooth muscle actin (r = 0.74, P<0.01) and glomerular desmin (r = 0.48, P<0.05). Baseline renal ACE did not correlate with focal glomerulosclerosis (r = 0.22, NS). In controls, no predictive values for renal parameters were observed. CONCLUSION: Individual differences in renal ACE activity predict the severity of adriamycin-induced renal damage in this outbred rat strain. This supports the assumption that differences in renal ACE activity predispose to a less favourable course of renal damage.", "entity": "Angiotensins", "aliases": "Angiotensin Angiotensins", "definition": "Oligopeptides which are important in the regulation of blood pressure (VASOCONSTRICTION) and fluid homeostasis via the RENIN-ANGIOTENSIN SYSTEM. These include angiotensins derived naturally from precursor ANGIOTENSINOGEN, and those synthesized.\n    ", "id": "MESH:D000809"}
{"mention": "renal damage", "mention_text": "BACKGROUND: In man, differences in angiotensin-converting enzyme (ACE) levels, related to ACE (I/D) genotype, are associated with renal prognosis. This raises the hypothesis that individual differences in renal ACE activity are involved in renal susceptibility to inflicted damage. Therefore, we studied the predictive effect of renal ACE activity for the severity of renal damage induced by a single injection of adriamycin in rats. METHODS: Renal ACE activity (Hip-His-Leu cleavage by cortical homogenates) was determined by renal biopsy in 27 adult male Wistar rats. After 1 week of recovery, proteinuria was induced by adriamycin [1.5 mg/kg intravenously (i.v.) n = 18; controls, saline i.v. n = 9]. Proteinuria was measured every 2 weeks. After 12 weeks, rats were sacrificed and their kidneys harvested. RESULTS: As anticipated, adriamycin elicited nephrotic range proteinuria, renal interstitial damage and mild focal glomerulosclerosis. Baseline renal ACE positively correlated with the relative rise in proteinuria after adriamycin (r = 0.62, P<0.01), renal interstitial alpha-smooth muscle actin (r = 0.49, P<0.05), interstitial macrophage influx (r = 0.56, P<0.05), interstitial collagen III (r = 0.53, P<0.05), glomerular alpha-smooth muscle actin (r = 0.74, P<0.01) and glomerular desmin (r = 0.48, P<0.05). Baseline renal ACE did not correlate with focal glomerulosclerosis (r = 0.22, NS). In controls, no predictive values for renal parameters were observed. CONCLUSION: Individual differences in renal ACE activity predict the severity of adriamycin-induced renal damage in this outbred rat strain. This supports the assumption that differences in renal ACE activity predispose to a less favourable course of renal damage.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "adriamycin", "mention_text": "BACKGROUND: In man, differences in angiotensin-converting enzyme (ACE) levels, related to ACE (I/D) genotype, are associated with renal prognosis. This raises the hypothesis that individual differences in renal ACE activity are involved in renal susceptibility to inflicted damage. Therefore, we studied the predictive effect of renal ACE activity for the severity of renal damage induced by a single injection of adriamycin in rats. METHODS: Renal ACE activity (Hip-His-Leu cleavage by cortical homogenates) was determined by renal biopsy in 27 adult male Wistar rats. After 1 week of recovery, proteinuria was induced by adriamycin [1.5 mg/kg intravenously (i.v.) n = 18; controls, saline i.v. n = 9]. Proteinuria was measured every 2 weeks. After 12 weeks, rats were sacrificed and their kidneys harvested. RESULTS: As anticipated, adriamycin elicited nephrotic range proteinuria, renal interstitial damage and mild focal glomerulosclerosis. Baseline renal ACE positively correlated with the relative rise in proteinuria after adriamycin (r = 0.62, P<0.01), renal interstitial alpha-smooth muscle actin (r = 0.49, P<0.05), interstitial macrophage influx (r = 0.56, P<0.05), interstitial collagen III (r = 0.53, P<0.05), glomerular alpha-smooth muscle actin (r = 0.74, P<0.01) and glomerular desmin (r = 0.48, P<0.05). Baseline renal ACE did not correlate with focal glomerulosclerosis (r = 0.22, NS). In controls, no predictive values for renal parameters were observed. CONCLUSION: Individual differences in renal ACE activity predict the severity of adriamycin-induced renal damage in this outbred rat strain. This supports the assumption that differences in renal ACE activity predispose to a less favourable course of renal damage.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "Hip-His-Leu", "mention_text": "BACKGROUND: In man, differences in angiotensin-converting enzyme (ACE) levels, related to ACE (I/D) genotype, are associated with renal prognosis. This raises the hypothesis that individual differences in renal ACE activity are involved in renal susceptibility to inflicted damage. Therefore, we studied the predictive effect of renal ACE activity for the severity of renal damage induced by a single injection of adriamycin in rats. METHODS: Renal ACE activity (Hip-His-Leu cleavage by cortical homogenates) was determined by renal biopsy in 27 adult male Wistar rats. After 1 week of recovery, proteinuria was induced by adriamycin [1.5 mg/kg intravenously (i.v.) n = 18; controls, saline i.v. n = 9]. Proteinuria was measured every 2 weeks. After 12 weeks, rats were sacrificed and their kidneys harvested. RESULTS: As anticipated, adriamycin elicited nephrotic range proteinuria, renal interstitial damage and mild focal glomerulosclerosis. Baseline renal ACE positively correlated with the relative rise in proteinuria after adriamycin (r = 0.62, P<0.01), renal interstitial alpha-smooth muscle actin (r = 0.49, P<0.05), interstitial macrophage influx (r = 0.56, P<0.05), interstitial collagen III (r = 0.53, P<0.05), glomerular alpha-smooth muscle actin (r = 0.74, P<0.01) and glomerular desmin (r = 0.48, P<0.05). Baseline renal ACE did not correlate with focal glomerulosclerosis (r = 0.22, NS). In controls, no predictive values for renal parameters were observed. CONCLUSION: Individual differences in renal ACE activity predict the severity of adriamycin-induced renal damage in this outbred rat strain. This supports the assumption that differences in renal ACE activity predispose to a less favourable course of renal damage.", "entity": "hippuryl-histidyl-leucine", "aliases": "Bz-Gly-His-Leu Hip-His-Leu N-(N-(N-benzoylglycyl)-L-histidinyl)-L-leucine benzoyl-glycyl-histidyl-leucine hippuryl-His-Leu hippuryl-L-histidyl-L-leucine hippuryl-histidyl-leucine", "definition": "", "id": "MESH:C010980"}
{"mention": "proteinuria", "mention_text": "BACKGROUND: In man, differences in angiotensin-converting enzyme (ACE) levels, related to ACE (I/D) genotype, are associated with renal prognosis. This raises the hypothesis that individual differences in renal ACE activity are involved in renal susceptibility to inflicted damage. Therefore, we studied the predictive effect of renal ACE activity for the severity of renal damage induced by a single injection of adriamycin in rats. METHODS: Renal ACE activity (Hip-His-Leu cleavage by cortical homogenates) was determined by renal biopsy in 27 adult male Wistar rats. After 1 week of recovery, proteinuria was induced by adriamycin [1.5 mg/kg intravenously (i.v.) n = 18; controls, saline i.v. n = 9]. Proteinuria was measured every 2 weeks. After 12 weeks, rats were sacrificed and their kidneys harvested. RESULTS: As anticipated, adriamycin elicited nephrotic range proteinuria, renal interstitial damage and mild focal glomerulosclerosis. Baseline renal ACE positively correlated with the relative rise in proteinuria after adriamycin (r = 0.62, P<0.01), renal interstitial alpha-smooth muscle actin (r = 0.49, P<0.05), interstitial macrophage influx (r = 0.56, P<0.05), interstitial collagen III (r = 0.53, P<0.05), glomerular alpha-smooth muscle actin (r = 0.74, P<0.01) and glomerular desmin (r = 0.48, P<0.05). Baseline renal ACE did not correlate with focal glomerulosclerosis (r = 0.22, NS). In controls, no predictive values for renal parameters were observed. CONCLUSION: Individual differences in renal ACE activity predict the severity of adriamycin-induced renal damage in this outbred rat strain. This supports the assumption that differences in renal ACE activity predispose to a less favourable course of renal damage.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "Proteinuria", "mention_text": "BACKGROUND: In man, differences in angiotensin-converting enzyme (ACE) levels, related to ACE (I/D) genotype, are associated with renal prognosis. This raises the hypothesis that individual differences in renal ACE activity are involved in renal susceptibility to inflicted damage. Therefore, we studied the predictive effect of renal ACE activity for the severity of renal damage induced by a single injection of adriamycin in rats. METHODS: Renal ACE activity (Hip-His-Leu cleavage by cortical homogenates) was determined by renal biopsy in 27 adult male Wistar rats. After 1 week of recovery, proteinuria was induced by adriamycin [1.5 mg/kg intravenously (i.v.) n = 18; controls, saline i.v. n = 9]. Proteinuria was measured every 2 weeks. After 12 weeks, rats were sacrificed and their kidneys harvested. RESULTS: As anticipated, adriamycin elicited nephrotic range proteinuria, renal interstitial damage and mild focal glomerulosclerosis. Baseline renal ACE positively correlated with the relative rise in proteinuria after adriamycin (r = 0.62, P<0.01), renal interstitial alpha-smooth muscle actin (r = 0.49, P<0.05), interstitial macrophage influx (r = 0.56, P<0.05), interstitial collagen III (r = 0.53, P<0.05), glomerular alpha-smooth muscle actin (r = 0.74, P<0.01) and glomerular desmin (r = 0.48, P<0.05). Baseline renal ACE did not correlate with focal glomerulosclerosis (r = 0.22, NS). In controls, no predictive values for renal parameters were observed. CONCLUSION: Individual differences in renal ACE activity predict the severity of adriamycin-induced renal damage in this outbred rat strain. This supports the assumption that differences in renal ACE activity predispose to a less favourable course of renal damage.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "nephrotic", "mention_text": "BACKGROUND: In man, differences in angiotensin-converting enzyme (ACE) levels, related to ACE (I/D) genotype, are associated with renal prognosis. This raises the hypothesis that individual differences in renal ACE activity are involved in renal susceptibility to inflicted damage. Therefore, we studied the predictive effect of renal ACE activity for the severity of renal damage induced by a single injection of adriamycin in rats. METHODS: Renal ACE activity (Hip-His-Leu cleavage by cortical homogenates) was determined by renal biopsy in 27 adult male Wistar rats. After 1 week of recovery, proteinuria was induced by adriamycin [1.5 mg/kg intravenously (i.v.) n = 18; controls, saline i.v. n = 9]. Proteinuria was measured every 2 weeks. After 12 weeks, rats were sacrificed and their kidneys harvested. RESULTS: As anticipated, adriamycin elicited nephrotic range proteinuria, renal interstitial damage and mild focal glomerulosclerosis. Baseline renal ACE positively correlated with the relative rise in proteinuria after adriamycin (r = 0.62, P<0.01), renal interstitial alpha-smooth muscle actin (r = 0.49, P<0.05), interstitial macrophage influx (r = 0.56, P<0.05), interstitial collagen III (r = 0.53, P<0.05), glomerular alpha-smooth muscle actin (r = 0.74, P<0.01) and glomerular desmin (r = 0.48, P<0.05). Baseline renal ACE did not correlate with focal glomerulosclerosis (r = 0.22, NS). In controls, no predictive values for renal parameters were observed. CONCLUSION: Individual differences in renal ACE activity predict the severity of adriamycin-induced renal damage in this outbred rat strain. This supports the assumption that differences in renal ACE activity predispose to a less favourable course of renal damage.", "entity": "Nephrotic Syndrome", "aliases": "Nephrotic Syndrome Syndromes", "definition": "A condition characterized by severe PROTEINURIA, greater than 3.5 g/day in an average adult. The substantial loss of protein in the urine results in complications such as HYPOPROTEINEMIA; generalized EDEMA; HYPERTENSION; and HYPERLIPIDEMIAS. Diseases associated with nephrotic syndrome generally cause chronic kidney dysfunction.\n    ", "id": "MESH:D009404"}
{"mention": "renal interstitial damage", "mention_text": "BACKGROUND: In man, differences in angiotensin-converting enzyme (ACE) levels, related to ACE (I/D) genotype, are associated with renal prognosis. This raises the hypothesis that individual differences in renal ACE activity are involved in renal susceptibility to inflicted damage. Therefore, we studied the predictive effect of renal ACE activity for the severity of renal damage induced by a single injection of adriamycin in rats. METHODS: Renal ACE activity (Hip-His-Leu cleavage by cortical homogenates) was determined by renal biopsy in 27 adult male Wistar rats. After 1 week of recovery, proteinuria was induced by adriamycin [1.5 mg/kg intravenously (i.v.) n = 18; controls, saline i.v. n = 9]. Proteinuria was measured every 2 weeks. After 12 weeks, rats were sacrificed and their kidneys harvested. RESULTS: As anticipated, adriamycin elicited nephrotic range proteinuria, renal interstitial damage and mild focal glomerulosclerosis. Baseline renal ACE positively correlated with the relative rise in proteinuria after adriamycin (r = 0.62, P<0.01), renal interstitial alpha-smooth muscle actin (r = 0.49, P<0.05), interstitial macrophage influx (r = 0.56, P<0.05), interstitial collagen III (r = 0.53, P<0.05), glomerular alpha-smooth muscle actin (r = 0.74, P<0.01) and glomerular desmin (r = 0.48, P<0.05). Baseline renal ACE did not correlate with focal glomerulosclerosis (r = 0.22, NS). In controls, no predictive values for renal parameters were observed. CONCLUSION: Individual differences in renal ACE activity predict the severity of adriamycin-induced renal damage in this outbred rat strain. This supports the assumption that differences in renal ACE activity predispose to a less favourable course of renal damage.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "focal glomerulosclerosis", "mention_text": "BACKGROUND: In man, differences in angiotensin-converting enzyme (ACE) levels, related to ACE (I/D) genotype, are associated with renal prognosis. This raises the hypothesis that individual differences in renal ACE activity are involved in renal susceptibility to inflicted damage. Therefore, we studied the predictive effect of renal ACE activity for the severity of renal damage induced by a single injection of adriamycin in rats. METHODS: Renal ACE activity (Hip-His-Leu cleavage by cortical homogenates) was determined by renal biopsy in 27 adult male Wistar rats. After 1 week of recovery, proteinuria was induced by adriamycin [1.5 mg/kg intravenously (i.v.) n = 18; controls, saline i.v. n = 9]. Proteinuria was measured every 2 weeks. After 12 weeks, rats were sacrificed and their kidneys harvested. RESULTS: As anticipated, adriamycin elicited nephrotic range proteinuria, renal interstitial damage and mild focal glomerulosclerosis. Baseline renal ACE positively correlated with the relative rise in proteinuria after adriamycin (r = 0.62, P<0.01), renal interstitial alpha-smooth muscle actin (r = 0.49, P<0.05), interstitial macrophage influx (r = 0.56, P<0.05), interstitial collagen III (r = 0.53, P<0.05), glomerular alpha-smooth muscle actin (r = 0.74, P<0.01) and glomerular desmin (r = 0.48, P<0.05). Baseline renal ACE did not correlate with focal glomerulosclerosis (r = 0.22, NS). In controls, no predictive values for renal parameters were observed. CONCLUSION: Individual differences in renal ACE activity predict the severity of adriamycin-induced renal damage in this outbred rat strain. This supports the assumption that differences in renal ACE activity predispose to a less favourable course of renal damage.", "entity": "Glomerulosclerosis, Focal Segmental", "aliases": "Focal Glomerulosclerosis Sclerosing Glomerulonephritides Glomerulonephritis Segmental Glomerular Hyalinosis", "definition": "A clinicopathological syndrome or diagnostic term for a type of glomerular injury that has multiple causes, primary or secondary. Clinical features include PROTEINURIA, reduced GLOMERULAR FILTRATION RATE, and EDEMA. Kidney biopsy initially indicates focal segmental glomerular consolidation (hyalinosis) or scarring which can progress to globally sclerotic glomeruli leading to eventual KIDNEY FAILURE.\n    ", "id": "MESH:D005923"}
{"mention": "nephrotoxicity", "mention_text": "Clinical nephrotoxicity of tobramycin and gentamicin. A prospective study.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "tobramycin", "mention_text": "Clinical nephrotoxicity of tobramycin and gentamicin. A prospective study.", "entity": "Tobramycin", "aliases": "Brulamycin Nebcin Nebicin Nebramycin Factor 6 Obracin Sulfate Tobramycin Tobracin", "definition": "An aminoglycoside, broad-spectrum antibiotic produced by Streptomyces tenebrarius. It is effective against gram-negative bacteria, especially the PSEUDOMONAS species. It is a 10% component of the antibiotic complex, NEBRAMYCIN, produced by the same species.\n    ", "id": "MESH:D014031"}
{"mention": "gentamicin", "mention_text": "Clinical nephrotoxicity of tobramycin and gentamicin. A prospective study.", "entity": "Gentamicins", "aliases": "G Myticin G-Myticin GMyticin Garamycin Gentacycol Gentamicin Sulfate (USP) Gentamicins Gentamycin Gentamycins Gentavet Genticin", "definition": "A complex of closely related aminoglycosides obtained from MICROMONOSPORA purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit PROTEIN BIOSYNTHESIS.\n    ", "id": "MESH:D005839"}
{"mention": "aminoglycoside", "mention_text": "Nearly 3.2 million people in this country receive aminoglycoside antibiotics annually. Gentamicin sulfate and tobramycin sulfate continue to demonstrate ototoxicity and nephrotoxicity in both animal and clinical studies. In this study, 62 patients with confirmed initial normal renal function and treated with 2 to 5 mg/kg/day of gentamicin sulfate or tobramycin sulfate for a minimum of seven days were followed up prospectively for the development of aminoglycoside-related renal failure, defined as at least a one-third reduction in renal function. In these 62 patients, no other causes for renal failure could be identified. Five of 33 (15%) of the tobramycin-treated patients and 16 of 29 (55.2%) of the gentamicin-treated patients had renal failure. Thus, gentamicin was associated with renal failure more than three times as often as was tobramycin.", "entity": "Aminoglycosides", "aliases": "Aminoglycosides", "definition": "Glycosylated compounds in which there is an amino substituent on the glycoside. Some of them are clinically important ANTIBIOTICS.\n    ", "id": "MESH:D000617"}
{"mention": "Gentamicin sulfate", "mention_text": "Nearly 3.2 million people in this country receive aminoglycoside antibiotics annually. Gentamicin sulfate and tobramycin sulfate continue to demonstrate ototoxicity and nephrotoxicity in both animal and clinical studies. In this study, 62 patients with confirmed initial normal renal function and treated with 2 to 5 mg/kg/day of gentamicin sulfate or tobramycin sulfate for a minimum of seven days were followed up prospectively for the development of aminoglycoside-related renal failure, defined as at least a one-third reduction in renal function. In these 62 patients, no other causes for renal failure could be identified. Five of 33 (15%) of the tobramycin-treated patients and 16 of 29 (55.2%) of the gentamicin-treated patients had renal failure. Thus, gentamicin was associated with renal failure more than three times as often as was tobramycin.", "entity": "Gentamicins", "aliases": "G Myticin G-Myticin GMyticin Garamycin Gentacycol Gentamicin Sulfate (USP) Gentamicins Gentamycin Gentamycins Gentavet Genticin", "definition": "A complex of closely related aminoglycosides obtained from MICROMONOSPORA purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit PROTEIN BIOSYNTHESIS.\n    ", "id": "MESH:D005839"}
{"mention": "tobramycin sulfate", "mention_text": "Nearly 3.2 million people in this country receive aminoglycoside antibiotics annually. Gentamicin sulfate and tobramycin sulfate continue to demonstrate ototoxicity and nephrotoxicity in both animal and clinical studies. In this study, 62 patients with confirmed initial normal renal function and treated with 2 to 5 mg/kg/day of gentamicin sulfate or tobramycin sulfate for a minimum of seven days were followed up prospectively for the development of aminoglycoside-related renal failure, defined as at least a one-third reduction in renal function. In these 62 patients, no other causes for renal failure could be identified. Five of 33 (15%) of the tobramycin-treated patients and 16 of 29 (55.2%) of the gentamicin-treated patients had renal failure. Thus, gentamicin was associated with renal failure more than three times as often as was tobramycin.", "entity": "Tobramycin", "aliases": "Brulamycin Nebcin Nebicin Nebramycin Factor 6 Obracin Sulfate Tobramycin Tobracin", "definition": "An aminoglycoside, broad-spectrum antibiotic produced by Streptomyces tenebrarius. It is effective against gram-negative bacteria, especially the PSEUDOMONAS species. It is a 10% component of the antibiotic complex, NEBRAMYCIN, produced by the same species.\n    ", "id": "MESH:D014031"}
{"mention": "ototoxicity", "mention_text": "Nearly 3.2 million people in this country receive aminoglycoside antibiotics annually. Gentamicin sulfate and tobramycin sulfate continue to demonstrate ototoxicity and nephrotoxicity in both animal and clinical studies. In this study, 62 patients with confirmed initial normal renal function and treated with 2 to 5 mg/kg/day of gentamicin sulfate or tobramycin sulfate for a minimum of seven days were followed up prospectively for the development of aminoglycoside-related renal failure, defined as at least a one-third reduction in renal function. In these 62 patients, no other causes for renal failure could be identified. Five of 33 (15%) of the tobramycin-treated patients and 16 of 29 (55.2%) of the gentamicin-treated patients had renal failure. Thus, gentamicin was associated with renal failure more than three times as often as was tobramycin.", "entity": "Hearing Disorders", "aliases": "Distorted Hearing Dysacusis Disorder Disorders Paracousis Paracusis", "definition": "Conditions that impair the transmission of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways.\n    ", "id": "MESH:D006311"}
{"mention": "nephrotoxicity", "mention_text": "Nearly 3.2 million people in this country receive aminoglycoside antibiotics annually. Gentamicin sulfate and tobramycin sulfate continue to demonstrate ototoxicity and nephrotoxicity in both animal and clinical studies. In this study, 62 patients with confirmed initial normal renal function and treated with 2 to 5 mg/kg/day of gentamicin sulfate or tobramycin sulfate for a minimum of seven days were followed up prospectively for the development of aminoglycoside-related renal failure, defined as at least a one-third reduction in renal function. In these 62 patients, no other causes for renal failure could be identified. Five of 33 (15%) of the tobramycin-treated patients and 16 of 29 (55.2%) of the gentamicin-treated patients had renal failure. Thus, gentamicin was associated with renal failure more than three times as often as was tobramycin.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "gentamicin sulfate", "mention_text": "Nearly 3.2 million people in this country receive aminoglycoside antibiotics annually. Gentamicin sulfate and tobramycin sulfate continue to demonstrate ototoxicity and nephrotoxicity in both animal and clinical studies. In this study, 62 patients with confirmed initial normal renal function and treated with 2 to 5 mg/kg/day of gentamicin sulfate or tobramycin sulfate for a minimum of seven days were followed up prospectively for the development of aminoglycoside-related renal failure, defined as at least a one-third reduction in renal function. In these 62 patients, no other causes for renal failure could be identified. Five of 33 (15%) of the tobramycin-treated patients and 16 of 29 (55.2%) of the gentamicin-treated patients had renal failure. Thus, gentamicin was associated with renal failure more than three times as often as was tobramycin.", "entity": "Gentamicins", "aliases": "G Myticin G-Myticin GMyticin Garamycin Gentacycol Gentamicin Sulfate (USP) Gentamicins Gentamycin Gentamycins Gentavet Genticin", "definition": "A complex of closely related aminoglycosides obtained from MICROMONOSPORA purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit PROTEIN BIOSYNTHESIS.\n    ", "id": "MESH:D005839"}
{"mention": "renal failure", "mention_text": "Nearly 3.2 million people in this country receive aminoglycoside antibiotics annually. Gentamicin sulfate and tobramycin sulfate continue to demonstrate ototoxicity and nephrotoxicity in both animal and clinical studies. In this study, 62 patients with confirmed initial normal renal function and treated with 2 to 5 mg/kg/day of gentamicin sulfate or tobramycin sulfate for a minimum of seven days were followed up prospectively for the development of aminoglycoside-related renal failure, defined as at least a one-third reduction in renal function. In these 62 patients, no other causes for renal failure could be identified. Five of 33 (15%) of the tobramycin-treated patients and 16 of 29 (55.2%) of the gentamicin-treated patients had renal failure. Thus, gentamicin was associated with renal failure more than three times as often as was tobramycin.", "entity": "Renal Insufficiency", "aliases": "Failure Kidney Renal Failures Insufficiency Insufficiencies", "definition": "Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.\n    ", "id": "MESH:D051437"}
{"mention": "tobramycin", "mention_text": "Nearly 3.2 million people in this country receive aminoglycoside antibiotics annually. Gentamicin sulfate and tobramycin sulfate continue to demonstrate ototoxicity and nephrotoxicity in both animal and clinical studies. In this study, 62 patients with confirmed initial normal renal function and treated with 2 to 5 mg/kg/day of gentamicin sulfate or tobramycin sulfate for a minimum of seven days were followed up prospectively for the development of aminoglycoside-related renal failure, defined as at least a one-third reduction in renal function. In these 62 patients, no other causes for renal failure could be identified. Five of 33 (15%) of the tobramycin-treated patients and 16 of 29 (55.2%) of the gentamicin-treated patients had renal failure. Thus, gentamicin was associated with renal failure more than three times as often as was tobramycin.", "entity": "Tobramycin", "aliases": "Brulamycin Nebcin Nebicin Nebramycin Factor 6 Obracin Sulfate Tobramycin Tobracin", "definition": "An aminoglycoside, broad-spectrum antibiotic produced by Streptomyces tenebrarius. It is effective against gram-negative bacteria, especially the PSEUDOMONAS species. It is a 10% component of the antibiotic complex, NEBRAMYCIN, produced by the same species.\n    ", "id": "MESH:D014031"}
{"mention": "gentamicin", "mention_text": "Nearly 3.2 million people in this country receive aminoglycoside antibiotics annually. Gentamicin sulfate and tobramycin sulfate continue to demonstrate ototoxicity and nephrotoxicity in both animal and clinical studies. In this study, 62 patients with confirmed initial normal renal function and treated with 2 to 5 mg/kg/day of gentamicin sulfate or tobramycin sulfate for a minimum of seven days were followed up prospectively for the development of aminoglycoside-related renal failure, defined as at least a one-third reduction in renal function. In these 62 patients, no other causes for renal failure could be identified. Five of 33 (15%) of the tobramycin-treated patients and 16 of 29 (55.2%) of the gentamicin-treated patients had renal failure. Thus, gentamicin was associated with renal failure more than three times as often as was tobramycin.", "entity": "Gentamicins", "aliases": "G Myticin G-Myticin GMyticin Garamycin Gentacycol Gentamicin Sulfate (USP) Gentamicins Gentamycin Gentamycins Gentavet Genticin", "definition": "A complex of closely related aminoglycosides obtained from MICROMONOSPORA purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit PROTEIN BIOSYNTHESIS.\n    ", "id": "MESH:D005839"}
{"mention": "MPEP", "mention_text": "Neuroprotective action of MPEP, a selective mGluR5 antagonist, in methamphetamine-induced dopaminergic neurotoxicity is associated with a decrease in dopamine outflow and inhibition of hyperthermia in rats.", "entity": "6-methyl-2-(phenylethynyl)pyridine", "aliases": "2-methyl-6-(phenylethynyl)pyridine 6-methyl-2-(phenylethynyl)pyridine MPEP cpd", "definition": "", "id": "MESH:C121465"}
{"mention": "methamphetamine", "mention_text": "Neuroprotective action of MPEP, a selective mGluR5 antagonist, in methamphetamine-induced dopaminergic neurotoxicity is associated with a decrease in dopamine outflow and inhibition of hyperthermia in rats.", "entity": "Methamphetamine", "aliases": "Abbott Brand of Methamphetamine Hydrochloride Deoxyephedrine Desoxyephedrine Desoxyn Langly Madrine Metamfetamine Methylamphetamine N N-Methylamphetamine", "definition": "A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.\n    ", "id": "MESH:D008694"}
{"mention": "neurotoxicity", "mention_text": "Neuroprotective action of MPEP, a selective mGluR5 antagonist, in methamphetamine-induced dopaminergic neurotoxicity is associated with a decrease in dopamine outflow and inhibition of hyperthermia in rats.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "dopamine", "mention_text": "Neuroprotective action of MPEP, a selective mGluR5 antagonist, in methamphetamine-induced dopaminergic neurotoxicity is associated with a decrease in dopamine outflow and inhibition of hyperthermia in rats.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "hyperthermia", "mention_text": "Neuroprotective action of MPEP, a selective mGluR5 antagonist, in methamphetamine-induced dopaminergic neurotoxicity is associated with a decrease in dopamine outflow and inhibition of hyperthermia in rats.", "entity": "Fever", "aliases": "Fever Fevers Hyperthermia Hyperthermias Pyrexia Pyrexias", "definition": "An abnormal elevation of body temperature, usually as a result of a pathologic process.\n    ", "id": "MESH:D005334"}
{"mention": "glutamate", "mention_text": "The aim of this study was to examine the role of metabotropic glutamate receptor 5 (mGluR5) in the toxic action of methamphetamine on dopaminergic neurones in rats. Methamphetamine (10 mg/kg sc), administered five times, reduced the levels of dopamine and its metabolites in striatal tissue when measured 72 h after the last injection. A selective antagonist of mGluR5, 2-methyl-6-(phenylethynyl)pyridine (MPEP; 5 mg/kg ip), when administered five times immediately before each methamphetamine injection reversed the above-mentioned methamphetamine effects. A single MPEP (5 mg/kg ip) injection reduced the basal extracellular dopamine level in the striatum, as well as dopamine release stimulated either by methamphetamine (10 mg/kg sc) or by intrastriatally administered veratridine (100 microM). Moreover, it transiently diminished the methamphetamine (10 mg/kg sc)-induced hyperthermia and reduced basal body temperature. MPEP administered into the striatum at high concentrations (500 microM) increased extracellular dopamine levels, while lower concentrations (50-100 microM) were devoid of any effect. The results of this study suggest that the blockade of mGluR5 by MPEP may protect dopaminergic neurones against methamphetamine-induced toxicity. Neuroprotection rendered by MPEP may be associated with the reduction of the methamphetamine-induced dopamine efflux in the striatum due to the blockade of extrastriatal mGluR5, and with a decrease in hyperthermia.", "entity": "Glutamic Acid", "aliases": "Aluminum L Glutamate L-Glutamate D D-Glutamate Potassium Glutamic Acid (D)-Isomer L-Glutamic", "definition": "A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.\n    ", "id": "MESH:D018698"}
{"mention": "methamphetamine", "mention_text": "The aim of this study was to examine the role of metabotropic glutamate receptor 5 (mGluR5) in the toxic action of methamphetamine on dopaminergic neurones in rats. Methamphetamine (10 mg/kg sc), administered five times, reduced the levels of dopamine and its metabolites in striatal tissue when measured 72 h after the last injection. A selective antagonist of mGluR5, 2-methyl-6-(phenylethynyl)pyridine (MPEP; 5 mg/kg ip), when administered five times immediately before each methamphetamine injection reversed the above-mentioned methamphetamine effects. A single MPEP (5 mg/kg ip) injection reduced the basal extracellular dopamine level in the striatum, as well as dopamine release stimulated either by methamphetamine (10 mg/kg sc) or by intrastriatally administered veratridine (100 microM). Moreover, it transiently diminished the methamphetamine (10 mg/kg sc)-induced hyperthermia and reduced basal body temperature. MPEP administered into the striatum at high concentrations (500 microM) increased extracellular dopamine levels, while lower concentrations (50-100 microM) were devoid of any effect. The results of this study suggest that the blockade of mGluR5 by MPEP may protect dopaminergic neurones against methamphetamine-induced toxicity. Neuroprotection rendered by MPEP may be associated with the reduction of the methamphetamine-induced dopamine efflux in the striatum due to the blockade of extrastriatal mGluR5, and with a decrease in hyperthermia.", "entity": "Methamphetamine", "aliases": "Abbott Brand of Methamphetamine Hydrochloride Deoxyephedrine Desoxyephedrine Desoxyn Langly Madrine Metamfetamine Methylamphetamine N N-Methylamphetamine", "definition": "A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.\n    ", "id": "MESH:D008694"}
{"mention": "Methamphetamine", "mention_text": "The aim of this study was to examine the role of metabotropic glutamate receptor 5 (mGluR5) in the toxic action of methamphetamine on dopaminergic neurones in rats. Methamphetamine (10 mg/kg sc), administered five times, reduced the levels of dopamine and its metabolites in striatal tissue when measured 72 h after the last injection. A selective antagonist of mGluR5, 2-methyl-6-(phenylethynyl)pyridine (MPEP; 5 mg/kg ip), when administered five times immediately before each methamphetamine injection reversed the above-mentioned methamphetamine effects. A single MPEP (5 mg/kg ip) injection reduced the basal extracellular dopamine level in the striatum, as well as dopamine release stimulated either by methamphetamine (10 mg/kg sc) or by intrastriatally administered veratridine (100 microM). Moreover, it transiently diminished the methamphetamine (10 mg/kg sc)-induced hyperthermia and reduced basal body temperature. MPEP administered into the striatum at high concentrations (500 microM) increased extracellular dopamine levels, while lower concentrations (50-100 microM) were devoid of any effect. The results of this study suggest that the blockade of mGluR5 by MPEP may protect dopaminergic neurones against methamphetamine-induced toxicity. Neuroprotection rendered by MPEP may be associated with the reduction of the methamphetamine-induced dopamine efflux in the striatum due to the blockade of extrastriatal mGluR5, and with a decrease in hyperthermia.", "entity": "Methamphetamine", "aliases": "Abbott Brand of Methamphetamine Hydrochloride Deoxyephedrine Desoxyephedrine Desoxyn Langly Madrine Metamfetamine Methylamphetamine N N-Methylamphetamine", "definition": "A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.\n    ", "id": "MESH:D008694"}
{"mention": "dopamine", "mention_text": "The aim of this study was to examine the role of metabotropic glutamate receptor 5 (mGluR5) in the toxic action of methamphetamine on dopaminergic neurones in rats. Methamphetamine (10 mg/kg sc), administered five times, reduced the levels of dopamine and its metabolites in striatal tissue when measured 72 h after the last injection. A selective antagonist of mGluR5, 2-methyl-6-(phenylethynyl)pyridine (MPEP; 5 mg/kg ip), when administered five times immediately before each methamphetamine injection reversed the above-mentioned methamphetamine effects. A single MPEP (5 mg/kg ip) injection reduced the basal extracellular dopamine level in the striatum, as well as dopamine release stimulated either by methamphetamine (10 mg/kg sc) or by intrastriatally administered veratridine (100 microM). Moreover, it transiently diminished the methamphetamine (10 mg/kg sc)-induced hyperthermia and reduced basal body temperature. MPEP administered into the striatum at high concentrations (500 microM) increased extracellular dopamine levels, while lower concentrations (50-100 microM) were devoid of any effect. The results of this study suggest that the blockade of mGluR5 by MPEP may protect dopaminergic neurones against methamphetamine-induced toxicity. Neuroprotection rendered by MPEP may be associated with the reduction of the methamphetamine-induced dopamine efflux in the striatum due to the blockade of extrastriatal mGluR5, and with a decrease in hyperthermia.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "2-methyl-6-(phenylethynyl)pyridine", "mention_text": "The aim of this study was to examine the role of metabotropic glutamate receptor 5 (mGluR5) in the toxic action of methamphetamine on dopaminergic neurones in rats. Methamphetamine (10 mg/kg sc), administered five times, reduced the levels of dopamine and its metabolites in striatal tissue when measured 72 h after the last injection. A selective antagonist of mGluR5, 2-methyl-6-(phenylethynyl)pyridine (MPEP; 5 mg/kg ip), when administered five times immediately before each methamphetamine injection reversed the above-mentioned methamphetamine effects. A single MPEP (5 mg/kg ip) injection reduced the basal extracellular dopamine level in the striatum, as well as dopamine release stimulated either by methamphetamine (10 mg/kg sc) or by intrastriatally administered veratridine (100 microM). Moreover, it transiently diminished the methamphetamine (10 mg/kg sc)-induced hyperthermia and reduced basal body temperature. MPEP administered into the striatum at high concentrations (500 microM) increased extracellular dopamine levels, while lower concentrations (50-100 microM) were devoid of any effect. The results of this study suggest that the blockade of mGluR5 by MPEP may protect dopaminergic neurones against methamphetamine-induced toxicity. Neuroprotection rendered by MPEP may be associated with the reduction of the methamphetamine-induced dopamine efflux in the striatum due to the blockade of extrastriatal mGluR5, and with a decrease in hyperthermia.", "entity": "6-methyl-2-(phenylethynyl)pyridine", "aliases": "2-methyl-6-(phenylethynyl)pyridine 6-methyl-2-(phenylethynyl)pyridine MPEP cpd", "definition": "", "id": "MESH:C121465"}
{"mention": "MPEP", "mention_text": "The aim of this study was to examine the role of metabotropic glutamate receptor 5 (mGluR5) in the toxic action of methamphetamine on dopaminergic neurones in rats. Methamphetamine (10 mg/kg sc), administered five times, reduced the levels of dopamine and its metabolites in striatal tissue when measured 72 h after the last injection. A selective antagonist of mGluR5, 2-methyl-6-(phenylethynyl)pyridine (MPEP; 5 mg/kg ip), when administered five times immediately before each methamphetamine injection reversed the above-mentioned methamphetamine effects. A single MPEP (5 mg/kg ip) injection reduced the basal extracellular dopamine level in the striatum, as well as dopamine release stimulated either by methamphetamine (10 mg/kg sc) or by intrastriatally administered veratridine (100 microM). Moreover, it transiently diminished the methamphetamine (10 mg/kg sc)-induced hyperthermia and reduced basal body temperature. MPEP administered into the striatum at high concentrations (500 microM) increased extracellular dopamine levels, while lower concentrations (50-100 microM) were devoid of any effect. The results of this study suggest that the blockade of mGluR5 by MPEP may protect dopaminergic neurones against methamphetamine-induced toxicity. Neuroprotection rendered by MPEP may be associated with the reduction of the methamphetamine-induced dopamine efflux in the striatum due to the blockade of extrastriatal mGluR5, and with a decrease in hyperthermia.", "entity": "6-methyl-2-(phenylethynyl)pyridine", "aliases": "2-methyl-6-(phenylethynyl)pyridine 6-methyl-2-(phenylethynyl)pyridine MPEP cpd", "definition": "", "id": "MESH:C121465"}
{"mention": "veratridine", "mention_text": "The aim of this study was to examine the role of metabotropic glutamate receptor 5 (mGluR5) in the toxic action of methamphetamine on dopaminergic neurones in rats. Methamphetamine (10 mg/kg sc), administered five times, reduced the levels of dopamine and its metabolites in striatal tissue when measured 72 h after the last injection. A selective antagonist of mGluR5, 2-methyl-6-(phenylethynyl)pyridine (MPEP; 5 mg/kg ip), when administered five times immediately before each methamphetamine injection reversed the above-mentioned methamphetamine effects. A single MPEP (5 mg/kg ip) injection reduced the basal extracellular dopamine level in the striatum, as well as dopamine release stimulated either by methamphetamine (10 mg/kg sc) or by intrastriatally administered veratridine (100 microM). Moreover, it transiently diminished the methamphetamine (10 mg/kg sc)-induced hyperthermia and reduced basal body temperature. MPEP administered into the striatum at high concentrations (500 microM) increased extracellular dopamine levels, while lower concentrations (50-100 microM) were devoid of any effect. The results of this study suggest that the blockade of mGluR5 by MPEP may protect dopaminergic neurones against methamphetamine-induced toxicity. Neuroprotection rendered by MPEP may be associated with the reduction of the methamphetamine-induced dopamine efflux in the striatum due to the blockade of extrastriatal mGluR5, and with a decrease in hyperthermia.", "entity": "Veratridine", "aliases": "Veratridine", "definition": "A benzoate-cevane found in VERATRUM and Schoenocaulon. It activates SODIUM CHANNELS to stay open longer than normal.\n    ", "id": "MESH:D014701"}
{"mention": "hyperthermia", "mention_text": "The aim of this study was to examine the role of metabotropic glutamate receptor 5 (mGluR5) in the toxic action of methamphetamine on dopaminergic neurones in rats. Methamphetamine (10 mg/kg sc), administered five times, reduced the levels of dopamine and its metabolites in striatal tissue when measured 72 h after the last injection. A selective antagonist of mGluR5, 2-methyl-6-(phenylethynyl)pyridine (MPEP; 5 mg/kg ip), when administered five times immediately before each methamphetamine injection reversed the above-mentioned methamphetamine effects. A single MPEP (5 mg/kg ip) injection reduced the basal extracellular dopamine level in the striatum, as well as dopamine release stimulated either by methamphetamine (10 mg/kg sc) or by intrastriatally administered veratridine (100 microM). Moreover, it transiently diminished the methamphetamine (10 mg/kg sc)-induced hyperthermia and reduced basal body temperature. MPEP administered into the striatum at high concentrations (500 microM) increased extracellular dopamine levels, while lower concentrations (50-100 microM) were devoid of any effect. The results of this study suggest that the blockade of mGluR5 by MPEP may protect dopaminergic neurones against methamphetamine-induced toxicity. Neuroprotection rendered by MPEP may be associated with the reduction of the methamphetamine-induced dopamine efflux in the striatum due to the blockade of extrastriatal mGluR5, and with a decrease in hyperthermia.", "entity": "Fever", "aliases": "Fever Fevers Hyperthermia Hyperthermias Pyrexia Pyrexias", "definition": "An abnormal elevation of body temperature, usually as a result of a pathologic process.\n    ", "id": "MESH:D005334"}
{"mention": "toxicity", "mention_text": "The aim of this study was to examine the role of metabotropic glutamate receptor 5 (mGluR5) in the toxic action of methamphetamine on dopaminergic neurones in rats. Methamphetamine (10 mg/kg sc), administered five times, reduced the levels of dopamine and its metabolites in striatal tissue when measured 72 h after the last injection. A selective antagonist of mGluR5, 2-methyl-6-(phenylethynyl)pyridine (MPEP; 5 mg/kg ip), when administered five times immediately before each methamphetamine injection reversed the above-mentioned methamphetamine effects. A single MPEP (5 mg/kg ip) injection reduced the basal extracellular dopamine level in the striatum, as well as dopamine release stimulated either by methamphetamine (10 mg/kg sc) or by intrastriatally administered veratridine (100 microM). Moreover, it transiently diminished the methamphetamine (10 mg/kg sc)-induced hyperthermia and reduced basal body temperature. MPEP administered into the striatum at high concentrations (500 microM) increased extracellular dopamine levels, while lower concentrations (50-100 microM) were devoid of any effect. The results of this study suggest that the blockade of mGluR5 by MPEP may protect dopaminergic neurones against methamphetamine-induced toxicity. Neuroprotection rendered by MPEP may be associated with the reduction of the methamphetamine-induced dopamine efflux in the striatum due to the blockade of extrastriatal mGluR5, and with a decrease in hyperthermia.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "desipramine HCl", "mention_text": "Pharmacokinetics of desipramine HCl when administered with cinacalcet HCl.", "entity": "Desipramine", "aliases": "Apo-Desipramine Apotex Brand of Desipramine Hydrochloride Aventis Behring Demethylimipramine Desmethylimipramine Norpramin Novartis Novo-Desipramine Novopharm Nu Pharm Nu-Desipramine Nu-Pharm PMS-Desipramine Pertofran Pertofrane Pertrofran Petylyl Pharmascience Ratiopharm Rhône Poulenc Rorer Rhône-Poulenc Temmler ratio-Desipramine", "definition": "A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholinergic activity, through its affinity to muscarinic receptors.\n    ", "id": "MESH:D003891"}
{"mention": "cinacalcet HCl", "mention_text": "Pharmacokinetics of desipramine HCl when administered with cinacalcet HCl.", "entity": "cinacalcet", "aliases": "AMG 073 AMG073 KRN 1493 Sensipar alpha-methyl-N-(3-(3-(trifluoromethyl)phenyl)propyl)-1-naphthalenemethanamine (alphaR)-hydrochloride cinacalcet hydrochloride", "definition": "", "id": "MESH:C476217"}
{"mention": "cinacalcet", "mention_text": "OBJECTIVE: In vitro work has demonstrated that cinacalcet is a strong inhibitor of cytochrome P450 isoenzyme (CYP) 2D6. The purpose of this study was to evaluate the effect of cinacalcet on CYP2D6 activity, using desipramine as a probe substrate, in healthy subjects. METHODS: Seventeen subjects who were genotyped as CYP2D6 extensive metabolizers were enrolled in this randomized, open-label, crossover study to receive a single oral dose of desipramine (50 mg) on two separate occasions, once alone and once after multiple doses of cinacalcet (90 mg for 7 days). Blood samples were obtained predose and up to 72 h postdose. RESULTS: Fourteen subjects completed both treatment arms. Relative to desipramine alone, mean AUC and C(max) of desipramine increased 3.6- and 1.8-fold when coadministered with cinacalcet. The t (1/2,z) of desipramine was longer when desipramine was coadministered with cinacalcet (21.0 versus 43.3 hs). The t (max) was similar between the regimens. Fewer subjects reported adverse events following treatment with desipramine alone than when receiving desipramine with cinacalcet (33 versus 86%), the most frequent of which (nausea and headache) have been reported for patients treated with either desipramine or cinacalcet. CONCLUSION: This study demonstrates that cinacalcet is a strong inhibitor of CYP2D6. These data suggest that during concomitant treatment with cinacalcet, dose adjustment may be necessary for drugs that demonstrate a narrow therapeutic index and are metabolized by CYP2D6.", "entity": "cinacalcet", "aliases": "AMG 073 AMG073 KRN 1493 Sensipar alpha-methyl-N-(3-(3-(trifluoromethyl)phenyl)propyl)-1-naphthalenemethanamine (alphaR)-hydrochloride cinacalcet hydrochloride", "definition": "", "id": "MESH:C476217"}
{"mention": "desipramine", "mention_text": "OBJECTIVE: In vitro work has demonstrated that cinacalcet is a strong inhibitor of cytochrome P450 isoenzyme (CYP) 2D6. The purpose of this study was to evaluate the effect of cinacalcet on CYP2D6 activity, using desipramine as a probe substrate, in healthy subjects. METHODS: Seventeen subjects who were genotyped as CYP2D6 extensive metabolizers were enrolled in this randomized, open-label, crossover study to receive a single oral dose of desipramine (50 mg) on two separate occasions, once alone and once after multiple doses of cinacalcet (90 mg for 7 days). Blood samples were obtained predose and up to 72 h postdose. RESULTS: Fourteen subjects completed both treatment arms. Relative to desipramine alone, mean AUC and C(max) of desipramine increased 3.6- and 1.8-fold when coadministered with cinacalcet. The t (1/2,z) of desipramine was longer when desipramine was coadministered with cinacalcet (21.0 versus 43.3 hs). The t (max) was similar between the regimens. Fewer subjects reported adverse events following treatment with desipramine alone than when receiving desipramine with cinacalcet (33 versus 86%), the most frequent of which (nausea and headache) have been reported for patients treated with either desipramine or cinacalcet. CONCLUSION: This study demonstrates that cinacalcet is a strong inhibitor of CYP2D6. These data suggest that during concomitant treatment with cinacalcet, dose adjustment may be necessary for drugs that demonstrate a narrow therapeutic index and are metabolized by CYP2D6.", "entity": "Desipramine", "aliases": "Apo-Desipramine Apotex Brand of Desipramine Hydrochloride Aventis Behring Demethylimipramine Desmethylimipramine Norpramin Novartis Novo-Desipramine Novopharm Nu Pharm Nu-Desipramine Nu-Pharm PMS-Desipramine Pertofran Pertofrane Pertrofran Petylyl Pharmascience Ratiopharm Rhône Poulenc Rorer Rhône-Poulenc Temmler ratio-Desipramine", "definition": "A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholinergic activity, through its affinity to muscarinic receptors.\n    ", "id": "MESH:D003891"}
{"mention": "nausea", "mention_text": "OBJECTIVE: In vitro work has demonstrated that cinacalcet is a strong inhibitor of cytochrome P450 isoenzyme (CYP) 2D6. The purpose of this study was to evaluate the effect of cinacalcet on CYP2D6 activity, using desipramine as a probe substrate, in healthy subjects. METHODS: Seventeen subjects who were genotyped as CYP2D6 extensive metabolizers were enrolled in this randomized, open-label, crossover study to receive a single oral dose of desipramine (50 mg) on two separate occasions, once alone and once after multiple doses of cinacalcet (90 mg for 7 days). Blood samples were obtained predose and up to 72 h postdose. RESULTS: Fourteen subjects completed both treatment arms. Relative to desipramine alone, mean AUC and C(max) of desipramine increased 3.6- and 1.8-fold when coadministered with cinacalcet. The t (1/2,z) of desipramine was longer when desipramine was coadministered with cinacalcet (21.0 versus 43.3 hs). The t (max) was similar between the regimens. Fewer subjects reported adverse events following treatment with desipramine alone than when receiving desipramine with cinacalcet (33 versus 86%), the most frequent of which (nausea and headache) have been reported for patients treated with either desipramine or cinacalcet. CONCLUSION: This study demonstrates that cinacalcet is a strong inhibitor of CYP2D6. These data suggest that during concomitant treatment with cinacalcet, dose adjustment may be necessary for drugs that demonstrate a narrow therapeutic index and are metabolized by CYP2D6.", "entity": "Nausea", "aliases": "Nausea", "definition": "An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.\n    ", "id": "MESH:D009325"}
{"mention": "headache", "mention_text": "OBJECTIVE: In vitro work has demonstrated that cinacalcet is a strong inhibitor of cytochrome P450 isoenzyme (CYP) 2D6. The purpose of this study was to evaluate the effect of cinacalcet on CYP2D6 activity, using desipramine as a probe substrate, in healthy subjects. METHODS: Seventeen subjects who were genotyped as CYP2D6 extensive metabolizers were enrolled in this randomized, open-label, crossover study to receive a single oral dose of desipramine (50 mg) on two separate occasions, once alone and once after multiple doses of cinacalcet (90 mg for 7 days). Blood samples were obtained predose and up to 72 h postdose. RESULTS: Fourteen subjects completed both treatment arms. Relative to desipramine alone, mean AUC and C(max) of desipramine increased 3.6- and 1.8-fold when coadministered with cinacalcet. The t (1/2,z) of desipramine was longer when desipramine was coadministered with cinacalcet (21.0 versus 43.3 hs). The t (max) was similar between the regimens. Fewer subjects reported adverse events following treatment with desipramine alone than when receiving desipramine with cinacalcet (33 versus 86%), the most frequent of which (nausea and headache) have been reported for patients treated with either desipramine or cinacalcet. CONCLUSION: This study demonstrates that cinacalcet is a strong inhibitor of CYP2D6. These data suggest that during concomitant treatment with cinacalcet, dose adjustment may be necessary for drugs that demonstrate a narrow therapeutic index and are metabolized by CYP2D6.", "entity": "Headache", "aliases": "Bilateral Headache Headaches Cephalalgia Cephalalgias Cephalgia Cephalgias Cephalodynia Cephalodynias Cranial Pain Pains Generalized Head Ocular Orthostatic Periorbital Retro-Ocular Sharp Throbbing Unilateral Vertex Hemicrania Retro", "definition": "The symptom of PAIN in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of HEADACHE DISORDERS.\n    ", "id": "MESH:D006261"}
{"mention": "L-DOPA", "mention_text": "Proteomic analysis of striatal proteins in the rat model of L-DOPA-induced dyskinesia.", "entity": "Levodopa", "aliases": "3 Hydroxy L tyrosine 3-Hydroxy-L-tyrosine Dopaflex Dopar 3,4 Dihydroxyphenylalanine Dopa L-3,4-Dihydroxyphenylalanine L-Dopa Larodopa Levodopa Levopa Medphano Brand of Roberts Roche", "definition": "The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.\n    ", "id": "MESH:D007980"}
{"mention": "dyskinesia", "mention_text": "Proteomic analysis of striatal proteins in the rat model of L-DOPA-induced dyskinesia.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "L-DOPA", "mention_text": "L-DOPA-induced dyskinesia (LID) is among the motor complications that arise in Parkinson's disease (PD) patients after a prolonged treatment with L-DOPA. To this day, transcriptome analysis has been performed in a rat model of LID [Neurobiol. Dis., 17 (2004), 219] but information regarding the proteome is still lacking. In the present study, we investigated the changes occurring at the protein level in striatal samples obtained from the unilaterally 6-hydroxydopamine-lesion rat model of PD treated with saline, L-DOPA or bromocriptine using two-dimensional difference gel electrophoresis and mass spectrometry (MS). Rats treated with L-DOPA were allocated to two groups based on the presence or absence of LID. Among the 2000 spots compared for statistical difference, 67 spots were significantly changed in abundance and identified using matrix-assisted laser desorption/ionization time-of-flight MS, atmospheric pressure matrix-assisted laser desorption/ionization and HPLC coupled tandem MS (LC/MS/MS). Out of these 67 proteins, LID significantly changed the expression level of five proteins: alphabeta-crystalin, gamma-enolase, guanidoacetate methyltransferase, vinculin, and proteasome alpha-2 subunit. Complementary techniques such as western immunoblotting and immunohistochemistry were performed to investigate the validity of the data obtained using the proteomic approach. In conclusion, this study provides new insights into the protein changes occurring in LID.", "entity": "Levodopa", "aliases": "3 Hydroxy L tyrosine 3-Hydroxy-L-tyrosine Dopaflex Dopar 3,4 Dihydroxyphenylalanine Dopa L-3,4-Dihydroxyphenylalanine L-Dopa Larodopa Levodopa Levopa Medphano Brand of Roberts Roche", "definition": "The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.\n    ", "id": "MESH:D007980"}
{"mention": "dyskinesia", "mention_text": "L-DOPA-induced dyskinesia (LID) is among the motor complications that arise in Parkinson's disease (PD) patients after a prolonged treatment with L-DOPA. To this day, transcriptome analysis has been performed in a rat model of LID [Neurobiol. Dis., 17 (2004), 219] but information regarding the proteome is still lacking. In the present study, we investigated the changes occurring at the protein level in striatal samples obtained from the unilaterally 6-hydroxydopamine-lesion rat model of PD treated with saline, L-DOPA or bromocriptine using two-dimensional difference gel electrophoresis and mass spectrometry (MS). Rats treated with L-DOPA were allocated to two groups based on the presence or absence of LID. Among the 2000 spots compared for statistical difference, 67 spots were significantly changed in abundance and identified using matrix-assisted laser desorption/ionization time-of-flight MS, atmospheric pressure matrix-assisted laser desorption/ionization and HPLC coupled tandem MS (LC/MS/MS). Out of these 67 proteins, LID significantly changed the expression level of five proteins: alphabeta-crystalin, gamma-enolase, guanidoacetate methyltransferase, vinculin, and proteasome alpha-2 subunit. Complementary techniques such as western immunoblotting and immunohistochemistry were performed to investigate the validity of the data obtained using the proteomic approach. In conclusion, this study provides new insights into the protein changes occurring in LID.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "LID", "mention_text": "L-DOPA-induced dyskinesia (LID) is among the motor complications that arise in Parkinson's disease (PD) patients after a prolonged treatment with L-DOPA. To this day, transcriptome analysis has been performed in a rat model of LID [Neurobiol. Dis., 17 (2004), 219] but information regarding the proteome is still lacking. In the present study, we investigated the changes occurring at the protein level in striatal samples obtained from the unilaterally 6-hydroxydopamine-lesion rat model of PD treated with saline, L-DOPA or bromocriptine using two-dimensional difference gel electrophoresis and mass spectrometry (MS). Rats treated with L-DOPA were allocated to two groups based on the presence or absence of LID. Among the 2000 spots compared for statistical difference, 67 spots were significantly changed in abundance and identified using matrix-assisted laser desorption/ionization time-of-flight MS, atmospheric pressure matrix-assisted laser desorption/ionization and HPLC coupled tandem MS (LC/MS/MS). Out of these 67 proteins, LID significantly changed the expression level of five proteins: alphabeta-crystalin, gamma-enolase, guanidoacetate methyltransferase, vinculin, and proteasome alpha-2 subunit. Complementary techniques such as western immunoblotting and immunohistochemistry were performed to investigate the validity of the data obtained using the proteomic approach. In conclusion, this study provides new insights into the protein changes occurring in LID.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "Parkinson's disease", "mention_text": "L-DOPA-induced dyskinesia (LID) is among the motor complications that arise in Parkinson's disease (PD) patients after a prolonged treatment with L-DOPA. To this day, transcriptome analysis has been performed in a rat model of LID [Neurobiol. Dis., 17 (2004), 219] but information regarding the proteome is still lacking. In the present study, we investigated the changes occurring at the protein level in striatal samples obtained from the unilaterally 6-hydroxydopamine-lesion rat model of PD treated with saline, L-DOPA or bromocriptine using two-dimensional difference gel electrophoresis and mass spectrometry (MS). Rats treated with L-DOPA were allocated to two groups based on the presence or absence of LID. Among the 2000 spots compared for statistical difference, 67 spots were significantly changed in abundance and identified using matrix-assisted laser desorption/ionization time-of-flight MS, atmospheric pressure matrix-assisted laser desorption/ionization and HPLC coupled tandem MS (LC/MS/MS). Out of these 67 proteins, LID significantly changed the expression level of five proteins: alphabeta-crystalin, gamma-enolase, guanidoacetate methyltransferase, vinculin, and proteasome alpha-2 subunit. Complementary techniques such as western immunoblotting and immunohistochemistry were performed to investigate the validity of the data obtained using the proteomic approach. In conclusion, this study provides new insights into the protein changes occurring in LID.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "PD", "mention_text": "L-DOPA-induced dyskinesia (LID) is among the motor complications that arise in Parkinson's disease (PD) patients after a prolonged treatment with L-DOPA. To this day, transcriptome analysis has been performed in a rat model of LID [Neurobiol. Dis., 17 (2004), 219] but information regarding the proteome is still lacking. In the present study, we investigated the changes occurring at the protein level in striatal samples obtained from the unilaterally 6-hydroxydopamine-lesion rat model of PD treated with saline, L-DOPA or bromocriptine using two-dimensional difference gel electrophoresis and mass spectrometry (MS). Rats treated with L-DOPA were allocated to two groups based on the presence or absence of LID. Among the 2000 spots compared for statistical difference, 67 spots were significantly changed in abundance and identified using matrix-assisted laser desorption/ionization time-of-flight MS, atmospheric pressure matrix-assisted laser desorption/ionization and HPLC coupled tandem MS (LC/MS/MS). Out of these 67 proteins, LID significantly changed the expression level of five proteins: alphabeta-crystalin, gamma-enolase, guanidoacetate methyltransferase, vinculin, and proteasome alpha-2 subunit. Complementary techniques such as western immunoblotting and immunohistochemistry were performed to investigate the validity of the data obtained using the proteomic approach. In conclusion, this study provides new insights into the protein changes occurring in LID.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "6-hydroxydopamine", "mention_text": "L-DOPA-induced dyskinesia (LID) is among the motor complications that arise in Parkinson's disease (PD) patients after a prolonged treatment with L-DOPA. To this day, transcriptome analysis has been performed in a rat model of LID [Neurobiol. Dis., 17 (2004), 219] but information regarding the proteome is still lacking. In the present study, we investigated the changes occurring at the protein level in striatal samples obtained from the unilaterally 6-hydroxydopamine-lesion rat model of PD treated with saline, L-DOPA or bromocriptine using two-dimensional difference gel electrophoresis and mass spectrometry (MS). Rats treated with L-DOPA were allocated to two groups based on the presence or absence of LID. Among the 2000 spots compared for statistical difference, 67 spots were significantly changed in abundance and identified using matrix-assisted laser desorption/ionization time-of-flight MS, atmospheric pressure matrix-assisted laser desorption/ionization and HPLC coupled tandem MS (LC/MS/MS). Out of these 67 proteins, LID significantly changed the expression level of five proteins: alphabeta-crystalin, gamma-enolase, guanidoacetate methyltransferase, vinculin, and proteasome alpha-2 subunit. Complementary techniques such as western immunoblotting and immunohistochemistry were performed to investigate the validity of the data obtained using the proteomic approach. In conclusion, this study provides new insights into the protein changes occurring in LID.", "entity": "Oxidopamine", "aliases": "6 Hydroxydopamine 6-Hydroxydopamine 6-OHDA Hydrobromide Oxidopamine Hydrochloride", "definition": "A neurotransmitter analogue that depletes noradrenergic stores in nerve endings and induces a reduction of dopamine levels in the brain. Its mechanism of action is related to the production of cytolytic free-radicals.\n    ", "id": "MESH:D016627"}
{"mention": "bromocriptine", "mention_text": "L-DOPA-induced dyskinesia (LID) is among the motor complications that arise in Parkinson's disease (PD) patients after a prolonged treatment with L-DOPA. To this day, transcriptome analysis has been performed in a rat model of LID [Neurobiol. Dis., 17 (2004), 219] but information regarding the proteome is still lacking. In the present study, we investigated the changes occurring at the protein level in striatal samples obtained from the unilaterally 6-hydroxydopamine-lesion rat model of PD treated with saline, L-DOPA or bromocriptine using two-dimensional difference gel electrophoresis and mass spectrometry (MS). Rats treated with L-DOPA were allocated to two groups based on the presence or absence of LID. Among the 2000 spots compared for statistical difference, 67 spots were significantly changed in abundance and identified using matrix-assisted laser desorption/ionization time-of-flight MS, atmospheric pressure matrix-assisted laser desorption/ionization and HPLC coupled tandem MS (LC/MS/MS). Out of these 67 proteins, LID significantly changed the expression level of five proteins: alphabeta-crystalin, gamma-enolase, guanidoacetate methyltransferase, vinculin, and proteasome alpha-2 subunit. Complementary techniques such as western immunoblotting and immunohistochemistry were performed to investigate the validity of the data obtained using the proteomic approach. In conclusion, this study provides new insights into the protein changes occurring in LID.", "entity": "Bromocriptine", "aliases": "2 Bromo alpha ergocryptine ergokryptine Bromoergocryptine Mesylate Methanesulfonate Bromoergokryptine 2-Bromo-alpha-ergocryptine 2-Bromo-alpha-ergokryptine 2-Bromoergocryptine 2-Bromoergokryptine Bromocriptin Bromocriptine Bromocryptin CB 154 CB-154 CB154 Parlodel", "definition": "A semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion.\n    ", "id": "MESH:D001971"}
{"mention": "allergic reactions", "mention_text": "Pseudo-allergic reactions to corticosteroids: diagnosis and alternatives.", "entity": "Drug Hypersensitivity", "aliases": "Allergies Drug Allergy Hypersensitivities Hypersensitivity", "definition": "Immunologically mediated adverse reactions to medicinal substances used legally or illegally.\n    ", "id": "MESH:D004342"}
{"mention": "corticosteroids", "mention_text": "Pseudo-allergic reactions to corticosteroids: diagnosis and alternatives.", "entity": "Adrenal Cortex Hormones", "aliases": "Adrenal Cortex Hormones Corticoids Corticosteroids", "definition": "", "id": "MESH:D000305"}
{"mention": "paramethasone", "mention_text": "Two patients treated with parenteral paramethasone (Triniol) and dexamethasone (Sedionbel) are described. A few minutes after administration of the drugs, they presented urticaria (patients 1 and 2) and conjunctivitis (patient 1). The purpose of our study was to determine the cause of the patients' reactions, the immunological mechanisms involved and whether these patients would be able to tolerate any kind of corticoid. Clinical examinations and skin, oral and parenteral challenges with different corticosteroids and ELISA tests were performed. In the two patients, skin and ELISA tests with paramethasone were negative, as was the prick test with each of its excipients. A single-blind parenteral challenge with Triniol was positive in both patients after the administration of 1 ml of the drug, and negative with its excipients. We also carried out oral and parenteral challenges with other corticosteroids and found intolerance to some of them. These results suggest that paramethasone caused pseudoallergic reactions in our patients. Corticosteroids different from paramethasone also produced hypersensitivity reactions in these patients; however, a few of them were tolerated. The basic mechanisms of those reactions are not yet fully understood. To our knowledge, this is the first report of a pseudo-allergy caused by paramethasone.", "entity": "Paramethasone", "aliases": "Paramethasone", "definition": "A glucocorticoid with the general properties of corticosteroids. It has been used by mouth in the treatment of all conditions in which corticosteroid therapy is indicated except adrenal-deficiency states for which its lack of sodium-retaining properties makes it less suitable than HYDROCORTISONE with supplementary FLUDROCORTISONE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p737)\n    ", "id": "MESH:D010248"}
{"mention": "dexamethasone", "mention_text": "Two patients treated with parenteral paramethasone (Triniol) and dexamethasone (Sedionbel) are described. A few minutes after administration of the drugs, they presented urticaria (patients 1 and 2) and conjunctivitis (patient 1). The purpose of our study was to determine the cause of the patients' reactions, the immunological mechanisms involved and whether these patients would be able to tolerate any kind of corticoid. Clinical examinations and skin, oral and parenteral challenges with different corticosteroids and ELISA tests were performed. In the two patients, skin and ELISA tests with paramethasone were negative, as was the prick test with each of its excipients. A single-blind parenteral challenge with Triniol was positive in both patients after the administration of 1 ml of the drug, and negative with its excipients. We also carried out oral and parenteral challenges with other corticosteroids and found intolerance to some of them. These results suggest that paramethasone caused pseudoallergic reactions in our patients. Corticosteroids different from paramethasone also produced hypersensitivity reactions in these patients; however, a few of them were tolerated. The basic mechanisms of those reactions are not yet fully understood. To our knowledge, this is the first report of a pseudo-allergy caused by paramethasone.", "entity": "Dexamethasone", "aliases": "Alcon Brand of Dexamethasone Decaject L.A. Decaject-L.A. Decameth Decaspray Dexasone Dexpak ECR Foy Hexadecadrol Hexadrol ICN Maxidex Merck Merz 1 2 Methylfluorprednisolone Millicorten Oradexon", "definition": "An anti-inflammatory 9-fluoro-glucocorticoid.\n    ", "id": "MESH:D003907"}
{"mention": "urticaria", "mention_text": "Two patients treated with parenteral paramethasone (Triniol) and dexamethasone (Sedionbel) are described. A few minutes after administration of the drugs, they presented urticaria (patients 1 and 2) and conjunctivitis (patient 1). The purpose of our study was to determine the cause of the patients' reactions, the immunological mechanisms involved and whether these patients would be able to tolerate any kind of corticoid. Clinical examinations and skin, oral and parenteral challenges with different corticosteroids and ELISA tests were performed. In the two patients, skin and ELISA tests with paramethasone were negative, as was the prick test with each of its excipients. A single-blind parenteral challenge with Triniol was positive in both patients after the administration of 1 ml of the drug, and negative with its excipients. We also carried out oral and parenteral challenges with other corticosteroids and found intolerance to some of them. These results suggest that paramethasone caused pseudoallergic reactions in our patients. Corticosteroids different from paramethasone also produced hypersensitivity reactions in these patients; however, a few of them were tolerated. The basic mechanisms of those reactions are not yet fully understood. To our knowledge, this is the first report of a pseudo-allergy caused by paramethasone.", "entity": "Urticaria", "aliases": "Hives Urticaria Urticarias", "definition": "A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress.\n    ", "id": "MESH:D014581"}
{"mention": "conjunctivitis", "mention_text": "Two patients treated with parenteral paramethasone (Triniol) and dexamethasone (Sedionbel) are described. A few minutes after administration of the drugs, they presented urticaria (patients 1 and 2) and conjunctivitis (patient 1). The purpose of our study was to determine the cause of the patients' reactions, the immunological mechanisms involved and whether these patients would be able to tolerate any kind of corticoid. Clinical examinations and skin, oral and parenteral challenges with different corticosteroids and ELISA tests were performed. In the two patients, skin and ELISA tests with paramethasone were negative, as was the prick test with each of its excipients. A single-blind parenteral challenge with Triniol was positive in both patients after the administration of 1 ml of the drug, and negative with its excipients. We also carried out oral and parenteral challenges with other corticosteroids and found intolerance to some of them. These results suggest that paramethasone caused pseudoallergic reactions in our patients. Corticosteroids different from paramethasone also produced hypersensitivity reactions in these patients; however, a few of them were tolerated. The basic mechanisms of those reactions are not yet fully understood. To our knowledge, this is the first report of a pseudo-allergy caused by paramethasone.", "entity": "Conjunctivitis", "aliases": "Conjunctivitides Conjunctivitis", "definition": "", "id": "MESH:D003231"}
{"mention": "corticosteroids", "mention_text": "Two patients treated with parenteral paramethasone (Triniol) and dexamethasone (Sedionbel) are described. A few minutes after administration of the drugs, they presented urticaria (patients 1 and 2) and conjunctivitis (patient 1). The purpose of our study was to determine the cause of the patients' reactions, the immunological mechanisms involved and whether these patients would be able to tolerate any kind of corticoid. Clinical examinations and skin, oral and parenteral challenges with different corticosteroids and ELISA tests were performed. In the two patients, skin and ELISA tests with paramethasone were negative, as was the prick test with each of its excipients. A single-blind parenteral challenge with Triniol was positive in both patients after the administration of 1 ml of the drug, and negative with its excipients. We also carried out oral and parenteral challenges with other corticosteroids and found intolerance to some of them. These results suggest that paramethasone caused pseudoallergic reactions in our patients. Corticosteroids different from paramethasone also produced hypersensitivity reactions in these patients; however, a few of them were tolerated. The basic mechanisms of those reactions are not yet fully understood. To our knowledge, this is the first report of a pseudo-allergy caused by paramethasone.", "entity": "Adrenal Cortex Hormones", "aliases": "Adrenal Cortex Hormones Corticoids Corticosteroids", "definition": "", "id": "MESH:D000305"}
{"mention": "hypersensitivity", "mention_text": "Two patients treated with parenteral paramethasone (Triniol) and dexamethasone (Sedionbel) are described. A few minutes after administration of the drugs, they presented urticaria (patients 1 and 2) and conjunctivitis (patient 1). The purpose of our study was to determine the cause of the patients' reactions, the immunological mechanisms involved and whether these patients would be able to tolerate any kind of corticoid. Clinical examinations and skin, oral and parenteral challenges with different corticosteroids and ELISA tests were performed. In the two patients, skin and ELISA tests with paramethasone were negative, as was the prick test with each of its excipients. A single-blind parenteral challenge with Triniol was positive in both patients after the administration of 1 ml of the drug, and negative with its excipients. We also carried out oral and parenteral challenges with other corticosteroids and found intolerance to some of them. These results suggest that paramethasone caused pseudoallergic reactions in our patients. Corticosteroids different from paramethasone also produced hypersensitivity reactions in these patients; however, a few of them were tolerated. The basic mechanisms of those reactions are not yet fully understood. To our knowledge, this is the first report of a pseudo-allergy caused by paramethasone.", "entity": "Drug Hypersensitivity", "aliases": "Allergies Drug Allergy Hypersensitivities Hypersensitivity", "definition": "Immunologically mediated adverse reactions to medicinal substances used legally or illegally.\n    ", "id": "MESH:D004342"}
{"mention": "allergy", "mention_text": "Two patients treated with parenteral paramethasone (Triniol) and dexamethasone (Sedionbel) are described. A few minutes after administration of the drugs, they presented urticaria (patients 1 and 2) and conjunctivitis (patient 1). The purpose of our study was to determine the cause of the patients' reactions, the immunological mechanisms involved and whether these patients would be able to tolerate any kind of corticoid. Clinical examinations and skin, oral and parenteral challenges with different corticosteroids and ELISA tests were performed. In the two patients, skin and ELISA tests with paramethasone were negative, as was the prick test with each of its excipients. A single-blind parenteral challenge with Triniol was positive in both patients after the administration of 1 ml of the drug, and negative with its excipients. We also carried out oral and parenteral challenges with other corticosteroids and found intolerance to some of them. These results suggest that paramethasone caused pseudoallergic reactions in our patients. Corticosteroids different from paramethasone also produced hypersensitivity reactions in these patients; however, a few of them were tolerated. The basic mechanisms of those reactions are not yet fully understood. To our knowledge, this is the first report of a pseudo-allergy caused by paramethasone.", "entity": "Drug Hypersensitivity", "aliases": "Allergies Drug Allergy Hypersensitivities Hypersensitivity", "definition": "Immunologically mediated adverse reactions to medicinal substances used legally or illegally.\n    ", "id": "MESH:D004342"}
{"mention": "Valproic acid", "mention_text": "Valproic acid induced encephalopathy--19 new cases in Germany from 1994 to 2003--a side effect associated to VPA-therapy not only in young children.", "entity": "Valproic Acid", "aliases": "2 Propylpentanoic Acid 2-Propylpentanoic Acetate Dipropyl Propylisopropylacetic Valproic Calcium Valproate Convulsofin Depakene Depakine Depakote Divalproex Sodium Ergenyl Magnesium Semisodium Salt (2:1) Vupral", "definition": "A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.\n    ", "id": "MESH:D014635"}
{"mention": "encephalopathy", "mention_text": "Valproic acid induced encephalopathy--19 new cases in Germany from 1994 to 2003--a side effect associated to VPA-therapy not only in young children.", "entity": "Brain Diseases", "aliases": "Brain Disease Diseases Disorder Disorders CNS Intracranial Central Nervous System Encephalon", "definition": "Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.\n    ", "id": "MESH:D001927"}
{"mention": "VPA", "mention_text": "Valproic acid induced encephalopathy--19 new cases in Germany from 1994 to 2003--a side effect associated to VPA-therapy not only in young children.", "entity": "Valproic Acid", "aliases": "2 Propylpentanoic Acid 2-Propylpentanoic Acetate Dipropyl Propylisopropylacetic Valproic Calcium Valproate Convulsofin Depakene Depakine Depakote Divalproex Sodium Ergenyl Magnesium Semisodium Salt (2:1) Vupral", "definition": "A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.\n    ", "id": "MESH:D014635"}
{"mention": "Valproic acid", "mention_text": "Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well-tolerated. Rare serious complications may occur in some patients, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity and VPA-induced encephalopathy. The typical signs of VPA-induced encephalopathy are impaired consciousness, sometimes marked EEG background slowing, increased seizure frequency, with or without hyperammonemia. There is still no proof of causative effect of VPA in patients with encephalopathy, but only of an association with an assumed causal relation. We report 19 patients with VPA-associated encephalopathy in Germany from the years 1994 to 2003, none of whom had been published previously.", "entity": "Valproic Acid", "aliases": "2 Propylpentanoic Acid 2-Propylpentanoic Acetate Dipropyl Propylisopropylacetic Valproic Calcium Valproate Convulsofin Depakene Depakine Depakote Divalproex Sodium Ergenyl Magnesium Semisodium Salt (2:1) Vupral", "definition": "A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.\n    ", "id": "MESH:D014635"}
{"mention": "VPA", "mention_text": "Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well-tolerated. Rare serious complications may occur in some patients, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity and VPA-induced encephalopathy. The typical signs of VPA-induced encephalopathy are impaired consciousness, sometimes marked EEG background slowing, increased seizure frequency, with or without hyperammonemia. There is still no proof of causative effect of VPA in patients with encephalopathy, but only of an association with an assumed causal relation. We report 19 patients with VPA-associated encephalopathy in Germany from the years 1994 to 2003, none of whom had been published previously.", "entity": "Valproic Acid", "aliases": "2 Propylpentanoic Acid 2-Propylpentanoic Acetate Dipropyl Propylisopropylacetic Valproic Calcium Valproate Convulsofin Depakene Depakine Depakote Divalproex Sodium Ergenyl Magnesium Semisodium Salt (2:1) Vupral", "definition": "A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.\n    ", "id": "MESH:D014635"}
{"mention": "pancreatitis", "mention_text": "Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well-tolerated. Rare serious complications may occur in some patients, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity and VPA-induced encephalopathy. The typical signs of VPA-induced encephalopathy are impaired consciousness, sometimes marked EEG background slowing, increased seizure frequency, with or without hyperammonemia. There is still no proof of causative effect of VPA in patients with encephalopathy, but only of an association with an assumed causal relation. We report 19 patients with VPA-associated encephalopathy in Germany from the years 1994 to 2003, none of whom had been published previously.", "entity": "Pancreatitis", "aliases": "Pancreatitides Pancreatitis", "definition": "INFLAMMATION of the PANCREAS. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of CHRONIC PANCREATITIS (International Symposium on Acute Pancreatitis, Atlanta, 1992). The two most common forms of acute pancreatitis are ALCOHOLIC PANCREATITIS and gallstone pancreatitis.\n    ", "id": "MESH:D010195"}
{"mention": "bone marrow suppression", "mention_text": "Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well-tolerated. Rare serious complications may occur in some patients, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity and VPA-induced encephalopathy. The typical signs of VPA-induced encephalopathy are impaired consciousness, sometimes marked EEG background slowing, increased seizure frequency, with or without hyperammonemia. There is still no proof of causative effect of VPA in patients with encephalopathy, but only of an association with an assumed causal relation. We report 19 patients with VPA-associated encephalopathy in Germany from the years 1994 to 2003, none of whom had been published previously.", "entity": "Bone Marrow Diseases", "aliases": "Bone Marrow Disease Diseases", "definition": "", "id": "MESH:D001855"}
{"mention": "hepatotoxicity", "mention_text": "Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well-tolerated. Rare serious complications may occur in some patients, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity and VPA-induced encephalopathy. The typical signs of VPA-induced encephalopathy are impaired consciousness, sometimes marked EEG background slowing, increased seizure frequency, with or without hyperammonemia. There is still no proof of causative effect of VPA in patients with encephalopathy, but only of an association with an assumed causal relation. We report 19 patients with VPA-associated encephalopathy in Germany from the years 1994 to 2003, none of whom had been published previously.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "encephalopathy", "mention_text": "Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well-tolerated. Rare serious complications may occur in some patients, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity and VPA-induced encephalopathy. The typical signs of VPA-induced encephalopathy are impaired consciousness, sometimes marked EEG background slowing, increased seizure frequency, with or without hyperammonemia. There is still no proof of causative effect of VPA in patients with encephalopathy, but only of an association with an assumed causal relation. We report 19 patients with VPA-associated encephalopathy in Germany from the years 1994 to 2003, none of whom had been published previously.", "entity": "Brain Diseases", "aliases": "Brain Disease Diseases Disorder Disorders CNS Intracranial Central Nervous System Encephalon", "definition": "Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.\n    ", "id": "MESH:D001927"}
{"mention": "impaired consciousness", "mention_text": "Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well-tolerated. Rare serious complications may occur in some patients, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity and VPA-induced encephalopathy. The typical signs of VPA-induced encephalopathy are impaired consciousness, sometimes marked EEG background slowing, increased seizure frequency, with or without hyperammonemia. There is still no proof of causative effect of VPA in patients with encephalopathy, but only of an association with an assumed causal relation. We report 19 patients with VPA-associated encephalopathy in Germany from the years 1994 to 2003, none of whom had been published previously.", "entity": "Consciousness Disorders", "aliases": "Altered Level of Consciousness Disorder Disorders Depressed Semiconsciousness", "definition": "Organic mental disorders in which there is impairment of the ability to maintain awareness of self and environment and to respond to environmental stimuli. Dysfunction of the cerebral hemispheres or brain stem RETICULAR FORMATION may result in this condition.\n    ", "id": "MESH:D003244"}
{"mention": "seizure", "mention_text": "Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well-tolerated. Rare serious complications may occur in some patients, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity and VPA-induced encephalopathy. The typical signs of VPA-induced encephalopathy are impaired consciousness, sometimes marked EEG background slowing, increased seizure frequency, with or without hyperammonemia. There is still no proof of causative effect of VPA in patients with encephalopathy, but only of an association with an assumed causal relation. We report 19 patients with VPA-associated encephalopathy in Germany from the years 1994 to 2003, none of whom had been published previously.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "hyperammonemia", "mention_text": "Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well-tolerated. Rare serious complications may occur in some patients, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity and VPA-induced encephalopathy. The typical signs of VPA-induced encephalopathy are impaired consciousness, sometimes marked EEG background slowing, increased seizure frequency, with or without hyperammonemia. There is still no proof of causative effect of VPA in patients with encephalopathy, but only of an association with an assumed causal relation. We report 19 patients with VPA-associated encephalopathy in Germany from the years 1994 to 2003, none of whom had been published previously.", "entity": "Hyperammonemia", "aliases": "Hyperammonemia", "definition": "Elevated level of AMMONIA in the blood. It is a sign of defective CATABOLISM of AMINO ACIDS or ammonia to UREA.\n    ", "id": "MESH:D022124"}
{"mention": "Haemolytic-uraemic syndrome", "mention_text": "Haemolytic-uraemic syndrome after treatment with metronidazole.", "entity": "Hemolytic-Uremic Syndrome", "aliases": "Gasser Syndrome Gasser's Gassers Hemolytic Uremic Hemolytic-Uremic", "definition": "A syndrome that is associated with microvascular diseases of the KIDNEY, such as RENAL CORTICAL NECROSIS. It is characterized by hemolytic anemia (ANEMIA, HEMOLYTIC); THROMBOCYTOPENIA; and ACUTE RENAL FAILURE.\n    ", "id": "MESH:D006463"}
{"mention": "metronidazole", "mention_text": "Haemolytic-uraemic syndrome after treatment with metronidazole.", "entity": "Metronidazole", "aliases": "2 Methyl 5 nitroimidazole 1 ethanol 2-Methyl-5-nitroimidazole-1-ethanol Bayer 5360 Clont Danizol Flagyl Gineflavir Hydrochloride Metronidazole Metric MetroGel Metrodzhil Metrogyl Monohydrochloride Phosphate Phosphoester Satric Trichazol Trichopol Trivazol Vagilen", "definition": "A nitroimidazole used to treat AMEBIASIS; VAGINITIS; TRICHOMONAS INFECTIONS; GIARDIASIS; ANAEROBIC BACTERIA; and TREPONEMAL INFECTIONS. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed).\n    ", "id": "MESH:D008795"}
{"mention": "haemolytic-uraemic syndrome", "mention_text": "This paper describes the clinical features of six children who developed the haemolytic-uraemic syndrome after treatment with metronidazole. These children were older and were more likely to have undergone recent bowel surgery than are other children with this condition. While the involvement of metronidazole in the aetiology of the haemolytic-uraemic syndrome is not established firmly, the action of this drug in sensitizing tissues to oxidation injury and the reported evidence of oxidation changes in the haemolytic-uraemic syndrome suggest a possible link between metronidazole treatment and some cases of the haemolytic-uraemic syndrome.", "entity": "Hemolytic-Uremic Syndrome", "aliases": "Gasser Syndrome Gasser's Gassers Hemolytic Uremic Hemolytic-Uremic", "definition": "A syndrome that is associated with microvascular diseases of the KIDNEY, such as RENAL CORTICAL NECROSIS. It is characterized by hemolytic anemia (ANEMIA, HEMOLYTIC); THROMBOCYTOPENIA; and ACUTE RENAL FAILURE.\n    ", "id": "MESH:D006463"}
{"mention": "metronidazole", "mention_text": "This paper describes the clinical features of six children who developed the haemolytic-uraemic syndrome after treatment with metronidazole. These children were older and were more likely to have undergone recent bowel surgery than are other children with this condition. While the involvement of metronidazole in the aetiology of the haemolytic-uraemic syndrome is not established firmly, the action of this drug in sensitizing tissues to oxidation injury and the reported evidence of oxidation changes in the haemolytic-uraemic syndrome suggest a possible link between metronidazole treatment and some cases of the haemolytic-uraemic syndrome.", "entity": "Metronidazole", "aliases": "2 Methyl 5 nitroimidazole 1 ethanol 2-Methyl-5-nitroimidazole-1-ethanol Bayer 5360 Clont Danizol Flagyl Gineflavir Hydrochloride Metronidazole Metric MetroGel Metrodzhil Metrogyl Monohydrochloride Phosphate Phosphoester Satric Trichazol Trichopol Trivazol Vagilen", "definition": "A nitroimidazole used to treat AMEBIASIS; VAGINITIS; TRICHOMONAS INFECTIONS; GIARDIASIS; ANAEROBIC BACTERIA; and TREPONEMAL INFECTIONS. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed).\n    ", "id": "MESH:D008795"}
{"mention": "sensorineural hearing loss", "mention_text": "Risk factors of sensorineural hearing loss in preterm infants.", "entity": "Hearing Loss, Sensorineural", "aliases": "Cochlear Hearing Loss Sensorineural", "definition": "Hearing loss resulting from damage to the COCHLEA and the sensorineural elements which lie internally beyond the oval and round windows. These elements include the AUDITORY NERVE and its connections in the BRAINSTEM.\n    ", "id": "MESH:D006319"}
{"mention": "sensorineural hearing loss", "mention_text": "Among 547 preterm infants of < or = 34 weeks gestation born between 1987 and 1991, 8 children (1.46%) developed severe progressive and bilateral sensorineural hearing loss. Perinatal risk factors of infants with hearing loss were compared with those of two control groups matched for gestation and birth weight and for perinatal complications. Our observations demonstrated an association of hearing loss with a higher incidence of perinatal complications. Ototoxicity appeared closely related to a prolonged administration and higher total dose of ototoxic drugs, particularly aminoglycosides and furosemide. Finally, we strongly recommend to prospectively and regularly perform audiologic assessment in sick preterm children as hearing loss is of delayed onset and in most cases bilateral and severe.", "entity": "Hearing Loss, Sensorineural", "aliases": "Cochlear Hearing Loss Sensorineural", "definition": "Hearing loss resulting from damage to the COCHLEA and the sensorineural elements which lie internally beyond the oval and round windows. These elements include the AUDITORY NERVE and its connections in the BRAINSTEM.\n    ", "id": "MESH:D006319"}
{"mention": "hearing loss", "mention_text": "Among 547 preterm infants of < or = 34 weeks gestation born between 1987 and 1991, 8 children (1.46%) developed severe progressive and bilateral sensorineural hearing loss. Perinatal risk factors of infants with hearing loss were compared with those of two control groups matched for gestation and birth weight and for perinatal complications. Our observations demonstrated an association of hearing loss with a higher incidence of perinatal complications. Ototoxicity appeared closely related to a prolonged administration and higher total dose of ototoxic drugs, particularly aminoglycosides and furosemide. Finally, we strongly recommend to prospectively and regularly perform audiologic assessment in sick preterm children as hearing loss is of delayed onset and in most cases bilateral and severe.", "entity": "Hearing Loss", "aliases": "Hearing Impairment Loss Hypoacuses Hypoacusis", "definition": "A general term for the complete or partial loss of the ability to hear from one or both ears.\n    ", "id": "MESH:D034381"}
{"mention": "Ototoxicity", "mention_text": "Among 547 preterm infants of < or = 34 weeks gestation born between 1987 and 1991, 8 children (1.46%) developed severe progressive and bilateral sensorineural hearing loss. Perinatal risk factors of infants with hearing loss were compared with those of two control groups matched for gestation and birth weight and for perinatal complications. Our observations demonstrated an association of hearing loss with a higher incidence of perinatal complications. Ototoxicity appeared closely related to a prolonged administration and higher total dose of ototoxic drugs, particularly aminoglycosides and furosemide. Finally, we strongly recommend to prospectively and regularly perform audiologic assessment in sick preterm children as hearing loss is of delayed onset and in most cases bilateral and severe.", "entity": "Hearing Disorders", "aliases": "Distorted Hearing Dysacusis Disorder Disorders Paracousis Paracusis", "definition": "Conditions that impair the transmission of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways.\n    ", "id": "MESH:D006311"}
{"mention": "ototoxic", "mention_text": "Among 547 preterm infants of < or = 34 weeks gestation born between 1987 and 1991, 8 children (1.46%) developed severe progressive and bilateral sensorineural hearing loss. Perinatal risk factors of infants with hearing loss were compared with those of two control groups matched for gestation and birth weight and for perinatal complications. Our observations demonstrated an association of hearing loss with a higher incidence of perinatal complications. Ototoxicity appeared closely related to a prolonged administration and higher total dose of ototoxic drugs, particularly aminoglycosides and furosemide. Finally, we strongly recommend to prospectively and regularly perform audiologic assessment in sick preterm children as hearing loss is of delayed onset and in most cases bilateral and severe.", "entity": "Hearing Disorders", "aliases": "Distorted Hearing Dysacusis Disorder Disorders Paracousis Paracusis", "definition": "Conditions that impair the transmission of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways.\n    ", "id": "MESH:D006311"}
{"mention": "aminoglycosides", "mention_text": "Among 547 preterm infants of < or = 34 weeks gestation born between 1987 and 1991, 8 children (1.46%) developed severe progressive and bilateral sensorineural hearing loss. Perinatal risk factors of infants with hearing loss were compared with those of two control groups matched for gestation and birth weight and for perinatal complications. Our observations demonstrated an association of hearing loss with a higher incidence of perinatal complications. Ototoxicity appeared closely related to a prolonged administration and higher total dose of ototoxic drugs, particularly aminoglycosides and furosemide. Finally, we strongly recommend to prospectively and regularly perform audiologic assessment in sick preterm children as hearing loss is of delayed onset and in most cases bilateral and severe.", "entity": "Aminoglycosides", "aliases": "Aminoglycosides", "definition": "Glycosylated compounds in which there is an amino substituent on the glycoside. Some of them are clinically important ANTIBIOTICS.\n    ", "id": "MESH:D000617"}
{"mention": "furosemide", "mention_text": "Among 547 preterm infants of < or = 34 weeks gestation born between 1987 and 1991, 8 children (1.46%) developed severe progressive and bilateral sensorineural hearing loss. Perinatal risk factors of infants with hearing loss were compared with those of two control groups matched for gestation and birth weight and for perinatal complications. Our observations demonstrated an association of hearing loss with a higher incidence of perinatal complications. Ototoxicity appeared closely related to a prolonged administration and higher total dose of ototoxic drugs, particularly aminoglycosides and furosemide. Finally, we strongly recommend to prospectively and regularly perform audiologic assessment in sick preterm children as hearing loss is of delayed onset and in most cases bilateral and severe.", "entity": "Furosemide", "aliases": "Errolon Frusemid Frusemide Furanthril Furantral Furosemide Monohydrochloride Monosodium Salt Fursemide Fusid Lasix Salix (brand of furosemide)", "definition": "A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for EDEMA and chronic RENAL INSUFFICIENCY.\n    ", "id": "MESH:D005665"}
{"mention": "cimetidine", "mention_text": "Pharmacokinetic and clinical studies in patients with cimetidine-associated mental confusion.", "entity": "Cimetidine", "aliases": "Altramet Biomet Biomet400 Cimetidine HCl Hydrochloride Eureceptor Histodil N-Cyano-N'-methyl-N''-(2-(((5-methyl-1H-imidazol-4-yl)methyl)thio)ethyl)guanidine SK&F 92334 SK&F-92334 SK&F92334 SKF SKF-92334 SKF92334 Tagamet", "definition": "A histamine congener, it competitively inhibits HISTAMINE binding to HISTAMINE H2 RECEPTORS. Cimetidine has a range of pharmacological actions. It inhibits GASTRIC ACID secretion, as well as PEPSIN and GASTRIN output.\n    ", "id": "MESH:D002927"}
{"mention": "confusion", "mention_text": "Pharmacokinetic and clinical studies in patients with cimetidine-associated mental confusion.", "entity": "Confusion", "aliases": "Bewilderment Confusion Post Ictal Post-Ictal Reactive Confusional State States Disorientation", "definition": "A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation.\n    ", "id": "MESH:D003221"}
{"mention": "cimetidine", "mention_text": "15 cases of cimetidine-associated mental confusion have been reported. In order that this syndrome might be investigated changes in mental status (M.S.) were correlated with serum concentrations and renal and hepatic function in 36 patients, 30 patients had no M.S. change on cimetidine and 6 had moderate to severe changes. These 6 patients had both renal and liver dysfunction (P less than 0.05), as well as cimetidine trough-concentrations of more than 1.25 microgram/ml (P less than 0.05). The severity of M.S. changes increased as trough-concentrations rose, 5 patients had lumbar puncture. The cerebrospinal fluid: serum ratio of cimetidine concentrations was 0.24:1 and indicates that cimetidine passes the blood-brain barrier; it also raises the possibility that M.S. changes are due to blockade of histamine H2-receptors in the central nervous system. Patients likely to have both raised trough-concentrations and mental confusion are those with both severe renal and hepatic dysfunction. They should be closely observed and should be given reduced doses of cimetidine.", "entity": "Cimetidine", "aliases": "Altramet Biomet Biomet400 Cimetidine HCl Hydrochloride Eureceptor Histodil N-Cyano-N'-methyl-N''-(2-(((5-methyl-1H-imidazol-4-yl)methyl)thio)ethyl)guanidine SK&F 92334 SK&F-92334 SK&F92334 SKF SKF-92334 SKF92334 Tagamet", "definition": "A histamine congener, it competitively inhibits HISTAMINE binding to HISTAMINE H2 RECEPTORS. Cimetidine has a range of pharmacological actions. It inhibits GASTRIC ACID secretion, as well as PEPSIN and GASTRIN output.\n    ", "id": "MESH:D002927"}
{"mention": "confusion", "mention_text": "15 cases of cimetidine-associated mental confusion have been reported. In order that this syndrome might be investigated changes in mental status (M.S.) were correlated with serum concentrations and renal and hepatic function in 36 patients, 30 patients had no M.S. change on cimetidine and 6 had moderate to severe changes. These 6 patients had both renal and liver dysfunction (P less than 0.05), as well as cimetidine trough-concentrations of more than 1.25 microgram/ml (P less than 0.05). The severity of M.S. changes increased as trough-concentrations rose, 5 patients had lumbar puncture. The cerebrospinal fluid: serum ratio of cimetidine concentrations was 0.24:1 and indicates that cimetidine passes the blood-brain barrier; it also raises the possibility that M.S. changes are due to blockade of histamine H2-receptors in the central nervous system. Patients likely to have both raised trough-concentrations and mental confusion are those with both severe renal and hepatic dysfunction. They should be closely observed and should be given reduced doses of cimetidine.", "entity": "Confusion", "aliases": "Bewilderment Confusion Post Ictal Post-Ictal Reactive Confusional State States Disorientation", "definition": "A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation.\n    ", "id": "MESH:D003221"}
{"mention": "liver dysfunction", "mention_text": "15 cases of cimetidine-associated mental confusion have been reported. In order that this syndrome might be investigated changes in mental status (M.S.) were correlated with serum concentrations and renal and hepatic function in 36 patients, 30 patients had no M.S. change on cimetidine and 6 had moderate to severe changes. These 6 patients had both renal and liver dysfunction (P less than 0.05), as well as cimetidine trough-concentrations of more than 1.25 microgram/ml (P less than 0.05). The severity of M.S. changes increased as trough-concentrations rose, 5 patients had lumbar puncture. The cerebrospinal fluid: serum ratio of cimetidine concentrations was 0.24:1 and indicates that cimetidine passes the blood-brain barrier; it also raises the possibility that M.S. changes are due to blockade of histamine H2-receptors in the central nervous system. Patients likely to have both raised trough-concentrations and mental confusion are those with both severe renal and hepatic dysfunction. They should be closely observed and should be given reduced doses of cimetidine.", "entity": "Liver Diseases", "aliases": "Disease Liver Diseases Dysfunction Dysfunctions", "definition": "Pathological processes of the LIVER.\n    ", "id": "MESH:D008107"}
{"mention": "histamine", "mention_text": "15 cases of cimetidine-associated mental confusion have been reported. In order that this syndrome might be investigated changes in mental status (M.S.) were correlated with serum concentrations and renal and hepatic function in 36 patients, 30 patients had no M.S. change on cimetidine and 6 had moderate to severe changes. These 6 patients had both renal and liver dysfunction (P less than 0.05), as well as cimetidine trough-concentrations of more than 1.25 microgram/ml (P less than 0.05). The severity of M.S. changes increased as trough-concentrations rose, 5 patients had lumbar puncture. The cerebrospinal fluid: serum ratio of cimetidine concentrations was 0.24:1 and indicates that cimetidine passes the blood-brain barrier; it also raises the possibility that M.S. changes are due to blockade of histamine H2-receptors in the central nervous system. Patients likely to have both raised trough-concentrations and mental confusion are those with both severe renal and hepatic dysfunction. They should be closely observed and should be given reduced doses of cimetidine.", "entity": "Histamine", "aliases": "Ceplene Dihydrochloride Histamine Hydrochloride Peremin", "definition": "An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.\n    ", "id": "MESH:D006632"}
{"mention": "hepatic dysfunction", "mention_text": "15 cases of cimetidine-associated mental confusion have been reported. In order that this syndrome might be investigated changes in mental status (M.S.) were correlated with serum concentrations and renal and hepatic function in 36 patients, 30 patients had no M.S. change on cimetidine and 6 had moderate to severe changes. These 6 patients had both renal and liver dysfunction (P less than 0.05), as well as cimetidine trough-concentrations of more than 1.25 microgram/ml (P less than 0.05). The severity of M.S. changes increased as trough-concentrations rose, 5 patients had lumbar puncture. The cerebrospinal fluid: serum ratio of cimetidine concentrations was 0.24:1 and indicates that cimetidine passes the blood-brain barrier; it also raises the possibility that M.S. changes are due to blockade of histamine H2-receptors in the central nervous system. Patients likely to have both raised trough-concentrations and mental confusion are those with both severe renal and hepatic dysfunction. They should be closely observed and should be given reduced doses of cimetidine.", "entity": "Liver Diseases", "aliases": "Disease Liver Diseases Dysfunction Dysfunctions", "definition": "Pathological processes of the LIVER.\n    ", "id": "MESH:D008107"}
{"mention": "extrahepatic cholestasis", "mention_text": "Different lobular distributions of altered hepatocyte tight junctions in rat models of intrahepatic and extrahepatic cholestasis.", "entity": "Cholestasis, Extrahepatic", "aliases": "Bile Duct Obstruction Extrahepatic Biliary Stasis Cholestasis", "definition": "Impairment of bile flow in the large BILE DUCTS by mechanical obstruction or stricture due to benign or malignant processes.\n    ", "id": "MESH:D001651"}
{"mention": "cholestasis", "mention_text": "Hepatocyte tight junctions (TJs), the only intercellular barrier between the sinusoidal and the canalicular spaces, play a key role in bile formation. Although hepatocyte TJs are impaired in cholestasis, attempts to localize the precise site of hepatocyte TJ damage by freeze-fracture electron microscopy have produced limited information. Recently, several TJ-associated proteins like ZO-1 and 7H6 have been identified and characterized. Immunolocalization of 7H6 appears to closely correlate with paracellular permeability. We used rat models of intrahepatic cholestasis by ethinyl estradiol (EE) treatment and extrahepatic cholestasis by bile duct ligation (BDL) to precisely determine the site of TJ damage. Alterations in hepatocyte TJs were assessed by double-immunolabeling for 7H6 and ZO-1 using a confocal laser scanning microscope. In control rats, immunostaining for 7H6 and ZO-1 colocalized to outline bile canaliculi in a continuous fashion. In contrast, 7H6 and ZO-1 immunostaining was more discontinuous, outlining the bile canaliculi after BDL. Immunostaining for 7H6, not ZO-1, decreased and predominantly appeared as discrete signals in the submembranous cytoplasm of periportal hepatocytes after BDL. After EE treatment, changes in immunostaining for 7H6 and ZO-1 were similar to those seen in periportal hepatocytes after BDL, but distributed more diffusely throughout the lobule. This study is the first to demonstrate that impairment of hepatocyte TJs occurs heterogenously in the liver lobule after BDL and suggests that BDL and EE treatments produce different lobular distributions of increased paracellular permeability.", "entity": "Cholestasis", "aliases": "Bile Duct Obstruction Obstructions Biliary Stases Stasis Cholestases Cholestasis", "definition": "Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).\n    ", "id": "MESH:D002779"}
{"mention": "intrahepatic cholestasis", "mention_text": "Hepatocyte tight junctions (TJs), the only intercellular barrier between the sinusoidal and the canalicular spaces, play a key role in bile formation. Although hepatocyte TJs are impaired in cholestasis, attempts to localize the precise site of hepatocyte TJ damage by freeze-fracture electron microscopy have produced limited information. Recently, several TJ-associated proteins like ZO-1 and 7H6 have been identified and characterized. Immunolocalization of 7H6 appears to closely correlate with paracellular permeability. We used rat models of intrahepatic cholestasis by ethinyl estradiol (EE) treatment and extrahepatic cholestasis by bile duct ligation (BDL) to precisely determine the site of TJ damage. Alterations in hepatocyte TJs were assessed by double-immunolabeling for 7H6 and ZO-1 using a confocal laser scanning microscope. In control rats, immunostaining for 7H6 and ZO-1 colocalized to outline bile canaliculi in a continuous fashion. In contrast, 7H6 and ZO-1 immunostaining was more discontinuous, outlining the bile canaliculi after BDL. Immunostaining for 7H6, not ZO-1, decreased and predominantly appeared as discrete signals in the submembranous cytoplasm of periportal hepatocytes after BDL. After EE treatment, changes in immunostaining for 7H6 and ZO-1 were similar to those seen in periportal hepatocytes after BDL, but distributed more diffusely throughout the lobule. This study is the first to demonstrate that impairment of hepatocyte TJs occurs heterogenously in the liver lobule after BDL and suggests that BDL and EE treatments produce different lobular distributions of increased paracellular permeability.", "entity": "Cholestasis, Intrahepatic", "aliases": "Bile Duct Obstruction Intrahepatic Biliary Stases Stasis Cholestases Cholestasis", "definition": "Impairment of bile flow due to injury to the HEPATOCYTES; BILE CANALICULI; or the intrahepatic bile ducts (BILE DUCTS, INTRAHEPATIC).\n    ", "id": "MESH:D002780"}
{"mention": "ethinyl estradiol", "mention_text": "Hepatocyte tight junctions (TJs), the only intercellular barrier between the sinusoidal and the canalicular spaces, play a key role in bile formation. Although hepatocyte TJs are impaired in cholestasis, attempts to localize the precise site of hepatocyte TJ damage by freeze-fracture electron microscopy have produced limited information. Recently, several TJ-associated proteins like ZO-1 and 7H6 have been identified and characterized. Immunolocalization of 7H6 appears to closely correlate with paracellular permeability. We used rat models of intrahepatic cholestasis by ethinyl estradiol (EE) treatment and extrahepatic cholestasis by bile duct ligation (BDL) to precisely determine the site of TJ damage. Alterations in hepatocyte TJs were assessed by double-immunolabeling for 7H6 and ZO-1 using a confocal laser scanning microscope. In control rats, immunostaining for 7H6 and ZO-1 colocalized to outline bile canaliculi in a continuous fashion. In contrast, 7H6 and ZO-1 immunostaining was more discontinuous, outlining the bile canaliculi after BDL. Immunostaining for 7H6, not ZO-1, decreased and predominantly appeared as discrete signals in the submembranous cytoplasm of periportal hepatocytes after BDL. After EE treatment, changes in immunostaining for 7H6 and ZO-1 were similar to those seen in periportal hepatocytes after BDL, but distributed more diffusely throughout the lobule. This study is the first to demonstrate that impairment of hepatocyte TJs occurs heterogenously in the liver lobule after BDL and suggests that BDL and EE treatments produce different lobular distributions of increased paracellular permeability.", "entity": "Ethinyl Estradiol", "aliases": "Effik Brand of Ethinyl Estradiol Estinyl Ethynyl Hemihydrate (8 alpha)-Isomer alpha,17 alpha,9 beta,13 alpha,14 beta)-Isomer (9 beta,17 Oestradiol Ethinyl-Oestradiol Ethinylestradiol Jenapharm Ethinyloestradiol Lynoral Microfollin Forte Organon Progynon C Schering Schering-Plough", "definition": "A semisynthetic alkylated ESTRADIOL with a 17-alpha-ethinyl substitution. It has high estrogenic potency when administered orally, and is often used as the estrogenic component in ORAL CONTRACEPTIVES.\n    ", "id": "MESH:D004997"}
{"mention": "EE", "mention_text": "Hepatocyte tight junctions (TJs), the only intercellular barrier between the sinusoidal and the canalicular spaces, play a key role in bile formation. Although hepatocyte TJs are impaired in cholestasis, attempts to localize the precise site of hepatocyte TJ damage by freeze-fracture electron microscopy have produced limited information. Recently, several TJ-associated proteins like ZO-1 and 7H6 have been identified and characterized. Immunolocalization of 7H6 appears to closely correlate with paracellular permeability. We used rat models of intrahepatic cholestasis by ethinyl estradiol (EE) treatment and extrahepatic cholestasis by bile duct ligation (BDL) to precisely determine the site of TJ damage. Alterations in hepatocyte TJs were assessed by double-immunolabeling for 7H6 and ZO-1 using a confocal laser scanning microscope. In control rats, immunostaining for 7H6 and ZO-1 colocalized to outline bile canaliculi in a continuous fashion. In contrast, 7H6 and ZO-1 immunostaining was more discontinuous, outlining the bile canaliculi after BDL. Immunostaining for 7H6, not ZO-1, decreased and predominantly appeared as discrete signals in the submembranous cytoplasm of periportal hepatocytes after BDL. After EE treatment, changes in immunostaining for 7H6 and ZO-1 were similar to those seen in periportal hepatocytes after BDL, but distributed more diffusely throughout the lobule. This study is the first to demonstrate that impairment of hepatocyte TJs occurs heterogenously in the liver lobule after BDL and suggests that BDL and EE treatments produce different lobular distributions of increased paracellular permeability.", "entity": "Ethinyl Estradiol", "aliases": "Effik Brand of Ethinyl Estradiol Estinyl Ethynyl Hemihydrate (8 alpha)-Isomer alpha,17 alpha,9 beta,13 alpha,14 beta)-Isomer (9 beta,17 Oestradiol Ethinyl-Oestradiol Ethinylestradiol Jenapharm Ethinyloestradiol Lynoral Microfollin Forte Organon Progynon C Schering Schering-Plough", "definition": "A semisynthetic alkylated ESTRADIOL with a 17-alpha-ethinyl substitution. It has high estrogenic potency when administered orally, and is often used as the estrogenic component in ORAL CONTRACEPTIVES.\n    ", "id": "MESH:D004997"}
{"mention": "extrahepatic cholestasis", "mention_text": "Hepatocyte tight junctions (TJs), the only intercellular barrier between the sinusoidal and the canalicular spaces, play a key role in bile formation. Although hepatocyte TJs are impaired in cholestasis, attempts to localize the precise site of hepatocyte TJ damage by freeze-fracture electron microscopy have produced limited information. Recently, several TJ-associated proteins like ZO-1 and 7H6 have been identified and characterized. Immunolocalization of 7H6 appears to closely correlate with paracellular permeability. We used rat models of intrahepatic cholestasis by ethinyl estradiol (EE) treatment and extrahepatic cholestasis by bile duct ligation (BDL) to precisely determine the site of TJ damage. Alterations in hepatocyte TJs were assessed by double-immunolabeling for 7H6 and ZO-1 using a confocal laser scanning microscope. In control rats, immunostaining for 7H6 and ZO-1 colocalized to outline bile canaliculi in a continuous fashion. In contrast, 7H6 and ZO-1 immunostaining was more discontinuous, outlining the bile canaliculi after BDL. Immunostaining for 7H6, not ZO-1, decreased and predominantly appeared as discrete signals in the submembranous cytoplasm of periportal hepatocytes after BDL. After EE treatment, changes in immunostaining for 7H6 and ZO-1 were similar to those seen in periportal hepatocytes after BDL, but distributed more diffusely throughout the lobule. This study is the first to demonstrate that impairment of hepatocyte TJs occurs heterogenously in the liver lobule after BDL and suggests that BDL and EE treatments produce different lobular distributions of increased paracellular permeability.", "entity": "Cholestasis, Extrahepatic", "aliases": "Bile Duct Obstruction Extrahepatic Biliary Stasis Cholestasis", "definition": "Impairment of bile flow in the large BILE DUCTS by mechanical obstruction or stricture due to benign or malignant processes.\n    ", "id": "MESH:D001651"}
{"mention": "beta-thalassemic", "mention_text": "Long term audiological evaluation of beta-thalassemic patients.", "entity": "beta-Thalassemia", "aliases": "Anemia Cooley Cooley's Cooleys Erythroblastic Mediterranean Anemias Disease Hemoglobin F Intermedia Thalassemia Intermedias Major (beta-Thalassemia Major) Majors Microcytemia beta Type Microcytemias Minor Minor) Minors (beta Thalassemias beta-Thalassemia", "definition": "A disorder characterized by reduced synthesis of the beta chains of hemoglobin. There is retardation of hemoglobin A synthesis in the heterozygous form (thalassemia minor), which is asymptomatic, while in the homozygous form (thalassemia major, Cooley's anemia, Mediterranean anemia, erythroblastic anemia), which can result in severe complications and even death, hemoglobin A synthesis is absent.\n    ", "id": "MESH:D017086"}
{"mention": "hearing loss", "mention_text": "OBJECTIVE: The objective of this study was to identify the incidence and to monitor the progression of hearing loss in children and young adults with beta-thalassemia major. METHODS: One hundred and four (104) patients aged 6-35 years (mean 17,2 years) participated in the study. All patients were on a regular transfusion-chelation program maintaining a mean hemoglobin level of 9.5 gr/dl. Subjects were receiving desferrioxamine (DFO) chelation treatment with a mean daily dose of 50-60 mg/kg, 5-6 days a week during the first six years of the study, which was then reduced to 40-50 mg/kg for the following eight years. Patients were followed for 8-14 years. RESULTS: Overall, 21 out of 104 patients (20.2%) presented with high frequency sensorineural hearing loss (SNHL), either unilateral or bilateral. No ototoxic factor, other than DFO, was present in any of the patients. Patients with SNHL presented with relatively lower serum ferritin levels than those with normal hearing, however, no statistically significant difference was observed. Subjects with SNHL were submitted to DFO reduction or temporary withdrawal. Following intervention, 7 out of 21 affected patients recovered, 10 remained stable and 4 demonstrated aggravation. CONCLUSION: The findings are indicative of DFO's contributing role in the development of hearing impairment. Regular audiologic evaluation is imperative in all thalassemic patients so that early changes may be recognized and treatment may be judiciously adjusted in order to prevent or reverse hearing impairment.", "entity": "Hearing Loss", "aliases": "Hearing Impairment Loss Hypoacuses Hypoacusis", "definition": "A general term for the complete or partial loss of the ability to hear from one or both ears.\n    ", "id": "MESH:D034381"}
{"mention": "beta-thalassemia", "mention_text": "OBJECTIVE: The objective of this study was to identify the incidence and to monitor the progression of hearing loss in children and young adults with beta-thalassemia major. METHODS: One hundred and four (104) patients aged 6-35 years (mean 17,2 years) participated in the study. All patients were on a regular transfusion-chelation program maintaining a mean hemoglobin level of 9.5 gr/dl. Subjects were receiving desferrioxamine (DFO) chelation treatment with a mean daily dose of 50-60 mg/kg, 5-6 days a week during the first six years of the study, which was then reduced to 40-50 mg/kg for the following eight years. Patients were followed for 8-14 years. RESULTS: Overall, 21 out of 104 patients (20.2%) presented with high frequency sensorineural hearing loss (SNHL), either unilateral or bilateral. No ototoxic factor, other than DFO, was present in any of the patients. Patients with SNHL presented with relatively lower serum ferritin levels than those with normal hearing, however, no statistically significant difference was observed. Subjects with SNHL were submitted to DFO reduction or temporary withdrawal. Following intervention, 7 out of 21 affected patients recovered, 10 remained stable and 4 demonstrated aggravation. CONCLUSION: The findings are indicative of DFO's contributing role in the development of hearing impairment. Regular audiologic evaluation is imperative in all thalassemic patients so that early changes may be recognized and treatment may be judiciously adjusted in order to prevent or reverse hearing impairment.", "entity": "beta-Thalassemia", "aliases": "Anemia Cooley Cooley's Cooleys Erythroblastic Mediterranean Anemias Disease Hemoglobin F Intermedia Thalassemia Intermedias Major (beta-Thalassemia Major) Majors Microcytemia beta Type Microcytemias Minor Minor) Minors (beta Thalassemias beta-Thalassemia", "definition": "A disorder characterized by reduced synthesis of the beta chains of hemoglobin. There is retardation of hemoglobin A synthesis in the heterozygous form (thalassemia minor), which is asymptomatic, while in the homozygous form (thalassemia major, Cooley's anemia, Mediterranean anemia, erythroblastic anemia), which can result in severe complications and even death, hemoglobin A synthesis is absent.\n    ", "id": "MESH:D017086"}
{"mention": "desferrioxamine", "mention_text": "OBJECTIVE: The objective of this study was to identify the incidence and to monitor the progression of hearing loss in children and young adults with beta-thalassemia major. METHODS: One hundred and four (104) patients aged 6-35 years (mean 17,2 years) participated in the study. All patients were on a regular transfusion-chelation program maintaining a mean hemoglobin level of 9.5 gr/dl. Subjects were receiving desferrioxamine (DFO) chelation treatment with a mean daily dose of 50-60 mg/kg, 5-6 days a week during the first six years of the study, which was then reduced to 40-50 mg/kg for the following eight years. Patients were followed for 8-14 years. RESULTS: Overall, 21 out of 104 patients (20.2%) presented with high frequency sensorineural hearing loss (SNHL), either unilateral or bilateral. No ototoxic factor, other than DFO, was present in any of the patients. Patients with SNHL presented with relatively lower serum ferritin levels than those with normal hearing, however, no statistically significant difference was observed. Subjects with SNHL were submitted to DFO reduction or temporary withdrawal. Following intervention, 7 out of 21 affected patients recovered, 10 remained stable and 4 demonstrated aggravation. CONCLUSION: The findings are indicative of DFO's contributing role in the development of hearing impairment. Regular audiologic evaluation is imperative in all thalassemic patients so that early changes may be recognized and treatment may be judiciously adjusted in order to prevent or reverse hearing impairment.", "entity": "Deferoxamine", "aliases": "B Deferoxamine Desferrioxamine Mesilate Mesylate Methanesulfonate Deferoximine Deferrioxamine Desferal Desferioximine Desferroxamine", "definition": "Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form.\n    ", "id": "MESH:D003676"}
{"mention": "DFO", "mention_text": "OBJECTIVE: The objective of this study was to identify the incidence and to monitor the progression of hearing loss in children and young adults with beta-thalassemia major. METHODS: One hundred and four (104) patients aged 6-35 years (mean 17,2 years) participated in the study. All patients were on a regular transfusion-chelation program maintaining a mean hemoglobin level of 9.5 gr/dl. Subjects were receiving desferrioxamine (DFO) chelation treatment with a mean daily dose of 50-60 mg/kg, 5-6 days a week during the first six years of the study, which was then reduced to 40-50 mg/kg for the following eight years. Patients were followed for 8-14 years. RESULTS: Overall, 21 out of 104 patients (20.2%) presented with high frequency sensorineural hearing loss (SNHL), either unilateral or bilateral. No ototoxic factor, other than DFO, was present in any of the patients. Patients with SNHL presented with relatively lower serum ferritin levels than those with normal hearing, however, no statistically significant difference was observed. Subjects with SNHL were submitted to DFO reduction or temporary withdrawal. Following intervention, 7 out of 21 affected patients recovered, 10 remained stable and 4 demonstrated aggravation. CONCLUSION: The findings are indicative of DFO's contributing role in the development of hearing impairment. Regular audiologic evaluation is imperative in all thalassemic patients so that early changes may be recognized and treatment may be judiciously adjusted in order to prevent or reverse hearing impairment.", "entity": "Deferoxamine", "aliases": "B Deferoxamine Desferrioxamine Mesilate Mesylate Methanesulfonate Deferoximine Deferrioxamine Desferal Desferioximine Desferroxamine", "definition": "Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form.\n    ", "id": "MESH:D003676"}
{"mention": "sensorineural hearing loss", "mention_text": "OBJECTIVE: The objective of this study was to identify the incidence and to monitor the progression of hearing loss in children and young adults with beta-thalassemia major. METHODS: One hundred and four (104) patients aged 6-35 years (mean 17,2 years) participated in the study. All patients were on a regular transfusion-chelation program maintaining a mean hemoglobin level of 9.5 gr/dl. Subjects were receiving desferrioxamine (DFO) chelation treatment with a mean daily dose of 50-60 mg/kg, 5-6 days a week during the first six years of the study, which was then reduced to 40-50 mg/kg for the following eight years. Patients were followed for 8-14 years. RESULTS: Overall, 21 out of 104 patients (20.2%) presented with high frequency sensorineural hearing loss (SNHL), either unilateral or bilateral. No ototoxic factor, other than DFO, was present in any of the patients. Patients with SNHL presented with relatively lower serum ferritin levels than those with normal hearing, however, no statistically significant difference was observed. Subjects with SNHL were submitted to DFO reduction or temporary withdrawal. Following intervention, 7 out of 21 affected patients recovered, 10 remained stable and 4 demonstrated aggravation. CONCLUSION: The findings are indicative of DFO's contributing role in the development of hearing impairment. Regular audiologic evaluation is imperative in all thalassemic patients so that early changes may be recognized and treatment may be judiciously adjusted in order to prevent or reverse hearing impairment.", "entity": "Hearing Loss, Sensorineural", "aliases": "Cochlear Hearing Loss Sensorineural", "definition": "Hearing loss resulting from damage to the COCHLEA and the sensorineural elements which lie internally beyond the oval and round windows. These elements include the AUDITORY NERVE and its connections in the BRAINSTEM.\n    ", "id": "MESH:D006319"}
{"mention": "SNHL", "mention_text": "OBJECTIVE: The objective of this study was to identify the incidence and to monitor the progression of hearing loss in children and young adults with beta-thalassemia major. METHODS: One hundred and four (104) patients aged 6-35 years (mean 17,2 years) participated in the study. All patients were on a regular transfusion-chelation program maintaining a mean hemoglobin level of 9.5 gr/dl. Subjects were receiving desferrioxamine (DFO) chelation treatment with a mean daily dose of 50-60 mg/kg, 5-6 days a week during the first six years of the study, which was then reduced to 40-50 mg/kg for the following eight years. Patients were followed for 8-14 years. RESULTS: Overall, 21 out of 104 patients (20.2%) presented with high frequency sensorineural hearing loss (SNHL), either unilateral or bilateral. No ototoxic factor, other than DFO, was present in any of the patients. Patients with SNHL presented with relatively lower serum ferritin levels than those with normal hearing, however, no statistically significant difference was observed. Subjects with SNHL were submitted to DFO reduction or temporary withdrawal. Following intervention, 7 out of 21 affected patients recovered, 10 remained stable and 4 demonstrated aggravation. CONCLUSION: The findings are indicative of DFO's contributing role in the development of hearing impairment. Regular audiologic evaluation is imperative in all thalassemic patients so that early changes may be recognized and treatment may be judiciously adjusted in order to prevent or reverse hearing impairment.", "entity": "Hearing Loss, Sensorineural", "aliases": "Cochlear Hearing Loss Sensorineural", "definition": "Hearing loss resulting from damage to the COCHLEA and the sensorineural elements which lie internally beyond the oval and round windows. These elements include the AUDITORY NERVE and its connections in the BRAINSTEM.\n    ", "id": "MESH:D006319"}
{"mention": "ototoxic", "mention_text": "OBJECTIVE: The objective of this study was to identify the incidence and to monitor the progression of hearing loss in children and young adults with beta-thalassemia major. METHODS: One hundred and four (104) patients aged 6-35 years (mean 17,2 years) participated in the study. All patients were on a regular transfusion-chelation program maintaining a mean hemoglobin level of 9.5 gr/dl. Subjects were receiving desferrioxamine (DFO) chelation treatment with a mean daily dose of 50-60 mg/kg, 5-6 days a week during the first six years of the study, which was then reduced to 40-50 mg/kg for the following eight years. Patients were followed for 8-14 years. RESULTS: Overall, 21 out of 104 patients (20.2%) presented with high frequency sensorineural hearing loss (SNHL), either unilateral or bilateral. No ototoxic factor, other than DFO, was present in any of the patients. Patients with SNHL presented with relatively lower serum ferritin levels than those with normal hearing, however, no statistically significant difference was observed. Subjects with SNHL were submitted to DFO reduction or temporary withdrawal. Following intervention, 7 out of 21 affected patients recovered, 10 remained stable and 4 demonstrated aggravation. CONCLUSION: The findings are indicative of DFO's contributing role in the development of hearing impairment. Regular audiologic evaluation is imperative in all thalassemic patients so that early changes may be recognized and treatment may be judiciously adjusted in order to prevent or reverse hearing impairment.", "entity": "Hearing Disorders", "aliases": "Distorted Hearing Dysacusis Disorder Disorders Paracousis Paracusis", "definition": "Conditions that impair the transmission of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways.\n    ", "id": "MESH:D006311"}
{"mention": "hearing impairment", "mention_text": "OBJECTIVE: The objective of this study was to identify the incidence and to monitor the progression of hearing loss in children and young adults with beta-thalassemia major. METHODS: One hundred and four (104) patients aged 6-35 years (mean 17,2 years) participated in the study. All patients were on a regular transfusion-chelation program maintaining a mean hemoglobin level of 9.5 gr/dl. Subjects were receiving desferrioxamine (DFO) chelation treatment with a mean daily dose of 50-60 mg/kg, 5-6 days a week during the first six years of the study, which was then reduced to 40-50 mg/kg for the following eight years. Patients were followed for 8-14 years. RESULTS: Overall, 21 out of 104 patients (20.2%) presented with high frequency sensorineural hearing loss (SNHL), either unilateral or bilateral. No ototoxic factor, other than DFO, was present in any of the patients. Patients with SNHL presented with relatively lower serum ferritin levels than those with normal hearing, however, no statistically significant difference was observed. Subjects with SNHL were submitted to DFO reduction or temporary withdrawal. Following intervention, 7 out of 21 affected patients recovered, 10 remained stable and 4 demonstrated aggravation. CONCLUSION: The findings are indicative of DFO's contributing role in the development of hearing impairment. Regular audiologic evaluation is imperative in all thalassemic patients so that early changes may be recognized and treatment may be judiciously adjusted in order to prevent or reverse hearing impairment.", "entity": "Hearing Loss", "aliases": "Hearing Impairment Loss Hypoacuses Hypoacusis", "definition": "A general term for the complete or partial loss of the ability to hear from one or both ears.\n    ", "id": "MESH:D034381"}
{"mention": "thalassemic", "mention_text": "OBJECTIVE: The objective of this study was to identify the incidence and to monitor the progression of hearing loss in children and young adults with beta-thalassemia major. METHODS: One hundred and four (104) patients aged 6-35 years (mean 17,2 years) participated in the study. All patients were on a regular transfusion-chelation program maintaining a mean hemoglobin level of 9.5 gr/dl. Subjects were receiving desferrioxamine (DFO) chelation treatment with a mean daily dose of 50-60 mg/kg, 5-6 days a week during the first six years of the study, which was then reduced to 40-50 mg/kg for the following eight years. Patients were followed for 8-14 years. RESULTS: Overall, 21 out of 104 patients (20.2%) presented with high frequency sensorineural hearing loss (SNHL), either unilateral or bilateral. No ototoxic factor, other than DFO, was present in any of the patients. Patients with SNHL presented with relatively lower serum ferritin levels than those with normal hearing, however, no statistically significant difference was observed. Subjects with SNHL were submitted to DFO reduction or temporary withdrawal. Following intervention, 7 out of 21 affected patients recovered, 10 remained stable and 4 demonstrated aggravation. CONCLUSION: The findings are indicative of DFO's contributing role in the development of hearing impairment. Regular audiologic evaluation is imperative in all thalassemic patients so that early changes may be recognized and treatment may be judiciously adjusted in order to prevent or reverse hearing impairment.", "entity": "Thalassemia", "aliases": "Thalassemia Thalassemias", "definition": "A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia.\n    ", "id": "MESH:D013789"}
{"mention": "enalapril", "mention_text": "Design and analysis of the HYPREN-trial: safety of enalapril and prazosin in the initial treatment phase of patients with congestive heart failure.", "entity": "Enalapril", "aliases": "Enalapril Maleate MK 421 MK-421 MK421 Renitec Renitek", "definition": "One of the ANGIOTENSIN-CONVERTING ENZYME INHIBITORS that is used to treat hypertension.\n    ", "id": "MESH:D004656"}
{"mention": "prazosin", "mention_text": "Design and analysis of the HYPREN-trial: safety of enalapril and prazosin in the initial treatment phase of patients with congestive heart failure.", "entity": "Prazosin", "aliases": "Douglas Brand of Prazosin Hydrochloride Furazosin HCL Minipress Pfizer Pratsiol", "definition": "A selective adrenergic alpha-1 antagonist used in the treatment of HEART FAILURE; HYPERTENSION; PHEOCHROMOCYTOMA; RAYNAUD DISEASE; PROSTATIC HYPERTROPHY; and URINARY RETENTION.\n    ", "id": "MESH:D011224"}
{"mention": "congestive heart failure", "mention_text": "Design and analysis of the HYPREN-trial: safety of enalapril and prazosin in the initial treatment phase of patients with congestive heart failure.", "entity": "Heart Failure", "aliases": "Cardiac Failure Congestive Heart Decompensation Left Sided Left-Sided Right Right-Sided Myocardial", "definition": "A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.\n    ", "id": "MESH:D006333"}
{"mention": "angiotensin converting enzyme (ACE) inhibitors", "mention_text": "Since the introduction of angiotensin converting enzyme (ACE) inhibitors into the adjunctive treatment of patients with congestive heart failure, cases of severe hypotension, especially on the first day of treatment, have occasionally been reported. To assess the safety of the ACE inhibitor enalapril a multicenter, randomized, prazosin-controlled trial was designed that compared the incidence and severity of symptomatic hypotension on the first day of treatment. Trial medication was 2.5 mg enalapril or 0.5 prazosin. Subjects were 1210 inpatients with New York Heart Association (NYHA) functional class II and III. Patients who received enalapril experienced clinically and statistically significantly less symptomatic hypotension (5.2%) than the patients who received prazosin (12.9%). All patients recovered. It was concluded that treatment with enalapril was well tolerated and it is, therefore, unreasonable to restrict the initiation of treatment with enalapril to inpatients.", "entity": "Angiotensin-Converting Enzyme Inhibitors", "aliases": "ACE Inhibitors Angiotensin Converting Enzyme Antagonists I I-Converting Angiotensin-Converting Kininase II", "definition": "A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility.\n    ", "id": "MESH:D000806"}
{"mention": "congestive heart failure", "mention_text": "Since the introduction of angiotensin converting enzyme (ACE) inhibitors into the adjunctive treatment of patients with congestive heart failure, cases of severe hypotension, especially on the first day of treatment, have occasionally been reported. To assess the safety of the ACE inhibitor enalapril a multicenter, randomized, prazosin-controlled trial was designed that compared the incidence and severity of symptomatic hypotension on the first day of treatment. Trial medication was 2.5 mg enalapril or 0.5 prazosin. Subjects were 1210 inpatients with New York Heart Association (NYHA) functional class II and III. Patients who received enalapril experienced clinically and statistically significantly less symptomatic hypotension (5.2%) than the patients who received prazosin (12.9%). All patients recovered. It was concluded that treatment with enalapril was well tolerated and it is, therefore, unreasonable to restrict the initiation of treatment with enalapril to inpatients.", "entity": "Heart Failure", "aliases": "Cardiac Failure Congestive Heart Decompensation Left Sided Left-Sided Right Right-Sided Myocardial", "definition": "A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.\n    ", "id": "MESH:D006333"}
{"mention": "hypotension", "mention_text": "Since the introduction of angiotensin converting enzyme (ACE) inhibitors into the adjunctive treatment of patients with congestive heart failure, cases of severe hypotension, especially on the first day of treatment, have occasionally been reported. To assess the safety of the ACE inhibitor enalapril a multicenter, randomized, prazosin-controlled trial was designed that compared the incidence and severity of symptomatic hypotension on the first day of treatment. Trial medication was 2.5 mg enalapril or 0.5 prazosin. Subjects were 1210 inpatients with New York Heart Association (NYHA) functional class II and III. Patients who received enalapril experienced clinically and statistically significantly less symptomatic hypotension (5.2%) than the patients who received prazosin (12.9%). All patients recovered. It was concluded that treatment with enalapril was well tolerated and it is, therefore, unreasonable to restrict the initiation of treatment with enalapril to inpatients.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "ACE inhibitor", "mention_text": "Since the introduction of angiotensin converting enzyme (ACE) inhibitors into the adjunctive treatment of patients with congestive heart failure, cases of severe hypotension, especially on the first day of treatment, have occasionally been reported. To assess the safety of the ACE inhibitor enalapril a multicenter, randomized, prazosin-controlled trial was designed that compared the incidence and severity of symptomatic hypotension on the first day of treatment. Trial medication was 2.5 mg enalapril or 0.5 prazosin. Subjects were 1210 inpatients with New York Heart Association (NYHA) functional class II and III. Patients who received enalapril experienced clinically and statistically significantly less symptomatic hypotension (5.2%) than the patients who received prazosin (12.9%). All patients recovered. It was concluded that treatment with enalapril was well tolerated and it is, therefore, unreasonable to restrict the initiation of treatment with enalapril to inpatients.", "entity": "Angiotensin-Converting Enzyme Inhibitors", "aliases": "ACE Inhibitors Angiotensin Converting Enzyme Antagonists I I-Converting Angiotensin-Converting Kininase II", "definition": "A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility.\n    ", "id": "MESH:D000806"}
{"mention": "enalapril", "mention_text": "Since the introduction of angiotensin converting enzyme (ACE) inhibitors into the adjunctive treatment of patients with congestive heart failure, cases of severe hypotension, especially on the first day of treatment, have occasionally been reported. To assess the safety of the ACE inhibitor enalapril a multicenter, randomized, prazosin-controlled trial was designed that compared the incidence and severity of symptomatic hypotension on the first day of treatment. Trial medication was 2.5 mg enalapril or 0.5 prazosin. Subjects were 1210 inpatients with New York Heart Association (NYHA) functional class II and III. Patients who received enalapril experienced clinically and statistically significantly less symptomatic hypotension (5.2%) than the patients who received prazosin (12.9%). All patients recovered. It was concluded that treatment with enalapril was well tolerated and it is, therefore, unreasonable to restrict the initiation of treatment with enalapril to inpatients.", "entity": "Enalapril", "aliases": "Enalapril Maleate MK 421 MK-421 MK421 Renitec Renitek", "definition": "One of the ANGIOTENSIN-CONVERTING ENZYME INHIBITORS that is used to treat hypertension.\n    ", "id": "MESH:D004656"}
{"mention": "prazosin", "mention_text": "Since the introduction of angiotensin converting enzyme (ACE) inhibitors into the adjunctive treatment of patients with congestive heart failure, cases of severe hypotension, especially on the first day of treatment, have occasionally been reported. To assess the safety of the ACE inhibitor enalapril a multicenter, randomized, prazosin-controlled trial was designed that compared the incidence and severity of symptomatic hypotension on the first day of treatment. Trial medication was 2.5 mg enalapril or 0.5 prazosin. Subjects were 1210 inpatients with New York Heart Association (NYHA) functional class II and III. Patients who received enalapril experienced clinically and statistically significantly less symptomatic hypotension (5.2%) than the patients who received prazosin (12.9%). All patients recovered. It was concluded that treatment with enalapril was well tolerated and it is, therefore, unreasonable to restrict the initiation of treatment with enalapril to inpatients.", "entity": "Prazosin", "aliases": "Douglas Brand of Prazosin Hydrochloride Furazosin HCL Minipress Pfizer Pratsiol", "definition": "A selective adrenergic alpha-1 antagonist used in the treatment of HEART FAILURE; HYPERTENSION; PHEOCHROMOCYTOMA; RAYNAUD DISEASE; PROSTATIC HYPERTROPHY; and URINARY RETENTION.\n    ", "id": "MESH:D011224"}
{"mention": "azidothymidine", "mention_text": "Antagonism between interleukin 3 and erythropoietin in mice with azidothymidine-induced anemia and in bone marrow endothelial cells.", "entity": "Zidovudine", "aliases": "3' Azido 2',3' Dideoxythymidine deoxythymidine 3'-Azido-2',3'-Dideoxythymidine 3'-Azido-3'-deoxythymidine AZT (Antiviral) Antiviral Azidothymidine BW A509U BWA 509U BWA-509U BWA509U Retrovir Zidovudine", "definition": "A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.\n    ", "id": "MESH:D015215"}
{"mention": "anemia", "mention_text": "Antagonism between interleukin 3 and erythropoietin in mice with azidothymidine-induced anemia and in bone marrow endothelial cells.", "entity": "Anemia", "aliases": "Anemia Anemias", "definition": "A reduction in the number of circulating ERYTHROCYTES or in the quantity of HEMOGLOBIN.\n    ", "id": "MESH:D000740"}
{"mention": "Azidothymidine", "mention_text": "Azidothymidine (AZT)-induced anemia in mice can be reversed by the administration of IGF-IL-3 (fusion protein of insulin-like growth factor II (IGF II) and interleukin 3). Although interleukin 3 (IL-3) and erythropoietin (EPO) are known to act synergistically on hematopoietic cell proliferation in vitro, injection of IGF-IL-3 and EPO in AZT-treated mice resulted in a reduction of red cells and an increase of plasma EPO levels as compared to animals treated with IGF-IL-3 or EPO alone. We tested the hypothesis that the antagonistic effect of IL-3 and EPO on erythroid cells may be mediated by endothelial cells. Bovine liver erythroid cells were cultured on monolayers of human bone marrow endothelial cells previously treated with EPO and IGF-IL-3. There was a significant reduction of thymidine incorporation into both erythroid and endothelial cells in cultures pre-treated with IGF-IL-3 and EPO. Endothelial cell culture supernatants separated by ultrafiltration and ultracentrifugation from cells treated with EPO and IL-3 significantly reduced thymidine incorporation into erythroid cells as compared to identical fractions obtained from the media of cells cultured with EPO alone. These results suggest that endothelial cells treated simultaneously with EPO and IL-3 have a negative effect on erythroid cell production.", "entity": "Zidovudine", "aliases": "3' Azido 2',3' Dideoxythymidine deoxythymidine 3'-Azido-2',3'-Dideoxythymidine 3'-Azido-3'-deoxythymidine AZT (Antiviral) Antiviral Azidothymidine BW A509U BWA 509U BWA-509U BWA509U Retrovir Zidovudine", "definition": "A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.\n    ", "id": "MESH:D015215"}
{"mention": "AZT", "mention_text": "Azidothymidine (AZT)-induced anemia in mice can be reversed by the administration of IGF-IL-3 (fusion protein of insulin-like growth factor II (IGF II) and interleukin 3). Although interleukin 3 (IL-3) and erythropoietin (EPO) are known to act synergistically on hematopoietic cell proliferation in vitro, injection of IGF-IL-3 and EPO in AZT-treated mice resulted in a reduction of red cells and an increase of plasma EPO levels as compared to animals treated with IGF-IL-3 or EPO alone. We tested the hypothesis that the antagonistic effect of IL-3 and EPO on erythroid cells may be mediated by endothelial cells. Bovine liver erythroid cells were cultured on monolayers of human bone marrow endothelial cells previously treated with EPO and IGF-IL-3. There was a significant reduction of thymidine incorporation into both erythroid and endothelial cells in cultures pre-treated with IGF-IL-3 and EPO. Endothelial cell culture supernatants separated by ultrafiltration and ultracentrifugation from cells treated with EPO and IL-3 significantly reduced thymidine incorporation into erythroid cells as compared to identical fractions obtained from the media of cells cultured with EPO alone. These results suggest that endothelial cells treated simultaneously with EPO and IL-3 have a negative effect on erythroid cell production.", "entity": "Zidovudine", "aliases": "3' Azido 2',3' Dideoxythymidine deoxythymidine 3'-Azido-2',3'-Dideoxythymidine 3'-Azido-3'-deoxythymidine AZT (Antiviral) Antiviral Azidothymidine BW A509U BWA 509U BWA-509U BWA509U Retrovir Zidovudine", "definition": "A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.\n    ", "id": "MESH:D015215"}
{"mention": "anemia", "mention_text": "Azidothymidine (AZT)-induced anemia in mice can be reversed by the administration of IGF-IL-3 (fusion protein of insulin-like growth factor II (IGF II) and interleukin 3). Although interleukin 3 (IL-3) and erythropoietin (EPO) are known to act synergistically on hematopoietic cell proliferation in vitro, injection of IGF-IL-3 and EPO in AZT-treated mice resulted in a reduction of red cells and an increase of plasma EPO levels as compared to animals treated with IGF-IL-3 or EPO alone. We tested the hypothesis that the antagonistic effect of IL-3 and EPO on erythroid cells may be mediated by endothelial cells. Bovine liver erythroid cells were cultured on monolayers of human bone marrow endothelial cells previously treated with EPO and IGF-IL-3. There was a significant reduction of thymidine incorporation into both erythroid and endothelial cells in cultures pre-treated with IGF-IL-3 and EPO. Endothelial cell culture supernatants separated by ultrafiltration and ultracentrifugation from cells treated with EPO and IL-3 significantly reduced thymidine incorporation into erythroid cells as compared to identical fractions obtained from the media of cells cultured with EPO alone. These results suggest that endothelial cells treated simultaneously with EPO and IL-3 have a negative effect on erythroid cell production.", "entity": "Anemia", "aliases": "Anemia Anemias", "definition": "A reduction in the number of circulating ERYTHROCYTES or in the quantity of HEMOGLOBIN.\n    ", "id": "MESH:D000740"}
{"mention": "thymidine", "mention_text": "Azidothymidine (AZT)-induced anemia in mice can be reversed by the administration of IGF-IL-3 (fusion protein of insulin-like growth factor II (IGF II) and interleukin 3). Although interleukin 3 (IL-3) and erythropoietin (EPO) are known to act synergistically on hematopoietic cell proliferation in vitro, injection of IGF-IL-3 and EPO in AZT-treated mice resulted in a reduction of red cells and an increase of plasma EPO levels as compared to animals treated with IGF-IL-3 or EPO alone. We tested the hypothesis that the antagonistic effect of IL-3 and EPO on erythroid cells may be mediated by endothelial cells. Bovine liver erythroid cells were cultured on monolayers of human bone marrow endothelial cells previously treated with EPO and IGF-IL-3. There was a significant reduction of thymidine incorporation into both erythroid and endothelial cells in cultures pre-treated with IGF-IL-3 and EPO. Endothelial cell culture supernatants separated by ultrafiltration and ultracentrifugation from cells treated with EPO and IL-3 significantly reduced thymidine incorporation into erythroid cells as compared to identical fractions obtained from the media of cells cultured with EPO alone. These results suggest that endothelial cells treated simultaneously with EPO and IL-3 have a negative effect on erythroid cell production.", "entity": "Thymidine", "aliases": "2' Deoxythymidine 2'-Deoxythymidine Thymidine", "definition": "", "id": "MESH:D013936"}
{"mention": "Na", "mention_text": "Interactive effects of variations in [Na]o and [Ca]o on rat atrial spontaneous frequency.", "entity": "Sodium", "aliases": "Ion Level Sodium", "definition": "A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.\n    ", "id": "MESH:D012964"}
{"mention": "Ca", "mention_text": "Interactive effects of variations in [Na]o and [Ca]o on rat atrial spontaneous frequency.", "entity": "Calcium", "aliases": "Blood Coagulation Factor IV Calcium", "definition": "A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.\n    ", "id": "MESH:D002118"}
{"mention": "Na", "mention_text": "The effects of varying the extracellular concentrations of Na and Ca ([Na]o and [Ca]o) on both, the spontaneous beating and the negative chronotropic action of verapamil, were studied in the isolated rat atria. Basal frequency (BF) evaluated by surface electrogram was 223 +/- 4 beats/min. in control Krebs-Ringer containing 137 mM Na and 1.35 mM Ca (N). It decreased by 16 +/- 3% by lowering [Na]o to 78 mM (LNa), 23 +/- 2% by lowering simultaneously [Na]o to 78 mM and [Ca]o to 0.675 mM (LNa+LCa) and 31 +/- 5% by lowering [Na]o to 78 mM plus increasing [Ca]o to 3.6 mM (LNa+HCa). At normal [Na]o, decrease (0.675 mM) or increase (3.6 mM) of [Ca]o did not modify BF; a reduction of ten times (0.135 mM of normal [Ca]o was effective to reduce BF by 40 +/- 13%. All negative chronotropic effects were BF-dependent. Dose-dependent bradycardia induced by verapamil was potentiated by LNa, LCa, and HCa. Independent but not additive effects of Na and Ca are shown by decreases in the values of [verapamil]o needed to reduce BF by 30% (IC30) with the following order of inhibitory potency: LNa > LCa > HCa > N, resulting LNa+HCa similar to LNa. The [verapamil]o that arrested atrial beating (AC) was also potentiated with the order LNa = LNa+LCa = LNa+HCa = LCa > HCa = N. The results indicate that rat atrial spontaneous beating is more dependent on [Na]o than on [Ca]o in a range of +/- 50% of their normal concentration. Also the enhancement of verapamil effects on atrial beating was more pronounced at LNa than at LCa.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Sodium", "aliases": "Ion Level Sodium", "definition": "A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.\n    ", "id": "MESH:D012964"}
{"mention": "Ca", "mention_text": "The effects of varying the extracellular concentrations of Na and Ca ([Na]o and [Ca]o) on both, the spontaneous beating and the negative chronotropic action of verapamil, were studied in the isolated rat atria. Basal frequency (BF) evaluated by surface electrogram was 223 +/- 4 beats/min. in control Krebs-Ringer containing 137 mM Na and 1.35 mM Ca (N). It decreased by 16 +/- 3% by lowering [Na]o to 78 mM (LNa), 23 +/- 2% by lowering simultaneously [Na]o to 78 mM and [Ca]o to 0.675 mM (LNa+LCa) and 31 +/- 5% by lowering [Na]o to 78 mM plus increasing [Ca]o to 3.6 mM (LNa+HCa). At normal [Na]o, decrease (0.675 mM) or increase (3.6 mM) of [Ca]o did not modify BF; a reduction of ten times (0.135 mM of normal [Ca]o was effective to reduce BF by 40 +/- 13%. All negative chronotropic effects were BF-dependent. Dose-dependent bradycardia induced by verapamil was potentiated by LNa, LCa, and HCa. Independent but not additive effects of Na and Ca are shown by decreases in the values of [verapamil]o needed to reduce BF by 30% (IC30) with the following order of inhibitory potency: LNa > LCa > HCa > N, resulting LNa+HCa similar to LNa. The [verapamil]o that arrested atrial beating (AC) was also potentiated with the order LNa = LNa+LCa = LNa+HCa = LCa > HCa = N. The results indicate that rat atrial spontaneous beating is more dependent on [Na]o than on [Ca]o in a range of +/- 50% of their normal concentration. Also the enhancement of verapamil effects on atrial beating was more pronounced at LNa than at LCa.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Calcium", "aliases": "Blood Coagulation Factor IV Calcium", "definition": "A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.\n    ", "id": "MESH:D002118"}
{"mention": "verapamil", "mention_text": "The effects of varying the extracellular concentrations of Na and Ca ([Na]o and [Ca]o) on both, the spontaneous beating and the negative chronotropic action of verapamil, were studied in the isolated rat atria. Basal frequency (BF) evaluated by surface electrogram was 223 +/- 4 beats/min. in control Krebs-Ringer containing 137 mM Na and 1.35 mM Ca (N). It decreased by 16 +/- 3% by lowering [Na]o to 78 mM (LNa), 23 +/- 2% by lowering simultaneously [Na]o to 78 mM and [Ca]o to 0.675 mM (LNa+LCa) and 31 +/- 5% by lowering [Na]o to 78 mM plus increasing [Ca]o to 3.6 mM (LNa+HCa). At normal [Na]o, decrease (0.675 mM) or increase (3.6 mM) of [Ca]o did not modify BF; a reduction of ten times (0.135 mM of normal [Ca]o was effective to reduce BF by 40 +/- 13%. All negative chronotropic effects were BF-dependent. Dose-dependent bradycardia induced by verapamil was potentiated by LNa, LCa, and HCa. Independent but not additive effects of Na and Ca are shown by decreases in the values of [verapamil]o needed to reduce BF by 30% (IC30) with the following order of inhibitory potency: LNa > LCa > HCa > N, resulting LNa+HCa similar to LNa. The [verapamil]o that arrested atrial beating (AC) was also potentiated with the order LNa = LNa+LCa = LNa+HCa = LCa > HCa = N. The results indicate that rat atrial spontaneous beating is more dependent on [Na]o than on [Ca]o in a range of +/- 50% of their normal concentration. Also the enhancement of verapamil effects on atrial beating was more pronounced at LNa than at LCa.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Verapamil", "aliases": "Calan Cordilox Dexverapamil Falicard Finoptin Hydrochloride Verapamil Iproveratril Isoptin Isoptine Izoptin Lekoptin Sandoz Brand of", "definition": "A calcium channel blocker that is a class IV anti-arrhythmia agent.\n    ", "id": "MESH:D014700"}
{"mention": "bradycardia", "mention_text": "The effects of varying the extracellular concentrations of Na and Ca ([Na]o and [Ca]o) on both, the spontaneous beating and the negative chronotropic action of verapamil, were studied in the isolated rat atria. Basal frequency (BF) evaluated by surface electrogram was 223 +/- 4 beats/min. in control Krebs-Ringer containing 137 mM Na and 1.35 mM Ca (N). It decreased by 16 +/- 3% by lowering [Na]o to 78 mM (LNa), 23 +/- 2% by lowering simultaneously [Na]o to 78 mM and [Ca]o to 0.675 mM (LNa+LCa) and 31 +/- 5% by lowering [Na]o to 78 mM plus increasing [Ca]o to 3.6 mM (LNa+HCa). At normal [Na]o, decrease (0.675 mM) or increase (3.6 mM) of [Ca]o did not modify BF; a reduction of ten times (0.135 mM of normal [Ca]o was effective to reduce BF by 40 +/- 13%. All negative chronotropic effects were BF-dependent. Dose-dependent bradycardia induced by verapamil was potentiated by LNa, LCa, and HCa. Independent but not additive effects of Na and Ca are shown by decreases in the values of [verapamil]o needed to reduce BF by 30% (IC30) with the following order of inhibitory potency: LNa > LCa > HCa > N, resulting LNa+HCa similar to LNa. The [verapamil]o that arrested atrial beating (AC) was also potentiated with the order LNa = LNa+LCa = LNa+HCa = LCa > HCa = N. The results indicate that rat atrial spontaneous beating is more dependent on [Na]o than on [Ca]o in a range of +/- 50% of their normal concentration. Also the enhancement of verapamil effects on atrial beating was more pronounced at LNa than at LCa.(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Bradycardia", "aliases": "Bradyarrhythmia Bradyarrhythmias Bradycardia Bradycardias", "definition": "Cardiac arrhythmias that are characterized by excessively slow HEART RATE, usually below 50 beats per minute in human adults. They can be classified broadly into SINOATRIAL NODE dysfunction and ATRIOVENTRICULAR BLOCK.\n    ", "id": "MESH:D001919"}
{"mention": "Sodium", "mention_text": "Sodium status influences chronic amphotericin B nephrotoxicity in rats.", "entity": "Sodium", "aliases": "Ion Level Sodium", "definition": "A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.\n    ", "id": "MESH:D012964"}
{"mention": "amphotericin B", "mention_text": "Sodium status influences chronic amphotericin B nephrotoxicity in rats.", "entity": "Amphotericin B", "aliases": "Amphocil Amphotericin B Cholesterol Dispersion Colloidal Fungizone", "definition": "Macrolide antifungal antibiotic produced by Streptomyces nodosus obtained from soil of the Orinoco river region of Venezuela.\n    ", "id": "MESH:D000666"}
{"mention": "nephrotoxicity", "mention_text": "Sodium status influences chronic amphotericin B nephrotoxicity in rats.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "nephrotoxic", "mention_text": "The nephrotoxic potential of amphotericin B (5 mg/kg per day intraperitoneally for 3 weeks) has been investigated in salt-depleted, normal-salt, and salt-loaded rats. In salt-depleted rats, amphotericin B decreased creatinine clearance linearly with time, with an 85% reduction by week 3. In contrast, in normal-salt rats creatinine clearance was decreased but to a lesser extent at week 2 and 3, and in salt-loaded rats creatinine clearance did not change for 2 weeks and was decreased by 43% at week 3. All rats in the sodium-depleted group had histopathological evidence of patchy tubular cytoplasmic degeneration in tubules that was not observed in any normal-salt or salt-loaded rat. Concentrations of amphotericin B in plasma were not significantly different among the three groups at any time during the study. However, at the end of 3 weeks, amphotericin B levels in the kidneys and liver were significantly higher in salt-depleted and normal-salt rats than those in salt-loaded rats, with plasma/kidney ratios of 21, 14, and 8 in salt-depleted, normal-salt, and salt-loaded rats, respectively. In conclusion, reductions in creatinine clearance and renal amphotericin B accumulation after chronic amphotericin B administration were enhanced by salt depletion and attenuated by sodium loading in rats.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "amphotericin B", "mention_text": "The nephrotoxic potential of amphotericin B (5 mg/kg per day intraperitoneally for 3 weeks) has been investigated in salt-depleted, normal-salt, and salt-loaded rats. In salt-depleted rats, amphotericin B decreased creatinine clearance linearly with time, with an 85% reduction by week 3. In contrast, in normal-salt rats creatinine clearance was decreased but to a lesser extent at week 2 and 3, and in salt-loaded rats creatinine clearance did not change for 2 weeks and was decreased by 43% at week 3. All rats in the sodium-depleted group had histopathological evidence of patchy tubular cytoplasmic degeneration in tubules that was not observed in any normal-salt or salt-loaded rat. Concentrations of amphotericin B in plasma were not significantly different among the three groups at any time during the study. However, at the end of 3 weeks, amphotericin B levels in the kidneys and liver were significantly higher in salt-depleted and normal-salt rats than those in salt-loaded rats, with plasma/kidney ratios of 21, 14, and 8 in salt-depleted, normal-salt, and salt-loaded rats, respectively. In conclusion, reductions in creatinine clearance and renal amphotericin B accumulation after chronic amphotericin B administration were enhanced by salt depletion and attenuated by sodium loading in rats.", "entity": "Amphotericin B", "aliases": "Amphocil Amphotericin B Cholesterol Dispersion Colloidal Fungizone", "definition": "Macrolide antifungal antibiotic produced by Streptomyces nodosus obtained from soil of the Orinoco river region of Venezuela.\n    ", "id": "MESH:D000666"}
{"mention": "creatinine", "mention_text": "The nephrotoxic potential of amphotericin B (5 mg/kg per day intraperitoneally for 3 weeks) has been investigated in salt-depleted, normal-salt, and salt-loaded rats. In salt-depleted rats, amphotericin B decreased creatinine clearance linearly with time, with an 85% reduction by week 3. In contrast, in normal-salt rats creatinine clearance was decreased but to a lesser extent at week 2 and 3, and in salt-loaded rats creatinine clearance did not change for 2 weeks and was decreased by 43% at week 3. All rats in the sodium-depleted group had histopathological evidence of patchy tubular cytoplasmic degeneration in tubules that was not observed in any normal-salt or salt-loaded rat. Concentrations of amphotericin B in plasma were not significantly different among the three groups at any time during the study. However, at the end of 3 weeks, amphotericin B levels in the kidneys and liver were significantly higher in salt-depleted and normal-salt rats than those in salt-loaded rats, with plasma/kidney ratios of 21, 14, and 8 in salt-depleted, normal-salt, and salt-loaded rats, respectively. In conclusion, reductions in creatinine clearance and renal amphotericin B accumulation after chronic amphotericin B administration were enhanced by salt depletion and attenuated by sodium loading in rats.", "entity": "Creatinine", "aliases": "Creatinine Sulfate Salt Krebiozen", "definition": "", "id": "MESH:D003404"}
{"mention": "sodium", "mention_text": "The nephrotoxic potential of amphotericin B (5 mg/kg per day intraperitoneally for 3 weeks) has been investigated in salt-depleted, normal-salt, and salt-loaded rats. In salt-depleted rats, amphotericin B decreased creatinine clearance linearly with time, with an 85% reduction by week 3. In contrast, in normal-salt rats creatinine clearance was decreased but to a lesser extent at week 2 and 3, and in salt-loaded rats creatinine clearance did not change for 2 weeks and was decreased by 43% at week 3. All rats in the sodium-depleted group had histopathological evidence of patchy tubular cytoplasmic degeneration in tubules that was not observed in any normal-salt or salt-loaded rat. Concentrations of amphotericin B in plasma were not significantly different among the three groups at any time during the study. However, at the end of 3 weeks, amphotericin B levels in the kidneys and liver were significantly higher in salt-depleted and normal-salt rats than those in salt-loaded rats, with plasma/kidney ratios of 21, 14, and 8 in salt-depleted, normal-salt, and salt-loaded rats, respectively. In conclusion, reductions in creatinine clearance and renal amphotericin B accumulation after chronic amphotericin B administration were enhanced by salt depletion and attenuated by sodium loading in rats.", "entity": "Sodium", "aliases": "Ion Level Sodium", "definition": "A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.\n    ", "id": "MESH:D012964"}
{"mention": "inferior colliculus lesion", "mention_text": "Reversible inferior colliculus lesion in metronidazole-induced encephalopathy: magnetic resonance findings on diffusion-weighted and fluid attenuated inversion recovery imaging.", "entity": "Brain Diseases", "aliases": "Brain Disease Diseases Disorder Disorders CNS Intracranial Central Nervous System Encephalon", "definition": "Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.\n    ", "id": "MESH:D001927"}
{"mention": "metronidazole", "mention_text": "Reversible inferior colliculus lesion in metronidazole-induced encephalopathy: magnetic resonance findings on diffusion-weighted and fluid attenuated inversion recovery imaging.", "entity": "Metronidazole", "aliases": "2 Methyl 5 nitroimidazole 1 ethanol 2-Methyl-5-nitroimidazole-1-ethanol Bayer 5360 Clont Danizol Flagyl Gineflavir Hydrochloride Metronidazole Metric MetroGel Metrodzhil Metrogyl Monohydrochloride Phosphate Phosphoester Satric Trichazol Trichopol Trivazol Vagilen", "definition": "A nitroimidazole used to treat AMEBIASIS; VAGINITIS; TRICHOMONAS INFECTIONS; GIARDIASIS; ANAEROBIC BACTERIA; and TREPONEMAL INFECTIONS. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed).\n    ", "id": "MESH:D008795"}
{"mention": "encephalopathy", "mention_text": "Reversible inferior colliculus lesion in metronidazole-induced encephalopathy: magnetic resonance findings on diffusion-weighted and fluid attenuated inversion recovery imaging.", "entity": "Brain Diseases", "aliases": "Brain Disease Diseases Disorder Disorders CNS Intracranial Central Nervous System Encephalon", "definition": "Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.\n    ", "id": "MESH:D001927"}
{"mention": "inferior colliculus lesions", "mention_text": "OBJECTIVE: This is to present reversible inferior colliculus lesions in metronidazole-induced encephalopathy, to focus on the diffusion-weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) imaging. MATERIALS AND METHODS: From November 2005 to September 2007, 8 patients (5 men and 3 women) were diagnosed as having metronidazole-induced encephalopathy (age range; 43-78 years). They had been taking metronidazole (total dosage, 45-120 g; duration, 30 days to 2 months) to treat the infection in various organs. Initial brain magnetic resonance imaging (MRI) were obtained after the hospitalization, including DWI (8/8), apparent diffusion coefficient (ADC) map (4/8), FLAIR (7/8), and T2-weighted image (8/8). Follow-up MRIs were performed on 5 patients from third to 14th days after discontinuation of metronidazole administration. Findings of initial and follow-up MRIs were retrospectively evaluated by 2 neuroradiologists by consensus, to analyze the presence of abnormal signal intensities, their locations, and signal changes on follow-up images. RESULTS: Initial MRIs showed abnormal high signal intensities on DWI and FLAIR (or T2-weighted image) at the dentate nucleus (8/8), inferior colliculus (6/8), corpus callosum (2/8), pons (2/8), medulla (1/8), and bilateral cerebral white matter (1/8). High-signal intensity lesions on DWI tended to show low signal intensity on ADC map (3/4), but in one patient, high signal intensity was shown at bilateral dentate nuclei on not only DWI but also ADC map. All the lesions in dentate, inferior colliculus, pons, and medullas had been resolved completely on follow-up MRIs in 5 patients, but in 1 patient of them, corpus callosal lesion persisted. CONCLUSIONS: Reversible inferior colliculus lesions could be considered as the characteristic for metronidazole-induced encephalopathy, next to the dentate nucleus involvement.", "entity": "Brain Diseases", "aliases": "Brain Disease Diseases Disorder Disorders CNS Intracranial Central Nervous System Encephalon", "definition": "Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.\n    ", "id": "MESH:D001927"}
{"mention": "metronidazole", "mention_text": "OBJECTIVE: This is to present reversible inferior colliculus lesions in metronidazole-induced encephalopathy, to focus on the diffusion-weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) imaging. MATERIALS AND METHODS: From November 2005 to September 2007, 8 patients (5 men and 3 women) were diagnosed as having metronidazole-induced encephalopathy (age range; 43-78 years). They had been taking metronidazole (total dosage, 45-120 g; duration, 30 days to 2 months) to treat the infection in various organs. Initial brain magnetic resonance imaging (MRI) were obtained after the hospitalization, including DWI (8/8), apparent diffusion coefficient (ADC) map (4/8), FLAIR (7/8), and T2-weighted image (8/8). Follow-up MRIs were performed on 5 patients from third to 14th days after discontinuation of metronidazole administration. Findings of initial and follow-up MRIs were retrospectively evaluated by 2 neuroradiologists by consensus, to analyze the presence of abnormal signal intensities, their locations, and signal changes on follow-up images. RESULTS: Initial MRIs showed abnormal high signal intensities on DWI and FLAIR (or T2-weighted image) at the dentate nucleus (8/8), inferior colliculus (6/8), corpus callosum (2/8), pons (2/8), medulla (1/8), and bilateral cerebral white matter (1/8). High-signal intensity lesions on DWI tended to show low signal intensity on ADC map (3/4), but in one patient, high signal intensity was shown at bilateral dentate nuclei on not only DWI but also ADC map. All the lesions in dentate, inferior colliculus, pons, and medullas had been resolved completely on follow-up MRIs in 5 patients, but in 1 patient of them, corpus callosal lesion persisted. CONCLUSIONS: Reversible inferior colliculus lesions could be considered as the characteristic for metronidazole-induced encephalopathy, next to the dentate nucleus involvement.", "entity": "Metronidazole", "aliases": "2 Methyl 5 nitroimidazole 1 ethanol 2-Methyl-5-nitroimidazole-1-ethanol Bayer 5360 Clont Danizol Flagyl Gineflavir Hydrochloride Metronidazole Metric MetroGel Metrodzhil Metrogyl Monohydrochloride Phosphate Phosphoester Satric Trichazol Trichopol Trivazol Vagilen", "definition": "A nitroimidazole used to treat AMEBIASIS; VAGINITIS; TRICHOMONAS INFECTIONS; GIARDIASIS; ANAEROBIC BACTERIA; and TREPONEMAL INFECTIONS. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed).\n    ", "id": "MESH:D008795"}
{"mention": "encephalopathy", "mention_text": "OBJECTIVE: This is to present reversible inferior colliculus lesions in metronidazole-induced encephalopathy, to focus on the diffusion-weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) imaging. MATERIALS AND METHODS: From November 2005 to September 2007, 8 patients (5 men and 3 women) were diagnosed as having metronidazole-induced encephalopathy (age range; 43-78 years). They had been taking metronidazole (total dosage, 45-120 g; duration, 30 days to 2 months) to treat the infection in various organs. Initial brain magnetic resonance imaging (MRI) were obtained after the hospitalization, including DWI (8/8), apparent diffusion coefficient (ADC) map (4/8), FLAIR (7/8), and T2-weighted image (8/8). Follow-up MRIs were performed on 5 patients from third to 14th days after discontinuation of metronidazole administration. Findings of initial and follow-up MRIs were retrospectively evaluated by 2 neuroradiologists by consensus, to analyze the presence of abnormal signal intensities, their locations, and signal changes on follow-up images. RESULTS: Initial MRIs showed abnormal high signal intensities on DWI and FLAIR (or T2-weighted image) at the dentate nucleus (8/8), inferior colliculus (6/8), corpus callosum (2/8), pons (2/8), medulla (1/8), and bilateral cerebral white matter (1/8). High-signal intensity lesions on DWI tended to show low signal intensity on ADC map (3/4), but in one patient, high signal intensity was shown at bilateral dentate nuclei on not only DWI but also ADC map. All the lesions in dentate, inferior colliculus, pons, and medullas had been resolved completely on follow-up MRIs in 5 patients, but in 1 patient of them, corpus callosal lesion persisted. CONCLUSIONS: Reversible inferior colliculus lesions could be considered as the characteristic for metronidazole-induced encephalopathy, next to the dentate nucleus involvement.", "entity": "Brain Diseases", "aliases": "Brain Disease Diseases Disorder Disorders CNS Intracranial Central Nervous System Encephalon", "definition": "Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.\n    ", "id": "MESH:D001927"}
{"mention": "infection", "mention_text": "OBJECTIVE: This is to present reversible inferior colliculus lesions in metronidazole-induced encephalopathy, to focus on the diffusion-weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) imaging. MATERIALS AND METHODS: From November 2005 to September 2007, 8 patients (5 men and 3 women) were diagnosed as having metronidazole-induced encephalopathy (age range; 43-78 years). They had been taking metronidazole (total dosage, 45-120 g; duration, 30 days to 2 months) to treat the infection in various organs. Initial brain magnetic resonance imaging (MRI) were obtained after the hospitalization, including DWI (8/8), apparent diffusion coefficient (ADC) map (4/8), FLAIR (7/8), and T2-weighted image (8/8). Follow-up MRIs were performed on 5 patients from third to 14th days after discontinuation of metronidazole administration. Findings of initial and follow-up MRIs were retrospectively evaluated by 2 neuroradiologists by consensus, to analyze the presence of abnormal signal intensities, their locations, and signal changes on follow-up images. RESULTS: Initial MRIs showed abnormal high signal intensities on DWI and FLAIR (or T2-weighted image) at the dentate nucleus (8/8), inferior colliculus (6/8), corpus callosum (2/8), pons (2/8), medulla (1/8), and bilateral cerebral white matter (1/8). High-signal intensity lesions on DWI tended to show low signal intensity on ADC map (3/4), but in one patient, high signal intensity was shown at bilateral dentate nuclei on not only DWI but also ADC map. All the lesions in dentate, inferior colliculus, pons, and medullas had been resolved completely on follow-up MRIs in 5 patients, but in 1 patient of them, corpus callosal lesion persisted. CONCLUSIONS: Reversible inferior colliculus lesions could be considered as the characteristic for metronidazole-induced encephalopathy, next to the dentate nucleus involvement.", "entity": "Infection", "aliases": "Infection Infections", "definition": "Invasion of the host organism by microorganisms that can cause pathological conditions or diseases.\n    ", "id": "MESH:D007239"}
{"mention": "callosal lesion", "mention_text": "OBJECTIVE: This is to present reversible inferior colliculus lesions in metronidazole-induced encephalopathy, to focus on the diffusion-weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) imaging. MATERIALS AND METHODS: From November 2005 to September 2007, 8 patients (5 men and 3 women) were diagnosed as having metronidazole-induced encephalopathy (age range; 43-78 years). They had been taking metronidazole (total dosage, 45-120 g; duration, 30 days to 2 months) to treat the infection in various organs. Initial brain magnetic resonance imaging (MRI) were obtained after the hospitalization, including DWI (8/8), apparent diffusion coefficient (ADC) map (4/8), FLAIR (7/8), and T2-weighted image (8/8). Follow-up MRIs were performed on 5 patients from third to 14th days after discontinuation of metronidazole administration. Findings of initial and follow-up MRIs were retrospectively evaluated by 2 neuroradiologists by consensus, to analyze the presence of abnormal signal intensities, their locations, and signal changes on follow-up images. RESULTS: Initial MRIs showed abnormal high signal intensities on DWI and FLAIR (or T2-weighted image) at the dentate nucleus (8/8), inferior colliculus (6/8), corpus callosum (2/8), pons (2/8), medulla (1/8), and bilateral cerebral white matter (1/8). High-signal intensity lesions on DWI tended to show low signal intensity on ADC map (3/4), but in one patient, high signal intensity was shown at bilateral dentate nuclei on not only DWI but also ADC map. All the lesions in dentate, inferior colliculus, pons, and medullas had been resolved completely on follow-up MRIs in 5 patients, but in 1 patient of them, corpus callosal lesion persisted. CONCLUSIONS: Reversible inferior colliculus lesions could be considered as the characteristic for metronidazole-induced encephalopathy, next to the dentate nucleus involvement.", "entity": "Brain Diseases", "aliases": "Brain Disease Diseases Disorder Disorders CNS Intracranial Central Nervous System Encephalon", "definition": "Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.\n    ", "id": "MESH:D001927"}
{"mention": "morphine", "mention_text": "Comparison of the respiratory effects of i.v. infusions of morphine and regional analgesia by extradural block.", "entity": "Morphine", "aliases": "Chloride Morphine Contin MS Duramorph Morphia Sulfate (2:1) Anhydrous Pentahydrate Oramorph SR SDZ 202 250 202-250 202250 SDZ202 SDZ202-250 SDZ202250", "definition": "The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.\n    ", "id": "MESH:D009020"}
{"mention": "apnoea", "mention_text": "The incidence of postoperative respiratory apnoea was compared between five patients receiving a continuous i.v. infusion of morphine (mean 73.6 mg) and five patients receiving a continuous extradural infusion of 0.25% bupivacaine (mean 192 mg) in the 24-h period following upper abdominal surgery. Monitoring consisted of airflow detection by a carbon dioxide analyser, chest wall movement detected by pneumatic capsules, and continuous electrocardiograph recorded with a Holter ambulatory monitor. Both obstructive (P less than 0.05) and central apnoea (P less than 0.05) occurred more frequently in patients who had a morphine infusion. There was also a higher incidence of tachyarrhythmias (P less than 0.05) and ventricular ectopic beats (P less than 0.05) in the morphine infusion group.", "entity": "Apnea", "aliases": "Apnea Apneas", "definition": "A transient absence of spontaneous respiration.\n    ", "id": "MESH:D001049"}
{"mention": "morphine", "mention_text": "The incidence of postoperative respiratory apnoea was compared between five patients receiving a continuous i.v. infusion of morphine (mean 73.6 mg) and five patients receiving a continuous extradural infusion of 0.25% bupivacaine (mean 192 mg) in the 24-h period following upper abdominal surgery. Monitoring consisted of airflow detection by a carbon dioxide analyser, chest wall movement detected by pneumatic capsules, and continuous electrocardiograph recorded with a Holter ambulatory monitor. Both obstructive (P less than 0.05) and central apnoea (P less than 0.05) occurred more frequently in patients who had a morphine infusion. There was also a higher incidence of tachyarrhythmias (P less than 0.05) and ventricular ectopic beats (P less than 0.05) in the morphine infusion group.", "entity": "Morphine", "aliases": "Chloride Morphine Contin MS Duramorph Morphia Sulfate (2:1) Anhydrous Pentahydrate Oramorph SR SDZ 202 250 202-250 202250 SDZ202 SDZ202-250 SDZ202250", "definition": "The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.\n    ", "id": "MESH:D009020"}
{"mention": "bupivacaine", "mention_text": "The incidence of postoperative respiratory apnoea was compared between five patients receiving a continuous i.v. infusion of morphine (mean 73.6 mg) and five patients receiving a continuous extradural infusion of 0.25% bupivacaine (mean 192 mg) in the 24-h period following upper abdominal surgery. Monitoring consisted of airflow detection by a carbon dioxide analyser, chest wall movement detected by pneumatic capsules, and continuous electrocardiograph recorded with a Holter ambulatory monitor. Both obstructive (P less than 0.05) and central apnoea (P less than 0.05) occurred more frequently in patients who had a morphine infusion. There was also a higher incidence of tachyarrhythmias (P less than 0.05) and ventricular ectopic beats (P less than 0.05) in the morphine infusion group.", "entity": "Bupivacaine", "aliases": "1-Butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide Abbott Brand of Bupivacaine Hydrochloride Anhydrous Astra AstraZeneca Aventis Braun Bupivacaina Bupivacain Janapharm RPR Bupivacain-RPR Carbonate Monohydrochloride Monohydrate Buvacaina Carbostesin Dolanaest Inibsa Jenapharm Marcain Marcaine Pisa Sensorcaine Strathmann Svedocain Sin Vasoconstr", "definition": "A widely used local anesthetic agent.\n    ", "id": "MESH:D002045"}
{"mention": "carbon dioxide", "mention_text": "The incidence of postoperative respiratory apnoea was compared between five patients receiving a continuous i.v. infusion of morphine (mean 73.6 mg) and five patients receiving a continuous extradural infusion of 0.25% bupivacaine (mean 192 mg) in the 24-h period following upper abdominal surgery. Monitoring consisted of airflow detection by a carbon dioxide analyser, chest wall movement detected by pneumatic capsules, and continuous electrocardiograph recorded with a Holter ambulatory monitor. Both obstructive (P less than 0.05) and central apnoea (P less than 0.05) occurred more frequently in patients who had a morphine infusion. There was also a higher incidence of tachyarrhythmias (P less than 0.05) and ventricular ectopic beats (P less than 0.05) in the morphine infusion group.", "entity": "Carbon Dioxide", "aliases": "Anhydride Carbonic Carbon Dioxide", "definition": "A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals.\n    ", "id": "MESH:D002245"}
{"mention": "central apnoea", "mention_text": "The incidence of postoperative respiratory apnoea was compared between five patients receiving a continuous i.v. infusion of morphine (mean 73.6 mg) and five patients receiving a continuous extradural infusion of 0.25% bupivacaine (mean 192 mg) in the 24-h period following upper abdominal surgery. Monitoring consisted of airflow detection by a carbon dioxide analyser, chest wall movement detected by pneumatic capsules, and continuous electrocardiograph recorded with a Holter ambulatory monitor. Both obstructive (P less than 0.05) and central apnoea (P less than 0.05) occurred more frequently in patients who had a morphine infusion. There was also a higher incidence of tachyarrhythmias (P less than 0.05) and ventricular ectopic beats (P less than 0.05) in the morphine infusion group.", "entity": "Sleep Apnea, Central", "aliases": "Alveolar Hypoventilation Central Hypoventilations Apnea Sleep Apneas Breathing Sleep-Disordered Breathings Syndrome Primary Secondary Disordered Newborn Ondine of Lethal", "definition": "A condition associated with multiple episodes of sleep apnea which are distinguished from obstructive sleep apnea (SLEEP APNEA, OBSTRUCTIVE) by the complete cessation of efforts to breathe. This disorder is associated with dysfunction of central nervous system centers that regulate respiration.\n    ", "id": "MESH:D020182"}
{"mention": "tachyarrhythmias", "mention_text": "The incidence of postoperative respiratory apnoea was compared between five patients receiving a continuous i.v. infusion of morphine (mean 73.6 mg) and five patients receiving a continuous extradural infusion of 0.25% bupivacaine (mean 192 mg) in the 24-h period following upper abdominal surgery. Monitoring consisted of airflow detection by a carbon dioxide analyser, chest wall movement detected by pneumatic capsules, and continuous electrocardiograph recorded with a Holter ambulatory monitor. Both obstructive (P less than 0.05) and central apnoea (P less than 0.05) occurred more frequently in patients who had a morphine infusion. There was also a higher incidence of tachyarrhythmias (P less than 0.05) and ventricular ectopic beats (P less than 0.05) in the morphine infusion group.", "entity": "Tachycardia", "aliases": "Tachyarrhythmia Tachyarrhythmias Tachycardia Tachycardias", "definition": "Abnormally rapid heartbeat, usually with a HEART RATE above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia.\n    ", "id": "MESH:D013610"}
{"mention": "ventricular ectopic beats", "mention_text": "The incidence of postoperative respiratory apnoea was compared between five patients receiving a continuous i.v. infusion of morphine (mean 73.6 mg) and five patients receiving a continuous extradural infusion of 0.25% bupivacaine (mean 192 mg) in the 24-h period following upper abdominal surgery. Monitoring consisted of airflow detection by a carbon dioxide analyser, chest wall movement detected by pneumatic capsules, and continuous electrocardiograph recorded with a Holter ambulatory monitor. Both obstructive (P less than 0.05) and central apnoea (P less than 0.05) occurred more frequently in patients who had a morphine infusion. There was also a higher incidence of tachyarrhythmias (P less than 0.05) and ventricular ectopic beats (P less than 0.05) in the morphine infusion group.", "entity": "Ventricular Premature Complexes", "aliases": "Ectopic Beat Ventricular Beats Extrasystole Premature Complex Contraction Contractions Extrasystoles Complexes", "definition": "A type of cardiac arrhythmia with premature contractions of the HEART VENTRICLES. It is characterized by the premature QRS complex on ECG that is of abnormal shape and great duration (generally >129 msec). It is the most common form of all cardiac arrhythmias. Premature ventricular complexes have no clinical significance except in concurrence with heart diseases.\n    ", "id": "MESH:D018879"}
{"mention": "epileptic", "mention_text": "Magnetic resonance volumetry of the cerebellum in epileptic patients after phenytoin overdosages.", "entity": "Epilepsy", "aliases": "Aura Auras Awakening Epilepsy Cryptogenic Epilepsies Epileptic Seizure Seizures Disorder Disorders Single", "definition": "A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313)\n    ", "id": "MESH:D004827"}
{"mention": "phenytoin", "mention_text": "Magnetic resonance volumetry of the cerebellum in epileptic patients after phenytoin overdosages.", "entity": "Phenytoin", "aliases": "5,5-Diphenylhydantoin Antisacer Difenin Dihydan Dilantin Diphenylhydantoin Diphenylhydantoinate Sodium Epamin Epanutin Fenitoin Hydantol Park Davis brand of Phenytoin Pfizer Brand Phizer", "definition": "An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs.\n    ", "id": "MESH:D010672"}
{"mention": "overdosages", "mention_text": "Magnetic resonance volumetry of the cerebellum in epileptic patients after phenytoin overdosages.", "entity": "Drug Overdose", "aliases": "Drug Overdose Overdoses", "definition": "Accidental or deliberate use of a medication or street drug in excess of normal dosage.\n    ", "id": "MESH:D062787"}
{"mention": "phenytoin", "mention_text": "The aim of this study was to evaluate the relationship between phenytoin medication and cerebellar atrophy in patients who had experienced clinical intoxication. Five females and 6 males, 21-59 years of age, were examined with a 1.5-T whole-body system using a circular polarized head coil. Conventional spin echo images were acquired in the sagittal and transverse orientation. In addition, we performed a high-resolution 3D gradient echo, T1-weighted sequences at a 1-mm slice thickness. The images were subsequently processed to obtain volumetric data for the cerebellum. Cerebellar volume for the patient group ranged between 67.66 and 131.08 ml (mean 108.9 ml). In addition 3D gradient echo data sets from 10 healthy male and 10 healthy female age-matched volunteers were used to compare cerebellar volumes. Using linear regression we found that no correlation exists between seizure duration, elevation of phenytoin serum levels and cerebellar volume. However, multiple regression for the daily dosage, duration of phenytoin treatment and cerebellar volume revealed a correlation of these parameters. We conclude that phenytoin overdosage does not necessarily result in cerebellar atrophy and it is unlikely that phenytoin medication was the only cause of cerebellar atrophy in the remaining patients. Quantitative morphometric studies of the cerebellum provide valuable insights into the pathogenesis of cerebellar disorders.", "entity": "Phenytoin", "aliases": "5,5-Diphenylhydantoin Antisacer Difenin Dihydan Dilantin Diphenylhydantoin Diphenylhydantoinate Sodium Epamin Epanutin Fenitoin Hydantol Park Davis brand of Phenytoin Pfizer Brand Phizer", "definition": "An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs.\n    ", "id": "MESH:D010672"}
{"mention": "cerebellar atrophy", "mention_text": "The aim of this study was to evaluate the relationship between phenytoin medication and cerebellar atrophy in patients who had experienced clinical intoxication. Five females and 6 males, 21-59 years of age, were examined with a 1.5-T whole-body system using a circular polarized head coil. Conventional spin echo images were acquired in the sagittal and transverse orientation. In addition, we performed a high-resolution 3D gradient echo, T1-weighted sequences at a 1-mm slice thickness. The images were subsequently processed to obtain volumetric data for the cerebellum. Cerebellar volume for the patient group ranged between 67.66 and 131.08 ml (mean 108.9 ml). In addition 3D gradient echo data sets from 10 healthy male and 10 healthy female age-matched volunteers were used to compare cerebellar volumes. Using linear regression we found that no correlation exists between seizure duration, elevation of phenytoin serum levels and cerebellar volume. However, multiple regression for the daily dosage, duration of phenytoin treatment and cerebellar volume revealed a correlation of these parameters. We conclude that phenytoin overdosage does not necessarily result in cerebellar atrophy and it is unlikely that phenytoin medication was the only cause of cerebellar atrophy in the remaining patients. Quantitative morphometric studies of the cerebellum provide valuable insights into the pathogenesis of cerebellar disorders.", "entity": "Cerebellar Diseases", "aliases": "Cerebellar Disease Diseases Disorder Disorders Dysfunction Dysfunctions Syndrome Syndromes Cerebellum", "definition": "Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, GAIT ATAXIA, and MUSCLE HYPOTONIA.\n    ", "id": "MESH:D002526"}
{"mention": "seizure", "mention_text": "The aim of this study was to evaluate the relationship between phenytoin medication and cerebellar atrophy in patients who had experienced clinical intoxication. Five females and 6 males, 21-59 years of age, were examined with a 1.5-T whole-body system using a circular polarized head coil. Conventional spin echo images were acquired in the sagittal and transverse orientation. In addition, we performed a high-resolution 3D gradient echo, T1-weighted sequences at a 1-mm slice thickness. The images were subsequently processed to obtain volumetric data for the cerebellum. Cerebellar volume for the patient group ranged between 67.66 and 131.08 ml (mean 108.9 ml). In addition 3D gradient echo data sets from 10 healthy male and 10 healthy female age-matched volunteers were used to compare cerebellar volumes. Using linear regression we found that no correlation exists between seizure duration, elevation of phenytoin serum levels and cerebellar volume. However, multiple regression for the daily dosage, duration of phenytoin treatment and cerebellar volume revealed a correlation of these parameters. We conclude that phenytoin overdosage does not necessarily result in cerebellar atrophy and it is unlikely that phenytoin medication was the only cause of cerebellar atrophy in the remaining patients. Quantitative morphometric studies of the cerebellum provide valuable insights into the pathogenesis of cerebellar disorders.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "overdosage", "mention_text": "The aim of this study was to evaluate the relationship between phenytoin medication and cerebellar atrophy in patients who had experienced clinical intoxication. Five females and 6 males, 21-59 years of age, were examined with a 1.5-T whole-body system using a circular polarized head coil. Conventional spin echo images were acquired in the sagittal and transverse orientation. In addition, we performed a high-resolution 3D gradient echo, T1-weighted sequences at a 1-mm slice thickness. The images were subsequently processed to obtain volumetric data for the cerebellum. Cerebellar volume for the patient group ranged between 67.66 and 131.08 ml (mean 108.9 ml). In addition 3D gradient echo data sets from 10 healthy male and 10 healthy female age-matched volunteers were used to compare cerebellar volumes. Using linear regression we found that no correlation exists between seizure duration, elevation of phenytoin serum levels and cerebellar volume. However, multiple regression for the daily dosage, duration of phenytoin treatment and cerebellar volume revealed a correlation of these parameters. We conclude that phenytoin overdosage does not necessarily result in cerebellar atrophy and it is unlikely that phenytoin medication was the only cause of cerebellar atrophy in the remaining patients. Quantitative morphometric studies of the cerebellum provide valuable insights into the pathogenesis of cerebellar disorders.", "entity": "Drug Overdose", "aliases": "Drug Overdose Overdoses", "definition": "Accidental or deliberate use of a medication or street drug in excess of normal dosage.\n    ", "id": "MESH:D062787"}
{"mention": "cerebellar disorders", "mention_text": "The aim of this study was to evaluate the relationship between phenytoin medication and cerebellar atrophy in patients who had experienced clinical intoxication. Five females and 6 males, 21-59 years of age, were examined with a 1.5-T whole-body system using a circular polarized head coil. Conventional spin echo images were acquired in the sagittal and transverse orientation. In addition, we performed a high-resolution 3D gradient echo, T1-weighted sequences at a 1-mm slice thickness. The images were subsequently processed to obtain volumetric data for the cerebellum. Cerebellar volume for the patient group ranged between 67.66 and 131.08 ml (mean 108.9 ml). In addition 3D gradient echo data sets from 10 healthy male and 10 healthy female age-matched volunteers were used to compare cerebellar volumes. Using linear regression we found that no correlation exists between seizure duration, elevation of phenytoin serum levels and cerebellar volume. However, multiple regression for the daily dosage, duration of phenytoin treatment and cerebellar volume revealed a correlation of these parameters. We conclude that phenytoin overdosage does not necessarily result in cerebellar atrophy and it is unlikely that phenytoin medication was the only cause of cerebellar atrophy in the remaining patients. Quantitative morphometric studies of the cerebellum provide valuable insights into the pathogenesis of cerebellar disorders.", "entity": "Cerebellar Diseases", "aliases": "Cerebellar Disease Diseases Disorder Disorders Dysfunction Dysfunctions Syndrome Syndromes Cerebellum", "definition": "Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, GAIT ATAXIA, and MUSCLE HYPOTONIA.\n    ", "id": "MESH:D002526"}
{"mention": "myocardial damage", "mention_text": "Evaluation of cardiac troponin I and T levels as markers of myocardial damage in doxorubicin-induced cardiomyopathy rats, and their relationship with echocardiographic and histological findings.", "entity": "Cardiomyopathies", "aliases": "Cardiomyopathies Primary Secondary Cardiomyopathy Disease Myocardial Diseases Myocardiopathies Myocardiopathy", "definition": "A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).\n    ", "id": "MESH:D009202"}
{"mention": "doxorubicin", "mention_text": "Evaluation of cardiac troponin I and T levels as markers of myocardial damage in doxorubicin-induced cardiomyopathy rats, and their relationship with echocardiographic and histological findings.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "cardiomyopathy", "mention_text": "Evaluation of cardiac troponin I and T levels as markers of myocardial damage in doxorubicin-induced cardiomyopathy rats, and their relationship with echocardiographic and histological findings.", "entity": "Cardiomyopathies", "aliases": "Cardiomyopathies Primary Secondary Cardiomyopathy Disease Myocardial Diseases Myocardiopathies Myocardiopathy", "definition": "A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).\n    ", "id": "MESH:D009202"}
{"mention": "myocardial cell injury", "mention_text": "BACKGROUND: Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. We investigated the diagnostic value of cTnI and cTnT for the diagnosis of myocardial damage in a rat model of doxorubicin (DOX)-induced cardiomyopathy, and we examined the relationship between serial cTnI and cTnT with the development of cardiac disorders monitored by echocardiography and histological examinations in this model. METHODS: Thirty-five Wistar rats were given 1.5 mg/kg DOX, i.v., weekly for up to 8 weeks for a total cumulative dose of 12 mg/kg BW. Ten rats received saline as a control group. cTnI was measured with Access(R) (ng/ml) and a research immunoassay (pg/ml), and compared with cTnT, CK-MB mass and CK. By using transthoracic echocardiography, anterior and posterior wall thickness, LV diameters and LV fractional shortening (FS) were measured in all rats before DOX or saline, and at weeks 6 and 9 after treatment in all surviving rats. Histology was performed in DOX-rats at 6 and 9 weeks after the last DOX dose and in all controls. RESULTS: Eighteen of the DOX rats died prematurely of general toxicity during the 9-week period. End-diastolic (ED) and end-systolic (ES) LV diameters/BW significantly increased, whereas LV FS was decreased after 9 weeks in the DOX group (p<0.001). These parameters remained unchanged in controls. Histological evaluation of hearts from all rats given DOX revealed significant slight degrees of perivascular and interstitial fibrosis. In 7 of the 18 rats, degeneration and myocyte vacuolisation were found. Only five of the controls exhibited evidence of very slight perivascular fibrosis. A significant rise in cTnT was found in DOX rats after cumulative doses of 7.5 and 12 mg/kg in comparison with baseline (p<0.05). cTnT found in rats after 12 mg/kg were significantly greater than that found after 7.5 mg/kg DOX. Maximal cTnI (pg/ml) and cTnT levels were significantly increased in DOX rats compared with controls (p=0.006, 0.007). cTnI (ng/ml), CK-MB mass and CK remained unchanged in DOX rats compared with controls. All markers remained stable in controls. Analysis of data revealed a significant correlation between maximal cTnT and ED and ES LV diameters/BW (r=0.81 and 0.65; p<0.0001). A significant relationship was observed between maximal cTnT and the extent of myocardial morphological changes, and between LV diameters/BW and histological findings. CONCLUSIONS: Among markers of ischemic injury after DOX in rats, cTnT showed the greatest ability to detect myocardial damage assessed by echocardiographic detection and histological changes. Although there was a discrepancy between the amount of cTnI and cTnT after DOX, probably due to heterogeneity in cross-reactivities of mAbs to various cTnI and cTnT forms, it is likely that cTnT in rats after DOX indicates cell damage determined by the magnitude of injury induced and that cTnT should be a useful marker for the prediction of experimentally induced cardiotoxicity and possibly for cardioprotective experiments.", "entity": "Cardiomyopathies", "aliases": "Cardiomyopathies Primary Secondary Cardiomyopathy Disease Myocardial Diseases Myocardiopathies Myocardiopathy", "definition": "A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).\n    ", "id": "MESH:D009202"}
{"mention": "myocardial damage", "mention_text": "BACKGROUND: Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. We investigated the diagnostic value of cTnI and cTnT for the diagnosis of myocardial damage in a rat model of doxorubicin (DOX)-induced cardiomyopathy, and we examined the relationship between serial cTnI and cTnT with the development of cardiac disorders monitored by echocardiography and histological examinations in this model. METHODS: Thirty-five Wistar rats were given 1.5 mg/kg DOX, i.v., weekly for up to 8 weeks for a total cumulative dose of 12 mg/kg BW. Ten rats received saline as a control group. cTnI was measured with Access(R) (ng/ml) and a research immunoassay (pg/ml), and compared with cTnT, CK-MB mass and CK. By using transthoracic echocardiography, anterior and posterior wall thickness, LV diameters and LV fractional shortening (FS) were measured in all rats before DOX or saline, and at weeks 6 and 9 after treatment in all surviving rats. Histology was performed in DOX-rats at 6 and 9 weeks after the last DOX dose and in all controls. RESULTS: Eighteen of the DOX rats died prematurely of general toxicity during the 9-week period. End-diastolic (ED) and end-systolic (ES) LV diameters/BW significantly increased, whereas LV FS was decreased after 9 weeks in the DOX group (p<0.001). These parameters remained unchanged in controls. Histological evaluation of hearts from all rats given DOX revealed significant slight degrees of perivascular and interstitial fibrosis. In 7 of the 18 rats, degeneration and myocyte vacuolisation were found. Only five of the controls exhibited evidence of very slight perivascular fibrosis. A significant rise in cTnT was found in DOX rats after cumulative doses of 7.5 and 12 mg/kg in comparison with baseline (p<0.05). cTnT found in rats after 12 mg/kg were significantly greater than that found after 7.5 mg/kg DOX. Maximal cTnI (pg/ml) and cTnT levels were significantly increased in DOX rats compared with controls (p=0.006, 0.007). cTnI (ng/ml), CK-MB mass and CK remained unchanged in DOX rats compared with controls. All markers remained stable in controls. Analysis of data revealed a significant correlation between maximal cTnT and ED and ES LV diameters/BW (r=0.81 and 0.65; p<0.0001). A significant relationship was observed between maximal cTnT and the extent of myocardial morphological changes, and between LV diameters/BW and histological findings. CONCLUSIONS: Among markers of ischemic injury after DOX in rats, cTnT showed the greatest ability to detect myocardial damage assessed by echocardiographic detection and histological changes. Although there was a discrepancy between the amount of cTnI and cTnT after DOX, probably due to heterogeneity in cross-reactivities of mAbs to various cTnI and cTnT forms, it is likely that cTnT in rats after DOX indicates cell damage determined by the magnitude of injury induced and that cTnT should be a useful marker for the prediction of experimentally induced cardiotoxicity and possibly for cardioprotective experiments.", "entity": "Cardiomyopathies", "aliases": "Cardiomyopathies Primary Secondary Cardiomyopathy Disease Myocardial Diseases Myocardiopathies Myocardiopathy", "definition": "A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).\n    ", "id": "MESH:D009202"}
{"mention": "doxorubicin", "mention_text": "BACKGROUND: Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. We investigated the diagnostic value of cTnI and cTnT for the diagnosis of myocardial damage in a rat model of doxorubicin (DOX)-induced cardiomyopathy, and we examined the relationship between serial cTnI and cTnT with the development of cardiac disorders monitored by echocardiography and histological examinations in this model. METHODS: Thirty-five Wistar rats were given 1.5 mg/kg DOX, i.v., weekly for up to 8 weeks for a total cumulative dose of 12 mg/kg BW. Ten rats received saline as a control group. cTnI was measured with Access(R) (ng/ml) and a research immunoassay (pg/ml), and compared with cTnT, CK-MB mass and CK. By using transthoracic echocardiography, anterior and posterior wall thickness, LV diameters and LV fractional shortening (FS) were measured in all rats before DOX or saline, and at weeks 6 and 9 after treatment in all surviving rats. Histology was performed in DOX-rats at 6 and 9 weeks after the last DOX dose and in all controls. RESULTS: Eighteen of the DOX rats died prematurely of general toxicity during the 9-week period. End-diastolic (ED) and end-systolic (ES) LV diameters/BW significantly increased, whereas LV FS was decreased after 9 weeks in the DOX group (p<0.001). These parameters remained unchanged in controls. Histological evaluation of hearts from all rats given DOX revealed significant slight degrees of perivascular and interstitial fibrosis. In 7 of the 18 rats, degeneration and myocyte vacuolisation were found. Only five of the controls exhibited evidence of very slight perivascular fibrosis. A significant rise in cTnT was found in DOX rats after cumulative doses of 7.5 and 12 mg/kg in comparison with baseline (p<0.05). cTnT found in rats after 12 mg/kg were significantly greater than that found after 7.5 mg/kg DOX. Maximal cTnI (pg/ml) and cTnT levels were significantly increased in DOX rats compared with controls (p=0.006, 0.007). cTnI (ng/ml), CK-MB mass and CK remained unchanged in DOX rats compared with controls. All markers remained stable in controls. Analysis of data revealed a significant correlation between maximal cTnT and ED and ES LV diameters/BW (r=0.81 and 0.65; p<0.0001). A significant relationship was observed between maximal cTnT and the extent of myocardial morphological changes, and between LV diameters/BW and histological findings. CONCLUSIONS: Among markers of ischemic injury after DOX in rats, cTnT showed the greatest ability to detect myocardial damage assessed by echocardiographic detection and histological changes. Although there was a discrepancy between the amount of cTnI and cTnT after DOX, probably due to heterogeneity in cross-reactivities of mAbs to various cTnI and cTnT forms, it is likely that cTnT in rats after DOX indicates cell damage determined by the magnitude of injury induced and that cTnT should be a useful marker for the prediction of experimentally induced cardiotoxicity and possibly for cardioprotective experiments.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "DOX", "mention_text": "BACKGROUND: Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. We investigated the diagnostic value of cTnI and cTnT for the diagnosis of myocardial damage in a rat model of doxorubicin (DOX)-induced cardiomyopathy, and we examined the relationship between serial cTnI and cTnT with the development of cardiac disorders monitored by echocardiography and histological examinations in this model. METHODS: Thirty-five Wistar rats were given 1.5 mg/kg DOX, i.v., weekly for up to 8 weeks for a total cumulative dose of 12 mg/kg BW. Ten rats received saline as a control group. cTnI was measured with Access(R) (ng/ml) and a research immunoassay (pg/ml), and compared with cTnT, CK-MB mass and CK. By using transthoracic echocardiography, anterior and posterior wall thickness, LV diameters and LV fractional shortening (FS) were measured in all rats before DOX or saline, and at weeks 6 and 9 after treatment in all surviving rats. Histology was performed in DOX-rats at 6 and 9 weeks after the last DOX dose and in all controls. RESULTS: Eighteen of the DOX rats died prematurely of general toxicity during the 9-week period. End-diastolic (ED) and end-systolic (ES) LV diameters/BW significantly increased, whereas LV FS was decreased after 9 weeks in the DOX group (p<0.001). These parameters remained unchanged in controls. Histological evaluation of hearts from all rats given DOX revealed significant slight degrees of perivascular and interstitial fibrosis. In 7 of the 18 rats, degeneration and myocyte vacuolisation were found. Only five of the controls exhibited evidence of very slight perivascular fibrosis. A significant rise in cTnT was found in DOX rats after cumulative doses of 7.5 and 12 mg/kg in comparison with baseline (p<0.05). cTnT found in rats after 12 mg/kg were significantly greater than that found after 7.5 mg/kg DOX. Maximal cTnI (pg/ml) and cTnT levels were significantly increased in DOX rats compared with controls (p=0.006, 0.007). cTnI (ng/ml), CK-MB mass and CK remained unchanged in DOX rats compared with controls. All markers remained stable in controls. Analysis of data revealed a significant correlation between maximal cTnT and ED and ES LV diameters/BW (r=0.81 and 0.65; p<0.0001). A significant relationship was observed between maximal cTnT and the extent of myocardial morphological changes, and between LV diameters/BW and histological findings. CONCLUSIONS: Among markers of ischemic injury after DOX in rats, cTnT showed the greatest ability to detect myocardial damage assessed by echocardiographic detection and histological changes. Although there was a discrepancy between the amount of cTnI and cTnT after DOX, probably due to heterogeneity in cross-reactivities of mAbs to various cTnI and cTnT forms, it is likely that cTnT in rats after DOX indicates cell damage determined by the magnitude of injury induced and that cTnT should be a useful marker for the prediction of experimentally induced cardiotoxicity and possibly for cardioprotective experiments.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "cardiomyopathy", "mention_text": "BACKGROUND: Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. We investigated the diagnostic value of cTnI and cTnT for the diagnosis of myocardial damage in a rat model of doxorubicin (DOX)-induced cardiomyopathy, and we examined the relationship between serial cTnI and cTnT with the development of cardiac disorders monitored by echocardiography and histological examinations in this model. METHODS: Thirty-five Wistar rats were given 1.5 mg/kg DOX, i.v., weekly for up to 8 weeks for a total cumulative dose of 12 mg/kg BW. Ten rats received saline as a control group. cTnI was measured with Access(R) (ng/ml) and a research immunoassay (pg/ml), and compared with cTnT, CK-MB mass and CK. By using transthoracic echocardiography, anterior and posterior wall thickness, LV diameters and LV fractional shortening (FS) were measured in all rats before DOX or saline, and at weeks 6 and 9 after treatment in all surviving rats. Histology was performed in DOX-rats at 6 and 9 weeks after the last DOX dose and in all controls. RESULTS: Eighteen of the DOX rats died prematurely of general toxicity during the 9-week period. End-diastolic (ED) and end-systolic (ES) LV diameters/BW significantly increased, whereas LV FS was decreased after 9 weeks in the DOX group (p<0.001). These parameters remained unchanged in controls. Histological evaluation of hearts from all rats given DOX revealed significant slight degrees of perivascular and interstitial fibrosis. In 7 of the 18 rats, degeneration and myocyte vacuolisation were found. Only five of the controls exhibited evidence of very slight perivascular fibrosis. A significant rise in cTnT was found in DOX rats after cumulative doses of 7.5 and 12 mg/kg in comparison with baseline (p<0.05). cTnT found in rats after 12 mg/kg were significantly greater than that found after 7.5 mg/kg DOX. Maximal cTnI (pg/ml) and cTnT levels were significantly increased in DOX rats compared with controls (p=0.006, 0.007). cTnI (ng/ml), CK-MB mass and CK remained unchanged in DOX rats compared with controls. All markers remained stable in controls. Analysis of data revealed a significant correlation between maximal cTnT and ED and ES LV diameters/BW (r=0.81 and 0.65; p<0.0001). A significant relationship was observed between maximal cTnT and the extent of myocardial morphological changes, and between LV diameters/BW and histological findings. CONCLUSIONS: Among markers of ischemic injury after DOX in rats, cTnT showed the greatest ability to detect myocardial damage assessed by echocardiographic detection and histological changes. Although there was a discrepancy between the amount of cTnI and cTnT after DOX, probably due to heterogeneity in cross-reactivities of mAbs to various cTnI and cTnT forms, it is likely that cTnT in rats after DOX indicates cell damage determined by the magnitude of injury induced and that cTnT should be a useful marker for the prediction of experimentally induced cardiotoxicity and possibly for cardioprotective experiments.", "entity": "Cardiomyopathies", "aliases": "Cardiomyopathies Primary Secondary Cardiomyopathy Disease Myocardial Diseases Myocardiopathies Myocardiopathy", "definition": "A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).\n    ", "id": "MESH:D009202"}
{"mention": "cardiac disorders", "mention_text": "BACKGROUND: Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. We investigated the diagnostic value of cTnI and cTnT for the diagnosis of myocardial damage in a rat model of doxorubicin (DOX)-induced cardiomyopathy, and we examined the relationship between serial cTnI and cTnT with the development of cardiac disorders monitored by echocardiography and histological examinations in this model. METHODS: Thirty-five Wistar rats were given 1.5 mg/kg DOX, i.v., weekly for up to 8 weeks for a total cumulative dose of 12 mg/kg BW. Ten rats received saline as a control group. cTnI was measured with Access(R) (ng/ml) and a research immunoassay (pg/ml), and compared with cTnT, CK-MB mass and CK. By using transthoracic echocardiography, anterior and posterior wall thickness, LV diameters and LV fractional shortening (FS) were measured in all rats before DOX or saline, and at weeks 6 and 9 after treatment in all surviving rats. Histology was performed in DOX-rats at 6 and 9 weeks after the last DOX dose and in all controls. RESULTS: Eighteen of the DOX rats died prematurely of general toxicity during the 9-week period. End-diastolic (ED) and end-systolic (ES) LV diameters/BW significantly increased, whereas LV FS was decreased after 9 weeks in the DOX group (p<0.001). These parameters remained unchanged in controls. Histological evaluation of hearts from all rats given DOX revealed significant slight degrees of perivascular and interstitial fibrosis. In 7 of the 18 rats, degeneration and myocyte vacuolisation were found. Only five of the controls exhibited evidence of very slight perivascular fibrosis. A significant rise in cTnT was found in DOX rats after cumulative doses of 7.5 and 12 mg/kg in comparison with baseline (p<0.05). cTnT found in rats after 12 mg/kg were significantly greater than that found after 7.5 mg/kg DOX. Maximal cTnI (pg/ml) and cTnT levels were significantly increased in DOX rats compared with controls (p=0.006, 0.007). cTnI (ng/ml), CK-MB mass and CK remained unchanged in DOX rats compared with controls. All markers remained stable in controls. Analysis of data revealed a significant correlation between maximal cTnT and ED and ES LV diameters/BW (r=0.81 and 0.65; p<0.0001). A significant relationship was observed between maximal cTnT and the extent of myocardial morphological changes, and between LV diameters/BW and histological findings. CONCLUSIONS: Among markers of ischemic injury after DOX in rats, cTnT showed the greatest ability to detect myocardial damage assessed by echocardiographic detection and histological changes. Although there was a discrepancy between the amount of cTnI and cTnT after DOX, probably due to heterogeneity in cross-reactivities of mAbs to various cTnI and cTnT forms, it is likely that cTnT in rats after DOX indicates cell damage determined by the magnitude of injury induced and that cTnT should be a useful marker for the prediction of experimentally induced cardiotoxicity and possibly for cardioprotective experiments.", "entity": "Heart Diseases", "aliases": "Cardiac Disease Diseases Heart", "definition": "Pathological conditions involving the HEART including its structural and functional abnormalities.\n    ", "id": "MESH:D006331"}
{"mention": "toxicity", "mention_text": "BACKGROUND: Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. We investigated the diagnostic value of cTnI and cTnT for the diagnosis of myocardial damage in a rat model of doxorubicin (DOX)-induced cardiomyopathy, and we examined the relationship between serial cTnI and cTnT with the development of cardiac disorders monitored by echocardiography and histological examinations in this model. METHODS: Thirty-five Wistar rats were given 1.5 mg/kg DOX, i.v., weekly for up to 8 weeks for a total cumulative dose of 12 mg/kg BW. Ten rats received saline as a control group. cTnI was measured with Access(R) (ng/ml) and a research immunoassay (pg/ml), and compared with cTnT, CK-MB mass and CK. By using transthoracic echocardiography, anterior and posterior wall thickness, LV diameters and LV fractional shortening (FS) were measured in all rats before DOX or saline, and at weeks 6 and 9 after treatment in all surviving rats. Histology was performed in DOX-rats at 6 and 9 weeks after the last DOX dose and in all controls. RESULTS: Eighteen of the DOX rats died prematurely of general toxicity during the 9-week period. End-diastolic (ED) and end-systolic (ES) LV diameters/BW significantly increased, whereas LV FS was decreased after 9 weeks in the DOX group (p<0.001). These parameters remained unchanged in controls. Histological evaluation of hearts from all rats given DOX revealed significant slight degrees of perivascular and interstitial fibrosis. In 7 of the 18 rats, degeneration and myocyte vacuolisation were found. Only five of the controls exhibited evidence of very slight perivascular fibrosis. A significant rise in cTnT was found in DOX rats after cumulative doses of 7.5 and 12 mg/kg in comparison with baseline (p<0.05). cTnT found in rats after 12 mg/kg were significantly greater than that found after 7.5 mg/kg DOX. Maximal cTnI (pg/ml) and cTnT levels were significantly increased in DOX rats compared with controls (p=0.006, 0.007). cTnI (ng/ml), CK-MB mass and CK remained unchanged in DOX rats compared with controls. All markers remained stable in controls. Analysis of data revealed a significant correlation between maximal cTnT and ED and ES LV diameters/BW (r=0.81 and 0.65; p<0.0001). A significant relationship was observed between maximal cTnT and the extent of myocardial morphological changes, and between LV diameters/BW and histological findings. CONCLUSIONS: Among markers of ischemic injury after DOX in rats, cTnT showed the greatest ability to detect myocardial damage assessed by echocardiographic detection and histological changes. Although there was a discrepancy between the amount of cTnI and cTnT after DOX, probably due to heterogeneity in cross-reactivities of mAbs to various cTnI and cTnT forms, it is likely that cTnT in rats after DOX indicates cell damage determined by the magnitude of injury induced and that cTnT should be a useful marker for the prediction of experimentally induced cardiotoxicity and possibly for cardioprotective experiments.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "fibrosis", "mention_text": "BACKGROUND: Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. We investigated the diagnostic value of cTnI and cTnT for the diagnosis of myocardial damage in a rat model of doxorubicin (DOX)-induced cardiomyopathy, and we examined the relationship between serial cTnI and cTnT with the development of cardiac disorders monitored by echocardiography and histological examinations in this model. METHODS: Thirty-five Wistar rats were given 1.5 mg/kg DOX, i.v., weekly for up to 8 weeks for a total cumulative dose of 12 mg/kg BW. Ten rats received saline as a control group. cTnI was measured with Access(R) (ng/ml) and a research immunoassay (pg/ml), and compared with cTnT, CK-MB mass and CK. By using transthoracic echocardiography, anterior and posterior wall thickness, LV diameters and LV fractional shortening (FS) were measured in all rats before DOX or saline, and at weeks 6 and 9 after treatment in all surviving rats. Histology was performed in DOX-rats at 6 and 9 weeks after the last DOX dose and in all controls. RESULTS: Eighteen of the DOX rats died prematurely of general toxicity during the 9-week period. End-diastolic (ED) and end-systolic (ES) LV diameters/BW significantly increased, whereas LV FS was decreased after 9 weeks in the DOX group (p<0.001). These parameters remained unchanged in controls. Histological evaluation of hearts from all rats given DOX revealed significant slight degrees of perivascular and interstitial fibrosis. In 7 of the 18 rats, degeneration and myocyte vacuolisation were found. Only five of the controls exhibited evidence of very slight perivascular fibrosis. A significant rise in cTnT was found in DOX rats after cumulative doses of 7.5 and 12 mg/kg in comparison with baseline (p<0.05). cTnT found in rats after 12 mg/kg were significantly greater than that found after 7.5 mg/kg DOX. Maximal cTnI (pg/ml) and cTnT levels were significantly increased in DOX rats compared with controls (p=0.006, 0.007). cTnI (ng/ml), CK-MB mass and CK remained unchanged in DOX rats compared with controls. All markers remained stable in controls. Analysis of data revealed a significant correlation between maximal cTnT and ED and ES LV diameters/BW (r=0.81 and 0.65; p<0.0001). A significant relationship was observed between maximal cTnT and the extent of myocardial morphological changes, and between LV diameters/BW and histological findings. CONCLUSIONS: Among markers of ischemic injury after DOX in rats, cTnT showed the greatest ability to detect myocardial damage assessed by echocardiographic detection and histological changes. Although there was a discrepancy between the amount of cTnI and cTnT after DOX, probably due to heterogeneity in cross-reactivities of mAbs to various cTnI and cTnT forms, it is likely that cTnT in rats after DOX indicates cell damage determined by the magnitude of injury induced and that cTnT should be a useful marker for the prediction of experimentally induced cardiotoxicity and possibly for cardioprotective experiments.", "entity": "Fibrosis", "aliases": "Cirrhosis Fibroses Fibrosis", "definition": "Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.\n    ", "id": "MESH:D005355"}
{"mention": "ischemic injury", "mention_text": "BACKGROUND: Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. We investigated the diagnostic value of cTnI and cTnT for the diagnosis of myocardial damage in a rat model of doxorubicin (DOX)-induced cardiomyopathy, and we examined the relationship between serial cTnI and cTnT with the development of cardiac disorders monitored by echocardiography and histological examinations in this model. METHODS: Thirty-five Wistar rats were given 1.5 mg/kg DOX, i.v., weekly for up to 8 weeks for a total cumulative dose of 12 mg/kg BW. Ten rats received saline as a control group. cTnI was measured with Access(R) (ng/ml) and a research immunoassay (pg/ml), and compared with cTnT, CK-MB mass and CK. By using transthoracic echocardiography, anterior and posterior wall thickness, LV diameters and LV fractional shortening (FS) were measured in all rats before DOX or saline, and at weeks 6 and 9 after treatment in all surviving rats. Histology was performed in DOX-rats at 6 and 9 weeks after the last DOX dose and in all controls. RESULTS: Eighteen of the DOX rats died prematurely of general toxicity during the 9-week period. End-diastolic (ED) and end-systolic (ES) LV diameters/BW significantly increased, whereas LV FS was decreased after 9 weeks in the DOX group (p<0.001). These parameters remained unchanged in controls. Histological evaluation of hearts from all rats given DOX revealed significant slight degrees of perivascular and interstitial fibrosis. In 7 of the 18 rats, degeneration and myocyte vacuolisation were found. Only five of the controls exhibited evidence of very slight perivascular fibrosis. A significant rise in cTnT was found in DOX rats after cumulative doses of 7.5 and 12 mg/kg in comparison with baseline (p<0.05). cTnT found in rats after 12 mg/kg were significantly greater than that found after 7.5 mg/kg DOX. Maximal cTnI (pg/ml) and cTnT levels were significantly increased in DOX rats compared with controls (p=0.006, 0.007). cTnI (ng/ml), CK-MB mass and CK remained unchanged in DOX rats compared with controls. All markers remained stable in controls. Analysis of data revealed a significant correlation between maximal cTnT and ED and ES LV diameters/BW (r=0.81 and 0.65; p<0.0001). A significant relationship was observed between maximal cTnT and the extent of myocardial morphological changes, and between LV diameters/BW and histological findings. CONCLUSIONS: Among markers of ischemic injury after DOX in rats, cTnT showed the greatest ability to detect myocardial damage assessed by echocardiographic detection and histological changes. Although there was a discrepancy between the amount of cTnI and cTnT after DOX, probably due to heterogeneity in cross-reactivities of mAbs to various cTnI and cTnT forms, it is likely that cTnT in rats after DOX indicates cell damage determined by the magnitude of injury induced and that cTnT should be a useful marker for the prediction of experimentally induced cardiotoxicity and possibly for cardioprotective experiments.", "entity": "Myocardial Ischemia", "aliases": "Disease Ischemic Heart Diseases Ischemia Myocardial Ischemias", "definition": "A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).\n    ", "id": "MESH:D017202"}
{"mention": "cardiotoxicity", "mention_text": "BACKGROUND: Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. We investigated the diagnostic value of cTnI and cTnT for the diagnosis of myocardial damage in a rat model of doxorubicin (DOX)-induced cardiomyopathy, and we examined the relationship between serial cTnI and cTnT with the development of cardiac disorders monitored by echocardiography and histological examinations in this model. METHODS: Thirty-five Wistar rats were given 1.5 mg/kg DOX, i.v., weekly for up to 8 weeks for a total cumulative dose of 12 mg/kg BW. Ten rats received saline as a control group. cTnI was measured with Access(R) (ng/ml) and a research immunoassay (pg/ml), and compared with cTnT, CK-MB mass and CK. By using transthoracic echocardiography, anterior and posterior wall thickness, LV diameters and LV fractional shortening (FS) were measured in all rats before DOX or saline, and at weeks 6 and 9 after treatment in all surviving rats. Histology was performed in DOX-rats at 6 and 9 weeks after the last DOX dose and in all controls. RESULTS: Eighteen of the DOX rats died prematurely of general toxicity during the 9-week period. End-diastolic (ED) and end-systolic (ES) LV diameters/BW significantly increased, whereas LV FS was decreased after 9 weeks in the DOX group (p<0.001). These parameters remained unchanged in controls. Histological evaluation of hearts from all rats given DOX revealed significant slight degrees of perivascular and interstitial fibrosis. In 7 of the 18 rats, degeneration and myocyte vacuolisation were found. Only five of the controls exhibited evidence of very slight perivascular fibrosis. A significant rise in cTnT was found in DOX rats after cumulative doses of 7.5 and 12 mg/kg in comparison with baseline (p<0.05). cTnT found in rats after 12 mg/kg were significantly greater than that found after 7.5 mg/kg DOX. Maximal cTnI (pg/ml) and cTnT levels were significantly increased in DOX rats compared with controls (p=0.006, 0.007). cTnI (ng/ml), CK-MB mass and CK remained unchanged in DOX rats compared with controls. All markers remained stable in controls. Analysis of data revealed a significant correlation between maximal cTnT and ED and ES LV diameters/BW (r=0.81 and 0.65; p<0.0001). A significant relationship was observed between maximal cTnT and the extent of myocardial morphological changes, and between LV diameters/BW and histological findings. CONCLUSIONS: Among markers of ischemic injury after DOX in rats, cTnT showed the greatest ability to detect myocardial damage assessed by echocardiographic detection and histological changes. Although there was a discrepancy between the amount of cTnI and cTnT after DOX, probably due to heterogeneity in cross-reactivities of mAbs to various cTnI and cTnT forms, it is likely that cTnT in rats after DOX indicates cell damage determined by the magnitude of injury induced and that cTnT should be a useful marker for the prediction of experimentally induced cardiotoxicity and possibly for cardioprotective experiments.", "entity": "Cardiotoxicity", "aliases": "Cardiac Toxicities Toxicity Cardiotoxicities Cardiotoxicity", "definition": "Damage to the heart or its function secondary to exposure to toxic substances such as drugs used in CHEMOTHERAPY; IMMUNOTHERAPY; or RADIATION.\n    ", "id": "MESH:D066126"}
{"mention": "pain", "mention_text": "Calcineurin-inhibitor induced pain syndrome (CIPS): a severe disabling complication after organ transplantation.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "pain", "mention_text": "Bone pain after transplantation is a frequent complication that can be caused by several diseases. Treatment strategies depend on the correct diagnosis of the pain. Nine patients with severe pain in their feet, which was registered after transplantation, were investigated. Bone scans showed an increased tracer uptake of the foot bones. Magnetic resonance imaging demonstrated bone marrow oedema in the painful bones. Pain was not explained by other diseases causing foot pain, like reflex sympathetic dystrophy, polyneuropathy, Morton's neuralgia, gout, osteoporosis, avascular necrosis, intermittent claudication, orthopaedic foot deformities, stress fractures, and hyperparathyroidism. The reduction of cyclosporine- or tacrolimus trough levels and the administration of calcium channel blockers led to relief of pain. The Calcineurin-inhibitor Induced Pain Syndrome (CIPS) is a rare but severe side effect of cyclosporine or tacrolimus and is accurately diagnosed by its typical presentation, magnetic resonance imaging and bone scans. Incorrect diagnosis of the syndrome will lead to a significant reduction of life quality in patients suffering from CIPS.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "bone marrow", "mention_text": "Bone pain after transplantation is a frequent complication that can be caused by several diseases. Treatment strategies depend on the correct diagnosis of the pain. Nine patients with severe pain in their feet, which was registered after transplantation, were investigated. Bone scans showed an increased tracer uptake of the foot bones. Magnetic resonance imaging demonstrated bone marrow oedema in the painful bones. Pain was not explained by other diseases causing foot pain, like reflex sympathetic dystrophy, polyneuropathy, Morton's neuralgia, gout, osteoporosis, avascular necrosis, intermittent claudication, orthopaedic foot deformities, stress fractures, and hyperparathyroidism. The reduction of cyclosporine- or tacrolimus trough levels and the administration of calcium channel blockers led to relief of pain. The Calcineurin-inhibitor Induced Pain Syndrome (CIPS) is a rare but severe side effect of cyclosporine or tacrolimus and is accurately diagnosed by its typical presentation, magnetic resonance imaging and bone scans. Incorrect diagnosis of the syndrome will lead to a significant reduction of life quality in patients suffering from CIPS.", "entity": "Bone Marrow Diseases", "aliases": "Bone Marrow Disease Diseases", "definition": "", "id": "MESH:D001855"}
{"mention": "oedema", "mention_text": "Bone pain after transplantation is a frequent complication that can be caused by several diseases. Treatment strategies depend on the correct diagnosis of the pain. Nine patients with severe pain in their feet, which was registered after transplantation, were investigated. Bone scans showed an increased tracer uptake of the foot bones. Magnetic resonance imaging demonstrated bone marrow oedema in the painful bones. Pain was not explained by other diseases causing foot pain, like reflex sympathetic dystrophy, polyneuropathy, Morton's neuralgia, gout, osteoporosis, avascular necrosis, intermittent claudication, orthopaedic foot deformities, stress fractures, and hyperparathyroidism. The reduction of cyclosporine- or tacrolimus trough levels and the administration of calcium channel blockers led to relief of pain. The Calcineurin-inhibitor Induced Pain Syndrome (CIPS) is a rare but severe side effect of cyclosporine or tacrolimus and is accurately diagnosed by its typical presentation, magnetic resonance imaging and bone scans. Incorrect diagnosis of the syndrome will lead to a significant reduction of life quality in patients suffering from CIPS.", "entity": "Edema", "aliases": "Anasarca Dropsy Edema Hydrops", "definition": "Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE.\n    ", "id": "MESH:D004487"}
{"mention": "Pain", "mention_text": "Bone pain after transplantation is a frequent complication that can be caused by several diseases. Treatment strategies depend on the correct diagnosis of the pain. Nine patients with severe pain in their feet, which was registered after transplantation, were investigated. Bone scans showed an increased tracer uptake of the foot bones. Magnetic resonance imaging demonstrated bone marrow oedema in the painful bones. Pain was not explained by other diseases causing foot pain, like reflex sympathetic dystrophy, polyneuropathy, Morton's neuralgia, gout, osteoporosis, avascular necrosis, intermittent claudication, orthopaedic foot deformities, stress fractures, and hyperparathyroidism. The reduction of cyclosporine- or tacrolimus trough levels and the administration of calcium channel blockers led to relief of pain. The Calcineurin-inhibitor Induced Pain Syndrome (CIPS) is a rare but severe side effect of cyclosporine or tacrolimus and is accurately diagnosed by its typical presentation, magnetic resonance imaging and bone scans. Incorrect diagnosis of the syndrome will lead to a significant reduction of life quality in patients suffering from CIPS.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "reflex sympathetic dystrophy", "mention_text": "Bone pain after transplantation is a frequent complication that can be caused by several diseases. Treatment strategies depend on the correct diagnosis of the pain. Nine patients with severe pain in their feet, which was registered after transplantation, were investigated. Bone scans showed an increased tracer uptake of the foot bones. Magnetic resonance imaging demonstrated bone marrow oedema in the painful bones. Pain was not explained by other diseases causing foot pain, like reflex sympathetic dystrophy, polyneuropathy, Morton's neuralgia, gout, osteoporosis, avascular necrosis, intermittent claudication, orthopaedic foot deformities, stress fractures, and hyperparathyroidism. The reduction of cyclosporine- or tacrolimus trough levels and the administration of calcium channel blockers led to relief of pain. The Calcineurin-inhibitor Induced Pain Syndrome (CIPS) is a rare but severe side effect of cyclosporine or tacrolimus and is accurately diagnosed by its typical presentation, magnetic resonance imaging and bone scans. Incorrect diagnosis of the syndrome will lead to a significant reduction of life quality in patients suffering from CIPS.", "entity": "Reflex Sympathetic Dystrophy", "aliases": "Algodystrophic Syndrome Algodystrophies Algodystrophy Atrophies Sudek's Atrophy Sudek CPRS Type I Is Cervical Sympathetic Dystrophies Dystrophy Complex Regional Pain Reflex RSD (Reflex Dystrophy) RSDs Dystrophia Shoulder Hand Shoulder-Hand Syndromes Sudeks Dystrophias", "definition": "A syndrome characterized by severe burning pain in an extremity accompanied by sudomotor, vasomotor, and trophic changes in bone without an associated specific nerve injury. This condition is most often precipitated by trauma to soft tissue or nerve complexes. The skin over the affected region is usually erythematous and demonstrates hypersensitivity to tactile stimuli and erythema. (Adams et al., Principles of Neurology, 6th ed, p1360; Pain 1995 Oct;63(1):127-33)\n    ", "id": "MESH:D012019"}
{"mention": "polyneuropathy", "mention_text": "Bone pain after transplantation is a frequent complication that can be caused by several diseases. Treatment strategies depend on the correct diagnosis of the pain. Nine patients with severe pain in their feet, which was registered after transplantation, were investigated. Bone scans showed an increased tracer uptake of the foot bones. Magnetic resonance imaging demonstrated bone marrow oedema in the painful bones. Pain was not explained by other diseases causing foot pain, like reflex sympathetic dystrophy, polyneuropathy, Morton's neuralgia, gout, osteoporosis, avascular necrosis, intermittent claudication, orthopaedic foot deformities, stress fractures, and hyperparathyroidism. The reduction of cyclosporine- or tacrolimus trough levels and the administration of calcium channel blockers led to relief of pain. The Calcineurin-inhibitor Induced Pain Syndrome (CIPS) is a rare but severe side effect of cyclosporine or tacrolimus and is accurately diagnosed by its typical presentation, magnetic resonance imaging and bone scans. Incorrect diagnosis of the syndrome will lead to a significant reduction of life quality in patients suffering from CIPS.", "entity": "Polyneuropathies", "aliases": "Acquired Polyneuropathies Polyneuropathy Critical Illness Familial Inherited Motor", "definition": "Diseases of multiple peripheral nerves simultaneously. Polyneuropathies usually are characterized by symmetrical, bilateral distal motor and sensory impairment with a graded increase in severity distally. The pathological processes affecting peripheral nerves include degeneration of the axon, myelin or both. The various forms of polyneuropathy are categorized by the type of nerve affected (e.g., sensory, motor, or autonomic), by the distribution of nerve injury (e.g., distal vs. proximal), by nerve component primarily affected (e.g., demyelinating vs. axonal), by etiology, or by pattern of inheritance.\n    ", "id": "MESH:D011115"}
{"mention": "Morton's neuralgia", "mention_text": "Bone pain after transplantation is a frequent complication that can be caused by several diseases. Treatment strategies depend on the correct diagnosis of the pain. Nine patients with severe pain in their feet, which was registered after transplantation, were investigated. Bone scans showed an increased tracer uptake of the foot bones. Magnetic resonance imaging demonstrated bone marrow oedema in the painful bones. Pain was not explained by other diseases causing foot pain, like reflex sympathetic dystrophy, polyneuropathy, Morton's neuralgia, gout, osteoporosis, avascular necrosis, intermittent claudication, orthopaedic foot deformities, stress fractures, and hyperparathyroidism. The reduction of cyclosporine- or tacrolimus trough levels and the administration of calcium channel blockers led to relief of pain. The Calcineurin-inhibitor Induced Pain Syndrome (CIPS) is a rare but severe side effect of cyclosporine or tacrolimus and is accurately diagnosed by its typical presentation, magnetic resonance imaging and bone scans. Incorrect diagnosis of the syndrome will lead to a significant reduction of life quality in patients suffering from CIPS.", "entity": "Neuralgia", "aliases": "Atypical Neuralgia Neuralgias Iliohypogastric Nerve Ilioinguinal Pain Paroxysmal Pains Perineal Stump Supraorbital Vidian Neurodynia Neurodynias Neuropathic", "definition": "Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve.\n    ", "id": "MESH:D009437"}
{"mention": "gout", "mention_text": "Bone pain after transplantation is a frequent complication that can be caused by several diseases. Treatment strategies depend on the correct diagnosis of the pain. Nine patients with severe pain in their feet, which was registered after transplantation, were investigated. Bone scans showed an increased tracer uptake of the foot bones. Magnetic resonance imaging demonstrated bone marrow oedema in the painful bones. Pain was not explained by other diseases causing foot pain, like reflex sympathetic dystrophy, polyneuropathy, Morton's neuralgia, gout, osteoporosis, avascular necrosis, intermittent claudication, orthopaedic foot deformities, stress fractures, and hyperparathyroidism. The reduction of cyclosporine- or tacrolimus trough levels and the administration of calcium channel blockers led to relief of pain. The Calcineurin-inhibitor Induced Pain Syndrome (CIPS) is a rare but severe side effect of cyclosporine or tacrolimus and is accurately diagnosed by its typical presentation, magnetic resonance imaging and bone scans. Incorrect diagnosis of the syndrome will lead to a significant reduction of life quality in patients suffering from CIPS.", "entity": "Gout", "aliases": "Gout Gouts", "definition": "Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi.\n    ", "id": "MESH:D006073"}
{"mention": "osteoporosis", "mention_text": "Bone pain after transplantation is a frequent complication that can be caused by several diseases. Treatment strategies depend on the correct diagnosis of the pain. Nine patients with severe pain in their feet, which was registered after transplantation, were investigated. Bone scans showed an increased tracer uptake of the foot bones. Magnetic resonance imaging demonstrated bone marrow oedema in the painful bones. Pain was not explained by other diseases causing foot pain, like reflex sympathetic dystrophy, polyneuropathy, Morton's neuralgia, gout, osteoporosis, avascular necrosis, intermittent claudication, orthopaedic foot deformities, stress fractures, and hyperparathyroidism. The reduction of cyclosporine- or tacrolimus trough levels and the administration of calcium channel blockers led to relief of pain. The Calcineurin-inhibitor Induced Pain Syndrome (CIPS) is a rare but severe side effect of cyclosporine or tacrolimus and is accurately diagnosed by its typical presentation, magnetic resonance imaging and bone scans. Incorrect diagnosis of the syndrome will lead to a significant reduction of life quality in patients suffering from CIPS.", "entity": "Osteoporosis", "aliases": "Age Related Osteoporosis Age-Related Bone Loss Losses Osteoporoses Senile Involutional Post Traumatic Post-Traumatic", "definition": "Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis (OSTEOPOROSIS, POSTMENOPAUSAL) and age-related or senile osteoporosis.\n    ", "id": "MESH:D010024"}
{"mention": "avascular necrosis", "mention_text": "Bone pain after transplantation is a frequent complication that can be caused by several diseases. Treatment strategies depend on the correct diagnosis of the pain. Nine patients with severe pain in their feet, which was registered after transplantation, were investigated. Bone scans showed an increased tracer uptake of the foot bones. Magnetic resonance imaging demonstrated bone marrow oedema in the painful bones. Pain was not explained by other diseases causing foot pain, like reflex sympathetic dystrophy, polyneuropathy, Morton's neuralgia, gout, osteoporosis, avascular necrosis, intermittent claudication, orthopaedic foot deformities, stress fractures, and hyperparathyroidism. The reduction of cyclosporine- or tacrolimus trough levels and the administration of calcium channel blockers led to relief of pain. The Calcineurin-inhibitor Induced Pain Syndrome (CIPS) is a rare but severe side effect of cyclosporine or tacrolimus and is accurately diagnosed by its typical presentation, magnetic resonance imaging and bone scans. Incorrect diagnosis of the syndrome will lead to a significant reduction of life quality in patients suffering from CIPS.", "entity": "Osteonecrosis", "aliases": "Aseptic Necrosis of Bone Avascular Kienbock Disease Kienbock's Kienboeck Kienboeck's Kienboecks Osteonecroses Osteonecrosis", "definition": "Death of a bone or part of a bone, either atraumatic or posttraumatic.\n    ", "id": "MESH:D010020"}
{"mention": "intermittent claudication", "mention_text": "Bone pain after transplantation is a frequent complication that can be caused by several diseases. Treatment strategies depend on the correct diagnosis of the pain. Nine patients with severe pain in their feet, which was registered after transplantation, were investigated. Bone scans showed an increased tracer uptake of the foot bones. Magnetic resonance imaging demonstrated bone marrow oedema in the painful bones. Pain was not explained by other diseases causing foot pain, like reflex sympathetic dystrophy, polyneuropathy, Morton's neuralgia, gout, osteoporosis, avascular necrosis, intermittent claudication, orthopaedic foot deformities, stress fractures, and hyperparathyroidism. The reduction of cyclosporine- or tacrolimus trough levels and the administration of calcium channel blockers led to relief of pain. The Calcineurin-inhibitor Induced Pain Syndrome (CIPS) is a rare but severe side effect of cyclosporine or tacrolimus and is accurately diagnosed by its typical presentation, magnetic resonance imaging and bone scans. Incorrect diagnosis of the syndrome will lead to a significant reduction of life quality in patients suffering from CIPS.", "entity": "Intermittent Claudication", "aliases": "Claudication Intermittent", "definition": "A symptom complex characterized by pain and weakness in SKELETAL MUSCLE group associated with exercise, such as leg pain and weakness brought on by walking. Such muscle limpness disappears after a brief rest and is often relates to arterial STENOSIS; muscle ISCHEMIA; and accumulation of LACTATE.\n    ", "id": "MESH:D007383"}
{"mention": "foot deformities", "mention_text": "Bone pain after transplantation is a frequent complication that can be caused by several diseases. Treatment strategies depend on the correct diagnosis of the pain. Nine patients with severe pain in their feet, which was registered after transplantation, were investigated. Bone scans showed an increased tracer uptake of the foot bones. Magnetic resonance imaging demonstrated bone marrow oedema in the painful bones. Pain was not explained by other diseases causing foot pain, like reflex sympathetic dystrophy, polyneuropathy, Morton's neuralgia, gout, osteoporosis, avascular necrosis, intermittent claudication, orthopaedic foot deformities, stress fractures, and hyperparathyroidism. The reduction of cyclosporine- or tacrolimus trough levels and the administration of calcium channel blockers led to relief of pain. The Calcineurin-inhibitor Induced Pain Syndrome (CIPS) is a rare but severe side effect of cyclosporine or tacrolimus and is accurately diagnosed by its typical presentation, magnetic resonance imaging and bone scans. Incorrect diagnosis of the syndrome will lead to a significant reduction of life quality in patients suffering from CIPS.", "entity": "Foot Deformities", "aliases": "Cavus Deformities Deformity Foot Metatarsal Pes Talipes", "definition": "Alterations or deviations from normal shape or size which result in a disfigurement of the foot.\n    ", "id": "MESH:D005530"}
{"mention": "stress fractures", "mention_text": "Bone pain after transplantation is a frequent complication that can be caused by several diseases. Treatment strategies depend on the correct diagnosis of the pain. Nine patients with severe pain in their feet, which was registered after transplantation, were investigated. Bone scans showed an increased tracer uptake of the foot bones. Magnetic resonance imaging demonstrated bone marrow oedema in the painful bones. Pain was not explained by other diseases causing foot pain, like reflex sympathetic dystrophy, polyneuropathy, Morton's neuralgia, gout, osteoporosis, avascular necrosis, intermittent claudication, orthopaedic foot deformities, stress fractures, and hyperparathyroidism. The reduction of cyclosporine- or tacrolimus trough levels and the administration of calcium channel blockers led to relief of pain. The Calcineurin-inhibitor Induced Pain Syndrome (CIPS) is a rare but severe side effect of cyclosporine or tacrolimus and is accurately diagnosed by its typical presentation, magnetic resonance imaging and bone scans. Incorrect diagnosis of the syndrome will lead to a significant reduction of life quality in patients suffering from CIPS.", "entity": "Fractures, Stress", "aliases": "Fatigue Fracture Fractures Insufficiency March Stress", "definition": "Fractures due to the strain caused by repetitive exercise. They are thought to arise from a combination of MUSCLE FATIGUE and bone failure, and occur in situations where BONE REMODELING predominates over repair. The most common sites of stress fractures are the METATARSUS; FIBULA; TIBIA; and FEMORAL NECK.\n    ", "id": "MESH:D015775"}
{"mention": "hyperparathyroidism", "mention_text": "Bone pain after transplantation is a frequent complication that can be caused by several diseases. Treatment strategies depend on the correct diagnosis of the pain. Nine patients with severe pain in their feet, which was registered after transplantation, were investigated. Bone scans showed an increased tracer uptake of the foot bones. Magnetic resonance imaging demonstrated bone marrow oedema in the painful bones. Pain was not explained by other diseases causing foot pain, like reflex sympathetic dystrophy, polyneuropathy, Morton's neuralgia, gout, osteoporosis, avascular necrosis, intermittent claudication, orthopaedic foot deformities, stress fractures, and hyperparathyroidism. The reduction of cyclosporine- or tacrolimus trough levels and the administration of calcium channel blockers led to relief of pain. The Calcineurin-inhibitor Induced Pain Syndrome (CIPS) is a rare but severe side effect of cyclosporine or tacrolimus and is accurately diagnosed by its typical presentation, magnetic resonance imaging and bone scans. Incorrect diagnosis of the syndrome will lead to a significant reduction of life quality in patients suffering from CIPS.", "entity": "Hyperparathyroidism", "aliases": "Hyperparathyroidism", "definition": "A condition of abnormally elevated output of PARATHYROID HORMONE (or PTH) triggering responses that increase blood CALCIUM. It is characterized by HYPERCALCEMIA and BONE RESORPTION, eventually leading to bone diseases. PRIMARY HYPERPARATHYROIDISM is caused by parathyroid HYPERPLASIA or PARATHYROID NEOPLASMS. SECONDARY HYPERPARATHYROIDISM is increased PTH secretion in response to HYPOCALCEMIA, usually caused by chronic KIDNEY DISEASES.\n    ", "id": "MESH:D006961"}
{"mention": "cyclosporine", "mention_text": "Bone pain after transplantation is a frequent complication that can be caused by several diseases. Treatment strategies depend on the correct diagnosis of the pain. Nine patients with severe pain in their feet, which was registered after transplantation, were investigated. Bone scans showed an increased tracer uptake of the foot bones. Magnetic resonance imaging demonstrated bone marrow oedema in the painful bones. Pain was not explained by other diseases causing foot pain, like reflex sympathetic dystrophy, polyneuropathy, Morton's neuralgia, gout, osteoporosis, avascular necrosis, intermittent claudication, orthopaedic foot deformities, stress fractures, and hyperparathyroidism. The reduction of cyclosporine- or tacrolimus trough levels and the administration of calcium channel blockers led to relief of pain. The Calcineurin-inhibitor Induced Pain Syndrome (CIPS) is a rare but severe side effect of cyclosporine or tacrolimus and is accurately diagnosed by its typical presentation, magnetic resonance imaging and bone scans. Incorrect diagnosis of the syndrome will lead to a significant reduction of life quality in patients suffering from CIPS.", "entity": "Cyclosporine", "aliases": "Ciclosporin CsA Neoral CsA-Neoral CsANeoral CyA NOF CyA-NOF Cyclosporin A Cyclosporine OL 27 400 27-400 27400 Sandimmun Sandimmune", "definition": "A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).\n    ", "id": "MESH:D016572"}
{"mention": "tacrolimus", "mention_text": "Bone pain after transplantation is a frequent complication that can be caused by several diseases. Treatment strategies depend on the correct diagnosis of the pain. Nine patients with severe pain in their feet, which was registered after transplantation, were investigated. Bone scans showed an increased tracer uptake of the foot bones. Magnetic resonance imaging demonstrated bone marrow oedema in the painful bones. Pain was not explained by other diseases causing foot pain, like reflex sympathetic dystrophy, polyneuropathy, Morton's neuralgia, gout, osteoporosis, avascular necrosis, intermittent claudication, orthopaedic foot deformities, stress fractures, and hyperparathyroidism. The reduction of cyclosporine- or tacrolimus trough levels and the administration of calcium channel blockers led to relief of pain. The Calcineurin-inhibitor Induced Pain Syndrome (CIPS) is a rare but severe side effect of cyclosporine or tacrolimus and is accurately diagnosed by its typical presentation, magnetic resonance imaging and bone scans. Incorrect diagnosis of the syndrome will lead to a significant reduction of life quality in patients suffering from CIPS.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "calcium", "mention_text": "Bone pain after transplantation is a frequent complication that can be caused by several diseases. Treatment strategies depend on the correct diagnosis of the pain. Nine patients with severe pain in their feet, which was registered after transplantation, were investigated. Bone scans showed an increased tracer uptake of the foot bones. Magnetic resonance imaging demonstrated bone marrow oedema in the painful bones. Pain was not explained by other diseases causing foot pain, like reflex sympathetic dystrophy, polyneuropathy, Morton's neuralgia, gout, osteoporosis, avascular necrosis, intermittent claudication, orthopaedic foot deformities, stress fractures, and hyperparathyroidism. The reduction of cyclosporine- or tacrolimus trough levels and the administration of calcium channel blockers led to relief of pain. The Calcineurin-inhibitor Induced Pain Syndrome (CIPS) is a rare but severe side effect of cyclosporine or tacrolimus and is accurately diagnosed by its typical presentation, magnetic resonance imaging and bone scans. Incorrect diagnosis of the syndrome will lead to a significant reduction of life quality in patients suffering from CIPS.", "entity": "Calcium", "aliases": "Blood Coagulation Factor IV Calcium", "definition": "A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.\n    ", "id": "MESH:D002118"}
{"mention": "propofol", "mention_text": "The haemodynamic effects of propofol in combination with ephedrine in elderly patients (ASA groups 3 and 4).", "entity": "Propofol", "aliases": "2,6 Diisopropylphenol 2,6-Bis(1-methylethyl)phenol 2,6-Diisopropylphenol Abbott Brand of Propofol Alpha Aquafol Astra AstraZeneca Braun Curamed Diprivan Disoprivan Disoprofol Fresenius Kabi Fresofol ICI 35,868 35868 ICI-35,868 ICI-35868 ICI35,868 ICI35868 Ivofol Juste Parnell Pisa MCT Rovi Propofol-Lipuro Recofol Schering Zeneca", "definition": "An intravenous anesthetic agent which has the advantage of a very rapid onset after infusion or bolus injection plus a very short recovery period of a couple of minutes. (From Smith and Reynard, Textbook of Pharmacology, 1992, 1st ed, p206). Propofol has been used as ANTICONVULSANTS and ANTIEMETICS.\n    ", "id": "MESH:D015742"}
{"mention": "ephedrine", "mention_text": "The haemodynamic effects of propofol in combination with ephedrine in elderly patients (ASA groups 3 and 4).", "entity": "Ephedrine", "aliases": "Ephedrine Erythro Isomer Hydrochloride Renaudin Sulfate of Brand Sal Phedrine Sal-Phedrine SalPhedrine Wendt", "definition": "A phenethylamine found in EPHEDRA SINICA. PSEUDOEPHEDRINE is an isomer. It is an alpha- and beta-adrenergic agonist that may also enhance release of norepinephrine. It has been used for asthma, heart failure, rhinitis, and urinary incontinence, and for its central nervous system stimulatory effects in the treatment of narcolepsy and depression. It has become less extensively used with the advent of more selective agonists.\n    ", "id": "MESH:D004809"}
{"mention": "propofol", "mention_text": "The marked vasodilator and negative inotropic effects of propofol are disadvantages in frail elderly patients. We investigated the safety and efficacy of adding different doses of ephedrine to propofol in order to obtund the hypotensive response. The haemodynamic effects of adding 15, 20 or 25 mg of ephedrine to 200 mg of propofol were compared to control in 40 ASA 3/4 patients over 60 years presenting for genito-urinary surgery. The addition of ephedrine to propofol appears to be an effective method of obtunding the hypotensive response to propofol at all doses used in this study. However, marked tachycardia associated with the use of ephedrine in combination with propofol occurred in the majority of patients, occasionally reaching high levels in individual patients. Due to the risk of this tachycardia inducing myocardial ischemia, we would not recommend the use in elderly patients of any of the ephedrine/propofol/mixtures studied.", "entity": "Propofol", "aliases": "2,6 Diisopropylphenol 2,6-Bis(1-methylethyl)phenol 2,6-Diisopropylphenol Abbott Brand of Propofol Alpha Aquafol Astra AstraZeneca Braun Curamed Diprivan Disoprivan Disoprofol Fresenius Kabi Fresofol ICI 35,868 35868 ICI-35,868 ICI-35868 ICI35,868 ICI35868 Ivofol Juste Parnell Pisa MCT Rovi Propofol-Lipuro Recofol Schering Zeneca", "definition": "An intravenous anesthetic agent which has the advantage of a very rapid onset after infusion or bolus injection plus a very short recovery period of a couple of minutes. (From Smith and Reynard, Textbook of Pharmacology, 1992, 1st ed, p206). Propofol has been used as ANTICONVULSANTS and ANTIEMETICS.\n    ", "id": "MESH:D015742"}
{"mention": "ephedrine", "mention_text": "The marked vasodilator and negative inotropic effects of propofol are disadvantages in frail elderly patients. We investigated the safety and efficacy of adding different doses of ephedrine to propofol in order to obtund the hypotensive response. The haemodynamic effects of adding 15, 20 or 25 mg of ephedrine to 200 mg of propofol were compared to control in 40 ASA 3/4 patients over 60 years presenting for genito-urinary surgery. The addition of ephedrine to propofol appears to be an effective method of obtunding the hypotensive response to propofol at all doses used in this study. However, marked tachycardia associated with the use of ephedrine in combination with propofol occurred in the majority of patients, occasionally reaching high levels in individual patients. Due to the risk of this tachycardia inducing myocardial ischemia, we would not recommend the use in elderly patients of any of the ephedrine/propofol/mixtures studied.", "entity": "Ephedrine", "aliases": "Ephedrine Erythro Isomer Hydrochloride Renaudin Sulfate of Brand Sal Phedrine Sal-Phedrine SalPhedrine Wendt", "definition": "A phenethylamine found in EPHEDRA SINICA. PSEUDOEPHEDRINE is an isomer. It is an alpha- and beta-adrenergic agonist that may also enhance release of norepinephrine. It has been used for asthma, heart failure, rhinitis, and urinary incontinence, and for its central nervous system stimulatory effects in the treatment of narcolepsy and depression. It has become less extensively used with the advent of more selective agonists.\n    ", "id": "MESH:D004809"}
{"mention": "hypotensive", "mention_text": "The marked vasodilator and negative inotropic effects of propofol are disadvantages in frail elderly patients. We investigated the safety and efficacy of adding different doses of ephedrine to propofol in order to obtund the hypotensive response. The haemodynamic effects of adding 15, 20 or 25 mg of ephedrine to 200 mg of propofol were compared to control in 40 ASA 3/4 patients over 60 years presenting for genito-urinary surgery. The addition of ephedrine to propofol appears to be an effective method of obtunding the hypotensive response to propofol at all doses used in this study. However, marked tachycardia associated with the use of ephedrine in combination with propofol occurred in the majority of patients, occasionally reaching high levels in individual patients. Due to the risk of this tachycardia inducing myocardial ischemia, we would not recommend the use in elderly patients of any of the ephedrine/propofol/mixtures studied.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "tachycardia", "mention_text": "The marked vasodilator and negative inotropic effects of propofol are disadvantages in frail elderly patients. We investigated the safety and efficacy of adding different doses of ephedrine to propofol in order to obtund the hypotensive response. The haemodynamic effects of adding 15, 20 or 25 mg of ephedrine to 200 mg of propofol were compared to control in 40 ASA 3/4 patients over 60 years presenting for genito-urinary surgery. The addition of ephedrine to propofol appears to be an effective method of obtunding the hypotensive response to propofol at all doses used in this study. However, marked tachycardia associated with the use of ephedrine in combination with propofol occurred in the majority of patients, occasionally reaching high levels in individual patients. Due to the risk of this tachycardia inducing myocardial ischemia, we would not recommend the use in elderly patients of any of the ephedrine/propofol/mixtures studied.", "entity": "Tachycardia", "aliases": "Tachyarrhythmia Tachyarrhythmias Tachycardia Tachycardias", "definition": "Abnormally rapid heartbeat, usually with a HEART RATE above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia.\n    ", "id": "MESH:D013610"}
{"mention": "myocardial ischemia", "mention_text": "The marked vasodilator and negative inotropic effects of propofol are disadvantages in frail elderly patients. We investigated the safety and efficacy of adding different doses of ephedrine to propofol in order to obtund the hypotensive response. The haemodynamic effects of adding 15, 20 or 25 mg of ephedrine to 200 mg of propofol were compared to control in 40 ASA 3/4 patients over 60 years presenting for genito-urinary surgery. The addition of ephedrine to propofol appears to be an effective method of obtunding the hypotensive response to propofol at all doses used in this study. However, marked tachycardia associated with the use of ephedrine in combination with propofol occurred in the majority of patients, occasionally reaching high levels in individual patients. Due to the risk of this tachycardia inducing myocardial ischemia, we would not recommend the use in elderly patients of any of the ephedrine/propofol/mixtures studied.", "entity": "Myocardial Ischemia", "aliases": "Disease Ischemic Heart Diseases Ischemia Myocardial Ischemias", "definition": "A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).\n    ", "id": "MESH:D017202"}
{"mention": "Neurotoxicity", "mention_text": "Neurotoxicity of halogenated hydroxyquinolines: clinical analysis of cases reported outside Japan.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "halogenated hydroxyquinolines", "mention_text": "Neurotoxicity of halogenated hydroxyquinolines: clinical analysis of cases reported outside Japan.", "entity": "Hydroxyquinolines", "aliases": "Chiniofon Hydroxyquinolines Quinolinols", "definition": "The 8-hydroxy derivatives inhibit various enzymes and their halogenated derivatives, though neurotoxic, are used as topical anti-infective agents, among other uses.\n    ", "id": "MESH:D006912"}
{"mention": "neurotoxic", "mention_text": "An analysis is presented of 220 cases of possible neurotoxic reactions to halogenated hydroxyquinolines reported from outside Japan. In 80 cases insufficient information was available for adequate comment and in 29 a relationship to the administration of clioquinol could be excluded. Of the remainder, a relationship to clioquinol was considered probable in 42 and possible in 69 cases. In six of the probable cases the neurological disturbance consisted of an acute reversible encephalopathy usually related to the ingestion of a high dose of clioquinol over a short period. The most common manifestation, observed in 15 further cases, was isolated optic atrophy. This was most frequently found in children, many of whom had received clioquinol as treatment for acrodermatitis enteropathica. In the remaining cases, a combination of myelopathy, visual disturbance, and peripheral neuropathy was the most common manifestation. Isolated myelopathy or peripheral neuropathy, or these manifestations occurring together, were infrequent. The onset of all manifestations (except toxic encephalopathy) was usually subacute, with subsequent partial recovery. Older subjects tended to display more side effects. The full syndrome of subacute myelo-optic neuropathy was more frequent in women, but they tended to have taken greater quantities of the drug.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "halogenated hydroxyquinolines", "mention_text": "An analysis is presented of 220 cases of possible neurotoxic reactions to halogenated hydroxyquinolines reported from outside Japan. In 80 cases insufficient information was available for adequate comment and in 29 a relationship to the administration of clioquinol could be excluded. Of the remainder, a relationship to clioquinol was considered probable in 42 and possible in 69 cases. In six of the probable cases the neurological disturbance consisted of an acute reversible encephalopathy usually related to the ingestion of a high dose of clioquinol over a short period. The most common manifestation, observed in 15 further cases, was isolated optic atrophy. This was most frequently found in children, many of whom had received clioquinol as treatment for acrodermatitis enteropathica. In the remaining cases, a combination of myelopathy, visual disturbance, and peripheral neuropathy was the most common manifestation. Isolated myelopathy or peripheral neuropathy, or these manifestations occurring together, were infrequent. The onset of all manifestations (except toxic encephalopathy) was usually subacute, with subsequent partial recovery. Older subjects tended to display more side effects. The full syndrome of subacute myelo-optic neuropathy was more frequent in women, but they tended to have taken greater quantities of the drug.", "entity": "Hydroxyquinolines", "aliases": "Chiniofon Hydroxyquinolines Quinolinols", "definition": "The 8-hydroxy derivatives inhibit various enzymes and their halogenated derivatives, though neurotoxic, are used as topical anti-infective agents, among other uses.\n    ", "id": "MESH:D006912"}
{"mention": "clioquinol", "mention_text": "An analysis is presented of 220 cases of possible neurotoxic reactions to halogenated hydroxyquinolines reported from outside Japan. In 80 cases insufficient information was available for adequate comment and in 29 a relationship to the administration of clioquinol could be excluded. Of the remainder, a relationship to clioquinol was considered probable in 42 and possible in 69 cases. In six of the probable cases the neurological disturbance consisted of an acute reversible encephalopathy usually related to the ingestion of a high dose of clioquinol over a short period. The most common manifestation, observed in 15 further cases, was isolated optic atrophy. This was most frequently found in children, many of whom had received clioquinol as treatment for acrodermatitis enteropathica. In the remaining cases, a combination of myelopathy, visual disturbance, and peripheral neuropathy was the most common manifestation. Isolated myelopathy or peripheral neuropathy, or these manifestations occurring together, were infrequent. The onset of all manifestations (except toxic encephalopathy) was usually subacute, with subsequent partial recovery. Older subjects tended to display more side effects. The full syndrome of subacute myelo-optic neuropathy was more frequent in women, but they tended to have taken greater quantities of the drug.", "entity": "Clioquinol", "aliases": "5 Chloro 7 iodo 8 quinolinol 5-Chloro-7-iodo-8-quinolinol Chinoform Chloroiodoquine Clioquinol Entero Septol Vioform Entero-Septol Entero-Vioform EnteroSeptol EnteroVioform Enteroquinol Iodochlorhydroxyquin Iodochloroxyquinoline", "definition": "A potentially neurotoxic 8-hydroxyquinoline derivative long used as a topical anti-infective, intestinal antiamebic, and vaginal trichomonacide. The oral preparation has been shown to cause subacute myelo-optic neuropathy and has been banned worldwide.\n    ", "id": "MESH:D007464"}
{"mention": "neurological disturbance", "mention_text": "An analysis is presented of 220 cases of possible neurotoxic reactions to halogenated hydroxyquinolines reported from outside Japan. In 80 cases insufficient information was available for adequate comment and in 29 a relationship to the administration of clioquinol could be excluded. Of the remainder, a relationship to clioquinol was considered probable in 42 and possible in 69 cases. In six of the probable cases the neurological disturbance consisted of an acute reversible encephalopathy usually related to the ingestion of a high dose of clioquinol over a short period. The most common manifestation, observed in 15 further cases, was isolated optic atrophy. This was most frequently found in children, many of whom had received clioquinol as treatment for acrodermatitis enteropathica. In the remaining cases, a combination of myelopathy, visual disturbance, and peripheral neuropathy was the most common manifestation. Isolated myelopathy or peripheral neuropathy, or these manifestations occurring together, were infrequent. The onset of all manifestations (except toxic encephalopathy) was usually subacute, with subsequent partial recovery. Older subjects tended to display more side effects. The full syndrome of subacute myelo-optic neuropathy was more frequent in women, but they tended to have taken greater quantities of the drug.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "encephalopathy", "mention_text": "An analysis is presented of 220 cases of possible neurotoxic reactions to halogenated hydroxyquinolines reported from outside Japan. In 80 cases insufficient information was available for adequate comment and in 29 a relationship to the administration of clioquinol could be excluded. Of the remainder, a relationship to clioquinol was considered probable in 42 and possible in 69 cases. In six of the probable cases the neurological disturbance consisted of an acute reversible encephalopathy usually related to the ingestion of a high dose of clioquinol over a short period. The most common manifestation, observed in 15 further cases, was isolated optic atrophy. This was most frequently found in children, many of whom had received clioquinol as treatment for acrodermatitis enteropathica. In the remaining cases, a combination of myelopathy, visual disturbance, and peripheral neuropathy was the most common manifestation. Isolated myelopathy or peripheral neuropathy, or these manifestations occurring together, were infrequent. The onset of all manifestations (except toxic encephalopathy) was usually subacute, with subsequent partial recovery. Older subjects tended to display more side effects. The full syndrome of subacute myelo-optic neuropathy was more frequent in women, but they tended to have taken greater quantities of the drug.", "entity": "Brain Diseases", "aliases": "Brain Disease Diseases Disorder Disorders CNS Intracranial Central Nervous System Encephalon", "definition": "Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.\n    ", "id": "MESH:D001927"}
{"mention": "optic atrophy", "mention_text": "An analysis is presented of 220 cases of possible neurotoxic reactions to halogenated hydroxyquinolines reported from outside Japan. In 80 cases insufficient information was available for adequate comment and in 29 a relationship to the administration of clioquinol could be excluded. Of the remainder, a relationship to clioquinol was considered probable in 42 and possible in 69 cases. In six of the probable cases the neurological disturbance consisted of an acute reversible encephalopathy usually related to the ingestion of a high dose of clioquinol over a short period. The most common manifestation, observed in 15 further cases, was isolated optic atrophy. This was most frequently found in children, many of whom had received clioquinol as treatment for acrodermatitis enteropathica. In the remaining cases, a combination of myelopathy, visual disturbance, and peripheral neuropathy was the most common manifestation. Isolated myelopathy or peripheral neuropathy, or these manifestations occurring together, were infrequent. The onset of all manifestations (except toxic encephalopathy) was usually subacute, with subsequent partial recovery. Older subjects tended to display more side effects. The full syndrome of subacute myelo-optic neuropathy was more frequent in women, but they tended to have taken greater quantities of the drug.", "entity": "Optic Atrophy", "aliases": "Atrophy Optic", "definition": "Atrophy of the optic disk which may be congenital or acquired. This condition indicates a deficiency in the number of nerve fibers which arise in the RETINA and converge to form the OPTIC DISK; OPTIC NERVE; OPTIC CHIASM; and optic tracts. GLAUCOMA; ISCHEMIA; inflammation, a chronic elevation of intracranial pressure, toxins, optic nerve compression, and inherited conditions (see OPTIC ATROPHIES, HEREDITARY) are relatively common causes of this condition.\n    ", "id": "MESH:D009896"}
{"mention": "acrodermatitis enteropathica", "mention_text": "An analysis is presented of 220 cases of possible neurotoxic reactions to halogenated hydroxyquinolines reported from outside Japan. In 80 cases insufficient information was available for adequate comment and in 29 a relationship to the administration of clioquinol could be excluded. Of the remainder, a relationship to clioquinol was considered probable in 42 and possible in 69 cases. In six of the probable cases the neurological disturbance consisted of an acute reversible encephalopathy usually related to the ingestion of a high dose of clioquinol over a short period. The most common manifestation, observed in 15 further cases, was isolated optic atrophy. This was most frequently found in children, many of whom had received clioquinol as treatment for acrodermatitis enteropathica. In the remaining cases, a combination of myelopathy, visual disturbance, and peripheral neuropathy was the most common manifestation. Isolated myelopathy or peripheral neuropathy, or these manifestations occurring together, were infrequent. The onset of all manifestations (except toxic encephalopathy) was usually subacute, with subsequent partial recovery. Older subjects tended to display more side effects. The full syndrome of subacute myelo-optic neuropathy was more frequent in women, but they tended to have taken greater quantities of the drug.", "entity": "Acrodermatitis enteropathica", "aliases": "Acrodermatitis Enteropathica Zinc-Deficiency Type enteropathica zinc deficiency type", "definition": "", "id": "MESH:C538178"}
{"mention": "myelopathy", "mention_text": "An analysis is presented of 220 cases of possible neurotoxic reactions to halogenated hydroxyquinolines reported from outside Japan. In 80 cases insufficient information was available for adequate comment and in 29 a relationship to the administration of clioquinol could be excluded. Of the remainder, a relationship to clioquinol was considered probable in 42 and possible in 69 cases. In six of the probable cases the neurological disturbance consisted of an acute reversible encephalopathy usually related to the ingestion of a high dose of clioquinol over a short period. The most common manifestation, observed in 15 further cases, was isolated optic atrophy. This was most frequently found in children, many of whom had received clioquinol as treatment for acrodermatitis enteropathica. In the remaining cases, a combination of myelopathy, visual disturbance, and peripheral neuropathy was the most common manifestation. Isolated myelopathy or peripheral neuropathy, or these manifestations occurring together, were infrequent. The onset of all manifestations (except toxic encephalopathy) was usually subacute, with subsequent partial recovery. Older subjects tended to display more side effects. The full syndrome of subacute myelo-optic neuropathy was more frequent in women, but they tended to have taken greater quantities of the drug.", "entity": "Spinal Cord Diseases", "aliases": "Myelopathies Myelopathy Spinal Cord Disease Diseases Disorder Disorders", "definition": "Pathologic conditions which feature SPINAL CORD damage or dysfunction, including disorders involving the meninges and perimeningeal spaces surrounding the spinal cord. Traumatic injuries, vascular diseases, infections, and inflammatory/autoimmune processes may affect the spinal cord.\n    ", "id": "MESH:D013118"}
{"mention": "visual disturbance", "mention_text": "An analysis is presented of 220 cases of possible neurotoxic reactions to halogenated hydroxyquinolines reported from outside Japan. In 80 cases insufficient information was available for adequate comment and in 29 a relationship to the administration of clioquinol could be excluded. Of the remainder, a relationship to clioquinol was considered probable in 42 and possible in 69 cases. In six of the probable cases the neurological disturbance consisted of an acute reversible encephalopathy usually related to the ingestion of a high dose of clioquinol over a short period. The most common manifestation, observed in 15 further cases, was isolated optic atrophy. This was most frequently found in children, many of whom had received clioquinol as treatment for acrodermatitis enteropathica. In the remaining cases, a combination of myelopathy, visual disturbance, and peripheral neuropathy was the most common manifestation. Isolated myelopathy or peripheral neuropathy, or these manifestations occurring together, were infrequent. The onset of all manifestations (except toxic encephalopathy) was usually subacute, with subsequent partial recovery. Older subjects tended to display more side effects. The full syndrome of subacute myelo-optic neuropathy was more frequent in women, but they tended to have taken greater quantities of the drug.", "entity": "Vision Disorders", "aliases": "Blindness Day Disabilities Vision Disability Disorder Visual Disorders Hemeralopia Hemeralopias Impairment Impairments Macropsia Macropsias Metamorphopsia Metamorphopsias Micropsia Micropsias", "definition": "Visual impairments limiting one or more of the basic functions of the eye: visual acuity, dark adaptation, color vision, or peripheral vision. These may result from EYE DISEASES; OPTIC NERVE DISEASES; VISUAL PATHWAY diseases; OCCIPITAL LOBE diseases; OCULAR MOTILITY DISORDERS; and other conditions (From Newell, Ophthalmology: Principles and Concepts, 7th ed, p132).\n    ", "id": "MESH:D014786"}
{"mention": "peripheral neuropathy", "mention_text": "An analysis is presented of 220 cases of possible neurotoxic reactions to halogenated hydroxyquinolines reported from outside Japan. In 80 cases insufficient information was available for adequate comment and in 29 a relationship to the administration of clioquinol could be excluded. Of the remainder, a relationship to clioquinol was considered probable in 42 and possible in 69 cases. In six of the probable cases the neurological disturbance consisted of an acute reversible encephalopathy usually related to the ingestion of a high dose of clioquinol over a short period. The most common manifestation, observed in 15 further cases, was isolated optic atrophy. This was most frequently found in children, many of whom had received clioquinol as treatment for acrodermatitis enteropathica. In the remaining cases, a combination of myelopathy, visual disturbance, and peripheral neuropathy was the most common manifestation. Isolated myelopathy or peripheral neuropathy, or these manifestations occurring together, were infrequent. The onset of all manifestations (except toxic encephalopathy) was usually subacute, with subsequent partial recovery. Older subjects tended to display more side effects. The full syndrome of subacute myelo-optic neuropathy was more frequent in women, but they tended to have taken greater quantities of the drug.", "entity": "Peripheral Nervous System Diseases", "aliases": "Nerve Disease Peripheral Diseases Neuropathy PNS (Peripheral Nervous System) System Disorders Neuropathies", "definition": "Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.\n    ", "id": "MESH:D010523"}
{"mention": "optic neuropathy", "mention_text": "An analysis is presented of 220 cases of possible neurotoxic reactions to halogenated hydroxyquinolines reported from outside Japan. In 80 cases insufficient information was available for adequate comment and in 29 a relationship to the administration of clioquinol could be excluded. Of the remainder, a relationship to clioquinol was considered probable in 42 and possible in 69 cases. In six of the probable cases the neurological disturbance consisted of an acute reversible encephalopathy usually related to the ingestion of a high dose of clioquinol over a short period. The most common manifestation, observed in 15 further cases, was isolated optic atrophy. This was most frequently found in children, many of whom had received clioquinol as treatment for acrodermatitis enteropathica. In the remaining cases, a combination of myelopathy, visual disturbance, and peripheral neuropathy was the most common manifestation. Isolated myelopathy or peripheral neuropathy, or these manifestations occurring together, were infrequent. The onset of all manifestations (except toxic encephalopathy) was usually subacute, with subsequent partial recovery. Older subjects tended to display more side effects. The full syndrome of subacute myelo-optic neuropathy was more frequent in women, but they tended to have taken greater quantities of the drug.", "entity": "Optic Nerve Diseases", "aliases": "Cranial Nerve II Diseases Disorder Disk Optic Disorders Foster Kennedy Syndrome Foster-Kennedy Lesion Neural-Optical Lesions Neural Optical Neuropathies Neuropathy Disease Second", "definition": "Conditions which produce injury or dysfunction of the second cranial or optic nerve, which is generally considered a component of the central nervous system. Damage to optic nerve fibers may occur at or near their origin in the retina, at the optic disk, or in the nerve, optic chiasm, optic tract, or lateral geniculate nuclei. Clinical manifestations may include decreased visual acuity and contrast sensitivity, impaired color vision, and an afferent pupillary defect.\n    ", "id": "MESH:D009901"}
{"mention": "Epileptic seizures", "mention_text": "Epileptic seizures following cortical application of fibrin sealants containing tranexamic acid in rats.", "entity": "Epilepsy", "aliases": "Aura Auras Awakening Epilepsy Cryptogenic Epilepsies Epileptic Seizure Seizures Disorder Disorders Single", "definition": "A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313)\n    ", "id": "MESH:D004827"}
{"mention": "tranexamic acid", "mention_text": "Epileptic seizures following cortical application of fibrin sealants containing tranexamic acid in rats.", "entity": "Tranexamic Acid", "aliases": "AMCA AMCHA Abbott Brand of Tranexamic Acid Amchafibrin Anvitoff Cyklokapron Exacyl Fides Ecopharma KABI 2161 Pfizer Pharmygiène Sanofi Synthelabo Spotof Transamin Ugurol t-AMCHA trans-4-(Aminomethyl)cyclohexanecarboxylic", "definition": "Antifibrinolytic hemostatic used in severe hemorrhage.\n    ", "id": "MESH:D014148"}
{"mention": "tranexamic acid", "mention_text": "BACKGROUND: Fibrin sealants (FS) derived from human plasma are frequently used in neurosurgery. In order to increase clot stability, FS typically contain aprotinin, a natural fibrinolysis inhibitor. Recently, synthetic fibrinolysis inhibitors such as tranexamic acid (tAMCA) have been considered as substitutes for aprotinin. However, tAMCA has been shown to cause epileptic seizures. We wanted to study whether tAMCA retains its convulsive action if incorporated into a FS. METHOD: FS containing aprotinin or different concentrations of tAMCA (0.5-47.5 mg/ml) were applied to the pial surface of the cortex of anaesthetized rats. The response of the animals was evaluated using electroencephalography and by monitoring the clinical behaviour during and after recovery from anaesthesia. FINDINGS: FS containing tAMCA caused paroxysmal brain activity which was associated with distinct convulsive behaviours. The degree of these seizures increased with increasing concentration of tAMCA. Thus, FS containing 47.5 mg/ml tAMCA evoked generalized seizures in all tested rats (n=6) while the lowest concentration of tAMCA (0.5 mg/ml) only evoked brief episodes of jerk-correlated convulsive potentials in 1 of 6 rats. In contrast, FS containing aprotinin did not evoke any paroxysmal activity. INTERPRETATION: Tranexamic acid retains its convulsive action within FS. Thus, use of FS containing tAMCA for surgery within or close to the CNS may pose a substantial risk to the patient.", "entity": "Tranexamic Acid", "aliases": "AMCA AMCHA Abbott Brand of Tranexamic Acid Amchafibrin Anvitoff Cyklokapron Exacyl Fides Ecopharma KABI 2161 Pfizer Pharmygiène Sanofi Synthelabo Spotof Transamin Ugurol t-AMCHA trans-4-(Aminomethyl)cyclohexanecarboxylic", "definition": "Antifibrinolytic hemostatic used in severe hemorrhage.\n    ", "id": "MESH:D014148"}
{"mention": "tAMCA", "mention_text": "BACKGROUND: Fibrin sealants (FS) derived from human plasma are frequently used in neurosurgery. In order to increase clot stability, FS typically contain aprotinin, a natural fibrinolysis inhibitor. Recently, synthetic fibrinolysis inhibitors such as tranexamic acid (tAMCA) have been considered as substitutes for aprotinin. However, tAMCA has been shown to cause epileptic seizures. We wanted to study whether tAMCA retains its convulsive action if incorporated into a FS. METHOD: FS containing aprotinin or different concentrations of tAMCA (0.5-47.5 mg/ml) were applied to the pial surface of the cortex of anaesthetized rats. The response of the animals was evaluated using electroencephalography and by monitoring the clinical behaviour during and after recovery from anaesthesia. FINDINGS: FS containing tAMCA caused paroxysmal brain activity which was associated with distinct convulsive behaviours. The degree of these seizures increased with increasing concentration of tAMCA. Thus, FS containing 47.5 mg/ml tAMCA evoked generalized seizures in all tested rats (n=6) while the lowest concentration of tAMCA (0.5 mg/ml) only evoked brief episodes of jerk-correlated convulsive potentials in 1 of 6 rats. In contrast, FS containing aprotinin did not evoke any paroxysmal activity. INTERPRETATION: Tranexamic acid retains its convulsive action within FS. Thus, use of FS containing tAMCA for surgery within or close to the CNS may pose a substantial risk to the patient.", "entity": "Tranexamic Acid", "aliases": "AMCA AMCHA Abbott Brand of Tranexamic Acid Amchafibrin Anvitoff Cyklokapron Exacyl Fides Ecopharma KABI 2161 Pfizer Pharmygiène Sanofi Synthelabo Spotof Transamin Ugurol t-AMCHA trans-4-(Aminomethyl)cyclohexanecarboxylic", "definition": "Antifibrinolytic hemostatic used in severe hemorrhage.\n    ", "id": "MESH:D014148"}
{"mention": "epileptic seizures", "mention_text": "BACKGROUND: Fibrin sealants (FS) derived from human plasma are frequently used in neurosurgery. In order to increase clot stability, FS typically contain aprotinin, a natural fibrinolysis inhibitor. Recently, synthetic fibrinolysis inhibitors such as tranexamic acid (tAMCA) have been considered as substitutes for aprotinin. However, tAMCA has been shown to cause epileptic seizures. We wanted to study whether tAMCA retains its convulsive action if incorporated into a FS. METHOD: FS containing aprotinin or different concentrations of tAMCA (0.5-47.5 mg/ml) were applied to the pial surface of the cortex of anaesthetized rats. The response of the animals was evaluated using electroencephalography and by monitoring the clinical behaviour during and after recovery from anaesthesia. FINDINGS: FS containing tAMCA caused paroxysmal brain activity which was associated with distinct convulsive behaviours. The degree of these seizures increased with increasing concentration of tAMCA. Thus, FS containing 47.5 mg/ml tAMCA evoked generalized seizures in all tested rats (n=6) while the lowest concentration of tAMCA (0.5 mg/ml) only evoked brief episodes of jerk-correlated convulsive potentials in 1 of 6 rats. In contrast, FS containing aprotinin did not evoke any paroxysmal activity. INTERPRETATION: Tranexamic acid retains its convulsive action within FS. Thus, use of FS containing tAMCA for surgery within or close to the CNS may pose a substantial risk to the patient.", "entity": "Epilepsy", "aliases": "Aura Auras Awakening Epilepsy Cryptogenic Epilepsies Epileptic Seizure Seizures Disorder Disorders Single", "definition": "A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313)\n    ", "id": "MESH:D004827"}
{"mention": "convulsive", "mention_text": "BACKGROUND: Fibrin sealants (FS) derived from human plasma are frequently used in neurosurgery. In order to increase clot stability, FS typically contain aprotinin, a natural fibrinolysis inhibitor. Recently, synthetic fibrinolysis inhibitors such as tranexamic acid (tAMCA) have been considered as substitutes for aprotinin. However, tAMCA has been shown to cause epileptic seizures. We wanted to study whether tAMCA retains its convulsive action if incorporated into a FS. METHOD: FS containing aprotinin or different concentrations of tAMCA (0.5-47.5 mg/ml) were applied to the pial surface of the cortex of anaesthetized rats. The response of the animals was evaluated using electroencephalography and by monitoring the clinical behaviour during and after recovery from anaesthesia. FINDINGS: FS containing tAMCA caused paroxysmal brain activity which was associated with distinct convulsive behaviours. The degree of these seizures increased with increasing concentration of tAMCA. Thus, FS containing 47.5 mg/ml tAMCA evoked generalized seizures in all tested rats (n=6) while the lowest concentration of tAMCA (0.5 mg/ml) only evoked brief episodes of jerk-correlated convulsive potentials in 1 of 6 rats. In contrast, FS containing aprotinin did not evoke any paroxysmal activity. INTERPRETATION: Tranexamic acid retains its convulsive action within FS. Thus, use of FS containing tAMCA for surgery within or close to the CNS may pose a substantial risk to the patient.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "seizures", "mention_text": "BACKGROUND: Fibrin sealants (FS) derived from human plasma are frequently used in neurosurgery. In order to increase clot stability, FS typically contain aprotinin, a natural fibrinolysis inhibitor. Recently, synthetic fibrinolysis inhibitors such as tranexamic acid (tAMCA) have been considered as substitutes for aprotinin. However, tAMCA has been shown to cause epileptic seizures. We wanted to study whether tAMCA retains its convulsive action if incorporated into a FS. METHOD: FS containing aprotinin or different concentrations of tAMCA (0.5-47.5 mg/ml) were applied to the pial surface of the cortex of anaesthetized rats. The response of the animals was evaluated using electroencephalography and by monitoring the clinical behaviour during and after recovery from anaesthesia. FINDINGS: FS containing tAMCA caused paroxysmal brain activity which was associated with distinct convulsive behaviours. The degree of these seizures increased with increasing concentration of tAMCA. Thus, FS containing 47.5 mg/ml tAMCA evoked generalized seizures in all tested rats (n=6) while the lowest concentration of tAMCA (0.5 mg/ml) only evoked brief episodes of jerk-correlated convulsive potentials in 1 of 6 rats. In contrast, FS containing aprotinin did not evoke any paroxysmal activity. INTERPRETATION: Tranexamic acid retains its convulsive action within FS. Thus, use of FS containing tAMCA for surgery within or close to the CNS may pose a substantial risk to the patient.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "generalized seizures", "mention_text": "BACKGROUND: Fibrin sealants (FS) derived from human plasma are frequently used in neurosurgery. In order to increase clot stability, FS typically contain aprotinin, a natural fibrinolysis inhibitor. Recently, synthetic fibrinolysis inhibitors such as tranexamic acid (tAMCA) have been considered as substitutes for aprotinin. However, tAMCA has been shown to cause epileptic seizures. We wanted to study whether tAMCA retains its convulsive action if incorporated into a FS. METHOD: FS containing aprotinin or different concentrations of tAMCA (0.5-47.5 mg/ml) were applied to the pial surface of the cortex of anaesthetized rats. The response of the animals was evaluated using electroencephalography and by monitoring the clinical behaviour during and after recovery from anaesthesia. FINDINGS: FS containing tAMCA caused paroxysmal brain activity which was associated with distinct convulsive behaviours. The degree of these seizures increased with increasing concentration of tAMCA. Thus, FS containing 47.5 mg/ml tAMCA evoked generalized seizures in all tested rats (n=6) while the lowest concentration of tAMCA (0.5 mg/ml) only evoked brief episodes of jerk-correlated convulsive potentials in 1 of 6 rats. In contrast, FS containing aprotinin did not evoke any paroxysmal activity. INTERPRETATION: Tranexamic acid retains its convulsive action within FS. Thus, use of FS containing tAMCA for surgery within or close to the CNS may pose a substantial risk to the patient.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "Tranexamic acid", "mention_text": "BACKGROUND: Fibrin sealants (FS) derived from human plasma are frequently used in neurosurgery. In order to increase clot stability, FS typically contain aprotinin, a natural fibrinolysis inhibitor. Recently, synthetic fibrinolysis inhibitors such as tranexamic acid (tAMCA) have been considered as substitutes for aprotinin. However, tAMCA has been shown to cause epileptic seizures. We wanted to study whether tAMCA retains its convulsive action if incorporated into a FS. METHOD: FS containing aprotinin or different concentrations of tAMCA (0.5-47.5 mg/ml) were applied to the pial surface of the cortex of anaesthetized rats. The response of the animals was evaluated using electroencephalography and by monitoring the clinical behaviour during and after recovery from anaesthesia. FINDINGS: FS containing tAMCA caused paroxysmal brain activity which was associated with distinct convulsive behaviours. The degree of these seizures increased with increasing concentration of tAMCA. Thus, FS containing 47.5 mg/ml tAMCA evoked generalized seizures in all tested rats (n=6) while the lowest concentration of tAMCA (0.5 mg/ml) only evoked brief episodes of jerk-correlated convulsive potentials in 1 of 6 rats. In contrast, FS containing aprotinin did not evoke any paroxysmal activity. INTERPRETATION: Tranexamic acid retains its convulsive action within FS. Thus, use of FS containing tAMCA for surgery within or close to the CNS may pose a substantial risk to the patient.", "entity": "Tranexamic Acid", "aliases": "AMCA AMCHA Abbott Brand of Tranexamic Acid Amchafibrin Anvitoff Cyklokapron Exacyl Fides Ecopharma KABI 2161 Pfizer Pharmygiène Sanofi Synthelabo Spotof Transamin Ugurol t-AMCHA trans-4-(Aminomethyl)cyclohexanecarboxylic", "definition": "Antifibrinolytic hemostatic used in severe hemorrhage.\n    ", "id": "MESH:D014148"}
{"mention": "sugar dependency", "mention_text": "A diet promoting sugar dependency causes behavioral cross-sensitization to a low dose of amphetamine.", "entity": "Substance-Related Disorders", "aliases": "Abuse Drug Substance Abuses Addiction Dependence Disorder Use Habituation Disorders Organic Mental Induced Substance-Induced Substance-Related", "definition": "Disorders related to substance abuse.\n    ", "id": "MESH:D019966"}
{"mention": "behavioral cross-sensitization", "mention_text": "A diet promoting sugar dependency causes behavioral cross-sensitization to a low dose of amphetamine.", "entity": "Hyperkinesis", "aliases": "Generalized Hyperkinesia Hyperkinesias Hyperactivity Motor Hyperkinesis Hyperkinetic Movement Movements", "definition": "Excessive movement of muscles of the body as a whole, which may be associated with organic or psychological disorders.\n    ", "id": "MESH:D006948"}
{"mention": "amphetamine", "mention_text": "A diet promoting sugar dependency causes behavioral cross-sensitization to a low dose of amphetamine.", "entity": "Amphetamine", "aliases": "Amfetamine Amphetamine Sulfate (2:1) Centramina Desoxynorephedrin Fenamine Levoamphetamine Miquel Brand of Mydrial Phenamine Phenopromin Thyramine l l-Amphetamine levo levo-Amphetamine", "definition": "A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE.\n    ", "id": "MESH:D000661"}
{"mention": "drug dependency", "mention_text": "Previous research in this laboratory has shown that a diet of intermittent excessive sugar consumption produces a state with neurochemical and behavioral similarities to drug dependency. The present study examined whether female rats on various regimens of sugar access would show behavioral cross-sensitization to a low dose of amphetamine. After a 30-min baseline measure of locomotor activity (day 0), animals were maintained on a cyclic diet of 12-h deprivation followed by 12-h access to 10% sucrose solution and chow pellets (12 h access starting 4 h after onset of the dark period) for 21 days. Locomotor activity was measured again for 30 min at the beginning of days 1 and 21 of sugar access. Beginning on day 22, all rats were maintained on ad libitum chow. Nine days later locomotor activity was measured in response to a single low dose of amphetamine (0.5 mg/kg). The animals that had experienced cyclic sucrose and chow were hyperactive in response to amphetamine compared with four control groups (ad libitum 10% sucrose and chow followed by amphetamine injection, cyclic chow followed by amphetamine injection, ad libitum chow with amphetamine, or cyclic 10% sucrose and chow with a saline injection). These results suggest that a diet comprised of alternating deprivation and access to a sugar solution and chow produces bingeing on sugar that leads to a long lasting state of increased sensitivity to amphetamine, possibly due to a lasting alteration in the dopamine system.", "entity": "Substance-Related Disorders", "aliases": "Abuse Drug Substance Abuses Addiction Dependence Disorder Use Habituation Disorders Organic Mental Induced Substance-Induced Substance-Related", "definition": "Disorders related to substance abuse.\n    ", "id": "MESH:D019966"}
{"mention": "behavioral cross-sensitization", "mention_text": "Previous research in this laboratory has shown that a diet of intermittent excessive sugar consumption produces a state with neurochemical and behavioral similarities to drug dependency. The present study examined whether female rats on various regimens of sugar access would show behavioral cross-sensitization to a low dose of amphetamine. After a 30-min baseline measure of locomotor activity (day 0), animals were maintained on a cyclic diet of 12-h deprivation followed by 12-h access to 10% sucrose solution and chow pellets (12 h access starting 4 h after onset of the dark period) for 21 days. Locomotor activity was measured again for 30 min at the beginning of days 1 and 21 of sugar access. Beginning on day 22, all rats were maintained on ad libitum chow. Nine days later locomotor activity was measured in response to a single low dose of amphetamine (0.5 mg/kg). The animals that had experienced cyclic sucrose and chow were hyperactive in response to amphetamine compared with four control groups (ad libitum 10% sucrose and chow followed by amphetamine injection, cyclic chow followed by amphetamine injection, ad libitum chow with amphetamine, or cyclic 10% sucrose and chow with a saline injection). These results suggest that a diet comprised of alternating deprivation and access to a sugar solution and chow produces bingeing on sugar that leads to a long lasting state of increased sensitivity to amphetamine, possibly due to a lasting alteration in the dopamine system.", "entity": "Hyperkinesis", "aliases": "Generalized Hyperkinesia Hyperkinesias Hyperactivity Motor Hyperkinesis Hyperkinetic Movement Movements", "definition": "Excessive movement of muscles of the body as a whole, which may be associated with organic or psychological disorders.\n    ", "id": "MESH:D006948"}
{"mention": "amphetamine", "mention_text": "Previous research in this laboratory has shown that a diet of intermittent excessive sugar consumption produces a state with neurochemical and behavioral similarities to drug dependency. The present study examined whether female rats on various regimens of sugar access would show behavioral cross-sensitization to a low dose of amphetamine. After a 30-min baseline measure of locomotor activity (day 0), animals were maintained on a cyclic diet of 12-h deprivation followed by 12-h access to 10% sucrose solution and chow pellets (12 h access starting 4 h after onset of the dark period) for 21 days. Locomotor activity was measured again for 30 min at the beginning of days 1 and 21 of sugar access. Beginning on day 22, all rats were maintained on ad libitum chow. Nine days later locomotor activity was measured in response to a single low dose of amphetamine (0.5 mg/kg). The animals that had experienced cyclic sucrose and chow were hyperactive in response to amphetamine compared with four control groups (ad libitum 10% sucrose and chow followed by amphetamine injection, cyclic chow followed by amphetamine injection, ad libitum chow with amphetamine, or cyclic 10% sucrose and chow with a saline injection). These results suggest that a diet comprised of alternating deprivation and access to a sugar solution and chow produces bingeing on sugar that leads to a long lasting state of increased sensitivity to amphetamine, possibly due to a lasting alteration in the dopamine system.", "entity": "Amphetamine", "aliases": "Amfetamine Amphetamine Sulfate (2:1) Centramina Desoxynorephedrin Fenamine Levoamphetamine Miquel Brand of Mydrial Phenamine Phenopromin Thyramine l l-Amphetamine levo levo-Amphetamine", "definition": "A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE.\n    ", "id": "MESH:D000661"}
{"mention": "sucrose", "mention_text": "Previous research in this laboratory has shown that a diet of intermittent excessive sugar consumption produces a state with neurochemical and behavioral similarities to drug dependency. The present study examined whether female rats on various regimens of sugar access would show behavioral cross-sensitization to a low dose of amphetamine. After a 30-min baseline measure of locomotor activity (day 0), animals were maintained on a cyclic diet of 12-h deprivation followed by 12-h access to 10% sucrose solution and chow pellets (12 h access starting 4 h after onset of the dark period) for 21 days. Locomotor activity was measured again for 30 min at the beginning of days 1 and 21 of sugar access. Beginning on day 22, all rats were maintained on ad libitum chow. Nine days later locomotor activity was measured in response to a single low dose of amphetamine (0.5 mg/kg). The animals that had experienced cyclic sucrose and chow were hyperactive in response to amphetamine compared with four control groups (ad libitum 10% sucrose and chow followed by amphetamine injection, cyclic chow followed by amphetamine injection, ad libitum chow with amphetamine, or cyclic 10% sucrose and chow with a saline injection). These results suggest that a diet comprised of alternating deprivation and access to a sugar solution and chow produces bingeing on sugar that leads to a long lasting state of increased sensitivity to amphetamine, possibly due to a lasting alteration in the dopamine system.", "entity": "Sucrose", "aliases": "Saccharose Sucrose", "definition": "A nonreducing disaccharide composed of GLUCOSE and FRUCTOSE linked via their anomeric carbons. It is obtained commercially from SUGARCANE, sugar beet (BETA VULGARIS), and other plants and used extensively as a food and a sweetener.\n    ", "id": "MESH:D013395"}
{"mention": "hyperactive", "mention_text": "Previous research in this laboratory has shown that a diet of intermittent excessive sugar consumption produces a state with neurochemical and behavioral similarities to drug dependency. The present study examined whether female rats on various regimens of sugar access would show behavioral cross-sensitization to a low dose of amphetamine. After a 30-min baseline measure of locomotor activity (day 0), animals were maintained on a cyclic diet of 12-h deprivation followed by 12-h access to 10% sucrose solution and chow pellets (12 h access starting 4 h after onset of the dark period) for 21 days. Locomotor activity was measured again for 30 min at the beginning of days 1 and 21 of sugar access. Beginning on day 22, all rats were maintained on ad libitum chow. Nine days later locomotor activity was measured in response to a single low dose of amphetamine (0.5 mg/kg). The animals that had experienced cyclic sucrose and chow were hyperactive in response to amphetamine compared with four control groups (ad libitum 10% sucrose and chow followed by amphetamine injection, cyclic chow followed by amphetamine injection, ad libitum chow with amphetamine, or cyclic 10% sucrose and chow with a saline injection). These results suggest that a diet comprised of alternating deprivation and access to a sugar solution and chow produces bingeing on sugar that leads to a long lasting state of increased sensitivity to amphetamine, possibly due to a lasting alteration in the dopamine system.", "entity": "Hyperkinesis", "aliases": "Generalized Hyperkinesia Hyperkinesias Hyperactivity Motor Hyperkinesis Hyperkinetic Movement Movements", "definition": "Excessive movement of muscles of the body as a whole, which may be associated with organic or psychological disorders.\n    ", "id": "MESH:D006948"}
{"mention": "dopamine", "mention_text": "Previous research in this laboratory has shown that a diet of intermittent excessive sugar consumption produces a state with neurochemical and behavioral similarities to drug dependency. The present study examined whether female rats on various regimens of sugar access would show behavioral cross-sensitization to a low dose of amphetamine. After a 30-min baseline measure of locomotor activity (day 0), animals were maintained on a cyclic diet of 12-h deprivation followed by 12-h access to 10% sucrose solution and chow pellets (12 h access starting 4 h after onset of the dark period) for 21 days. Locomotor activity was measured again for 30 min at the beginning of days 1 and 21 of sugar access. Beginning on day 22, all rats were maintained on ad libitum chow. Nine days later locomotor activity was measured in response to a single low dose of amphetamine (0.5 mg/kg). The animals that had experienced cyclic sucrose and chow were hyperactive in response to amphetamine compared with four control groups (ad libitum 10% sucrose and chow followed by amphetamine injection, cyclic chow followed by amphetamine injection, ad libitum chow with amphetamine, or cyclic 10% sucrose and chow with a saline injection). These results suggest that a diet comprised of alternating deprivation and access to a sugar solution and chow produces bingeing on sugar that leads to a long lasting state of increased sensitivity to amphetamine, possibly due to a lasting alteration in the dopamine system.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "D-penicillamine", "mention_text": "D-penicillamine-induced angiopathy in rats. The effect of high dose D-penicillamine treatment on aortic permeability to albumin and on the ultrastructure of the vessel.", "entity": "Penicillamine", "aliases": "Copper Penicillaminate Cuprenil Cuprimine D 3 Mercaptovaline Penicillamine D-3-Mercaptovaline D-Penicillamine Dimethylcysteine Metalcaptase beta,beta beta,beta-Dimethylcysteine", "definition": "3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease.\n    ", "id": "MESH:D010396"}
{"mention": "angiopathy", "mention_text": "D-penicillamine-induced angiopathy in rats. The effect of high dose D-penicillamine treatment on aortic permeability to albumin and on the ultrastructure of the vessel.", "entity": "Aortic Diseases", "aliases": "Aortic Disease Diseases", "definition": "Pathological processes involving any part of the AORTA.\n    ", "id": "MESH:D001018"}
{"mention": "D-penicillamine", "mention_text": "Male Sprague-Dawley rats were treated with D-penicillamine (D-pen) 500 mg/kg/day for 10 or 42 days. Pair fed rats served as controls. Changes in aortic morphology were examined by light- and transmission-electron microscopy (TEM). In addition, the endothelial permeability and the penetration through the aortic wall of albumin were studied 10 minutes, 24 and 48 hours after i. v. injection of human serum 131I-albumin (131I-HSA). TEM revealed extensive elastolysis in the arterial wall of D-pen-treated rats, consistent with an inhibitory effect on crosslink formation. In experimental animals excess deposition of collagen and glycoaminoglycans was observed in the subendothelial and medial layer of the aortic wall, together with prominent basal membrane substance around aortic smooth muscle cells. The aorta/serum-ratio and the radioactive build-up 24 and 48 hours after injection of 131I-HSA was reduced in animals treated with D-pen for 42 days, indicating an impeded transmural transport of tracer which may be caused by a steric exclusion effect of abundant hyaluronate. The endothelial ultrastructure was unaffected by D-pen, and no differences in aortic 131I-HSA radioactivity or aorta/serum-ratio were recorded between experimental and control groups 10 minutes after tracer injection, indicating that the permeability of the endothelial barrier to albumin remained unaffected by D-pen treatment. These observations support the hypothesis that treatment with high doses of D-pen may induce a fibroproliferative response in rat aorta, possibly by an inhibitory effect on the cross-linking of collagen and elastin.", "entity": "Penicillamine", "aliases": "Copper Penicillaminate Cuprenil Cuprimine D 3 Mercaptovaline Penicillamine D-3-Mercaptovaline D-Penicillamine Dimethylcysteine Metalcaptase beta,beta beta,beta-Dimethylcysteine", "definition": "3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease.\n    ", "id": "MESH:D010396"}
{"mention": "D-pen", "mention_text": "Male Sprague-Dawley rats were treated with D-penicillamine (D-pen) 500 mg/kg/day for 10 or 42 days. Pair fed rats served as controls. Changes in aortic morphology were examined by light- and transmission-electron microscopy (TEM). In addition, the endothelial permeability and the penetration through the aortic wall of albumin were studied 10 minutes, 24 and 48 hours after i. v. injection of human serum 131I-albumin (131I-HSA). TEM revealed extensive elastolysis in the arterial wall of D-pen-treated rats, consistent with an inhibitory effect on crosslink formation. In experimental animals excess deposition of collagen and glycoaminoglycans was observed in the subendothelial and medial layer of the aortic wall, together with prominent basal membrane substance around aortic smooth muscle cells. The aorta/serum-ratio and the radioactive build-up 24 and 48 hours after injection of 131I-HSA was reduced in animals treated with D-pen for 42 days, indicating an impeded transmural transport of tracer which may be caused by a steric exclusion effect of abundant hyaluronate. The endothelial ultrastructure was unaffected by D-pen, and no differences in aortic 131I-HSA radioactivity or aorta/serum-ratio were recorded between experimental and control groups 10 minutes after tracer injection, indicating that the permeability of the endothelial barrier to albumin remained unaffected by D-pen treatment. These observations support the hypothesis that treatment with high doses of D-pen may induce a fibroproliferative response in rat aorta, possibly by an inhibitory effect on the cross-linking of collagen and elastin.", "entity": "Penicillamine", "aliases": "Copper Penicillaminate Cuprenil Cuprimine D 3 Mercaptovaline Penicillamine D-3-Mercaptovaline D-Penicillamine Dimethylcysteine Metalcaptase beta,beta beta,beta-Dimethylcysteine", "definition": "3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease.\n    ", "id": "MESH:D010396"}
{"mention": "hyaluronate", "mention_text": "Male Sprague-Dawley rats were treated with D-penicillamine (D-pen) 500 mg/kg/day for 10 or 42 days. Pair fed rats served as controls. Changes in aortic morphology were examined by light- and transmission-electron microscopy (TEM). In addition, the endothelial permeability and the penetration through the aortic wall of albumin were studied 10 minutes, 24 and 48 hours after i. v. injection of human serum 131I-albumin (131I-HSA). TEM revealed extensive elastolysis in the arterial wall of D-pen-treated rats, consistent with an inhibitory effect on crosslink formation. In experimental animals excess deposition of collagen and glycoaminoglycans was observed in the subendothelial and medial layer of the aortic wall, together with prominent basal membrane substance around aortic smooth muscle cells. The aorta/serum-ratio and the radioactive build-up 24 and 48 hours after injection of 131I-HSA was reduced in animals treated with D-pen for 42 days, indicating an impeded transmural transport of tracer which may be caused by a steric exclusion effect of abundant hyaluronate. The endothelial ultrastructure was unaffected by D-pen, and no differences in aortic 131I-HSA radioactivity or aorta/serum-ratio were recorded between experimental and control groups 10 minutes after tracer injection, indicating that the permeability of the endothelial barrier to albumin remained unaffected by D-pen treatment. These observations support the hypothesis that treatment with high doses of D-pen may induce a fibroproliferative response in rat aorta, possibly by an inhibitory effect on the cross-linking of collagen and elastin.", "entity": "Hyaluronic Acid", "aliases": "Acid Hyaluronic Advanced Medical Optics Brand of Sodium Hyaluronidate Inc. Hyaluronate Akorn Amo Vitrax Amvisc Anika Therapeutics Bausch and Lomb Biolon Etamucine Healon Hyaluronan Hyvisc Luronit", "definition": "A natural high-viscosity mucopolysaccharide with alternating beta (1-3) glucuronide and beta (1-4) glucosaminidic bonds. It is found in the UMBILICAL CORD, in VITREOUS BODY and in SYNOVIAL FLUID. A high urinary level is found in PROGERIA.\n    ", "id": "MESH:D006820"}
{"mention": "anthracycline", "mention_text": "Brain natriuretic peptide is a predictor of anthracycline-induced cardiotoxicity.", "entity": "Anthracyclines", "aliases": "Anthracyclines", "definition": "Organic compounds that have a tetrahydronaphthacenedione ring structure attached by a glycosidic linkage to the amino sugar daunosamine.\n    ", "id": "MESH:D018943"}
{"mention": "cardiotoxicity", "mention_text": "Brain natriuretic peptide is a predictor of anthracycline-induced cardiotoxicity.", "entity": "Cardiotoxicity", "aliases": "Cardiac Toxicities Toxicity Cardiotoxicities Cardiotoxicity", "definition": "Damage to the heart or its function secondary to exposure to toxic substances such as drugs used in CHEMOTHERAPY; IMMUNOTHERAPY; or RADIATION.\n    ", "id": "MESH:D066126"}
{"mention": "Anthracyclines", "mention_text": "Anthracyclines are effective antineoplastic drugs, but they frequently cause dose-related cardiotoxicity. The cardiotoxicity of conventional anthracycline therapy highlights a need to search for methods that are highly sensitive and capable of predicting cardiac dysfunction. We measured the plasma level of brain natriuretic peptide (BNP) to determine whether BNP might serve as a simple diagnostic indicator of anthracycline-induced cardiotoxicity in patients with acute leukemia treated with a daunorubicin (DNR)-containing regimen. Thirteen patients with acute leukemia were treated with a DNR-containing regimen. Cardiac functions were evaluated with radionuclide angiography before chemotherapies. The plasma levels of atrial natriuretic peptide (ANP) and BNP were measured at the time of radionuclide angiography. Three patients developed congestive heart failure after the completion of chemotherapy. Five patients were diagnosed as having subclinical heart failure after the completion of chemotherapy. The plasma levels of BNP in all the patients with clinical and subclinical heart failure increased above the normal limit (40 pg/ml) before the detection of clinical or subclinical heart failure by radionuclide angiography. On the other hand, BNP did not increase in the patients without heart failure given DNR, even at more than 700 mg/m(2). The plasma level of ANP did not always increase in all the patients with clinical and subclinical heart failure. These preliminary results suggest that BNP may be useful as an early and sensitive indicator of anthracycline-induced cardiotoxicity.", "entity": "Anthracyclines", "aliases": "Anthracyclines", "definition": "Organic compounds that have a tetrahydronaphthacenedione ring structure attached by a glycosidic linkage to the amino sugar daunosamine.\n    ", "id": "MESH:D018943"}
{"mention": "cardiotoxicity", "mention_text": "Anthracyclines are effective antineoplastic drugs, but they frequently cause dose-related cardiotoxicity. The cardiotoxicity of conventional anthracycline therapy highlights a need to search for methods that are highly sensitive and capable of predicting cardiac dysfunction. We measured the plasma level of brain natriuretic peptide (BNP) to determine whether BNP might serve as a simple diagnostic indicator of anthracycline-induced cardiotoxicity in patients with acute leukemia treated with a daunorubicin (DNR)-containing regimen. Thirteen patients with acute leukemia were treated with a DNR-containing regimen. Cardiac functions were evaluated with radionuclide angiography before chemotherapies. The plasma levels of atrial natriuretic peptide (ANP) and BNP were measured at the time of radionuclide angiography. Three patients developed congestive heart failure after the completion of chemotherapy. Five patients were diagnosed as having subclinical heart failure after the completion of chemotherapy. The plasma levels of BNP in all the patients with clinical and subclinical heart failure increased above the normal limit (40 pg/ml) before the detection of clinical or subclinical heart failure by radionuclide angiography. On the other hand, BNP did not increase in the patients without heart failure given DNR, even at more than 700 mg/m(2). The plasma level of ANP did not always increase in all the patients with clinical and subclinical heart failure. These preliminary results suggest that BNP may be useful as an early and sensitive indicator of anthracycline-induced cardiotoxicity.", "entity": "Cardiotoxicity", "aliases": "Cardiac Toxicities Toxicity Cardiotoxicities Cardiotoxicity", "definition": "Damage to the heart or its function secondary to exposure to toxic substances such as drugs used in CHEMOTHERAPY; IMMUNOTHERAPY; or RADIATION.\n    ", "id": "MESH:D066126"}
{"mention": "anthracycline", "mention_text": "Anthracyclines are effective antineoplastic drugs, but they frequently cause dose-related cardiotoxicity. The cardiotoxicity of conventional anthracycline therapy highlights a need to search for methods that are highly sensitive and capable of predicting cardiac dysfunction. We measured the plasma level of brain natriuretic peptide (BNP) to determine whether BNP might serve as a simple diagnostic indicator of anthracycline-induced cardiotoxicity in patients with acute leukemia treated with a daunorubicin (DNR)-containing regimen. Thirteen patients with acute leukemia were treated with a DNR-containing regimen. Cardiac functions were evaluated with radionuclide angiography before chemotherapies. The plasma levels of atrial natriuretic peptide (ANP) and BNP were measured at the time of radionuclide angiography. Three patients developed congestive heart failure after the completion of chemotherapy. Five patients were diagnosed as having subclinical heart failure after the completion of chemotherapy. The plasma levels of BNP in all the patients with clinical and subclinical heart failure increased above the normal limit (40 pg/ml) before the detection of clinical or subclinical heart failure by radionuclide angiography. On the other hand, BNP did not increase in the patients without heart failure given DNR, even at more than 700 mg/m(2). The plasma level of ANP did not always increase in all the patients with clinical and subclinical heart failure. These preliminary results suggest that BNP may be useful as an early and sensitive indicator of anthracycline-induced cardiotoxicity.", "entity": "Anthracyclines", "aliases": "Anthracyclines", "definition": "Organic compounds that have a tetrahydronaphthacenedione ring structure attached by a glycosidic linkage to the amino sugar daunosamine.\n    ", "id": "MESH:D018943"}
{"mention": "cardiac dysfunction", "mention_text": "Anthracyclines are effective antineoplastic drugs, but they frequently cause dose-related cardiotoxicity. The cardiotoxicity of conventional anthracycline therapy highlights a need to search for methods that are highly sensitive and capable of predicting cardiac dysfunction. We measured the plasma level of brain natriuretic peptide (BNP) to determine whether BNP might serve as a simple diagnostic indicator of anthracycline-induced cardiotoxicity in patients with acute leukemia treated with a daunorubicin (DNR)-containing regimen. Thirteen patients with acute leukemia were treated with a DNR-containing regimen. Cardiac functions were evaluated with radionuclide angiography before chemotherapies. The plasma levels of atrial natriuretic peptide (ANP) and BNP were measured at the time of radionuclide angiography. Three patients developed congestive heart failure after the completion of chemotherapy. Five patients were diagnosed as having subclinical heart failure after the completion of chemotherapy. The plasma levels of BNP in all the patients with clinical and subclinical heart failure increased above the normal limit (40 pg/ml) before the detection of clinical or subclinical heart failure by radionuclide angiography. On the other hand, BNP did not increase in the patients without heart failure given DNR, even at more than 700 mg/m(2). The plasma level of ANP did not always increase in all the patients with clinical and subclinical heart failure. These preliminary results suggest that BNP may be useful as an early and sensitive indicator of anthracycline-induced cardiotoxicity.", "entity": "Heart Diseases", "aliases": "Cardiac Disease Diseases Heart", "definition": "Pathological conditions involving the HEART including its structural and functional abnormalities.\n    ", "id": "MESH:D006331"}
{"mention": "acute leukemia", "mention_text": "Anthracyclines are effective antineoplastic drugs, but they frequently cause dose-related cardiotoxicity. The cardiotoxicity of conventional anthracycline therapy highlights a need to search for methods that are highly sensitive and capable of predicting cardiac dysfunction. We measured the plasma level of brain natriuretic peptide (BNP) to determine whether BNP might serve as a simple diagnostic indicator of anthracycline-induced cardiotoxicity in patients with acute leukemia treated with a daunorubicin (DNR)-containing regimen. Thirteen patients with acute leukemia were treated with a DNR-containing regimen. Cardiac functions were evaluated with radionuclide angiography before chemotherapies. The plasma levels of atrial natriuretic peptide (ANP) and BNP were measured at the time of radionuclide angiography. Three patients developed congestive heart failure after the completion of chemotherapy. Five patients were diagnosed as having subclinical heart failure after the completion of chemotherapy. The plasma levels of BNP in all the patients with clinical and subclinical heart failure increased above the normal limit (40 pg/ml) before the detection of clinical or subclinical heart failure by radionuclide angiography. On the other hand, BNP did not increase in the patients without heart failure given DNR, even at more than 700 mg/m(2). The plasma level of ANP did not always increase in all the patients with clinical and subclinical heart failure. These preliminary results suggest that BNP may be useful as an early and sensitive indicator of anthracycline-induced cardiotoxicity.", "entity": "Leukemia, Myeloid, Acute", "aliases": "ANLL Acute Myeloblastic Leukemia Leukemias Myelocytic Myelogenous Myeloid with Maturation without Nonlymphoblastic Nonlymphocytic M1 M2", "definition": "Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.\n    ", "id": "MESH:D015470"}
{"mention": "daunorubicin", "mention_text": "Anthracyclines are effective antineoplastic drugs, but they frequently cause dose-related cardiotoxicity. The cardiotoxicity of conventional anthracycline therapy highlights a need to search for methods that are highly sensitive and capable of predicting cardiac dysfunction. We measured the plasma level of brain natriuretic peptide (BNP) to determine whether BNP might serve as a simple diagnostic indicator of anthracycline-induced cardiotoxicity in patients with acute leukemia treated with a daunorubicin (DNR)-containing regimen. Thirteen patients with acute leukemia were treated with a DNR-containing regimen. Cardiac functions were evaluated with radionuclide angiography before chemotherapies. The plasma levels of atrial natriuretic peptide (ANP) and BNP were measured at the time of radionuclide angiography. Three patients developed congestive heart failure after the completion of chemotherapy. Five patients were diagnosed as having subclinical heart failure after the completion of chemotherapy. The plasma levels of BNP in all the patients with clinical and subclinical heart failure increased above the normal limit (40 pg/ml) before the detection of clinical or subclinical heart failure by radionuclide angiography. On the other hand, BNP did not increase in the patients without heart failure given DNR, even at more than 700 mg/m(2). The plasma level of ANP did not always increase in all the patients with clinical and subclinical heart failure. These preliminary results suggest that BNP may be useful as an early and sensitive indicator of anthracycline-induced cardiotoxicity.", "entity": "Daunorubicin", "aliases": "Cerubidine Dauno Rubidomycine Dauno-Rubidomycine Daunoblastin Daunoblastine Daunomycin Daunorubicin Hydrochloride NSC 82151 NSC-82151 NSC82151 Rubidomycin Rubomycin", "definition": "A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.\n    ", "id": "MESH:D003630"}
{"mention": "DNR", "mention_text": "Anthracyclines are effective antineoplastic drugs, but they frequently cause dose-related cardiotoxicity. The cardiotoxicity of conventional anthracycline therapy highlights a need to search for methods that are highly sensitive and capable of predicting cardiac dysfunction. We measured the plasma level of brain natriuretic peptide (BNP) to determine whether BNP might serve as a simple diagnostic indicator of anthracycline-induced cardiotoxicity in patients with acute leukemia treated with a daunorubicin (DNR)-containing regimen. Thirteen patients with acute leukemia were treated with a DNR-containing regimen. Cardiac functions were evaluated with radionuclide angiography before chemotherapies. The plasma levels of atrial natriuretic peptide (ANP) and BNP were measured at the time of radionuclide angiography. Three patients developed congestive heart failure after the completion of chemotherapy. Five patients were diagnosed as having subclinical heart failure after the completion of chemotherapy. The plasma levels of BNP in all the patients with clinical and subclinical heart failure increased above the normal limit (40 pg/ml) before the detection of clinical or subclinical heart failure by radionuclide angiography. On the other hand, BNP did not increase in the patients without heart failure given DNR, even at more than 700 mg/m(2). The plasma level of ANP did not always increase in all the patients with clinical and subclinical heart failure. These preliminary results suggest that BNP may be useful as an early and sensitive indicator of anthracycline-induced cardiotoxicity.", "entity": "Daunorubicin", "aliases": "Cerubidine Dauno Rubidomycine Dauno-Rubidomycine Daunoblastin Daunoblastine Daunomycin Daunorubicin Hydrochloride NSC 82151 NSC-82151 NSC82151 Rubidomycin Rubomycin", "definition": "A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.\n    ", "id": "MESH:D003630"}
{"mention": "congestive heart failure", "mention_text": "Anthracyclines are effective antineoplastic drugs, but they frequently cause dose-related cardiotoxicity. The cardiotoxicity of conventional anthracycline therapy highlights a need to search for methods that are highly sensitive and capable of predicting cardiac dysfunction. We measured the plasma level of brain natriuretic peptide (BNP) to determine whether BNP might serve as a simple diagnostic indicator of anthracycline-induced cardiotoxicity in patients with acute leukemia treated with a daunorubicin (DNR)-containing regimen. Thirteen patients with acute leukemia were treated with a DNR-containing regimen. Cardiac functions were evaluated with radionuclide angiography before chemotherapies. The plasma levels of atrial natriuretic peptide (ANP) and BNP were measured at the time of radionuclide angiography. Three patients developed congestive heart failure after the completion of chemotherapy. Five patients were diagnosed as having subclinical heart failure after the completion of chemotherapy. The plasma levels of BNP in all the patients with clinical and subclinical heart failure increased above the normal limit (40 pg/ml) before the detection of clinical or subclinical heart failure by radionuclide angiography. On the other hand, BNP did not increase in the patients without heart failure given DNR, even at more than 700 mg/m(2). The plasma level of ANP did not always increase in all the patients with clinical and subclinical heart failure. These preliminary results suggest that BNP may be useful as an early and sensitive indicator of anthracycline-induced cardiotoxicity.", "entity": "Heart Failure", "aliases": "Cardiac Failure Congestive Heart Decompensation Left Sided Left-Sided Right Right-Sided Myocardial", "definition": "A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.\n    ", "id": "MESH:D006333"}
{"mention": "heart failure", "mention_text": "Anthracyclines are effective antineoplastic drugs, but they frequently cause dose-related cardiotoxicity. The cardiotoxicity of conventional anthracycline therapy highlights a need to search for methods that are highly sensitive and capable of predicting cardiac dysfunction. We measured the plasma level of brain natriuretic peptide (BNP) to determine whether BNP might serve as a simple diagnostic indicator of anthracycline-induced cardiotoxicity in patients with acute leukemia treated with a daunorubicin (DNR)-containing regimen. Thirteen patients with acute leukemia were treated with a DNR-containing regimen. Cardiac functions were evaluated with radionuclide angiography before chemotherapies. The plasma levels of atrial natriuretic peptide (ANP) and BNP were measured at the time of radionuclide angiography. Three patients developed congestive heart failure after the completion of chemotherapy. Five patients were diagnosed as having subclinical heart failure after the completion of chemotherapy. The plasma levels of BNP in all the patients with clinical and subclinical heart failure increased above the normal limit (40 pg/ml) before the detection of clinical or subclinical heart failure by radionuclide angiography. On the other hand, BNP did not increase in the patients without heart failure given DNR, even at more than 700 mg/m(2). The plasma level of ANP did not always increase in all the patients with clinical and subclinical heart failure. These preliminary results suggest that BNP may be useful as an early and sensitive indicator of anthracycline-induced cardiotoxicity.", "entity": "Heart Failure", "aliases": "Cardiac Failure Congestive Heart Decompensation Left Sided Left-Sided Right Right-Sided Myocardial", "definition": "A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.\n    ", "id": "MESH:D006333"}
{"mention": "birth defects", "mention_text": "Antibacterial medication use during pregnancy and risk of birth defects: National Birth Defects Prevention Study.", "entity": "Abnormalities, Drug-Induced", "aliases": "Abnormalities Drug Induced Drug-Induced Abnormality", "definition": "Congenital abnormalities caused by medicinal substances or drugs of abuse given to or taken by the mother, or to which she is inadvertently exposed during the manufacture of such substances. The concept excludes abnormalities resulting from exposure to non-medicinal chemicals in the environment.\n    ", "id": "MESH:D000014"}
{"mention": "Birth Defects", "mention_text": "Antibacterial medication use during pregnancy and risk of birth defects: National Birth Defects Prevention Study.", "entity": "Abnormalities, Drug-Induced", "aliases": "Abnormalities Drug Induced Drug-Induced Abnormality", "definition": "Congenital abnormalities caused by medicinal substances or drugs of abuse given to or taken by the mother, or to which she is inadvertently exposed during the manufacture of such substances. The concept excludes abnormalities resulting from exposure to non-medicinal chemicals in the environment.\n    ", "id": "MESH:D000014"}
{"mention": "birth defects", "mention_text": "OBJECTIVE: To estimate the association between antibacterial medications and selected birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based, multisite, case-control study of women who had pregnancies affected by 1 of more than 30 eligible major birth defects identified via birth defect surveillance programs in 10 states (n = 13 155) and control women randomly selected from the same geographical regions (n = 4941). MAIN EXPOSURE: Reported maternal use of antibacterials (1 month before pregnancy through the end of the first trimester). MAIN OUTCOME MEASURE: Odds ratios (ORs) measuring the association between antibacterial use and selected birth defects adjusted for potential confounders. RESULTS: The reported use of antibacterials increased during pregnancy, peaking during the third month. Sulfonamides were associated with anencephaly (adjusted OR [AOR] = 3.4; 95% confidence interval [CI], 1.3-8.8), hypoplastic left heart syndrome (AOR = 3.2; 95% CI, 1.3-7.6), coarctation of the aorta (AOR = 2.7; 95% CI, 1.3-5.6), choanal atresia (AOR = 8.0; 95% CI, 2.7-23.5), transverse limb deficiency (AOR = 2.5; 95% CI, 1.0-5.9), and diaphragmatic hernia (AOR = 2.4; 95% CI, 1.1-5.4). Nitrofurantoins were associated with anophthalmia or microphthalmos (AOR = 3.7; 95% CI, 1.1-12.2), hypoplastic left heart syndrome (AOR = 4.2; 95% CI, 1.9-9.1), atrial septal defects (AOR = 1.9; 95% CI, 1.1-3.4), and cleft lip with cleft palate (AOR = 2.1; 95% CI, 1.2-3.9). Other antibacterial agents that showed associations included erythromycins (2 defects), penicillins (1 defect), cephalosporins (1 defect), and quinolones (1 defect). CONCLUSIONS: Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects. Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny.", "entity": "Abnormalities, Drug-Induced", "aliases": "Abnormalities Drug Induced Drug-Induced Abnormality", "definition": "Congenital abnormalities caused by medicinal substances or drugs of abuse given to or taken by the mother, or to which she is inadvertently exposed during the manufacture of such substances. The concept excludes abnormalities resulting from exposure to non-medicinal chemicals in the environment.\n    ", "id": "MESH:D000014"}
{"mention": "birth defect", "mention_text": "OBJECTIVE: To estimate the association between antibacterial medications and selected birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based, multisite, case-control study of women who had pregnancies affected by 1 of more than 30 eligible major birth defects identified via birth defect surveillance programs in 10 states (n = 13 155) and control women randomly selected from the same geographical regions (n = 4941). MAIN EXPOSURE: Reported maternal use of antibacterials (1 month before pregnancy through the end of the first trimester). MAIN OUTCOME MEASURE: Odds ratios (ORs) measuring the association between antibacterial use and selected birth defects adjusted for potential confounders. RESULTS: The reported use of antibacterials increased during pregnancy, peaking during the third month. Sulfonamides were associated with anencephaly (adjusted OR [AOR] = 3.4; 95% confidence interval [CI], 1.3-8.8), hypoplastic left heart syndrome (AOR = 3.2; 95% CI, 1.3-7.6), coarctation of the aorta (AOR = 2.7; 95% CI, 1.3-5.6), choanal atresia (AOR = 8.0; 95% CI, 2.7-23.5), transverse limb deficiency (AOR = 2.5; 95% CI, 1.0-5.9), and diaphragmatic hernia (AOR = 2.4; 95% CI, 1.1-5.4). Nitrofurantoins were associated with anophthalmia or microphthalmos (AOR = 3.7; 95% CI, 1.1-12.2), hypoplastic left heart syndrome (AOR = 4.2; 95% CI, 1.9-9.1), atrial septal defects (AOR = 1.9; 95% CI, 1.1-3.4), and cleft lip with cleft palate (AOR = 2.1; 95% CI, 1.2-3.9). Other antibacterial agents that showed associations included erythromycins (2 defects), penicillins (1 defect), cephalosporins (1 defect), and quinolones (1 defect). CONCLUSIONS: Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects. Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny.", "entity": "Abnormalities, Drug-Induced", "aliases": "Abnormalities Drug Induced Drug-Induced Abnormality", "definition": "Congenital abnormalities caused by medicinal substances or drugs of abuse given to or taken by the mother, or to which she is inadvertently exposed during the manufacture of such substances. The concept excludes abnormalities resulting from exposure to non-medicinal chemicals in the environment.\n    ", "id": "MESH:D000014"}
{"mention": "Sulfonamides", "mention_text": "OBJECTIVE: To estimate the association between antibacterial medications and selected birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based, multisite, case-control study of women who had pregnancies affected by 1 of more than 30 eligible major birth defects identified via birth defect surveillance programs in 10 states (n = 13 155) and control women randomly selected from the same geographical regions (n = 4941). MAIN EXPOSURE: Reported maternal use of antibacterials (1 month before pregnancy through the end of the first trimester). MAIN OUTCOME MEASURE: Odds ratios (ORs) measuring the association between antibacterial use and selected birth defects adjusted for potential confounders. RESULTS: The reported use of antibacterials increased during pregnancy, peaking during the third month. Sulfonamides were associated with anencephaly (adjusted OR [AOR] = 3.4; 95% confidence interval [CI], 1.3-8.8), hypoplastic left heart syndrome (AOR = 3.2; 95% CI, 1.3-7.6), coarctation of the aorta (AOR = 2.7; 95% CI, 1.3-5.6), choanal atresia (AOR = 8.0; 95% CI, 2.7-23.5), transverse limb deficiency (AOR = 2.5; 95% CI, 1.0-5.9), and diaphragmatic hernia (AOR = 2.4; 95% CI, 1.1-5.4). Nitrofurantoins were associated with anophthalmia or microphthalmos (AOR = 3.7; 95% CI, 1.1-12.2), hypoplastic left heart syndrome (AOR = 4.2; 95% CI, 1.9-9.1), atrial septal defects (AOR = 1.9; 95% CI, 1.1-3.4), and cleft lip with cleft palate (AOR = 2.1; 95% CI, 1.2-3.9). Other antibacterial agents that showed associations included erythromycins (2 defects), penicillins (1 defect), cephalosporins (1 defect), and quinolones (1 defect). CONCLUSIONS: Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects. Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny.", "entity": "Sulfonamides", "aliases": "Mixtures Sulfonamide Sulfonamides", "definition": "A group of compounds that contain the structure SO2NH2.\n    ", "id": "MESH:D013449"}
{"mention": "anencephaly", "mention_text": "OBJECTIVE: To estimate the association between antibacterial medications and selected birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based, multisite, case-control study of women who had pregnancies affected by 1 of more than 30 eligible major birth defects identified via birth defect surveillance programs in 10 states (n = 13 155) and control women randomly selected from the same geographical regions (n = 4941). MAIN EXPOSURE: Reported maternal use of antibacterials (1 month before pregnancy through the end of the first trimester). MAIN OUTCOME MEASURE: Odds ratios (ORs) measuring the association between antibacterial use and selected birth defects adjusted for potential confounders. RESULTS: The reported use of antibacterials increased during pregnancy, peaking during the third month. Sulfonamides were associated with anencephaly (adjusted OR [AOR] = 3.4; 95% confidence interval [CI], 1.3-8.8), hypoplastic left heart syndrome (AOR = 3.2; 95% CI, 1.3-7.6), coarctation of the aorta (AOR = 2.7; 95% CI, 1.3-5.6), choanal atresia (AOR = 8.0; 95% CI, 2.7-23.5), transverse limb deficiency (AOR = 2.5; 95% CI, 1.0-5.9), and diaphragmatic hernia (AOR = 2.4; 95% CI, 1.1-5.4). Nitrofurantoins were associated with anophthalmia or microphthalmos (AOR = 3.7; 95% CI, 1.1-12.2), hypoplastic left heart syndrome (AOR = 4.2; 95% CI, 1.9-9.1), atrial septal defects (AOR = 1.9; 95% CI, 1.1-3.4), and cleft lip with cleft palate (AOR = 2.1; 95% CI, 1.2-3.9). Other antibacterial agents that showed associations included erythromycins (2 defects), penicillins (1 defect), cephalosporins (1 defect), and quinolones (1 defect). CONCLUSIONS: Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects. Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny.", "entity": "Anencephaly", "aliases": "Absence of Brain Congenital Anencephalia Anencephalias Anencephalies Partial Anencephalus Anencephaly Hemicranial Incomplete Aprosencephalies Aprosencephaly", "definition": "A malformation of the nervous system caused by failure of the anterior neuropore to close. Infants are born with intact spinal cords, cerebellums, and brainstems, but lack formation of neural structures above this level. The skull is only partially formed but the eyes are usually normal. This condition may be associated with folate deficiency. Affected infants are only capable of primitive (brain stem) reflexes and usually do not survive for more than two weeks. (From Menkes, Textbook of Child Neurology, 5th ed, p247)\n    ", "id": "MESH:D000757"}
{"mention": "hypoplastic left heart syndrome", "mention_text": "OBJECTIVE: To estimate the association between antibacterial medications and selected birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based, multisite, case-control study of women who had pregnancies affected by 1 of more than 30 eligible major birth defects identified via birth defect surveillance programs in 10 states (n = 13 155) and control women randomly selected from the same geographical regions (n = 4941). MAIN EXPOSURE: Reported maternal use of antibacterials (1 month before pregnancy through the end of the first trimester). MAIN OUTCOME MEASURE: Odds ratios (ORs) measuring the association between antibacterial use and selected birth defects adjusted for potential confounders. RESULTS: The reported use of antibacterials increased during pregnancy, peaking during the third month. Sulfonamides were associated with anencephaly (adjusted OR [AOR] = 3.4; 95% confidence interval [CI], 1.3-8.8), hypoplastic left heart syndrome (AOR = 3.2; 95% CI, 1.3-7.6), coarctation of the aorta (AOR = 2.7; 95% CI, 1.3-5.6), choanal atresia (AOR = 8.0; 95% CI, 2.7-23.5), transverse limb deficiency (AOR = 2.5; 95% CI, 1.0-5.9), and diaphragmatic hernia (AOR = 2.4; 95% CI, 1.1-5.4). Nitrofurantoins were associated with anophthalmia or microphthalmos (AOR = 3.7; 95% CI, 1.1-12.2), hypoplastic left heart syndrome (AOR = 4.2; 95% CI, 1.9-9.1), atrial septal defects (AOR = 1.9; 95% CI, 1.1-3.4), and cleft lip with cleft palate (AOR = 2.1; 95% CI, 1.2-3.9). Other antibacterial agents that showed associations included erythromycins (2 defects), penicillins (1 defect), cephalosporins (1 defect), and quinolones (1 defect). CONCLUSIONS: Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects. Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny.", "entity": "Hypoplastic Left Heart Syndrome", "aliases": "Hypoplastic Left Heart Syndrome Hypoplasia", "definition": "A condition caused by underdevelopment of the whole left half of the heart. It is characterized by hypoplasia of the left cardiac chambers (HEART ATRIUM; HEART VENTRICLE), the AORTA, the AORTIC VALVE, and the MITRAL VALVE. Severe symptoms appear in early infancy when DUCTUS ARTERIOSUS closes.\n    ", "id": "MESH:D018636"}
{"mention": "coarctation of the aorta", "mention_text": "OBJECTIVE: To estimate the association between antibacterial medications and selected birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based, multisite, case-control study of women who had pregnancies affected by 1 of more than 30 eligible major birth defects identified via birth defect surveillance programs in 10 states (n = 13 155) and control women randomly selected from the same geographical regions (n = 4941). MAIN EXPOSURE: Reported maternal use of antibacterials (1 month before pregnancy through the end of the first trimester). MAIN OUTCOME MEASURE: Odds ratios (ORs) measuring the association between antibacterial use and selected birth defects adjusted for potential confounders. RESULTS: The reported use of antibacterials increased during pregnancy, peaking during the third month. Sulfonamides were associated with anencephaly (adjusted OR [AOR] = 3.4; 95% confidence interval [CI], 1.3-8.8), hypoplastic left heart syndrome (AOR = 3.2; 95% CI, 1.3-7.6), coarctation of the aorta (AOR = 2.7; 95% CI, 1.3-5.6), choanal atresia (AOR = 8.0; 95% CI, 2.7-23.5), transverse limb deficiency (AOR = 2.5; 95% CI, 1.0-5.9), and diaphragmatic hernia (AOR = 2.4; 95% CI, 1.1-5.4). Nitrofurantoins were associated with anophthalmia or microphthalmos (AOR = 3.7; 95% CI, 1.1-12.2), hypoplastic left heart syndrome (AOR = 4.2; 95% CI, 1.9-9.1), atrial septal defects (AOR = 1.9; 95% CI, 1.1-3.4), and cleft lip with cleft palate (AOR = 2.1; 95% CI, 1.2-3.9). Other antibacterial agents that showed associations included erythromycins (2 defects), penicillins (1 defect), cephalosporins (1 defect), and quinolones (1 defect). CONCLUSIONS: Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects. Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny.", "entity": "Aortic Coarctation", "aliases": "Aorta Coarctation Coarctations Dominant Aortic of the", "definition": "A birth defect characterized by the narrowing of the AORTA that can be of varying degree and at any point from the transverse arch to the iliac bifurcation. Aortic coarctation causes arterial HYPERTENSION before the point of narrowing and arterial HYPOTENSION beyond the narrowed portion.\n    ", "id": "MESH:D001017"}
{"mention": "choanal atresia", "mention_text": "OBJECTIVE: To estimate the association between antibacterial medications and selected birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based, multisite, case-control study of women who had pregnancies affected by 1 of more than 30 eligible major birth defects identified via birth defect surveillance programs in 10 states (n = 13 155) and control women randomly selected from the same geographical regions (n = 4941). MAIN EXPOSURE: Reported maternal use of antibacterials (1 month before pregnancy through the end of the first trimester). MAIN OUTCOME MEASURE: Odds ratios (ORs) measuring the association between antibacterial use and selected birth defects adjusted for potential confounders. RESULTS: The reported use of antibacterials increased during pregnancy, peaking during the third month. Sulfonamides were associated with anencephaly (adjusted OR [AOR] = 3.4; 95% confidence interval [CI], 1.3-8.8), hypoplastic left heart syndrome (AOR = 3.2; 95% CI, 1.3-7.6), coarctation of the aorta (AOR = 2.7; 95% CI, 1.3-5.6), choanal atresia (AOR = 8.0; 95% CI, 2.7-23.5), transverse limb deficiency (AOR = 2.5; 95% CI, 1.0-5.9), and diaphragmatic hernia (AOR = 2.4; 95% CI, 1.1-5.4). Nitrofurantoins were associated with anophthalmia or microphthalmos (AOR = 3.7; 95% CI, 1.1-12.2), hypoplastic left heart syndrome (AOR = 4.2; 95% CI, 1.9-9.1), atrial septal defects (AOR = 1.9; 95% CI, 1.1-3.4), and cleft lip with cleft palate (AOR = 2.1; 95% CI, 1.2-3.9). Other antibacterial agents that showed associations included erythromycins (2 defects), penicillins (1 defect), cephalosporins (1 defect), and quinolones (1 defect). CONCLUSIONS: Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects. Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny.", "entity": "Choanal Atresia", "aliases": "Atresia Choanal Atresias", "definition": "A congenital abnormality that is characterized by a blocked CHOANAE, the opening between the nose and the NASOPHARYNX. Blockage can be unilateral or bilateral; bony or membranous.\n    ", "id": "MESH:D002754"}
{"mention": "transverse limb deficiency", "mention_text": "OBJECTIVE: To estimate the association between antibacterial medications and selected birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based, multisite, case-control study of women who had pregnancies affected by 1 of more than 30 eligible major birth defects identified via birth defect surveillance programs in 10 states (n = 13 155) and control women randomly selected from the same geographical regions (n = 4941). MAIN EXPOSURE: Reported maternal use of antibacterials (1 month before pregnancy through the end of the first trimester). MAIN OUTCOME MEASURE: Odds ratios (ORs) measuring the association between antibacterial use and selected birth defects adjusted for potential confounders. RESULTS: The reported use of antibacterials increased during pregnancy, peaking during the third month. Sulfonamides were associated with anencephaly (adjusted OR [AOR] = 3.4; 95% confidence interval [CI], 1.3-8.8), hypoplastic left heart syndrome (AOR = 3.2; 95% CI, 1.3-7.6), coarctation of the aorta (AOR = 2.7; 95% CI, 1.3-5.6), choanal atresia (AOR = 8.0; 95% CI, 2.7-23.5), transverse limb deficiency (AOR = 2.5; 95% CI, 1.0-5.9), and diaphragmatic hernia (AOR = 2.4; 95% CI, 1.1-5.4). Nitrofurantoins were associated with anophthalmia or microphthalmos (AOR = 3.7; 95% CI, 1.1-12.2), hypoplastic left heart syndrome (AOR = 4.2; 95% CI, 1.9-9.1), atrial septal defects (AOR = 1.9; 95% CI, 1.1-3.4), and cleft lip with cleft palate (AOR = 2.1; 95% CI, 1.2-3.9). Other antibacterial agents that showed associations included erythromycins (2 defects), penicillins (1 defect), cephalosporins (1 defect), and quinolones (1 defect). CONCLUSIONS: Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects. Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny.", "entity": "Limb Deformities, Congenital", "aliases": "Congenital Limb Deformities Deformity", "definition": "Congenital structural deformities of the upper and lower extremities collectively or unspecified.\n    ", "id": "MESH:D017880"}
{"mention": "diaphragmatic hernia", "mention_text": "OBJECTIVE: To estimate the association between antibacterial medications and selected birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based, multisite, case-control study of women who had pregnancies affected by 1 of more than 30 eligible major birth defects identified via birth defect surveillance programs in 10 states (n = 13 155) and control women randomly selected from the same geographical regions (n = 4941). MAIN EXPOSURE: Reported maternal use of antibacterials (1 month before pregnancy through the end of the first trimester). MAIN OUTCOME MEASURE: Odds ratios (ORs) measuring the association between antibacterial use and selected birth defects adjusted for potential confounders. RESULTS: The reported use of antibacterials increased during pregnancy, peaking during the third month. Sulfonamides were associated with anencephaly (adjusted OR [AOR] = 3.4; 95% confidence interval [CI], 1.3-8.8), hypoplastic left heart syndrome (AOR = 3.2; 95% CI, 1.3-7.6), coarctation of the aorta (AOR = 2.7; 95% CI, 1.3-5.6), choanal atresia (AOR = 8.0; 95% CI, 2.7-23.5), transverse limb deficiency (AOR = 2.5; 95% CI, 1.0-5.9), and diaphragmatic hernia (AOR = 2.4; 95% CI, 1.1-5.4). Nitrofurantoins were associated with anophthalmia or microphthalmos (AOR = 3.7; 95% CI, 1.1-12.2), hypoplastic left heart syndrome (AOR = 4.2; 95% CI, 1.9-9.1), atrial septal defects (AOR = 1.9; 95% CI, 1.1-3.4), and cleft lip with cleft palate (AOR = 2.1; 95% CI, 1.2-3.9). Other antibacterial agents that showed associations included erythromycins (2 defects), penicillins (1 defect), cephalosporins (1 defect), and quinolones (1 defect). CONCLUSIONS: Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects. Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny.", "entity": "Hernia, Diaphragmatic", "aliases": "Diaphragmatic Hernia Hernias", "definition": "Protrusion of abdominal structures into the THORAX as a result of congenital or traumatic defects in the respiratory DIAPHRAGM.\n    ", "id": "MESH:D006548"}
{"mention": "Nitrofurantoins", "mention_text": "OBJECTIVE: To estimate the association between antibacterial medications and selected birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based, multisite, case-control study of women who had pregnancies affected by 1 of more than 30 eligible major birth defects identified via birth defect surveillance programs in 10 states (n = 13 155) and control women randomly selected from the same geographical regions (n = 4941). MAIN EXPOSURE: Reported maternal use of antibacterials (1 month before pregnancy through the end of the first trimester). MAIN OUTCOME MEASURE: Odds ratios (ORs) measuring the association between antibacterial use and selected birth defects adjusted for potential confounders. RESULTS: The reported use of antibacterials increased during pregnancy, peaking during the third month. Sulfonamides were associated with anencephaly (adjusted OR [AOR] = 3.4; 95% confidence interval [CI], 1.3-8.8), hypoplastic left heart syndrome (AOR = 3.2; 95% CI, 1.3-7.6), coarctation of the aorta (AOR = 2.7; 95% CI, 1.3-5.6), choanal atresia (AOR = 8.0; 95% CI, 2.7-23.5), transverse limb deficiency (AOR = 2.5; 95% CI, 1.0-5.9), and diaphragmatic hernia (AOR = 2.4; 95% CI, 1.1-5.4). Nitrofurantoins were associated with anophthalmia or microphthalmos (AOR = 3.7; 95% CI, 1.1-12.2), hypoplastic left heart syndrome (AOR = 4.2; 95% CI, 1.9-9.1), atrial septal defects (AOR = 1.9; 95% CI, 1.1-3.4), and cleft lip with cleft palate (AOR = 2.1; 95% CI, 1.2-3.9). Other antibacterial agents that showed associations included erythromycins (2 defects), penicillins (1 defect), cephalosporins (1 defect), and quinolones (1 defect). CONCLUSIONS: Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects. Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny.", "entity": "Nitrofurantoin", "aliases": "Furadantin Furadantine Furadoine Furadonine Furantoin Macrodantin Monohydrate Nitrofurantoin Sodium Salt", "definition": "A urinary anti-infective agent effective against most gram-positive and gram-negative organisms. Although sulfonamides and antibiotics are usually the agents of choice for urinary tract infections, nitrofurantoin is widely used for prophylaxis and long-term suppression.\n    ", "id": "MESH:D009582"}
{"mention": "anophthalmia", "mention_text": "OBJECTIVE: To estimate the association between antibacterial medications and selected birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based, multisite, case-control study of women who had pregnancies affected by 1 of more than 30 eligible major birth defects identified via birth defect surveillance programs in 10 states (n = 13 155) and control women randomly selected from the same geographical regions (n = 4941). MAIN EXPOSURE: Reported maternal use of antibacterials (1 month before pregnancy through the end of the first trimester). MAIN OUTCOME MEASURE: Odds ratios (ORs) measuring the association between antibacterial use and selected birth defects adjusted for potential confounders. RESULTS: The reported use of antibacterials increased during pregnancy, peaking during the third month. Sulfonamides were associated with anencephaly (adjusted OR [AOR] = 3.4; 95% confidence interval [CI], 1.3-8.8), hypoplastic left heart syndrome (AOR = 3.2; 95% CI, 1.3-7.6), coarctation of the aorta (AOR = 2.7; 95% CI, 1.3-5.6), choanal atresia (AOR = 8.0; 95% CI, 2.7-23.5), transverse limb deficiency (AOR = 2.5; 95% CI, 1.0-5.9), and diaphragmatic hernia (AOR = 2.4; 95% CI, 1.1-5.4). Nitrofurantoins were associated with anophthalmia or microphthalmos (AOR = 3.7; 95% CI, 1.1-12.2), hypoplastic left heart syndrome (AOR = 4.2; 95% CI, 1.9-9.1), atrial septal defects (AOR = 1.9; 95% CI, 1.1-3.4), and cleft lip with cleft palate (AOR = 2.1; 95% CI, 1.2-3.9). Other antibacterial agents that showed associations included erythromycins (2 defects), penicillins (1 defect), cephalosporins (1 defect), and quinolones (1 defect). CONCLUSIONS: Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects. Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny.", "entity": "Anophthalmos", "aliases": "Anophthalmia Anophthalmias Anophthalmos", "definition": "Congenital absence of the eye or eyes.\n    ", "id": "MESH:D000853"}
{"mention": "microphthalmos", "mention_text": "OBJECTIVE: To estimate the association between antibacterial medications and selected birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based, multisite, case-control study of women who had pregnancies affected by 1 of more than 30 eligible major birth defects identified via birth defect surveillance programs in 10 states (n = 13 155) and control women randomly selected from the same geographical regions (n = 4941). MAIN EXPOSURE: Reported maternal use of antibacterials (1 month before pregnancy through the end of the first trimester). MAIN OUTCOME MEASURE: Odds ratios (ORs) measuring the association between antibacterial use and selected birth defects adjusted for potential confounders. RESULTS: The reported use of antibacterials increased during pregnancy, peaking during the third month. Sulfonamides were associated with anencephaly (adjusted OR [AOR] = 3.4; 95% confidence interval [CI], 1.3-8.8), hypoplastic left heart syndrome (AOR = 3.2; 95% CI, 1.3-7.6), coarctation of the aorta (AOR = 2.7; 95% CI, 1.3-5.6), choanal atresia (AOR = 8.0; 95% CI, 2.7-23.5), transverse limb deficiency (AOR = 2.5; 95% CI, 1.0-5.9), and diaphragmatic hernia (AOR = 2.4; 95% CI, 1.1-5.4). Nitrofurantoins were associated with anophthalmia or microphthalmos (AOR = 3.7; 95% CI, 1.1-12.2), hypoplastic left heart syndrome (AOR = 4.2; 95% CI, 1.9-9.1), atrial septal defects (AOR = 1.9; 95% CI, 1.1-3.4), and cleft lip with cleft palate (AOR = 2.1; 95% CI, 1.2-3.9). Other antibacterial agents that showed associations included erythromycins (2 defects), penicillins (1 defect), cephalosporins (1 defect), and quinolones (1 defect). CONCLUSIONS: Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects. Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny.", "entity": "Microphthalmos", "aliases": "Microphthalmia Microphthalmos", "definition": "Congenital or developmental anomaly in which the eyeballs are abnormally small.\n    ", "id": "MESH:D008850"}
{"mention": "atrial septal defects", "mention_text": "OBJECTIVE: To estimate the association between antibacterial medications and selected birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based, multisite, case-control study of women who had pregnancies affected by 1 of more than 30 eligible major birth defects identified via birth defect surveillance programs in 10 states (n = 13 155) and control women randomly selected from the same geographical regions (n = 4941). MAIN EXPOSURE: Reported maternal use of antibacterials (1 month before pregnancy through the end of the first trimester). MAIN OUTCOME MEASURE: Odds ratios (ORs) measuring the association between antibacterial use and selected birth defects adjusted for potential confounders. RESULTS: The reported use of antibacterials increased during pregnancy, peaking during the third month. Sulfonamides were associated with anencephaly (adjusted OR [AOR] = 3.4; 95% confidence interval [CI], 1.3-8.8), hypoplastic left heart syndrome (AOR = 3.2; 95% CI, 1.3-7.6), coarctation of the aorta (AOR = 2.7; 95% CI, 1.3-5.6), choanal atresia (AOR = 8.0; 95% CI, 2.7-23.5), transverse limb deficiency (AOR = 2.5; 95% CI, 1.0-5.9), and diaphragmatic hernia (AOR = 2.4; 95% CI, 1.1-5.4). Nitrofurantoins were associated with anophthalmia or microphthalmos (AOR = 3.7; 95% CI, 1.1-12.2), hypoplastic left heart syndrome (AOR = 4.2; 95% CI, 1.9-9.1), atrial septal defects (AOR = 1.9; 95% CI, 1.1-3.4), and cleft lip with cleft palate (AOR = 2.1; 95% CI, 1.2-3.9). Other antibacterial agents that showed associations included erythromycins (2 defects), penicillins (1 defect), cephalosporins (1 defect), and quinolones (1 defect). CONCLUSIONS: Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects. Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny.", "entity": "Heart Septal Defects, Atrial", "aliases": "Atrial Septal Defect Defects Heart Ostium Primum Persistent Secundum", "definition": "Developmental abnormalities in any portion of the ATRIAL SEPTUM resulting in abnormal communications between the two upper chambers of the heart. Classification of atrial septal defects is based on location of the communication and types of incomplete fusion of atrial septa with the ENDOCARDIAL CUSHIONS in the fetal heart. They include ostium primum, ostium secundum, sinus venosus, and coronary sinus defects.\n    ", "id": "MESH:D006344"}
{"mention": "cleft lip", "mention_text": "OBJECTIVE: To estimate the association between antibacterial medications and selected birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based, multisite, case-control study of women who had pregnancies affected by 1 of more than 30 eligible major birth defects identified via birth defect surveillance programs in 10 states (n = 13 155) and control women randomly selected from the same geographical regions (n = 4941). MAIN EXPOSURE: Reported maternal use of antibacterials (1 month before pregnancy through the end of the first trimester). MAIN OUTCOME MEASURE: Odds ratios (ORs) measuring the association between antibacterial use and selected birth defects adjusted for potential confounders. RESULTS: The reported use of antibacterials increased during pregnancy, peaking during the third month. Sulfonamides were associated with anencephaly (adjusted OR [AOR] = 3.4; 95% confidence interval [CI], 1.3-8.8), hypoplastic left heart syndrome (AOR = 3.2; 95% CI, 1.3-7.6), coarctation of the aorta (AOR = 2.7; 95% CI, 1.3-5.6), choanal atresia (AOR = 8.0; 95% CI, 2.7-23.5), transverse limb deficiency (AOR = 2.5; 95% CI, 1.0-5.9), and diaphragmatic hernia (AOR = 2.4; 95% CI, 1.1-5.4). Nitrofurantoins were associated with anophthalmia or microphthalmos (AOR = 3.7; 95% CI, 1.1-12.2), hypoplastic left heart syndrome (AOR = 4.2; 95% CI, 1.9-9.1), atrial septal defects (AOR = 1.9; 95% CI, 1.1-3.4), and cleft lip with cleft palate (AOR = 2.1; 95% CI, 1.2-3.9). Other antibacterial agents that showed associations included erythromycins (2 defects), penicillins (1 defect), cephalosporins (1 defect), and quinolones (1 defect). CONCLUSIONS: Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects. Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny.", "entity": "Cleft Lip", "aliases": "Cleft Lip Lips Harelip Harelips", "definition": "Congenital defect in the upper lip where the maxillary prominence fails to merge with the merged medial nasal prominences. It is thought to be caused by faulty migration of the mesoderm in the head region.\n    ", "id": "MESH:D002971"}
{"mention": "cleft palate", "mention_text": "OBJECTIVE: To estimate the association between antibacterial medications and selected birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based, multisite, case-control study of women who had pregnancies affected by 1 of more than 30 eligible major birth defects identified via birth defect surveillance programs in 10 states (n = 13 155) and control women randomly selected from the same geographical regions (n = 4941). MAIN EXPOSURE: Reported maternal use of antibacterials (1 month before pregnancy through the end of the first trimester). MAIN OUTCOME MEASURE: Odds ratios (ORs) measuring the association between antibacterial use and selected birth defects adjusted for potential confounders. RESULTS: The reported use of antibacterials increased during pregnancy, peaking during the third month. Sulfonamides were associated with anencephaly (adjusted OR [AOR] = 3.4; 95% confidence interval [CI], 1.3-8.8), hypoplastic left heart syndrome (AOR = 3.2; 95% CI, 1.3-7.6), coarctation of the aorta (AOR = 2.7; 95% CI, 1.3-5.6), choanal atresia (AOR = 8.0; 95% CI, 2.7-23.5), transverse limb deficiency (AOR = 2.5; 95% CI, 1.0-5.9), and diaphragmatic hernia (AOR = 2.4; 95% CI, 1.1-5.4). Nitrofurantoins were associated with anophthalmia or microphthalmos (AOR = 3.7; 95% CI, 1.1-12.2), hypoplastic left heart syndrome (AOR = 4.2; 95% CI, 1.9-9.1), atrial septal defects (AOR = 1.9; 95% CI, 1.1-3.4), and cleft lip with cleft palate (AOR = 2.1; 95% CI, 1.2-3.9). Other antibacterial agents that showed associations included erythromycins (2 defects), penicillins (1 defect), cephalosporins (1 defect), and quinolones (1 defect). CONCLUSIONS: Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects. Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny.", "entity": "Cleft Palate", "aliases": "Cleft Palate Isolated Palates", "definition": "Congenital fissure of the soft and/or hard palate, due to faulty fusion.\n    ", "id": "MESH:D002972"}
{"mention": "erythromycins", "mention_text": "OBJECTIVE: To estimate the association between antibacterial medications and selected birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based, multisite, case-control study of women who had pregnancies affected by 1 of more than 30 eligible major birth defects identified via birth defect surveillance programs in 10 states (n = 13 155) and control women randomly selected from the same geographical regions (n = 4941). MAIN EXPOSURE: Reported maternal use of antibacterials (1 month before pregnancy through the end of the first trimester). MAIN OUTCOME MEASURE: Odds ratios (ORs) measuring the association between antibacterial use and selected birth defects adjusted for potential confounders. RESULTS: The reported use of antibacterials increased during pregnancy, peaking during the third month. Sulfonamides were associated with anencephaly (adjusted OR [AOR] = 3.4; 95% confidence interval [CI], 1.3-8.8), hypoplastic left heart syndrome (AOR = 3.2; 95% CI, 1.3-7.6), coarctation of the aorta (AOR = 2.7; 95% CI, 1.3-5.6), choanal atresia (AOR = 8.0; 95% CI, 2.7-23.5), transverse limb deficiency (AOR = 2.5; 95% CI, 1.0-5.9), and diaphragmatic hernia (AOR = 2.4; 95% CI, 1.1-5.4). Nitrofurantoins were associated with anophthalmia or microphthalmos (AOR = 3.7; 95% CI, 1.1-12.2), hypoplastic left heart syndrome (AOR = 4.2; 95% CI, 1.9-9.1), atrial septal defects (AOR = 1.9; 95% CI, 1.1-3.4), and cleft lip with cleft palate (AOR = 2.1; 95% CI, 1.2-3.9). Other antibacterial agents that showed associations included erythromycins (2 defects), penicillins (1 defect), cephalosporins (1 defect), and quinolones (1 defect). CONCLUSIONS: Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects. Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny.", "entity": "Erythromycin", "aliases": "C Erythromycin Erycette Erymax A Lactate Phosphate Ilotycin T Stat T-Stat TStat", "definition": "A bacteriostatic antibiotic macrolide produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins.\n    ", "id": "MESH:D004917"}
{"mention": "penicillins", "mention_text": "OBJECTIVE: To estimate the association between antibacterial medications and selected birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based, multisite, case-control study of women who had pregnancies affected by 1 of more than 30 eligible major birth defects identified via birth defect surveillance programs in 10 states (n = 13 155) and control women randomly selected from the same geographical regions (n = 4941). MAIN EXPOSURE: Reported maternal use of antibacterials (1 month before pregnancy through the end of the first trimester). MAIN OUTCOME MEASURE: Odds ratios (ORs) measuring the association between antibacterial use and selected birth defects adjusted for potential confounders. RESULTS: The reported use of antibacterials increased during pregnancy, peaking during the third month. Sulfonamides were associated with anencephaly (adjusted OR [AOR] = 3.4; 95% confidence interval [CI], 1.3-8.8), hypoplastic left heart syndrome (AOR = 3.2; 95% CI, 1.3-7.6), coarctation of the aorta (AOR = 2.7; 95% CI, 1.3-5.6), choanal atresia (AOR = 8.0; 95% CI, 2.7-23.5), transverse limb deficiency (AOR = 2.5; 95% CI, 1.0-5.9), and diaphragmatic hernia (AOR = 2.4; 95% CI, 1.1-5.4). Nitrofurantoins were associated with anophthalmia or microphthalmos (AOR = 3.7; 95% CI, 1.1-12.2), hypoplastic left heart syndrome (AOR = 4.2; 95% CI, 1.9-9.1), atrial septal defects (AOR = 1.9; 95% CI, 1.1-3.4), and cleft lip with cleft palate (AOR = 2.1; 95% CI, 1.2-3.9). Other antibacterial agents that showed associations included erythromycins (2 defects), penicillins (1 defect), cephalosporins (1 defect), and quinolones (1 defect). CONCLUSIONS: Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects. Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny.", "entity": "Penicillins", "aliases": "Antibiotics Penicillin Penicillins", "definition": "A group of antibiotics that contain 6-aminopenicillanic acid with a side chain attached to the 6-amino group. The penicillin nucleus is the chief structural requirement for biological activity. The side-chain structure determines many of the antibacterial and pharmacological characteristics. (Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1065)\n    ", "id": "MESH:D010406"}
{"mention": "cephalosporins", "mention_text": "OBJECTIVE: To estimate the association between antibacterial medications and selected birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based, multisite, case-control study of women who had pregnancies affected by 1 of more than 30 eligible major birth defects identified via birth defect surveillance programs in 10 states (n = 13 155) and control women randomly selected from the same geographical regions (n = 4941). MAIN EXPOSURE: Reported maternal use of antibacterials (1 month before pregnancy through the end of the first trimester). MAIN OUTCOME MEASURE: Odds ratios (ORs) measuring the association between antibacterial use and selected birth defects adjusted for potential confounders. RESULTS: The reported use of antibacterials increased during pregnancy, peaking during the third month. Sulfonamides were associated with anencephaly (adjusted OR [AOR] = 3.4; 95% confidence interval [CI], 1.3-8.8), hypoplastic left heart syndrome (AOR = 3.2; 95% CI, 1.3-7.6), coarctation of the aorta (AOR = 2.7; 95% CI, 1.3-5.6), choanal atresia (AOR = 8.0; 95% CI, 2.7-23.5), transverse limb deficiency (AOR = 2.5; 95% CI, 1.0-5.9), and diaphragmatic hernia (AOR = 2.4; 95% CI, 1.1-5.4). Nitrofurantoins were associated with anophthalmia or microphthalmos (AOR = 3.7; 95% CI, 1.1-12.2), hypoplastic left heart syndrome (AOR = 4.2; 95% CI, 1.9-9.1), atrial septal defects (AOR = 1.9; 95% CI, 1.1-3.4), and cleft lip with cleft palate (AOR = 2.1; 95% CI, 1.2-3.9). Other antibacterial agents that showed associations included erythromycins (2 defects), penicillins (1 defect), cephalosporins (1 defect), and quinolones (1 defect). CONCLUSIONS: Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects. Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny.", "entity": "Cephalosporins", "aliases": "Acids Cephalosporanic Antibiotics Cephalosporin Cephalosporins", "definition": "A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus ACREMONIUM. They contain the beta-lactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid.\n    ", "id": "MESH:D002511"}
{"mention": "quinolones", "mention_text": "OBJECTIVE: To estimate the association between antibacterial medications and selected birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based, multisite, case-control study of women who had pregnancies affected by 1 of more than 30 eligible major birth defects identified via birth defect surveillance programs in 10 states (n = 13 155) and control women randomly selected from the same geographical regions (n = 4941). MAIN EXPOSURE: Reported maternal use of antibacterials (1 month before pregnancy through the end of the first trimester). MAIN OUTCOME MEASURE: Odds ratios (ORs) measuring the association between antibacterial use and selected birth defects adjusted for potential confounders. RESULTS: The reported use of antibacterials increased during pregnancy, peaking during the third month. Sulfonamides were associated with anencephaly (adjusted OR [AOR] = 3.4; 95% confidence interval [CI], 1.3-8.8), hypoplastic left heart syndrome (AOR = 3.2; 95% CI, 1.3-7.6), coarctation of the aorta (AOR = 2.7; 95% CI, 1.3-5.6), choanal atresia (AOR = 8.0; 95% CI, 2.7-23.5), transverse limb deficiency (AOR = 2.5; 95% CI, 1.0-5.9), and diaphragmatic hernia (AOR = 2.4; 95% CI, 1.1-5.4). Nitrofurantoins were associated with anophthalmia or microphthalmos (AOR = 3.7; 95% CI, 1.1-12.2), hypoplastic left heart syndrome (AOR = 4.2; 95% CI, 1.9-9.1), atrial septal defects (AOR = 1.9; 95% CI, 1.1-3.4), and cleft lip with cleft palate (AOR = 2.1; 95% CI, 1.2-3.9). Other antibacterial agents that showed associations included erythromycins (2 defects), penicillins (1 defect), cephalosporins (1 defect), and quinolones (1 defect). CONCLUSIONS: Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects. Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny.", "entity": "Quinolones", "aliases": "Ketoquinolines Oxoquinolines Quinolinones Quinolones", "definition": "A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID.\n    ", "id": "MESH:D015363"}
{"mention": "nitrofurantoins", "mention_text": "OBJECTIVE: To estimate the association between antibacterial medications and selected birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based, multisite, case-control study of women who had pregnancies affected by 1 of more than 30 eligible major birth defects identified via birth defect surveillance programs in 10 states (n = 13 155) and control women randomly selected from the same geographical regions (n = 4941). MAIN EXPOSURE: Reported maternal use of antibacterials (1 month before pregnancy through the end of the first trimester). MAIN OUTCOME MEASURE: Odds ratios (ORs) measuring the association between antibacterial use and selected birth defects adjusted for potential confounders. RESULTS: The reported use of antibacterials increased during pregnancy, peaking during the third month. Sulfonamides were associated with anencephaly (adjusted OR [AOR] = 3.4; 95% confidence interval [CI], 1.3-8.8), hypoplastic left heart syndrome (AOR = 3.2; 95% CI, 1.3-7.6), coarctation of the aorta (AOR = 2.7; 95% CI, 1.3-5.6), choanal atresia (AOR = 8.0; 95% CI, 2.7-23.5), transverse limb deficiency (AOR = 2.5; 95% CI, 1.0-5.9), and diaphragmatic hernia (AOR = 2.4; 95% CI, 1.1-5.4). Nitrofurantoins were associated with anophthalmia or microphthalmos (AOR = 3.7; 95% CI, 1.1-12.2), hypoplastic left heart syndrome (AOR = 4.2; 95% CI, 1.9-9.1), atrial septal defects (AOR = 1.9; 95% CI, 1.1-3.4), and cleft lip with cleft palate (AOR = 2.1; 95% CI, 1.2-3.9). Other antibacterial agents that showed associations included erythromycins (2 defects), penicillins (1 defect), cephalosporins (1 defect), and quinolones (1 defect). CONCLUSIONS: Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects. Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny.", "entity": "Nitrofurantoin", "aliases": "Furadantin Furadantine Furadoine Furadonine Furantoin Macrodantin Monohydrate Nitrofurantoin Sodium Salt", "definition": "A urinary anti-infective agent effective against most gram-positive and gram-negative organisms. Although sulfonamides and antibiotics are usually the agents of choice for urinary tract infections, nitrofurantoin is widely used for prophylaxis and long-term suppression.\n    ", "id": "MESH:D009582"}
{"mention": "neoplasms", "mention_text": "Incidence of neoplasms in patients with rheumatoid arthritis exposed to different treatment regimens.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "rheumatoid arthritis", "mention_text": "Incidence of neoplasms in patients with rheumatoid arthritis exposed to different treatment regimens.", "entity": "Arthritis, Rheumatoid", "aliases": "Arthritis Rheumatoid", "definition": "A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.\n    ", "id": "MESH:D001172"}
{"mention": "rheumatoid arthritis", "mention_text": "Immunosuppressive drugs have been used during the last 30 years in treatment of patients with severe rheumatoid arthritis. The drugs commonly used are cyclophosphamide and chlorambucil (alkylating agents), azathioprine (purine analogue), and methotrexate (folic acid analogue). There is evidence that all four immunosuppressive drugs can reduce synovitis, but disease activity almost always recurs after therapy is stopped. Since adverse reactions are frequent, less than 50 percent of patients are able to continue a particular drug for more than one year. Since it takes three to 12 months to achieve maximal effects, those patients who are unable to continue the drug receive little benefit from it. Patients treated with alkylating agents have an increased risk of development of acute nonlymphocytic leukemia, and both alkylating agents and azathioprine are associated with the development of non-Hodgkin's lymphoma. Cyclophosphamide therapy increases the risk of carcinoma of the bladder. There have been several long-term studies of patients with rheumatoid arthritis treated with azathioprine and cyclophosphamide and the incidence of most of the common cancers is not increased. Data on the possible increased risk of malignancy in rheumatoid arthritis are still being collected, and until further information is available, the use of immunosuppressive drugs, particularly alkylating agents, in the treatment of rheumatoid arthritis should be reserved for patients with severe progressive disease or life-threatening complications.", "entity": "Arthritis, Rheumatoid", "aliases": "Arthritis Rheumatoid", "definition": "A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.\n    ", "id": "MESH:D001172"}
{"mention": "cyclophosphamide", "mention_text": "Immunosuppressive drugs have been used during the last 30 years in treatment of patients with severe rheumatoid arthritis. The drugs commonly used are cyclophosphamide and chlorambucil (alkylating agents), azathioprine (purine analogue), and methotrexate (folic acid analogue). There is evidence that all four immunosuppressive drugs can reduce synovitis, but disease activity almost always recurs after therapy is stopped. Since adverse reactions are frequent, less than 50 percent of patients are able to continue a particular drug for more than one year. Since it takes three to 12 months to achieve maximal effects, those patients who are unable to continue the drug receive little benefit from it. Patients treated with alkylating agents have an increased risk of development of acute nonlymphocytic leukemia, and both alkylating agents and azathioprine are associated with the development of non-Hodgkin's lymphoma. Cyclophosphamide therapy increases the risk of carcinoma of the bladder. There have been several long-term studies of patients with rheumatoid arthritis treated with azathioprine and cyclophosphamide and the incidence of most of the common cancers is not increased. Data on the possible increased risk of malignancy in rheumatoid arthritis are still being collected, and until further information is available, the use of immunosuppressive drugs, particularly alkylating agents, in the treatment of rheumatoid arthritis should be reserved for patients with severe progressive disease or life-threatening complications.", "entity": "Cyclophosphamide", "aliases": "Anhydrous Cyclophosphamide B 518 B-518 B518 Monohydrate (R)-Isomer (S)-Isomer Cyclophosphane Cytophosphan Cytophosphane Cytoxan Endoxan NSC 26271 NSC-26271 NSC26271 Neosar Procytox Sendoxan", "definition": "Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.\n    ", "id": "MESH:D003520"}
{"mention": "chlorambucil", "mention_text": "Immunosuppressive drugs have been used during the last 30 years in treatment of patients with severe rheumatoid arthritis. The drugs commonly used are cyclophosphamide and chlorambucil (alkylating agents), azathioprine (purine analogue), and methotrexate (folic acid analogue). There is evidence that all four immunosuppressive drugs can reduce synovitis, but disease activity almost always recurs after therapy is stopped. Since adverse reactions are frequent, less than 50 percent of patients are able to continue a particular drug for more than one year. Since it takes three to 12 months to achieve maximal effects, those patients who are unable to continue the drug receive little benefit from it. Patients treated with alkylating agents have an increased risk of development of acute nonlymphocytic leukemia, and both alkylating agents and azathioprine are associated with the development of non-Hodgkin's lymphoma. Cyclophosphamide therapy increases the risk of carcinoma of the bladder. There have been several long-term studies of patients with rheumatoid arthritis treated with azathioprine and cyclophosphamide and the incidence of most of the common cancers is not increased. Data on the possible increased risk of malignancy in rheumatoid arthritis are still being collected, and until further information is available, the use of immunosuppressive drugs, particularly alkylating agents, in the treatment of rheumatoid arthritis should be reserved for patients with severe progressive disease or life-threatening complications.", "entity": "Chlorambucil", "aliases": "4-(Bis(2-chloroethyl)amino)benzenebutanoic Acid Amboclorin CB 1348 CB-1348 CB1348 Chlorambucil Chloraminophene Chlorbutin Glaxo Wellcome Brand of GlaxoSmithKline Leukeran Lympholysin N,N-Di-(2-chloroethyl)-p-aminophenylbutyric NSC 3088 NSC-3088 NSC3088", "definition": "A nitrogen mustard alkylating agent used as antineoplastic for chronic lymphocytic leukemia, Hodgkin's disease, and others. Although it is less toxic than most other nitrogen mustards, it has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (Merck Index, 11th ed)\n    ", "id": "MESH:D002699"}
{"mention": "alkylating agents", "mention_text": "Immunosuppressive drugs have been used during the last 30 years in treatment of patients with severe rheumatoid arthritis. The drugs commonly used are cyclophosphamide and chlorambucil (alkylating agents), azathioprine (purine analogue), and methotrexate (folic acid analogue). There is evidence that all four immunosuppressive drugs can reduce synovitis, but disease activity almost always recurs after therapy is stopped. Since adverse reactions are frequent, less than 50 percent of patients are able to continue a particular drug for more than one year. Since it takes three to 12 months to achieve maximal effects, those patients who are unable to continue the drug receive little benefit from it. Patients treated with alkylating agents have an increased risk of development of acute nonlymphocytic leukemia, and both alkylating agents and azathioprine are associated with the development of non-Hodgkin's lymphoma. Cyclophosphamide therapy increases the risk of carcinoma of the bladder. There have been several long-term studies of patients with rheumatoid arthritis treated with azathioprine and cyclophosphamide and the incidence of most of the common cancers is not increased. Data on the possible increased risk of malignancy in rheumatoid arthritis are still being collected, and until further information is available, the use of immunosuppressive drugs, particularly alkylating agents, in the treatment of rheumatoid arthritis should be reserved for patients with severe progressive disease or life-threatening complications.", "entity": "Alkylating Agents", "aliases": "Agents Alkylating Alkylators", "definition": "Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases.\n    ", "id": "MESH:D000477"}
{"mention": "azathioprine", "mention_text": "Immunosuppressive drugs have been used during the last 30 years in treatment of patients with severe rheumatoid arthritis. The drugs commonly used are cyclophosphamide and chlorambucil (alkylating agents), azathioprine (purine analogue), and methotrexate (folic acid analogue). There is evidence that all four immunosuppressive drugs can reduce synovitis, but disease activity almost always recurs after therapy is stopped. Since adverse reactions are frequent, less than 50 percent of patients are able to continue a particular drug for more than one year. Since it takes three to 12 months to achieve maximal effects, those patients who are unable to continue the drug receive little benefit from it. Patients treated with alkylating agents have an increased risk of development of acute nonlymphocytic leukemia, and both alkylating agents and azathioprine are associated with the development of non-Hodgkin's lymphoma. Cyclophosphamide therapy increases the risk of carcinoma of the bladder. There have been several long-term studies of patients with rheumatoid arthritis treated with azathioprine and cyclophosphamide and the incidence of most of the common cancers is not increased. Data on the possible increased risk of malignancy in rheumatoid arthritis are still being collected, and until further information is available, the use of immunosuppressive drugs, particularly alkylating agents, in the treatment of rheumatoid arthritis should be reserved for patients with severe progressive disease or life-threatening complications.", "entity": "Azathioprine", "aliases": "Azathioprine Sodium Salt Sulfate Azothioprine Immuran Imuran Imurel", "definition": "An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance has been listed as a known carcinogen. (Merck Index, 11th ed)\n    ", "id": "MESH:D001379"}
{"mention": "purine", "mention_text": "Immunosuppressive drugs have been used during the last 30 years in treatment of patients with severe rheumatoid arthritis. The drugs commonly used are cyclophosphamide and chlorambucil (alkylating agents), azathioprine (purine analogue), and methotrexate (folic acid analogue). There is evidence that all four immunosuppressive drugs can reduce synovitis, but disease activity almost always recurs after therapy is stopped. Since adverse reactions are frequent, less than 50 percent of patients are able to continue a particular drug for more than one year. Since it takes three to 12 months to achieve maximal effects, those patients who are unable to continue the drug receive little benefit from it. Patients treated with alkylating agents have an increased risk of development of acute nonlymphocytic leukemia, and both alkylating agents and azathioprine are associated with the development of non-Hodgkin's lymphoma. Cyclophosphamide therapy increases the risk of carcinoma of the bladder. There have been several long-term studies of patients with rheumatoid arthritis treated with azathioprine and cyclophosphamide and the incidence of most of the common cancers is not increased. Data on the possible increased risk of malignancy in rheumatoid arthritis are still being collected, and until further information is available, the use of immunosuppressive drugs, particularly alkylating agents, in the treatment of rheumatoid arthritis should be reserved for patients with severe progressive disease or life-threatening complications.", "entity": "Purines", "aliases": "Purines", "definition": "A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.\n    ", "id": "MESH:D011687"}
{"mention": "methotrexate", "mention_text": "Immunosuppressive drugs have been used during the last 30 years in treatment of patients with severe rheumatoid arthritis. The drugs commonly used are cyclophosphamide and chlorambucil (alkylating agents), azathioprine (purine analogue), and methotrexate (folic acid analogue). There is evidence that all four immunosuppressive drugs can reduce synovitis, but disease activity almost always recurs after therapy is stopped. Since adverse reactions are frequent, less than 50 percent of patients are able to continue a particular drug for more than one year. Since it takes three to 12 months to achieve maximal effects, those patients who are unable to continue the drug receive little benefit from it. Patients treated with alkylating agents have an increased risk of development of acute nonlymphocytic leukemia, and both alkylating agents and azathioprine are associated with the development of non-Hodgkin's lymphoma. Cyclophosphamide therapy increases the risk of carcinoma of the bladder. There have been several long-term studies of patients with rheumatoid arthritis treated with azathioprine and cyclophosphamide and the incidence of most of the common cancers is not increased. Data on the possible increased risk of malignancy in rheumatoid arthritis are still being collected, and until further information is available, the use of immunosuppressive drugs, particularly alkylating agents, in the treatment of rheumatoid arthritis should be reserved for patients with severe progressive disease or life-threatening complications.", "entity": "Methotrexate", "aliases": "Amethopterin Dicesium Salt Methotrexate Hydrate Sodium (D)-Isomer (DL)-Isomer Disodium Mexate", "definition": "An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.\n    ", "id": "MESH:D008727"}
{"mention": "folic acid", "mention_text": "Immunosuppressive drugs have been used during the last 30 years in treatment of patients with severe rheumatoid arthritis. The drugs commonly used are cyclophosphamide and chlorambucil (alkylating agents), azathioprine (purine analogue), and methotrexate (folic acid analogue). There is evidence that all four immunosuppressive drugs can reduce synovitis, but disease activity almost always recurs after therapy is stopped. Since adverse reactions are frequent, less than 50 percent of patients are able to continue a particular drug for more than one year. Since it takes three to 12 months to achieve maximal effects, those patients who are unable to continue the drug receive little benefit from it. Patients treated with alkylating agents have an increased risk of development of acute nonlymphocytic leukemia, and both alkylating agents and azathioprine are associated with the development of non-Hodgkin's lymphoma. Cyclophosphamide therapy increases the risk of carcinoma of the bladder. There have been several long-term studies of patients with rheumatoid arthritis treated with azathioprine and cyclophosphamide and the incidence of most of the common cancers is not increased. Data on the possible increased risk of malignancy in rheumatoid arthritis are still being collected, and until further information is available, the use of immunosuppressive drugs, particularly alkylating agents, in the treatment of rheumatoid arthritis should be reserved for patients with severe progressive disease or life-threatening complications.", "entity": "Folic Acid", "aliases": "B9 Vitamin Folacin Folate Folic Acid (D)-Isomer (DL)-Isomer Calcium Salt (1:1) Monopotassium Monosodium Potassium Sodium Folvite Pteroylglutamic M", "definition": "A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses (POACEAE). Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia.\n    ", "id": "MESH:D005492"}
{"mention": "synovitis", "mention_text": "Immunosuppressive drugs have been used during the last 30 years in treatment of patients with severe rheumatoid arthritis. The drugs commonly used are cyclophosphamide and chlorambucil (alkylating agents), azathioprine (purine analogue), and methotrexate (folic acid analogue). There is evidence that all four immunosuppressive drugs can reduce synovitis, but disease activity almost always recurs after therapy is stopped. Since adverse reactions are frequent, less than 50 percent of patients are able to continue a particular drug for more than one year. Since it takes three to 12 months to achieve maximal effects, those patients who are unable to continue the drug receive little benefit from it. Patients treated with alkylating agents have an increased risk of development of acute nonlymphocytic leukemia, and both alkylating agents and azathioprine are associated with the development of non-Hodgkin's lymphoma. Cyclophosphamide therapy increases the risk of carcinoma of the bladder. There have been several long-term studies of patients with rheumatoid arthritis treated with azathioprine and cyclophosphamide and the incidence of most of the common cancers is not increased. Data on the possible increased risk of malignancy in rheumatoid arthritis are still being collected, and until further information is available, the use of immunosuppressive drugs, particularly alkylating agents, in the treatment of rheumatoid arthritis should be reserved for patients with severe progressive disease or life-threatening complications.", "entity": "Synovitis", "aliases": "Synovitides Synovitis", "definition": "Inflammation of a synovial membrane. It is usually painful, particularly on motion, and is characterized by a fluctuating swelling due to effusion within a synovial sac. (Dorland, 27th ed)\n    ", "id": "MESH:D013585"}
{"mention": "acute nonlymphocytic leukemia", "mention_text": "Immunosuppressive drugs have been used during the last 30 years in treatment of patients with severe rheumatoid arthritis. The drugs commonly used are cyclophosphamide and chlorambucil (alkylating agents), azathioprine (purine analogue), and methotrexate (folic acid analogue). There is evidence that all four immunosuppressive drugs can reduce synovitis, but disease activity almost always recurs after therapy is stopped. Since adverse reactions are frequent, less than 50 percent of patients are able to continue a particular drug for more than one year. Since it takes three to 12 months to achieve maximal effects, those patients who are unable to continue the drug receive little benefit from it. Patients treated with alkylating agents have an increased risk of development of acute nonlymphocytic leukemia, and both alkylating agents and azathioprine are associated with the development of non-Hodgkin's lymphoma. Cyclophosphamide therapy increases the risk of carcinoma of the bladder. There have been several long-term studies of patients with rheumatoid arthritis treated with azathioprine and cyclophosphamide and the incidence of most of the common cancers is not increased. Data on the possible increased risk of malignancy in rheumatoid arthritis are still being collected, and until further information is available, the use of immunosuppressive drugs, particularly alkylating agents, in the treatment of rheumatoid arthritis should be reserved for patients with severe progressive disease or life-threatening complications.", "entity": "Leukemia, Myeloid, Acute", "aliases": "ANLL Acute Myeloblastic Leukemia Leukemias Myelocytic Myelogenous Myeloid with Maturation without Nonlymphoblastic Nonlymphocytic M1 M2", "definition": "Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.\n    ", "id": "MESH:D015470"}
{"mention": "non-Hodgkin's lymphoma", "mention_text": "Immunosuppressive drugs have been used during the last 30 years in treatment of patients with severe rheumatoid arthritis. The drugs commonly used are cyclophosphamide and chlorambucil (alkylating agents), azathioprine (purine analogue), and methotrexate (folic acid analogue). There is evidence that all four immunosuppressive drugs can reduce synovitis, but disease activity almost always recurs after therapy is stopped. Since adverse reactions are frequent, less than 50 percent of patients are able to continue a particular drug for more than one year. Since it takes three to 12 months to achieve maximal effects, those patients who are unable to continue the drug receive little benefit from it. Patients treated with alkylating agents have an increased risk of development of acute nonlymphocytic leukemia, and both alkylating agents and azathioprine are associated with the development of non-Hodgkin's lymphoma. Cyclophosphamide therapy increases the risk of carcinoma of the bladder. There have been several long-term studies of patients with rheumatoid arthritis treated with azathioprine and cyclophosphamide and the incidence of most of the common cancers is not increased. Data on the possible increased risk of malignancy in rheumatoid arthritis are still being collected, and until further information is available, the use of immunosuppressive drugs, particularly alkylating agents, in the treatment of rheumatoid arthritis should be reserved for patients with severe progressive disease or life-threatening complications.", "entity": "Lymphoma, Non-Hodgkin", "aliases": "Diffuse Lymphoma Lymphomas Mixed Cell Small and Large Mixed-Cell Cleaved Cleaved-Cell Undifferentiated High-Grade Intermediate-Grade Low-Grade Lymphatic Sarcoma Sarcomas Lymphocytic-Histiocytic Atypical Lymphoid High Grade Intermediate Low Lymphocytic Histiocytic Non Hodgkin Hodgkin's Hodgkins Non-Hodgkin Non-Hodgkin's Familial Non-Hodgkins Nonhodgkin Nonhodgkin's Nonhodgkins Pleomorphic Non-Cleaved-Cell Noncleaved Noncleaved-Cell Lymphosarcoma Lymphosarcomas Reticulosarcoma Reticulosarcomas Ret", "definition": "Any of a group of malignant tumors of lymphoid tissue that differ from HODGKIN DISEASE, being more heterogeneous with respect to malignant cell lineage, clinical course, prognosis, and therapy. The only common feature among these tumors is the absence of giant REED-STERNBERG CELLS, a characteristic of Hodgkin's disease.\n    ", "id": "MESH:D008228"}
{"mention": "Cyclophosphamide", "mention_text": "Immunosuppressive drugs have been used during the last 30 years in treatment of patients with severe rheumatoid arthritis. The drugs commonly used are cyclophosphamide and chlorambucil (alkylating agents), azathioprine (purine analogue), and methotrexate (folic acid analogue). There is evidence that all four immunosuppressive drugs can reduce synovitis, but disease activity almost always recurs after therapy is stopped. Since adverse reactions are frequent, less than 50 percent of patients are able to continue a particular drug for more than one year. Since it takes three to 12 months to achieve maximal effects, those patients who are unable to continue the drug receive little benefit from it. Patients treated with alkylating agents have an increased risk of development of acute nonlymphocytic leukemia, and both alkylating agents and azathioprine are associated with the development of non-Hodgkin's lymphoma. Cyclophosphamide therapy increases the risk of carcinoma of the bladder. There have been several long-term studies of patients with rheumatoid arthritis treated with azathioprine and cyclophosphamide and the incidence of most of the common cancers is not increased. Data on the possible increased risk of malignancy in rheumatoid arthritis are still being collected, and until further information is available, the use of immunosuppressive drugs, particularly alkylating agents, in the treatment of rheumatoid arthritis should be reserved for patients with severe progressive disease or life-threatening complications.", "entity": "Cyclophosphamide", "aliases": "Anhydrous Cyclophosphamide B 518 B-518 B518 Monohydrate (R)-Isomer (S)-Isomer Cyclophosphane Cytophosphan Cytophosphane Cytoxan Endoxan NSC 26271 NSC-26271 NSC26271 Neosar Procytox Sendoxan", "definition": "Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.\n    ", "id": "MESH:D003520"}
{"mention": "carcinoma of the bladder", "mention_text": "Immunosuppressive drugs have been used during the last 30 years in treatment of patients with severe rheumatoid arthritis. The drugs commonly used are cyclophosphamide and chlorambucil (alkylating agents), azathioprine (purine analogue), and methotrexate (folic acid analogue). There is evidence that all four immunosuppressive drugs can reduce synovitis, but disease activity almost always recurs after therapy is stopped. Since adverse reactions are frequent, less than 50 percent of patients are able to continue a particular drug for more than one year. Since it takes three to 12 months to achieve maximal effects, those patients who are unable to continue the drug receive little benefit from it. Patients treated with alkylating agents have an increased risk of development of acute nonlymphocytic leukemia, and both alkylating agents and azathioprine are associated with the development of non-Hodgkin's lymphoma. Cyclophosphamide therapy increases the risk of carcinoma of the bladder. There have been several long-term studies of patients with rheumatoid arthritis treated with azathioprine and cyclophosphamide and the incidence of most of the common cancers is not increased. Data on the possible increased risk of malignancy in rheumatoid arthritis are still being collected, and until further information is available, the use of immunosuppressive drugs, particularly alkylating agents, in the treatment of rheumatoid arthritis should be reserved for patients with severe progressive disease or life-threatening complications.", "entity": "Urinary Bladder Neoplasms", "aliases": "Bladder Cancer Cancers Neoplasm Neoplasms Tumor Tumors of the Urinary Malignant", "definition": "Tumors or cancer of the URINARY BLADDER.\n    ", "id": "MESH:D001749"}
{"mention": "carcinoma", "mention_text": "Immunosuppressive drugs have been used during the last 30 years in treatment of patients with severe rheumatoid arthritis. The drugs commonly used are cyclophosphamide and chlorambucil (alkylating agents), azathioprine (purine analogue), and methotrexate (folic acid analogue). There is evidence that all four immunosuppressive drugs can reduce synovitis, but disease activity almost always recurs after therapy is stopped. Since adverse reactions are frequent, less than 50 percent of patients are able to continue a particular drug for more than one year. Since it takes three to 12 months to achieve maximal effects, those patients who are unable to continue the drug receive little benefit from it. Patients treated with alkylating agents have an increased risk of development of acute nonlymphocytic leukemia, and both alkylating agents and azathioprine are associated with the development of non-Hodgkin's lymphoma. Cyclophosphamide therapy increases the risk of carcinoma of the bladder. There have been several long-term studies of patients with rheumatoid arthritis treated with azathioprine and cyclophosphamide and the incidence of most of the common cancers is not increased. Data on the possible increased risk of malignancy in rheumatoid arthritis are still being collected, and until further information is available, the use of immunosuppressive drugs, particularly alkylating agents, in the treatment of rheumatoid arthritis should be reserved for patients with severe progressive disease or life-threatening complications.", "entity": "Carcinoma", "aliases": "Anaplastic Carcinoma Carcinomas Spindle Cell Spindle-Cell Undifferentiated Carcinomatoses Carcinomatosis Epithelial Neoplasm Malignant Neoplasms Tumor Tumors Epithelioma Epitheliomas", "definition": "A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm but is often wrongly used as a synonym for \"cancer.\" (From Dorland, 27th ed)\n    ", "id": "MESH:D002277"}
{"mention": "cancers", "mention_text": "Immunosuppressive drugs have been used during the last 30 years in treatment of patients with severe rheumatoid arthritis. The drugs commonly used are cyclophosphamide and chlorambucil (alkylating agents), azathioprine (purine analogue), and methotrexate (folic acid analogue). There is evidence that all four immunosuppressive drugs can reduce synovitis, but disease activity almost always recurs after therapy is stopped. Since adverse reactions are frequent, less than 50 percent of patients are able to continue a particular drug for more than one year. Since it takes three to 12 months to achieve maximal effects, those patients who are unable to continue the drug receive little benefit from it. Patients treated with alkylating agents have an increased risk of development of acute nonlymphocytic leukemia, and both alkylating agents and azathioprine are associated with the development of non-Hodgkin's lymphoma. Cyclophosphamide therapy increases the risk of carcinoma of the bladder. There have been several long-term studies of patients with rheumatoid arthritis treated with azathioprine and cyclophosphamide and the incidence of most of the common cancers is not increased. Data on the possible increased risk of malignancy in rheumatoid arthritis are still being collected, and until further information is available, the use of immunosuppressive drugs, particularly alkylating agents, in the treatment of rheumatoid arthritis should be reserved for patients with severe progressive disease or life-threatening complications.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "malignancy", "mention_text": "Immunosuppressive drugs have been used during the last 30 years in treatment of patients with severe rheumatoid arthritis. The drugs commonly used are cyclophosphamide and chlorambucil (alkylating agents), azathioprine (purine analogue), and methotrexate (folic acid analogue). There is evidence that all four immunosuppressive drugs can reduce synovitis, but disease activity almost always recurs after therapy is stopped. Since adverse reactions are frequent, less than 50 percent of patients are able to continue a particular drug for more than one year. Since it takes three to 12 months to achieve maximal effects, those patients who are unable to continue the drug receive little benefit from it. Patients treated with alkylating agents have an increased risk of development of acute nonlymphocytic leukemia, and both alkylating agents and azathioprine are associated with the development of non-Hodgkin's lymphoma. Cyclophosphamide therapy increases the risk of carcinoma of the bladder. There have been several long-term studies of patients with rheumatoid arthritis treated with azathioprine and cyclophosphamide and the incidence of most of the common cancers is not increased. Data on the possible increased risk of malignancy in rheumatoid arthritis are still being collected, and until further information is available, the use of immunosuppressive drugs, particularly alkylating agents, in the treatment of rheumatoid arthritis should be reserved for patients with severe progressive disease or life-threatening complications.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "hepatic injury", "mention_text": "Patterns of hepatic injury induced by methyldopa.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "methyldopa", "mention_text": "Patterns of hepatic injury induced by methyldopa.", "entity": "Methyldopa", "aliases": "Aldomet Alphamethyldopa Alphapharm Brand of Methyldopa Apo Apo-Methyldopa Apotex Biopat Cahill May Roberts Clonmel Dopamet Dopegit Dopegyt Dopergit Hydopa Meldopa Merck Sharp & Dohme Nu-Pharm Orion Methyldopate Nu Medopa Pharm Nu-Medopa Rhône Poulenc Rorer Rhône-Poulenc Sembrina alpha Methyl L Dopa alpha-Methyl-L-Dopa alpha-Methyldopa", "definition": "An alpha-2 adrenergic agonist that has both central and peripheral nervous system effects. Its primary clinical use is as an antihypertensive agent.\n    ", "id": "MESH:D008750"}
{"mention": "liver disease", "mention_text": "Twelve patients with liver disease related to methyldopa were seen between 1967 and 1977. Illness occurred within 1--9 weeks of commencement of therapy in 9 patients, the remaining 3 patients having received the drug for 13 months, 15 months and 7 years before experiencing symptoms. Jaundice with tender hepatomegaly, usually preceded by symptoms of malaise, anorexia, nausea and vomiting, and associated with upper abdominal pain, was an invariable finding in all patients. Biochemical liver function tests indicated hepatocellular necrosis and correlated with histopathological evidence of hepatic injury, the spectrum of which ranged from fatty change and focal hepatocellular necrosis to massive hepatic necrosis. Most patients showed moderate to severe acute hepatitis or chronic active hepatitis with associated cholestasis. The drug was withdrawn on presentation to hospital in 11 patients, with rapid clinical improvement in 9. One patient died, having presented in hepatic failure, and another, who had been taking methyldopa for 7 years, showed slower clinical and biochemical resolution over a period of several months. The remaining patient in the series developed fulminant hepatitis when the drug was accidentally recommenced 1 year after a prior episode of methyldopa-induced hepatitis. In this latter patient, and in 2 others, the causal relationship between methyldopa and hepatic dysfunction was proved with the recurrence of hepatitis within 2 weeks of re-exposure to the drug.", "entity": "Liver Diseases", "aliases": "Disease Liver Diseases Dysfunction Dysfunctions", "definition": "Pathological processes of the LIVER.\n    ", "id": "MESH:D008107"}
{"mention": "methyldopa", "mention_text": "Twelve patients with liver disease related to methyldopa were seen between 1967 and 1977. Illness occurred within 1--9 weeks of commencement of therapy in 9 patients, the remaining 3 patients having received the drug for 13 months, 15 months and 7 years before experiencing symptoms. Jaundice with tender hepatomegaly, usually preceded by symptoms of malaise, anorexia, nausea and vomiting, and associated with upper abdominal pain, was an invariable finding in all patients. Biochemical liver function tests indicated hepatocellular necrosis and correlated with histopathological evidence of hepatic injury, the spectrum of which ranged from fatty change and focal hepatocellular necrosis to massive hepatic necrosis. Most patients showed moderate to severe acute hepatitis or chronic active hepatitis with associated cholestasis. The drug was withdrawn on presentation to hospital in 11 patients, with rapid clinical improvement in 9. One patient died, having presented in hepatic failure, and another, who had been taking methyldopa for 7 years, showed slower clinical and biochemical resolution over a period of several months. The remaining patient in the series developed fulminant hepatitis when the drug was accidentally recommenced 1 year after a prior episode of methyldopa-induced hepatitis. In this latter patient, and in 2 others, the causal relationship between methyldopa and hepatic dysfunction was proved with the recurrence of hepatitis within 2 weeks of re-exposure to the drug.", "entity": "Methyldopa", "aliases": "Aldomet Alphamethyldopa Alphapharm Brand of Methyldopa Apo Apo-Methyldopa Apotex Biopat Cahill May Roberts Clonmel Dopamet Dopegit Dopegyt Dopergit Hydopa Meldopa Merck Sharp & Dohme Nu-Pharm Orion Methyldopate Nu Medopa Pharm Nu-Medopa Rhône Poulenc Rorer Rhône-Poulenc Sembrina alpha Methyl L Dopa alpha-Methyl-L-Dopa alpha-Methyldopa", "definition": "An alpha-2 adrenergic agonist that has both central and peripheral nervous system effects. Its primary clinical use is as an antihypertensive agent.\n    ", "id": "MESH:D008750"}
{"mention": "Jaundice", "mention_text": "Twelve patients with liver disease related to methyldopa were seen between 1967 and 1977. Illness occurred within 1--9 weeks of commencement of therapy in 9 patients, the remaining 3 patients having received the drug for 13 months, 15 months and 7 years before experiencing symptoms. Jaundice with tender hepatomegaly, usually preceded by symptoms of malaise, anorexia, nausea and vomiting, and associated with upper abdominal pain, was an invariable finding in all patients. Biochemical liver function tests indicated hepatocellular necrosis and correlated with histopathological evidence of hepatic injury, the spectrum of which ranged from fatty change and focal hepatocellular necrosis to massive hepatic necrosis. Most patients showed moderate to severe acute hepatitis or chronic active hepatitis with associated cholestasis. The drug was withdrawn on presentation to hospital in 11 patients, with rapid clinical improvement in 9. One patient died, having presented in hepatic failure, and another, who had been taking methyldopa for 7 years, showed slower clinical and biochemical resolution over a period of several months. The remaining patient in the series developed fulminant hepatitis when the drug was accidentally recommenced 1 year after a prior episode of methyldopa-induced hepatitis. In this latter patient, and in 2 others, the causal relationship between methyldopa and hepatic dysfunction was proved with the recurrence of hepatitis within 2 weeks of re-exposure to the drug.", "entity": "Jaundice", "aliases": "Hemolytic Jaundice Jaundices Icterus", "definition": "A clinical manifestation of HYPERBILIRUBINEMIA, characterized by the yellowish staining of the SKIN; MUCOUS MEMBRANE; and SCLERA. Clinical jaundice usually is a sign of LIVER dysfunction.\n    ", "id": "MESH:D007565"}
{"mention": "hepatomegaly", "mention_text": "Twelve patients with liver disease related to methyldopa were seen between 1967 and 1977. Illness occurred within 1--9 weeks of commencement of therapy in 9 patients, the remaining 3 patients having received the drug for 13 months, 15 months and 7 years before experiencing symptoms. Jaundice with tender hepatomegaly, usually preceded by symptoms of malaise, anorexia, nausea and vomiting, and associated with upper abdominal pain, was an invariable finding in all patients. Biochemical liver function tests indicated hepatocellular necrosis and correlated with histopathological evidence of hepatic injury, the spectrum of which ranged from fatty change and focal hepatocellular necrosis to massive hepatic necrosis. Most patients showed moderate to severe acute hepatitis or chronic active hepatitis with associated cholestasis. The drug was withdrawn on presentation to hospital in 11 patients, with rapid clinical improvement in 9. One patient died, having presented in hepatic failure, and another, who had been taking methyldopa for 7 years, showed slower clinical and biochemical resolution over a period of several months. The remaining patient in the series developed fulminant hepatitis when the drug was accidentally recommenced 1 year after a prior episode of methyldopa-induced hepatitis. In this latter patient, and in 2 others, the causal relationship between methyldopa and hepatic dysfunction was proved with the recurrence of hepatitis within 2 weeks of re-exposure to the drug.", "entity": "Hepatomegaly", "aliases": "Enlarged Liver Hepatomegaly", "definition": "Enlargement of the liver.\n    ", "id": "MESH:D006529"}
{"mention": "anorexia", "mention_text": "Twelve patients with liver disease related to methyldopa were seen between 1967 and 1977. Illness occurred within 1--9 weeks of commencement of therapy in 9 patients, the remaining 3 patients having received the drug for 13 months, 15 months and 7 years before experiencing symptoms. Jaundice with tender hepatomegaly, usually preceded by symptoms of malaise, anorexia, nausea and vomiting, and associated with upper abdominal pain, was an invariable finding in all patients. Biochemical liver function tests indicated hepatocellular necrosis and correlated with histopathological evidence of hepatic injury, the spectrum of which ranged from fatty change and focal hepatocellular necrosis to massive hepatic necrosis. Most patients showed moderate to severe acute hepatitis or chronic active hepatitis with associated cholestasis. The drug was withdrawn on presentation to hospital in 11 patients, with rapid clinical improvement in 9. One patient died, having presented in hepatic failure, and another, who had been taking methyldopa for 7 years, showed slower clinical and biochemical resolution over a period of several months. The remaining patient in the series developed fulminant hepatitis when the drug was accidentally recommenced 1 year after a prior episode of methyldopa-induced hepatitis. In this latter patient, and in 2 others, the causal relationship between methyldopa and hepatic dysfunction was proved with the recurrence of hepatitis within 2 weeks of re-exposure to the drug.", "entity": "Anorexia", "aliases": "Anorexia Anorexias", "definition": "The lack or loss of APPETITE accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder ANOREXIA NERVOSA.\n    ", "id": "MESH:D000855"}
{"mention": "nausea", "mention_text": "Twelve patients with liver disease related to methyldopa were seen between 1967 and 1977. Illness occurred within 1--9 weeks of commencement of therapy in 9 patients, the remaining 3 patients having received the drug for 13 months, 15 months and 7 years before experiencing symptoms. Jaundice with tender hepatomegaly, usually preceded by symptoms of malaise, anorexia, nausea and vomiting, and associated with upper abdominal pain, was an invariable finding in all patients. Biochemical liver function tests indicated hepatocellular necrosis and correlated with histopathological evidence of hepatic injury, the spectrum of which ranged from fatty change and focal hepatocellular necrosis to massive hepatic necrosis. Most patients showed moderate to severe acute hepatitis or chronic active hepatitis with associated cholestasis. The drug was withdrawn on presentation to hospital in 11 patients, with rapid clinical improvement in 9. One patient died, having presented in hepatic failure, and another, who had been taking methyldopa for 7 years, showed slower clinical and biochemical resolution over a period of several months. The remaining patient in the series developed fulminant hepatitis when the drug was accidentally recommenced 1 year after a prior episode of methyldopa-induced hepatitis. In this latter patient, and in 2 others, the causal relationship between methyldopa and hepatic dysfunction was proved with the recurrence of hepatitis within 2 weeks of re-exposure to the drug.", "entity": "Nausea", "aliases": "Nausea", "definition": "An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.\n    ", "id": "MESH:D009325"}
{"mention": "vomiting", "mention_text": "Twelve patients with liver disease related to methyldopa were seen between 1967 and 1977. Illness occurred within 1--9 weeks of commencement of therapy in 9 patients, the remaining 3 patients having received the drug for 13 months, 15 months and 7 years before experiencing symptoms. Jaundice with tender hepatomegaly, usually preceded by symptoms of malaise, anorexia, nausea and vomiting, and associated with upper abdominal pain, was an invariable finding in all patients. Biochemical liver function tests indicated hepatocellular necrosis and correlated with histopathological evidence of hepatic injury, the spectrum of which ranged from fatty change and focal hepatocellular necrosis to massive hepatic necrosis. Most patients showed moderate to severe acute hepatitis or chronic active hepatitis with associated cholestasis. The drug was withdrawn on presentation to hospital in 11 patients, with rapid clinical improvement in 9. One patient died, having presented in hepatic failure, and another, who had been taking methyldopa for 7 years, showed slower clinical and biochemical resolution over a period of several months. The remaining patient in the series developed fulminant hepatitis when the drug was accidentally recommenced 1 year after a prior episode of methyldopa-induced hepatitis. In this latter patient, and in 2 others, the causal relationship between methyldopa and hepatic dysfunction was proved with the recurrence of hepatitis within 2 weeks of re-exposure to the drug.", "entity": "Vomiting", "aliases": "Emesis Vomiting", "definition": "The forcible expulsion of the contents of the STOMACH through the MOUTH.\n    ", "id": "MESH:D014839"}
{"mention": "abdominal pain", "mention_text": "Twelve patients with liver disease related to methyldopa were seen between 1967 and 1977. Illness occurred within 1--9 weeks of commencement of therapy in 9 patients, the remaining 3 patients having received the drug for 13 months, 15 months and 7 years before experiencing symptoms. Jaundice with tender hepatomegaly, usually preceded by symptoms of malaise, anorexia, nausea and vomiting, and associated with upper abdominal pain, was an invariable finding in all patients. Biochemical liver function tests indicated hepatocellular necrosis and correlated with histopathological evidence of hepatic injury, the spectrum of which ranged from fatty change and focal hepatocellular necrosis to massive hepatic necrosis. Most patients showed moderate to severe acute hepatitis or chronic active hepatitis with associated cholestasis. The drug was withdrawn on presentation to hospital in 11 patients, with rapid clinical improvement in 9. One patient died, having presented in hepatic failure, and another, who had been taking methyldopa for 7 years, showed slower clinical and biochemical resolution over a period of several months. The remaining patient in the series developed fulminant hepatitis when the drug was accidentally recommenced 1 year after a prior episode of methyldopa-induced hepatitis. In this latter patient, and in 2 others, the causal relationship between methyldopa and hepatic dysfunction was proved with the recurrence of hepatitis within 2 weeks of re-exposure to the drug.", "entity": "Abdominal Pain", "aliases": "Abdominal Pain Pains", "definition": "Sensation of discomfort, distress, or agony in the abdominal region; generally associated with functional disorders, tissue injuries, or diseases.\n    ", "id": "MESH:D015746"}
{"mention": "necrosis", "mention_text": "Twelve patients with liver disease related to methyldopa were seen between 1967 and 1977. Illness occurred within 1--9 weeks of commencement of therapy in 9 patients, the remaining 3 patients having received the drug for 13 months, 15 months and 7 years before experiencing symptoms. Jaundice with tender hepatomegaly, usually preceded by symptoms of malaise, anorexia, nausea and vomiting, and associated with upper abdominal pain, was an invariable finding in all patients. Biochemical liver function tests indicated hepatocellular necrosis and correlated with histopathological evidence of hepatic injury, the spectrum of which ranged from fatty change and focal hepatocellular necrosis to massive hepatic necrosis. Most patients showed moderate to severe acute hepatitis or chronic active hepatitis with associated cholestasis. The drug was withdrawn on presentation to hospital in 11 patients, with rapid clinical improvement in 9. One patient died, having presented in hepatic failure, and another, who had been taking methyldopa for 7 years, showed slower clinical and biochemical resolution over a period of several months. The remaining patient in the series developed fulminant hepatitis when the drug was accidentally recommenced 1 year after a prior episode of methyldopa-induced hepatitis. In this latter patient, and in 2 others, the causal relationship between methyldopa and hepatic dysfunction was proved with the recurrence of hepatitis within 2 weeks of re-exposure to the drug.", "entity": "Necrosis", "aliases": "Necroses Necrosis", "definition": "The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. Distinguish it from APOPTOSIS which is a normal, regulated cellular process.\n    ", "id": "MESH:D009336"}
{"mention": "hepatic injury", "mention_text": "Twelve patients with liver disease related to methyldopa were seen between 1967 and 1977. Illness occurred within 1--9 weeks of commencement of therapy in 9 patients, the remaining 3 patients having received the drug for 13 months, 15 months and 7 years before experiencing symptoms. Jaundice with tender hepatomegaly, usually preceded by symptoms of malaise, anorexia, nausea and vomiting, and associated with upper abdominal pain, was an invariable finding in all patients. Biochemical liver function tests indicated hepatocellular necrosis and correlated with histopathological evidence of hepatic injury, the spectrum of which ranged from fatty change and focal hepatocellular necrosis to massive hepatic necrosis. Most patients showed moderate to severe acute hepatitis or chronic active hepatitis with associated cholestasis. The drug was withdrawn on presentation to hospital in 11 patients, with rapid clinical improvement in 9. One patient died, having presented in hepatic failure, and another, who had been taking methyldopa for 7 years, showed slower clinical and biochemical resolution over a period of several months. The remaining patient in the series developed fulminant hepatitis when the drug was accidentally recommenced 1 year after a prior episode of methyldopa-induced hepatitis. In this latter patient, and in 2 others, the causal relationship between methyldopa and hepatic dysfunction was proved with the recurrence of hepatitis within 2 weeks of re-exposure to the drug.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "fatty change", "mention_text": "Twelve patients with liver disease related to methyldopa were seen between 1967 and 1977. Illness occurred within 1--9 weeks of commencement of therapy in 9 patients, the remaining 3 patients having received the drug for 13 months, 15 months and 7 years before experiencing symptoms. Jaundice with tender hepatomegaly, usually preceded by symptoms of malaise, anorexia, nausea and vomiting, and associated with upper abdominal pain, was an invariable finding in all patients. Biochemical liver function tests indicated hepatocellular necrosis and correlated with histopathological evidence of hepatic injury, the spectrum of which ranged from fatty change and focal hepatocellular necrosis to massive hepatic necrosis. Most patients showed moderate to severe acute hepatitis or chronic active hepatitis with associated cholestasis. The drug was withdrawn on presentation to hospital in 11 patients, with rapid clinical improvement in 9. One patient died, having presented in hepatic failure, and another, who had been taking methyldopa for 7 years, showed slower clinical and biochemical resolution over a period of several months. The remaining patient in the series developed fulminant hepatitis when the drug was accidentally recommenced 1 year after a prior episode of methyldopa-induced hepatitis. In this latter patient, and in 2 others, the causal relationship between methyldopa and hepatic dysfunction was proved with the recurrence of hepatitis within 2 weeks of re-exposure to the drug.", "entity": "Fatty Liver", "aliases": "Fatty Liver Steatoses Steatosis Steatohepatitides Steatohepatitis Visceral of", "definition": "Lipid infiltration of the hepatic parenchymal cells resulting in a yellow-colored liver. The abnormal lipid accumulation is usually in the form of TRIGLYCERIDES, either as a single large droplet or multiple small droplets. Fatty liver is caused by an imbalance in the metabolism of FATTY ACIDS.\n    ", "id": "MESH:D005234"}
{"mention": "massive hepatic necrosis", "mention_text": "Twelve patients with liver disease related to methyldopa were seen between 1967 and 1977. Illness occurred within 1--9 weeks of commencement of therapy in 9 patients, the remaining 3 patients having received the drug for 13 months, 15 months and 7 years before experiencing symptoms. Jaundice with tender hepatomegaly, usually preceded by symptoms of malaise, anorexia, nausea and vomiting, and associated with upper abdominal pain, was an invariable finding in all patients. Biochemical liver function tests indicated hepatocellular necrosis and correlated with histopathological evidence of hepatic injury, the spectrum of which ranged from fatty change and focal hepatocellular necrosis to massive hepatic necrosis. Most patients showed moderate to severe acute hepatitis or chronic active hepatitis with associated cholestasis. The drug was withdrawn on presentation to hospital in 11 patients, with rapid clinical improvement in 9. One patient died, having presented in hepatic failure, and another, who had been taking methyldopa for 7 years, showed slower clinical and biochemical resolution over a period of several months. The remaining patient in the series developed fulminant hepatitis when the drug was accidentally recommenced 1 year after a prior episode of methyldopa-induced hepatitis. In this latter patient, and in 2 others, the causal relationship between methyldopa and hepatic dysfunction was proved with the recurrence of hepatitis within 2 weeks of re-exposure to the drug.", "entity": "Massive Hepatic Necrosis", "aliases": "Acute Yellow Atrophies Atrophy of Liver Hepatic Necrosis Massive", "definition": "Extensive and rapid death of parenchymal cells in the LIVER, often due to exposure to toxic materials. It is characterized by a soft, flabby, yellow-brown wrinkled, and shrunken liver. It was called \"acute yellow atrophy\".\n    ", "id": "MESH:D047508"}
{"mention": "acute hepatitis", "mention_text": "Twelve patients with liver disease related to methyldopa were seen between 1967 and 1977. Illness occurred within 1--9 weeks of commencement of therapy in 9 patients, the remaining 3 patients having received the drug for 13 months, 15 months and 7 years before experiencing symptoms. Jaundice with tender hepatomegaly, usually preceded by symptoms of malaise, anorexia, nausea and vomiting, and associated with upper abdominal pain, was an invariable finding in all patients. Biochemical liver function tests indicated hepatocellular necrosis and correlated with histopathological evidence of hepatic injury, the spectrum of which ranged from fatty change and focal hepatocellular necrosis to massive hepatic necrosis. Most patients showed moderate to severe acute hepatitis or chronic active hepatitis with associated cholestasis. The drug was withdrawn on presentation to hospital in 11 patients, with rapid clinical improvement in 9. One patient died, having presented in hepatic failure, and another, who had been taking methyldopa for 7 years, showed slower clinical and biochemical resolution over a period of several months. The remaining patient in the series developed fulminant hepatitis when the drug was accidentally recommenced 1 year after a prior episode of methyldopa-induced hepatitis. In this latter patient, and in 2 others, the causal relationship between methyldopa and hepatic dysfunction was proved with the recurrence of hepatitis within 2 weeks of re-exposure to the drug.", "entity": "Liver Failure, Acute", "aliases": "Acute Hepatic Failure Liver Fulminant Failures Fulminating", "definition": "A form of rapid-onset LIVER FAILURE, also known as fulminant hepatic failure, caused by severe liver injury or massive loss of HEPATOCYTES. It is characterized by sudden development of liver dysfunction and JAUNDICE. Acute liver failure may progress to exhibit cerebral dysfunction even HEPATIC COMA depending on the etiology that includes hepatic ISCHEMIA, drug toxicity, malignant infiltration, and viral hepatitis such as post-transfusion HEPATITIS B and HEPATITIS C.\n    ", "id": "MESH:D017114"}
{"mention": "chronic active hepatitis", "mention_text": "Twelve patients with liver disease related to methyldopa were seen between 1967 and 1977. Illness occurred within 1--9 weeks of commencement of therapy in 9 patients, the remaining 3 patients having received the drug for 13 months, 15 months and 7 years before experiencing symptoms. Jaundice with tender hepatomegaly, usually preceded by symptoms of malaise, anorexia, nausea and vomiting, and associated with upper abdominal pain, was an invariable finding in all patients. Biochemical liver function tests indicated hepatocellular necrosis and correlated with histopathological evidence of hepatic injury, the spectrum of which ranged from fatty change and focal hepatocellular necrosis to massive hepatic necrosis. Most patients showed moderate to severe acute hepatitis or chronic active hepatitis with associated cholestasis. The drug was withdrawn on presentation to hospital in 11 patients, with rapid clinical improvement in 9. One patient died, having presented in hepatic failure, and another, who had been taking methyldopa for 7 years, showed slower clinical and biochemical resolution over a period of several months. The remaining patient in the series developed fulminant hepatitis when the drug was accidentally recommenced 1 year after a prior episode of methyldopa-induced hepatitis. In this latter patient, and in 2 others, the causal relationship between methyldopa and hepatic dysfunction was proved with the recurrence of hepatitis within 2 weeks of re-exposure to the drug.", "entity": "Hepatitis, Chronic", "aliases": "Chronic Active Hepatitis Cryptogenic Persistent Hepatitides", "definition": "INFLAMMATION of the LIVER with ongoing hepatocellular injury for 6 months or more, characterized by NECROSIS of HEPATOCYTES and inflammatory cell (LEUKOCYTES) infiltration. Chronic hepatitis can be caused by viruses, medications, autoimmune diseases, and other unknown factors.\n    ", "id": "MESH:D006521"}
{"mention": "cholestasis", "mention_text": "Twelve patients with liver disease related to methyldopa were seen between 1967 and 1977. Illness occurred within 1--9 weeks of commencement of therapy in 9 patients, the remaining 3 patients having received the drug for 13 months, 15 months and 7 years before experiencing symptoms. Jaundice with tender hepatomegaly, usually preceded by symptoms of malaise, anorexia, nausea and vomiting, and associated with upper abdominal pain, was an invariable finding in all patients. Biochemical liver function tests indicated hepatocellular necrosis and correlated with histopathological evidence of hepatic injury, the spectrum of which ranged from fatty change and focal hepatocellular necrosis to massive hepatic necrosis. Most patients showed moderate to severe acute hepatitis or chronic active hepatitis with associated cholestasis. The drug was withdrawn on presentation to hospital in 11 patients, with rapid clinical improvement in 9. One patient died, having presented in hepatic failure, and another, who had been taking methyldopa for 7 years, showed slower clinical and biochemical resolution over a period of several months. The remaining patient in the series developed fulminant hepatitis when the drug was accidentally recommenced 1 year after a prior episode of methyldopa-induced hepatitis. In this latter patient, and in 2 others, the causal relationship between methyldopa and hepatic dysfunction was proved with the recurrence of hepatitis within 2 weeks of re-exposure to the drug.", "entity": "Cholestasis", "aliases": "Bile Duct Obstruction Obstructions Biliary Stases Stasis Cholestases Cholestasis", "definition": "Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).\n    ", "id": "MESH:D002779"}
{"mention": "hepatic failure", "mention_text": "Twelve patients with liver disease related to methyldopa were seen between 1967 and 1977. Illness occurred within 1--9 weeks of commencement of therapy in 9 patients, the remaining 3 patients having received the drug for 13 months, 15 months and 7 years before experiencing symptoms. Jaundice with tender hepatomegaly, usually preceded by symptoms of malaise, anorexia, nausea and vomiting, and associated with upper abdominal pain, was an invariable finding in all patients. Biochemical liver function tests indicated hepatocellular necrosis and correlated with histopathological evidence of hepatic injury, the spectrum of which ranged from fatty change and focal hepatocellular necrosis to massive hepatic necrosis. Most patients showed moderate to severe acute hepatitis or chronic active hepatitis with associated cholestasis. The drug was withdrawn on presentation to hospital in 11 patients, with rapid clinical improvement in 9. One patient died, having presented in hepatic failure, and another, who had been taking methyldopa for 7 years, showed slower clinical and biochemical resolution over a period of several months. The remaining patient in the series developed fulminant hepatitis when the drug was accidentally recommenced 1 year after a prior episode of methyldopa-induced hepatitis. In this latter patient, and in 2 others, the causal relationship between methyldopa and hepatic dysfunction was proved with the recurrence of hepatitis within 2 weeks of re-exposure to the drug.", "entity": "Liver Failure", "aliases": "Hepatic Failure Liver", "definition": "Severe inability of the LIVER to perform its normal metabolic functions, as evidenced by severe JAUNDICE and abnormal serum levels of AMMONIA; BILIRUBIN; ALKALINE PHOSPHATASE; ASPARTATE AMINOTRANSFERASE; LACTATE DEHYDROGENASES; and albumin/globulin ratio. (Blakiston's Gould Medical Dictionary, 4th ed)\n    ", "id": "MESH:D017093"}
{"mention": "fulminant hepatitis", "mention_text": "Twelve patients with liver disease related to methyldopa were seen between 1967 and 1977. Illness occurred within 1--9 weeks of commencement of therapy in 9 patients, the remaining 3 patients having received the drug for 13 months, 15 months and 7 years before experiencing symptoms. Jaundice with tender hepatomegaly, usually preceded by symptoms of malaise, anorexia, nausea and vomiting, and associated with upper abdominal pain, was an invariable finding in all patients. Biochemical liver function tests indicated hepatocellular necrosis and correlated with histopathological evidence of hepatic injury, the spectrum of which ranged from fatty change and focal hepatocellular necrosis to massive hepatic necrosis. Most patients showed moderate to severe acute hepatitis or chronic active hepatitis with associated cholestasis. The drug was withdrawn on presentation to hospital in 11 patients, with rapid clinical improvement in 9. One patient died, having presented in hepatic failure, and another, who had been taking methyldopa for 7 years, showed slower clinical and biochemical resolution over a period of several months. The remaining patient in the series developed fulminant hepatitis when the drug was accidentally recommenced 1 year after a prior episode of methyldopa-induced hepatitis. In this latter patient, and in 2 others, the causal relationship between methyldopa and hepatic dysfunction was proved with the recurrence of hepatitis within 2 weeks of re-exposure to the drug.", "entity": "Liver Failure, Acute", "aliases": "Acute Hepatic Failure Liver Fulminant Failures Fulminating", "definition": "A form of rapid-onset LIVER FAILURE, also known as fulminant hepatic failure, caused by severe liver injury or massive loss of HEPATOCYTES. It is characterized by sudden development of liver dysfunction and JAUNDICE. Acute liver failure may progress to exhibit cerebral dysfunction even HEPATIC COMA depending on the etiology that includes hepatic ISCHEMIA, drug toxicity, malignant infiltration, and viral hepatitis such as post-transfusion HEPATITIS B and HEPATITIS C.\n    ", "id": "MESH:D017114"}
{"mention": "hepatitis", "mention_text": "Twelve patients with liver disease related to methyldopa were seen between 1967 and 1977. Illness occurred within 1--9 weeks of commencement of therapy in 9 patients, the remaining 3 patients having received the drug for 13 months, 15 months and 7 years before experiencing symptoms. Jaundice with tender hepatomegaly, usually preceded by symptoms of malaise, anorexia, nausea and vomiting, and associated with upper abdominal pain, was an invariable finding in all patients. Biochemical liver function tests indicated hepatocellular necrosis and correlated with histopathological evidence of hepatic injury, the spectrum of which ranged from fatty change and focal hepatocellular necrosis to massive hepatic necrosis. Most patients showed moderate to severe acute hepatitis or chronic active hepatitis with associated cholestasis. The drug was withdrawn on presentation to hospital in 11 patients, with rapid clinical improvement in 9. One patient died, having presented in hepatic failure, and another, who had been taking methyldopa for 7 years, showed slower clinical and biochemical resolution over a period of several months. The remaining patient in the series developed fulminant hepatitis when the drug was accidentally recommenced 1 year after a prior episode of methyldopa-induced hepatitis. In this latter patient, and in 2 others, the causal relationship between methyldopa and hepatic dysfunction was proved with the recurrence of hepatitis within 2 weeks of re-exposure to the drug.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "hepatic dysfunction", "mention_text": "Twelve patients with liver disease related to methyldopa were seen between 1967 and 1977. Illness occurred within 1--9 weeks of commencement of therapy in 9 patients, the remaining 3 patients having received the drug for 13 months, 15 months and 7 years before experiencing symptoms. Jaundice with tender hepatomegaly, usually preceded by symptoms of malaise, anorexia, nausea and vomiting, and associated with upper abdominal pain, was an invariable finding in all patients. Biochemical liver function tests indicated hepatocellular necrosis and correlated with histopathological evidence of hepatic injury, the spectrum of which ranged from fatty change and focal hepatocellular necrosis to massive hepatic necrosis. Most patients showed moderate to severe acute hepatitis or chronic active hepatitis with associated cholestasis. The drug was withdrawn on presentation to hospital in 11 patients, with rapid clinical improvement in 9. One patient died, having presented in hepatic failure, and another, who had been taking methyldopa for 7 years, showed slower clinical and biochemical resolution over a period of several months. The remaining patient in the series developed fulminant hepatitis when the drug was accidentally recommenced 1 year after a prior episode of methyldopa-induced hepatitis. In this latter patient, and in 2 others, the causal relationship between methyldopa and hepatic dysfunction was proved with the recurrence of hepatitis within 2 weeks of re-exposure to the drug.", "entity": "Liver Diseases", "aliases": "Disease Liver Diseases Dysfunction Dysfunctions", "definition": "Pathological processes of the LIVER.\n    ", "id": "MESH:D008107"}
{"mention": "paclitaxel", "mention_text": "A phase I/II study of paclitaxel plus cisplatin as first-line therapy for head and neck cancers: preliminary results.", "entity": "Paclitaxel", "aliases": "7 epi Taxol 7-epi-Taxol Anzatax Bris Bristol-Myers Brand of Paclitaxel Squibb Bull Ivax Lemery NSC 125973 NSC-125973 NSC125973 Onxol (4 alpha)-Isomer Paxene Praxel A", "definition": "A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.\n    ", "id": "MESH:D017239"}
{"mention": "cisplatin", "mention_text": "A phase I/II study of paclitaxel plus cisplatin as first-line therapy for head and neck cancers: preliminary results.", "entity": "Cisplatin", "aliases": "Biocisplatinum Cisplatin Diamminodichloride Platinum Dichlorodiammineplatinum NSC-119875 Platidiam Platino Platinol cis Diamminedichloroplatinum cis-Diamminedichloroplatinum cis-Diamminedichloroplatinum(II) cis-Dichlorodiammineplatinum(II) cis-Platinum", "definition": "An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.\n    ", "id": "MESH:D002945"}
{"mention": "head and neck cancers", "mention_text": "A phase I/II study of paclitaxel plus cisplatin as first-line therapy for head and neck cancers: preliminary results.", "entity": "Head and Neck Neoplasms", "aliases": "Cancer of Head and Neck the Neoplasms Neoplasm UADT Upper Aerodigestive Tract", "definition": "Soft tissue tumors or cancer arising from the mucosal surfaces of the LIP; oral cavity; PHARYNX; LARYNX; and cervical esophagus. Other sites included are the NOSE and PARANASAL SINUSES; SALIVARY GLANDS; THYROID GLAND and PARATHYROID GLANDS; and MELANOMA and non-melanoma skin cancers of the head and neck. (from Holland et al., Cancer Medicine, 4th ed, p1651)\n    ", "id": "MESH:D006258"}
{"mention": "head and neck carcinomas", "mention_text": "Improved outcomes among patients with head and neck carcinomas require investigations of new drugs for induction therapy. Preliminary results of an Eastern Cooperative Oncology Group study of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) reported a 37% response rate in patients with head and neck cancer, and the paclitaxel/cisplatin combination has been used successfully and has significantly improved median response duration in ovarian cancer patients. We initiated a phase I/II trial to determine the response and toxicity of escalating paclitaxel doses combined with fixed-dose cisplatin with granulocyte colony-stimulating factor support in patients with untreated locally advanced inoperable head and neck carcinoma. To date, 23 men with a median age of 50 years and good performance status have entered the trial. Primary tumor sites were oropharynx, 10 patients; hypopharynx, four; larynx, two; oral cavity, three; unknown primary, two; and nasal cavity and parotid gland, one each. Of 20 patients evaluable for toxicity, four had stage III and 16 had stage IV disease. Treatment, given every 21 days for a maximum of three cycles, consisted of paclitaxel by 3-hour infusion followed the next day by a fixed dose of cisplatin (75 mg/m2). The dose levels incorporate escalating paclitaxel doses, and intrapatient escalations within a given dose level are permitted if toxicity permits. At the time of this writing, dose level 4 (260, 270, and 280 mg/m2) is being evaluated; three patients from this level are evaluable. With paclitaxel doses of 200 mg/m2 and higher, granulocyte colony-stimulating factor 5 micrograms/kg/d is given (days 4 through 12). Of 18 patients evaluable for response, seven (39%) achieved a complete response and six (33%) achieved a partial response. Three patients had no change and disease progressed in two. The overall response rate is 72%. Eleven responding patients had subsequent surgery/radiotherapy or radical radiotherapy. Two pathologic complete responses were observed in patients who had achieved clinical complete responses. Alopecia, paresthesias, and arthralgias/myalgias have occurred frequently, but with one exception (a grade 3 myalgia) they have been grade 1 or 2. No dose-limiting hematologic toxicity has been seen. Paclitaxel/cisplatin is an effective first-line regimen for locoregionally advanced head and neck cancer and continued study is warranted. Results thus far suggest no dose-response effect for paclitaxel doses above 200 mg/m2.", "entity": "Head and Neck Neoplasms", "aliases": "Cancer of Head and Neck the Neoplasms Neoplasm UADT Upper Aerodigestive Tract", "definition": "Soft tissue tumors or cancer arising from the mucosal surfaces of the LIP; oral cavity; PHARYNX; LARYNX; and cervical esophagus. Other sites included are the NOSE and PARANASAL SINUSES; SALIVARY GLANDS; THYROID GLAND and PARATHYROID GLANDS; and MELANOMA and non-melanoma skin cancers of the head and neck. (from Holland et al., Cancer Medicine, 4th ed, p1651)\n    ", "id": "MESH:D006258"}
{"mention": "paclitaxel", "mention_text": "Improved outcomes among patients with head and neck carcinomas require investigations of new drugs for induction therapy. Preliminary results of an Eastern Cooperative Oncology Group study of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) reported a 37% response rate in patients with head and neck cancer, and the paclitaxel/cisplatin combination has been used successfully and has significantly improved median response duration in ovarian cancer patients. We initiated a phase I/II trial to determine the response and toxicity of escalating paclitaxel doses combined with fixed-dose cisplatin with granulocyte colony-stimulating factor support in patients with untreated locally advanced inoperable head and neck carcinoma. To date, 23 men with a median age of 50 years and good performance status have entered the trial. Primary tumor sites were oropharynx, 10 patients; hypopharynx, four; larynx, two; oral cavity, three; unknown primary, two; and nasal cavity and parotid gland, one each. Of 20 patients evaluable for toxicity, four had stage III and 16 had stage IV disease. Treatment, given every 21 days for a maximum of three cycles, consisted of paclitaxel by 3-hour infusion followed the next day by a fixed dose of cisplatin (75 mg/m2). The dose levels incorporate escalating paclitaxel doses, and intrapatient escalations within a given dose level are permitted if toxicity permits. At the time of this writing, dose level 4 (260, 270, and 280 mg/m2) is being evaluated; three patients from this level are evaluable. With paclitaxel doses of 200 mg/m2 and higher, granulocyte colony-stimulating factor 5 micrograms/kg/d is given (days 4 through 12). Of 18 patients evaluable for response, seven (39%) achieved a complete response and six (33%) achieved a partial response. Three patients had no change and disease progressed in two. The overall response rate is 72%. Eleven responding patients had subsequent surgery/radiotherapy or radical radiotherapy. Two pathologic complete responses were observed in patients who had achieved clinical complete responses. Alopecia, paresthesias, and arthralgias/myalgias have occurred frequently, but with one exception (a grade 3 myalgia) they have been grade 1 or 2. No dose-limiting hematologic toxicity has been seen. Paclitaxel/cisplatin is an effective first-line regimen for locoregionally advanced head and neck cancer and continued study is warranted. Results thus far suggest no dose-response effect for paclitaxel doses above 200 mg/m2.", "entity": "Paclitaxel", "aliases": "7 epi Taxol 7-epi-Taxol Anzatax Bris Bristol-Myers Brand of Paclitaxel Squibb Bull Ivax Lemery NSC 125973 NSC-125973 NSC125973 Onxol (4 alpha)-Isomer Paxene Praxel A", "definition": "A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.\n    ", "id": "MESH:D017239"}
{"mention": "Taxol", "mention_text": "Improved outcomes among patients with head and neck carcinomas require investigations of new drugs for induction therapy. Preliminary results of an Eastern Cooperative Oncology Group study of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) reported a 37% response rate in patients with head and neck cancer, and the paclitaxel/cisplatin combination has been used successfully and has significantly improved median response duration in ovarian cancer patients. We initiated a phase I/II trial to determine the response and toxicity of escalating paclitaxel doses combined with fixed-dose cisplatin with granulocyte colony-stimulating factor support in patients with untreated locally advanced inoperable head and neck carcinoma. To date, 23 men with a median age of 50 years and good performance status have entered the trial. Primary tumor sites were oropharynx, 10 patients; hypopharynx, four; larynx, two; oral cavity, three; unknown primary, two; and nasal cavity and parotid gland, one each. Of 20 patients evaluable for toxicity, four had stage III and 16 had stage IV disease. Treatment, given every 21 days for a maximum of three cycles, consisted of paclitaxel by 3-hour infusion followed the next day by a fixed dose of cisplatin (75 mg/m2). The dose levels incorporate escalating paclitaxel doses, and intrapatient escalations within a given dose level are permitted if toxicity permits. At the time of this writing, dose level 4 (260, 270, and 280 mg/m2) is being evaluated; three patients from this level are evaluable. With paclitaxel doses of 200 mg/m2 and higher, granulocyte colony-stimulating factor 5 micrograms/kg/d is given (days 4 through 12). Of 18 patients evaluable for response, seven (39%) achieved a complete response and six (33%) achieved a partial response. Three patients had no change and disease progressed in two. The overall response rate is 72%. Eleven responding patients had subsequent surgery/radiotherapy or radical radiotherapy. Two pathologic complete responses were observed in patients who had achieved clinical complete responses. Alopecia, paresthesias, and arthralgias/myalgias have occurred frequently, but with one exception (a grade 3 myalgia) they have been grade 1 or 2. No dose-limiting hematologic toxicity has been seen. Paclitaxel/cisplatin is an effective first-line regimen for locoregionally advanced head and neck cancer and continued study is warranted. Results thus far suggest no dose-response effect for paclitaxel doses above 200 mg/m2.", "entity": "Paclitaxel", "aliases": "7 epi Taxol 7-epi-Taxol Anzatax Bris Bristol-Myers Brand of Paclitaxel Squibb Bull Ivax Lemery NSC 125973 NSC-125973 NSC125973 Onxol (4 alpha)-Isomer Paxene Praxel A", "definition": "A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.\n    ", "id": "MESH:D017239"}
{"mention": "head and neck cancer", "mention_text": "Improved outcomes among patients with head and neck carcinomas require investigations of new drugs for induction therapy. Preliminary results of an Eastern Cooperative Oncology Group study of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) reported a 37% response rate in patients with head and neck cancer, and the paclitaxel/cisplatin combination has been used successfully and has significantly improved median response duration in ovarian cancer patients. We initiated a phase I/II trial to determine the response and toxicity of escalating paclitaxel doses combined with fixed-dose cisplatin with granulocyte colony-stimulating factor support in patients with untreated locally advanced inoperable head and neck carcinoma. To date, 23 men with a median age of 50 years and good performance status have entered the trial. Primary tumor sites were oropharynx, 10 patients; hypopharynx, four; larynx, two; oral cavity, three; unknown primary, two; and nasal cavity and parotid gland, one each. Of 20 patients evaluable for toxicity, four had stage III and 16 had stage IV disease. Treatment, given every 21 days for a maximum of three cycles, consisted of paclitaxel by 3-hour infusion followed the next day by a fixed dose of cisplatin (75 mg/m2). The dose levels incorporate escalating paclitaxel doses, and intrapatient escalations within a given dose level are permitted if toxicity permits. At the time of this writing, dose level 4 (260, 270, and 280 mg/m2) is being evaluated; three patients from this level are evaluable. With paclitaxel doses of 200 mg/m2 and higher, granulocyte colony-stimulating factor 5 micrograms/kg/d is given (days 4 through 12). Of 18 patients evaluable for response, seven (39%) achieved a complete response and six (33%) achieved a partial response. Three patients had no change and disease progressed in two. The overall response rate is 72%. Eleven responding patients had subsequent surgery/radiotherapy or radical radiotherapy. Two pathologic complete responses were observed in patients who had achieved clinical complete responses. Alopecia, paresthesias, and arthralgias/myalgias have occurred frequently, but with one exception (a grade 3 myalgia) they have been grade 1 or 2. No dose-limiting hematologic toxicity has been seen. Paclitaxel/cisplatin is an effective first-line regimen for locoregionally advanced head and neck cancer and continued study is warranted. Results thus far suggest no dose-response effect for paclitaxel doses above 200 mg/m2.", "entity": "Head and Neck Neoplasms", "aliases": "Cancer of Head and Neck the Neoplasms Neoplasm UADT Upper Aerodigestive Tract", "definition": "Soft tissue tumors or cancer arising from the mucosal surfaces of the LIP; oral cavity; PHARYNX; LARYNX; and cervical esophagus. Other sites included are the NOSE and PARANASAL SINUSES; SALIVARY GLANDS; THYROID GLAND and PARATHYROID GLANDS; and MELANOMA and non-melanoma skin cancers of the head and neck. (from Holland et al., Cancer Medicine, 4th ed, p1651)\n    ", "id": "MESH:D006258"}
{"mention": "cisplatin", "mention_text": "Improved outcomes among patients with head and neck carcinomas require investigations of new drugs for induction therapy. Preliminary results of an Eastern Cooperative Oncology Group study of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) reported a 37% response rate in patients with head and neck cancer, and the paclitaxel/cisplatin combination has been used successfully and has significantly improved median response duration in ovarian cancer patients. We initiated a phase I/II trial to determine the response and toxicity of escalating paclitaxel doses combined with fixed-dose cisplatin with granulocyte colony-stimulating factor support in patients with untreated locally advanced inoperable head and neck carcinoma. To date, 23 men with a median age of 50 years and good performance status have entered the trial. Primary tumor sites were oropharynx, 10 patients; hypopharynx, four; larynx, two; oral cavity, three; unknown primary, two; and nasal cavity and parotid gland, one each. Of 20 patients evaluable for toxicity, four had stage III and 16 had stage IV disease. Treatment, given every 21 days for a maximum of three cycles, consisted of paclitaxel by 3-hour infusion followed the next day by a fixed dose of cisplatin (75 mg/m2). The dose levels incorporate escalating paclitaxel doses, and intrapatient escalations within a given dose level are permitted if toxicity permits. At the time of this writing, dose level 4 (260, 270, and 280 mg/m2) is being evaluated; three patients from this level are evaluable. With paclitaxel doses of 200 mg/m2 and higher, granulocyte colony-stimulating factor 5 micrograms/kg/d is given (days 4 through 12). Of 18 patients evaluable for response, seven (39%) achieved a complete response and six (33%) achieved a partial response. Three patients had no change and disease progressed in two. The overall response rate is 72%. Eleven responding patients had subsequent surgery/radiotherapy or radical radiotherapy. Two pathologic complete responses were observed in patients who had achieved clinical complete responses. Alopecia, paresthesias, and arthralgias/myalgias have occurred frequently, but with one exception (a grade 3 myalgia) they have been grade 1 or 2. No dose-limiting hematologic toxicity has been seen. Paclitaxel/cisplatin is an effective first-line regimen for locoregionally advanced head and neck cancer and continued study is warranted. Results thus far suggest no dose-response effect for paclitaxel doses above 200 mg/m2.", "entity": "Cisplatin", "aliases": "Biocisplatinum Cisplatin Diamminodichloride Platinum Dichlorodiammineplatinum NSC-119875 Platidiam Platino Platinol cis Diamminedichloroplatinum cis-Diamminedichloroplatinum cis-Diamminedichloroplatinum(II) cis-Dichlorodiammineplatinum(II) cis-Platinum", "definition": "An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.\n    ", "id": "MESH:D002945"}
{"mention": "ovarian cancer", "mention_text": "Improved outcomes among patients with head and neck carcinomas require investigations of new drugs for induction therapy. Preliminary results of an Eastern Cooperative Oncology Group study of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) reported a 37% response rate in patients with head and neck cancer, and the paclitaxel/cisplatin combination has been used successfully and has significantly improved median response duration in ovarian cancer patients. We initiated a phase I/II trial to determine the response and toxicity of escalating paclitaxel doses combined with fixed-dose cisplatin with granulocyte colony-stimulating factor support in patients with untreated locally advanced inoperable head and neck carcinoma. To date, 23 men with a median age of 50 years and good performance status have entered the trial. Primary tumor sites were oropharynx, 10 patients; hypopharynx, four; larynx, two; oral cavity, three; unknown primary, two; and nasal cavity and parotid gland, one each. Of 20 patients evaluable for toxicity, four had stage III and 16 had stage IV disease. Treatment, given every 21 days for a maximum of three cycles, consisted of paclitaxel by 3-hour infusion followed the next day by a fixed dose of cisplatin (75 mg/m2). The dose levels incorporate escalating paclitaxel doses, and intrapatient escalations within a given dose level are permitted if toxicity permits. At the time of this writing, dose level 4 (260, 270, and 280 mg/m2) is being evaluated; three patients from this level are evaluable. With paclitaxel doses of 200 mg/m2 and higher, granulocyte colony-stimulating factor 5 micrograms/kg/d is given (days 4 through 12). Of 18 patients evaluable for response, seven (39%) achieved a complete response and six (33%) achieved a partial response. Three patients had no change and disease progressed in two. The overall response rate is 72%. Eleven responding patients had subsequent surgery/radiotherapy or radical radiotherapy. Two pathologic complete responses were observed in patients who had achieved clinical complete responses. Alopecia, paresthesias, and arthralgias/myalgias have occurred frequently, but with one exception (a grade 3 myalgia) they have been grade 1 or 2. No dose-limiting hematologic toxicity has been seen. Paclitaxel/cisplatin is an effective first-line regimen for locoregionally advanced head and neck cancer and continued study is warranted. Results thus far suggest no dose-response effect for paclitaxel doses above 200 mg/m2.", "entity": "Ovarian Neoplasms", "aliases": "Cancer of Ovary the Ovarian Cancers Neoplasm Neoplasms", "definition": "Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.\n    ", "id": "MESH:D010051"}
{"mention": "toxicity", "mention_text": "Improved outcomes among patients with head and neck carcinomas require investigations of new drugs for induction therapy. Preliminary results of an Eastern Cooperative Oncology Group study of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) reported a 37% response rate in patients with head and neck cancer, and the paclitaxel/cisplatin combination has been used successfully and has significantly improved median response duration in ovarian cancer patients. We initiated a phase I/II trial to determine the response and toxicity of escalating paclitaxel doses combined with fixed-dose cisplatin with granulocyte colony-stimulating factor support in patients with untreated locally advanced inoperable head and neck carcinoma. To date, 23 men with a median age of 50 years and good performance status have entered the trial. Primary tumor sites were oropharynx, 10 patients; hypopharynx, four; larynx, two; oral cavity, three; unknown primary, two; and nasal cavity and parotid gland, one each. Of 20 patients evaluable for toxicity, four had stage III and 16 had stage IV disease. Treatment, given every 21 days for a maximum of three cycles, consisted of paclitaxel by 3-hour infusion followed the next day by a fixed dose of cisplatin (75 mg/m2). The dose levels incorporate escalating paclitaxel doses, and intrapatient escalations within a given dose level are permitted if toxicity permits. At the time of this writing, dose level 4 (260, 270, and 280 mg/m2) is being evaluated; three patients from this level are evaluable. With paclitaxel doses of 200 mg/m2 and higher, granulocyte colony-stimulating factor 5 micrograms/kg/d is given (days 4 through 12). Of 18 patients evaluable for response, seven (39%) achieved a complete response and six (33%) achieved a partial response. Three patients had no change and disease progressed in two. The overall response rate is 72%. Eleven responding patients had subsequent surgery/radiotherapy or radical radiotherapy. Two pathologic complete responses were observed in patients who had achieved clinical complete responses. Alopecia, paresthesias, and arthralgias/myalgias have occurred frequently, but with one exception (a grade 3 myalgia) they have been grade 1 or 2. No dose-limiting hematologic toxicity has been seen. Paclitaxel/cisplatin is an effective first-line regimen for locoregionally advanced head and neck cancer and continued study is warranted. Results thus far suggest no dose-response effect for paclitaxel doses above 200 mg/m2.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "head and neck carcinoma", "mention_text": "Improved outcomes among patients with head and neck carcinomas require investigations of new drugs for induction therapy. Preliminary results of an Eastern Cooperative Oncology Group study of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) reported a 37% response rate in patients with head and neck cancer, and the paclitaxel/cisplatin combination has been used successfully and has significantly improved median response duration in ovarian cancer patients. We initiated a phase I/II trial to determine the response and toxicity of escalating paclitaxel doses combined with fixed-dose cisplatin with granulocyte colony-stimulating factor support in patients with untreated locally advanced inoperable head and neck carcinoma. To date, 23 men with a median age of 50 years and good performance status have entered the trial. Primary tumor sites were oropharynx, 10 patients; hypopharynx, four; larynx, two; oral cavity, three; unknown primary, two; and nasal cavity and parotid gland, one each. Of 20 patients evaluable for toxicity, four had stage III and 16 had stage IV disease. Treatment, given every 21 days for a maximum of three cycles, consisted of paclitaxel by 3-hour infusion followed the next day by a fixed dose of cisplatin (75 mg/m2). The dose levels incorporate escalating paclitaxel doses, and intrapatient escalations within a given dose level are permitted if toxicity permits. At the time of this writing, dose level 4 (260, 270, and 280 mg/m2) is being evaluated; three patients from this level are evaluable. With paclitaxel doses of 200 mg/m2 and higher, granulocyte colony-stimulating factor 5 micrograms/kg/d is given (days 4 through 12). Of 18 patients evaluable for response, seven (39%) achieved a complete response and six (33%) achieved a partial response. Three patients had no change and disease progressed in two. The overall response rate is 72%. Eleven responding patients had subsequent surgery/radiotherapy or radical radiotherapy. Two pathologic complete responses were observed in patients who had achieved clinical complete responses. Alopecia, paresthesias, and arthralgias/myalgias have occurred frequently, but with one exception (a grade 3 myalgia) they have been grade 1 or 2. No dose-limiting hematologic toxicity has been seen. Paclitaxel/cisplatin is an effective first-line regimen for locoregionally advanced head and neck cancer and continued study is warranted. Results thus far suggest no dose-response effect for paclitaxel doses above 200 mg/m2.", "entity": "Head and Neck Neoplasms", "aliases": "Cancer of Head and Neck the Neoplasms Neoplasm UADT Upper Aerodigestive Tract", "definition": "Soft tissue tumors or cancer arising from the mucosal surfaces of the LIP; oral cavity; PHARYNX; LARYNX; and cervical esophagus. Other sites included are the NOSE and PARANASAL SINUSES; SALIVARY GLANDS; THYROID GLAND and PARATHYROID GLANDS; and MELANOMA and non-melanoma skin cancers of the head and neck. (from Holland et al., Cancer Medicine, 4th ed, p1651)\n    ", "id": "MESH:D006258"}
{"mention": "tumor", "mention_text": "Improved outcomes among patients with head and neck carcinomas require investigations of new drugs for induction therapy. Preliminary results of an Eastern Cooperative Oncology Group study of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) reported a 37% response rate in patients with head and neck cancer, and the paclitaxel/cisplatin combination has been used successfully and has significantly improved median response duration in ovarian cancer patients. We initiated a phase I/II trial to determine the response and toxicity of escalating paclitaxel doses combined with fixed-dose cisplatin with granulocyte colony-stimulating factor support in patients with untreated locally advanced inoperable head and neck carcinoma. To date, 23 men with a median age of 50 years and good performance status have entered the trial. Primary tumor sites were oropharynx, 10 patients; hypopharynx, four; larynx, two; oral cavity, three; unknown primary, two; and nasal cavity and parotid gland, one each. Of 20 patients evaluable for toxicity, four had stage III and 16 had stage IV disease. Treatment, given every 21 days for a maximum of three cycles, consisted of paclitaxel by 3-hour infusion followed the next day by a fixed dose of cisplatin (75 mg/m2). The dose levels incorporate escalating paclitaxel doses, and intrapatient escalations within a given dose level are permitted if toxicity permits. At the time of this writing, dose level 4 (260, 270, and 280 mg/m2) is being evaluated; three patients from this level are evaluable. With paclitaxel doses of 200 mg/m2 and higher, granulocyte colony-stimulating factor 5 micrograms/kg/d is given (days 4 through 12). Of 18 patients evaluable for response, seven (39%) achieved a complete response and six (33%) achieved a partial response. Three patients had no change and disease progressed in two. The overall response rate is 72%. Eleven responding patients had subsequent surgery/radiotherapy or radical radiotherapy. Two pathologic complete responses were observed in patients who had achieved clinical complete responses. Alopecia, paresthesias, and arthralgias/myalgias have occurred frequently, but with one exception (a grade 3 myalgia) they have been grade 1 or 2. No dose-limiting hematologic toxicity has been seen. Paclitaxel/cisplatin is an effective first-line regimen for locoregionally advanced head and neck cancer and continued study is warranted. Results thus far suggest no dose-response effect for paclitaxel doses above 200 mg/m2.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "Alopecia", "mention_text": "Improved outcomes among patients with head and neck carcinomas require investigations of new drugs for induction therapy. Preliminary results of an Eastern Cooperative Oncology Group study of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) reported a 37% response rate in patients with head and neck cancer, and the paclitaxel/cisplatin combination has been used successfully and has significantly improved median response duration in ovarian cancer patients. We initiated a phase I/II trial to determine the response and toxicity of escalating paclitaxel doses combined with fixed-dose cisplatin with granulocyte colony-stimulating factor support in patients with untreated locally advanced inoperable head and neck carcinoma. To date, 23 men with a median age of 50 years and good performance status have entered the trial. Primary tumor sites were oropharynx, 10 patients; hypopharynx, four; larynx, two; oral cavity, three; unknown primary, two; and nasal cavity and parotid gland, one each. Of 20 patients evaluable for toxicity, four had stage III and 16 had stage IV disease. Treatment, given every 21 days for a maximum of three cycles, consisted of paclitaxel by 3-hour infusion followed the next day by a fixed dose of cisplatin (75 mg/m2). The dose levels incorporate escalating paclitaxel doses, and intrapatient escalations within a given dose level are permitted if toxicity permits. At the time of this writing, dose level 4 (260, 270, and 280 mg/m2) is being evaluated; three patients from this level are evaluable. With paclitaxel doses of 200 mg/m2 and higher, granulocyte colony-stimulating factor 5 micrograms/kg/d is given (days 4 through 12). Of 18 patients evaluable for response, seven (39%) achieved a complete response and six (33%) achieved a partial response. Three patients had no change and disease progressed in two. The overall response rate is 72%. Eleven responding patients had subsequent surgery/radiotherapy or radical radiotherapy. Two pathologic complete responses were observed in patients who had achieved clinical complete responses. Alopecia, paresthesias, and arthralgias/myalgias have occurred frequently, but with one exception (a grade 3 myalgia) they have been grade 1 or 2. No dose-limiting hematologic toxicity has been seen. Paclitaxel/cisplatin is an effective first-line regimen for locoregionally advanced head and neck cancer and continued study is warranted. Results thus far suggest no dose-response effect for paclitaxel doses above 200 mg/m2.", "entity": "Alopecia", "aliases": "Alopecia Cicatrisata Cicatrisatas Androgenetic 1 Male Pattern Androgenic Baldness Female Pseudopelade", "definition": "Absence of hair from areas where it is normally present.\n    ", "id": "MESH:D000505"}
{"mention": "paresthesias", "mention_text": "Improved outcomes among patients with head and neck carcinomas require investigations of new drugs for induction therapy. Preliminary results of an Eastern Cooperative Oncology Group study of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) reported a 37% response rate in patients with head and neck cancer, and the paclitaxel/cisplatin combination has been used successfully and has significantly improved median response duration in ovarian cancer patients. We initiated a phase I/II trial to determine the response and toxicity of escalating paclitaxel doses combined with fixed-dose cisplatin with granulocyte colony-stimulating factor support in patients with untreated locally advanced inoperable head and neck carcinoma. To date, 23 men with a median age of 50 years and good performance status have entered the trial. Primary tumor sites were oropharynx, 10 patients; hypopharynx, four; larynx, two; oral cavity, three; unknown primary, two; and nasal cavity and parotid gland, one each. Of 20 patients evaluable for toxicity, four had stage III and 16 had stage IV disease. Treatment, given every 21 days for a maximum of three cycles, consisted of paclitaxel by 3-hour infusion followed the next day by a fixed dose of cisplatin (75 mg/m2). The dose levels incorporate escalating paclitaxel doses, and intrapatient escalations within a given dose level are permitted if toxicity permits. At the time of this writing, dose level 4 (260, 270, and 280 mg/m2) is being evaluated; three patients from this level are evaluable. With paclitaxel doses of 200 mg/m2 and higher, granulocyte colony-stimulating factor 5 micrograms/kg/d is given (days 4 through 12). Of 18 patients evaluable for response, seven (39%) achieved a complete response and six (33%) achieved a partial response. Three patients had no change and disease progressed in two. The overall response rate is 72%. Eleven responding patients had subsequent surgery/radiotherapy or radical radiotherapy. Two pathologic complete responses were observed in patients who had achieved clinical complete responses. Alopecia, paresthesias, and arthralgias/myalgias have occurred frequently, but with one exception (a grade 3 myalgia) they have been grade 1 or 2. No dose-limiting hematologic toxicity has been seen. Paclitaxel/cisplatin is an effective first-line regimen for locoregionally advanced head and neck cancer and continued study is warranted. Results thus far suggest no dose-response effect for paclitaxel doses above 200 mg/m2.", "entity": "Paresthesia", "aliases": "Distal Paresthesia Paresthesias Dysesthesia Dysesthesias Formication Formications Painful", "definition": "Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation.\n    ", "id": "MESH:D010292"}
{"mention": "arthralgias", "mention_text": "Improved outcomes among patients with head and neck carcinomas require investigations of new drugs for induction therapy. Preliminary results of an Eastern Cooperative Oncology Group study of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) reported a 37% response rate in patients with head and neck cancer, and the paclitaxel/cisplatin combination has been used successfully and has significantly improved median response duration in ovarian cancer patients. We initiated a phase I/II trial to determine the response and toxicity of escalating paclitaxel doses combined with fixed-dose cisplatin with granulocyte colony-stimulating factor support in patients with untreated locally advanced inoperable head and neck carcinoma. To date, 23 men with a median age of 50 years and good performance status have entered the trial. Primary tumor sites were oropharynx, 10 patients; hypopharynx, four; larynx, two; oral cavity, three; unknown primary, two; and nasal cavity and parotid gland, one each. Of 20 patients evaluable for toxicity, four had stage III and 16 had stage IV disease. Treatment, given every 21 days for a maximum of three cycles, consisted of paclitaxel by 3-hour infusion followed the next day by a fixed dose of cisplatin (75 mg/m2). The dose levels incorporate escalating paclitaxel doses, and intrapatient escalations within a given dose level are permitted if toxicity permits. At the time of this writing, dose level 4 (260, 270, and 280 mg/m2) is being evaluated; three patients from this level are evaluable. With paclitaxel doses of 200 mg/m2 and higher, granulocyte colony-stimulating factor 5 micrograms/kg/d is given (days 4 through 12). Of 18 patients evaluable for response, seven (39%) achieved a complete response and six (33%) achieved a partial response. Three patients had no change and disease progressed in two. The overall response rate is 72%. Eleven responding patients had subsequent surgery/radiotherapy or radical radiotherapy. Two pathologic complete responses were observed in patients who had achieved clinical complete responses. Alopecia, paresthesias, and arthralgias/myalgias have occurred frequently, but with one exception (a grade 3 myalgia) they have been grade 1 or 2. No dose-limiting hematologic toxicity has been seen. Paclitaxel/cisplatin is an effective first-line regimen for locoregionally advanced head and neck cancer and continued study is warranted. Results thus far suggest no dose-response effect for paclitaxel doses above 200 mg/m2.", "entity": "Arthralgia", "aliases": "Arthralgia Arthralgias Joint Pain Pains Polyarthralgia Polyarthralgias", "definition": "Pain in the joint.\n    ", "id": "MESH:D018771"}
{"mention": "myalgias", "mention_text": "Improved outcomes among patients with head and neck carcinomas require investigations of new drugs for induction therapy. Preliminary results of an Eastern Cooperative Oncology Group study of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) reported a 37% response rate in patients with head and neck cancer, and the paclitaxel/cisplatin combination has been used successfully and has significantly improved median response duration in ovarian cancer patients. We initiated a phase I/II trial to determine the response and toxicity of escalating paclitaxel doses combined with fixed-dose cisplatin with granulocyte colony-stimulating factor support in patients with untreated locally advanced inoperable head and neck carcinoma. To date, 23 men with a median age of 50 years and good performance status have entered the trial. Primary tumor sites were oropharynx, 10 patients; hypopharynx, four; larynx, two; oral cavity, three; unknown primary, two; and nasal cavity and parotid gland, one each. Of 20 patients evaluable for toxicity, four had stage III and 16 had stage IV disease. Treatment, given every 21 days for a maximum of three cycles, consisted of paclitaxel by 3-hour infusion followed the next day by a fixed dose of cisplatin (75 mg/m2). The dose levels incorporate escalating paclitaxel doses, and intrapatient escalations within a given dose level are permitted if toxicity permits. At the time of this writing, dose level 4 (260, 270, and 280 mg/m2) is being evaluated; three patients from this level are evaluable. With paclitaxel doses of 200 mg/m2 and higher, granulocyte colony-stimulating factor 5 micrograms/kg/d is given (days 4 through 12). Of 18 patients evaluable for response, seven (39%) achieved a complete response and six (33%) achieved a partial response. Three patients had no change and disease progressed in two. The overall response rate is 72%. Eleven responding patients had subsequent surgery/radiotherapy or radical radiotherapy. Two pathologic complete responses were observed in patients who had achieved clinical complete responses. Alopecia, paresthesias, and arthralgias/myalgias have occurred frequently, but with one exception (a grade 3 myalgia) they have been grade 1 or 2. No dose-limiting hematologic toxicity has been seen. Paclitaxel/cisplatin is an effective first-line regimen for locoregionally advanced head and neck cancer and continued study is warranted. Results thus far suggest no dose-response effect for paclitaxel doses above 200 mg/m2.", "entity": "Myalgia", "aliases": "Muscle Pain Soreness Sorenesses Tenderness Myalgia Pains", "definition": "Painful sensation in the muscles.\n    ", "id": "MESH:D063806"}
{"mention": "myalgia", "mention_text": "Improved outcomes among patients with head and neck carcinomas require investigations of new drugs for induction therapy. Preliminary results of an Eastern Cooperative Oncology Group study of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) reported a 37% response rate in patients with head and neck cancer, and the paclitaxel/cisplatin combination has been used successfully and has significantly improved median response duration in ovarian cancer patients. We initiated a phase I/II trial to determine the response and toxicity of escalating paclitaxel doses combined with fixed-dose cisplatin with granulocyte colony-stimulating factor support in patients with untreated locally advanced inoperable head and neck carcinoma. To date, 23 men with a median age of 50 years and good performance status have entered the trial. Primary tumor sites were oropharynx, 10 patients; hypopharynx, four; larynx, two; oral cavity, three; unknown primary, two; and nasal cavity and parotid gland, one each. Of 20 patients evaluable for toxicity, four had stage III and 16 had stage IV disease. Treatment, given every 21 days for a maximum of three cycles, consisted of paclitaxel by 3-hour infusion followed the next day by a fixed dose of cisplatin (75 mg/m2). The dose levels incorporate escalating paclitaxel doses, and intrapatient escalations within a given dose level are permitted if toxicity permits. At the time of this writing, dose level 4 (260, 270, and 280 mg/m2) is being evaluated; three patients from this level are evaluable. With paclitaxel doses of 200 mg/m2 and higher, granulocyte colony-stimulating factor 5 micrograms/kg/d is given (days 4 through 12). Of 18 patients evaluable for response, seven (39%) achieved a complete response and six (33%) achieved a partial response. Three patients had no change and disease progressed in two. The overall response rate is 72%. Eleven responding patients had subsequent surgery/radiotherapy or radical radiotherapy. Two pathologic complete responses were observed in patients who had achieved clinical complete responses. Alopecia, paresthesias, and arthralgias/myalgias have occurred frequently, but with one exception (a grade 3 myalgia) they have been grade 1 or 2. No dose-limiting hematologic toxicity has been seen. Paclitaxel/cisplatin is an effective first-line regimen for locoregionally advanced head and neck cancer and continued study is warranted. Results thus far suggest no dose-response effect for paclitaxel doses above 200 mg/m2.", "entity": "Myalgia", "aliases": "Muscle Pain Soreness Sorenesses Tenderness Myalgia Pains", "definition": "Painful sensation in the muscles.\n    ", "id": "MESH:D063806"}
{"mention": "Paclitaxel", "mention_text": "Improved outcomes among patients with head and neck carcinomas require investigations of new drugs for induction therapy. Preliminary results of an Eastern Cooperative Oncology Group study of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) reported a 37% response rate in patients with head and neck cancer, and the paclitaxel/cisplatin combination has been used successfully and has significantly improved median response duration in ovarian cancer patients. We initiated a phase I/II trial to determine the response and toxicity of escalating paclitaxel doses combined with fixed-dose cisplatin with granulocyte colony-stimulating factor support in patients with untreated locally advanced inoperable head and neck carcinoma. To date, 23 men with a median age of 50 years and good performance status have entered the trial. Primary tumor sites were oropharynx, 10 patients; hypopharynx, four; larynx, two; oral cavity, three; unknown primary, two; and nasal cavity and parotid gland, one each. Of 20 patients evaluable for toxicity, four had stage III and 16 had stage IV disease. Treatment, given every 21 days for a maximum of three cycles, consisted of paclitaxel by 3-hour infusion followed the next day by a fixed dose of cisplatin (75 mg/m2). The dose levels incorporate escalating paclitaxel doses, and intrapatient escalations within a given dose level are permitted if toxicity permits. At the time of this writing, dose level 4 (260, 270, and 280 mg/m2) is being evaluated; three patients from this level are evaluable. With paclitaxel doses of 200 mg/m2 and higher, granulocyte colony-stimulating factor 5 micrograms/kg/d is given (days 4 through 12). Of 18 patients evaluable for response, seven (39%) achieved a complete response and six (33%) achieved a partial response. Three patients had no change and disease progressed in two. The overall response rate is 72%. Eleven responding patients had subsequent surgery/radiotherapy or radical radiotherapy. Two pathologic complete responses were observed in patients who had achieved clinical complete responses. Alopecia, paresthesias, and arthralgias/myalgias have occurred frequently, but with one exception (a grade 3 myalgia) they have been grade 1 or 2. No dose-limiting hematologic toxicity has been seen. Paclitaxel/cisplatin is an effective first-line regimen for locoregionally advanced head and neck cancer and continued study is warranted. Results thus far suggest no dose-response effect for paclitaxel doses above 200 mg/m2.", "entity": "Paclitaxel", "aliases": "7 epi Taxol 7-epi-Taxol Anzatax Bris Bristol-Myers Brand of Paclitaxel Squibb Bull Ivax Lemery NSC 125973 NSC-125973 NSC125973 Onxol (4 alpha)-Isomer Paxene Praxel A", "definition": "A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.\n    ", "id": "MESH:D017239"}
{"mention": "4'-0-tetrahydropyranyladriamycin", "mention_text": "A phase I study of 4'-0-tetrahydropyranyladriamycin. Clinical pharmacology and pharmacokinetics.", "entity": "pirarubicin", "aliases": "4'-O-tetrahydropyranyladriamycin 4'-O-tetrahydropyranyldoxorubicin 4'-O-tetrapyranyldoxorubicin Aventis brand of pirarubicin THP-ADM THP-DOX THP-adriamycin THP-doxorubicin Theprubicin Théprubicine hydrochloride thepirubicin therarubicin", "definition": "", "id": "MESH:C027260"}
{"mention": "4'-0-tetrahydropyranyladriamycin", "mention_text": "A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks.", "entity": "pirarubicin", "aliases": "4'-O-tetrahydropyranyladriamycin 4'-O-tetrahydropyranyldoxorubicin 4'-O-tetrapyranyldoxorubicin Aventis brand of pirarubicin THP-ADM THP-DOX THP-adriamycin THP-doxorubicin Theprubicin Théprubicine hydrochloride thepirubicin therarubicin", "definition": "", "id": "MESH:C027260"}
{"mention": "Pirarubicin", "mention_text": "A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks.", "entity": "pirarubicin", "aliases": "4'-O-tetrahydropyranyladriamycin 4'-O-tetrahydropyranyldoxorubicin 4'-O-tetrapyranyldoxorubicin Aventis brand of pirarubicin THP-ADM THP-DOX THP-adriamycin THP-doxorubicin Theprubicin Théprubicine hydrochloride thepirubicin therarubicin", "definition": "", "id": "MESH:C027260"}
{"mention": "tumors", "mention_text": "A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "hepatic dysfunction", "mention_text": "A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks.", "entity": "Liver Diseases", "aliases": "Disease Liver Diseases Dysfunction Dysfunctions", "definition": "Pathological processes of the LIVER.\n    ", "id": "MESH:D008107"}
{"mention": "granulocytopenia", "mention_text": "A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks.", "entity": "Agranulocytosis", "aliases": "Agranulocytoses Agranulocytosis Granulocytopenia Granulocytopenias", "definition": "A decrease in the number of GRANULOCYTES; (BASOPHILS; EOSINOPHILS; and NEUTROPHILS).\n    ", "id": "MESH:D000380"}
{"mention": "thrombocytopenia", "mention_text": "A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks.", "entity": "Thrombocytopenia", "aliases": "Thrombocytopenia Thrombocytopenias Thrombopenia Thrombopenias", "definition": "A subnormal level of BLOOD PLATELETS.\n    ", "id": "MESH:D013921"}
{"mention": "anemia", "mention_text": "A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks.", "entity": "Anemia", "aliases": "Anemia Anemias", "definition": "A reduction in the number of circulating ERYTHROCYTES or in the quantity of HEMOGLOBIN.\n    ", "id": "MESH:D000740"}
{"mention": "nausea", "mention_text": "A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks.", "entity": "Nausea", "aliases": "Nausea", "definition": "An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.\n    ", "id": "MESH:D009325"}
{"mention": "alopecia", "mention_text": "A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks.", "entity": "Alopecia", "aliases": "Alopecia Cicatrisata Cicatrisatas Androgenetic 1 Male Pattern Androgenic Baldness Female Pseudopelade", "definition": "Absence of hair from areas where it is normally present.\n    ", "id": "MESH:D000505"}
{"mention": "phlebitis", "mention_text": "A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks.", "entity": "Phlebitis", "aliases": "Periphlebitides Periphlebitis Phlebitides Phlebitis", "definition": "Inflammation of a vein, often a vein in the leg. Phlebitis associated with a blood clot is called (THROMBOPHLEBITIS).\n    ", "id": "MESH:D010689"}
{"mention": "mucositis", "mention_text": "A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks.", "entity": "Mucositis", "aliases": "Mucositides Mucositis", "definition": "An INFLAMMATION of the MUCOSA with burning or tingling sensation. It is characterized by atrophy of the squamous EPITHELIUM, vascular damage, inflammatory infiltration, and ulceration. It usually occurs at the mucous lining of the MOUTH, the GASTROINTESTINAL TRACT or the airway due to chemical irritations, CHEMOTHERAPY, or radiation therapy (RADIOTHERAPY).\n    ", "id": "MESH:D052016"}
{"mention": "Myelosuppression", "mention_text": "A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks.", "entity": "Bone Marrow Diseases", "aliases": "Bone Marrow Disease Diseases", "definition": "", "id": "MESH:D001855"}
{"mention": "Adriamycinol", "mention_text": "A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks.", "entity": "adriamycinol", "aliases": "13-dihydrodoxorubicin adriamycinol hydrochloride 8S-(8alpha,8R*,10alpha)-isomer doxorubicinol", "definition": "", "id": "MESH:C010013"}
{"mention": "doxorubicin", "mention_text": "A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "adriamycinone", "mention_text": "A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks.", "entity": "adriamycin aglycone", "aliases": "4'-deoxydoxorubicin 7-deoxyaglycone 4-DOX-DONE adriamycin aglycone adriamycinon adriamycinone doxorubicinone", "definition": "", "id": "MESH:C010012"}
{"mention": "tetrahydropyranyladriamycinol", "mention_text": "A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks.", "entity": "pirarubicin", "aliases": "4'-O-tetrahydropyranyladriamycin 4'-O-tetrahydropyranyldoxorubicin 4'-O-tetrapyranyldoxorubicin Aventis brand of pirarubicin THP-ADM THP-DOX THP-adriamycin THP-doxorubicin Theprubicin Théprubicine hydrochloride thepirubicin therarubicin", "definition": "", "id": "MESH:C027260"}
{"mention": "mesothelioma", "mention_text": "A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks.", "entity": "Mesothelioma", "aliases": "Mesothelioma Mesotheliomas", "definition": "A tumor derived from mesothelial tissue (peritoneum, pleura, pericardium). It appears as broad sheets of cells, with some regions containing spindle-shaped, sarcoma-like cells and other regions showing adenomatous patterns. Pleural mesotheliomas have been linked to exposure to asbestos. (Dorland, 27th ed)\n    ", "id": "MESH:D008654"}
{"mention": "leiomyosarcoma", "mention_text": "A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks.", "entity": "Leiomyosarcoma", "aliases": "Epithelioid Leiomyosarcoma Leiomyosarcomas Myxoid", "definition": "A sarcoma containing large spindle cells of smooth muscle. Although it rarely occurs in soft tissue, it is common in the viscera. It is the most common soft tissue sarcoma of the gastrointestinal tract and uterus. The median age of patients is 60 years. (From Dorland, 27th ed; Holland et al., Cancer Medicine, 3d ed, p1865)\n    ", "id": "MESH:D007890"}
{"mention": "basal cell carcinoma", "mention_text": "A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks.", "entity": "Carcinoma, Basal Cell", "aliases": "Basal Cell Carcinoma Carcinomas Epithelioma Epitheliomas Pigmented Rodent Ulcer Ulcers", "definition": "A malignant skin neoplasm that seldom metastasizes but has potentialities for local invasion and destruction. Clinically it is divided into types: nodular, cicatricial, morphaic, and erythematoid (pagetoid). They develop on hair-bearing skin, most commonly on sun-exposed areas. Approximately 85% are found on the head and neck area and the remaining 15% on the trunk and limbs. (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1471)\n    ", "id": "MESH:D002280"}
{"mention": "gamma-hexachlorocyclohexane", "mention_text": "Differential effects of gamma-hexachlorocyclohexane (lindane) on pharmacologically-induced seizures.", "entity": "Lindane", "aliases": "BHC Insecticide Benzene Hexachloride Chinoin Brand of Lindane Delitex Gamma 666 Gamma-666 Gamma666 Gammexane Hexachlorane gamma-Benzene Hexachlorocyclohexane Infectopharm Jacutin Kwell PMS PMS-Lindane PMSLindane Pharmascience Scabecid Scabene Scabisan Stiefel Tetocid gamma gamma-Hexachlorocyclohexane", "definition": "An organochlorine insecticide that has been used as a pediculicide and a scabicide. It has been shown to cause cancer.\n    ", "id": "MESH:D001556"}
{"mention": "lindane", "mention_text": "Differential effects of gamma-hexachlorocyclohexane (lindane) on pharmacologically-induced seizures.", "entity": "Lindane", "aliases": "BHC Insecticide Benzene Hexachloride Chinoin Brand of Lindane Delitex Gamma 666 Gamma-666 Gamma666 Gammexane Hexachlorane gamma-Benzene Hexachlorocyclohexane Infectopharm Jacutin Kwell PMS PMS-Lindane PMSLindane Pharmascience Scabecid Scabene Scabisan Stiefel Tetocid gamma gamma-Hexachlorocyclohexane", "definition": "An organochlorine insecticide that has been used as a pediculicide and a scabicide. It has been shown to cause cancer.\n    ", "id": "MESH:D001556"}
{"mention": "seizures", "mention_text": "Differential effects of gamma-hexachlorocyclohexane (lindane) on pharmacologically-induced seizures.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "Gamma-hexachlorocyclohexane", "mention_text": "Gamma-hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to decrease seizure threshold to pentylenetrazol (PTZ) 3 h after exposure to gamma-HCH and conversely increase threshold to PTZ-induced seizures 24 h after exposure to gamma-HCH (Vohland et al. 1981). In this study, the severity of response to other seizure-inducing agents was tested in mice 1 and 24 h after intraperitoneal administration of 80 mg/kg gamma-HCH. One hour after the administration of gamma-HCH, the activity of seizure-inducing agents was increased, regardless of their mechanism, while 24 h after gamma-HCH a differential response was observed. Seizure activity due to PTZ and picrotoxin (PTX) was significantly decreased; however, seizure activity due to 3-mercaptopropionic acid (MPA), bicuculline (BCC), methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate (DMCM), or strychnine (STR) was not different from control. In vitro, gamma-HCH, pentylenetetrazol and picrotoxin were shown to inhibit 3H-TBOB binding in mouse whole brain, with IC50 values of 4.6, 404 and 9.4 microM, respectively. MPA, BCC, DMCM, and STR showed no inhibition of 3H-TBOB (t-butyl bicyclo-orthobenzoate) binding at concentrations of 100 micron. The pharmacological challenge data suggest that tolerance may occur to seizure activity induced by PTZ and PTX 24 h after gamma-HCH, since the response to only these two seizure-inducing agents is decreased. The in vitro data suggest that the site responsible for the decrease in seizure activity 24 h after gamma-HCH may be the GABA-A receptor-linked chloride channel.", "entity": "Lindane", "aliases": "BHC Insecticide Benzene Hexachloride Chinoin Brand of Lindane Delitex Gamma 666 Gamma-666 Gamma666 Gammexane Hexachlorane gamma-Benzene Hexachlorocyclohexane Infectopharm Jacutin Kwell PMS PMS-Lindane PMSLindane Pharmascience Scabecid Scabene Scabisan Stiefel Tetocid gamma gamma-Hexachlorocyclohexane", "definition": "An organochlorine insecticide that has been used as a pediculicide and a scabicide. It has been shown to cause cancer.\n    ", "id": "MESH:D001556"}
{"mention": "gamma-HCH", "mention_text": "Gamma-hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to decrease seizure threshold to pentylenetrazol (PTZ) 3 h after exposure to gamma-HCH and conversely increase threshold to PTZ-induced seizures 24 h after exposure to gamma-HCH (Vohland et al. 1981). In this study, the severity of response to other seizure-inducing agents was tested in mice 1 and 24 h after intraperitoneal administration of 80 mg/kg gamma-HCH. One hour after the administration of gamma-HCH, the activity of seizure-inducing agents was increased, regardless of their mechanism, while 24 h after gamma-HCH a differential response was observed. Seizure activity due to PTZ and picrotoxin (PTX) was significantly decreased; however, seizure activity due to 3-mercaptopropionic acid (MPA), bicuculline (BCC), methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate (DMCM), or strychnine (STR) was not different from control. In vitro, gamma-HCH, pentylenetetrazol and picrotoxin were shown to inhibit 3H-TBOB binding in mouse whole brain, with IC50 values of 4.6, 404 and 9.4 microM, respectively. MPA, BCC, DMCM, and STR showed no inhibition of 3H-TBOB (t-butyl bicyclo-orthobenzoate) binding at concentrations of 100 micron. The pharmacological challenge data suggest that tolerance may occur to seizure activity induced by PTZ and PTX 24 h after gamma-HCH, since the response to only these two seizure-inducing agents is decreased. The in vitro data suggest that the site responsible for the decrease in seizure activity 24 h after gamma-HCH may be the GABA-A receptor-linked chloride channel.", "entity": "Lindane", "aliases": "BHC Insecticide Benzene Hexachloride Chinoin Brand of Lindane Delitex Gamma 666 Gamma-666 Gamma666 Gammexane Hexachlorane gamma-Benzene Hexachlorocyclohexane Infectopharm Jacutin Kwell PMS PMS-Lindane PMSLindane Pharmascience Scabecid Scabene Scabisan Stiefel Tetocid gamma gamma-Hexachlorocyclohexane", "definition": "An organochlorine insecticide that has been used as a pediculicide and a scabicide. It has been shown to cause cancer.\n    ", "id": "MESH:D001556"}
{"mention": "lindane", "mention_text": "Gamma-hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to decrease seizure threshold to pentylenetrazol (PTZ) 3 h after exposure to gamma-HCH and conversely increase threshold to PTZ-induced seizures 24 h after exposure to gamma-HCH (Vohland et al. 1981). In this study, the severity of response to other seizure-inducing agents was tested in mice 1 and 24 h after intraperitoneal administration of 80 mg/kg gamma-HCH. One hour after the administration of gamma-HCH, the activity of seizure-inducing agents was increased, regardless of their mechanism, while 24 h after gamma-HCH a differential response was observed. Seizure activity due to PTZ and picrotoxin (PTX) was significantly decreased; however, seizure activity due to 3-mercaptopropionic acid (MPA), bicuculline (BCC), methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate (DMCM), or strychnine (STR) was not different from control. In vitro, gamma-HCH, pentylenetetrazol and picrotoxin were shown to inhibit 3H-TBOB binding in mouse whole brain, with IC50 values of 4.6, 404 and 9.4 microM, respectively. MPA, BCC, DMCM, and STR showed no inhibition of 3H-TBOB (t-butyl bicyclo-orthobenzoate) binding at concentrations of 100 micron. The pharmacological challenge data suggest that tolerance may occur to seizure activity induced by PTZ and PTX 24 h after gamma-HCH, since the response to only these two seizure-inducing agents is decreased. The in vitro data suggest that the site responsible for the decrease in seizure activity 24 h after gamma-HCH may be the GABA-A receptor-linked chloride channel.", "entity": "Lindane", "aliases": "BHC Insecticide Benzene Hexachloride Chinoin Brand of Lindane Delitex Gamma 666 Gamma-666 Gamma666 Gammexane Hexachlorane gamma-Benzene Hexachlorocyclohexane Infectopharm Jacutin Kwell PMS PMS-Lindane PMSLindane Pharmascience Scabecid Scabene Scabisan Stiefel Tetocid gamma gamma-Hexachlorocyclohexane", "definition": "An organochlorine insecticide that has been used as a pediculicide and a scabicide. It has been shown to cause cancer.\n    ", "id": "MESH:D001556"}
{"mention": "seizure", "mention_text": "Gamma-hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to decrease seizure threshold to pentylenetrazol (PTZ) 3 h after exposure to gamma-HCH and conversely increase threshold to PTZ-induced seizures 24 h after exposure to gamma-HCH (Vohland et al. 1981). In this study, the severity of response to other seizure-inducing agents was tested in mice 1 and 24 h after intraperitoneal administration of 80 mg/kg gamma-HCH. One hour after the administration of gamma-HCH, the activity of seizure-inducing agents was increased, regardless of their mechanism, while 24 h after gamma-HCH a differential response was observed. Seizure activity due to PTZ and picrotoxin (PTX) was significantly decreased; however, seizure activity due to 3-mercaptopropionic acid (MPA), bicuculline (BCC), methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate (DMCM), or strychnine (STR) was not different from control. In vitro, gamma-HCH, pentylenetetrazol and picrotoxin were shown to inhibit 3H-TBOB binding in mouse whole brain, with IC50 values of 4.6, 404 and 9.4 microM, respectively. MPA, BCC, DMCM, and STR showed no inhibition of 3H-TBOB (t-butyl bicyclo-orthobenzoate) binding at concentrations of 100 micron. The pharmacological challenge data suggest that tolerance may occur to seizure activity induced by PTZ and PTX 24 h after gamma-HCH, since the response to only these two seizure-inducing agents is decreased. The in vitro data suggest that the site responsible for the decrease in seizure activity 24 h after gamma-HCH may be the GABA-A receptor-linked chloride channel.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "PTZ", "mention_text": "Gamma-hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to decrease seizure threshold to pentylenetrazol (PTZ) 3 h after exposure to gamma-HCH and conversely increase threshold to PTZ-induced seizures 24 h after exposure to gamma-HCH (Vohland et al. 1981). In this study, the severity of response to other seizure-inducing agents was tested in mice 1 and 24 h after intraperitoneal administration of 80 mg/kg gamma-HCH. One hour after the administration of gamma-HCH, the activity of seizure-inducing agents was increased, regardless of their mechanism, while 24 h after gamma-HCH a differential response was observed. Seizure activity due to PTZ and picrotoxin (PTX) was significantly decreased; however, seizure activity due to 3-mercaptopropionic acid (MPA), bicuculline (BCC), methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate (DMCM), or strychnine (STR) was not different from control. In vitro, gamma-HCH, pentylenetetrazol and picrotoxin were shown to inhibit 3H-TBOB binding in mouse whole brain, with IC50 values of 4.6, 404 and 9.4 microM, respectively. MPA, BCC, DMCM, and STR showed no inhibition of 3H-TBOB (t-butyl bicyclo-orthobenzoate) binding at concentrations of 100 micron. The pharmacological challenge data suggest that tolerance may occur to seizure activity induced by PTZ and PTX 24 h after gamma-HCH, since the response to only these two seizure-inducing agents is decreased. The in vitro data suggest that the site responsible for the decrease in seizure activity 24 h after gamma-HCH may be the GABA-A receptor-linked chloride channel.", "entity": "Pentylenetetrazole", "aliases": "Cardiazol Corasol Corazol Corazole Korazol Korazole Leptazole Metrazol Metrazole Pentamethylenetetrazole Pentazol Pentetrazole Pentylenetetrazol Pentylenetetrazole", "definition": "A pharmaceutical agent that displays activity as a central nervous system and respiratory stimulant. It is considered a non-competitive GAMMA-AMINOBUTYRIC ACID antagonist. Pentylenetetrazole has been used experimentally to study seizure phenomenon and to identify pharmaceuticals that may control seizure susceptibility.\n    ", "id": "MESH:D010433"}
{"mention": "seizures", "mention_text": "Gamma-hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to decrease seizure threshold to pentylenetrazol (PTZ) 3 h after exposure to gamma-HCH and conversely increase threshold to PTZ-induced seizures 24 h after exposure to gamma-HCH (Vohland et al. 1981). In this study, the severity of response to other seizure-inducing agents was tested in mice 1 and 24 h after intraperitoneal administration of 80 mg/kg gamma-HCH. One hour after the administration of gamma-HCH, the activity of seizure-inducing agents was increased, regardless of their mechanism, while 24 h after gamma-HCH a differential response was observed. Seizure activity due to PTZ and picrotoxin (PTX) was significantly decreased; however, seizure activity due to 3-mercaptopropionic acid (MPA), bicuculline (BCC), methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate (DMCM), or strychnine (STR) was not different from control. In vitro, gamma-HCH, pentylenetetrazol and picrotoxin were shown to inhibit 3H-TBOB binding in mouse whole brain, with IC50 values of 4.6, 404 and 9.4 microM, respectively. MPA, BCC, DMCM, and STR showed no inhibition of 3H-TBOB (t-butyl bicyclo-orthobenzoate) binding at concentrations of 100 micron. The pharmacological challenge data suggest that tolerance may occur to seizure activity induced by PTZ and PTX 24 h after gamma-HCH, since the response to only these two seizure-inducing agents is decreased. The in vitro data suggest that the site responsible for the decrease in seizure activity 24 h after gamma-HCH may be the GABA-A receptor-linked chloride channel.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "Seizure", "mention_text": "Gamma-hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to decrease seizure threshold to pentylenetrazol (PTZ) 3 h after exposure to gamma-HCH and conversely increase threshold to PTZ-induced seizures 24 h after exposure to gamma-HCH (Vohland et al. 1981). In this study, the severity of response to other seizure-inducing agents was tested in mice 1 and 24 h after intraperitoneal administration of 80 mg/kg gamma-HCH. One hour after the administration of gamma-HCH, the activity of seizure-inducing agents was increased, regardless of their mechanism, while 24 h after gamma-HCH a differential response was observed. Seizure activity due to PTZ and picrotoxin (PTX) was significantly decreased; however, seizure activity due to 3-mercaptopropionic acid (MPA), bicuculline (BCC), methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate (DMCM), or strychnine (STR) was not different from control. In vitro, gamma-HCH, pentylenetetrazol and picrotoxin were shown to inhibit 3H-TBOB binding in mouse whole brain, with IC50 values of 4.6, 404 and 9.4 microM, respectively. MPA, BCC, DMCM, and STR showed no inhibition of 3H-TBOB (t-butyl bicyclo-orthobenzoate) binding at concentrations of 100 micron. The pharmacological challenge data suggest that tolerance may occur to seizure activity induced by PTZ and PTX 24 h after gamma-HCH, since the response to only these two seizure-inducing agents is decreased. The in vitro data suggest that the site responsible for the decrease in seizure activity 24 h after gamma-HCH may be the GABA-A receptor-linked chloride channel.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "picrotoxin", "mention_text": "Gamma-hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to decrease seizure threshold to pentylenetrazol (PTZ) 3 h after exposure to gamma-HCH and conversely increase threshold to PTZ-induced seizures 24 h after exposure to gamma-HCH (Vohland et al. 1981). In this study, the severity of response to other seizure-inducing agents was tested in mice 1 and 24 h after intraperitoneal administration of 80 mg/kg gamma-HCH. One hour after the administration of gamma-HCH, the activity of seizure-inducing agents was increased, regardless of their mechanism, while 24 h after gamma-HCH a differential response was observed. Seizure activity due to PTZ and picrotoxin (PTX) was significantly decreased; however, seizure activity due to 3-mercaptopropionic acid (MPA), bicuculline (BCC), methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate (DMCM), or strychnine (STR) was not different from control. In vitro, gamma-HCH, pentylenetetrazol and picrotoxin were shown to inhibit 3H-TBOB binding in mouse whole brain, with IC50 values of 4.6, 404 and 9.4 microM, respectively. MPA, BCC, DMCM, and STR showed no inhibition of 3H-TBOB (t-butyl bicyclo-orthobenzoate) binding at concentrations of 100 micron. The pharmacological challenge data suggest that tolerance may occur to seizure activity induced by PTZ and PTX 24 h after gamma-HCH, since the response to only these two seizure-inducing agents is decreased. The in vitro data suggest that the site responsible for the decrease in seizure activity 24 h after gamma-HCH may be the GABA-A receptor-linked chloride channel.", "entity": "Picrotoxin", "aliases": "Picrotoxin", "definition": "A noncompetitive antagonist at GABA-A receptors and thus a convulsant. Picrotoxin blocks the GAMMA-AMINOBUTYRIC ACID-activated chloride ionophore. Although it is most often used as a research tool, it has been used as a CNS stimulant and an antidote in poisoning by CNS depressants, especially the barbiturates.\n    ", "id": "MESH:D010852"}
{"mention": "PTX", "mention_text": "Gamma-hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to decrease seizure threshold to pentylenetrazol (PTZ) 3 h after exposure to gamma-HCH and conversely increase threshold to PTZ-induced seizures 24 h after exposure to gamma-HCH (Vohland et al. 1981). In this study, the severity of response to other seizure-inducing agents was tested in mice 1 and 24 h after intraperitoneal administration of 80 mg/kg gamma-HCH. One hour after the administration of gamma-HCH, the activity of seizure-inducing agents was increased, regardless of their mechanism, while 24 h after gamma-HCH a differential response was observed. Seizure activity due to PTZ and picrotoxin (PTX) was significantly decreased; however, seizure activity due to 3-mercaptopropionic acid (MPA), bicuculline (BCC), methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate (DMCM), or strychnine (STR) was not different from control. In vitro, gamma-HCH, pentylenetetrazol and picrotoxin were shown to inhibit 3H-TBOB binding in mouse whole brain, with IC50 values of 4.6, 404 and 9.4 microM, respectively. MPA, BCC, DMCM, and STR showed no inhibition of 3H-TBOB (t-butyl bicyclo-orthobenzoate) binding at concentrations of 100 micron. The pharmacological challenge data suggest that tolerance may occur to seizure activity induced by PTZ and PTX 24 h after gamma-HCH, since the response to only these two seizure-inducing agents is decreased. The in vitro data suggest that the site responsible for the decrease in seizure activity 24 h after gamma-HCH may be the GABA-A receptor-linked chloride channel.", "entity": "Picrotoxin", "aliases": "Picrotoxin", "definition": "A noncompetitive antagonist at GABA-A receptors and thus a convulsant. Picrotoxin blocks the GAMMA-AMINOBUTYRIC ACID-activated chloride ionophore. Although it is most often used as a research tool, it has been used as a CNS stimulant and an antidote in poisoning by CNS depressants, especially the barbiturates.\n    ", "id": "MESH:D010852"}
{"mention": "3-mercaptopropionic acid", "mention_text": "Gamma-hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to decrease seizure threshold to pentylenetrazol (PTZ) 3 h after exposure to gamma-HCH and conversely increase threshold to PTZ-induced seizures 24 h after exposure to gamma-HCH (Vohland et al. 1981). In this study, the severity of response to other seizure-inducing agents was tested in mice 1 and 24 h after intraperitoneal administration of 80 mg/kg gamma-HCH. One hour after the administration of gamma-HCH, the activity of seizure-inducing agents was increased, regardless of their mechanism, while 24 h after gamma-HCH a differential response was observed. Seizure activity due to PTZ and picrotoxin (PTX) was significantly decreased; however, seizure activity due to 3-mercaptopropionic acid (MPA), bicuculline (BCC), methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate (DMCM), or strychnine (STR) was not different from control. In vitro, gamma-HCH, pentylenetetrazol and picrotoxin were shown to inhibit 3H-TBOB binding in mouse whole brain, with IC50 values of 4.6, 404 and 9.4 microM, respectively. MPA, BCC, DMCM, and STR showed no inhibition of 3H-TBOB (t-butyl bicyclo-orthobenzoate) binding at concentrations of 100 micron. The pharmacological challenge data suggest that tolerance may occur to seizure activity induced by PTZ and PTX 24 h after gamma-HCH, since the response to only these two seizure-inducing agents is decreased. The in vitro data suggest that the site responsible for the decrease in seizure activity 24 h after gamma-HCH may be the GABA-A receptor-linked chloride channel.", "entity": "3-Mercaptopropionic Acid", "aliases": "3 Mercaptopropanoic Acid Mercaptopropionic 3-Mercaptopropanoic 3-Mercaptopropionic beta Mercaptopropionate beta-Mercaptopropionate", "definition": "An inhibitor of glutamate decarboxylase. It decreases the GAMMA-AMINOBUTYRIC ACID concentration in the brain, thereby causing convulsions.\n    ", "id": "MESH:D015097"}
{"mention": "MPA", "mention_text": "Gamma-hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to decrease seizure threshold to pentylenetrazol (PTZ) 3 h after exposure to gamma-HCH and conversely increase threshold to PTZ-induced seizures 24 h after exposure to gamma-HCH (Vohland et al. 1981). In this study, the severity of response to other seizure-inducing agents was tested in mice 1 and 24 h after intraperitoneal administration of 80 mg/kg gamma-HCH. One hour after the administration of gamma-HCH, the activity of seizure-inducing agents was increased, regardless of their mechanism, while 24 h after gamma-HCH a differential response was observed. Seizure activity due to PTZ and picrotoxin (PTX) was significantly decreased; however, seizure activity due to 3-mercaptopropionic acid (MPA), bicuculline (BCC), methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate (DMCM), or strychnine (STR) was not different from control. In vitro, gamma-HCH, pentylenetetrazol and picrotoxin were shown to inhibit 3H-TBOB binding in mouse whole brain, with IC50 values of 4.6, 404 and 9.4 microM, respectively. MPA, BCC, DMCM, and STR showed no inhibition of 3H-TBOB (t-butyl bicyclo-orthobenzoate) binding at concentrations of 100 micron. The pharmacological challenge data suggest that tolerance may occur to seizure activity induced by PTZ and PTX 24 h after gamma-HCH, since the response to only these two seizure-inducing agents is decreased. The in vitro data suggest that the site responsible for the decrease in seizure activity 24 h after gamma-HCH may be the GABA-A receptor-linked chloride channel.", "entity": "3-Mercaptopropionic Acid", "aliases": "3 Mercaptopropanoic Acid Mercaptopropionic 3-Mercaptopropanoic 3-Mercaptopropionic beta Mercaptopropionate beta-Mercaptopropionate", "definition": "An inhibitor of glutamate decarboxylase. It decreases the GAMMA-AMINOBUTYRIC ACID concentration in the brain, thereby causing convulsions.\n    ", "id": "MESH:D015097"}
{"mention": "bicuculline", "mention_text": "Gamma-hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to decrease seizure threshold to pentylenetrazol (PTZ) 3 h after exposure to gamma-HCH and conversely increase threshold to PTZ-induced seizures 24 h after exposure to gamma-HCH (Vohland et al. 1981). In this study, the severity of response to other seizure-inducing agents was tested in mice 1 and 24 h after intraperitoneal administration of 80 mg/kg gamma-HCH. One hour after the administration of gamma-HCH, the activity of seizure-inducing agents was increased, regardless of their mechanism, while 24 h after gamma-HCH a differential response was observed. Seizure activity due to PTZ and picrotoxin (PTX) was significantly decreased; however, seizure activity due to 3-mercaptopropionic acid (MPA), bicuculline (BCC), methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate (DMCM), or strychnine (STR) was not different from control. In vitro, gamma-HCH, pentylenetetrazol and picrotoxin were shown to inhibit 3H-TBOB binding in mouse whole brain, with IC50 values of 4.6, 404 and 9.4 microM, respectively. MPA, BCC, DMCM, and STR showed no inhibition of 3H-TBOB (t-butyl bicyclo-orthobenzoate) binding at concentrations of 100 micron. The pharmacological challenge data suggest that tolerance may occur to seizure activity induced by PTZ and PTX 24 h after gamma-HCH, since the response to only these two seizure-inducing agents is decreased. The in vitro data suggest that the site responsible for the decrease in seizure activity 24 h after gamma-HCH may be the GABA-A receptor-linked chloride channel.", "entity": "Bicuculline", "aliases": "6-(5,6,7,8-Tetrahydro-6-methyl-1,3-dioxolo(4,5-g)isoquinolin-5-yl)furo(3,4-e)1,3-benzodioxol-8(6H)one Bicuculline", "definition": "An isoquinoline alkaloid obtained from Dicentra cucullaria and other plants. It is a competitive antagonist for GABA-A receptors.\n    ", "id": "MESH:D001640"}
{"mention": "BCC", "mention_text": "Gamma-hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to decrease seizure threshold to pentylenetrazol (PTZ) 3 h after exposure to gamma-HCH and conversely increase threshold to PTZ-induced seizures 24 h after exposure to gamma-HCH (Vohland et al. 1981). In this study, the severity of response to other seizure-inducing agents was tested in mice 1 and 24 h after intraperitoneal administration of 80 mg/kg gamma-HCH. One hour after the administration of gamma-HCH, the activity of seizure-inducing agents was increased, regardless of their mechanism, while 24 h after gamma-HCH a differential response was observed. Seizure activity due to PTZ and picrotoxin (PTX) was significantly decreased; however, seizure activity due to 3-mercaptopropionic acid (MPA), bicuculline (BCC), methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate (DMCM), or strychnine (STR) was not different from control. In vitro, gamma-HCH, pentylenetetrazol and picrotoxin were shown to inhibit 3H-TBOB binding in mouse whole brain, with IC50 values of 4.6, 404 and 9.4 microM, respectively. MPA, BCC, DMCM, and STR showed no inhibition of 3H-TBOB (t-butyl bicyclo-orthobenzoate) binding at concentrations of 100 micron. The pharmacological challenge data suggest that tolerance may occur to seizure activity induced by PTZ and PTX 24 h after gamma-HCH, since the response to only these two seizure-inducing agents is decreased. The in vitro data suggest that the site responsible for the decrease in seizure activity 24 h after gamma-HCH may be the GABA-A receptor-linked chloride channel.", "entity": "Bicuculline", "aliases": "6-(5,6,7,8-Tetrahydro-6-methyl-1,3-dioxolo(4,5-g)isoquinolin-5-yl)furo(3,4-e)1,3-benzodioxol-8(6H)one Bicuculline", "definition": "An isoquinoline alkaloid obtained from Dicentra cucullaria and other plants. It is a competitive antagonist for GABA-A receptors.\n    ", "id": "MESH:D001640"}
{"mention": "methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate", "mention_text": "Gamma-hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to decrease seizure threshold to pentylenetrazol (PTZ) 3 h after exposure to gamma-HCH and conversely increase threshold to PTZ-induced seizures 24 h after exposure to gamma-HCH (Vohland et al. 1981). In this study, the severity of response to other seizure-inducing agents was tested in mice 1 and 24 h after intraperitoneal administration of 80 mg/kg gamma-HCH. One hour after the administration of gamma-HCH, the activity of seizure-inducing agents was increased, regardless of their mechanism, while 24 h after gamma-HCH a differential response was observed. Seizure activity due to PTZ and picrotoxin (PTX) was significantly decreased; however, seizure activity due to 3-mercaptopropionic acid (MPA), bicuculline (BCC), methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate (DMCM), or strychnine (STR) was not different from control. In vitro, gamma-HCH, pentylenetetrazol and picrotoxin were shown to inhibit 3H-TBOB binding in mouse whole brain, with IC50 values of 4.6, 404 and 9.4 microM, respectively. MPA, BCC, DMCM, and STR showed no inhibition of 3H-TBOB (t-butyl bicyclo-orthobenzoate) binding at concentrations of 100 micron. The pharmacological challenge data suggest that tolerance may occur to seizure activity induced by PTZ and PTX 24 h after gamma-HCH, since the response to only these two seizure-inducing agents is decreased. The in vitro data suggest that the site responsible for the decrease in seizure activity 24 h after gamma-HCH may be the GABA-A receptor-linked chloride channel.", "entity": "methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate", "aliases": "DMCM methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate", "definition": "", "id": "MESH:C034818"}
{"mention": "DMCM", "mention_text": "Gamma-hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to decrease seizure threshold to pentylenetrazol (PTZ) 3 h after exposure to gamma-HCH and conversely increase threshold to PTZ-induced seizures 24 h after exposure to gamma-HCH (Vohland et al. 1981). In this study, the severity of response to other seizure-inducing agents was tested in mice 1 and 24 h after intraperitoneal administration of 80 mg/kg gamma-HCH. One hour after the administration of gamma-HCH, the activity of seizure-inducing agents was increased, regardless of their mechanism, while 24 h after gamma-HCH a differential response was observed. Seizure activity due to PTZ and picrotoxin (PTX) was significantly decreased; however, seizure activity due to 3-mercaptopropionic acid (MPA), bicuculline (BCC), methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate (DMCM), or strychnine (STR) was not different from control. In vitro, gamma-HCH, pentylenetetrazol and picrotoxin were shown to inhibit 3H-TBOB binding in mouse whole brain, with IC50 values of 4.6, 404 and 9.4 microM, respectively. MPA, BCC, DMCM, and STR showed no inhibition of 3H-TBOB (t-butyl bicyclo-orthobenzoate) binding at concentrations of 100 micron. The pharmacological challenge data suggest that tolerance may occur to seizure activity induced by PTZ and PTX 24 h after gamma-HCH, since the response to only these two seizure-inducing agents is decreased. The in vitro data suggest that the site responsible for the decrease in seizure activity 24 h after gamma-HCH may be the GABA-A receptor-linked chloride channel.", "entity": "methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate", "aliases": "DMCM methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate", "definition": "", "id": "MESH:C034818"}
{"mention": "strychnine", "mention_text": "Gamma-hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to decrease seizure threshold to pentylenetrazol (PTZ) 3 h after exposure to gamma-HCH and conversely increase threshold to PTZ-induced seizures 24 h after exposure to gamma-HCH (Vohland et al. 1981). In this study, the severity of response to other seizure-inducing agents was tested in mice 1 and 24 h after intraperitoneal administration of 80 mg/kg gamma-HCH. One hour after the administration of gamma-HCH, the activity of seizure-inducing agents was increased, regardless of their mechanism, while 24 h after gamma-HCH a differential response was observed. Seizure activity due to PTZ and picrotoxin (PTX) was significantly decreased; however, seizure activity due to 3-mercaptopropionic acid (MPA), bicuculline (BCC), methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate (DMCM), or strychnine (STR) was not different from control. In vitro, gamma-HCH, pentylenetetrazol and picrotoxin were shown to inhibit 3H-TBOB binding in mouse whole brain, with IC50 values of 4.6, 404 and 9.4 microM, respectively. MPA, BCC, DMCM, and STR showed no inhibition of 3H-TBOB (t-butyl bicyclo-orthobenzoate) binding at concentrations of 100 micron. The pharmacological challenge data suggest that tolerance may occur to seizure activity induced by PTZ and PTX 24 h after gamma-HCH, since the response to only these two seizure-inducing agents is decreased. The in vitro data suggest that the site responsible for the decrease in seizure activity 24 h after gamma-HCH may be the GABA-A receptor-linked chloride channel.", "entity": "Strychnine", "aliases": "Nitrate Strychnine", "definition": "An alkaloid found in the seeds of STRYCHNOS NUX-VOMICA. It is a competitive antagonist at glycine receptors and thus a convulsant. It has been used as an analeptic, in the treatment of nonketotic hyperglycinemia and sleep apnea, and as a rat poison.\n    ", "id": "MESH:D013331"}
{"mention": "STR", "mention_text": "Gamma-hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to decrease seizure threshold to pentylenetrazol (PTZ) 3 h after exposure to gamma-HCH and conversely increase threshold to PTZ-induced seizures 24 h after exposure to gamma-HCH (Vohland et al. 1981). In this study, the severity of response to other seizure-inducing agents was tested in mice 1 and 24 h after intraperitoneal administration of 80 mg/kg gamma-HCH. One hour after the administration of gamma-HCH, the activity of seizure-inducing agents was increased, regardless of their mechanism, while 24 h after gamma-HCH a differential response was observed. Seizure activity due to PTZ and picrotoxin (PTX) was significantly decreased; however, seizure activity due to 3-mercaptopropionic acid (MPA), bicuculline (BCC), methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate (DMCM), or strychnine (STR) was not different from control. In vitro, gamma-HCH, pentylenetetrazol and picrotoxin were shown to inhibit 3H-TBOB binding in mouse whole brain, with IC50 values of 4.6, 404 and 9.4 microM, respectively. MPA, BCC, DMCM, and STR showed no inhibition of 3H-TBOB (t-butyl bicyclo-orthobenzoate) binding at concentrations of 100 micron. The pharmacological challenge data suggest that tolerance may occur to seizure activity induced by PTZ and PTX 24 h after gamma-HCH, since the response to only these two seizure-inducing agents is decreased. The in vitro data suggest that the site responsible for the decrease in seizure activity 24 h after gamma-HCH may be the GABA-A receptor-linked chloride channel.", "entity": "Strychnine", "aliases": "Nitrate Strychnine", "definition": "An alkaloid found in the seeds of STRYCHNOS NUX-VOMICA. It is a competitive antagonist at glycine receptors and thus a convulsant. It has been used as an analeptic, in the treatment of nonketotic hyperglycinemia and sleep apnea, and as a rat poison.\n    ", "id": "MESH:D013331"}
{"mention": "pentylenetetrazol", "mention_text": "Gamma-hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to decrease seizure threshold to pentylenetrazol (PTZ) 3 h after exposure to gamma-HCH and conversely increase threshold to PTZ-induced seizures 24 h after exposure to gamma-HCH (Vohland et al. 1981). In this study, the severity of response to other seizure-inducing agents was tested in mice 1 and 24 h after intraperitoneal administration of 80 mg/kg gamma-HCH. One hour after the administration of gamma-HCH, the activity of seizure-inducing agents was increased, regardless of their mechanism, while 24 h after gamma-HCH a differential response was observed. Seizure activity due to PTZ and picrotoxin (PTX) was significantly decreased; however, seizure activity due to 3-mercaptopropionic acid (MPA), bicuculline (BCC), methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate (DMCM), or strychnine (STR) was not different from control. In vitro, gamma-HCH, pentylenetetrazol and picrotoxin were shown to inhibit 3H-TBOB binding in mouse whole brain, with IC50 values of 4.6, 404 and 9.4 microM, respectively. MPA, BCC, DMCM, and STR showed no inhibition of 3H-TBOB (t-butyl bicyclo-orthobenzoate) binding at concentrations of 100 micron. The pharmacological challenge data suggest that tolerance may occur to seizure activity induced by PTZ and PTX 24 h after gamma-HCH, since the response to only these two seizure-inducing agents is decreased. The in vitro data suggest that the site responsible for the decrease in seizure activity 24 h after gamma-HCH may be the GABA-A receptor-linked chloride channel.", "entity": "Pentylenetetrazole", "aliases": "Cardiazol Corasol Corazol Corazole Korazol Korazole Leptazole Metrazol Metrazole Pentamethylenetetrazole Pentazol Pentetrazole Pentylenetetrazol Pentylenetetrazole", "definition": "A pharmaceutical agent that displays activity as a central nervous system and respiratory stimulant. It is considered a non-competitive GAMMA-AMINOBUTYRIC ACID antagonist. Pentylenetetrazole has been used experimentally to study seizure phenomenon and to identify pharmaceuticals that may control seizure susceptibility.\n    ", "id": "MESH:D010433"}
{"mention": "3H-TBOB", "mention_text": "Gamma-hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to decrease seizure threshold to pentylenetrazol (PTZ) 3 h after exposure to gamma-HCH and conversely increase threshold to PTZ-induced seizures 24 h after exposure to gamma-HCH (Vohland et al. 1981). In this study, the severity of response to other seizure-inducing agents was tested in mice 1 and 24 h after intraperitoneal administration of 80 mg/kg gamma-HCH. One hour after the administration of gamma-HCH, the activity of seizure-inducing agents was increased, regardless of their mechanism, while 24 h after gamma-HCH a differential response was observed. Seizure activity due to PTZ and picrotoxin (PTX) was significantly decreased; however, seizure activity due to 3-mercaptopropionic acid (MPA), bicuculline (BCC), methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate (DMCM), or strychnine (STR) was not different from control. In vitro, gamma-HCH, pentylenetetrazol and picrotoxin were shown to inhibit 3H-TBOB binding in mouse whole brain, with IC50 values of 4.6, 404 and 9.4 microM, respectively. MPA, BCC, DMCM, and STR showed no inhibition of 3H-TBOB (t-butyl bicyclo-orthobenzoate) binding at concentrations of 100 micron. The pharmacological challenge data suggest that tolerance may occur to seizure activity induced by PTZ and PTX 24 h after gamma-HCH, since the response to only these two seizure-inducing agents is decreased. The in vitro data suggest that the site responsible for the decrease in seizure activity 24 h after gamma-HCH may be the GABA-A receptor-linked chloride channel.", "entity": "tert-butylbicyclo-2-benzoate", "aliases": "TBOB t-BB2B tert-butylbicyclo-2-benzoate tert-butylbicyclo-ortho-benzoate", "definition": "", "id": "MESH:C046308"}
{"mention": "t-butyl bicyclo-orthobenzoate", "mention_text": "Gamma-hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to decrease seizure threshold to pentylenetrazol (PTZ) 3 h after exposure to gamma-HCH and conversely increase threshold to PTZ-induced seizures 24 h after exposure to gamma-HCH (Vohland et al. 1981). In this study, the severity of response to other seizure-inducing agents was tested in mice 1 and 24 h after intraperitoneal administration of 80 mg/kg gamma-HCH. One hour after the administration of gamma-HCH, the activity of seizure-inducing agents was increased, regardless of their mechanism, while 24 h after gamma-HCH a differential response was observed. Seizure activity due to PTZ and picrotoxin (PTX) was significantly decreased; however, seizure activity due to 3-mercaptopropionic acid (MPA), bicuculline (BCC), methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate (DMCM), or strychnine (STR) was not different from control. In vitro, gamma-HCH, pentylenetetrazol and picrotoxin were shown to inhibit 3H-TBOB binding in mouse whole brain, with IC50 values of 4.6, 404 and 9.4 microM, respectively. MPA, BCC, DMCM, and STR showed no inhibition of 3H-TBOB (t-butyl bicyclo-orthobenzoate) binding at concentrations of 100 micron. The pharmacological challenge data suggest that tolerance may occur to seizure activity induced by PTZ and PTX 24 h after gamma-HCH, since the response to only these two seizure-inducing agents is decreased. The in vitro data suggest that the site responsible for the decrease in seizure activity 24 h after gamma-HCH may be the GABA-A receptor-linked chloride channel.", "entity": "tert-butylbicyclo-2-benzoate", "aliases": "TBOB t-BB2B tert-butylbicyclo-2-benzoate tert-butylbicyclo-ortho-benzoate", "definition": "", "id": "MESH:C046308"}
{"mention": "GABA", "mention_text": "Gamma-hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to decrease seizure threshold to pentylenetrazol (PTZ) 3 h after exposure to gamma-HCH and conversely increase threshold to PTZ-induced seizures 24 h after exposure to gamma-HCH (Vohland et al. 1981). In this study, the severity of response to other seizure-inducing agents was tested in mice 1 and 24 h after intraperitoneal administration of 80 mg/kg gamma-HCH. One hour after the administration of gamma-HCH, the activity of seizure-inducing agents was increased, regardless of their mechanism, while 24 h after gamma-HCH a differential response was observed. Seizure activity due to PTZ and picrotoxin (PTX) was significantly decreased; however, seizure activity due to 3-mercaptopropionic acid (MPA), bicuculline (BCC), methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate (DMCM), or strychnine (STR) was not different from control. In vitro, gamma-HCH, pentylenetetrazol and picrotoxin were shown to inhibit 3H-TBOB binding in mouse whole brain, with IC50 values of 4.6, 404 and 9.4 microM, respectively. MPA, BCC, DMCM, and STR showed no inhibition of 3H-TBOB (t-butyl bicyclo-orthobenzoate) binding at concentrations of 100 micron. The pharmacological challenge data suggest that tolerance may occur to seizure activity induced by PTZ and PTX 24 h after gamma-HCH, since the response to only these two seizure-inducing agents is decreased. The in vitro data suggest that the site responsible for the decrease in seizure activity 24 h after gamma-HCH may be the GABA-A receptor-linked chloride channel.", "entity": "gamma-Aminobutyric Acid", "aliases": "4 Aminobutanoic Acid Aminobutyric 4-Aminobutanoic 4-Aminobutyric Hydrochloride gamma-Aminobutyric Aminalon Aminalone GABA Lithium Gammalon gamma Monolithium Salt Monosodium Calcium (2:1) Zinc", "definition": "The most common inhibitory neurotransmitter in the central nervous system.\n    ", "id": "MESH:D005680"}
{"mention": "orbital toxicity", "mention_text": "Severe ocular and orbital toxicity after intracarotid injection of carboplatin for recurrent glioblastomas.", "entity": "Orbital Diseases", "aliases": "Disease Orbital Diseases", "definition": "Diseases of the bony orbit and contents except the eyeball.\n    ", "id": "MESH:D009916"}
{"mention": "carboplatin", "mention_text": "Severe ocular and orbital toxicity after intracarotid injection of carboplatin for recurrent glioblastomas.", "entity": "Carboplatin", "aliases": "Almirall Brand of Carboplatin Blastocarb Bristol-Myers Squibb CBDCA Carboplat Carbosin Carbotec Chiesi Columbia Ercar JM 8 JM-8 JM8 Lemery NSC 241240 NSC-241240 NSC241240 Nealorin Neocarbo Neocorp Paraplatin Paraplatine Pharmachemie Platinwas Prasfarma Ribocarbo cis-Diammine(cyclobutanedicarboxylato)platinum II ribosepharm", "definition": "An organoplatinum compound that possesses antineoplastic activity.\n    ", "id": "MESH:D016190"}
{"mention": "glioblastomas", "mention_text": "Severe ocular and orbital toxicity after intracarotid injection of carboplatin for recurrent glioblastomas.", "entity": "Glioblastoma", "aliases": "Astrocytoma Grade IV Astrocytomas Giant Cell Glioblastoma Glioblastomas Multiforme", "definition": "A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.\n    ", "id": "MESH:D005909"}
{"mention": "Glioblastoma", "mention_text": "BACKGROUND: Glioblastoma is a malignant tumor that occurs in the cerebrum during adulthood. With current treatment regimens including combined surgery, radiation and chemotherapy, the average life expectancy of the patients is limited to approximately 1 year. Therefore, patients with glioblastoma sometimes have intracarotid injection of carcinostatics added to the treatment regimen. Generally, carboplatin is said to have milder side effects than cisplatin, whose ocular and orbital toxicity are well known. However, we experienced a case of severe ocular and orbital toxicity after intracarotid injection of carboplatin, which is infrequently reported. CASE: A 58-year-old man received an intracarotid injection of carboplatin for recurrent glioblastomas in his left temporal lobe. He complained of pain and visual disturbance in the ipsilateral eye 30 h after the injection. Various ocular symptoms and findings caused by carboplatin toxicity were seen. RESULTS: He was treated with intravenous administration of corticosteroids and glycerin for 6 days after the injection. Although the intraocular pressure elevation caused by secondary acute angle-closure glaucoma decreased and ocular pain diminished, inexorable papilledema and exudative retinal detachment continued for 3 weeks. Finally, 6 weeks later, diffuse chorioretinal atrophy with optic atrophy occurred and the vision in his left eye was lost. CONCLUSION: When performing intracarotid injection of carboplatin, we must be aware of its potentially blinding ocular toxicity. It is recommended that further studies and investigations are undertaken in the effort to minimize such severe side effects.", "entity": "Glioblastoma", "aliases": "Astrocytoma Grade IV Astrocytomas Giant Cell Glioblastoma Glioblastomas Multiforme", "definition": "A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.\n    ", "id": "MESH:D005909"}
{"mention": "malignant tumor", "mention_text": "BACKGROUND: Glioblastoma is a malignant tumor that occurs in the cerebrum during adulthood. With current treatment regimens including combined surgery, radiation and chemotherapy, the average life expectancy of the patients is limited to approximately 1 year. Therefore, patients with glioblastoma sometimes have intracarotid injection of carcinostatics added to the treatment regimen. Generally, carboplatin is said to have milder side effects than cisplatin, whose ocular and orbital toxicity are well known. However, we experienced a case of severe ocular and orbital toxicity after intracarotid injection of carboplatin, which is infrequently reported. CASE: A 58-year-old man received an intracarotid injection of carboplatin for recurrent glioblastomas in his left temporal lobe. He complained of pain and visual disturbance in the ipsilateral eye 30 h after the injection. Various ocular symptoms and findings caused by carboplatin toxicity were seen. RESULTS: He was treated with intravenous administration of corticosteroids and glycerin for 6 days after the injection. Although the intraocular pressure elevation caused by secondary acute angle-closure glaucoma decreased and ocular pain diminished, inexorable papilledema and exudative retinal detachment continued for 3 weeks. Finally, 6 weeks later, diffuse chorioretinal atrophy with optic atrophy occurred and the vision in his left eye was lost. CONCLUSION: When performing intracarotid injection of carboplatin, we must be aware of its potentially blinding ocular toxicity. It is recommended that further studies and investigations are undertaken in the effort to minimize such severe side effects.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "glioblastoma", "mention_text": "BACKGROUND: Glioblastoma is a malignant tumor that occurs in the cerebrum during adulthood. With current treatment regimens including combined surgery, radiation and chemotherapy, the average life expectancy of the patients is limited to approximately 1 year. Therefore, patients with glioblastoma sometimes have intracarotid injection of carcinostatics added to the treatment regimen. Generally, carboplatin is said to have milder side effects than cisplatin, whose ocular and orbital toxicity are well known. However, we experienced a case of severe ocular and orbital toxicity after intracarotid injection of carboplatin, which is infrequently reported. CASE: A 58-year-old man received an intracarotid injection of carboplatin for recurrent glioblastomas in his left temporal lobe. He complained of pain and visual disturbance in the ipsilateral eye 30 h after the injection. Various ocular symptoms and findings caused by carboplatin toxicity were seen. RESULTS: He was treated with intravenous administration of corticosteroids and glycerin for 6 days after the injection. Although the intraocular pressure elevation caused by secondary acute angle-closure glaucoma decreased and ocular pain diminished, inexorable papilledema and exudative retinal detachment continued for 3 weeks. Finally, 6 weeks later, diffuse chorioretinal atrophy with optic atrophy occurred and the vision in his left eye was lost. CONCLUSION: When performing intracarotid injection of carboplatin, we must be aware of its potentially blinding ocular toxicity. It is recommended that further studies and investigations are undertaken in the effort to minimize such severe side effects.", "entity": "Glioblastoma", "aliases": "Astrocytoma Grade IV Astrocytomas Giant Cell Glioblastoma Glioblastomas Multiforme", "definition": "A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.\n    ", "id": "MESH:D005909"}
{"mention": "carboplatin", "mention_text": "BACKGROUND: Glioblastoma is a malignant tumor that occurs in the cerebrum during adulthood. With current treatment regimens including combined surgery, radiation and chemotherapy, the average life expectancy of the patients is limited to approximately 1 year. Therefore, patients with glioblastoma sometimes have intracarotid injection of carcinostatics added to the treatment regimen. Generally, carboplatin is said to have milder side effects than cisplatin, whose ocular and orbital toxicity are well known. However, we experienced a case of severe ocular and orbital toxicity after intracarotid injection of carboplatin, which is infrequently reported. CASE: A 58-year-old man received an intracarotid injection of carboplatin for recurrent glioblastomas in his left temporal lobe. He complained of pain and visual disturbance in the ipsilateral eye 30 h after the injection. Various ocular symptoms and findings caused by carboplatin toxicity were seen. RESULTS: He was treated with intravenous administration of corticosteroids and glycerin for 6 days after the injection. Although the intraocular pressure elevation caused by secondary acute angle-closure glaucoma decreased and ocular pain diminished, inexorable papilledema and exudative retinal detachment continued for 3 weeks. Finally, 6 weeks later, diffuse chorioretinal atrophy with optic atrophy occurred and the vision in his left eye was lost. CONCLUSION: When performing intracarotid injection of carboplatin, we must be aware of its potentially blinding ocular toxicity. It is recommended that further studies and investigations are undertaken in the effort to minimize such severe side effects.", "entity": "Carboplatin", "aliases": "Almirall Brand of Carboplatin Blastocarb Bristol-Myers Squibb CBDCA Carboplat Carbosin Carbotec Chiesi Columbia Ercar JM 8 JM-8 JM8 Lemery NSC 241240 NSC-241240 NSC241240 Nealorin Neocarbo Neocorp Paraplatin Paraplatine Pharmachemie Platinwas Prasfarma Ribocarbo cis-Diammine(cyclobutanedicarboxylato)platinum II ribosepharm", "definition": "An organoplatinum compound that possesses antineoplastic activity.\n    ", "id": "MESH:D016190"}
{"mention": "cisplatin", "mention_text": "BACKGROUND: Glioblastoma is a malignant tumor that occurs in the cerebrum during adulthood. With current treatment regimens including combined surgery, radiation and chemotherapy, the average life expectancy of the patients is limited to approximately 1 year. Therefore, patients with glioblastoma sometimes have intracarotid injection of carcinostatics added to the treatment regimen. Generally, carboplatin is said to have milder side effects than cisplatin, whose ocular and orbital toxicity are well known. However, we experienced a case of severe ocular and orbital toxicity after intracarotid injection of carboplatin, which is infrequently reported. CASE: A 58-year-old man received an intracarotid injection of carboplatin for recurrent glioblastomas in his left temporal lobe. He complained of pain and visual disturbance in the ipsilateral eye 30 h after the injection. Various ocular symptoms and findings caused by carboplatin toxicity were seen. RESULTS: He was treated with intravenous administration of corticosteroids and glycerin for 6 days after the injection. Although the intraocular pressure elevation caused by secondary acute angle-closure glaucoma decreased and ocular pain diminished, inexorable papilledema and exudative retinal detachment continued for 3 weeks. Finally, 6 weeks later, diffuse chorioretinal atrophy with optic atrophy occurred and the vision in his left eye was lost. CONCLUSION: When performing intracarotid injection of carboplatin, we must be aware of its potentially blinding ocular toxicity. It is recommended that further studies and investigations are undertaken in the effort to minimize such severe side effects.", "entity": "Cisplatin", "aliases": "Biocisplatinum Cisplatin Diamminodichloride Platinum Dichlorodiammineplatinum NSC-119875 Platidiam Platino Platinol cis Diamminedichloroplatinum cis-Diamminedichloroplatinum cis-Diamminedichloroplatinum(II) cis-Dichlorodiammineplatinum(II) cis-Platinum", "definition": "An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.\n    ", "id": "MESH:D002945"}
{"mention": "orbital toxicity", "mention_text": "BACKGROUND: Glioblastoma is a malignant tumor that occurs in the cerebrum during adulthood. With current treatment regimens including combined surgery, radiation and chemotherapy, the average life expectancy of the patients is limited to approximately 1 year. Therefore, patients with glioblastoma sometimes have intracarotid injection of carcinostatics added to the treatment regimen. Generally, carboplatin is said to have milder side effects than cisplatin, whose ocular and orbital toxicity are well known. However, we experienced a case of severe ocular and orbital toxicity after intracarotid injection of carboplatin, which is infrequently reported. CASE: A 58-year-old man received an intracarotid injection of carboplatin for recurrent glioblastomas in his left temporal lobe. He complained of pain and visual disturbance in the ipsilateral eye 30 h after the injection. Various ocular symptoms and findings caused by carboplatin toxicity were seen. RESULTS: He was treated with intravenous administration of corticosteroids and glycerin for 6 days after the injection. Although the intraocular pressure elevation caused by secondary acute angle-closure glaucoma decreased and ocular pain diminished, inexorable papilledema and exudative retinal detachment continued for 3 weeks. Finally, 6 weeks later, diffuse chorioretinal atrophy with optic atrophy occurred and the vision in his left eye was lost. CONCLUSION: When performing intracarotid injection of carboplatin, we must be aware of its potentially blinding ocular toxicity. It is recommended that further studies and investigations are undertaken in the effort to minimize such severe side effects.", "entity": "Orbital Diseases", "aliases": "Disease Orbital Diseases", "definition": "Diseases of the bony orbit and contents except the eyeball.\n    ", "id": "MESH:D009916"}
{"mention": "glioblastomas", "mention_text": "BACKGROUND: Glioblastoma is a malignant tumor that occurs in the cerebrum during adulthood. With current treatment regimens including combined surgery, radiation and chemotherapy, the average life expectancy of the patients is limited to approximately 1 year. Therefore, patients with glioblastoma sometimes have intracarotid injection of carcinostatics added to the treatment regimen. Generally, carboplatin is said to have milder side effects than cisplatin, whose ocular and orbital toxicity are well known. However, we experienced a case of severe ocular and orbital toxicity after intracarotid injection of carboplatin, which is infrequently reported. CASE: A 58-year-old man received an intracarotid injection of carboplatin for recurrent glioblastomas in his left temporal lobe. He complained of pain and visual disturbance in the ipsilateral eye 30 h after the injection. Various ocular symptoms and findings caused by carboplatin toxicity were seen. RESULTS: He was treated with intravenous administration of corticosteroids and glycerin for 6 days after the injection. Although the intraocular pressure elevation caused by secondary acute angle-closure glaucoma decreased and ocular pain diminished, inexorable papilledema and exudative retinal detachment continued for 3 weeks. Finally, 6 weeks later, diffuse chorioretinal atrophy with optic atrophy occurred and the vision in his left eye was lost. CONCLUSION: When performing intracarotid injection of carboplatin, we must be aware of its potentially blinding ocular toxicity. It is recommended that further studies and investigations are undertaken in the effort to minimize such severe side effects.", "entity": "Glioblastoma", "aliases": "Astrocytoma Grade IV Astrocytomas Giant Cell Glioblastoma Glioblastomas Multiforme", "definition": "A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.\n    ", "id": "MESH:D005909"}
{"mention": "visual disturbance in the ipsilateral eye", "mention_text": "BACKGROUND: Glioblastoma is a malignant tumor that occurs in the cerebrum during adulthood. With current treatment regimens including combined surgery, radiation and chemotherapy, the average life expectancy of the patients is limited to approximately 1 year. Therefore, patients with glioblastoma sometimes have intracarotid injection of carcinostatics added to the treatment regimen. Generally, carboplatin is said to have milder side effects than cisplatin, whose ocular and orbital toxicity are well known. However, we experienced a case of severe ocular and orbital toxicity after intracarotid injection of carboplatin, which is infrequently reported. CASE: A 58-year-old man received an intracarotid injection of carboplatin for recurrent glioblastomas in his left temporal lobe. He complained of pain and visual disturbance in the ipsilateral eye 30 h after the injection. Various ocular symptoms and findings caused by carboplatin toxicity were seen. RESULTS: He was treated with intravenous administration of corticosteroids and glycerin for 6 days after the injection. Although the intraocular pressure elevation caused by secondary acute angle-closure glaucoma decreased and ocular pain diminished, inexorable papilledema and exudative retinal detachment continued for 3 weeks. Finally, 6 weeks later, diffuse chorioretinal atrophy with optic atrophy occurred and the vision in his left eye was lost. CONCLUSION: When performing intracarotid injection of carboplatin, we must be aware of its potentially blinding ocular toxicity. It is recommended that further studies and investigations are undertaken in the effort to minimize such severe side effects.", "entity": "Vision Disorders", "aliases": "Blindness Day Disabilities Vision Disability Disorder Visual Disorders Hemeralopia Hemeralopias Impairment Impairments Macropsia Macropsias Metamorphopsia Metamorphopsias Micropsia Micropsias", "definition": "Visual impairments limiting one or more of the basic functions of the eye: visual acuity, dark adaptation, color vision, or peripheral vision. These may result from EYE DISEASES; OPTIC NERVE DISEASES; VISUAL PATHWAY diseases; OCCIPITAL LOBE diseases; OCULAR MOTILITY DISORDERS; and other conditions (From Newell, Ophthalmology: Principles and Concepts, 7th ed, p132).\n    ", "id": "MESH:D014786"}
{"mention": "toxicity", "mention_text": "BACKGROUND: Glioblastoma is a malignant tumor that occurs in the cerebrum during adulthood. With current treatment regimens including combined surgery, radiation and chemotherapy, the average life expectancy of the patients is limited to approximately 1 year. Therefore, patients with glioblastoma sometimes have intracarotid injection of carcinostatics added to the treatment regimen. Generally, carboplatin is said to have milder side effects than cisplatin, whose ocular and orbital toxicity are well known. However, we experienced a case of severe ocular and orbital toxicity after intracarotid injection of carboplatin, which is infrequently reported. CASE: A 58-year-old man received an intracarotid injection of carboplatin for recurrent glioblastomas in his left temporal lobe. He complained of pain and visual disturbance in the ipsilateral eye 30 h after the injection. Various ocular symptoms and findings caused by carboplatin toxicity were seen. RESULTS: He was treated with intravenous administration of corticosteroids and glycerin for 6 days after the injection. Although the intraocular pressure elevation caused by secondary acute angle-closure glaucoma decreased and ocular pain diminished, inexorable papilledema and exudative retinal detachment continued for 3 weeks. Finally, 6 weeks later, diffuse chorioretinal atrophy with optic atrophy occurred and the vision in his left eye was lost. CONCLUSION: When performing intracarotid injection of carboplatin, we must be aware of its potentially blinding ocular toxicity. It is recommended that further studies and investigations are undertaken in the effort to minimize such severe side effects.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "glycerin", "mention_text": "BACKGROUND: Glioblastoma is a malignant tumor that occurs in the cerebrum during adulthood. With current treatment regimens including combined surgery, radiation and chemotherapy, the average life expectancy of the patients is limited to approximately 1 year. Therefore, patients with glioblastoma sometimes have intracarotid injection of carcinostatics added to the treatment regimen. Generally, carboplatin is said to have milder side effects than cisplatin, whose ocular and orbital toxicity are well known. However, we experienced a case of severe ocular and orbital toxicity after intracarotid injection of carboplatin, which is infrequently reported. CASE: A 58-year-old man received an intracarotid injection of carboplatin for recurrent glioblastomas in his left temporal lobe. He complained of pain and visual disturbance in the ipsilateral eye 30 h after the injection. Various ocular symptoms and findings caused by carboplatin toxicity were seen. RESULTS: He was treated with intravenous administration of corticosteroids and glycerin for 6 days after the injection. Although the intraocular pressure elevation caused by secondary acute angle-closure glaucoma decreased and ocular pain diminished, inexorable papilledema and exudative retinal detachment continued for 3 weeks. Finally, 6 weeks later, diffuse chorioretinal atrophy with optic atrophy occurred and the vision in his left eye was lost. CONCLUSION: When performing intracarotid injection of carboplatin, we must be aware of its potentially blinding ocular toxicity. It is recommended that further studies and investigations are undertaken in the effort to minimize such severe side effects.", "entity": "Glycerol", "aliases": "1,2,3-Trihydroxypropane Glycerin Glycerine Glycerol", "definition": "A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent.\n    ", "id": "MESH:D005990"}
{"mention": "glaucoma", "mention_text": "BACKGROUND: Glioblastoma is a malignant tumor that occurs in the cerebrum during adulthood. With current treatment regimens including combined surgery, radiation and chemotherapy, the average life expectancy of the patients is limited to approximately 1 year. Therefore, patients with glioblastoma sometimes have intracarotid injection of carcinostatics added to the treatment regimen. Generally, carboplatin is said to have milder side effects than cisplatin, whose ocular and orbital toxicity are well known. However, we experienced a case of severe ocular and orbital toxicity after intracarotid injection of carboplatin, which is infrequently reported. CASE: A 58-year-old man received an intracarotid injection of carboplatin for recurrent glioblastomas in his left temporal lobe. He complained of pain and visual disturbance in the ipsilateral eye 30 h after the injection. Various ocular symptoms and findings caused by carboplatin toxicity were seen. RESULTS: He was treated with intravenous administration of corticosteroids and glycerin for 6 days after the injection. Although the intraocular pressure elevation caused by secondary acute angle-closure glaucoma decreased and ocular pain diminished, inexorable papilledema and exudative retinal detachment continued for 3 weeks. Finally, 6 weeks later, diffuse chorioretinal atrophy with optic atrophy occurred and the vision in his left eye was lost. CONCLUSION: When performing intracarotid injection of carboplatin, we must be aware of its potentially blinding ocular toxicity. It is recommended that further studies and investigations are undertaken in the effort to minimize such severe side effects.", "entity": "Glaucoma", "aliases": "Glaucoma Glaucomas", "definition": "An ocular disease, occurring in many forms, having as its primary characteristics an unstable or a sustained increase in the intraocular pressure which the eye cannot withstand without damage to its structure or impairment of its function. The consequences of the increased pressure may be manifested in a variety of symptoms, depending upon type and severity, such as excavation of the optic disk, hardness of the eyeball, corneal anesthesia, reduced visual acuity, seeing of colored halos around lights, disturbed dark adaptation, visual field defects, and headaches. (Dictionary of Visual Science, 4th ed)\n    ", "id": "MESH:D005901"}
{"mention": "ocular pain", "mention_text": "BACKGROUND: Glioblastoma is a malignant tumor that occurs in the cerebrum during adulthood. With current treatment regimens including combined surgery, radiation and chemotherapy, the average life expectancy of the patients is limited to approximately 1 year. Therefore, patients with glioblastoma sometimes have intracarotid injection of carcinostatics added to the treatment regimen. Generally, carboplatin is said to have milder side effects than cisplatin, whose ocular and orbital toxicity are well known. However, we experienced a case of severe ocular and orbital toxicity after intracarotid injection of carboplatin, which is infrequently reported. CASE: A 58-year-old man received an intracarotid injection of carboplatin for recurrent glioblastomas in his left temporal lobe. He complained of pain and visual disturbance in the ipsilateral eye 30 h after the injection. Various ocular symptoms and findings caused by carboplatin toxicity were seen. RESULTS: He was treated with intravenous administration of corticosteroids and glycerin for 6 days after the injection. Although the intraocular pressure elevation caused by secondary acute angle-closure glaucoma decreased and ocular pain diminished, inexorable papilledema and exudative retinal detachment continued for 3 weeks. Finally, 6 weeks later, diffuse chorioretinal atrophy with optic atrophy occurred and the vision in his left eye was lost. CONCLUSION: When performing intracarotid injection of carboplatin, we must be aware of its potentially blinding ocular toxicity. It is recommended that further studies and investigations are undertaken in the effort to minimize such severe side effects.", "entity": "Eye Pain", "aliases": "Eye Pain Pains", "definition": "A dull or sharp painful sensation associated with the outer or inner structures of the eyeball, having different causes.\n    ", "id": "MESH:D058447"}
{"mention": "papilledema", "mention_text": "BACKGROUND: Glioblastoma is a malignant tumor that occurs in the cerebrum during adulthood. With current treatment regimens including combined surgery, radiation and chemotherapy, the average life expectancy of the patients is limited to approximately 1 year. Therefore, patients with glioblastoma sometimes have intracarotid injection of carcinostatics added to the treatment regimen. Generally, carboplatin is said to have milder side effects than cisplatin, whose ocular and orbital toxicity are well known. However, we experienced a case of severe ocular and orbital toxicity after intracarotid injection of carboplatin, which is infrequently reported. CASE: A 58-year-old man received an intracarotid injection of carboplatin for recurrent glioblastomas in his left temporal lobe. He complained of pain and visual disturbance in the ipsilateral eye 30 h after the injection. Various ocular symptoms and findings caused by carboplatin toxicity were seen. RESULTS: He was treated with intravenous administration of corticosteroids and glycerin for 6 days after the injection. Although the intraocular pressure elevation caused by secondary acute angle-closure glaucoma decreased and ocular pain diminished, inexorable papilledema and exudative retinal detachment continued for 3 weeks. Finally, 6 weeks later, diffuse chorioretinal atrophy with optic atrophy occurred and the vision in his left eye was lost. CONCLUSION: When performing intracarotid injection of carboplatin, we must be aware of its potentially blinding ocular toxicity. It is recommended that further studies and investigations are undertaken in the effort to minimize such severe side effects.", "entity": "Papilledema", "aliases": "Choked Disk Disks Decreased Intraocular Pressure Associated Papilledema Pressure-Associated Edema Optic Papilla Retinal Edemas Increased Intracranial Nerve Papillitides Papillitis with Papilledemas", "definition": "Swelling of the OPTIC DISK, usually in association with increased intracranial pressure, characterized by hyperemia, blurring of the disk margins, microhemorrhages, blind spot enlargement, and engorgement of retinal veins. Chronic papilledema may cause OPTIC ATROPHY and visual loss. (Miller et al., Clinical Neuro-Ophthalmology, 4th ed, p175)\n    ", "id": "MESH:D010211"}
{"mention": "retinal detachment", "mention_text": "BACKGROUND: Glioblastoma is a malignant tumor that occurs in the cerebrum during adulthood. With current treatment regimens including combined surgery, radiation and chemotherapy, the average life expectancy of the patients is limited to approximately 1 year. Therefore, patients with glioblastoma sometimes have intracarotid injection of carcinostatics added to the treatment regimen. Generally, carboplatin is said to have milder side effects than cisplatin, whose ocular and orbital toxicity are well known. However, we experienced a case of severe ocular and orbital toxicity after intracarotid injection of carboplatin, which is infrequently reported. CASE: A 58-year-old man received an intracarotid injection of carboplatin for recurrent glioblastomas in his left temporal lobe. He complained of pain and visual disturbance in the ipsilateral eye 30 h after the injection. Various ocular symptoms and findings caused by carboplatin toxicity were seen. RESULTS: He was treated with intravenous administration of corticosteroids and glycerin for 6 days after the injection. Although the intraocular pressure elevation caused by secondary acute angle-closure glaucoma decreased and ocular pain diminished, inexorable papilledema and exudative retinal detachment continued for 3 weeks. Finally, 6 weeks later, diffuse chorioretinal atrophy with optic atrophy occurred and the vision in his left eye was lost. CONCLUSION: When performing intracarotid injection of carboplatin, we must be aware of its potentially blinding ocular toxicity. It is recommended that further studies and investigations are undertaken in the effort to minimize such severe side effects.", "entity": "Retinal Detachment", "aliases": "Detachment Retinal Detachments Pigment Epithelial", "definition": "Separation of the inner layers of the retina (neural retina) from the pigment epithelium. Retinal detachment occurs more commonly in men than in women, in eyes with degenerative myopia, in aging and in aphakia. It may occur after an uncomplicated cataract extraction, but it is seen more often if vitreous humor has been lost during surgery. (Dorland, 27th ed; Newell, Ophthalmology: Principles and Concepts, 7th ed, p310-12).\n    ", "id": "MESH:D012163"}
{"mention": "chorioretinal atrophy", "mention_text": "BACKGROUND: Glioblastoma is a malignant tumor that occurs in the cerebrum during adulthood. With current treatment regimens including combined surgery, radiation and chemotherapy, the average life expectancy of the patients is limited to approximately 1 year. Therefore, patients with glioblastoma sometimes have intracarotid injection of carcinostatics added to the treatment regimen. Generally, carboplatin is said to have milder side effects than cisplatin, whose ocular and orbital toxicity are well known. However, we experienced a case of severe ocular and orbital toxicity after intracarotid injection of carboplatin, which is infrequently reported. CASE: A 58-year-old man received an intracarotid injection of carboplatin for recurrent glioblastomas in his left temporal lobe. He complained of pain and visual disturbance in the ipsilateral eye 30 h after the injection. Various ocular symptoms and findings caused by carboplatin toxicity were seen. RESULTS: He was treated with intravenous administration of corticosteroids and glycerin for 6 days after the injection. Although the intraocular pressure elevation caused by secondary acute angle-closure glaucoma decreased and ocular pain diminished, inexorable papilledema and exudative retinal detachment continued for 3 weeks. Finally, 6 weeks later, diffuse chorioretinal atrophy with optic atrophy occurred and the vision in his left eye was lost. CONCLUSION: When performing intracarotid injection of carboplatin, we must be aware of its potentially blinding ocular toxicity. It is recommended that further studies and investigations are undertaken in the effort to minimize such severe side effects.", "entity": "Sveinsson Chorioretinal Atrophy", "aliases": "Atrophia Areata Helicoidal Peripapillary Chorioretinal Degeneration Icelandic Type Sveinsson Atrophy", "definition": "", "id": "MESH:C566236"}
{"mention": "optic atrophy", "mention_text": "BACKGROUND: Glioblastoma is a malignant tumor that occurs in the cerebrum during adulthood. With current treatment regimens including combined surgery, radiation and chemotherapy, the average life expectancy of the patients is limited to approximately 1 year. Therefore, patients with glioblastoma sometimes have intracarotid injection of carcinostatics added to the treatment regimen. Generally, carboplatin is said to have milder side effects than cisplatin, whose ocular and orbital toxicity are well known. However, we experienced a case of severe ocular and orbital toxicity after intracarotid injection of carboplatin, which is infrequently reported. CASE: A 58-year-old man received an intracarotid injection of carboplatin for recurrent glioblastomas in his left temporal lobe. He complained of pain and visual disturbance in the ipsilateral eye 30 h after the injection. Various ocular symptoms and findings caused by carboplatin toxicity were seen. RESULTS: He was treated with intravenous administration of corticosteroids and glycerin for 6 days after the injection. Although the intraocular pressure elevation caused by secondary acute angle-closure glaucoma decreased and ocular pain diminished, inexorable papilledema and exudative retinal detachment continued for 3 weeks. Finally, 6 weeks later, diffuse chorioretinal atrophy with optic atrophy occurred and the vision in his left eye was lost. CONCLUSION: When performing intracarotid injection of carboplatin, we must be aware of its potentially blinding ocular toxicity. It is recommended that further studies and investigations are undertaken in the effort to minimize such severe side effects.", "entity": "Optic Atrophy", "aliases": "Atrophy Optic", "definition": "Atrophy of the optic disk which may be congenital or acquired. This condition indicates a deficiency in the number of nerve fibers which arise in the RETINA and converge to form the OPTIC DISK; OPTIC NERVE; OPTIC CHIASM; and optic tracts. GLAUCOMA; ISCHEMIA; inflammation, a chronic elevation of intracranial pressure, toxins, optic nerve compression, and inherited conditions (see OPTIC ATROPHIES, HEREDITARY) are relatively common causes of this condition.\n    ", "id": "MESH:D009896"}
{"mention": "ocular toxicity", "mention_text": "BACKGROUND: Glioblastoma is a malignant tumor that occurs in the cerebrum during adulthood. With current treatment regimens including combined surgery, radiation and chemotherapy, the average life expectancy of the patients is limited to approximately 1 year. Therefore, patients with glioblastoma sometimes have intracarotid injection of carcinostatics added to the treatment regimen. Generally, carboplatin is said to have milder side effects than cisplatin, whose ocular and orbital toxicity are well known. However, we experienced a case of severe ocular and orbital toxicity after intracarotid injection of carboplatin, which is infrequently reported. CASE: A 58-year-old man received an intracarotid injection of carboplatin for recurrent glioblastomas in his left temporal lobe. He complained of pain and visual disturbance in the ipsilateral eye 30 h after the injection. Various ocular symptoms and findings caused by carboplatin toxicity were seen. RESULTS: He was treated with intravenous administration of corticosteroids and glycerin for 6 days after the injection. Although the intraocular pressure elevation caused by secondary acute angle-closure glaucoma decreased and ocular pain diminished, inexorable papilledema and exudative retinal detachment continued for 3 weeks. Finally, 6 weeks later, diffuse chorioretinal atrophy with optic atrophy occurred and the vision in his left eye was lost. CONCLUSION: When performing intracarotid injection of carboplatin, we must be aware of its potentially blinding ocular toxicity. It is recommended that further studies and investigations are undertaken in the effort to minimize such severe side effects.", "entity": "Eye Diseases", "aliases": "Disease Eye Diseases", "definition": "Diseases affecting the eye.\n    ", "id": "MESH:D005128"}
{"mention": "amsacrine", "mention_text": "Phase II study of the amsacrine analogue CI-921 (NSC 343499) in non-small cell lung cancer.", "entity": "Amsacrine", "aliases": "AMSA P D P-D PD Acridine Cain's Amsacrina Amsacrine Gödecke Brand Amsidine Amsidyl Cain Cains of NSC 141549 156303 249992 NSC-141549 NSC-156303 NSC-249992 NSC141549 NSC156303 NSC249992 Parke Davis Lactate SN 11841 SN-11841 SN11841 m-AMSA meta meta-AMSA", "definition": "Aminoacridine derivative that is a potent intercalating antineoplastic agent. It is effective in the treatment of acute leukemias and malignant lymphomas, but has poor activity in the treatment of solid tumors. It is frequently used in combination with other antineoplastic agents in chemotherapy protocols. It produces consistent but acceptable myelosuppression and cardiotoxic effects.\n    ", "id": "MESH:D000677"}
{"mention": "CI-921", "mention_text": "Phase II study of the amsacrine analogue CI-921 (NSC 343499) in non-small cell lung cancer.", "entity": "asulacrine", "aliases": "4-Acridinecarboxamide 9-((2-methoxy-4-((methylsulfonyl)amino)phenyl)amino)-N,5-dimethyl- CI 921 CI-921 N-5-dimethyl-9-((2-methoxy-4-methylsulfonylamino)phenylamino)-4-acridinecarboxamide NSC 343499 NSC-343499 asulacrine", "definition": "", "id": "MESH:C042315"}
{"mention": "NSC 343499", "mention_text": "Phase II study of the amsacrine analogue CI-921 (NSC 343499) in non-small cell lung cancer.", "entity": "asulacrine", "aliases": "4-Acridinecarboxamide 9-((2-methoxy-4-((methylsulfonyl)amino)phenyl)amino)-N,5-dimethyl- CI 921 CI-921 N-5-dimethyl-9-((2-methoxy-4-methylsulfonylamino)phenylamino)-4-acridinecarboxamide NSC 343499 NSC-343499 asulacrine", "definition": "", "id": "MESH:C042315"}
{"mention": "non-small cell lung cancer", "mention_text": "Phase II study of the amsacrine analogue CI-921 (NSC 343499) in non-small cell lung cancer.", "entity": "Carcinoma, Non-Small-Cell Lung", "aliases": "Carcinoma Non Small Cell Lung Non-Small Non-Small-Cell Carcinomas Cancer Nonsmall", "definition": "A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.\n    ", "id": "MESH:D002289"}
{"mention": "CI-921", "mention_text": "CI-921 (NSC 343499; 9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide) is a topoisomerase II poison with high experimental antitumour activity. It was administered by 15 min infusion to 16 evaluable patients with non-small cell lung cancer (NSCLC) (7 with no prior treatment, 9 patients in relapse following surgery/radiotherapy) at a dose (648 mg/m2 divided over 3 days, repeated every 3 weeks) determined by phase I trial. Patients had a median performance status of 1 (WHO), and median age of 61 years. The histology comprised squamous carcinoma (11), adenocarcinoma (1), mixed histology (2), bronchio-alveolar carcinoma (1) and large cell undifferentiated carcinoma (1). Neutropenia grade greater than or equal to 3 was seen in 15 patients, infections with recovery in 3, and grand mal seizures in 1 patient. Grade less than or equal to 2 nausea and vomiting occurred in 66% courses and phlebitis in the infusion arm in 37%. 1 patient with squamous cell carcinoma achieved a partial response lasting 5 months. Further testing in this and other tumour types using multiple daily schedules is warranted.", "entity": "asulacrine", "aliases": "4-Acridinecarboxamide 9-((2-methoxy-4-((methylsulfonyl)amino)phenyl)amino)-N,5-dimethyl- CI 921 CI-921 N-5-dimethyl-9-((2-methoxy-4-methylsulfonylamino)phenylamino)-4-acridinecarboxamide NSC 343499 NSC-343499 asulacrine", "definition": "", "id": "MESH:C042315"}
{"mention": "NSC 343499", "mention_text": "CI-921 (NSC 343499; 9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide) is a topoisomerase II poison with high experimental antitumour activity. It was administered by 15 min infusion to 16 evaluable patients with non-small cell lung cancer (NSCLC) (7 with no prior treatment, 9 patients in relapse following surgery/radiotherapy) at a dose (648 mg/m2 divided over 3 days, repeated every 3 weeks) determined by phase I trial. Patients had a median performance status of 1 (WHO), and median age of 61 years. The histology comprised squamous carcinoma (11), adenocarcinoma (1), mixed histology (2), bronchio-alveolar carcinoma (1) and large cell undifferentiated carcinoma (1). Neutropenia grade greater than or equal to 3 was seen in 15 patients, infections with recovery in 3, and grand mal seizures in 1 patient. Grade less than or equal to 2 nausea and vomiting occurred in 66% courses and phlebitis in the infusion arm in 37%. 1 patient with squamous cell carcinoma achieved a partial response lasting 5 months. Further testing in this and other tumour types using multiple daily schedules is warranted.", "entity": "asulacrine", "aliases": "4-Acridinecarboxamide 9-((2-methoxy-4-((methylsulfonyl)amino)phenyl)amino)-N,5-dimethyl- CI 921 CI-921 N-5-dimethyl-9-((2-methoxy-4-methylsulfonylamino)phenylamino)-4-acridinecarboxamide NSC 343499 NSC-343499 asulacrine", "definition": "", "id": "MESH:C042315"}
{"mention": "9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide", "mention_text": "CI-921 (NSC 343499; 9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide) is a topoisomerase II poison with high experimental antitumour activity. It was administered by 15 min infusion to 16 evaluable patients with non-small cell lung cancer (NSCLC) (7 with no prior treatment, 9 patients in relapse following surgery/radiotherapy) at a dose (648 mg/m2 divided over 3 days, repeated every 3 weeks) determined by phase I trial. Patients had a median performance status of 1 (WHO), and median age of 61 years. The histology comprised squamous carcinoma (11), adenocarcinoma (1), mixed histology (2), bronchio-alveolar carcinoma (1) and large cell undifferentiated carcinoma (1). Neutropenia grade greater than or equal to 3 was seen in 15 patients, infections with recovery in 3, and grand mal seizures in 1 patient. Grade less than or equal to 2 nausea and vomiting occurred in 66% courses and phlebitis in the infusion arm in 37%. 1 patient with squamous cell carcinoma achieved a partial response lasting 5 months. Further testing in this and other tumour types using multiple daily schedules is warranted.", "entity": "asulacrine", "aliases": "4-Acridinecarboxamide 9-((2-methoxy-4-((methylsulfonyl)amino)phenyl)amino)-N,5-dimethyl- CI 921 CI-921 N-5-dimethyl-9-((2-methoxy-4-methylsulfonylamino)phenylamino)-4-acridinecarboxamide NSC 343499 NSC-343499 asulacrine", "definition": "", "id": "MESH:C042315"}
{"mention": "non-small cell lung cancer", "mention_text": "CI-921 (NSC 343499; 9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide) is a topoisomerase II poison with high experimental antitumour activity. It was administered by 15 min infusion to 16 evaluable patients with non-small cell lung cancer (NSCLC) (7 with no prior treatment, 9 patients in relapse following surgery/radiotherapy) at a dose (648 mg/m2 divided over 3 days, repeated every 3 weeks) determined by phase I trial. Patients had a median performance status of 1 (WHO), and median age of 61 years. The histology comprised squamous carcinoma (11), adenocarcinoma (1), mixed histology (2), bronchio-alveolar carcinoma (1) and large cell undifferentiated carcinoma (1). Neutropenia grade greater than or equal to 3 was seen in 15 patients, infections with recovery in 3, and grand mal seizures in 1 patient. Grade less than or equal to 2 nausea and vomiting occurred in 66% courses and phlebitis in the infusion arm in 37%. 1 patient with squamous cell carcinoma achieved a partial response lasting 5 months. Further testing in this and other tumour types using multiple daily schedules is warranted.", "entity": "Carcinoma, Non-Small-Cell Lung", "aliases": "Carcinoma Non Small Cell Lung Non-Small Non-Small-Cell Carcinomas Cancer Nonsmall", "definition": "A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.\n    ", "id": "MESH:D002289"}
{"mention": "NSCLC", "mention_text": "CI-921 (NSC 343499; 9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide) is a topoisomerase II poison with high experimental antitumour activity. It was administered by 15 min infusion to 16 evaluable patients with non-small cell lung cancer (NSCLC) (7 with no prior treatment, 9 patients in relapse following surgery/radiotherapy) at a dose (648 mg/m2 divided over 3 days, repeated every 3 weeks) determined by phase I trial. Patients had a median performance status of 1 (WHO), and median age of 61 years. The histology comprised squamous carcinoma (11), adenocarcinoma (1), mixed histology (2), bronchio-alveolar carcinoma (1) and large cell undifferentiated carcinoma (1). Neutropenia grade greater than or equal to 3 was seen in 15 patients, infections with recovery in 3, and grand mal seizures in 1 patient. Grade less than or equal to 2 nausea and vomiting occurred in 66% courses and phlebitis in the infusion arm in 37%. 1 patient with squamous cell carcinoma achieved a partial response lasting 5 months. Further testing in this and other tumour types using multiple daily schedules is warranted.", "entity": "Carcinoma, Non-Small-Cell Lung", "aliases": "Carcinoma Non Small Cell Lung Non-Small Non-Small-Cell Carcinomas Cancer Nonsmall", "definition": "A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.\n    ", "id": "MESH:D002289"}
{"mention": "squamous carcinoma", "mention_text": "CI-921 (NSC 343499; 9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide) is a topoisomerase II poison with high experimental antitumour activity. It was administered by 15 min infusion to 16 evaluable patients with non-small cell lung cancer (NSCLC) (7 with no prior treatment, 9 patients in relapse following surgery/radiotherapy) at a dose (648 mg/m2 divided over 3 days, repeated every 3 weeks) determined by phase I trial. Patients had a median performance status of 1 (WHO), and median age of 61 years. The histology comprised squamous carcinoma (11), adenocarcinoma (1), mixed histology (2), bronchio-alveolar carcinoma (1) and large cell undifferentiated carcinoma (1). Neutropenia grade greater than or equal to 3 was seen in 15 patients, infections with recovery in 3, and grand mal seizures in 1 patient. Grade less than or equal to 2 nausea and vomiting occurred in 66% courses and phlebitis in the infusion arm in 37%. 1 patient with squamous cell carcinoma achieved a partial response lasting 5 months. Further testing in this and other tumour types using multiple daily schedules is warranted.", "entity": "Carcinoma, Squamous Cell", "aliases": "Carcinoma Epidermoid Planocellular Squamous Cell Carcinomas", "definition": "A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)\n    ", "id": "MESH:D002294"}
{"mention": "adenocarcinoma", "mention_text": "CI-921 (NSC 343499; 9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide) is a topoisomerase II poison with high experimental antitumour activity. It was administered by 15 min infusion to 16 evaluable patients with non-small cell lung cancer (NSCLC) (7 with no prior treatment, 9 patients in relapse following surgery/radiotherapy) at a dose (648 mg/m2 divided over 3 days, repeated every 3 weeks) determined by phase I trial. Patients had a median performance status of 1 (WHO), and median age of 61 years. The histology comprised squamous carcinoma (11), adenocarcinoma (1), mixed histology (2), bronchio-alveolar carcinoma (1) and large cell undifferentiated carcinoma (1). Neutropenia grade greater than or equal to 3 was seen in 15 patients, infections with recovery in 3, and grand mal seizures in 1 patient. Grade less than or equal to 2 nausea and vomiting occurred in 66% courses and phlebitis in the infusion arm in 37%. 1 patient with squamous cell carcinoma achieved a partial response lasting 5 months. Further testing in this and other tumour types using multiple daily schedules is warranted.", "entity": "Adenocarcinoma", "aliases": "Adenocarcinoma Basal Cell Granular Oxyphilic Tubular Adenocarcinomas Adenoma Malignant Adenomas Carcinoma Cribriform Carcinomas", "definition": "A malignant epithelial tumor with a glandular organization.\n    ", "id": "MESH:D000230"}
{"mention": "bronchio-alveolar carcinoma", "mention_text": "CI-921 (NSC 343499; 9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide) is a topoisomerase II poison with high experimental antitumour activity. It was administered by 15 min infusion to 16 evaluable patients with non-small cell lung cancer (NSCLC) (7 with no prior treatment, 9 patients in relapse following surgery/radiotherapy) at a dose (648 mg/m2 divided over 3 days, repeated every 3 weeks) determined by phase I trial. Patients had a median performance status of 1 (WHO), and median age of 61 years. The histology comprised squamous carcinoma (11), adenocarcinoma (1), mixed histology (2), bronchio-alveolar carcinoma (1) and large cell undifferentiated carcinoma (1). Neutropenia grade greater than or equal to 3 was seen in 15 patients, infections with recovery in 3, and grand mal seizures in 1 patient. Grade less than or equal to 2 nausea and vomiting occurred in 66% courses and phlebitis in the infusion arm in 37%. 1 patient with squamous cell carcinoma achieved a partial response lasting 5 months. Further testing in this and other tumour types using multiple daily schedules is warranted.", "entity": "Adenocarcinoma, Bronchiolo-Alveolar", "aliases": "Adenocarcinoma Alveolar Bronchiolo Bronchiolo-Alveolar Adenocarcinomas Carcinoma Carcinomas Cell Bronchiolar Bronchioloalveolar", "definition": "A carcinoma thought to be derived from epithelium of terminal bronchioles, in which the neoplastic tissue extends along the alveolar walls and grows in small masses within the alveoli. Involvement may be uniformly diffuse and massive, or nodular, or lobular. The neoplastic cells are cuboidal or columnar and form papillary structures. Mucin may be demonstrated in some of the cells and in the material in the alveoli, which also includes denuded cells. Metastases in regional lymph nodes, and in even more distant sites, are known to occur, but are infrequent. (From Stedman, 25th ed)\n    ", "id": "MESH:D002282"}
{"mention": "undifferentiated carcinoma", "mention_text": "CI-921 (NSC 343499; 9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide) is a topoisomerase II poison with high experimental antitumour activity. It was administered by 15 min infusion to 16 evaluable patients with non-small cell lung cancer (NSCLC) (7 with no prior treatment, 9 patients in relapse following surgery/radiotherapy) at a dose (648 mg/m2 divided over 3 days, repeated every 3 weeks) determined by phase I trial. Patients had a median performance status of 1 (WHO), and median age of 61 years. The histology comprised squamous carcinoma (11), adenocarcinoma (1), mixed histology (2), bronchio-alveolar carcinoma (1) and large cell undifferentiated carcinoma (1). Neutropenia grade greater than or equal to 3 was seen in 15 patients, infections with recovery in 3, and grand mal seizures in 1 patient. Grade less than or equal to 2 nausea and vomiting occurred in 66% courses and phlebitis in the infusion arm in 37%. 1 patient with squamous cell carcinoma achieved a partial response lasting 5 months. Further testing in this and other tumour types using multiple daily schedules is warranted.", "entity": "Carcinoma", "aliases": "Anaplastic Carcinoma Carcinomas Spindle Cell Spindle-Cell Undifferentiated Carcinomatoses Carcinomatosis Epithelial Neoplasm Malignant Neoplasms Tumor Tumors Epithelioma Epitheliomas", "definition": "A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm but is often wrongly used as a synonym for \"cancer.\" (From Dorland, 27th ed)\n    ", "id": "MESH:D002277"}
{"mention": "Neutropenia", "mention_text": "CI-921 (NSC 343499; 9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide) is a topoisomerase II poison with high experimental antitumour activity. It was administered by 15 min infusion to 16 evaluable patients with non-small cell lung cancer (NSCLC) (7 with no prior treatment, 9 patients in relapse following surgery/radiotherapy) at a dose (648 mg/m2 divided over 3 days, repeated every 3 weeks) determined by phase I trial. Patients had a median performance status of 1 (WHO), and median age of 61 years. The histology comprised squamous carcinoma (11), adenocarcinoma (1), mixed histology (2), bronchio-alveolar carcinoma (1) and large cell undifferentiated carcinoma (1). Neutropenia grade greater than or equal to 3 was seen in 15 patients, infections with recovery in 3, and grand mal seizures in 1 patient. Grade less than or equal to 2 nausea and vomiting occurred in 66% courses and phlebitis in the infusion arm in 37%. 1 patient with squamous cell carcinoma achieved a partial response lasting 5 months. Further testing in this and other tumour types using multiple daily schedules is warranted.", "entity": "Neutropenia", "aliases": "Neutropenia Neutropenias", "definition": "A decrease in the number of NEUTROPHILS found in the blood.\n    ", "id": "MESH:D009503"}
{"mention": "infections", "mention_text": "CI-921 (NSC 343499; 9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide) is a topoisomerase II poison with high experimental antitumour activity. It was administered by 15 min infusion to 16 evaluable patients with non-small cell lung cancer (NSCLC) (7 with no prior treatment, 9 patients in relapse following surgery/radiotherapy) at a dose (648 mg/m2 divided over 3 days, repeated every 3 weeks) determined by phase I trial. Patients had a median performance status of 1 (WHO), and median age of 61 years. The histology comprised squamous carcinoma (11), adenocarcinoma (1), mixed histology (2), bronchio-alveolar carcinoma (1) and large cell undifferentiated carcinoma (1). Neutropenia grade greater than or equal to 3 was seen in 15 patients, infections with recovery in 3, and grand mal seizures in 1 patient. Grade less than or equal to 2 nausea and vomiting occurred in 66% courses and phlebitis in the infusion arm in 37%. 1 patient with squamous cell carcinoma achieved a partial response lasting 5 months. Further testing in this and other tumour types using multiple daily schedules is warranted.", "entity": "Infection", "aliases": "Infection Infections", "definition": "Invasion of the host organism by microorganisms that can cause pathological conditions or diseases.\n    ", "id": "MESH:D007239"}
{"mention": "seizures", "mention_text": "CI-921 (NSC 343499; 9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide) is a topoisomerase II poison with high experimental antitumour activity. It was administered by 15 min infusion to 16 evaluable patients with non-small cell lung cancer (NSCLC) (7 with no prior treatment, 9 patients in relapse following surgery/radiotherapy) at a dose (648 mg/m2 divided over 3 days, repeated every 3 weeks) determined by phase I trial. Patients had a median performance status of 1 (WHO), and median age of 61 years. The histology comprised squamous carcinoma (11), adenocarcinoma (1), mixed histology (2), bronchio-alveolar carcinoma (1) and large cell undifferentiated carcinoma (1). Neutropenia grade greater than or equal to 3 was seen in 15 patients, infections with recovery in 3, and grand mal seizures in 1 patient. Grade less than or equal to 2 nausea and vomiting occurred in 66% courses and phlebitis in the infusion arm in 37%. 1 patient with squamous cell carcinoma achieved a partial response lasting 5 months. Further testing in this and other tumour types using multiple daily schedules is warranted.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "nausea", "mention_text": "CI-921 (NSC 343499; 9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide) is a topoisomerase II poison with high experimental antitumour activity. It was administered by 15 min infusion to 16 evaluable patients with non-small cell lung cancer (NSCLC) (7 with no prior treatment, 9 patients in relapse following surgery/radiotherapy) at a dose (648 mg/m2 divided over 3 days, repeated every 3 weeks) determined by phase I trial. Patients had a median performance status of 1 (WHO), and median age of 61 years. The histology comprised squamous carcinoma (11), adenocarcinoma (1), mixed histology (2), bronchio-alveolar carcinoma (1) and large cell undifferentiated carcinoma (1). Neutropenia grade greater than or equal to 3 was seen in 15 patients, infections with recovery in 3, and grand mal seizures in 1 patient. Grade less than or equal to 2 nausea and vomiting occurred in 66% courses and phlebitis in the infusion arm in 37%. 1 patient with squamous cell carcinoma achieved a partial response lasting 5 months. Further testing in this and other tumour types using multiple daily schedules is warranted.", "entity": "Nausea", "aliases": "Nausea", "definition": "An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.\n    ", "id": "MESH:D009325"}
{"mention": "vomiting", "mention_text": "CI-921 (NSC 343499; 9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide) is a topoisomerase II poison with high experimental antitumour activity. It was administered by 15 min infusion to 16 evaluable patients with non-small cell lung cancer (NSCLC) (7 with no prior treatment, 9 patients in relapse following surgery/radiotherapy) at a dose (648 mg/m2 divided over 3 days, repeated every 3 weeks) determined by phase I trial. Patients had a median performance status of 1 (WHO), and median age of 61 years. The histology comprised squamous carcinoma (11), adenocarcinoma (1), mixed histology (2), bronchio-alveolar carcinoma (1) and large cell undifferentiated carcinoma (1). Neutropenia grade greater than or equal to 3 was seen in 15 patients, infections with recovery in 3, and grand mal seizures in 1 patient. Grade less than or equal to 2 nausea and vomiting occurred in 66% courses and phlebitis in the infusion arm in 37%. 1 patient with squamous cell carcinoma achieved a partial response lasting 5 months. Further testing in this and other tumour types using multiple daily schedules is warranted.", "entity": "Vomiting", "aliases": "Emesis Vomiting", "definition": "The forcible expulsion of the contents of the STOMACH through the MOUTH.\n    ", "id": "MESH:D014839"}
{"mention": "phlebitis", "mention_text": "CI-921 (NSC 343499; 9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide) is a topoisomerase II poison with high experimental antitumour activity. It was administered by 15 min infusion to 16 evaluable patients with non-small cell lung cancer (NSCLC) (7 with no prior treatment, 9 patients in relapse following surgery/radiotherapy) at a dose (648 mg/m2 divided over 3 days, repeated every 3 weeks) determined by phase I trial. Patients had a median performance status of 1 (WHO), and median age of 61 years. The histology comprised squamous carcinoma (11), adenocarcinoma (1), mixed histology (2), bronchio-alveolar carcinoma (1) and large cell undifferentiated carcinoma (1). Neutropenia grade greater than or equal to 3 was seen in 15 patients, infections with recovery in 3, and grand mal seizures in 1 patient. Grade less than or equal to 2 nausea and vomiting occurred in 66% courses and phlebitis in the infusion arm in 37%. 1 patient with squamous cell carcinoma achieved a partial response lasting 5 months. Further testing in this and other tumour types using multiple daily schedules is warranted.", "entity": "Phlebitis", "aliases": "Periphlebitides Periphlebitis Phlebitides Phlebitis", "definition": "Inflammation of a vein, often a vein in the leg. Phlebitis associated with a blood clot is called (THROMBOPHLEBITIS).\n    ", "id": "MESH:D010689"}
{"mention": "squamous cell carcinoma", "mention_text": "CI-921 (NSC 343499; 9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide) is a topoisomerase II poison with high experimental antitumour activity. It was administered by 15 min infusion to 16 evaluable patients with non-small cell lung cancer (NSCLC) (7 with no prior treatment, 9 patients in relapse following surgery/radiotherapy) at a dose (648 mg/m2 divided over 3 days, repeated every 3 weeks) determined by phase I trial. Patients had a median performance status of 1 (WHO), and median age of 61 years. The histology comprised squamous carcinoma (11), adenocarcinoma (1), mixed histology (2), bronchio-alveolar carcinoma (1) and large cell undifferentiated carcinoma (1). Neutropenia grade greater than or equal to 3 was seen in 15 patients, infections with recovery in 3, and grand mal seizures in 1 patient. Grade less than or equal to 2 nausea and vomiting occurred in 66% courses and phlebitis in the infusion arm in 37%. 1 patient with squamous cell carcinoma achieved a partial response lasting 5 months. Further testing in this and other tumour types using multiple daily schedules is warranted.", "entity": "Carcinoma, Squamous Cell", "aliases": "Carcinoma Epidermoid Planocellular Squamous Cell Carcinomas", "definition": "A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)\n    ", "id": "MESH:D002294"}
{"mention": "tumour", "mention_text": "CI-921 (NSC 343499; 9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide) is a topoisomerase II poison with high experimental antitumour activity. It was administered by 15 min infusion to 16 evaluable patients with non-small cell lung cancer (NSCLC) (7 with no prior treatment, 9 patients in relapse following surgery/radiotherapy) at a dose (648 mg/m2 divided over 3 days, repeated every 3 weeks) determined by phase I trial. Patients had a median performance status of 1 (WHO), and median age of 61 years. The histology comprised squamous carcinoma (11), adenocarcinoma (1), mixed histology (2), bronchio-alveolar carcinoma (1) and large cell undifferentiated carcinoma (1). Neutropenia grade greater than or equal to 3 was seen in 15 patients, infections with recovery in 3, and grand mal seizures in 1 patient. Grade less than or equal to 2 nausea and vomiting occurred in 66% courses and phlebitis in the infusion arm in 37%. 1 patient with squamous cell carcinoma achieved a partial response lasting 5 months. Further testing in this and other tumour types using multiple daily schedules is warranted.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "Alpha-lipoic acid", "mention_text": "Alpha-lipoic acid prevents mitochondrial damage and neurotoxicity in experimental chemotherapy neuropathy.", "entity": "Thioctic Acid", "aliases": "Acid alpha-Lipoic Aliud Brand of Thioctic Alpha Lipogamma Lipon Stada Liponsaure Sofotec Lippon AL Alpha-Lipogamma Alpha-Lipon Alpha-Liponsaure Alpha-Lippon AlphaLipogamma AlphaLipon AlphaLiponsaure AlphaLippon Alphaflam Azulipont Azupharma Fenint Generosan Heumann Hexal Illa Tromethamine Injekt Thiogamma Juta Juthiac Lichtenstein Lipoic ratiopharm Liponsaure-ratiopharm Liponsaureratiopharm MTW Alphaliponsaure MTW-Alphaliponsaure MTWAlphaliponsaure Merck dura Neurium Pharmacia Pleomix N Pleomix-", "definition": "An octanoic acid bridged with two sulfurs so that it is sometimes also called a pentanoic acid in some naming schemes. It is biosynthesized by cleavage of LINOLEIC ACID and is a coenzyme of oxoglutarate dehydrogenase (KETOGLUTARATE DEHYDROGENASE COMPLEX). It is used in DIETARY SUPPLEMENTS.\n    ", "id": "MESH:D008063"}
{"mention": "mitochondrial damage", "mention_text": "Alpha-lipoic acid prevents mitochondrial damage and neurotoxicity in experimental chemotherapy neuropathy.", "entity": "Mitochondrial Diseases", "aliases": "Deficiencies Oxidative Phosphorylation Respiratory Chain Deficiency Disease Mitochondrial Disorder Disorders Electron Transport Diseases", "definition": "Diseases caused by abnormal function of the MITOCHONDRIA. They may be caused by mutations, acquired or inherited, in mitochondrial DNA or in nuclear genes that code for mitochondrial components. They may also be the result of acquired mitochondria dysfunction due to adverse effects of drugs, infections, or other environmental causes.\n    ", "id": "MESH:D028361"}
{"mention": "neurotoxicity", "mention_text": "Alpha-lipoic acid prevents mitochondrial damage and neurotoxicity in experimental chemotherapy neuropathy.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "neuropathy", "mention_text": "Alpha-lipoic acid prevents mitochondrial damage and neurotoxicity in experimental chemotherapy neuropathy.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "alpha-lipoic acid", "mention_text": "The study investigates if alpha-lipoic acid is neuroprotective against chemotherapy induced neurotoxicity, if mitochondrial damage plays a critical role in toxic neurodegenerative cascade, and if neuroprotective effects of alpha-lipoic acid depend on mitochondria protection. We used an in vitro model of chemotherapy induced peripheral neuropathy that closely mimic the in vivo condition by exposing primary cultures of dorsal root ganglion (DRG) sensory neurons to paclitaxel and cisplatin, two widely used and highly effective chemotherapeutic drugs. This approach allowed investigating the efficacy of alpha-lipoic acid in preventing axonal damage and apoptosis and the function and ultrastructural morphology of mitochondria after exposure to toxic agents and alpha-lipoic acid. Our results demonstrate that both cisplatin and paclitaxel cause early mitochondrial impairment with loss of membrane potential and induction of autophagic vacuoles in neurons. Alpha-lipoic acid exerts neuroprotective effects against chemotherapy induced neurotoxicity in sensory neurons: it rescues the mitochondrial toxicity and induces the expression of frataxin, an essential mitochondrial protein with anti-oxidant and chaperone properties. In conclusion mitochondrial toxicity is an early common event both in paclitaxel and cisplatin induced neurotoxicity. Alpha-lipoic acid protects sensory neurons through its anti-oxidant and mitochondrial regulatory functions, possibly inducing the expression of frataxin. These findings suggest that alpha-lipoic acid might reduce the risk of developing peripheral nerve toxicity in patients undergoing chemotherapy and encourage further confirmatory clinical trials.", "entity": "Thioctic Acid", "aliases": "Acid alpha-Lipoic Aliud Brand of Thioctic Alpha Lipogamma Lipon Stada Liponsaure Sofotec Lippon AL Alpha-Lipogamma Alpha-Lipon Alpha-Liponsaure Alpha-Lippon AlphaLipogamma AlphaLipon AlphaLiponsaure AlphaLippon Alphaflam Azulipont Azupharma Fenint Generosan Heumann Hexal Illa Tromethamine Injekt Thiogamma Juta Juthiac Lichtenstein Lipoic ratiopharm Liponsaure-ratiopharm Liponsaureratiopharm MTW Alphaliponsaure MTW-Alphaliponsaure MTWAlphaliponsaure Merck dura Neurium Pharmacia Pleomix N Pleomix-", "definition": "An octanoic acid bridged with two sulfurs so that it is sometimes also called a pentanoic acid in some naming schemes. It is biosynthesized by cleavage of LINOLEIC ACID and is a coenzyme of oxoglutarate dehydrogenase (KETOGLUTARATE DEHYDROGENASE COMPLEX). It is used in DIETARY SUPPLEMENTS.\n    ", "id": "MESH:D008063"}
{"mention": "neurotoxicity", "mention_text": "The study investigates if alpha-lipoic acid is neuroprotective against chemotherapy induced neurotoxicity, if mitochondrial damage plays a critical role in toxic neurodegenerative cascade, and if neuroprotective effects of alpha-lipoic acid depend on mitochondria protection. We used an in vitro model of chemotherapy induced peripheral neuropathy that closely mimic the in vivo condition by exposing primary cultures of dorsal root ganglion (DRG) sensory neurons to paclitaxel and cisplatin, two widely used and highly effective chemotherapeutic drugs. This approach allowed investigating the efficacy of alpha-lipoic acid in preventing axonal damage and apoptosis and the function and ultrastructural morphology of mitochondria after exposure to toxic agents and alpha-lipoic acid. Our results demonstrate that both cisplatin and paclitaxel cause early mitochondrial impairment with loss of membrane potential and induction of autophagic vacuoles in neurons. Alpha-lipoic acid exerts neuroprotective effects against chemotherapy induced neurotoxicity in sensory neurons: it rescues the mitochondrial toxicity and induces the expression of frataxin, an essential mitochondrial protein with anti-oxidant and chaperone properties. In conclusion mitochondrial toxicity is an early common event both in paclitaxel and cisplatin induced neurotoxicity. Alpha-lipoic acid protects sensory neurons through its anti-oxidant and mitochondrial regulatory functions, possibly inducing the expression of frataxin. These findings suggest that alpha-lipoic acid might reduce the risk of developing peripheral nerve toxicity in patients undergoing chemotherapy and encourage further confirmatory clinical trials.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "mitochondrial damage", "mention_text": "The study investigates if alpha-lipoic acid is neuroprotective against chemotherapy induced neurotoxicity, if mitochondrial damage plays a critical role in toxic neurodegenerative cascade, and if neuroprotective effects of alpha-lipoic acid depend on mitochondria protection. We used an in vitro model of chemotherapy induced peripheral neuropathy that closely mimic the in vivo condition by exposing primary cultures of dorsal root ganglion (DRG) sensory neurons to paclitaxel and cisplatin, two widely used and highly effective chemotherapeutic drugs. This approach allowed investigating the efficacy of alpha-lipoic acid in preventing axonal damage and apoptosis and the function and ultrastructural morphology of mitochondria after exposure to toxic agents and alpha-lipoic acid. Our results demonstrate that both cisplatin and paclitaxel cause early mitochondrial impairment with loss of membrane potential and induction of autophagic vacuoles in neurons. Alpha-lipoic acid exerts neuroprotective effects against chemotherapy induced neurotoxicity in sensory neurons: it rescues the mitochondrial toxicity and induces the expression of frataxin, an essential mitochondrial protein with anti-oxidant and chaperone properties. In conclusion mitochondrial toxicity is an early common event both in paclitaxel and cisplatin induced neurotoxicity. Alpha-lipoic acid protects sensory neurons through its anti-oxidant and mitochondrial regulatory functions, possibly inducing the expression of frataxin. These findings suggest that alpha-lipoic acid might reduce the risk of developing peripheral nerve toxicity in patients undergoing chemotherapy and encourage further confirmatory clinical trials.", "entity": "Mitochondrial Diseases", "aliases": "Deficiencies Oxidative Phosphorylation Respiratory Chain Deficiency Disease Mitochondrial Disorder Disorders Electron Transport Diseases", "definition": "Diseases caused by abnormal function of the MITOCHONDRIA. They may be caused by mutations, acquired or inherited, in mitochondrial DNA or in nuclear genes that code for mitochondrial components. They may also be the result of acquired mitochondria dysfunction due to adverse effects of drugs, infections, or other environmental causes.\n    ", "id": "MESH:D028361"}
{"mention": "toxic neurodegenerative cascade", "mention_text": "The study investigates if alpha-lipoic acid is neuroprotective against chemotherapy induced neurotoxicity, if mitochondrial damage plays a critical role in toxic neurodegenerative cascade, and if neuroprotective effects of alpha-lipoic acid depend on mitochondria protection. We used an in vitro model of chemotherapy induced peripheral neuropathy that closely mimic the in vivo condition by exposing primary cultures of dorsal root ganglion (DRG) sensory neurons to paclitaxel and cisplatin, two widely used and highly effective chemotherapeutic drugs. This approach allowed investigating the efficacy of alpha-lipoic acid in preventing axonal damage and apoptosis and the function and ultrastructural morphology of mitochondria after exposure to toxic agents and alpha-lipoic acid. Our results demonstrate that both cisplatin and paclitaxel cause early mitochondrial impairment with loss of membrane potential and induction of autophagic vacuoles in neurons. Alpha-lipoic acid exerts neuroprotective effects against chemotherapy induced neurotoxicity in sensory neurons: it rescues the mitochondrial toxicity and induces the expression of frataxin, an essential mitochondrial protein with anti-oxidant and chaperone properties. In conclusion mitochondrial toxicity is an early common event both in paclitaxel and cisplatin induced neurotoxicity. Alpha-lipoic acid protects sensory neurons through its anti-oxidant and mitochondrial regulatory functions, possibly inducing the expression of frataxin. These findings suggest that alpha-lipoic acid might reduce the risk of developing peripheral nerve toxicity in patients undergoing chemotherapy and encourage further confirmatory clinical trials.", "entity": "Nerve Degeneration", "aliases": "Degeneration Nerve Neuron Degenerations", "definition": "Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.\n    ", "id": "MESH:D009410"}
{"mention": "peripheral neuropathy", "mention_text": "The study investigates if alpha-lipoic acid is neuroprotective against chemotherapy induced neurotoxicity, if mitochondrial damage plays a critical role in toxic neurodegenerative cascade, and if neuroprotective effects of alpha-lipoic acid depend on mitochondria protection. We used an in vitro model of chemotherapy induced peripheral neuropathy that closely mimic the in vivo condition by exposing primary cultures of dorsal root ganglion (DRG) sensory neurons to paclitaxel and cisplatin, two widely used and highly effective chemotherapeutic drugs. This approach allowed investigating the efficacy of alpha-lipoic acid in preventing axonal damage and apoptosis and the function and ultrastructural morphology of mitochondria after exposure to toxic agents and alpha-lipoic acid. Our results demonstrate that both cisplatin and paclitaxel cause early mitochondrial impairment with loss of membrane potential and induction of autophagic vacuoles in neurons. Alpha-lipoic acid exerts neuroprotective effects against chemotherapy induced neurotoxicity in sensory neurons: it rescues the mitochondrial toxicity and induces the expression of frataxin, an essential mitochondrial protein with anti-oxidant and chaperone properties. In conclusion mitochondrial toxicity is an early common event both in paclitaxel and cisplatin induced neurotoxicity. Alpha-lipoic acid protects sensory neurons through its anti-oxidant and mitochondrial regulatory functions, possibly inducing the expression of frataxin. These findings suggest that alpha-lipoic acid might reduce the risk of developing peripheral nerve toxicity in patients undergoing chemotherapy and encourage further confirmatory clinical trials.", "entity": "Peripheral Nervous System Diseases", "aliases": "Nerve Disease Peripheral Diseases Neuropathy PNS (Peripheral Nervous System) System Disorders Neuropathies", "definition": "Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.\n    ", "id": "MESH:D010523"}
{"mention": "paclitaxel", "mention_text": "The study investigates if alpha-lipoic acid is neuroprotective against chemotherapy induced neurotoxicity, if mitochondrial damage plays a critical role in toxic neurodegenerative cascade, and if neuroprotective effects of alpha-lipoic acid depend on mitochondria protection. We used an in vitro model of chemotherapy induced peripheral neuropathy that closely mimic the in vivo condition by exposing primary cultures of dorsal root ganglion (DRG) sensory neurons to paclitaxel and cisplatin, two widely used and highly effective chemotherapeutic drugs. This approach allowed investigating the efficacy of alpha-lipoic acid in preventing axonal damage and apoptosis and the function and ultrastructural morphology of mitochondria after exposure to toxic agents and alpha-lipoic acid. Our results demonstrate that both cisplatin and paclitaxel cause early mitochondrial impairment with loss of membrane potential and induction of autophagic vacuoles in neurons. Alpha-lipoic acid exerts neuroprotective effects against chemotherapy induced neurotoxicity in sensory neurons: it rescues the mitochondrial toxicity and induces the expression of frataxin, an essential mitochondrial protein with anti-oxidant and chaperone properties. In conclusion mitochondrial toxicity is an early common event both in paclitaxel and cisplatin induced neurotoxicity. Alpha-lipoic acid protects sensory neurons through its anti-oxidant and mitochondrial regulatory functions, possibly inducing the expression of frataxin. These findings suggest that alpha-lipoic acid might reduce the risk of developing peripheral nerve toxicity in patients undergoing chemotherapy and encourage further confirmatory clinical trials.", "entity": "Paclitaxel", "aliases": "7 epi Taxol 7-epi-Taxol Anzatax Bris Bristol-Myers Brand of Paclitaxel Squibb Bull Ivax Lemery NSC 125973 NSC-125973 NSC125973 Onxol (4 alpha)-Isomer Paxene Praxel A", "definition": "A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.\n    ", "id": "MESH:D017239"}
{"mention": "cisplatin", "mention_text": "The study investigates if alpha-lipoic acid is neuroprotective against chemotherapy induced neurotoxicity, if mitochondrial damage plays a critical role in toxic neurodegenerative cascade, and if neuroprotective effects of alpha-lipoic acid depend on mitochondria protection. We used an in vitro model of chemotherapy induced peripheral neuropathy that closely mimic the in vivo condition by exposing primary cultures of dorsal root ganglion (DRG) sensory neurons to paclitaxel and cisplatin, two widely used and highly effective chemotherapeutic drugs. This approach allowed investigating the efficacy of alpha-lipoic acid in preventing axonal damage and apoptosis and the function and ultrastructural morphology of mitochondria after exposure to toxic agents and alpha-lipoic acid. Our results demonstrate that both cisplatin and paclitaxel cause early mitochondrial impairment with loss of membrane potential and induction of autophagic vacuoles in neurons. Alpha-lipoic acid exerts neuroprotective effects against chemotherapy induced neurotoxicity in sensory neurons: it rescues the mitochondrial toxicity and induces the expression of frataxin, an essential mitochondrial protein with anti-oxidant and chaperone properties. In conclusion mitochondrial toxicity is an early common event both in paclitaxel and cisplatin induced neurotoxicity. Alpha-lipoic acid protects sensory neurons through its anti-oxidant and mitochondrial regulatory functions, possibly inducing the expression of frataxin. These findings suggest that alpha-lipoic acid might reduce the risk of developing peripheral nerve toxicity in patients undergoing chemotherapy and encourage further confirmatory clinical trials.", "entity": "Cisplatin", "aliases": "Biocisplatinum Cisplatin Diamminodichloride Platinum Dichlorodiammineplatinum NSC-119875 Platidiam Platino Platinol cis Diamminedichloroplatinum cis-Diamminedichloroplatinum cis-Diamminedichloroplatinum(II) cis-Dichlorodiammineplatinum(II) cis-Platinum", "definition": "An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.\n    ", "id": "MESH:D002945"}
{"mention": "axonal damage", "mention_text": "The study investigates if alpha-lipoic acid is neuroprotective against chemotherapy induced neurotoxicity, if mitochondrial damage plays a critical role in toxic neurodegenerative cascade, and if neuroprotective effects of alpha-lipoic acid depend on mitochondria protection. We used an in vitro model of chemotherapy induced peripheral neuropathy that closely mimic the in vivo condition by exposing primary cultures of dorsal root ganglion (DRG) sensory neurons to paclitaxel and cisplatin, two widely used and highly effective chemotherapeutic drugs. This approach allowed investigating the efficacy of alpha-lipoic acid in preventing axonal damage and apoptosis and the function and ultrastructural morphology of mitochondria after exposure to toxic agents and alpha-lipoic acid. Our results demonstrate that both cisplatin and paclitaxel cause early mitochondrial impairment with loss of membrane potential and induction of autophagic vacuoles in neurons. Alpha-lipoic acid exerts neuroprotective effects against chemotherapy induced neurotoxicity in sensory neurons: it rescues the mitochondrial toxicity and induces the expression of frataxin, an essential mitochondrial protein with anti-oxidant and chaperone properties. In conclusion mitochondrial toxicity is an early common event both in paclitaxel and cisplatin induced neurotoxicity. Alpha-lipoic acid protects sensory neurons through its anti-oxidant and mitochondrial regulatory functions, possibly inducing the expression of frataxin. These findings suggest that alpha-lipoic acid might reduce the risk of developing peripheral nerve toxicity in patients undergoing chemotherapy and encourage further confirmatory clinical trials.", "entity": "Basal Ganglia Diseases", "aliases": "Basal Ganglia Disease Diseases Disorder Disorders Extrapyramidal Lenticulostriate", "definition": "Diseases of the BASAL GANGLIA including the PUTAMEN; GLOBUS PALLIDUS; claustrum; AMYGDALA; and CAUDATE NUCLEUS. DYSKINESIAS (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include CEREBROVASCULAR DISORDERS; NEURODEGENERATIVE DISEASES; and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D001480"}
{"mention": "mitochondrial impairment", "mention_text": "The study investigates if alpha-lipoic acid is neuroprotective against chemotherapy induced neurotoxicity, if mitochondrial damage plays a critical role in toxic neurodegenerative cascade, and if neuroprotective effects of alpha-lipoic acid depend on mitochondria protection. We used an in vitro model of chemotherapy induced peripheral neuropathy that closely mimic the in vivo condition by exposing primary cultures of dorsal root ganglion (DRG) sensory neurons to paclitaxel and cisplatin, two widely used and highly effective chemotherapeutic drugs. This approach allowed investigating the efficacy of alpha-lipoic acid in preventing axonal damage and apoptosis and the function and ultrastructural morphology of mitochondria after exposure to toxic agents and alpha-lipoic acid. Our results demonstrate that both cisplatin and paclitaxel cause early mitochondrial impairment with loss of membrane potential and induction of autophagic vacuoles in neurons. Alpha-lipoic acid exerts neuroprotective effects against chemotherapy induced neurotoxicity in sensory neurons: it rescues the mitochondrial toxicity and induces the expression of frataxin, an essential mitochondrial protein with anti-oxidant and chaperone properties. In conclusion mitochondrial toxicity is an early common event both in paclitaxel and cisplatin induced neurotoxicity. Alpha-lipoic acid protects sensory neurons through its anti-oxidant and mitochondrial regulatory functions, possibly inducing the expression of frataxin. These findings suggest that alpha-lipoic acid might reduce the risk of developing peripheral nerve toxicity in patients undergoing chemotherapy and encourage further confirmatory clinical trials.", "entity": "Mitochondrial Diseases", "aliases": "Deficiencies Oxidative Phosphorylation Respiratory Chain Deficiency Disease Mitochondrial Disorder Disorders Electron Transport Diseases", "definition": "Diseases caused by abnormal function of the MITOCHONDRIA. They may be caused by mutations, acquired or inherited, in mitochondrial DNA or in nuclear genes that code for mitochondrial components. They may also be the result of acquired mitochondria dysfunction due to adverse effects of drugs, infections, or other environmental causes.\n    ", "id": "MESH:D028361"}
{"mention": "Alpha-lipoic acid", "mention_text": "The study investigates if alpha-lipoic acid is neuroprotective against chemotherapy induced neurotoxicity, if mitochondrial damage plays a critical role in toxic neurodegenerative cascade, and if neuroprotective effects of alpha-lipoic acid depend on mitochondria protection. We used an in vitro model of chemotherapy induced peripheral neuropathy that closely mimic the in vivo condition by exposing primary cultures of dorsal root ganglion (DRG) sensory neurons to paclitaxel and cisplatin, two widely used and highly effective chemotherapeutic drugs. This approach allowed investigating the efficacy of alpha-lipoic acid in preventing axonal damage and apoptosis and the function and ultrastructural morphology of mitochondria after exposure to toxic agents and alpha-lipoic acid. Our results demonstrate that both cisplatin and paclitaxel cause early mitochondrial impairment with loss of membrane potential and induction of autophagic vacuoles in neurons. Alpha-lipoic acid exerts neuroprotective effects against chemotherapy induced neurotoxicity in sensory neurons: it rescues the mitochondrial toxicity and induces the expression of frataxin, an essential mitochondrial protein with anti-oxidant and chaperone properties. In conclusion mitochondrial toxicity is an early common event both in paclitaxel and cisplatin induced neurotoxicity. Alpha-lipoic acid protects sensory neurons through its anti-oxidant and mitochondrial regulatory functions, possibly inducing the expression of frataxin. These findings suggest that alpha-lipoic acid might reduce the risk of developing peripheral nerve toxicity in patients undergoing chemotherapy and encourage further confirmatory clinical trials.", "entity": "Thioctic Acid", "aliases": "Acid alpha-Lipoic Aliud Brand of Thioctic Alpha Lipogamma Lipon Stada Liponsaure Sofotec Lippon AL Alpha-Lipogamma Alpha-Lipon Alpha-Liponsaure Alpha-Lippon AlphaLipogamma AlphaLipon AlphaLiponsaure AlphaLippon Alphaflam Azulipont Azupharma Fenint Generosan Heumann Hexal Illa Tromethamine Injekt Thiogamma Juta Juthiac Lichtenstein Lipoic ratiopharm Liponsaure-ratiopharm Liponsaureratiopharm MTW Alphaliponsaure MTW-Alphaliponsaure MTWAlphaliponsaure Merck dura Neurium Pharmacia Pleomix N Pleomix-", "definition": "An octanoic acid bridged with two sulfurs so that it is sometimes also called a pentanoic acid in some naming schemes. It is biosynthesized by cleavage of LINOLEIC ACID and is a coenzyme of oxoglutarate dehydrogenase (KETOGLUTARATE DEHYDROGENASE COMPLEX). It is used in DIETARY SUPPLEMENTS.\n    ", "id": "MESH:D008063"}
{"mention": "mitochondrial toxicity", "mention_text": "The study investigates if alpha-lipoic acid is neuroprotective against chemotherapy induced neurotoxicity, if mitochondrial damage plays a critical role in toxic neurodegenerative cascade, and if neuroprotective effects of alpha-lipoic acid depend on mitochondria protection. We used an in vitro model of chemotherapy induced peripheral neuropathy that closely mimic the in vivo condition by exposing primary cultures of dorsal root ganglion (DRG) sensory neurons to paclitaxel and cisplatin, two widely used and highly effective chemotherapeutic drugs. This approach allowed investigating the efficacy of alpha-lipoic acid in preventing axonal damage and apoptosis and the function and ultrastructural morphology of mitochondria after exposure to toxic agents and alpha-lipoic acid. Our results demonstrate that both cisplatin and paclitaxel cause early mitochondrial impairment with loss of membrane potential and induction of autophagic vacuoles in neurons. Alpha-lipoic acid exerts neuroprotective effects against chemotherapy induced neurotoxicity in sensory neurons: it rescues the mitochondrial toxicity and induces the expression of frataxin, an essential mitochondrial protein with anti-oxidant and chaperone properties. In conclusion mitochondrial toxicity is an early common event both in paclitaxel and cisplatin induced neurotoxicity. Alpha-lipoic acid protects sensory neurons through its anti-oxidant and mitochondrial regulatory functions, possibly inducing the expression of frataxin. These findings suggest that alpha-lipoic acid might reduce the risk of developing peripheral nerve toxicity in patients undergoing chemotherapy and encourage further confirmatory clinical trials.", "entity": "Mitochondrial Diseases", "aliases": "Deficiencies Oxidative Phosphorylation Respiratory Chain Deficiency Disease Mitochondrial Disorder Disorders Electron Transport Diseases", "definition": "Diseases caused by abnormal function of the MITOCHONDRIA. They may be caused by mutations, acquired or inherited, in mitochondrial DNA or in nuclear genes that code for mitochondrial components. They may also be the result of acquired mitochondria dysfunction due to adverse effects of drugs, infections, or other environmental causes.\n    ", "id": "MESH:D028361"}
{"mention": "peripheral nerve toxicity", "mention_text": "The study investigates if alpha-lipoic acid is neuroprotective against chemotherapy induced neurotoxicity, if mitochondrial damage plays a critical role in toxic neurodegenerative cascade, and if neuroprotective effects of alpha-lipoic acid depend on mitochondria protection. We used an in vitro model of chemotherapy induced peripheral neuropathy that closely mimic the in vivo condition by exposing primary cultures of dorsal root ganglion (DRG) sensory neurons to paclitaxel and cisplatin, two widely used and highly effective chemotherapeutic drugs. This approach allowed investigating the efficacy of alpha-lipoic acid in preventing axonal damage and apoptosis and the function and ultrastructural morphology of mitochondria after exposure to toxic agents and alpha-lipoic acid. Our results demonstrate that both cisplatin and paclitaxel cause early mitochondrial impairment with loss of membrane potential and induction of autophagic vacuoles in neurons. Alpha-lipoic acid exerts neuroprotective effects against chemotherapy induced neurotoxicity in sensory neurons: it rescues the mitochondrial toxicity and induces the expression of frataxin, an essential mitochondrial protein with anti-oxidant and chaperone properties. In conclusion mitochondrial toxicity is an early common event both in paclitaxel and cisplatin induced neurotoxicity. Alpha-lipoic acid protects sensory neurons through its anti-oxidant and mitochondrial regulatory functions, possibly inducing the expression of frataxin. These findings suggest that alpha-lipoic acid might reduce the risk of developing peripheral nerve toxicity in patients undergoing chemotherapy and encourage further confirmatory clinical trials.", "entity": "Peripheral Nervous System Diseases", "aliases": "Nerve Disease Peripheral Diseases Neuropathy PNS (Peripheral Nervous System) System Disorders Neuropathies", "definition": "Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.\n    ", "id": "MESH:D010523"}
{"mention": "stroke", "mention_text": "Optimising stroke prevention in non-valvular atrial fibrillation.", "entity": "Stroke", "aliases": "Acute Cerebrovascular Accident Accidents Stroke Strokes Apoplexy Brain Vascular CVA (Cerebrovascular Accident) CVAs Cerebral", "definition": "A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)\n    ", "id": "MESH:D020521"}
{"mention": "atrial fibrillation", "mention_text": "Optimising stroke prevention in non-valvular atrial fibrillation.", "entity": "Atrial Fibrillation", "aliases": "Atrial Fibrillation Fibrillations Auricular Familial", "definition": "Abnormal cardiac rhythm that is characterized by rapid, uncoordinated firing of electrical impulses in the upper chambers of the heart (HEART ATRIA). In such case, blood cannot be effectively pumped into the lower chambers of the heart (HEART VENTRICLES). It is caused by abnormal impulse generation.\n    ", "id": "MESH:D001281"}
{"mention": "Atrial fibrillation", "mention_text": "Atrial fibrillation is associated with substantial morbidity and mortality. Pooled data from trials comparing antithrombotic treatment with placebo have shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to aspirin in preventing strokes, with a relative risk reduction of 36%. Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as vitamin K antagonist drugs in the prevention of embolic events, but has been recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) study has demonstrated that warfarin is superior to platelet therapy (clopidogrel plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold promise in atrial fibrillation through cardiac remodelling. Preliminary studies suggest that statins could interfere with the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for the exclusion of left atrial appendage are under investigation in high-risk patients.", "entity": "Atrial Fibrillation", "aliases": "Atrial Fibrillation Fibrillations Auricular Familial", "definition": "Abnormal cardiac rhythm that is characterized by rapid, uncoordinated firing of electrical impulses in the upper chambers of the heart (HEART ATRIA). In such case, blood cannot be effectively pumped into the lower chambers of the heart (HEART VENTRICLES). It is caused by abnormal impulse generation.\n    ", "id": "MESH:D001281"}
{"mention": "warfarin", "mention_text": "Atrial fibrillation is associated with substantial morbidity and mortality. Pooled data from trials comparing antithrombotic treatment with placebo have shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to aspirin in preventing strokes, with a relative risk reduction of 36%. Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as vitamin K antagonist drugs in the prevention of embolic events, but has been recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) study has demonstrated that warfarin is superior to platelet therapy (clopidogrel plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold promise in atrial fibrillation through cardiac remodelling. Preliminary studies suggest that statins could interfere with the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for the exclusion of left atrial appendage are under investigation in high-risk patients.", "entity": "Warfarin", "aliases": "4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one Aldo Brand of Warfarin Sodium Aldocumar Antigen Apo-Warfarin Apotex Bailly Boots Bristol-Myers Squibb Coumadin Coumadine Estedi Gen-Warfarin Genpharm Goldshield Marevan Potassium Tedicumar Warfant", "definition": "An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.\n    ", "id": "MESH:D014859"}
{"mention": "stroke", "mention_text": "Atrial fibrillation is associated with substantial morbidity and mortality. Pooled data from trials comparing antithrombotic treatment with placebo have shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to aspirin in preventing strokes, with a relative risk reduction of 36%. Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as vitamin K antagonist drugs in the prevention of embolic events, but has been recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) study has demonstrated that warfarin is superior to platelet therapy (clopidogrel plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold promise in atrial fibrillation through cardiac remodelling. Preliminary studies suggest that statins could interfere with the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for the exclusion of left atrial appendage are under investigation in high-risk patients.", "entity": "Stroke", "aliases": "Acute Cerebrovascular Accident Accidents Stroke Strokes Apoplexy Brain Vascular CVA (Cerebrovascular Accident) CVAs Cerebral", "definition": "A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)\n    ", "id": "MESH:D020521"}
{"mention": "aspirin", "mention_text": "Atrial fibrillation is associated with substantial morbidity and mortality. Pooled data from trials comparing antithrombotic treatment with placebo have shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to aspirin in preventing strokes, with a relative risk reduction of 36%. Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as vitamin K antagonist drugs in the prevention of embolic events, but has been recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) study has demonstrated that warfarin is superior to platelet therapy (clopidogrel plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold promise in atrial fibrillation through cardiac remodelling. Preliminary studies suggest that statins could interfere with the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for the exclusion of left atrial appendage are under investigation in high-risk patients.", "entity": "Aspirin", "aliases": "2-(Acetyloxy)benzoic Acid Acetylsalicylic Acetysal Acylpyrin Aloxiprimum Aspirin Colfarit Dispril Easprin Ecotrin Endosprin Magnecyl Micristin Polopirin Polopiryna Solprin Solupsan Zorprin", "definition": "The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)\n    ", "id": "MESH:D001241"}
{"mention": "strokes", "mention_text": "Atrial fibrillation is associated with substantial morbidity and mortality. Pooled data from trials comparing antithrombotic treatment with placebo have shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to aspirin in preventing strokes, with a relative risk reduction of 36%. Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as vitamin K antagonist drugs in the prevention of embolic events, but has been recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) study has demonstrated that warfarin is superior to platelet therapy (clopidogrel plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold promise in atrial fibrillation through cardiac remodelling. Preliminary studies suggest that statins could interfere with the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for the exclusion of left atrial appendage are under investigation in high-risk patients.", "entity": "Stroke", "aliases": "Acute Cerebrovascular Accident Accidents Stroke Strokes Apoplexy Brain Vascular CVA (Cerebrovascular Accident) CVAs Cerebral", "definition": "A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)\n    ", "id": "MESH:D020521"}
{"mention": "Ximelagatran", "mention_text": "Atrial fibrillation is associated with substantial morbidity and mortality. Pooled data from trials comparing antithrombotic treatment with placebo have shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to aspirin in preventing strokes, with a relative risk reduction of 36%. Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as vitamin K antagonist drugs in the prevention of embolic events, but has been recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) study has demonstrated that warfarin is superior to platelet therapy (clopidogrel plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold promise in atrial fibrillation through cardiac remodelling. Preliminary studies suggest that statins could interfere with the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for the exclusion of left atrial appendage are under investigation in high-risk patients.", "entity": "ximelagatran", "aliases": "Exanta H 376 95 376-95 glycine N-((1)1-cyclohexyl-2-((2)-((((4-(amino(hydroxyimino)methyl)phenyl)methyl)amino)carbonyl)-1-azetidinyl)2-oxoethyl)-ethyl ester N-((1R)1-cyclohexyl-2-((2S)-((((4-(amino(hydroxyimino)methyl)phenyl)methyl)amino)carbonyl)-1-azetidinyl)2-oxoethyl)-ethyl xi-melagatran ximelagatran", "definition": "", "id": "MESH:C426686"}
{"mention": "vitamin K", "mention_text": "Atrial fibrillation is associated with substantial morbidity and mortality. Pooled data from trials comparing antithrombotic treatment with placebo have shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to aspirin in preventing strokes, with a relative risk reduction of 36%. Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as vitamin K antagonist drugs in the prevention of embolic events, but has been recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) study has demonstrated that warfarin is superior to platelet therapy (clopidogrel plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold promise in atrial fibrillation through cardiac remodelling. Preliminary studies suggest that statins could interfere with the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for the exclusion of left atrial appendage are under investigation in high-risk patients.", "entity": "Vitamin K", "aliases": "Vitamin K", "definition": "A lipid cofactor that is required for normal blood clotting. Several forms of vitamin K have been identified: VITAMIN K 1 (phytomenadione) derived from plants, VITAMIN K 2 (menaquinone) from bacteria, and synthetic naphthoquinone provitamins, VITAMIN K 3 (menadione). Vitamin K 3 provitamins, after being alkylated in vivo, exhibit the antifibrinolytic activity of vitamin K. Green leafy vegetables, liver, cheese, butter, and egg yolk are good sources of vitamin K.\n    ", "id": "MESH:D014812"}
{"mention": "embolic events", "mention_text": "Atrial fibrillation is associated with substantial morbidity and mortality. Pooled data from trials comparing antithrombotic treatment with placebo have shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to aspirin in preventing strokes, with a relative risk reduction of 36%. Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as vitamin K antagonist drugs in the prevention of embolic events, but has been recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) study has demonstrated that warfarin is superior to platelet therapy (clopidogrel plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold promise in atrial fibrillation through cardiac remodelling. Preliminary studies suggest that statins could interfere with the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for the exclusion of left atrial appendage are under investigation in high-risk patients.", "entity": "Embolism", "aliases": "Embolism Embolisms Embolus", "definition": "Blocking of a blood vessel by an embolus which can be a blood clot or other undissolved material in the blood stream.\n    ", "id": "MESH:D004617"}
{"mention": "abnormal liver function", "mention_text": "Atrial fibrillation is associated with substantial morbidity and mortality. Pooled data from trials comparing antithrombotic treatment with placebo have shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to aspirin in preventing strokes, with a relative risk reduction of 36%. Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as vitamin K antagonist drugs in the prevention of embolic events, but has been recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) study has demonstrated that warfarin is superior to platelet therapy (clopidogrel plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold promise in atrial fibrillation through cardiac remodelling. Preliminary studies suggest that statins could interfere with the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for the exclusion of left atrial appendage are under investigation in high-risk patients.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "Atrial Fibrillation", "mention_text": "Atrial fibrillation is associated with substantial morbidity and mortality. Pooled data from trials comparing antithrombotic treatment with placebo have shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to aspirin in preventing strokes, with a relative risk reduction of 36%. Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as vitamin K antagonist drugs in the prevention of embolic events, but has been recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) study has demonstrated that warfarin is superior to platelet therapy (clopidogrel plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold promise in atrial fibrillation through cardiac remodelling. Preliminary studies suggest that statins could interfere with the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for the exclusion of left atrial appendage are under investigation in high-risk patients.", "entity": "Atrial Fibrillation", "aliases": "Atrial Fibrillation Fibrillations Auricular Familial", "definition": "Abnormal cardiac rhythm that is characterized by rapid, uncoordinated firing of electrical impulses in the upper chambers of the heart (HEART ATRIA). In such case, blood cannot be effectively pumped into the lower chambers of the heart (HEART VENTRICLES). It is caused by abnormal impulse generation.\n    ", "id": "MESH:D001281"}
{"mention": "Clopidogrel", "mention_text": "Atrial fibrillation is associated with substantial morbidity and mortality. Pooled data from trials comparing antithrombotic treatment with placebo have shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to aspirin in preventing strokes, with a relative risk reduction of 36%. Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as vitamin K antagonist drugs in the prevention of embolic events, but has been recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) study has demonstrated that warfarin is superior to platelet therapy (clopidogrel plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold promise in atrial fibrillation through cardiac remodelling. Preliminary studies suggest that statins could interfere with the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for the exclusion of left atrial appendage are under investigation in high-risk patients.", "entity": "clopidogrel", "aliases": "BMS brand 1 of clopidogrel bisulfate 2 Iscover PCR 4099 PCR-4099 Plavix SC 25989C 25990C SR 25989 Sandoz besylate hydrochloride napadisilate (+)(S)-isomer clopidogrel-Mepha", "definition": "", "id": "MESH:C055162"}
{"mention": "Irbesartan", "mention_text": "Atrial fibrillation is associated with substantial morbidity and mortality. Pooled data from trials comparing antithrombotic treatment with placebo have shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to aspirin in preventing strokes, with a relative risk reduction of 36%. Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as vitamin K antagonist drugs in the prevention of embolic events, but has been recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) study has demonstrated that warfarin is superior to platelet therapy (clopidogrel plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold promise in atrial fibrillation through cardiac remodelling. Preliminary studies suggest that statins could interfere with the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for the exclusion of left atrial appendage are under investigation in high-risk patients.", "entity": "irbesartan", "aliases": "2-n-butyl-3-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl)-1,3-diazaspiro(4,4)non-1-en-4-one Aprovel Avapro BMS 186295 BMS-186295 Karvea SR 47436 SR-47436 irbesartan", "definition": "", "id": "MESH:C081309"}
{"mention": "clopidogrel", "mention_text": "Atrial fibrillation is associated with substantial morbidity and mortality. Pooled data from trials comparing antithrombotic treatment with placebo have shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to aspirin in preventing strokes, with a relative risk reduction of 36%. Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as vitamin K antagonist drugs in the prevention of embolic events, but has been recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) study has demonstrated that warfarin is superior to platelet therapy (clopidogrel plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold promise in atrial fibrillation through cardiac remodelling. Preliminary studies suggest that statins could interfere with the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for the exclusion of left atrial appendage are under investigation in high-risk patients.", "entity": "clopidogrel", "aliases": "BMS brand 1 of clopidogrel bisulfate 2 Iscover PCR 4099 PCR-4099 Plavix SC 25989C 25990C SR 25989 Sandoz besylate hydrochloride napadisilate (+)(S)-isomer clopidogrel-Mepha", "definition": "", "id": "MESH:C055162"}
{"mention": "Idraparinux", "mention_text": "Atrial fibrillation is associated with substantial morbidity and mortality. Pooled data from trials comparing antithrombotic treatment with placebo have shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to aspirin in preventing strokes, with a relative risk reduction of 36%. Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as vitamin K antagonist drugs in the prevention of embolic events, but has been recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) study has demonstrated that warfarin is superior to platelet therapy (clopidogrel plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold promise in atrial fibrillation through cardiac remodelling. Preliminary studies suggest that statins could interfere with the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for the exclusion of left atrial appendage are under investigation in high-risk patients.", "entity": "idraparinux", "aliases": "idraparinux", "definition": "", "id": "MESH:C479958"}
{"mention": "atrial fibrillation", "mention_text": "Atrial fibrillation is associated with substantial morbidity and mortality. Pooled data from trials comparing antithrombotic treatment with placebo have shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to aspirin in preventing strokes, with a relative risk reduction of 36%. Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as vitamin K antagonist drugs in the prevention of embolic events, but has been recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) study has demonstrated that warfarin is superior to platelet therapy (clopidogrel plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold promise in atrial fibrillation through cardiac remodelling. Preliminary studies suggest that statins could interfere with the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for the exclusion of left atrial appendage are under investigation in high-risk patients.", "entity": "Atrial Fibrillation", "aliases": "Atrial Fibrillation Fibrillations Auricular Familial", "definition": "Abnormal cardiac rhythm that is characterized by rapid, uncoordinated firing of electrical impulses in the upper chambers of the heart (HEART ATRIA). In such case, blood cannot be effectively pumped into the lower chambers of the heart (HEART VENTRICLES). It is caused by abnormal impulse generation.\n    ", "id": "MESH:D001281"}
{"mention": "Angiotensin", "mention_text": "Atrial fibrillation is associated with substantial morbidity and mortality. Pooled data from trials comparing antithrombotic treatment with placebo have shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to aspirin in preventing strokes, with a relative risk reduction of 36%. Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as vitamin K antagonist drugs in the prevention of embolic events, but has been recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) study has demonstrated that warfarin is superior to platelet therapy (clopidogrel plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold promise in atrial fibrillation through cardiac remodelling. Preliminary studies suggest that statins could interfere with the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for the exclusion of left atrial appendage are under investigation in high-risk patients.", "entity": "Angiotensins", "aliases": "Angiotensin Angiotensins", "definition": "Oligopeptides which are important in the regulation of blood pressure (VASOCONSTRICTION) and fluid homeostasis via the RENIN-ANGIOTENSIN SYSTEM. These include angiotensins derived naturally from precursor ANGIOTENSINOGEN, and those synthesized.\n    ", "id": "MESH:D000809"}
{"mention": "angiotensin II", "mention_text": "Atrial fibrillation is associated with substantial morbidity and mortality. Pooled data from trials comparing antithrombotic treatment with placebo have shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to aspirin in preventing strokes, with a relative risk reduction of 36%. Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as vitamin K antagonist drugs in the prevention of embolic events, but has been recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) study has demonstrated that warfarin is superior to platelet therapy (clopidogrel plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold promise in atrial fibrillation through cardiac remodelling. Preliminary studies suggest that statins could interfere with the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for the exclusion of left atrial appendage are under investigation in high-risk patients.", "entity": "Angiotensin II", "aliases": "5 L Isoleucine Angiotensin II 5-L-Isoleucine ANG-(1-8)Octapeptide Ile(5)- Isoleucine(5)- Val(5)- Valine(5)- Angiotensin-(1-8) Octapeptide Isoleucine(5)-Angiotensin Isoleucyl(5)-Angiotensin Valyl(5)-Angiotensin", "definition": "An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.\n    ", "id": "MESH:D000804"}
{"mention": "cardiac remodelling", "mention_text": "Atrial fibrillation is associated with substantial morbidity and mortality. Pooled data from trials comparing antithrombotic treatment with placebo have shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to aspirin in preventing strokes, with a relative risk reduction of 36%. Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as vitamin K antagonist drugs in the prevention of embolic events, but has been recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) study has demonstrated that warfarin is superior to platelet therapy (clopidogrel plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold promise in atrial fibrillation through cardiac remodelling. Preliminary studies suggest that statins could interfere with the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for the exclusion of left atrial appendage are under investigation in high-risk patients.", "entity": "Ventricular Remodeling", "aliases": "Cardiac Remodeling Ventricular Remodelings Left Ventricle Myocardial", "definition": "The geometric and structural changes that the HEART VENTRICLES undergo, usually following MYOCARDIAL INFARCTION. It comprises expansion of the infarct and dilatation of the healthy ventricle segments. While most prevalent in the left ventricle, it can also occur in the right ventricle.\n    ", "id": "MESH:D020257"}
{"mention": "statins", "mention_text": "Atrial fibrillation is associated with substantial morbidity and mortality. Pooled data from trials comparing antithrombotic treatment with placebo have shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to aspirin in preventing strokes, with a relative risk reduction of 36%. Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as vitamin K antagonist drugs in the prevention of embolic events, but has been recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) study has demonstrated that warfarin is superior to platelet therapy (clopidogrel plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold promise in atrial fibrillation through cardiac remodelling. Preliminary studies suggest that statins could interfere with the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for the exclusion of left atrial appendage are under investigation in high-risk patients.", "entity": "Simvastatin", "aliases": "MK 733 MK-733 MK733 Simvastatin Synvinolin Zocor", "definition": "A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL CHOLESTEROL.\n    ", "id": "MESH:D019821"}
{"mention": "cyclosporin A", "mention_text": "Interaction of cyclosporin A with antineoplastic agents.", "entity": "Cyclosporine", "aliases": "Ciclosporin CsA Neoral CsA-Neoral CsANeoral CyA NOF CyA-NOF Cyclosporin A Cyclosporine OL 27 400 27-400 27400 Sandimmun Sandimmune", "definition": "A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).\n    ", "id": "MESH:D016572"}
{"mention": "etoposide", "mention_text": "A synergistic effect of etoposide and cyclosporin A was observed in a patient with acute T-lymphocytic leukemia in relapse. The concomitant administration of etoposide and cyclosporin A resulted in eradication of hitherto refractory leukemic infiltration of bone marrow. Severe side effects in terms of mental confusion and progressive hyperbilirubinemia, however, point to an enhancement not only of antineoplastic effects but also of toxicity in normal tissues. This report demonstrates for the first time that the pharmacodynamic properties of cyclosporin A may not be confined strictly to suppression of normal T-cell functions.", "entity": "Etoposide", "aliases": "Baxter Brand of Etoposide Oncology Bristol Myers Squibb Bristol-Myers Celltop Demethyl Epipodophyllotoxin Ethylidine Glucoside Eposide Eposin Eto GRY Eto-GRY Etomedac Etopos Pierre Fabre Teva (5S)-Isomer (5a alpha)-Isomer alpha,9 alpha D Glucopyranosyl Isomer alpha-D-Glucopyranosyl Etoposido Ferrer Farma Exitop Gry Lastet Lemery Medac NSC 141540 NSC-141540 NSC141540 Novartis Onkoposid Onkoworks Pharmachemie Prasfarma Riboposid Sanfer Tedec Meiji Toposar VP 16 213 16-213 16213 VP-16 VP16 Vepesid ", "definition": "A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.\n    ", "id": "MESH:D005047"}
{"mention": "cyclosporin A", "mention_text": "A synergistic effect of etoposide and cyclosporin A was observed in a patient with acute T-lymphocytic leukemia in relapse. The concomitant administration of etoposide and cyclosporin A resulted in eradication of hitherto refractory leukemic infiltration of bone marrow. Severe side effects in terms of mental confusion and progressive hyperbilirubinemia, however, point to an enhancement not only of antineoplastic effects but also of toxicity in normal tissues. This report demonstrates for the first time that the pharmacodynamic properties of cyclosporin A may not be confined strictly to suppression of normal T-cell functions.", "entity": "Cyclosporine", "aliases": "Ciclosporin CsA Neoral CsA-Neoral CsANeoral CyA NOF CyA-NOF Cyclosporin A Cyclosporine OL 27 400 27-400 27400 Sandimmun Sandimmune", "definition": "A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).\n    ", "id": "MESH:D016572"}
{"mention": "acute T-lymphocytic leukemia", "mention_text": "A synergistic effect of etoposide and cyclosporin A was observed in a patient with acute T-lymphocytic leukemia in relapse. The concomitant administration of etoposide and cyclosporin A resulted in eradication of hitherto refractory leukemic infiltration of bone marrow. Severe side effects in terms of mental confusion and progressive hyperbilirubinemia, however, point to an enhancement not only of antineoplastic effects but also of toxicity in normal tissues. This report demonstrates for the first time that the pharmacodynamic properties of cyclosporin A may not be confined strictly to suppression of normal T-cell functions.", "entity": "Precursor T-Cell Lymphoblastic Leukemia-Lymphoma", "aliases": "Acute T-Cell Leukemia Leukemias T-Lymphocytic Lymphoblastic T Cell Lymphocytic Precursor Lymphoma Leukemia-Lymphoma T-ALL", "definition": "A leukemia/lymphoma found predominately in children and young adults and characterized LYMPHADENOPATHY and THYMUS GLAND involvement. It most frequently presents as a lymphoma, but a leukemic progression in the bone marrow is common.\n    ", "id": "MESH:D054218"}
{"mention": "leukemic infiltration", "mention_text": "A synergistic effect of etoposide and cyclosporin A was observed in a patient with acute T-lymphocytic leukemia in relapse. The concomitant administration of etoposide and cyclosporin A resulted in eradication of hitherto refractory leukemic infiltration of bone marrow. Severe side effects in terms of mental confusion and progressive hyperbilirubinemia, however, point to an enhancement not only of antineoplastic effects but also of toxicity in normal tissues. This report demonstrates for the first time that the pharmacodynamic properties of cyclosporin A may not be confined strictly to suppression of normal T-cell functions.", "entity": "Leukemic Infiltration", "aliases": "Infiltration Leukemic Infiltrations", "definition": "A pathologic change in leukemia in which leukemic cells permeate various organs at any stage of the disease. All types of leukemia show various degrees of infiltration, depending upon the type of leukemia. The degree of infiltration may vary from site to site. The liver and spleen are common sites of infiltration, the greatest appearing in myelocytic leukemia, but infiltration is seen also in the granulocytic and lymphocytic types. The kidney is also a common site and of the gastrointestinal system, the stomach and ileum are commonly involved. In lymphocytic leukemia the skin is often infiltrated. The central nervous system too is a common site.\n    ", "id": "MESH:D017254"}
{"mention": "confusion", "mention_text": "A synergistic effect of etoposide and cyclosporin A was observed in a patient with acute T-lymphocytic leukemia in relapse. The concomitant administration of etoposide and cyclosporin A resulted in eradication of hitherto refractory leukemic infiltration of bone marrow. Severe side effects in terms of mental confusion and progressive hyperbilirubinemia, however, point to an enhancement not only of antineoplastic effects but also of toxicity in normal tissues. This report demonstrates for the first time that the pharmacodynamic properties of cyclosporin A may not be confined strictly to suppression of normal T-cell functions.", "entity": "Confusion", "aliases": "Bewilderment Confusion Post Ictal Post-Ictal Reactive Confusional State States Disorientation", "definition": "A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation.\n    ", "id": "MESH:D003221"}
{"mention": "hyperbilirubinemia", "mention_text": "A synergistic effect of etoposide and cyclosporin A was observed in a patient with acute T-lymphocytic leukemia in relapse. The concomitant administration of etoposide and cyclosporin A resulted in eradication of hitherto refractory leukemic infiltration of bone marrow. Severe side effects in terms of mental confusion and progressive hyperbilirubinemia, however, point to an enhancement not only of antineoplastic effects but also of toxicity in normal tissues. This report demonstrates for the first time that the pharmacodynamic properties of cyclosporin A may not be confined strictly to suppression of normal T-cell functions.", "entity": "Hyperbilirubinemia", "aliases": "Bilirubinemia Bilirubinemias Hyperbilirubinemia Hyperbilirubinemias", "definition": "A condition characterized by an abnormal increase of BILIRUBIN in the blood, which may result in JAUNDICE. Bilirubin, a breakdown product of HEME, is normally excreted in the BILE or further catabolized before excretion in the urine.\n    ", "id": "MESH:D006932"}
{"mention": "toxicity", "mention_text": "A synergistic effect of etoposide and cyclosporin A was observed in a patient with acute T-lymphocytic leukemia in relapse. The concomitant administration of etoposide and cyclosporin A resulted in eradication of hitherto refractory leukemic infiltration of bone marrow. Severe side effects in terms of mental confusion and progressive hyperbilirubinemia, however, point to an enhancement not only of antineoplastic effects but also of toxicity in normal tissues. This report demonstrates for the first time that the pharmacodynamic properties of cyclosporin A may not be confined strictly to suppression of normal T-cell functions.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "cefonicid", "mention_text": "The hematologic effects of cefonicid and cefazedone in the dog: a potential model of cephalosporin hematotoxicity in man.", "entity": "Cefonicid", "aliases": "Cefonicid Disodium Salt Monosodium Sodium Monocid SK&F 75073 SK&F-75073 SK&F75073 SKF 2 SKF-75073-2 SKF750732", "definition": "A second-generation cephalosporin administered intravenously or intramuscularly. Its bactericidal action results from inhibition of cell wall synthesis. It is used for urinary tract infections, lower respiratory tract infections, and soft tissue and bone infections.\n    ", "id": "MESH:D015790"}
{"mention": "cefazedone", "mention_text": "The hematologic effects of cefonicid and cefazedone in the dog: a potential model of cephalosporin hematotoxicity in man.", "entity": "cefazedone", "aliases": "7-(2-(3,5-dichloro-4-oxo-1- pyridyl)acetamido)-3-(5-methyl-1,3,4-thiadiazol- 2-ylthiomethyl)-3-cephem-4-carboxylic acid EMD 30 087 EMD30087 Refosporen Refosporin cefazedone sodium monosodium salt", "definition": "", "id": "MESH:C021341"}
{"mention": "cephalosporin", "mention_text": "The hematologic effects of cefonicid and cefazedone in the dog: a potential model of cephalosporin hematotoxicity in man.", "entity": "Cephalosporins", "aliases": "Acids Cephalosporanic Antibiotics Cephalosporin Cephalosporins", "definition": "A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus ACREMONIUM. They contain the beta-lactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid.\n    ", "id": "MESH:D002511"}
{"mention": "hematotoxicity", "mention_text": "The hematologic effects of cefonicid and cefazedone in the dog: a potential model of cephalosporin hematotoxicity in man.", "entity": "Hematologic Diseases", "aliases": "Blood Disease Diseases Hematologic Hematological", "definition": "Disorders of the blood and blood forming tissues.\n    ", "id": "MESH:D006402"}
{"mention": "Cephalosporin", "mention_text": "Cephalosporin antibiotics cause a variety of hematologic disturbances in man, the pathogeneses and hematopathology of which remain poorly characterized. There is a need for a well-defined animal model in which these blood dyscrasias can be studied. In four subacute toxicity studies, the intravenous administration of cefonicid or cefazedone to beagle dogs caused a dose-dependent incidence of anemia, neutropenia, and thrombocytopenia after 1-3 months of treatment. A nonregenerative anemia was the most compromising of the cytopenias and occurred in approximately 50% of dogs receiving 400-500 mg/kg cefonicid or 540-840 mg/kg cefazedone. All three cytopenias were completely reversible following cessation of treatment; the time required for recovery of the erythron (approximately 1 month) was considerably longer than that of the granulocytes and platelets (hours to a few days). Upon rechallenge with either cephalosporin, the hematologic syndrome was reproduced in most dogs tested; cefonicid (but not cefazedone)-treated dogs showed a substantially reduced induction period (15 +/- 5 days) compared to that of the first exposure to the drug (61 +/- 24 days). This observation, along with the rapid rate of decline in red cell mass parameters of affected dogs, suggests that a hemolytic component complicated the red cell production problem and that multiple toxicologic mechanisms contributed to the cytopenia. We conclude that the administration of high doses of cefonicid or cefazedone to dogs can induce hematotoxicity similar to the cephalosporin-induced blood dyscrasias described in man and thus provides a useful model for studying the mechanisms of these disorders.", "entity": "Cephalosporins", "aliases": "Acids Cephalosporanic Antibiotics Cephalosporin Cephalosporins", "definition": "A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus ACREMONIUM. They contain the beta-lactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid.\n    ", "id": "MESH:D002511"}
{"mention": "hematologic disturbances", "mention_text": "Cephalosporin antibiotics cause a variety of hematologic disturbances in man, the pathogeneses and hematopathology of which remain poorly characterized. There is a need for a well-defined animal model in which these blood dyscrasias can be studied. In four subacute toxicity studies, the intravenous administration of cefonicid or cefazedone to beagle dogs caused a dose-dependent incidence of anemia, neutropenia, and thrombocytopenia after 1-3 months of treatment. A nonregenerative anemia was the most compromising of the cytopenias and occurred in approximately 50% of dogs receiving 400-500 mg/kg cefonicid or 540-840 mg/kg cefazedone. All three cytopenias were completely reversible following cessation of treatment; the time required for recovery of the erythron (approximately 1 month) was considerably longer than that of the granulocytes and platelets (hours to a few days). Upon rechallenge with either cephalosporin, the hematologic syndrome was reproduced in most dogs tested; cefonicid (but not cefazedone)-treated dogs showed a substantially reduced induction period (15 +/- 5 days) compared to that of the first exposure to the drug (61 +/- 24 days). This observation, along with the rapid rate of decline in red cell mass parameters of affected dogs, suggests that a hemolytic component complicated the red cell production problem and that multiple toxicologic mechanisms contributed to the cytopenia. We conclude that the administration of high doses of cefonicid or cefazedone to dogs can induce hematotoxicity similar to the cephalosporin-induced blood dyscrasias described in man and thus provides a useful model for studying the mechanisms of these disorders.", "entity": "Hematologic Diseases", "aliases": "Blood Disease Diseases Hematologic Hematological", "definition": "Disorders of the blood and blood forming tissues.\n    ", "id": "MESH:D006402"}
{"mention": "blood dyscrasias", "mention_text": "Cephalosporin antibiotics cause a variety of hematologic disturbances in man, the pathogeneses and hematopathology of which remain poorly characterized. There is a need for a well-defined animal model in which these blood dyscrasias can be studied. In four subacute toxicity studies, the intravenous administration of cefonicid or cefazedone to beagle dogs caused a dose-dependent incidence of anemia, neutropenia, and thrombocytopenia after 1-3 months of treatment. A nonregenerative anemia was the most compromising of the cytopenias and occurred in approximately 50% of dogs receiving 400-500 mg/kg cefonicid or 540-840 mg/kg cefazedone. All three cytopenias were completely reversible following cessation of treatment; the time required for recovery of the erythron (approximately 1 month) was considerably longer than that of the granulocytes and platelets (hours to a few days). Upon rechallenge with either cephalosporin, the hematologic syndrome was reproduced in most dogs tested; cefonicid (but not cefazedone)-treated dogs showed a substantially reduced induction period (15 +/- 5 days) compared to that of the first exposure to the drug (61 +/- 24 days). This observation, along with the rapid rate of decline in red cell mass parameters of affected dogs, suggests that a hemolytic component complicated the red cell production problem and that multiple toxicologic mechanisms contributed to the cytopenia. We conclude that the administration of high doses of cefonicid or cefazedone to dogs can induce hematotoxicity similar to the cephalosporin-induced blood dyscrasias described in man and thus provides a useful model for studying the mechanisms of these disorders.", "entity": "Hematologic Diseases", "aliases": "Blood Disease Diseases Hematologic Hematological", "definition": "Disorders of the blood and blood forming tissues.\n    ", "id": "MESH:D006402"}
{"mention": "toxicity", "mention_text": "Cephalosporin antibiotics cause a variety of hematologic disturbances in man, the pathogeneses and hematopathology of which remain poorly characterized. There is a need for a well-defined animal model in which these blood dyscrasias can be studied. In four subacute toxicity studies, the intravenous administration of cefonicid or cefazedone to beagle dogs caused a dose-dependent incidence of anemia, neutropenia, and thrombocytopenia after 1-3 months of treatment. A nonregenerative anemia was the most compromising of the cytopenias and occurred in approximately 50% of dogs receiving 400-500 mg/kg cefonicid or 540-840 mg/kg cefazedone. All three cytopenias were completely reversible following cessation of treatment; the time required for recovery of the erythron (approximately 1 month) was considerably longer than that of the granulocytes and platelets (hours to a few days). Upon rechallenge with either cephalosporin, the hematologic syndrome was reproduced in most dogs tested; cefonicid (but not cefazedone)-treated dogs showed a substantially reduced induction period (15 +/- 5 days) compared to that of the first exposure to the drug (61 +/- 24 days). This observation, along with the rapid rate of decline in red cell mass parameters of affected dogs, suggests that a hemolytic component complicated the red cell production problem and that multiple toxicologic mechanisms contributed to the cytopenia. We conclude that the administration of high doses of cefonicid or cefazedone to dogs can induce hematotoxicity similar to the cephalosporin-induced blood dyscrasias described in man and thus provides a useful model for studying the mechanisms of these disorders.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "cefonicid", "mention_text": "Cephalosporin antibiotics cause a variety of hematologic disturbances in man, the pathogeneses and hematopathology of which remain poorly characterized. There is a need for a well-defined animal model in which these blood dyscrasias can be studied. In four subacute toxicity studies, the intravenous administration of cefonicid or cefazedone to beagle dogs caused a dose-dependent incidence of anemia, neutropenia, and thrombocytopenia after 1-3 months of treatment. A nonregenerative anemia was the most compromising of the cytopenias and occurred in approximately 50% of dogs receiving 400-500 mg/kg cefonicid or 540-840 mg/kg cefazedone. All three cytopenias were completely reversible following cessation of treatment; the time required for recovery of the erythron (approximately 1 month) was considerably longer than that of the granulocytes and platelets (hours to a few days). Upon rechallenge with either cephalosporin, the hematologic syndrome was reproduced in most dogs tested; cefonicid (but not cefazedone)-treated dogs showed a substantially reduced induction period (15 +/- 5 days) compared to that of the first exposure to the drug (61 +/- 24 days). This observation, along with the rapid rate of decline in red cell mass parameters of affected dogs, suggests that a hemolytic component complicated the red cell production problem and that multiple toxicologic mechanisms contributed to the cytopenia. We conclude that the administration of high doses of cefonicid or cefazedone to dogs can induce hematotoxicity similar to the cephalosporin-induced blood dyscrasias described in man and thus provides a useful model for studying the mechanisms of these disorders.", "entity": "Cefonicid", "aliases": "Cefonicid Disodium Salt Monosodium Sodium Monocid SK&F 75073 SK&F-75073 SK&F75073 SKF 2 SKF-75073-2 SKF750732", "definition": "A second-generation cephalosporin administered intravenously or intramuscularly. Its bactericidal action results from inhibition of cell wall synthesis. It is used for urinary tract infections, lower respiratory tract infections, and soft tissue and bone infections.\n    ", "id": "MESH:D015790"}
{"mention": "cefazedone", "mention_text": "Cephalosporin antibiotics cause a variety of hematologic disturbances in man, the pathogeneses and hematopathology of which remain poorly characterized. There is a need for a well-defined animal model in which these blood dyscrasias can be studied. In four subacute toxicity studies, the intravenous administration of cefonicid or cefazedone to beagle dogs caused a dose-dependent incidence of anemia, neutropenia, and thrombocytopenia after 1-3 months of treatment. A nonregenerative anemia was the most compromising of the cytopenias and occurred in approximately 50% of dogs receiving 400-500 mg/kg cefonicid or 540-840 mg/kg cefazedone. All three cytopenias were completely reversible following cessation of treatment; the time required for recovery of the erythron (approximately 1 month) was considerably longer than that of the granulocytes and platelets (hours to a few days). Upon rechallenge with either cephalosporin, the hematologic syndrome was reproduced in most dogs tested; cefonicid (but not cefazedone)-treated dogs showed a substantially reduced induction period (15 +/- 5 days) compared to that of the first exposure to the drug (61 +/- 24 days). This observation, along with the rapid rate of decline in red cell mass parameters of affected dogs, suggests that a hemolytic component complicated the red cell production problem and that multiple toxicologic mechanisms contributed to the cytopenia. We conclude that the administration of high doses of cefonicid or cefazedone to dogs can induce hematotoxicity similar to the cephalosporin-induced blood dyscrasias described in man and thus provides a useful model for studying the mechanisms of these disorders.", "entity": "cefazedone", "aliases": "7-(2-(3,5-dichloro-4-oxo-1- pyridyl)acetamido)-3-(5-methyl-1,3,4-thiadiazol- 2-ylthiomethyl)-3-cephem-4-carboxylic acid EMD 30 087 EMD30087 Refosporen Refosporin cefazedone sodium monosodium salt", "definition": "", "id": "MESH:C021341"}
{"mention": "anemia", "mention_text": "Cephalosporin antibiotics cause a variety of hematologic disturbances in man, the pathogeneses and hematopathology of which remain poorly characterized. There is a need for a well-defined animal model in which these blood dyscrasias can be studied. In four subacute toxicity studies, the intravenous administration of cefonicid or cefazedone to beagle dogs caused a dose-dependent incidence of anemia, neutropenia, and thrombocytopenia after 1-3 months of treatment. A nonregenerative anemia was the most compromising of the cytopenias and occurred in approximately 50% of dogs receiving 400-500 mg/kg cefonicid or 540-840 mg/kg cefazedone. All three cytopenias were completely reversible following cessation of treatment; the time required for recovery of the erythron (approximately 1 month) was considerably longer than that of the granulocytes and platelets (hours to a few days). Upon rechallenge with either cephalosporin, the hematologic syndrome was reproduced in most dogs tested; cefonicid (but not cefazedone)-treated dogs showed a substantially reduced induction period (15 +/- 5 days) compared to that of the first exposure to the drug (61 +/- 24 days). This observation, along with the rapid rate of decline in red cell mass parameters of affected dogs, suggests that a hemolytic component complicated the red cell production problem and that multiple toxicologic mechanisms contributed to the cytopenia. We conclude that the administration of high doses of cefonicid or cefazedone to dogs can induce hematotoxicity similar to the cephalosporin-induced blood dyscrasias described in man and thus provides a useful model for studying the mechanisms of these disorders.", "entity": "Anemia", "aliases": "Anemia Anemias", "definition": "A reduction in the number of circulating ERYTHROCYTES or in the quantity of HEMOGLOBIN.\n    ", "id": "MESH:D000740"}
{"mention": "neutropenia", "mention_text": "Cephalosporin antibiotics cause a variety of hematologic disturbances in man, the pathogeneses and hematopathology of which remain poorly characterized. There is a need for a well-defined animal model in which these blood dyscrasias can be studied. In four subacute toxicity studies, the intravenous administration of cefonicid or cefazedone to beagle dogs caused a dose-dependent incidence of anemia, neutropenia, and thrombocytopenia after 1-3 months of treatment. A nonregenerative anemia was the most compromising of the cytopenias and occurred in approximately 50% of dogs receiving 400-500 mg/kg cefonicid or 540-840 mg/kg cefazedone. All three cytopenias were completely reversible following cessation of treatment; the time required for recovery of the erythron (approximately 1 month) was considerably longer than that of the granulocytes and platelets (hours to a few days). Upon rechallenge with either cephalosporin, the hematologic syndrome was reproduced in most dogs tested; cefonicid (but not cefazedone)-treated dogs showed a substantially reduced induction period (15 +/- 5 days) compared to that of the first exposure to the drug (61 +/- 24 days). This observation, along with the rapid rate of decline in red cell mass parameters of affected dogs, suggests that a hemolytic component complicated the red cell production problem and that multiple toxicologic mechanisms contributed to the cytopenia. We conclude that the administration of high doses of cefonicid or cefazedone to dogs can induce hematotoxicity similar to the cephalosporin-induced blood dyscrasias described in man and thus provides a useful model for studying the mechanisms of these disorders.", "entity": "Neutropenia", "aliases": "Neutropenia Neutropenias", "definition": "A decrease in the number of NEUTROPHILS found in the blood.\n    ", "id": "MESH:D009503"}
{"mention": "thrombocytopenia", "mention_text": "Cephalosporin antibiotics cause a variety of hematologic disturbances in man, the pathogeneses and hematopathology of which remain poorly characterized. There is a need for a well-defined animal model in which these blood dyscrasias can be studied. In four subacute toxicity studies, the intravenous administration of cefonicid or cefazedone to beagle dogs caused a dose-dependent incidence of anemia, neutropenia, and thrombocytopenia after 1-3 months of treatment. A nonregenerative anemia was the most compromising of the cytopenias and occurred in approximately 50% of dogs receiving 400-500 mg/kg cefonicid or 540-840 mg/kg cefazedone. All three cytopenias were completely reversible following cessation of treatment; the time required for recovery of the erythron (approximately 1 month) was considerably longer than that of the granulocytes and platelets (hours to a few days). Upon rechallenge with either cephalosporin, the hematologic syndrome was reproduced in most dogs tested; cefonicid (but not cefazedone)-treated dogs showed a substantially reduced induction period (15 +/- 5 days) compared to that of the first exposure to the drug (61 +/- 24 days). This observation, along with the rapid rate of decline in red cell mass parameters of affected dogs, suggests that a hemolytic component complicated the red cell production problem and that multiple toxicologic mechanisms contributed to the cytopenia. We conclude that the administration of high doses of cefonicid or cefazedone to dogs can induce hematotoxicity similar to the cephalosporin-induced blood dyscrasias described in man and thus provides a useful model for studying the mechanisms of these disorders.", "entity": "Thrombocytopenia", "aliases": "Thrombocytopenia Thrombocytopenias Thrombopenia Thrombopenias", "definition": "A subnormal level of BLOOD PLATELETS.\n    ", "id": "MESH:D013921"}
{"mention": "cytopenias", "mention_text": "Cephalosporin antibiotics cause a variety of hematologic disturbances in man, the pathogeneses and hematopathology of which remain poorly characterized. There is a need for a well-defined animal model in which these blood dyscrasias can be studied. In four subacute toxicity studies, the intravenous administration of cefonicid or cefazedone to beagle dogs caused a dose-dependent incidence of anemia, neutropenia, and thrombocytopenia after 1-3 months of treatment. A nonregenerative anemia was the most compromising of the cytopenias and occurred in approximately 50% of dogs receiving 400-500 mg/kg cefonicid or 540-840 mg/kg cefazedone. All three cytopenias were completely reversible following cessation of treatment; the time required for recovery of the erythron (approximately 1 month) was considerably longer than that of the granulocytes and platelets (hours to a few days). Upon rechallenge with either cephalosporin, the hematologic syndrome was reproduced in most dogs tested; cefonicid (but not cefazedone)-treated dogs showed a substantially reduced induction period (15 +/- 5 days) compared to that of the first exposure to the drug (61 +/- 24 days). This observation, along with the rapid rate of decline in red cell mass parameters of affected dogs, suggests that a hemolytic component complicated the red cell production problem and that multiple toxicologic mechanisms contributed to the cytopenia. We conclude that the administration of high doses of cefonicid or cefazedone to dogs can induce hematotoxicity similar to the cephalosporin-induced blood dyscrasias described in man and thus provides a useful model for studying the mechanisms of these disorders.", "entity": "Hematologic Diseases", "aliases": "Blood Disease Diseases Hematologic Hematological", "definition": "Disorders of the blood and blood forming tissues.\n    ", "id": "MESH:D006402"}
{"mention": "cephalosporin", "mention_text": "Cephalosporin antibiotics cause a variety of hematologic disturbances in man, the pathogeneses and hematopathology of which remain poorly characterized. There is a need for a well-defined animal model in which these blood dyscrasias can be studied. In four subacute toxicity studies, the intravenous administration of cefonicid or cefazedone to beagle dogs caused a dose-dependent incidence of anemia, neutropenia, and thrombocytopenia after 1-3 months of treatment. A nonregenerative anemia was the most compromising of the cytopenias and occurred in approximately 50% of dogs receiving 400-500 mg/kg cefonicid or 540-840 mg/kg cefazedone. All three cytopenias were completely reversible following cessation of treatment; the time required for recovery of the erythron (approximately 1 month) was considerably longer than that of the granulocytes and platelets (hours to a few days). Upon rechallenge with either cephalosporin, the hematologic syndrome was reproduced in most dogs tested; cefonicid (but not cefazedone)-treated dogs showed a substantially reduced induction period (15 +/- 5 days) compared to that of the first exposure to the drug (61 +/- 24 days). This observation, along with the rapid rate of decline in red cell mass parameters of affected dogs, suggests that a hemolytic component complicated the red cell production problem and that multiple toxicologic mechanisms contributed to the cytopenia. We conclude that the administration of high doses of cefonicid or cefazedone to dogs can induce hematotoxicity similar to the cephalosporin-induced blood dyscrasias described in man and thus provides a useful model for studying the mechanisms of these disorders.", "entity": "Cephalosporins", "aliases": "Acids Cephalosporanic Antibiotics Cephalosporin Cephalosporins", "definition": "A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus ACREMONIUM. They contain the beta-lactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid.\n    ", "id": "MESH:D002511"}
{"mention": "hematologic syndrome", "mention_text": "Cephalosporin antibiotics cause a variety of hematologic disturbances in man, the pathogeneses and hematopathology of which remain poorly characterized. There is a need for a well-defined animal model in which these blood dyscrasias can be studied. In four subacute toxicity studies, the intravenous administration of cefonicid or cefazedone to beagle dogs caused a dose-dependent incidence of anemia, neutropenia, and thrombocytopenia after 1-3 months of treatment. A nonregenerative anemia was the most compromising of the cytopenias and occurred in approximately 50% of dogs receiving 400-500 mg/kg cefonicid or 540-840 mg/kg cefazedone. All three cytopenias were completely reversible following cessation of treatment; the time required for recovery of the erythron (approximately 1 month) was considerably longer than that of the granulocytes and platelets (hours to a few days). Upon rechallenge with either cephalosporin, the hematologic syndrome was reproduced in most dogs tested; cefonicid (but not cefazedone)-treated dogs showed a substantially reduced induction period (15 +/- 5 days) compared to that of the first exposure to the drug (61 +/- 24 days). This observation, along with the rapid rate of decline in red cell mass parameters of affected dogs, suggests that a hemolytic component complicated the red cell production problem and that multiple toxicologic mechanisms contributed to the cytopenia. We conclude that the administration of high doses of cefonicid or cefazedone to dogs can induce hematotoxicity similar to the cephalosporin-induced blood dyscrasias described in man and thus provides a useful model for studying the mechanisms of these disorders.", "entity": "Hematologic Diseases", "aliases": "Blood Disease Diseases Hematologic Hematological", "definition": "Disorders of the blood and blood forming tissues.\n    ", "id": "MESH:D006402"}
{"mention": "hemolytic", "mention_text": "Cephalosporin antibiotics cause a variety of hematologic disturbances in man, the pathogeneses and hematopathology of which remain poorly characterized. There is a need for a well-defined animal model in which these blood dyscrasias can be studied. In four subacute toxicity studies, the intravenous administration of cefonicid or cefazedone to beagle dogs caused a dose-dependent incidence of anemia, neutropenia, and thrombocytopenia after 1-3 months of treatment. A nonregenerative anemia was the most compromising of the cytopenias and occurred in approximately 50% of dogs receiving 400-500 mg/kg cefonicid or 540-840 mg/kg cefazedone. All three cytopenias were completely reversible following cessation of treatment; the time required for recovery of the erythron (approximately 1 month) was considerably longer than that of the granulocytes and platelets (hours to a few days). Upon rechallenge with either cephalosporin, the hematologic syndrome was reproduced in most dogs tested; cefonicid (but not cefazedone)-treated dogs showed a substantially reduced induction period (15 +/- 5 days) compared to that of the first exposure to the drug (61 +/- 24 days). This observation, along with the rapid rate of decline in red cell mass parameters of affected dogs, suggests that a hemolytic component complicated the red cell production problem and that multiple toxicologic mechanisms contributed to the cytopenia. We conclude that the administration of high doses of cefonicid or cefazedone to dogs can induce hematotoxicity similar to the cephalosporin-induced blood dyscrasias described in man and thus provides a useful model for studying the mechanisms of these disorders.", "entity": "Hemolysis", "aliases": "Hemolysis", "definition": "The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.\n    ", "id": "MESH:D006461"}
{"mention": "cytopenia", "mention_text": "Cephalosporin antibiotics cause a variety of hematologic disturbances in man, the pathogeneses and hematopathology of which remain poorly characterized. There is a need for a well-defined animal model in which these blood dyscrasias can be studied. In four subacute toxicity studies, the intravenous administration of cefonicid or cefazedone to beagle dogs caused a dose-dependent incidence of anemia, neutropenia, and thrombocytopenia after 1-3 months of treatment. A nonregenerative anemia was the most compromising of the cytopenias and occurred in approximately 50% of dogs receiving 400-500 mg/kg cefonicid or 540-840 mg/kg cefazedone. All three cytopenias were completely reversible following cessation of treatment; the time required for recovery of the erythron (approximately 1 month) was considerably longer than that of the granulocytes and platelets (hours to a few days). Upon rechallenge with either cephalosporin, the hematologic syndrome was reproduced in most dogs tested; cefonicid (but not cefazedone)-treated dogs showed a substantially reduced induction period (15 +/- 5 days) compared to that of the first exposure to the drug (61 +/- 24 days). This observation, along with the rapid rate of decline in red cell mass parameters of affected dogs, suggests that a hemolytic component complicated the red cell production problem and that multiple toxicologic mechanisms contributed to the cytopenia. We conclude that the administration of high doses of cefonicid or cefazedone to dogs can induce hematotoxicity similar to the cephalosporin-induced blood dyscrasias described in man and thus provides a useful model for studying the mechanisms of these disorders.", "entity": "Hematologic Diseases", "aliases": "Blood Disease Diseases Hematologic Hematological", "definition": "Disorders of the blood and blood forming tissues.\n    ", "id": "MESH:D006402"}
{"mention": "hematotoxicity", "mention_text": "Cephalosporin antibiotics cause a variety of hematologic disturbances in man, the pathogeneses and hematopathology of which remain poorly characterized. There is a need for a well-defined animal model in which these blood dyscrasias can be studied. In four subacute toxicity studies, the intravenous administration of cefonicid or cefazedone to beagle dogs caused a dose-dependent incidence of anemia, neutropenia, and thrombocytopenia after 1-3 months of treatment. A nonregenerative anemia was the most compromising of the cytopenias and occurred in approximately 50% of dogs receiving 400-500 mg/kg cefonicid or 540-840 mg/kg cefazedone. All three cytopenias were completely reversible following cessation of treatment; the time required for recovery of the erythron (approximately 1 month) was considerably longer than that of the granulocytes and platelets (hours to a few days). Upon rechallenge with either cephalosporin, the hematologic syndrome was reproduced in most dogs tested; cefonicid (but not cefazedone)-treated dogs showed a substantially reduced induction period (15 +/- 5 days) compared to that of the first exposure to the drug (61 +/- 24 days). This observation, along with the rapid rate of decline in red cell mass parameters of affected dogs, suggests that a hemolytic component complicated the red cell production problem and that multiple toxicologic mechanisms contributed to the cytopenia. We conclude that the administration of high doses of cefonicid or cefazedone to dogs can induce hematotoxicity similar to the cephalosporin-induced blood dyscrasias described in man and thus provides a useful model for studying the mechanisms of these disorders.", "entity": "Hematologic Diseases", "aliases": "Blood Disease Diseases Hematologic Hematological", "definition": "Disorders of the blood and blood forming tissues.\n    ", "id": "MESH:D006402"}
{"mention": "pyridoxine", "mention_text": "A pyridoxine-dependent behavioral disorder unmasked by isoniazid.", "entity": "Pyridoxine", "aliases": "Pyridoxin Pyridoxine Hydrochloride Pyridoxol Rodex", "definition": "The 4-methanol form of VITAMIN B 6 which is converted to PYRIDOXAL PHOSPHATE which is a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. Although pyridoxine and Vitamin B 6 are still frequently used as synonyms, especially by medical researchers, this practice is erroneous and sometimes misleading (EE Snell; Ann NY Acad Sci, vol 585 pg 1, 1990).\n    ", "id": "MESH:D011736"}
{"mention": "behavioral disorder", "mention_text": "A pyridoxine-dependent behavioral disorder unmasked by isoniazid.", "entity": "Child Behavior Disorders", "aliases": "Behavior Disorders Child", "definition": "Disturbances considered to be pathological based on age and stage appropriateness, e.g., conduct disturbances and anaclitic depression. This concept does not include psychoneuroses, psychoses, or personality disorders with fixed patterns.\n    ", "id": "MESH:D002653"}
{"mention": "isoniazid", "mention_text": "A pyridoxine-dependent behavioral disorder unmasked by isoniazid.", "entity": "Isoniazid", "aliases": "Acid Vanillylidenehydrazide Isonicotinic Ftivazide Hydrazide Isonex Isoniazid Phthivazid Phthivazide Tubazide", "definition": "Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis.\n    ", "id": "MESH:D007538"}
{"mention": "behavioral deterioration", "mention_text": "A 3-year-old girl had behavioral deterioration, with hyperkinesis, irritability, and sleeping difficulties after the therapeutic administration of isoniazid. The administration of pharmacologic doses of pyridoxine hydrochloride led to a disappearance of symptoms. After discontinuing isoniazid therapy a similar pattern of behavior was noted that was controlled by pyridoxine. A placebo had no effect, but niacinamide was as effective as pyridoxine. Periodic withdrawal of pyridoxine was associated with return of the hyperkinesis. The level of pyridoxal in the blood was normal during the periods of relapse. Metabolic studies suggested a block in the kynurenine pathway of tryptophan metabolism. The patient has been followed for six years and has required pharmacologic doses of pyridoxine to control her behavior.", "entity": "Child Behavior Disorders", "aliases": "Behavior Disorders Child", "definition": "Disturbances considered to be pathological based on age and stage appropriateness, e.g., conduct disturbances and anaclitic depression. This concept does not include psychoneuroses, psychoses, or personality disorders with fixed patterns.\n    ", "id": "MESH:D002653"}
{"mention": "hyperkinesis", "mention_text": "A 3-year-old girl had behavioral deterioration, with hyperkinesis, irritability, and sleeping difficulties after the therapeutic administration of isoniazid. The administration of pharmacologic doses of pyridoxine hydrochloride led to a disappearance of symptoms. After discontinuing isoniazid therapy a similar pattern of behavior was noted that was controlled by pyridoxine. A placebo had no effect, but niacinamide was as effective as pyridoxine. Periodic withdrawal of pyridoxine was associated with return of the hyperkinesis. The level of pyridoxal in the blood was normal during the periods of relapse. Metabolic studies suggested a block in the kynurenine pathway of tryptophan metabolism. The patient has been followed for six years and has required pharmacologic doses of pyridoxine to control her behavior.", "entity": "Hyperkinesis", "aliases": "Generalized Hyperkinesia Hyperkinesias Hyperactivity Motor Hyperkinesis Hyperkinetic Movement Movements", "definition": "Excessive movement of muscles of the body as a whole, which may be associated with organic or psychological disorders.\n    ", "id": "MESH:D006948"}
{"mention": "irritability", "mention_text": "A 3-year-old girl had behavioral deterioration, with hyperkinesis, irritability, and sleeping difficulties after the therapeutic administration of isoniazid. The administration of pharmacologic doses of pyridoxine hydrochloride led to a disappearance of symptoms. After discontinuing isoniazid therapy a similar pattern of behavior was noted that was controlled by pyridoxine. A placebo had no effect, but niacinamide was as effective as pyridoxine. Periodic withdrawal of pyridoxine was associated with return of the hyperkinesis. The level of pyridoxal in the blood was normal during the periods of relapse. Metabolic studies suggested a block in the kynurenine pathway of tryptophan metabolism. The patient has been followed for six years and has required pharmacologic doses of pyridoxine to control her behavior.", "entity": "Mental Disorders", "aliases": "Behavior Disorders Diagnosis Psychiatric Disorder Mental", "definition": "Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.\n    ", "id": "MESH:D001523"}
{"mention": "sleeping difficulties", "mention_text": "A 3-year-old girl had behavioral deterioration, with hyperkinesis, irritability, and sleeping difficulties after the therapeutic administration of isoniazid. The administration of pharmacologic doses of pyridoxine hydrochloride led to a disappearance of symptoms. After discontinuing isoniazid therapy a similar pattern of behavior was noted that was controlled by pyridoxine. A placebo had no effect, but niacinamide was as effective as pyridoxine. Periodic withdrawal of pyridoxine was associated with return of the hyperkinesis. The level of pyridoxal in the blood was normal during the periods of relapse. Metabolic studies suggested a block in the kynurenine pathway of tryptophan metabolism. The patient has been followed for six years and has required pharmacologic doses of pyridoxine to control her behavior.", "entity": "Sleep Disorders", "aliases": "Long Sleeper Syndrome Syndromes Neurogenic Tachypnea Sleep-Related Tachypneas Phenotype Short Sleep Phenotypes Disorders Related Subwakefullness", "definition": "Conditions characterized by disturbances of usual sleep patterns or behaviors. Sleep disorders may be divided into three major categories: DYSSOMNIAS (i.e. disorders characterized by insomnia or hypersomnia), PARASOMNIAS (abnormal sleep behaviors), and sleep disorders secondary to medical or psychiatric disorders. (From Thorpy, Sleep Disorders Medicine, 1994, p187)\n    ", "id": "MESH:D012893"}
{"mention": "isoniazid", "mention_text": "A 3-year-old girl had behavioral deterioration, with hyperkinesis, irritability, and sleeping difficulties after the therapeutic administration of isoniazid. The administration of pharmacologic doses of pyridoxine hydrochloride led to a disappearance of symptoms. After discontinuing isoniazid therapy a similar pattern of behavior was noted that was controlled by pyridoxine. A placebo had no effect, but niacinamide was as effective as pyridoxine. Periodic withdrawal of pyridoxine was associated with return of the hyperkinesis. The level of pyridoxal in the blood was normal during the periods of relapse. Metabolic studies suggested a block in the kynurenine pathway of tryptophan metabolism. The patient has been followed for six years and has required pharmacologic doses of pyridoxine to control her behavior.", "entity": "Isoniazid", "aliases": "Acid Vanillylidenehydrazide Isonicotinic Ftivazide Hydrazide Isonex Isoniazid Phthivazid Phthivazide Tubazide", "definition": "Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis.\n    ", "id": "MESH:D007538"}
{"mention": "pyridoxine hydrochloride", "mention_text": "A 3-year-old girl had behavioral deterioration, with hyperkinesis, irritability, and sleeping difficulties after the therapeutic administration of isoniazid. The administration of pharmacologic doses of pyridoxine hydrochloride led to a disappearance of symptoms. After discontinuing isoniazid therapy a similar pattern of behavior was noted that was controlled by pyridoxine. A placebo had no effect, but niacinamide was as effective as pyridoxine. Periodic withdrawal of pyridoxine was associated with return of the hyperkinesis. The level of pyridoxal in the blood was normal during the periods of relapse. Metabolic studies suggested a block in the kynurenine pathway of tryptophan metabolism. The patient has been followed for six years and has required pharmacologic doses of pyridoxine to control her behavior.", "entity": "Pyridoxine", "aliases": "Pyridoxin Pyridoxine Hydrochloride Pyridoxol Rodex", "definition": "The 4-methanol form of VITAMIN B 6 which is converted to PYRIDOXAL PHOSPHATE which is a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. Although pyridoxine and Vitamin B 6 are still frequently used as synonyms, especially by medical researchers, this practice is erroneous and sometimes misleading (EE Snell; Ann NY Acad Sci, vol 585 pg 1, 1990).\n    ", "id": "MESH:D011736"}
{"mention": "pyridoxine", "mention_text": "A 3-year-old girl had behavioral deterioration, with hyperkinesis, irritability, and sleeping difficulties after the therapeutic administration of isoniazid. The administration of pharmacologic doses of pyridoxine hydrochloride led to a disappearance of symptoms. After discontinuing isoniazid therapy a similar pattern of behavior was noted that was controlled by pyridoxine. A placebo had no effect, but niacinamide was as effective as pyridoxine. Periodic withdrawal of pyridoxine was associated with return of the hyperkinesis. The level of pyridoxal in the blood was normal during the periods of relapse. Metabolic studies suggested a block in the kynurenine pathway of tryptophan metabolism. The patient has been followed for six years and has required pharmacologic doses of pyridoxine to control her behavior.", "entity": "Pyridoxine", "aliases": "Pyridoxin Pyridoxine Hydrochloride Pyridoxol Rodex", "definition": "The 4-methanol form of VITAMIN B 6 which is converted to PYRIDOXAL PHOSPHATE which is a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. Although pyridoxine and Vitamin B 6 are still frequently used as synonyms, especially by medical researchers, this practice is erroneous and sometimes misleading (EE Snell; Ann NY Acad Sci, vol 585 pg 1, 1990).\n    ", "id": "MESH:D011736"}
{"mention": "niacinamide", "mention_text": "A 3-year-old girl had behavioral deterioration, with hyperkinesis, irritability, and sleeping difficulties after the therapeutic administration of isoniazid. The administration of pharmacologic doses of pyridoxine hydrochloride led to a disappearance of symptoms. After discontinuing isoniazid therapy a similar pattern of behavior was noted that was controlled by pyridoxine. A placebo had no effect, but niacinamide was as effective as pyridoxine. Periodic withdrawal of pyridoxine was associated with return of the hyperkinesis. The level of pyridoxal in the blood was normal during the periods of relapse. Metabolic studies suggested a block in the kynurenine pathway of tryptophan metabolism. The patient has been followed for six years and has required pharmacologic doses of pyridoxine to control her behavior.", "entity": "Niacinamide", "aliases": "3 Pyridinecarboxamide 3-Pyridinecarboxamide Astra Brand of Niacinamide B Vitamin B3 Enduramide Jenapharm Nicotinsäureamid Merck Pharmagenix Nicobion Nicotinamide Papulex PP", "definition": "An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and PELLAGRA. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake.\n    ", "id": "MESH:D009536"}
{"mention": "pyridoxal", "mention_text": "A 3-year-old girl had behavioral deterioration, with hyperkinesis, irritability, and sleeping difficulties after the therapeutic administration of isoniazid. The administration of pharmacologic doses of pyridoxine hydrochloride led to a disappearance of symptoms. After discontinuing isoniazid therapy a similar pattern of behavior was noted that was controlled by pyridoxine. A placebo had no effect, but niacinamide was as effective as pyridoxine. Periodic withdrawal of pyridoxine was associated with return of the hyperkinesis. The level of pyridoxal in the blood was normal during the periods of relapse. Metabolic studies suggested a block in the kynurenine pathway of tryptophan metabolism. The patient has been followed for six years and has required pharmacologic doses of pyridoxine to control her behavior.", "entity": "Pyridoxal", "aliases": "Pyridoxal", "definition": "The 4-carboxyaldehyde form of VITAMIN B 6 which is converted to PYRIDOXAL PHOSPHATE which is a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid.\n    ", "id": "MESH:D011730"}
{"mention": "kynurenine", "mention_text": "A 3-year-old girl had behavioral deterioration, with hyperkinesis, irritability, and sleeping difficulties after the therapeutic administration of isoniazid. The administration of pharmacologic doses of pyridoxine hydrochloride led to a disappearance of symptoms. After discontinuing isoniazid therapy a similar pattern of behavior was noted that was controlled by pyridoxine. A placebo had no effect, but niacinamide was as effective as pyridoxine. Periodic withdrawal of pyridoxine was associated with return of the hyperkinesis. The level of pyridoxal in the blood was normal during the periods of relapse. Metabolic studies suggested a block in the kynurenine pathway of tryptophan metabolism. The patient has been followed for six years and has required pharmacologic doses of pyridoxine to control her behavior.", "entity": "Kynurenine", "aliases": "Kynurenine", "definition": "", "id": "MESH:D007737"}
{"mention": "tryptophan", "mention_text": "A 3-year-old girl had behavioral deterioration, with hyperkinesis, irritability, and sleeping difficulties after the therapeutic administration of isoniazid. The administration of pharmacologic doses of pyridoxine hydrochloride led to a disappearance of symptoms. After discontinuing isoniazid therapy a similar pattern of behavior was noted that was controlled by pyridoxine. A placebo had no effect, but niacinamide was as effective as pyridoxine. Periodic withdrawal of pyridoxine was associated with return of the hyperkinesis. The level of pyridoxal in the blood was normal during the periods of relapse. Metabolic studies suggested a block in the kynurenine pathway of tryptophan metabolism. The patient has been followed for six years and has required pharmacologic doses of pyridoxine to control her behavior.", "entity": "Tryptophan", "aliases": "Ardeydorm Ardeypharm Brand of Tryptophan Ardeytropin ICN Kalma L ratiopharm L-Tryptophan L-Tryptophan-ratiopharm Levotryptophan Lyphan Merck Naturruhe Niddapharm Optimax PMS PMS-Tryptophan Pharmascience Ratiopharm Trofan Tryptacin Tryptan Metabolism Alterations Upsher-Smith esparma ratio ratio-Tryptophan", "definition": "An essential amino acid that is necessary for normal growth in infants and for NITROGEN balance in adults. It is a precursor of INDOLE ALKALOIDS in plants. It is a precursor of SEROTONIN (hence its use as an antidepressant and sleep aid). It can be a precursor to NIACIN, albeit inefficiently, in mammals.\n    ", "id": "MESH:D014364"}
{"mention": "dopamine", "mention_text": "A selective dopamine D4 receptor antagonist, NRA0160: a preclinical neuropharmacological profile.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "NRA0160", "mention_text": "A selective dopamine D4 receptor antagonist, NRA0160: a preclinical neuropharmacological profile.", "entity": "NRA 0160", "aliases": "2-carbamoyl-4-(4-fluorophenyl)-5-(2-(4-(3-fluorobenzylidene)piperidine-1-yl)ethyl)thiazole NRA 0160 NRA0160", "definition": "", "id": "MESH:C121249"}
{"mention": "NRA0160", "mention_text": "NRA0160, 5 - [2- ( 4- ( 3 - fluorobenzylidene) piperidin-1-yl) ethyl] - 4 -(4-fluorophenyl) thiazole-2-carboxamide, has a high affinity for human cloned dopamine D4.2, D4.4 and D4.7 receptors, with Ki values of 0.5, 0.9 and 2.7 nM, respectively. NRA0160 is over 20,000fold more potent at the dopamine D4.2 receptor compared with the human cloned dopamine D2L receptor. NRA0160 has negligible affinity for the human cloned dopamine D3 receptor (Ki=39 nM), rat serotonin (5-HT)2A receptors (Ki=180 nM) and rat alpha1 adrenoceptor (Ki=237 nM). NRA0160 and clozapine antagonized locomotor hyperactivity induced by methamphetamine (MAP) in mice. NRA0160 and clozapine antagonized MAP-induced stereotyped behavior in mice, although their effects did not exceed 50% inhibition, even at the highest dose given. NRA0160 and clozapine significantly induced catalepsy in rats, although their effects did not exceed 50% induction even at the highest dose given. NRA0160 and clozapine significantly reversed the disruption of prepulse inhibition (PPI) in rats produced by apomorphine. NRA0160 and clozapine significantly shortened the phencyclidine (PCP)-induced prolonged swimming latency in rats in a water maze task. These findings suggest that NRA0160 may have unique antipsychotic activities without the liability of motor side effects typical of classical antipsychotics.", "entity": "NRA 0160", "aliases": "2-carbamoyl-4-(4-fluorophenyl)-5-(2-(4-(3-fluorobenzylidene)piperidine-1-yl)ethyl)thiazole NRA 0160 NRA0160", "definition": "", "id": "MESH:C121249"}
{"mention": "5 - [2- ( 4- ( 3 - fluorobenzylidene) piperidin-1-yl) ethyl] - 4 -(4-fluorophenyl) thiazole-2-carboxamide", "mention_text": "NRA0160, 5 - [2- ( 4- ( 3 - fluorobenzylidene) piperidin-1-yl) ethyl] - 4 -(4-fluorophenyl) thiazole-2-carboxamide, has a high affinity for human cloned dopamine D4.2, D4.4 and D4.7 receptors, with Ki values of 0.5, 0.9 and 2.7 nM, respectively. NRA0160 is over 20,000fold more potent at the dopamine D4.2 receptor compared with the human cloned dopamine D2L receptor. NRA0160 has negligible affinity for the human cloned dopamine D3 receptor (Ki=39 nM), rat serotonin (5-HT)2A receptors (Ki=180 nM) and rat alpha1 adrenoceptor (Ki=237 nM). NRA0160 and clozapine antagonized locomotor hyperactivity induced by methamphetamine (MAP) in mice. NRA0160 and clozapine antagonized MAP-induced stereotyped behavior in mice, although their effects did not exceed 50% inhibition, even at the highest dose given. NRA0160 and clozapine significantly induced catalepsy in rats, although their effects did not exceed 50% induction even at the highest dose given. NRA0160 and clozapine significantly reversed the disruption of prepulse inhibition (PPI) in rats produced by apomorphine. NRA0160 and clozapine significantly shortened the phencyclidine (PCP)-induced prolonged swimming latency in rats in a water maze task. These findings suggest that NRA0160 may have unique antipsychotic activities without the liability of motor side effects typical of classical antipsychotics.", "entity": "NRA 0160", "aliases": "2-carbamoyl-4-(4-fluorophenyl)-5-(2-(4-(3-fluorobenzylidene)piperidine-1-yl)ethyl)thiazole NRA 0160 NRA0160", "definition": "", "id": "MESH:C121249"}
{"mention": "dopamine", "mention_text": "NRA0160, 5 - [2- ( 4- ( 3 - fluorobenzylidene) piperidin-1-yl) ethyl] - 4 -(4-fluorophenyl) thiazole-2-carboxamide, has a high affinity for human cloned dopamine D4.2, D4.4 and D4.7 receptors, with Ki values of 0.5, 0.9 and 2.7 nM, respectively. NRA0160 is over 20,000fold more potent at the dopamine D4.2 receptor compared with the human cloned dopamine D2L receptor. NRA0160 has negligible affinity for the human cloned dopamine D3 receptor (Ki=39 nM), rat serotonin (5-HT)2A receptors (Ki=180 nM) and rat alpha1 adrenoceptor (Ki=237 nM). NRA0160 and clozapine antagonized locomotor hyperactivity induced by methamphetamine (MAP) in mice. NRA0160 and clozapine antagonized MAP-induced stereotyped behavior in mice, although their effects did not exceed 50% inhibition, even at the highest dose given. NRA0160 and clozapine significantly induced catalepsy in rats, although their effects did not exceed 50% induction even at the highest dose given. NRA0160 and clozapine significantly reversed the disruption of prepulse inhibition (PPI) in rats produced by apomorphine. NRA0160 and clozapine significantly shortened the phencyclidine (PCP)-induced prolonged swimming latency in rats in a water maze task. These findings suggest that NRA0160 may have unique antipsychotic activities without the liability of motor side effects typical of classical antipsychotics.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "serotonin", "mention_text": "NRA0160, 5 - [2- ( 4- ( 3 - fluorobenzylidene) piperidin-1-yl) ethyl] - 4 -(4-fluorophenyl) thiazole-2-carboxamide, has a high affinity for human cloned dopamine D4.2, D4.4 and D4.7 receptors, with Ki values of 0.5, 0.9 and 2.7 nM, respectively. NRA0160 is over 20,000fold more potent at the dopamine D4.2 receptor compared with the human cloned dopamine D2L receptor. NRA0160 has negligible affinity for the human cloned dopamine D3 receptor (Ki=39 nM), rat serotonin (5-HT)2A receptors (Ki=180 nM) and rat alpha1 adrenoceptor (Ki=237 nM). NRA0160 and clozapine antagonized locomotor hyperactivity induced by methamphetamine (MAP) in mice. NRA0160 and clozapine antagonized MAP-induced stereotyped behavior in mice, although their effects did not exceed 50% inhibition, even at the highest dose given. NRA0160 and clozapine significantly induced catalepsy in rats, although their effects did not exceed 50% induction even at the highest dose given. NRA0160 and clozapine significantly reversed the disruption of prepulse inhibition (PPI) in rats produced by apomorphine. NRA0160 and clozapine significantly shortened the phencyclidine (PCP)-induced prolonged swimming latency in rats in a water maze task. These findings suggest that NRA0160 may have unique antipsychotic activities without the liability of motor side effects typical of classical antipsychotics.", "entity": "Serotonin", "aliases": "3-(2-Aminoethyl)-1H-indol-5-ol 5 Hydroxytryptamine 5-HT 5-Hydroxytryptamine Enteramine Hippophaine Serotonin", "definition": "A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.\n    ", "id": "MESH:D012701"}
{"mention": "5-HT", "mention_text": "NRA0160, 5 - [2- ( 4- ( 3 - fluorobenzylidene) piperidin-1-yl) ethyl] - 4 -(4-fluorophenyl) thiazole-2-carboxamide, has a high affinity for human cloned dopamine D4.2, D4.4 and D4.7 receptors, with Ki values of 0.5, 0.9 and 2.7 nM, respectively. NRA0160 is over 20,000fold more potent at the dopamine D4.2 receptor compared with the human cloned dopamine D2L receptor. NRA0160 has negligible affinity for the human cloned dopamine D3 receptor (Ki=39 nM), rat serotonin (5-HT)2A receptors (Ki=180 nM) and rat alpha1 adrenoceptor (Ki=237 nM). NRA0160 and clozapine antagonized locomotor hyperactivity induced by methamphetamine (MAP) in mice. NRA0160 and clozapine antagonized MAP-induced stereotyped behavior in mice, although their effects did not exceed 50% inhibition, even at the highest dose given. NRA0160 and clozapine significantly induced catalepsy in rats, although their effects did not exceed 50% induction even at the highest dose given. NRA0160 and clozapine significantly reversed the disruption of prepulse inhibition (PPI) in rats produced by apomorphine. NRA0160 and clozapine significantly shortened the phencyclidine (PCP)-induced prolonged swimming latency in rats in a water maze task. These findings suggest that NRA0160 may have unique antipsychotic activities without the liability of motor side effects typical of classical antipsychotics.", "entity": "Serotonin", "aliases": "3-(2-Aminoethyl)-1H-indol-5-ol 5 Hydroxytryptamine 5-HT 5-Hydroxytryptamine Enteramine Hippophaine Serotonin", "definition": "A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.\n    ", "id": "MESH:D012701"}
{"mention": "clozapine", "mention_text": "NRA0160, 5 - [2- ( 4- ( 3 - fluorobenzylidene) piperidin-1-yl) ethyl] - 4 -(4-fluorophenyl) thiazole-2-carboxamide, has a high affinity for human cloned dopamine D4.2, D4.4 and D4.7 receptors, with Ki values of 0.5, 0.9 and 2.7 nM, respectively. NRA0160 is over 20,000fold more potent at the dopamine D4.2 receptor compared with the human cloned dopamine D2L receptor. NRA0160 has negligible affinity for the human cloned dopamine D3 receptor (Ki=39 nM), rat serotonin (5-HT)2A receptors (Ki=180 nM) and rat alpha1 adrenoceptor (Ki=237 nM). NRA0160 and clozapine antagonized locomotor hyperactivity induced by methamphetamine (MAP) in mice. NRA0160 and clozapine antagonized MAP-induced stereotyped behavior in mice, although their effects did not exceed 50% inhibition, even at the highest dose given. NRA0160 and clozapine significantly induced catalepsy in rats, although their effects did not exceed 50% induction even at the highest dose given. NRA0160 and clozapine significantly reversed the disruption of prepulse inhibition (PPI) in rats produced by apomorphine. NRA0160 and clozapine significantly shortened the phencyclidine (PCP)-induced prolonged swimming latency in rats in a water maze task. These findings suggest that NRA0160 may have unique antipsychotic activities without the liability of motor side effects typical of classical antipsychotics.", "entity": "Clozapine", "aliases": "Clozapine Clozaril Leponex", "definition": "A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.\n    ", "id": "MESH:D003024"}
{"mention": "hyperactivity", "mention_text": "NRA0160, 5 - [2- ( 4- ( 3 - fluorobenzylidene) piperidin-1-yl) ethyl] - 4 -(4-fluorophenyl) thiazole-2-carboxamide, has a high affinity for human cloned dopamine D4.2, D4.4 and D4.7 receptors, with Ki values of 0.5, 0.9 and 2.7 nM, respectively. NRA0160 is over 20,000fold more potent at the dopamine D4.2 receptor compared with the human cloned dopamine D2L receptor. NRA0160 has negligible affinity for the human cloned dopamine D3 receptor (Ki=39 nM), rat serotonin (5-HT)2A receptors (Ki=180 nM) and rat alpha1 adrenoceptor (Ki=237 nM). NRA0160 and clozapine antagonized locomotor hyperactivity induced by methamphetamine (MAP) in mice. NRA0160 and clozapine antagonized MAP-induced stereotyped behavior in mice, although their effects did not exceed 50% inhibition, even at the highest dose given. NRA0160 and clozapine significantly induced catalepsy in rats, although their effects did not exceed 50% induction even at the highest dose given. NRA0160 and clozapine significantly reversed the disruption of prepulse inhibition (PPI) in rats produced by apomorphine. NRA0160 and clozapine significantly shortened the phencyclidine (PCP)-induced prolonged swimming latency in rats in a water maze task. These findings suggest that NRA0160 may have unique antipsychotic activities without the liability of motor side effects typical of classical antipsychotics.", "entity": "Hyperkinesis", "aliases": "Generalized Hyperkinesia Hyperkinesias Hyperactivity Motor Hyperkinesis Hyperkinetic Movement Movements", "definition": "Excessive movement of muscles of the body as a whole, which may be associated with organic or psychological disorders.\n    ", "id": "MESH:D006948"}
{"mention": "methamphetamine", "mention_text": "NRA0160, 5 - [2- ( 4- ( 3 - fluorobenzylidene) piperidin-1-yl) ethyl] - 4 -(4-fluorophenyl) thiazole-2-carboxamide, has a high affinity for human cloned dopamine D4.2, D4.4 and D4.7 receptors, with Ki values of 0.5, 0.9 and 2.7 nM, respectively. NRA0160 is over 20,000fold more potent at the dopamine D4.2 receptor compared with the human cloned dopamine D2L receptor. NRA0160 has negligible affinity for the human cloned dopamine D3 receptor (Ki=39 nM), rat serotonin (5-HT)2A receptors (Ki=180 nM) and rat alpha1 adrenoceptor (Ki=237 nM). NRA0160 and clozapine antagonized locomotor hyperactivity induced by methamphetamine (MAP) in mice. NRA0160 and clozapine antagonized MAP-induced stereotyped behavior in mice, although their effects did not exceed 50% inhibition, even at the highest dose given. NRA0160 and clozapine significantly induced catalepsy in rats, although their effects did not exceed 50% induction even at the highest dose given. NRA0160 and clozapine significantly reversed the disruption of prepulse inhibition (PPI) in rats produced by apomorphine. NRA0160 and clozapine significantly shortened the phencyclidine (PCP)-induced prolonged swimming latency in rats in a water maze task. These findings suggest that NRA0160 may have unique antipsychotic activities without the liability of motor side effects typical of classical antipsychotics.", "entity": "Methamphetamine", "aliases": "Abbott Brand of Methamphetamine Hydrochloride Deoxyephedrine Desoxyephedrine Desoxyn Langly Madrine Metamfetamine Methylamphetamine N N-Methylamphetamine", "definition": "A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.\n    ", "id": "MESH:D008694"}
{"mention": "MAP", "mention_text": "NRA0160, 5 - [2- ( 4- ( 3 - fluorobenzylidene) piperidin-1-yl) ethyl] - 4 -(4-fluorophenyl) thiazole-2-carboxamide, has a high affinity for human cloned dopamine D4.2, D4.4 and D4.7 receptors, with Ki values of 0.5, 0.9 and 2.7 nM, respectively. NRA0160 is over 20,000fold more potent at the dopamine D4.2 receptor compared with the human cloned dopamine D2L receptor. NRA0160 has negligible affinity for the human cloned dopamine D3 receptor (Ki=39 nM), rat serotonin (5-HT)2A receptors (Ki=180 nM) and rat alpha1 adrenoceptor (Ki=237 nM). NRA0160 and clozapine antagonized locomotor hyperactivity induced by methamphetamine (MAP) in mice. NRA0160 and clozapine antagonized MAP-induced stereotyped behavior in mice, although their effects did not exceed 50% inhibition, even at the highest dose given. NRA0160 and clozapine significantly induced catalepsy in rats, although their effects did not exceed 50% induction even at the highest dose given. NRA0160 and clozapine significantly reversed the disruption of prepulse inhibition (PPI) in rats produced by apomorphine. NRA0160 and clozapine significantly shortened the phencyclidine (PCP)-induced prolonged swimming latency in rats in a water maze task. These findings suggest that NRA0160 may have unique antipsychotic activities without the liability of motor side effects typical of classical antipsychotics.", "entity": "Methamphetamine", "aliases": "Abbott Brand of Methamphetamine Hydrochloride Deoxyephedrine Desoxyephedrine Desoxyn Langly Madrine Metamfetamine Methylamphetamine N N-Methylamphetamine", "definition": "A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.\n    ", "id": "MESH:D008694"}
{"mention": "catalepsy", "mention_text": "NRA0160, 5 - [2- ( 4- ( 3 - fluorobenzylidene) piperidin-1-yl) ethyl] - 4 -(4-fluorophenyl) thiazole-2-carboxamide, has a high affinity for human cloned dopamine D4.2, D4.4 and D4.7 receptors, with Ki values of 0.5, 0.9 and 2.7 nM, respectively. NRA0160 is over 20,000fold more potent at the dopamine D4.2 receptor compared with the human cloned dopamine D2L receptor. NRA0160 has negligible affinity for the human cloned dopamine D3 receptor (Ki=39 nM), rat serotonin (5-HT)2A receptors (Ki=180 nM) and rat alpha1 adrenoceptor (Ki=237 nM). NRA0160 and clozapine antagonized locomotor hyperactivity induced by methamphetamine (MAP) in mice. NRA0160 and clozapine antagonized MAP-induced stereotyped behavior in mice, although their effects did not exceed 50% inhibition, even at the highest dose given. NRA0160 and clozapine significantly induced catalepsy in rats, although their effects did not exceed 50% induction even at the highest dose given. NRA0160 and clozapine significantly reversed the disruption of prepulse inhibition (PPI) in rats produced by apomorphine. NRA0160 and clozapine significantly shortened the phencyclidine (PCP)-induced prolonged swimming latency in rats in a water maze task. These findings suggest that NRA0160 may have unique antipsychotic activities without the liability of motor side effects typical of classical antipsychotics.", "entity": "Catalepsy", "aliases": "Anochlesia Anochlesias Catalepsies Catalepsy Cerea Flexibilitas Flexibilities Waxy Flexibility", "definition": "A condition characterized by inactivity, decreased responsiveness to stimuli, and a tendency to maintain an immobile posture. The limbs tend to remain in whatever position they are placed (waxy flexibility). Catalepsy may be associated with PSYCHOTIC DISORDERS (e.g., SCHIZOPHRENIA, CATATONIC), nervous system drug toxicity, and other conditions.\n    ", "id": "MESH:D002375"}
{"mention": "apomorphine", "mention_text": "NRA0160, 5 - [2- ( 4- ( 3 - fluorobenzylidene) piperidin-1-yl) ethyl] - 4 -(4-fluorophenyl) thiazole-2-carboxamide, has a high affinity for human cloned dopamine D4.2, D4.4 and D4.7 receptors, with Ki values of 0.5, 0.9 and 2.7 nM, respectively. NRA0160 is over 20,000fold more potent at the dopamine D4.2 receptor compared with the human cloned dopamine D2L receptor. NRA0160 has negligible affinity for the human cloned dopamine D3 receptor (Ki=39 nM), rat serotonin (5-HT)2A receptors (Ki=180 nM) and rat alpha1 adrenoceptor (Ki=237 nM). NRA0160 and clozapine antagonized locomotor hyperactivity induced by methamphetamine (MAP) in mice. NRA0160 and clozapine antagonized MAP-induced stereotyped behavior in mice, although their effects did not exceed 50% inhibition, even at the highest dose given. NRA0160 and clozapine significantly induced catalepsy in rats, although their effects did not exceed 50% induction even at the highest dose given. NRA0160 and clozapine significantly reversed the disruption of prepulse inhibition (PPI) in rats produced by apomorphine. NRA0160 and clozapine significantly shortened the phencyclidine (PCP)-induced prolonged swimming latency in rats in a water maze task. These findings suggest that NRA0160 may have unique antipsychotic activities without the liability of motor side effects typical of classical antipsychotics.", "entity": "Apomorphine", "aliases": "Aguettant Brand of Apomorphine Hydrochloride Anhydrous Apokinon Apomorphin Teclapharm Apomorphin-Teclapharm ApomorphinTeclapharm Chloride Hemihydrate Britaject Britannia", "definition": "A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use.\n    ", "id": "MESH:D001058"}
{"mention": "phencyclidine", "mention_text": "NRA0160, 5 - [2- ( 4- ( 3 - fluorobenzylidene) piperidin-1-yl) ethyl] - 4 -(4-fluorophenyl) thiazole-2-carboxamide, has a high affinity for human cloned dopamine D4.2, D4.4 and D4.7 receptors, with Ki values of 0.5, 0.9 and 2.7 nM, respectively. NRA0160 is over 20,000fold more potent at the dopamine D4.2 receptor compared with the human cloned dopamine D2L receptor. NRA0160 has negligible affinity for the human cloned dopamine D3 receptor (Ki=39 nM), rat serotonin (5-HT)2A receptors (Ki=180 nM) and rat alpha1 adrenoceptor (Ki=237 nM). NRA0160 and clozapine antagonized locomotor hyperactivity induced by methamphetamine (MAP) in mice. NRA0160 and clozapine antagonized MAP-induced stereotyped behavior in mice, although their effects did not exceed 50% inhibition, even at the highest dose given. NRA0160 and clozapine significantly induced catalepsy in rats, although their effects did not exceed 50% induction even at the highest dose given. NRA0160 and clozapine significantly reversed the disruption of prepulse inhibition (PPI) in rats produced by apomorphine. NRA0160 and clozapine significantly shortened the phencyclidine (PCP)-induced prolonged swimming latency in rats in a water maze task. These findings suggest that NRA0160 may have unique antipsychotic activities without the liability of motor side effects typical of classical antipsychotics.", "entity": "Phencyclidine", "aliases": "1-(1-Phenylcyclohexyl)piperidine Angel Dust CL 395 CL-395 CL395 GP 121 GP-121 GP121 Phencyclidine Hydrobromide Hydrochloride Sernyl Serylan", "definition": "A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to KETAMINE in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE). As a drug of abuse, it is known as PCP and Angel Dust.\n    ", "id": "MESH:D010622"}
{"mention": "PCP", "mention_text": "NRA0160, 5 - [2- ( 4- ( 3 - fluorobenzylidene) piperidin-1-yl) ethyl] - 4 -(4-fluorophenyl) thiazole-2-carboxamide, has a high affinity for human cloned dopamine D4.2, D4.4 and D4.7 receptors, with Ki values of 0.5, 0.9 and 2.7 nM, respectively. NRA0160 is over 20,000fold more potent at the dopamine D4.2 receptor compared with the human cloned dopamine D2L receptor. NRA0160 has negligible affinity for the human cloned dopamine D3 receptor (Ki=39 nM), rat serotonin (5-HT)2A receptors (Ki=180 nM) and rat alpha1 adrenoceptor (Ki=237 nM). NRA0160 and clozapine antagonized locomotor hyperactivity induced by methamphetamine (MAP) in mice. NRA0160 and clozapine antagonized MAP-induced stereotyped behavior in mice, although their effects did not exceed 50% inhibition, even at the highest dose given. NRA0160 and clozapine significantly induced catalepsy in rats, although their effects did not exceed 50% induction even at the highest dose given. NRA0160 and clozapine significantly reversed the disruption of prepulse inhibition (PPI) in rats produced by apomorphine. NRA0160 and clozapine significantly shortened the phencyclidine (PCP)-induced prolonged swimming latency in rats in a water maze task. These findings suggest that NRA0160 may have unique antipsychotic activities without the liability of motor side effects typical of classical antipsychotics.", "entity": "Phencyclidine", "aliases": "1-(1-Phenylcyclohexyl)piperidine Angel Dust CL 395 CL-395 CL395 GP 121 GP-121 GP121 Phencyclidine Hydrobromide Hydrochloride Sernyl Serylan", "definition": "A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to KETAMINE in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE). As a drug of abuse, it is known as PCP and Angel Dust.\n    ", "id": "MESH:D010622"}
{"mention": "cholestasis", "mention_text": "Prolonged cholestasis after troleandomycin-induced acute hepatitis.", "entity": "Cholestasis", "aliases": "Bile Duct Obstruction Obstructions Biliary Stases Stasis Cholestases Cholestasis", "definition": "Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).\n    ", "id": "MESH:D002779"}
{"mention": "troleandomycin", "mention_text": "Prolonged cholestasis after troleandomycin-induced acute hepatitis.", "entity": "Troleandomycin", "aliases": "Oleandocetin Pfizer Brand of Troleandomycin TAO Triacetyloleandomycin", "definition": "A macrolide antibiotic that is similar to ERYTHROMYCIN.\n    ", "id": "MESH:D014217"}
{"mention": "hepatitis", "mention_text": "Prolonged cholestasis after troleandomycin-induced acute hepatitis.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "troleandomycin", "mention_text": "We report the case of a patient in whom troleandomycin-induced hepatitis was followed by prolonged anicteric cholestasis. Jaundice occurred after administration of troleandomycin for 7 days and was associated with hypereosinophilia. Jaundice disappeared within 3 months but was followed by prolonged anicteric cholestasis marked by pruritus and high levels of alkaline phosphatase and gammaglutamyltransferase activities. Finally, pruritus disappeared within 19 months, and liver tests returned to normal 27 months after the onset of hepatitis. This observation demonstrates that prolonged cholestasis can follow troleandomycin-induced acute hepatitis.", "entity": "Troleandomycin", "aliases": "Oleandocetin Pfizer Brand of Troleandomycin TAO Triacetyloleandomycin", "definition": "A macrolide antibiotic that is similar to ERYTHROMYCIN.\n    ", "id": "MESH:D014217"}
{"mention": "hepatitis", "mention_text": "We report the case of a patient in whom troleandomycin-induced hepatitis was followed by prolonged anicteric cholestasis. Jaundice occurred after administration of troleandomycin for 7 days and was associated with hypereosinophilia. Jaundice disappeared within 3 months but was followed by prolonged anicteric cholestasis marked by pruritus and high levels of alkaline phosphatase and gammaglutamyltransferase activities. Finally, pruritus disappeared within 19 months, and liver tests returned to normal 27 months after the onset of hepatitis. This observation demonstrates that prolonged cholestasis can follow troleandomycin-induced acute hepatitis.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "cholestasis", "mention_text": "We report the case of a patient in whom troleandomycin-induced hepatitis was followed by prolonged anicteric cholestasis. Jaundice occurred after administration of troleandomycin for 7 days and was associated with hypereosinophilia. Jaundice disappeared within 3 months but was followed by prolonged anicteric cholestasis marked by pruritus and high levels of alkaline phosphatase and gammaglutamyltransferase activities. Finally, pruritus disappeared within 19 months, and liver tests returned to normal 27 months after the onset of hepatitis. This observation demonstrates that prolonged cholestasis can follow troleandomycin-induced acute hepatitis.", "entity": "Cholestasis", "aliases": "Bile Duct Obstruction Obstructions Biliary Stases Stasis Cholestases Cholestasis", "definition": "Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).\n    ", "id": "MESH:D002779"}
{"mention": "Jaundice", "mention_text": "We report the case of a patient in whom troleandomycin-induced hepatitis was followed by prolonged anicteric cholestasis. Jaundice occurred after administration of troleandomycin for 7 days and was associated with hypereosinophilia. Jaundice disappeared within 3 months but was followed by prolonged anicteric cholestasis marked by pruritus and high levels of alkaline phosphatase and gammaglutamyltransferase activities. Finally, pruritus disappeared within 19 months, and liver tests returned to normal 27 months after the onset of hepatitis. This observation demonstrates that prolonged cholestasis can follow troleandomycin-induced acute hepatitis.", "entity": "Jaundice", "aliases": "Hemolytic Jaundice Jaundices Icterus", "definition": "A clinical manifestation of HYPERBILIRUBINEMIA, characterized by the yellowish staining of the SKIN; MUCOUS MEMBRANE; and SCLERA. Clinical jaundice usually is a sign of LIVER dysfunction.\n    ", "id": "MESH:D007565"}
{"mention": "hypereosinophilia", "mention_text": "We report the case of a patient in whom troleandomycin-induced hepatitis was followed by prolonged anicteric cholestasis. Jaundice occurred after administration of troleandomycin for 7 days and was associated with hypereosinophilia. Jaundice disappeared within 3 months but was followed by prolonged anicteric cholestasis marked by pruritus and high levels of alkaline phosphatase and gammaglutamyltransferase activities. Finally, pruritus disappeared within 19 months, and liver tests returned to normal 27 months after the onset of hepatitis. This observation demonstrates that prolonged cholestasis can follow troleandomycin-induced acute hepatitis.", "entity": "Eosinophilia", "aliases": "Eosinophilia Tropical Eosinophilias", "definition": "Abnormal increase of EOSINOPHILS in the blood, tissues or organs.\n    ", "id": "MESH:D004802"}
{"mention": "pruritus", "mention_text": "We report the case of a patient in whom troleandomycin-induced hepatitis was followed by prolonged anicteric cholestasis. Jaundice occurred after administration of troleandomycin for 7 days and was associated with hypereosinophilia. Jaundice disappeared within 3 months but was followed by prolonged anicteric cholestasis marked by pruritus and high levels of alkaline phosphatase and gammaglutamyltransferase activities. Finally, pruritus disappeared within 19 months, and liver tests returned to normal 27 months after the onset of hepatitis. This observation demonstrates that prolonged cholestasis can follow troleandomycin-induced acute hepatitis.", "entity": "Pruritus", "aliases": "Itching Pruritis Pruritus", "definition": "An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief.\n    ", "id": "MESH:D011537"}
{"mention": "Lovastatin", "mention_text": "Lovastatin and simvastatin are the 2 best-known members of the class of hypolipidaemic agents known as HMG CoA reductase inhibitors. Clinical experience with lovastatin includes over 5000 patients, 700 of whom have been treated for 2 years or more, and experience with simvastatin includes over 3500 patients, of whom 350 have been treated for 18 months or more. Lovastatin has been marketed in the United States for over 6 months. Both agents show substantial clinical efficacy, with reductions in total cholesterol of over 30% and in LDL-cholesterol of 40% in clinical studies. Modest increases in HDL-cholesterol levels of about 10% are also reported. Clinical tolerability of both agents has been good, with fewer than 3% of patients withdrawn from treatment because of clinical adverse experiences. Ophthalmological examinations in over 1100 patients treated with one or the other agent have revealed no evidence of significant short term (up to 2 years) cataractogenic potential. One to 2% of patients have elevations of serum transaminases to greater than 3 times the upper limit of normal. These episodes are asymptomatic and reversible when therapy is discontinued. Minor elevations of creatine kinase levels are reported in about 5% of patients. Myopathy, associated in some cases with myoglobinuria, and in 2 cases with transient renal failure, has been rarely reported with lovastatin, especially in patients concomitantly treated with cyclosporin, gemfibrozil or niacin. Lovastatin and simvastatin are both effective and well-tolerated agents for lowering elevated levels of serum cholesterol. As wider use confirms their safety profile, they will gain increasing importance in the therapeutic approach to hypercholesterolaemia and its consequences.", "entity": "Lovastatin", "aliases": "1 alpha-Isomer Lovastatin 6 Methylcompactin 6-Methylcompactin (1 alpha(S*))-Isomer alpha Isomer MK 803 MK-803 MK803 Mevacor Mevinolin Monacolin K", "definition": "A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver.\n    ", "id": "MESH:D008148"}
{"mention": "simvastatin", "mention_text": "Lovastatin and simvastatin are the 2 best-known members of the class of hypolipidaemic agents known as HMG CoA reductase inhibitors. Clinical experience with lovastatin includes over 5000 patients, 700 of whom have been treated for 2 years or more, and experience with simvastatin includes over 3500 patients, of whom 350 have been treated for 18 months or more. Lovastatin has been marketed in the United States for over 6 months. Both agents show substantial clinical efficacy, with reductions in total cholesterol of over 30% and in LDL-cholesterol of 40% in clinical studies. Modest increases in HDL-cholesterol levels of about 10% are also reported. Clinical tolerability of both agents has been good, with fewer than 3% of patients withdrawn from treatment because of clinical adverse experiences. Ophthalmological examinations in over 1100 patients treated with one or the other agent have revealed no evidence of significant short term (up to 2 years) cataractogenic potential. One to 2% of patients have elevations of serum transaminases to greater than 3 times the upper limit of normal. These episodes are asymptomatic and reversible when therapy is discontinued. Minor elevations of creatine kinase levels are reported in about 5% of patients. Myopathy, associated in some cases with myoglobinuria, and in 2 cases with transient renal failure, has been rarely reported with lovastatin, especially in patients concomitantly treated with cyclosporin, gemfibrozil or niacin. Lovastatin and simvastatin are both effective and well-tolerated agents for lowering elevated levels of serum cholesterol. As wider use confirms their safety profile, they will gain increasing importance in the therapeutic approach to hypercholesterolaemia and its consequences.", "entity": "Simvastatin", "aliases": "MK 733 MK-733 MK733 Simvastatin Synvinolin Zocor", "definition": "A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL CHOLESTEROL.\n    ", "id": "MESH:D019821"}
{"mention": "lovastatin", "mention_text": "Lovastatin and simvastatin are the 2 best-known members of the class of hypolipidaemic agents known as HMG CoA reductase inhibitors. Clinical experience with lovastatin includes over 5000 patients, 700 of whom have been treated for 2 years or more, and experience with simvastatin includes over 3500 patients, of whom 350 have been treated for 18 months or more. Lovastatin has been marketed in the United States for over 6 months. Both agents show substantial clinical efficacy, with reductions in total cholesterol of over 30% and in LDL-cholesterol of 40% in clinical studies. Modest increases in HDL-cholesterol levels of about 10% are also reported. Clinical tolerability of both agents has been good, with fewer than 3% of patients withdrawn from treatment because of clinical adverse experiences. Ophthalmological examinations in over 1100 patients treated with one or the other agent have revealed no evidence of significant short term (up to 2 years) cataractogenic potential. One to 2% of patients have elevations of serum transaminases to greater than 3 times the upper limit of normal. These episodes are asymptomatic and reversible when therapy is discontinued. Minor elevations of creatine kinase levels are reported in about 5% of patients. Myopathy, associated in some cases with myoglobinuria, and in 2 cases with transient renal failure, has been rarely reported with lovastatin, especially in patients concomitantly treated with cyclosporin, gemfibrozil or niacin. Lovastatin and simvastatin are both effective and well-tolerated agents for lowering elevated levels of serum cholesterol. As wider use confirms their safety profile, they will gain increasing importance in the therapeutic approach to hypercholesterolaemia and its consequences.", "entity": "Lovastatin", "aliases": "1 alpha-Isomer Lovastatin 6 Methylcompactin 6-Methylcompactin (1 alpha(S*))-Isomer alpha Isomer MK 803 MK-803 MK803 Mevacor Mevinolin Monacolin K", "definition": "A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver.\n    ", "id": "MESH:D008148"}
{"mention": "cholesterol", "mention_text": "Lovastatin and simvastatin are the 2 best-known members of the class of hypolipidaemic agents known as HMG CoA reductase inhibitors. Clinical experience with lovastatin includes over 5000 patients, 700 of whom have been treated for 2 years or more, and experience with simvastatin includes over 3500 patients, of whom 350 have been treated for 18 months or more. Lovastatin has been marketed in the United States for over 6 months. Both agents show substantial clinical efficacy, with reductions in total cholesterol of over 30% and in LDL-cholesterol of 40% in clinical studies. Modest increases in HDL-cholesterol levels of about 10% are also reported. Clinical tolerability of both agents has been good, with fewer than 3% of patients withdrawn from treatment because of clinical adverse experiences. Ophthalmological examinations in over 1100 patients treated with one or the other agent have revealed no evidence of significant short term (up to 2 years) cataractogenic potential. One to 2% of patients have elevations of serum transaminases to greater than 3 times the upper limit of normal. These episodes are asymptomatic and reversible when therapy is discontinued. Minor elevations of creatine kinase levels are reported in about 5% of patients. Myopathy, associated in some cases with myoglobinuria, and in 2 cases with transient renal failure, has been rarely reported with lovastatin, especially in patients concomitantly treated with cyclosporin, gemfibrozil or niacin. Lovastatin and simvastatin are both effective and well-tolerated agents for lowering elevated levels of serum cholesterol. As wider use confirms their safety profile, they will gain increasing importance in the therapeutic approach to hypercholesterolaemia and its consequences.", "entity": "Cholesterol", "aliases": "Cholesterol Epicholesterol", "definition": "The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.\n    ", "id": "MESH:D002784"}
{"mention": "creatine", "mention_text": "Lovastatin and simvastatin are the 2 best-known members of the class of hypolipidaemic agents known as HMG CoA reductase inhibitors. Clinical experience with lovastatin includes over 5000 patients, 700 of whom have been treated for 2 years or more, and experience with simvastatin includes over 3500 patients, of whom 350 have been treated for 18 months or more. Lovastatin has been marketed in the United States for over 6 months. Both agents show substantial clinical efficacy, with reductions in total cholesterol of over 30% and in LDL-cholesterol of 40% in clinical studies. Modest increases in HDL-cholesterol levels of about 10% are also reported. Clinical tolerability of both agents has been good, with fewer than 3% of patients withdrawn from treatment because of clinical adverse experiences. Ophthalmological examinations in over 1100 patients treated with one or the other agent have revealed no evidence of significant short term (up to 2 years) cataractogenic potential. One to 2% of patients have elevations of serum transaminases to greater than 3 times the upper limit of normal. These episodes are asymptomatic and reversible when therapy is discontinued. Minor elevations of creatine kinase levels are reported in about 5% of patients. Myopathy, associated in some cases with myoglobinuria, and in 2 cases with transient renal failure, has been rarely reported with lovastatin, especially in patients concomitantly treated with cyclosporin, gemfibrozil or niacin. Lovastatin and simvastatin are both effective and well-tolerated agents for lowering elevated levels of serum cholesterol. As wider use confirms their safety profile, they will gain increasing importance in the therapeutic approach to hypercholesterolaemia and its consequences.", "entity": "Creatine", "aliases": "Creatine", "definition": "An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as CREATININE in the urine.\n    ", "id": "MESH:D003401"}
{"mention": "Myopathy", "mention_text": "Lovastatin and simvastatin are the 2 best-known members of the class of hypolipidaemic agents known as HMG CoA reductase inhibitors. Clinical experience with lovastatin includes over 5000 patients, 700 of whom have been treated for 2 years or more, and experience with simvastatin includes over 3500 patients, of whom 350 have been treated for 18 months or more. Lovastatin has been marketed in the United States for over 6 months. Both agents show substantial clinical efficacy, with reductions in total cholesterol of over 30% and in LDL-cholesterol of 40% in clinical studies. Modest increases in HDL-cholesterol levels of about 10% are also reported. Clinical tolerability of both agents has been good, with fewer than 3% of patients withdrawn from treatment because of clinical adverse experiences. Ophthalmological examinations in over 1100 patients treated with one or the other agent have revealed no evidence of significant short term (up to 2 years) cataractogenic potential. One to 2% of patients have elevations of serum transaminases to greater than 3 times the upper limit of normal. These episodes are asymptomatic and reversible when therapy is discontinued. Minor elevations of creatine kinase levels are reported in about 5% of patients. Myopathy, associated in some cases with myoglobinuria, and in 2 cases with transient renal failure, has been rarely reported with lovastatin, especially in patients concomitantly treated with cyclosporin, gemfibrozil or niacin. Lovastatin and simvastatin are both effective and well-tolerated agents for lowering elevated levels of serum cholesterol. As wider use confirms their safety profile, they will gain increasing importance in the therapeutic approach to hypercholesterolaemia and its consequences.", "entity": "Muscular Diseases", "aliases": "Muscle Disorder Disorders Muscular Disease Diseases Myopathic Condition Conditions Myopathies Myopathy", "definition": "Acquired, familial, and congenital disorders of SKELETAL MUSCLE and SMOOTH MUSCLE.\n    ", "id": "MESH:D009135"}
{"mention": "myoglobinuria", "mention_text": "Lovastatin and simvastatin are the 2 best-known members of the class of hypolipidaemic agents known as HMG CoA reductase inhibitors. Clinical experience with lovastatin includes over 5000 patients, 700 of whom have been treated for 2 years or more, and experience with simvastatin includes over 3500 patients, of whom 350 have been treated for 18 months or more. Lovastatin has been marketed in the United States for over 6 months. Both agents show substantial clinical efficacy, with reductions in total cholesterol of over 30% and in LDL-cholesterol of 40% in clinical studies. Modest increases in HDL-cholesterol levels of about 10% are also reported. Clinical tolerability of both agents has been good, with fewer than 3% of patients withdrawn from treatment because of clinical adverse experiences. Ophthalmological examinations in over 1100 patients treated with one or the other agent have revealed no evidence of significant short term (up to 2 years) cataractogenic potential. One to 2% of patients have elevations of serum transaminases to greater than 3 times the upper limit of normal. These episodes are asymptomatic and reversible when therapy is discontinued. Minor elevations of creatine kinase levels are reported in about 5% of patients. Myopathy, associated in some cases with myoglobinuria, and in 2 cases with transient renal failure, has been rarely reported with lovastatin, especially in patients concomitantly treated with cyclosporin, gemfibrozil or niacin. Lovastatin and simvastatin are both effective and well-tolerated agents for lowering elevated levels of serum cholesterol. As wider use confirms their safety profile, they will gain increasing importance in the therapeutic approach to hypercholesterolaemia and its consequences.", "entity": "Myoglobinuria", "aliases": "Myoglobinuria Myoglobinurias", "definition": "", "id": "MESH:D009212"}
{"mention": "renal failure", "mention_text": "Lovastatin and simvastatin are the 2 best-known members of the class of hypolipidaemic agents known as HMG CoA reductase inhibitors. Clinical experience with lovastatin includes over 5000 patients, 700 of whom have been treated for 2 years or more, and experience with simvastatin includes over 3500 patients, of whom 350 have been treated for 18 months or more. Lovastatin has been marketed in the United States for over 6 months. Both agents show substantial clinical efficacy, with reductions in total cholesterol of over 30% and in LDL-cholesterol of 40% in clinical studies. Modest increases in HDL-cholesterol levels of about 10% are also reported. Clinical tolerability of both agents has been good, with fewer than 3% of patients withdrawn from treatment because of clinical adverse experiences. Ophthalmological examinations in over 1100 patients treated with one or the other agent have revealed no evidence of significant short term (up to 2 years) cataractogenic potential. One to 2% of patients have elevations of serum transaminases to greater than 3 times the upper limit of normal. These episodes are asymptomatic and reversible when therapy is discontinued. Minor elevations of creatine kinase levels are reported in about 5% of patients. Myopathy, associated in some cases with myoglobinuria, and in 2 cases with transient renal failure, has been rarely reported with lovastatin, especially in patients concomitantly treated with cyclosporin, gemfibrozil or niacin. Lovastatin and simvastatin are both effective and well-tolerated agents for lowering elevated levels of serum cholesterol. As wider use confirms their safety profile, they will gain increasing importance in the therapeutic approach to hypercholesterolaemia and its consequences.", "entity": "Renal Insufficiency", "aliases": "Failure Kidney Renal Failures Insufficiency Insufficiencies", "definition": "Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.\n    ", "id": "MESH:D051437"}
{"mention": "cyclosporin", "mention_text": "Lovastatin and simvastatin are the 2 best-known members of the class of hypolipidaemic agents known as HMG CoA reductase inhibitors. Clinical experience with lovastatin includes over 5000 patients, 700 of whom have been treated for 2 years or more, and experience with simvastatin includes over 3500 patients, of whom 350 have been treated for 18 months or more. Lovastatin has been marketed in the United States for over 6 months. Both agents show substantial clinical efficacy, with reductions in total cholesterol of over 30% and in LDL-cholesterol of 40% in clinical studies. Modest increases in HDL-cholesterol levels of about 10% are also reported. Clinical tolerability of both agents has been good, with fewer than 3% of patients withdrawn from treatment because of clinical adverse experiences. Ophthalmological examinations in over 1100 patients treated with one or the other agent have revealed no evidence of significant short term (up to 2 years) cataractogenic potential. One to 2% of patients have elevations of serum transaminases to greater than 3 times the upper limit of normal. These episodes are asymptomatic and reversible when therapy is discontinued. Minor elevations of creatine kinase levels are reported in about 5% of patients. Myopathy, associated in some cases with myoglobinuria, and in 2 cases with transient renal failure, has been rarely reported with lovastatin, especially in patients concomitantly treated with cyclosporin, gemfibrozil or niacin. Lovastatin and simvastatin are both effective and well-tolerated agents for lowering elevated levels of serum cholesterol. As wider use confirms their safety profile, they will gain increasing importance in the therapeutic approach to hypercholesterolaemia and its consequences.", "entity": "Cyclosporine", "aliases": "Ciclosporin CsA Neoral CsA-Neoral CsANeoral CyA NOF CyA-NOF Cyclosporin A Cyclosporine OL 27 400 27-400 27400 Sandimmun Sandimmune", "definition": "A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).\n    ", "id": "MESH:D016572"}
{"mention": "gemfibrozil", "mention_text": "Lovastatin and simvastatin are the 2 best-known members of the class of hypolipidaemic agents known as HMG CoA reductase inhibitors. Clinical experience with lovastatin includes over 5000 patients, 700 of whom have been treated for 2 years or more, and experience with simvastatin includes over 3500 patients, of whom 350 have been treated for 18 months or more. Lovastatin has been marketed in the United States for over 6 months. Both agents show substantial clinical efficacy, with reductions in total cholesterol of over 30% and in LDL-cholesterol of 40% in clinical studies. Modest increases in HDL-cholesterol levels of about 10% are also reported. Clinical tolerability of both agents has been good, with fewer than 3% of patients withdrawn from treatment because of clinical adverse experiences. Ophthalmological examinations in over 1100 patients treated with one or the other agent have revealed no evidence of significant short term (up to 2 years) cataractogenic potential. One to 2% of patients have elevations of serum transaminases to greater than 3 times the upper limit of normal. These episodes are asymptomatic and reversible when therapy is discontinued. Minor elevations of creatine kinase levels are reported in about 5% of patients. Myopathy, associated in some cases with myoglobinuria, and in 2 cases with transient renal failure, has been rarely reported with lovastatin, especially in patients concomitantly treated with cyclosporin, gemfibrozil or niacin. Lovastatin and simvastatin are both effective and well-tolerated agents for lowering elevated levels of serum cholesterol. As wider use confirms their safety profile, they will gain increasing importance in the therapeutic approach to hypercholesterolaemia and its consequences.", "entity": "Gemfibrozil", "aliases": "1A Brand of Gemfibrozil Alphapharm Apo Apo-Gemfibrozil ApoGemfibrozil Apotex Ausgem Bayvit Gemfibrozilo Bexal Biochemie Bolutol Bull CI 719 CI-719 CI719 Cantabria Chem mart DBL Decrelip Douglas Farmasierra Faulding Ferrer Gemfi Pharma Gemfibrosil GenRX Healthsense SBPA Ur Gemhexal Gen Gen-Gemfibrozil GenGemfibrozil Genpharm Hexal Ipsen Jezil Lipazil Lipox Lipur Litarek Lopid R Menarini Novo Novo-Gemfibrozil Novopharm Nu Pharm Nu-Gemfibrozil Nu-Pharm NuGemfibrozil PMS PMS-Gemfibrozil Parke Davis ", "definition": "A lipid-regulating agent that lowers elevated serum lipids primarily by decreasing serum triglycerides with a variable reduction in total cholesterol.\n    ", "id": "MESH:D015248"}
{"mention": "niacin", "mention_text": "Lovastatin and simvastatin are the 2 best-known members of the class of hypolipidaemic agents known as HMG CoA reductase inhibitors. Clinical experience with lovastatin includes over 5000 patients, 700 of whom have been treated for 2 years or more, and experience with simvastatin includes over 3500 patients, of whom 350 have been treated for 18 months or more. Lovastatin has been marketed in the United States for over 6 months. Both agents show substantial clinical efficacy, with reductions in total cholesterol of over 30% and in LDL-cholesterol of 40% in clinical studies. Modest increases in HDL-cholesterol levels of about 10% are also reported. Clinical tolerability of both agents has been good, with fewer than 3% of patients withdrawn from treatment because of clinical adverse experiences. Ophthalmological examinations in over 1100 patients treated with one or the other agent have revealed no evidence of significant short term (up to 2 years) cataractogenic potential. One to 2% of patients have elevations of serum transaminases to greater than 3 times the upper limit of normal. These episodes are asymptomatic and reversible when therapy is discontinued. Minor elevations of creatine kinase levels are reported in about 5% of patients. Myopathy, associated in some cases with myoglobinuria, and in 2 cases with transient renal failure, has been rarely reported with lovastatin, especially in patients concomitantly treated with cyclosporin, gemfibrozil or niacin. Lovastatin and simvastatin are both effective and well-tolerated agents for lowering elevated levels of serum cholesterol. As wider use confirms their safety profile, they will gain increasing importance in the therapeutic approach to hypercholesterolaemia and its consequences.", "entity": "Niacin", "aliases": "3 Pyridinecarboxylic Acid 3-Pyridinecarboxylic Nicotinic Aluminum Salt Niacin Ammonium Calcium Enduracin Hydrochloride Induracin Lithium Nicotinate Magnesium Cobalt (2+) Copper Iron Hemihydrate Manganese Potassium Sodium Tartrate Tosylate Zinc Nicamin Nico 400 Nico-400 Nico400 Nicobid Nicocap Nicolar Wampocap", "definition": "A water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes NAD and NADP. It has PELLAGRA-curative, vasodilating, and antilipemic properties.\n    ", "id": "MESH:D009525"}
{"mention": "hypercholesterolaemia", "mention_text": "Lovastatin and simvastatin are the 2 best-known members of the class of hypolipidaemic agents known as HMG CoA reductase inhibitors. Clinical experience with lovastatin includes over 5000 patients, 700 of whom have been treated for 2 years or more, and experience with simvastatin includes over 3500 patients, of whom 350 have been treated for 18 months or more. Lovastatin has been marketed in the United States for over 6 months. Both agents show substantial clinical efficacy, with reductions in total cholesterol of over 30% and in LDL-cholesterol of 40% in clinical studies. Modest increases in HDL-cholesterol levels of about 10% are also reported. Clinical tolerability of both agents has been good, with fewer than 3% of patients withdrawn from treatment because of clinical adverse experiences. Ophthalmological examinations in over 1100 patients treated with one or the other agent have revealed no evidence of significant short term (up to 2 years) cataractogenic potential. One to 2% of patients have elevations of serum transaminases to greater than 3 times the upper limit of normal. These episodes are asymptomatic and reversible when therapy is discontinued. Minor elevations of creatine kinase levels are reported in about 5% of patients. Myopathy, associated in some cases with myoglobinuria, and in 2 cases with transient renal failure, has been rarely reported with lovastatin, especially in patients concomitantly treated with cyclosporin, gemfibrozil or niacin. Lovastatin and simvastatin are both effective and well-tolerated agents for lowering elevated levels of serum cholesterol. As wider use confirms their safety profile, they will gain increasing importance in the therapeutic approach to hypercholesterolaemia and its consequences.", "entity": "Hypercholesterolemia", "aliases": "Elevated Cholesterol Hypercholesteremia Hypercholesteremias Hypercholesterolemia Hypercholesterolemias", "definition": "A condition with abnormally high levels of CHOLESTEROL in the blood. It is defined as a cholesterol value exceeding the 95th percentile for the population.\n    ", "id": "MESH:D006937"}
{"mention": "Sulfasalazine", "mention_text": "Sulfasalazine-induced lupus erythematosus.", "entity": "Sulfasalazine", "aliases": "Alphapharm Brand of Sulfasalazine Ashbourne Asulfidine Azulfadine Azulfidine EN Colo Pleon Colo-Pleon FNA Henning Berlin Heyl Pfizer Pyralin Ratiopharm Salazopyrin Salazosulfapyridine Salicylazosulfapyridine Sanofi Synthelabo Sulfasalazin medac Sulfasalazin-Heyl Sulphasalazine Ucine Ulcol ratio ratio-Sulfasalazine", "definition": "A drug that is used in the management of inflammatory bowel diseases. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid (see MESALAMINE) released in the colon. (From Martindale, The Extra Pharmacopoeia, 30th ed, p907)\n    ", "id": "MESH:D012460"}
{"mention": "lupus erythematosus", "mention_text": "Sulfasalazine-induced lupus erythematosus.", "entity": "Lupus Erythematosus, Systemic", "aliases": "Disease Libman-Sacks Libman Sacks Lupus Erythematosus Disseminatus Systemic", "definition": "A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.\n    ", "id": "MESH:D008180"}
{"mention": "Pneumonitis", "mention_text": "Pneumonitis, bilateral pleural effusions, echocardiographic evidence of cardiac tamponade, and positive autoantibodies developed in a 43-year-old man, who was receiving long-term sulfasalazine therapy for chronic ulcerative colitis. After cessation of the sulfasalazine and completion of a six-week course of corticosteroids, these problems resolved over a period of four to six months. It is suggested that the patient had sulfasalazine-induced lupus, which manifested with serositis and pulmonary parenchymal involvement in the absence of joint symptoms. Physicians who use sulfasalazine to treat patients with inflammatory bowel disease should be aware of the signs of sulfasalazine-induced lupus syndrome.", "entity": "Pneumonia", "aliases": "Experimental Lung Inflammation Inflammations Pulmonary Lobar Pneumonia Pneumonias Pneumonitides Pneumonitis", "definition": "Inflammation of any part, segment or lobe, of the lung parenchyma.\n    ", "id": "MESH:D011014"}
{"mention": "pleural effusions", "mention_text": "Pneumonitis, bilateral pleural effusions, echocardiographic evidence of cardiac tamponade, and positive autoantibodies developed in a 43-year-old man, who was receiving long-term sulfasalazine therapy for chronic ulcerative colitis. After cessation of the sulfasalazine and completion of a six-week course of corticosteroids, these problems resolved over a period of four to six months. It is suggested that the patient had sulfasalazine-induced lupus, which manifested with serositis and pulmonary parenchymal involvement in the absence of joint symptoms. Physicians who use sulfasalazine to treat patients with inflammatory bowel disease should be aware of the signs of sulfasalazine-induced lupus syndrome.", "entity": "Pleural Effusion", "aliases": "Effusion Pleural Effusions", "definition": "Presence of fluid in the pleural cavity resulting from excessive transudation or exudation from the pleural surfaces. It is a sign of disease and not a diagnosis in itself.\n    ", "id": "MESH:D010996"}
{"mention": "cardiac tamponade", "mention_text": "Pneumonitis, bilateral pleural effusions, echocardiographic evidence of cardiac tamponade, and positive autoantibodies developed in a 43-year-old man, who was receiving long-term sulfasalazine therapy for chronic ulcerative colitis. After cessation of the sulfasalazine and completion of a six-week course of corticosteroids, these problems resolved over a period of four to six months. It is suggested that the patient had sulfasalazine-induced lupus, which manifested with serositis and pulmonary parenchymal involvement in the absence of joint symptoms. Physicians who use sulfasalazine to treat patients with inflammatory bowel disease should be aware of the signs of sulfasalazine-induced lupus syndrome.", "entity": "Cardiac Tamponade", "aliases": "Cardiac Tamponade Tamponades Pericardial", "definition": "Compression of the heart by accumulated fluid (PERICARDIAL EFFUSION) or blood (HEMOPERICARDIUM) in the PERICARDIUM surrounding the heart. The affected cardiac functions and CARDIAC OUTPUT can range from minimal to total hemodynamic collapse.\n    ", "id": "MESH:D002305"}
{"mention": "sulfasalazine", "mention_text": "Pneumonitis, bilateral pleural effusions, echocardiographic evidence of cardiac tamponade, and positive autoantibodies developed in a 43-year-old man, who was receiving long-term sulfasalazine therapy for chronic ulcerative colitis. After cessation of the sulfasalazine and completion of a six-week course of corticosteroids, these problems resolved over a period of four to six months. It is suggested that the patient had sulfasalazine-induced lupus, which manifested with serositis and pulmonary parenchymal involvement in the absence of joint symptoms. Physicians who use sulfasalazine to treat patients with inflammatory bowel disease should be aware of the signs of sulfasalazine-induced lupus syndrome.", "entity": "Sulfasalazine", "aliases": "Alphapharm Brand of Sulfasalazine Ashbourne Asulfidine Azulfadine Azulfidine EN Colo Pleon Colo-Pleon FNA Henning Berlin Heyl Pfizer Pyralin Ratiopharm Salazopyrin Salazosulfapyridine Salicylazosulfapyridine Sanofi Synthelabo Sulfasalazin medac Sulfasalazin-Heyl Sulphasalazine Ucine Ulcol ratio ratio-Sulfasalazine", "definition": "A drug that is used in the management of inflammatory bowel diseases. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid (see MESALAMINE) released in the colon. (From Martindale, The Extra Pharmacopoeia, 30th ed, p907)\n    ", "id": "MESH:D012460"}
{"mention": "ulcerative colitis", "mention_text": "Pneumonitis, bilateral pleural effusions, echocardiographic evidence of cardiac tamponade, and positive autoantibodies developed in a 43-year-old man, who was receiving long-term sulfasalazine therapy for chronic ulcerative colitis. After cessation of the sulfasalazine and completion of a six-week course of corticosteroids, these problems resolved over a period of four to six months. It is suggested that the patient had sulfasalazine-induced lupus, which manifested with serositis and pulmonary parenchymal involvement in the absence of joint symptoms. Physicians who use sulfasalazine to treat patients with inflammatory bowel disease should be aware of the signs of sulfasalazine-induced lupus syndrome.", "entity": "Colitis, Ulcerative", "aliases": "Colitis Gravis Ulcerative Idiopathic Proctocolitis Inflammatory Bowel Disease Type", "definition": "Inflammation of the COLON that is predominantly confined to the MUCOSA. Its major symptoms include DIARRHEA, rectal BLEEDING, the passage of MUCUS, and ABDOMINAL PAIN.\n    ", "id": "MESH:D003093"}
{"mention": "lupus", "mention_text": "Pneumonitis, bilateral pleural effusions, echocardiographic evidence of cardiac tamponade, and positive autoantibodies developed in a 43-year-old man, who was receiving long-term sulfasalazine therapy for chronic ulcerative colitis. After cessation of the sulfasalazine and completion of a six-week course of corticosteroids, these problems resolved over a period of four to six months. It is suggested that the patient had sulfasalazine-induced lupus, which manifested with serositis and pulmonary parenchymal involvement in the absence of joint symptoms. Physicians who use sulfasalazine to treat patients with inflammatory bowel disease should be aware of the signs of sulfasalazine-induced lupus syndrome.", "entity": "Lupus Erythematosus, Systemic", "aliases": "Disease Libman-Sacks Libman Sacks Lupus Erythematosus Disseminatus Systemic", "definition": "A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.\n    ", "id": "MESH:D008180"}
{"mention": "serositis", "mention_text": "Pneumonitis, bilateral pleural effusions, echocardiographic evidence of cardiac tamponade, and positive autoantibodies developed in a 43-year-old man, who was receiving long-term sulfasalazine therapy for chronic ulcerative colitis. After cessation of the sulfasalazine and completion of a six-week course of corticosteroids, these problems resolved over a period of four to six months. It is suggested that the patient had sulfasalazine-induced lupus, which manifested with serositis and pulmonary parenchymal involvement in the absence of joint symptoms. Physicians who use sulfasalazine to treat patients with inflammatory bowel disease should be aware of the signs of sulfasalazine-induced lupus syndrome.", "entity": "Serositis", "aliases": "Serositides Serositis", "definition": "Inflammation of a serous membrane.\n    ", "id": "MESH:D012700"}
{"mention": "inflammatory bowel disease", "mention_text": "Pneumonitis, bilateral pleural effusions, echocardiographic evidence of cardiac tamponade, and positive autoantibodies developed in a 43-year-old man, who was receiving long-term sulfasalazine therapy for chronic ulcerative colitis. After cessation of the sulfasalazine and completion of a six-week course of corticosteroids, these problems resolved over a period of four to six months. It is suggested that the patient had sulfasalazine-induced lupus, which manifested with serositis and pulmonary parenchymal involvement in the absence of joint symptoms. Physicians who use sulfasalazine to treat patients with inflammatory bowel disease should be aware of the signs of sulfasalazine-induced lupus syndrome.", "entity": "Inflammatory Bowel Diseases", "aliases": "Bowel Diseases Inflammatory Disease", "definition": "Chronic, non-specific inflammation of the GASTROINTESTINAL TRACT. Etiology may be genetic or environmental. This term includes CROHN DISEASE and ULCERATIVE COLITIS.\n    ", "id": "MESH:D015212"}
{"mention": "lupus syndrome", "mention_text": "Pneumonitis, bilateral pleural effusions, echocardiographic evidence of cardiac tamponade, and positive autoantibodies developed in a 43-year-old man, who was receiving long-term sulfasalazine therapy for chronic ulcerative colitis. After cessation of the sulfasalazine and completion of a six-week course of corticosteroids, these problems resolved over a period of four to six months. It is suggested that the patient had sulfasalazine-induced lupus, which manifested with serositis and pulmonary parenchymal involvement in the absence of joint symptoms. Physicians who use sulfasalazine to treat patients with inflammatory bowel disease should be aware of the signs of sulfasalazine-induced lupus syndrome.", "entity": "Lupus Erythematosus, Systemic", "aliases": "Disease Libman-Sacks Libman Sacks Lupus Erythematosus Disseminatus Systemic", "definition": "A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.\n    ", "id": "MESH:D008180"}
{"mention": "levodopa", "mention_text": "Optimization of levodopa therapy.", "entity": "Levodopa", "aliases": "3 Hydroxy L tyrosine 3-Hydroxy-L-tyrosine Dopaflex Dopar 3,4 Dihydroxyphenylalanine Dopa L-3,4-Dihydroxyphenylalanine L-Dopa Larodopa Levodopa Levopa Medphano Brand of Roberts Roche", "definition": "The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.\n    ", "id": "MESH:D007980"}
{"mention": "levodopa", "mention_text": "While there is no single correct starting dose for levodopa therapy, many individuals can be started on either the 25/100 or controlled-release formula, following the general rule not to attempt to titrate carbidopa-levodopa to the point of \"normality,\" which can lead to toxicity. The physician should also determine the proper use of any adjunctive medications; such combined therapy has become the standard approach to treatment. Following the initial period of therapy, emerging difficulties require a reassessment of therapeutic approaches, such as dosage adjustment or introduction of a dopamine agonist. Other possible adverse effects--such as gastrointestinal disorders, orthostatic hypotension, levodopa-induced psychosis, sleep disturbances or parasomnias, or drug interactions--also require carefully monitored individual treatment. Nonpharmacologic concerns can help the Parkinson's disease patient achieve and maintain optimal functioning, including daily exercise, physical therapy, and involvement with support groups.", "entity": "Levodopa", "aliases": "3 Hydroxy L tyrosine 3-Hydroxy-L-tyrosine Dopaflex Dopar 3,4 Dihydroxyphenylalanine Dopa L-3,4-Dihydroxyphenylalanine L-Dopa Larodopa Levodopa Levopa Medphano Brand of Roberts Roche", "definition": "The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.\n    ", "id": "MESH:D007980"}
{"mention": "carbidopa", "mention_text": "While there is no single correct starting dose for levodopa therapy, many individuals can be started on either the 25/100 or controlled-release formula, following the general rule not to attempt to titrate carbidopa-levodopa to the point of \"normality,\" which can lead to toxicity. The physician should also determine the proper use of any adjunctive medications; such combined therapy has become the standard approach to treatment. Following the initial period of therapy, emerging difficulties require a reassessment of therapeutic approaches, such as dosage adjustment or introduction of a dopamine agonist. Other possible adverse effects--such as gastrointestinal disorders, orthostatic hypotension, levodopa-induced psychosis, sleep disturbances or parasomnias, or drug interactions--also require carefully monitored individual treatment. Nonpharmacologic concerns can help the Parkinson's disease patient achieve and maintain optimal functioning, including daily exercise, physical therapy, and involvement with support groups.", "entity": "Carbidopa", "aliases": "Carbidopa (R)-Isomer (S)-Isomer Lodosin Lodosyn MK 485 486 MK-485 MK-486 MK485 MK486 Methyldopahydrazine", "definition": "An inhibitor of DOPA DECARBOXYLASE, preventing conversion of LEVODOPA to dopamine. It is used in PARKINSON DISEASE to reduce peripheral adverse effects of LEVODOPA. It has no antiparkinson actions by itself.\n    ", "id": "MESH:D002230"}
{"mention": "toxicity", "mention_text": "While there is no single correct starting dose for levodopa therapy, many individuals can be started on either the 25/100 or controlled-release formula, following the general rule not to attempt to titrate carbidopa-levodopa to the point of \"normality,\" which can lead to toxicity. The physician should also determine the proper use of any adjunctive medications; such combined therapy has become the standard approach to treatment. Following the initial period of therapy, emerging difficulties require a reassessment of therapeutic approaches, such as dosage adjustment or introduction of a dopamine agonist. Other possible adverse effects--such as gastrointestinal disorders, orthostatic hypotension, levodopa-induced psychosis, sleep disturbances or parasomnias, or drug interactions--also require carefully monitored individual treatment. Nonpharmacologic concerns can help the Parkinson's disease patient achieve and maintain optimal functioning, including daily exercise, physical therapy, and involvement with support groups.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "dopamine", "mention_text": "While there is no single correct starting dose for levodopa therapy, many individuals can be started on either the 25/100 or controlled-release formula, following the general rule not to attempt to titrate carbidopa-levodopa to the point of \"normality,\" which can lead to toxicity. The physician should also determine the proper use of any adjunctive medications; such combined therapy has become the standard approach to treatment. Following the initial period of therapy, emerging difficulties require a reassessment of therapeutic approaches, such as dosage adjustment or introduction of a dopamine agonist. Other possible adverse effects--such as gastrointestinal disorders, orthostatic hypotension, levodopa-induced psychosis, sleep disturbances or parasomnias, or drug interactions--also require carefully monitored individual treatment. Nonpharmacologic concerns can help the Parkinson's disease patient achieve and maintain optimal functioning, including daily exercise, physical therapy, and involvement with support groups.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "gastrointestinal disorders", "mention_text": "While there is no single correct starting dose for levodopa therapy, many individuals can be started on either the 25/100 or controlled-release formula, following the general rule not to attempt to titrate carbidopa-levodopa to the point of \"normality,\" which can lead to toxicity. The physician should also determine the proper use of any adjunctive medications; such combined therapy has become the standard approach to treatment. Following the initial period of therapy, emerging difficulties require a reassessment of therapeutic approaches, such as dosage adjustment or introduction of a dopamine agonist. Other possible adverse effects--such as gastrointestinal disorders, orthostatic hypotension, levodopa-induced psychosis, sleep disturbances or parasomnias, or drug interactions--also require carefully monitored individual treatment. Nonpharmacologic concerns can help the Parkinson's disease patient achieve and maintain optimal functioning, including daily exercise, physical therapy, and involvement with support groups.", "entity": "Gastrointestinal Diseases", "aliases": "Cholera Infantum Disease Gastrointestinal Diseases Disorder Functional Disorders", "definition": "Diseases in any segment of the GASTROINTESTINAL TRACT from ESOPHAGUS to RECTUM.\n    ", "id": "MESH:D005767"}
{"mention": "orthostatic hypotension", "mention_text": "While there is no single correct starting dose for levodopa therapy, many individuals can be started on either the 25/100 or controlled-release formula, following the general rule not to attempt to titrate carbidopa-levodopa to the point of \"normality,\" which can lead to toxicity. The physician should also determine the proper use of any adjunctive medications; such combined therapy has become the standard approach to treatment. Following the initial period of therapy, emerging difficulties require a reassessment of therapeutic approaches, such as dosage adjustment or introduction of a dopamine agonist. Other possible adverse effects--such as gastrointestinal disorders, orthostatic hypotension, levodopa-induced psychosis, sleep disturbances or parasomnias, or drug interactions--also require carefully monitored individual treatment. Nonpharmacologic concerns can help the Parkinson's disease patient achieve and maintain optimal functioning, including daily exercise, physical therapy, and involvement with support groups.", "entity": "Hypotension, Orthostatic", "aliases": "Hypotension Orthostatic Postural", "definition": "A significant drop in BLOOD PRESSURE after assuming a standing position. Orthostatic hypotension is a finding, and defined as a 20-mm Hg decrease in systolic pressure or a 10-mm Hg decrease in diastolic pressure 3 minutes after the person has risen from supine to standing. Symptoms generally include DIZZINESS, blurred vision, and SYNCOPE.\n    ", "id": "MESH:D007024"}
{"mention": "psychosis", "mention_text": "While there is no single correct starting dose for levodopa therapy, many individuals can be started on either the 25/100 or controlled-release formula, following the general rule not to attempt to titrate carbidopa-levodopa to the point of \"normality,\" which can lead to toxicity. The physician should also determine the proper use of any adjunctive medications; such combined therapy has become the standard approach to treatment. Following the initial period of therapy, emerging difficulties require a reassessment of therapeutic approaches, such as dosage adjustment or introduction of a dopamine agonist. Other possible adverse effects--such as gastrointestinal disorders, orthostatic hypotension, levodopa-induced psychosis, sleep disturbances or parasomnias, or drug interactions--also require carefully monitored individual treatment. Nonpharmacologic concerns can help the Parkinson's disease patient achieve and maintain optimal functioning, including daily exercise, physical therapy, and involvement with support groups.", "entity": "Psychotic Disorders", "aliases": "Brief Reactive Psychoses Psychosis Disorder Psychotic Schizoaffective Schizophreniform Disorders", "definition": "Disorders in which there is a loss of ego boundaries or a gross impairment in reality testing with delusions or prominent hallucinations. (From DSM-IV, 1994)\n    ", "id": "MESH:D011618"}
{"mention": "sleep disturbances", "mention_text": "While there is no single correct starting dose for levodopa therapy, many individuals can be started on either the 25/100 or controlled-release formula, following the general rule not to attempt to titrate carbidopa-levodopa to the point of \"normality,\" which can lead to toxicity. The physician should also determine the proper use of any adjunctive medications; such combined therapy has become the standard approach to treatment. Following the initial period of therapy, emerging difficulties require a reassessment of therapeutic approaches, such as dosage adjustment or introduction of a dopamine agonist. Other possible adverse effects--such as gastrointestinal disorders, orthostatic hypotension, levodopa-induced psychosis, sleep disturbances or parasomnias, or drug interactions--also require carefully monitored individual treatment. Nonpharmacologic concerns can help the Parkinson's disease patient achieve and maintain optimal functioning, including daily exercise, physical therapy, and involvement with support groups.", "entity": "Sleep Disorders", "aliases": "Long Sleeper Syndrome Syndromes Neurogenic Tachypnea Sleep-Related Tachypneas Phenotype Short Sleep Phenotypes Disorders Related Subwakefullness", "definition": "Conditions characterized by disturbances of usual sleep patterns or behaviors. Sleep disorders may be divided into three major categories: DYSSOMNIAS (i.e. disorders characterized by insomnia or hypersomnia), PARASOMNIAS (abnormal sleep behaviors), and sleep disorders secondary to medical or psychiatric disorders. (From Thorpy, Sleep Disorders Medicine, 1994, p187)\n    ", "id": "MESH:D012893"}
{"mention": "parasomnias", "mention_text": "While there is no single correct starting dose for levodopa therapy, many individuals can be started on either the 25/100 or controlled-release formula, following the general rule not to attempt to titrate carbidopa-levodopa to the point of \"normality,\" which can lead to toxicity. The physician should also determine the proper use of any adjunctive medications; such combined therapy has become the standard approach to treatment. Following the initial period of therapy, emerging difficulties require a reassessment of therapeutic approaches, such as dosage adjustment or introduction of a dopamine agonist. Other possible adverse effects--such as gastrointestinal disorders, orthostatic hypotension, levodopa-induced psychosis, sleep disturbances or parasomnias, or drug interactions--also require carefully monitored individual treatment. Nonpharmacologic concerns can help the Parkinson's disease patient achieve and maintain optimal functioning, including daily exercise, physical therapy, and involvement with support groups.", "entity": "Parasomnias", "aliases": "Benign Neonatal Sleep Myoclonus Drunkenness Drunkennesses Parasomnia Parasomnias Paroxysm Sensory Paroxysms Related Abnormal Swallowing Syndrome Sleep-Related", "definition": "Movements or behaviors associated with sleep, sleep stages, or partial arousals from sleep that may impair sleep maintenance. Parasomnias are generally divided into four groups: arousal disorders, sleep-wake transition disorders, parasomnias of REM sleep, and nonspecific parasomnias. (From Thorpy, Sleep Disorders Medicine, 1994, p191)\n    ", "id": "MESH:D020447"}
{"mention": "Parkinson's disease", "mention_text": "While there is no single correct starting dose for levodopa therapy, many individuals can be started on either the 25/100 or controlled-release formula, following the general rule not to attempt to titrate carbidopa-levodopa to the point of \"normality,\" which can lead to toxicity. The physician should also determine the proper use of any adjunctive medications; such combined therapy has become the standard approach to treatment. Following the initial period of therapy, emerging difficulties require a reassessment of therapeutic approaches, such as dosage adjustment or introduction of a dopamine agonist. Other possible adverse effects--such as gastrointestinal disorders, orthostatic hypotension, levodopa-induced psychosis, sleep disturbances or parasomnias, or drug interactions--also require carefully monitored individual treatment. Nonpharmacologic concerns can help the Parkinson's disease patient achieve and maintain optimal functioning, including daily exercise, physical therapy, and involvement with support groups.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "coma", "mention_text": "Alpha and beta coma in drug intoxication uncomplicated by cerebral hypoxia.", "entity": "Coma", "aliases": "Coma Comas Comatose Pseudocoma Pseudocomas", "definition": "A profound state of unconsciousness associated with depressed cerebral activity from which the individual cannot be aroused. Coma generally occurs when there is dysfunction or injury involving both cerebral hemispheres or the brain stem RETICULAR FORMATION.\n    ", "id": "MESH:D003128"}
{"mention": "cerebral hypoxia", "mention_text": "Alpha and beta coma in drug intoxication uncomplicated by cerebral hypoxia.", "entity": "Hypoxia, Brain", "aliases": "Anoxia Brain Cerebral Anoxic Damage Encephalopathies Encephalopathy Hypoxic Hypoxia", "definition": "A reduction in brain oxygen supply due to ANOXEMIA (a reduced amount of oxygen being carried in the blood by HEMOGLOBIN), or to a restriction of the blood supply to the brain, or both. Severe hypoxia is referred to as anoxia, and is a relatively common cause of injury to the central nervous system. Prolonged brain anoxia may lead to BRAIN DEATH or a PERSISTENT VEGETATIVE STATE. Histologically, this condition is characterized by neuronal loss which is most prominent in the HIPPOCAMPUS; GLOBUS PALLIDUS; CEREBELLUM; and inferior olives.\n    ", "id": "MESH:D002534"}
{"mention": "comatose", "mention_text": "Four patients who were rendered comatose or stuporous by drug intoxication, but who were not hypoxic, are described. Three patients received high doses of chlormethiazole for alcohol withdrawal symptoms, and one took a suicidal overdose of nitrazepam. The patient with nitrazepam overdose and two of those with chlormethiazole intoxication conformed to the criteria of 'alpha coma', showing non-reactive generalized or frontally predominant alpha activity in the EEG. The fourth patient who was unconscious after chlormethiazole administration exhibite generalized non-reactive activity in the slow beta range. All four recovered completely without neurological sequelae following the withdrawal of the offending agents. The similarities between the effects of structural lesions and pharmacological depression of the brain stem reticular formation are discussed. It is suggested that in both situations disturbed reticulo-thalamic interactions are important in the pathogenesis of alpha coma. It is concluded that when this electroencephalographic and behavioural picture is seen in drug intoxication, in the absence of significant hypoxaemia, a favourable outcome may be anticipated.", "entity": "Coma", "aliases": "Coma Comas Comatose Pseudocoma Pseudocomas", "definition": "A profound state of unconsciousness associated with depressed cerebral activity from which the individual cannot be aroused. Coma generally occurs when there is dysfunction or injury involving both cerebral hemispheres or the brain stem RETICULAR FORMATION.\n    ", "id": "MESH:D003128"}
{"mention": "stuporous", "mention_text": "Four patients who were rendered comatose or stuporous by drug intoxication, but who were not hypoxic, are described. Three patients received high doses of chlormethiazole for alcohol withdrawal symptoms, and one took a suicidal overdose of nitrazepam. The patient with nitrazepam overdose and two of those with chlormethiazole intoxication conformed to the criteria of 'alpha coma', showing non-reactive generalized or frontally predominant alpha activity in the EEG. The fourth patient who was unconscious after chlormethiazole administration exhibite generalized non-reactive activity in the slow beta range. All four recovered completely without neurological sequelae following the withdrawal of the offending agents. The similarities between the effects of structural lesions and pharmacological depression of the brain stem reticular formation are discussed. It is suggested that in both situations disturbed reticulo-thalamic interactions are important in the pathogenesis of alpha coma. It is concluded that when this electroencephalographic and behavioural picture is seen in drug intoxication, in the absence of significant hypoxaemia, a favourable outcome may be anticipated.", "entity": "Stupor", "aliases": "Narcosis Stupor", "definition": "A state of reduced sensibility and response to stimuli which is distinguished from COMA in that the person can be aroused by vigorous and repeated stimulation. The person is still conscious and can make voluntary movements. It can be induced by CENTRAL NERVOUS SYSTEM AGENTS. The word derives from Latin stupere and is related to stunned, stupid, dazed or LETHARGY.\n    ", "id": "MESH:D053608"}
{"mention": "chlormethiazole", "mention_text": "Four patients who were rendered comatose or stuporous by drug intoxication, but who were not hypoxic, are described. Three patients received high doses of chlormethiazole for alcohol withdrawal symptoms, and one took a suicidal overdose of nitrazepam. The patient with nitrazepam overdose and two of those with chlormethiazole intoxication conformed to the criteria of 'alpha coma', showing non-reactive generalized or frontally predominant alpha activity in the EEG. The fourth patient who was unconscious after chlormethiazole administration exhibite generalized non-reactive activity in the slow beta range. All four recovered completely without neurological sequelae following the withdrawal of the offending agents. The similarities between the effects of structural lesions and pharmacological depression of the brain stem reticular formation are discussed. It is suggested that in both situations disturbed reticulo-thalamic interactions are important in the pathogenesis of alpha coma. It is concluded that when this electroencephalographic and behavioural picture is seen in drug intoxication, in the absence of significant hypoxaemia, a favourable outcome may be anticipated.", "entity": "Chlormethiazole", "aliases": "Chlormethiazole Clomethiazole Distraneurin", "definition": "A sedative and anticonvulsant often used in the treatment of alcohol withdrawal. Chlormethiazole has also been proposed as a neuroprotective agent. The mechanism of its therapeutic activity is not entirely clear, but it does potentiate GAMMA-AMINOBUTYRIC ACID receptors response and it may also affect glycine receptors.\n    ", "id": "MESH:D002719"}
{"mention": "alcohol", "mention_text": "Four patients who were rendered comatose or stuporous by drug intoxication, but who were not hypoxic, are described. Three patients received high doses of chlormethiazole for alcohol withdrawal symptoms, and one took a suicidal overdose of nitrazepam. The patient with nitrazepam overdose and two of those with chlormethiazole intoxication conformed to the criteria of 'alpha coma', showing non-reactive generalized or frontally predominant alpha activity in the EEG. The fourth patient who was unconscious after chlormethiazole administration exhibite generalized non-reactive activity in the slow beta range. All four recovered completely without neurological sequelae following the withdrawal of the offending agents. The similarities between the effects of structural lesions and pharmacological depression of the brain stem reticular formation are discussed. It is suggested that in both situations disturbed reticulo-thalamic interactions are important in the pathogenesis of alpha coma. It is concluded that when this electroencephalographic and behavioural picture is seen in drug intoxication, in the absence of significant hypoxaemia, a favourable outcome may be anticipated.", "entity": "Ethanol", "aliases": "Absolute Alcohol Ethyl Grain Ethanol", "definition": "A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.\n    ", "id": "MESH:D000431"}
{"mention": "withdrawal symptoms", "mention_text": "Four patients who were rendered comatose or stuporous by drug intoxication, but who were not hypoxic, are described. Three patients received high doses of chlormethiazole for alcohol withdrawal symptoms, and one took a suicidal overdose of nitrazepam. The patient with nitrazepam overdose and two of those with chlormethiazole intoxication conformed to the criteria of 'alpha coma', showing non-reactive generalized or frontally predominant alpha activity in the EEG. The fourth patient who was unconscious after chlormethiazole administration exhibite generalized non-reactive activity in the slow beta range. All four recovered completely without neurological sequelae following the withdrawal of the offending agents. The similarities between the effects of structural lesions and pharmacological depression of the brain stem reticular formation are discussed. It is suggested that in both situations disturbed reticulo-thalamic interactions are important in the pathogenesis of alpha coma. It is concluded that when this electroencephalographic and behavioural picture is seen in drug intoxication, in the absence of significant hypoxaemia, a favourable outcome may be anticipated.", "entity": "Substance Withdrawal Syndrome", "aliases": "Drug Withdrawal Symptom Symptoms Substance Syndrome Syndromes", "definition": "Physiological and psychological symptoms associated with withdrawal from the use of a drug after prolonged administration or habituation. The concept includes withdrawal from smoking or drinking, as well as withdrawal from an administered drug.\n    ", "id": "MESH:D013375"}
{"mention": "overdose", "mention_text": "Four patients who were rendered comatose or stuporous by drug intoxication, but who were not hypoxic, are described. Three patients received high doses of chlormethiazole for alcohol withdrawal symptoms, and one took a suicidal overdose of nitrazepam. The patient with nitrazepam overdose and two of those with chlormethiazole intoxication conformed to the criteria of 'alpha coma', showing non-reactive generalized or frontally predominant alpha activity in the EEG. The fourth patient who was unconscious after chlormethiazole administration exhibite generalized non-reactive activity in the slow beta range. All four recovered completely without neurological sequelae following the withdrawal of the offending agents. The similarities between the effects of structural lesions and pharmacological depression of the brain stem reticular formation are discussed. It is suggested that in both situations disturbed reticulo-thalamic interactions are important in the pathogenesis of alpha coma. It is concluded that when this electroencephalographic and behavioural picture is seen in drug intoxication, in the absence of significant hypoxaemia, a favourable outcome may be anticipated.", "entity": "Drug Overdose", "aliases": "Drug Overdose Overdoses", "definition": "Accidental or deliberate use of a medication or street drug in excess of normal dosage.\n    ", "id": "MESH:D062787"}
{"mention": "nitrazepam", "mention_text": "Four patients who were rendered comatose or stuporous by drug intoxication, but who were not hypoxic, are described. Three patients received high doses of chlormethiazole for alcohol withdrawal symptoms, and one took a suicidal overdose of nitrazepam. The patient with nitrazepam overdose and two of those with chlormethiazole intoxication conformed to the criteria of 'alpha coma', showing non-reactive generalized or frontally predominant alpha activity in the EEG. The fourth patient who was unconscious after chlormethiazole administration exhibite generalized non-reactive activity in the slow beta range. All four recovered completely without neurological sequelae following the withdrawal of the offending agents. The similarities between the effects of structural lesions and pharmacological depression of the brain stem reticular formation are discussed. It is suggested that in both situations disturbed reticulo-thalamic interactions are important in the pathogenesis of alpha coma. It is concluded that when this electroencephalographic and behavioural picture is seen in drug intoxication, in the absence of significant hypoxaemia, a favourable outcome may be anticipated.", "entity": "Nitrazepam", "aliases": "Aliud Brand of Nitrazepam Allphar Alodorm Alphapharma Alpharma Alter CSP DDSA Dermatech Desitin Dormalon Dormicum Dormo-Puren Eatan ICN Imadorm Mogadon Nitrazadon Nitrazep AL Nitrazepam-neuraxpharm Nitrodiazepam Norgine Novanox Pfleger Protea Radedorm Remnos Rhoxal-nitrazepam Rhoxalpharma Scheurich Serenade Somnite Taurus United Drug Wernigerode ct-Arzneimittel imeson neuraxpharm", "definition": "A benzodiazepine derivative used as an anticonvulsant and hypnotic.\n    ", "id": "MESH:D009567"}
{"mention": "coma", "mention_text": "Four patients who were rendered comatose or stuporous by drug intoxication, but who were not hypoxic, are described. Three patients received high doses of chlormethiazole for alcohol withdrawal symptoms, and one took a suicidal overdose of nitrazepam. The patient with nitrazepam overdose and two of those with chlormethiazole intoxication conformed to the criteria of 'alpha coma', showing non-reactive generalized or frontally predominant alpha activity in the EEG. The fourth patient who was unconscious after chlormethiazole administration exhibite generalized non-reactive activity in the slow beta range. All four recovered completely without neurological sequelae following the withdrawal of the offending agents. The similarities between the effects of structural lesions and pharmacological depression of the brain stem reticular formation are discussed. It is suggested that in both situations disturbed reticulo-thalamic interactions are important in the pathogenesis of alpha coma. It is concluded that when this electroencephalographic and behavioural picture is seen in drug intoxication, in the absence of significant hypoxaemia, a favourable outcome may be anticipated.", "entity": "Coma", "aliases": "Coma Comas Comatose Pseudocoma Pseudocomas", "definition": "A profound state of unconsciousness associated with depressed cerebral activity from which the individual cannot be aroused. Coma generally occurs when there is dysfunction or injury involving both cerebral hemispheres or the brain stem RETICULAR FORMATION.\n    ", "id": "MESH:D003128"}
{"mention": "neurological sequelae", "mention_text": "Four patients who were rendered comatose or stuporous by drug intoxication, but who were not hypoxic, are described. Three patients received high doses of chlormethiazole for alcohol withdrawal symptoms, and one took a suicidal overdose of nitrazepam. The patient with nitrazepam overdose and two of those with chlormethiazole intoxication conformed to the criteria of 'alpha coma', showing non-reactive generalized or frontally predominant alpha activity in the EEG. The fourth patient who was unconscious after chlormethiazole administration exhibite generalized non-reactive activity in the slow beta range. All four recovered completely without neurological sequelae following the withdrawal of the offending agents. The similarities between the effects of structural lesions and pharmacological depression of the brain stem reticular formation are discussed. It is suggested that in both situations disturbed reticulo-thalamic interactions are important in the pathogenesis of alpha coma. It is concluded that when this electroencephalographic and behavioural picture is seen in drug intoxication, in the absence of significant hypoxaemia, a favourable outcome may be anticipated.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "depression", "mention_text": "Four patients who were rendered comatose or stuporous by drug intoxication, but who were not hypoxic, are described. Three patients received high doses of chlormethiazole for alcohol withdrawal symptoms, and one took a suicidal overdose of nitrazepam. The patient with nitrazepam overdose and two of those with chlormethiazole intoxication conformed to the criteria of 'alpha coma', showing non-reactive generalized or frontally predominant alpha activity in the EEG. The fourth patient who was unconscious after chlormethiazole administration exhibite generalized non-reactive activity in the slow beta range. All four recovered completely without neurological sequelae following the withdrawal of the offending agents. The similarities between the effects of structural lesions and pharmacological depression of the brain stem reticular formation are discussed. It is suggested that in both situations disturbed reticulo-thalamic interactions are important in the pathogenesis of alpha coma. It is concluded that when this electroencephalographic and behavioural picture is seen in drug intoxication, in the absence of significant hypoxaemia, a favourable outcome may be anticipated.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "hypoxaemia", "mention_text": "Four patients who were rendered comatose or stuporous by drug intoxication, but who were not hypoxic, are described. Three patients received high doses of chlormethiazole for alcohol withdrawal symptoms, and one took a suicidal overdose of nitrazepam. The patient with nitrazepam overdose and two of those with chlormethiazole intoxication conformed to the criteria of 'alpha coma', showing non-reactive generalized or frontally predominant alpha activity in the EEG. The fourth patient who was unconscious after chlormethiazole administration exhibite generalized non-reactive activity in the slow beta range. All four recovered completely without neurological sequelae following the withdrawal of the offending agents. The similarities between the effects of structural lesions and pharmacological depression of the brain stem reticular formation are discussed. It is suggested that in both situations disturbed reticulo-thalamic interactions are important in the pathogenesis of alpha coma. It is concluded that when this electroencephalographic and behavioural picture is seen in drug intoxication, in the absence of significant hypoxaemia, a favourable outcome may be anticipated.", "entity": "Anoxia", "aliases": "Anoxemia Anoxemias Anoxia Anoxias Deficiencies Oxygen Deficiency Hypoxemia Hypoxemias Hypoxia Hypoxias", "definition": "Relatively complete absence of oxygen in one or more tissues.\n    ", "id": "MESH:D000860"}
{"mention": "fentanyl", "mention_text": "Omitting fentanyl reduces nausea and vomiting, without increasing pain, after sevoflurane for day surgery.", "entity": "Fentanyl", "aliases": "Cephalon Brand of Fentanyl Buccal OraVescent Duragesic Durogesic Fentanest Citrate Fentora Janssen Pharmaceutica Phentanyl R 4263 R-4263 R4263 Sublimaze Transmucosal Oral", "definition": "A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1078)\n    ", "id": "MESH:D005283"}
{"mention": "nausea", "mention_text": "Omitting fentanyl reduces nausea and vomiting, without increasing pain, after sevoflurane for day surgery.", "entity": "Nausea", "aliases": "Nausea", "definition": "An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.\n    ", "id": "MESH:D009325"}
{"mention": "vomiting", "mention_text": "Omitting fentanyl reduces nausea and vomiting, without increasing pain, after sevoflurane for day surgery.", "entity": "Vomiting", "aliases": "Emesis Vomiting", "definition": "The forcible expulsion of the contents of the STOMACH through the MOUTH.\n    ", "id": "MESH:D014839"}
{"mention": "pain", "mention_text": "Omitting fentanyl reduces nausea and vomiting, without increasing pain, after sevoflurane for day surgery.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "sevoflurane", "mention_text": "Omitting fentanyl reduces nausea and vomiting, without increasing pain, after sevoflurane for day surgery.", "entity": "sevoflurane", "aliases": "BAX 3084 Ultane fluoromethyl hexafluoroisopropyl ether fluoromethyl-2,2,2-trifluoro-1-(trifluoromethyl)ethyl sevoflurane sevorane", "definition": "", "id": "MESH:C009250"}
{"mention": "sevoflurane", "mention_text": "BACKGROUND AND OBJECTIVE: Despite advantages of induction and maintenance of anaesthesia with sevoflurane, postoperative nausea and vomiting occurs frequently. Fentanyl is a commonly used supplement that may contribute to this, although it may also improve analgesia. METHODS: This double-blind study examined the incidence and severity of postoperative nausea and vomiting and pain in the first 24 h after sevoflurane anaesthesia in 216 adult day surgery patients. Patients were randomly allocated to either receive or not receive 1 1 fentanyl, while a third group received dexamethasone in addition to fentanyl. RESULTS: Omission of fentanyl did not reduce the overall incidence of postoperative nausea and vomiting, but did reduce the incidence of vomiting and/or moderate to severe nausea prior to discharge from 20% and 17% with fentanyl and fentanyl-dexamethasone, respectively, to 5% (P = 0.013). Antiemetic requirements were reduced from 24% and 31% to 7% (P = 0.0012). Dexamethasone had no significant effect on the incidence or severity of postoperative nausea and vomiting. Combining the two fentanyl groups revealed further significant benefits from the avoidance of opioids, reducing postoperative nausea and vomiting and nausea prior to discharge from 35% and 33% to 22% and 19% (P = 0.049 and P = 0.035), respectively, while nausea in the first 24 h was decreased from 42% to 27% (P = 0.034). Pain severity and analgesic requirements were unaffected by the omission of fentanyl. Fentanyl did reduce minor intraoperative movement but had no sevoflurane-sparing effect and increased respiratory depression, hypotension and bradycardia. CONCLUSION: As fentanyl exacerbated postoperative nausea and vomiting without an improvement in postoperative pain and also had adverse cardiorespiratory effects, it appears to be an unnecessary and possibly detrimental supplement to sevoflurane in day surgery.", "entity": "sevoflurane", "aliases": "BAX 3084 Ultane fluoromethyl hexafluoroisopropyl ether fluoromethyl-2,2,2-trifluoro-1-(trifluoromethyl)ethyl sevoflurane sevorane", "definition": "", "id": "MESH:C009250"}
{"mention": "postoperative nausea and vomiting", "mention_text": "BACKGROUND AND OBJECTIVE: Despite advantages of induction and maintenance of anaesthesia with sevoflurane, postoperative nausea and vomiting occurs frequently. Fentanyl is a commonly used supplement that may contribute to this, although it may also improve analgesia. METHODS: This double-blind study examined the incidence and severity of postoperative nausea and vomiting and pain in the first 24 h after sevoflurane anaesthesia in 216 adult day surgery patients. Patients were randomly allocated to either receive or not receive 1 1 fentanyl, while a third group received dexamethasone in addition to fentanyl. RESULTS: Omission of fentanyl did not reduce the overall incidence of postoperative nausea and vomiting, but did reduce the incidence of vomiting and/or moderate to severe nausea prior to discharge from 20% and 17% with fentanyl and fentanyl-dexamethasone, respectively, to 5% (P = 0.013). Antiemetic requirements were reduced from 24% and 31% to 7% (P = 0.0012). Dexamethasone had no significant effect on the incidence or severity of postoperative nausea and vomiting. Combining the two fentanyl groups revealed further significant benefits from the avoidance of opioids, reducing postoperative nausea and vomiting and nausea prior to discharge from 35% and 33% to 22% and 19% (P = 0.049 and P = 0.035), respectively, while nausea in the first 24 h was decreased from 42% to 27% (P = 0.034). Pain severity and analgesic requirements were unaffected by the omission of fentanyl. Fentanyl did reduce minor intraoperative movement but had no sevoflurane-sparing effect and increased respiratory depression, hypotension and bradycardia. CONCLUSION: As fentanyl exacerbated postoperative nausea and vomiting without an improvement in postoperative pain and also had adverse cardiorespiratory effects, it appears to be an unnecessary and possibly detrimental supplement to sevoflurane in day surgery.", "entity": "Postoperative Nausea and Vomiting", "aliases": "Emeses Postoperative Emesis Nausea and Vomiting PONV", "definition": "Emesis and queasiness occurring after anesthesia.\n    ", "id": "MESH:D020250"}
{"mention": "Fentanyl", "mention_text": "BACKGROUND AND OBJECTIVE: Despite advantages of induction and maintenance of anaesthesia with sevoflurane, postoperative nausea and vomiting occurs frequently. Fentanyl is a commonly used supplement that may contribute to this, although it may also improve analgesia. METHODS: This double-blind study examined the incidence and severity of postoperative nausea and vomiting and pain in the first 24 h after sevoflurane anaesthesia in 216 adult day surgery patients. Patients were randomly allocated to either receive or not receive 1 1 fentanyl, while a third group received dexamethasone in addition to fentanyl. RESULTS: Omission of fentanyl did not reduce the overall incidence of postoperative nausea and vomiting, but did reduce the incidence of vomiting and/or moderate to severe nausea prior to discharge from 20% and 17% with fentanyl and fentanyl-dexamethasone, respectively, to 5% (P = 0.013). Antiemetic requirements were reduced from 24% and 31% to 7% (P = 0.0012). Dexamethasone had no significant effect on the incidence or severity of postoperative nausea and vomiting. Combining the two fentanyl groups revealed further significant benefits from the avoidance of opioids, reducing postoperative nausea and vomiting and nausea prior to discharge from 35% and 33% to 22% and 19% (P = 0.049 and P = 0.035), respectively, while nausea in the first 24 h was decreased from 42% to 27% (P = 0.034). Pain severity and analgesic requirements were unaffected by the omission of fentanyl. Fentanyl did reduce minor intraoperative movement but had no sevoflurane-sparing effect and increased respiratory depression, hypotension and bradycardia. CONCLUSION: As fentanyl exacerbated postoperative nausea and vomiting without an improvement in postoperative pain and also had adverse cardiorespiratory effects, it appears to be an unnecessary and possibly detrimental supplement to sevoflurane in day surgery.", "entity": "Fentanyl", "aliases": "Cephalon Brand of Fentanyl Buccal OraVescent Duragesic Durogesic Fentanest Citrate Fentora Janssen Pharmaceutica Phentanyl R 4263 R-4263 R4263 Sublimaze Transmucosal Oral", "definition": "A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1078)\n    ", "id": "MESH:D005283"}
{"mention": "pain", "mention_text": "BACKGROUND AND OBJECTIVE: Despite advantages of induction and maintenance of anaesthesia with sevoflurane, postoperative nausea and vomiting occurs frequently. Fentanyl is a commonly used supplement that may contribute to this, although it may also improve analgesia. METHODS: This double-blind study examined the incidence and severity of postoperative nausea and vomiting and pain in the first 24 h after sevoflurane anaesthesia in 216 adult day surgery patients. Patients were randomly allocated to either receive or not receive 1 1 fentanyl, while a third group received dexamethasone in addition to fentanyl. RESULTS: Omission of fentanyl did not reduce the overall incidence of postoperative nausea and vomiting, but did reduce the incidence of vomiting and/or moderate to severe nausea prior to discharge from 20% and 17% with fentanyl and fentanyl-dexamethasone, respectively, to 5% (P = 0.013). Antiemetic requirements were reduced from 24% and 31% to 7% (P = 0.0012). Dexamethasone had no significant effect on the incidence or severity of postoperative nausea and vomiting. Combining the two fentanyl groups revealed further significant benefits from the avoidance of opioids, reducing postoperative nausea and vomiting and nausea prior to discharge from 35% and 33% to 22% and 19% (P = 0.049 and P = 0.035), respectively, while nausea in the first 24 h was decreased from 42% to 27% (P = 0.034). Pain severity and analgesic requirements were unaffected by the omission of fentanyl. Fentanyl did reduce minor intraoperative movement but had no sevoflurane-sparing effect and increased respiratory depression, hypotension and bradycardia. CONCLUSION: As fentanyl exacerbated postoperative nausea and vomiting without an improvement in postoperative pain and also had adverse cardiorespiratory effects, it appears to be an unnecessary and possibly detrimental supplement to sevoflurane in day surgery.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "fentanyl", "mention_text": "BACKGROUND AND OBJECTIVE: Despite advantages of induction and maintenance of anaesthesia with sevoflurane, postoperative nausea and vomiting occurs frequently. Fentanyl is a commonly used supplement that may contribute to this, although it may also improve analgesia. METHODS: This double-blind study examined the incidence and severity of postoperative nausea and vomiting and pain in the first 24 h after sevoflurane anaesthesia in 216 adult day surgery patients. Patients were randomly allocated to either receive or not receive 1 1 fentanyl, while a third group received dexamethasone in addition to fentanyl. RESULTS: Omission of fentanyl did not reduce the overall incidence of postoperative nausea and vomiting, but did reduce the incidence of vomiting and/or moderate to severe nausea prior to discharge from 20% and 17% with fentanyl and fentanyl-dexamethasone, respectively, to 5% (P = 0.013). Antiemetic requirements were reduced from 24% and 31% to 7% (P = 0.0012). Dexamethasone had no significant effect on the incidence or severity of postoperative nausea and vomiting. Combining the two fentanyl groups revealed further significant benefits from the avoidance of opioids, reducing postoperative nausea and vomiting and nausea prior to discharge from 35% and 33% to 22% and 19% (P = 0.049 and P = 0.035), respectively, while nausea in the first 24 h was decreased from 42% to 27% (P = 0.034). Pain severity and analgesic requirements were unaffected by the omission of fentanyl. Fentanyl did reduce minor intraoperative movement but had no sevoflurane-sparing effect and increased respiratory depression, hypotension and bradycardia. CONCLUSION: As fentanyl exacerbated postoperative nausea and vomiting without an improvement in postoperative pain and also had adverse cardiorespiratory effects, it appears to be an unnecessary and possibly detrimental supplement to sevoflurane in day surgery.", "entity": "Fentanyl", "aliases": "Cephalon Brand of Fentanyl Buccal OraVescent Duragesic Durogesic Fentanest Citrate Fentora Janssen Pharmaceutica Phentanyl R 4263 R-4263 R4263 Sublimaze Transmucosal Oral", "definition": "A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1078)\n    ", "id": "MESH:D005283"}
{"mention": "dexamethasone", "mention_text": "BACKGROUND AND OBJECTIVE: Despite advantages of induction and maintenance of anaesthesia with sevoflurane, postoperative nausea and vomiting occurs frequently. Fentanyl is a commonly used supplement that may contribute to this, although it may also improve analgesia. METHODS: This double-blind study examined the incidence and severity of postoperative nausea and vomiting and pain in the first 24 h after sevoflurane anaesthesia in 216 adult day surgery patients. Patients were randomly allocated to either receive or not receive 1 1 fentanyl, while a third group received dexamethasone in addition to fentanyl. RESULTS: Omission of fentanyl did not reduce the overall incidence of postoperative nausea and vomiting, but did reduce the incidence of vomiting and/or moderate to severe nausea prior to discharge from 20% and 17% with fentanyl and fentanyl-dexamethasone, respectively, to 5% (P = 0.013). Antiemetic requirements were reduced from 24% and 31% to 7% (P = 0.0012). Dexamethasone had no significant effect on the incidence or severity of postoperative nausea and vomiting. Combining the two fentanyl groups revealed further significant benefits from the avoidance of opioids, reducing postoperative nausea and vomiting and nausea prior to discharge from 35% and 33% to 22% and 19% (P = 0.049 and P = 0.035), respectively, while nausea in the first 24 h was decreased from 42% to 27% (P = 0.034). Pain severity and analgesic requirements were unaffected by the omission of fentanyl. Fentanyl did reduce minor intraoperative movement but had no sevoflurane-sparing effect and increased respiratory depression, hypotension and bradycardia. CONCLUSION: As fentanyl exacerbated postoperative nausea and vomiting without an improvement in postoperative pain and also had adverse cardiorespiratory effects, it appears to be an unnecessary and possibly detrimental supplement to sevoflurane in day surgery.", "entity": "Dexamethasone", "aliases": "Alcon Brand of Dexamethasone Decaject L.A. Decaject-L.A. Decameth Decaspray Dexasone Dexpak ECR Foy Hexadecadrol Hexadrol ICN Maxidex Merck Merz 1 2 Methylfluorprednisolone Millicorten Oradexon", "definition": "An anti-inflammatory 9-fluoro-glucocorticoid.\n    ", "id": "MESH:D003907"}
{"mention": "vomiting", "mention_text": "BACKGROUND AND OBJECTIVE: Despite advantages of induction and maintenance of anaesthesia with sevoflurane, postoperative nausea and vomiting occurs frequently. Fentanyl is a commonly used supplement that may contribute to this, although it may also improve analgesia. METHODS: This double-blind study examined the incidence and severity of postoperative nausea and vomiting and pain in the first 24 h after sevoflurane anaesthesia in 216 adult day surgery patients. Patients were randomly allocated to either receive or not receive 1 1 fentanyl, while a third group received dexamethasone in addition to fentanyl. RESULTS: Omission of fentanyl did not reduce the overall incidence of postoperative nausea and vomiting, but did reduce the incidence of vomiting and/or moderate to severe nausea prior to discharge from 20% and 17% with fentanyl and fentanyl-dexamethasone, respectively, to 5% (P = 0.013). Antiemetic requirements were reduced from 24% and 31% to 7% (P = 0.0012). Dexamethasone had no significant effect on the incidence or severity of postoperative nausea and vomiting. Combining the two fentanyl groups revealed further significant benefits from the avoidance of opioids, reducing postoperative nausea and vomiting and nausea prior to discharge from 35% and 33% to 22% and 19% (P = 0.049 and P = 0.035), respectively, while nausea in the first 24 h was decreased from 42% to 27% (P = 0.034). Pain severity and analgesic requirements were unaffected by the omission of fentanyl. Fentanyl did reduce minor intraoperative movement but had no sevoflurane-sparing effect and increased respiratory depression, hypotension and bradycardia. CONCLUSION: As fentanyl exacerbated postoperative nausea and vomiting without an improvement in postoperative pain and also had adverse cardiorespiratory effects, it appears to be an unnecessary and possibly detrimental supplement to sevoflurane in day surgery.", "entity": "Vomiting", "aliases": "Emesis Vomiting", "definition": "The forcible expulsion of the contents of the STOMACH through the MOUTH.\n    ", "id": "MESH:D014839"}
{"mention": "nausea", "mention_text": "BACKGROUND AND OBJECTIVE: Despite advantages of induction and maintenance of anaesthesia with sevoflurane, postoperative nausea and vomiting occurs frequently. Fentanyl is a commonly used supplement that may contribute to this, although it may also improve analgesia. METHODS: This double-blind study examined the incidence and severity of postoperative nausea and vomiting and pain in the first 24 h after sevoflurane anaesthesia in 216 adult day surgery patients. Patients were randomly allocated to either receive or not receive 1 1 fentanyl, while a third group received dexamethasone in addition to fentanyl. RESULTS: Omission of fentanyl did not reduce the overall incidence of postoperative nausea and vomiting, but did reduce the incidence of vomiting and/or moderate to severe nausea prior to discharge from 20% and 17% with fentanyl and fentanyl-dexamethasone, respectively, to 5% (P = 0.013). Antiemetic requirements were reduced from 24% and 31% to 7% (P = 0.0012). Dexamethasone had no significant effect on the incidence or severity of postoperative nausea and vomiting. Combining the two fentanyl groups revealed further significant benefits from the avoidance of opioids, reducing postoperative nausea and vomiting and nausea prior to discharge from 35% and 33% to 22% and 19% (P = 0.049 and P = 0.035), respectively, while nausea in the first 24 h was decreased from 42% to 27% (P = 0.034). Pain severity and analgesic requirements were unaffected by the omission of fentanyl. Fentanyl did reduce minor intraoperative movement but had no sevoflurane-sparing effect and increased respiratory depression, hypotension and bradycardia. CONCLUSION: As fentanyl exacerbated postoperative nausea and vomiting without an improvement in postoperative pain and also had adverse cardiorespiratory effects, it appears to be an unnecessary and possibly detrimental supplement to sevoflurane in day surgery.", "entity": "Nausea", "aliases": "Nausea", "definition": "An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.\n    ", "id": "MESH:D009325"}
{"mention": "Dexamethasone", "mention_text": "BACKGROUND AND OBJECTIVE: Despite advantages of induction and maintenance of anaesthesia with sevoflurane, postoperative nausea and vomiting occurs frequently. Fentanyl is a commonly used supplement that may contribute to this, although it may also improve analgesia. METHODS: This double-blind study examined the incidence and severity of postoperative nausea and vomiting and pain in the first 24 h after sevoflurane anaesthesia in 216 adult day surgery patients. Patients were randomly allocated to either receive or not receive 1 1 fentanyl, while a third group received dexamethasone in addition to fentanyl. RESULTS: Omission of fentanyl did not reduce the overall incidence of postoperative nausea and vomiting, but did reduce the incidence of vomiting and/or moderate to severe nausea prior to discharge from 20% and 17% with fentanyl and fentanyl-dexamethasone, respectively, to 5% (P = 0.013). Antiemetic requirements were reduced from 24% and 31% to 7% (P = 0.0012). Dexamethasone had no significant effect on the incidence or severity of postoperative nausea and vomiting. Combining the two fentanyl groups revealed further significant benefits from the avoidance of opioids, reducing postoperative nausea and vomiting and nausea prior to discharge from 35% and 33% to 22% and 19% (P = 0.049 and P = 0.035), respectively, while nausea in the first 24 h was decreased from 42% to 27% (P = 0.034). Pain severity and analgesic requirements were unaffected by the omission of fentanyl. Fentanyl did reduce minor intraoperative movement but had no sevoflurane-sparing effect and increased respiratory depression, hypotension and bradycardia. CONCLUSION: As fentanyl exacerbated postoperative nausea and vomiting without an improvement in postoperative pain and also had adverse cardiorespiratory effects, it appears to be an unnecessary and possibly detrimental supplement to sevoflurane in day surgery.", "entity": "Dexamethasone", "aliases": "Alcon Brand of Dexamethasone Decaject L.A. Decaject-L.A. Decameth Decaspray Dexasone Dexpak ECR Foy Hexadecadrol Hexadrol ICN Maxidex Merck Merz 1 2 Methylfluorprednisolone Millicorten Oradexon", "definition": "An anti-inflammatory 9-fluoro-glucocorticoid.\n    ", "id": "MESH:D003907"}
{"mention": "Pain", "mention_text": "BACKGROUND AND OBJECTIVE: Despite advantages of induction and maintenance of anaesthesia with sevoflurane, postoperative nausea and vomiting occurs frequently. Fentanyl is a commonly used supplement that may contribute to this, although it may also improve analgesia. METHODS: This double-blind study examined the incidence and severity of postoperative nausea and vomiting and pain in the first 24 h after sevoflurane anaesthesia in 216 adult day surgery patients. Patients were randomly allocated to either receive or not receive 1 1 fentanyl, while a third group received dexamethasone in addition to fentanyl. RESULTS: Omission of fentanyl did not reduce the overall incidence of postoperative nausea and vomiting, but did reduce the incidence of vomiting and/or moderate to severe nausea prior to discharge from 20% and 17% with fentanyl and fentanyl-dexamethasone, respectively, to 5% (P = 0.013). Antiemetic requirements were reduced from 24% and 31% to 7% (P = 0.0012). Dexamethasone had no significant effect on the incidence or severity of postoperative nausea and vomiting. Combining the two fentanyl groups revealed further significant benefits from the avoidance of opioids, reducing postoperative nausea and vomiting and nausea prior to discharge from 35% and 33% to 22% and 19% (P = 0.049 and P = 0.035), respectively, while nausea in the first 24 h was decreased from 42% to 27% (P = 0.034). Pain severity and analgesic requirements were unaffected by the omission of fentanyl. Fentanyl did reduce minor intraoperative movement but had no sevoflurane-sparing effect and increased respiratory depression, hypotension and bradycardia. CONCLUSION: As fentanyl exacerbated postoperative nausea and vomiting without an improvement in postoperative pain and also had adverse cardiorespiratory effects, it appears to be an unnecessary and possibly detrimental supplement to sevoflurane in day surgery.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "respiratory depression", "mention_text": "BACKGROUND AND OBJECTIVE: Despite advantages of induction and maintenance of anaesthesia with sevoflurane, postoperative nausea and vomiting occurs frequently. Fentanyl is a commonly used supplement that may contribute to this, although it may also improve analgesia. METHODS: This double-blind study examined the incidence and severity of postoperative nausea and vomiting and pain in the first 24 h after sevoflurane anaesthesia in 216 adult day surgery patients. Patients were randomly allocated to either receive or not receive 1 1 fentanyl, while a third group received dexamethasone in addition to fentanyl. RESULTS: Omission of fentanyl did not reduce the overall incidence of postoperative nausea and vomiting, but did reduce the incidence of vomiting and/or moderate to severe nausea prior to discharge from 20% and 17% with fentanyl and fentanyl-dexamethasone, respectively, to 5% (P = 0.013). Antiemetic requirements were reduced from 24% and 31% to 7% (P = 0.0012). Dexamethasone had no significant effect on the incidence or severity of postoperative nausea and vomiting. Combining the two fentanyl groups revealed further significant benefits from the avoidance of opioids, reducing postoperative nausea and vomiting and nausea prior to discharge from 35% and 33% to 22% and 19% (P = 0.049 and P = 0.035), respectively, while nausea in the first 24 h was decreased from 42% to 27% (P = 0.034). Pain severity and analgesic requirements were unaffected by the omission of fentanyl. Fentanyl did reduce minor intraoperative movement but had no sevoflurane-sparing effect and increased respiratory depression, hypotension and bradycardia. CONCLUSION: As fentanyl exacerbated postoperative nausea and vomiting without an improvement in postoperative pain and also had adverse cardiorespiratory effects, it appears to be an unnecessary and possibly detrimental supplement to sevoflurane in day surgery.", "entity": "Respiratory Insufficiency", "aliases": "Depressions Ventilatory Respiratory Depression Failure Insufficiency", "definition": "Failure to adequately provide oxygen to cells of the body and to remove excess carbon dioxide from them. (Stedman, 25th ed)\n    ", "id": "MESH:D012131"}
{"mention": "hypotension", "mention_text": "BACKGROUND AND OBJECTIVE: Despite advantages of induction and maintenance of anaesthesia with sevoflurane, postoperative nausea and vomiting occurs frequently. Fentanyl is a commonly used supplement that may contribute to this, although it may also improve analgesia. METHODS: This double-blind study examined the incidence and severity of postoperative nausea and vomiting and pain in the first 24 h after sevoflurane anaesthesia in 216 adult day surgery patients. Patients were randomly allocated to either receive or not receive 1 1 fentanyl, while a third group received dexamethasone in addition to fentanyl. RESULTS: Omission of fentanyl did not reduce the overall incidence of postoperative nausea and vomiting, but did reduce the incidence of vomiting and/or moderate to severe nausea prior to discharge from 20% and 17% with fentanyl and fentanyl-dexamethasone, respectively, to 5% (P = 0.013). Antiemetic requirements were reduced from 24% and 31% to 7% (P = 0.0012). Dexamethasone had no significant effect on the incidence or severity of postoperative nausea and vomiting. Combining the two fentanyl groups revealed further significant benefits from the avoidance of opioids, reducing postoperative nausea and vomiting and nausea prior to discharge from 35% and 33% to 22% and 19% (P = 0.049 and P = 0.035), respectively, while nausea in the first 24 h was decreased from 42% to 27% (P = 0.034). Pain severity and analgesic requirements were unaffected by the omission of fentanyl. Fentanyl did reduce minor intraoperative movement but had no sevoflurane-sparing effect and increased respiratory depression, hypotension and bradycardia. CONCLUSION: As fentanyl exacerbated postoperative nausea and vomiting without an improvement in postoperative pain and also had adverse cardiorespiratory effects, it appears to be an unnecessary and possibly detrimental supplement to sevoflurane in day surgery.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "bradycardia", "mention_text": "BACKGROUND AND OBJECTIVE: Despite advantages of induction and maintenance of anaesthesia with sevoflurane, postoperative nausea and vomiting occurs frequently. Fentanyl is a commonly used supplement that may contribute to this, although it may also improve analgesia. METHODS: This double-blind study examined the incidence and severity of postoperative nausea and vomiting and pain in the first 24 h after sevoflurane anaesthesia in 216 adult day surgery patients. Patients were randomly allocated to either receive or not receive 1 1 fentanyl, while a third group received dexamethasone in addition to fentanyl. RESULTS: Omission of fentanyl did not reduce the overall incidence of postoperative nausea and vomiting, but did reduce the incidence of vomiting and/or moderate to severe nausea prior to discharge from 20% and 17% with fentanyl and fentanyl-dexamethasone, respectively, to 5% (P = 0.013). Antiemetic requirements were reduced from 24% and 31% to 7% (P = 0.0012). Dexamethasone had no significant effect on the incidence or severity of postoperative nausea and vomiting. Combining the two fentanyl groups revealed further significant benefits from the avoidance of opioids, reducing postoperative nausea and vomiting and nausea prior to discharge from 35% and 33% to 22% and 19% (P = 0.049 and P = 0.035), respectively, while nausea in the first 24 h was decreased from 42% to 27% (P = 0.034). Pain severity and analgesic requirements were unaffected by the omission of fentanyl. Fentanyl did reduce minor intraoperative movement but had no sevoflurane-sparing effect and increased respiratory depression, hypotension and bradycardia. CONCLUSION: As fentanyl exacerbated postoperative nausea and vomiting without an improvement in postoperative pain and also had adverse cardiorespiratory effects, it appears to be an unnecessary and possibly detrimental supplement to sevoflurane in day surgery.", "entity": "Bradycardia", "aliases": "Bradyarrhythmia Bradyarrhythmias Bradycardia Bradycardias", "definition": "Cardiac arrhythmias that are characterized by excessively slow HEART RATE, usually below 50 beats per minute in human adults. They can be classified broadly into SINOATRIAL NODE dysfunction and ATRIOVENTRICULAR BLOCK.\n    ", "id": "MESH:D001919"}
{"mention": "postoperative pain", "mention_text": "BACKGROUND AND OBJECTIVE: Despite advantages of induction and maintenance of anaesthesia with sevoflurane, postoperative nausea and vomiting occurs frequently. Fentanyl is a commonly used supplement that may contribute to this, although it may also improve analgesia. METHODS: This double-blind study examined the incidence and severity of postoperative nausea and vomiting and pain in the first 24 h after sevoflurane anaesthesia in 216 adult day surgery patients. Patients were randomly allocated to either receive or not receive 1 1 fentanyl, while a third group received dexamethasone in addition to fentanyl. RESULTS: Omission of fentanyl did not reduce the overall incidence of postoperative nausea and vomiting, but did reduce the incidence of vomiting and/or moderate to severe nausea prior to discharge from 20% and 17% with fentanyl and fentanyl-dexamethasone, respectively, to 5% (P = 0.013). Antiemetic requirements were reduced from 24% and 31% to 7% (P = 0.0012). Dexamethasone had no significant effect on the incidence or severity of postoperative nausea and vomiting. Combining the two fentanyl groups revealed further significant benefits from the avoidance of opioids, reducing postoperative nausea and vomiting and nausea prior to discharge from 35% and 33% to 22% and 19% (P = 0.049 and P = 0.035), respectively, while nausea in the first 24 h was decreased from 42% to 27% (P = 0.034). Pain severity and analgesic requirements were unaffected by the omission of fentanyl. Fentanyl did reduce minor intraoperative movement but had no sevoflurane-sparing effect and increased respiratory depression, hypotension and bradycardia. CONCLUSION: As fentanyl exacerbated postoperative nausea and vomiting without an improvement in postoperative pain and also had adverse cardiorespiratory effects, it appears to be an unnecessary and possibly detrimental supplement to sevoflurane in day surgery.", "entity": "Pain, Postoperative", "aliases": "Pain Postoperative Pains", "definition": "Pain during the period after surgery.\n    ", "id": "MESH:D010149"}
{"mention": "Renal Fanconi syndrome", "mention_text": "Renal Fanconi syndrome and myopathy after liver transplantation: drug-related mitochondrial cytopathy?", "entity": "Fanconi Syndrome", "aliases": "Adult Fanconi Syndrome Bickel De Toni-Debre-Fanconi Diabete Pseudo-Phlorizin Diabetes Renotubular with Intestinal Malabsorption and Galactose Intolerance without Cystinosis Renal Type Glycogenosis Fanconi-Bickel Syndromes Glycogen Storage Disease XI Hepatic Amino Aciduria Glucosuria Nephropathy Hepatorenal Idiopathic Lignac Lignac-Fanconi Luder Sheldon Luder-Sheldon Neonatal Primary Proximal Tubular Dysfunction Pseudo Phlorizin", "definition": "A hereditary or acquired form of generalized dysfunction of the PROXIMAL KIDNEY TUBULE without primary involvement of the KIDNEY GLOMERULUS. It is usually characterized by the tubular wasting of nutrients and salts (GLUCOSE; AMINO ACIDS; PHOSPHATES; and BICARBONATES) resulting in HYPOKALEMIA; ACIDOSIS; HYPERCALCIURIA; and PROTEINURIA.\n    ", "id": "MESH:D005198"}
{"mention": "myopathy", "mention_text": "Renal Fanconi syndrome and myopathy after liver transplantation: drug-related mitochondrial cytopathy?", "entity": "Muscular Diseases", "aliases": "Muscle Disorder Disorders Muscular Disease Diseases Myopathic Condition Conditions Myopathies Myopathy", "definition": "Acquired, familial, and congenital disorders of SKELETAL MUSCLE and SMOOTH MUSCLE.\n    ", "id": "MESH:D009135"}
{"mention": "mitochondrial cytopathy", "mention_text": "Renal Fanconi syndrome and myopathy after liver transplantation: drug-related mitochondrial cytopathy?", "entity": "Mitochondrial cytopathy", "aliases": "Mitochondrial cytopathy", "definition": "", "id": "MESH:C540770"}
{"mention": "Wilson's disease", "mention_text": "Advances in the field of transplantation provide a better quality of life and allow more favorable conditions for growth and development in children. However, combinations of different therapeutic regimens require consideration of potential adverse reactions. We describe a 15-yr-old girl who had orthotopic liver transplantation because of Wilson's disease. Tacrolimus, MMF, and steroids were given as immunosuppressant. Lamivudine was added because of de nova hepatitis B infection during her follow-up. Three yr after transplantation she developed renal Fanconi syndrome with severe metabolic acidosis, hypophosphatemia, glycosuria, and aminoaciduria. Although tacrolimus was suspected to be the cause of late post-transplant renal acidosis and was replaced by sirolimus, acidosis, and electrolyte imbalance got worse. Proximal muscle weakness has developed during her follow-up. Fanconi syndrome, as well as myopathy, is well recognized in patients with mitochondrial disorders and caused by depletion of mtDNA. We suggest that our patient's tubular dysfunction and myopathy may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine.", "entity": "Hepatolenticular Degeneration", "aliases": "Cerebral Pseudoscleroses Pseudosclerosis Copper Storage Disease Degeneration Hepatocerebral Hepatolenticular Neurohepatic Progressive Lenticular Degenerations Diseases Hepato-Neurologic Wilson Kinnier-Wilson Hepatic Form of Hepato Neurologic Syndrome Kinnier Westphal Strumpell Westphal-Strumpell Syndromes Wilson's Wilsons", "definition": "A rare autosomal recessive disease characterized by the deposition of copper in the BRAIN; LIVER; CORNEA; and other organs. It is caused by defects in the ATP7B gene encoding copper-transporting ATPase 2 (EC 3.6.3.4), also known as the Wilson disease protein. The overload of copper inevitably leads to progressive liver and neurological dysfunction such as LIVER CIRRHOSIS; TREMOR; ATAXIA and intellectual deterioration. Hepatic dysfunction may precede neurologic dysfunction by several years.\n    ", "id": "MESH:D006527"}
{"mention": "Tacrolimus", "mention_text": "Advances in the field of transplantation provide a better quality of life and allow more favorable conditions for growth and development in children. However, combinations of different therapeutic regimens require consideration of potential adverse reactions. We describe a 15-yr-old girl who had orthotopic liver transplantation because of Wilson's disease. Tacrolimus, MMF, and steroids were given as immunosuppressant. Lamivudine was added because of de nova hepatitis B infection during her follow-up. Three yr after transplantation she developed renal Fanconi syndrome with severe metabolic acidosis, hypophosphatemia, glycosuria, and aminoaciduria. Although tacrolimus was suspected to be the cause of late post-transplant renal acidosis and was replaced by sirolimus, acidosis, and electrolyte imbalance got worse. Proximal muscle weakness has developed during her follow-up. Fanconi syndrome, as well as myopathy, is well recognized in patients with mitochondrial disorders and caused by depletion of mtDNA. We suggest that our patient's tubular dysfunction and myopathy may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "steroids", "mention_text": "Advances in the field of transplantation provide a better quality of life and allow more favorable conditions for growth and development in children. However, combinations of different therapeutic regimens require consideration of potential adverse reactions. We describe a 15-yr-old girl who had orthotopic liver transplantation because of Wilson's disease. Tacrolimus, MMF, and steroids were given as immunosuppressant. Lamivudine was added because of de nova hepatitis B infection during her follow-up. Three yr after transplantation she developed renal Fanconi syndrome with severe metabolic acidosis, hypophosphatemia, glycosuria, and aminoaciduria. Although tacrolimus was suspected to be the cause of late post-transplant renal acidosis and was replaced by sirolimus, acidosis, and electrolyte imbalance got worse. Proximal muscle weakness has developed during her follow-up. Fanconi syndrome, as well as myopathy, is well recognized in patients with mitochondrial disorders and caused by depletion of mtDNA. We suggest that our patient's tubular dysfunction and myopathy may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine.", "entity": "Steroids", "aliases": "Catatoxic Steroids", "definition": "A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)\n    ", "id": "MESH:D013256"}
{"mention": "Lamivudine", "mention_text": "Advances in the field of transplantation provide a better quality of life and allow more favorable conditions for growth and development in children. However, combinations of different therapeutic regimens require consideration of potential adverse reactions. We describe a 15-yr-old girl who had orthotopic liver transplantation because of Wilson's disease. Tacrolimus, MMF, and steroids were given as immunosuppressant. Lamivudine was added because of de nova hepatitis B infection during her follow-up. Three yr after transplantation she developed renal Fanconi syndrome with severe metabolic acidosis, hypophosphatemia, glycosuria, and aminoaciduria. Although tacrolimus was suspected to be the cause of late post-transplant renal acidosis and was replaced by sirolimus, acidosis, and electrolyte imbalance got worse. Proximal muscle weakness has developed during her follow-up. Fanconi syndrome, as well as myopathy, is well recognized in patients with mitochondrial disorders and caused by depletion of mtDNA. We suggest that our patient's tubular dysfunction and myopathy may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine.", "entity": "Lamivudine", "aliases": "2',3' Dideoxy 3' thiacytidine 2',3'-Dideoxy-3'-thiacytidine 3TC BCH 189 BCH-189 BCH189 Epivir GR-109714X GR109714X Lamivudine (2S-cis)-Isomer", "definition": "A reverse transcriptase inhibitor and ZALCITABINE analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease.\n    ", "id": "MESH:D019259"}
{"mention": "hepatitis B infection", "mention_text": "Advances in the field of transplantation provide a better quality of life and allow more favorable conditions for growth and development in children. However, combinations of different therapeutic regimens require consideration of potential adverse reactions. We describe a 15-yr-old girl who had orthotopic liver transplantation because of Wilson's disease. Tacrolimus, MMF, and steroids were given as immunosuppressant. Lamivudine was added because of de nova hepatitis B infection during her follow-up. Three yr after transplantation she developed renal Fanconi syndrome with severe metabolic acidosis, hypophosphatemia, glycosuria, and aminoaciduria. Although tacrolimus was suspected to be the cause of late post-transplant renal acidosis and was replaced by sirolimus, acidosis, and electrolyte imbalance got worse. Proximal muscle weakness has developed during her follow-up. Fanconi syndrome, as well as myopathy, is well recognized in patients with mitochondrial disorders and caused by depletion of mtDNA. We suggest that our patient's tubular dysfunction and myopathy may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine.", "entity": "Hepatitis B", "aliases": "Hepatitis B", "definition": "INFLAMMATION of the LIVER in humans caused by a member of the ORTHOHEPADNAVIRUS genus, HEPATITIS B VIRUS. It is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact.\n    ", "id": "MESH:D006509"}
{"mention": "renal Fanconi syndrome", "mention_text": "Advances in the field of transplantation provide a better quality of life and allow more favorable conditions for growth and development in children. However, combinations of different therapeutic regimens require consideration of potential adverse reactions. We describe a 15-yr-old girl who had orthotopic liver transplantation because of Wilson's disease. Tacrolimus, MMF, and steroids were given as immunosuppressant. Lamivudine was added because of de nova hepatitis B infection during her follow-up. Three yr after transplantation she developed renal Fanconi syndrome with severe metabolic acidosis, hypophosphatemia, glycosuria, and aminoaciduria. Although tacrolimus was suspected to be the cause of late post-transplant renal acidosis and was replaced by sirolimus, acidosis, and electrolyte imbalance got worse. Proximal muscle weakness has developed during her follow-up. Fanconi syndrome, as well as myopathy, is well recognized in patients with mitochondrial disorders and caused by depletion of mtDNA. We suggest that our patient's tubular dysfunction and myopathy may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine.", "entity": "Fanconi Syndrome", "aliases": "Adult Fanconi Syndrome Bickel De Toni-Debre-Fanconi Diabete Pseudo-Phlorizin Diabetes Renotubular with Intestinal Malabsorption and Galactose Intolerance without Cystinosis Renal Type Glycogenosis Fanconi-Bickel Syndromes Glycogen Storage Disease XI Hepatic Amino Aciduria Glucosuria Nephropathy Hepatorenal Idiopathic Lignac Lignac-Fanconi Luder Sheldon Luder-Sheldon Neonatal Primary Proximal Tubular Dysfunction Pseudo Phlorizin", "definition": "A hereditary or acquired form of generalized dysfunction of the PROXIMAL KIDNEY TUBULE without primary involvement of the KIDNEY GLOMERULUS. It is usually characterized by the tubular wasting of nutrients and salts (GLUCOSE; AMINO ACIDS; PHOSPHATES; and BICARBONATES) resulting in HYPOKALEMIA; ACIDOSIS; HYPERCALCIURIA; and PROTEINURIA.\n    ", "id": "MESH:D005198"}
{"mention": "metabolic acidosis", "mention_text": "Advances in the field of transplantation provide a better quality of life and allow more favorable conditions for growth and development in children. However, combinations of different therapeutic regimens require consideration of potential adverse reactions. We describe a 15-yr-old girl who had orthotopic liver transplantation because of Wilson's disease. Tacrolimus, MMF, and steroids were given as immunosuppressant. Lamivudine was added because of de nova hepatitis B infection during her follow-up. Three yr after transplantation she developed renal Fanconi syndrome with severe metabolic acidosis, hypophosphatemia, glycosuria, and aminoaciduria. Although tacrolimus was suspected to be the cause of late post-transplant renal acidosis and was replaced by sirolimus, acidosis, and electrolyte imbalance got worse. Proximal muscle weakness has developed during her follow-up. Fanconi syndrome, as well as myopathy, is well recognized in patients with mitochondrial disorders and caused by depletion of mtDNA. We suggest that our patient's tubular dysfunction and myopathy may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine.", "entity": "Acidosis", "aliases": "Acidoses Metabolic Acidosis", "definition": "A pathologic condition of acid accumulation or depletion of base in the body. The two main types are RESPIRATORY ACIDOSIS and metabolic acidosis, due to metabolic acid build up.\n    ", "id": "MESH:D000138"}
{"mention": "hypophosphatemia", "mention_text": "Advances in the field of transplantation provide a better quality of life and allow more favorable conditions for growth and development in children. However, combinations of different therapeutic regimens require consideration of potential adverse reactions. We describe a 15-yr-old girl who had orthotopic liver transplantation because of Wilson's disease. Tacrolimus, MMF, and steroids were given as immunosuppressant. Lamivudine was added because of de nova hepatitis B infection during her follow-up. Three yr after transplantation she developed renal Fanconi syndrome with severe metabolic acidosis, hypophosphatemia, glycosuria, and aminoaciduria. Although tacrolimus was suspected to be the cause of late post-transplant renal acidosis and was replaced by sirolimus, acidosis, and electrolyte imbalance got worse. Proximal muscle weakness has developed during her follow-up. Fanconi syndrome, as well as myopathy, is well recognized in patients with mitochondrial disorders and caused by depletion of mtDNA. We suggest that our patient's tubular dysfunction and myopathy may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine.", "entity": "Hypophosphatemia", "aliases": "Hypophosphatemia Hypophosphatemias", "definition": "A condition of an abnormally low level of PHOSPHATES in the blood.\n    ", "id": "MESH:D017674"}
{"mention": "glycosuria", "mention_text": "Advances in the field of transplantation provide a better quality of life and allow more favorable conditions for growth and development in children. However, combinations of different therapeutic regimens require consideration of potential adverse reactions. We describe a 15-yr-old girl who had orthotopic liver transplantation because of Wilson's disease. Tacrolimus, MMF, and steroids were given as immunosuppressant. Lamivudine was added because of de nova hepatitis B infection during her follow-up. Three yr after transplantation she developed renal Fanconi syndrome with severe metabolic acidosis, hypophosphatemia, glycosuria, and aminoaciduria. Although tacrolimus was suspected to be the cause of late post-transplant renal acidosis and was replaced by sirolimus, acidosis, and electrolyte imbalance got worse. Proximal muscle weakness has developed during her follow-up. Fanconi syndrome, as well as myopathy, is well recognized in patients with mitochondrial disorders and caused by depletion of mtDNA. We suggest that our patient's tubular dysfunction and myopathy may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine.", "entity": "Glycosuria", "aliases": "Glycosuria", "definition": "The appearance of an abnormally large amount of GLUCOSE in the urine, such as more than 500 mg/day in adults. It can be due to HYPERGLYCEMIA or genetic defects in renal reabsorption (RENAL GLYCOSURIA).\n    ", "id": "MESH:D006029"}
{"mention": "aminoaciduria", "mention_text": "Advances in the field of transplantation provide a better quality of life and allow more favorable conditions for growth and development in children. However, combinations of different therapeutic regimens require consideration of potential adverse reactions. We describe a 15-yr-old girl who had orthotopic liver transplantation because of Wilson's disease. Tacrolimus, MMF, and steroids were given as immunosuppressant. Lamivudine was added because of de nova hepatitis B infection during her follow-up. Three yr after transplantation she developed renal Fanconi syndrome with severe metabolic acidosis, hypophosphatemia, glycosuria, and aminoaciduria. Although tacrolimus was suspected to be the cause of late post-transplant renal acidosis and was replaced by sirolimus, acidosis, and electrolyte imbalance got worse. Proximal muscle weakness has developed during her follow-up. Fanconi syndrome, as well as myopathy, is well recognized in patients with mitochondrial disorders and caused by depletion of mtDNA. We suggest that our patient's tubular dysfunction and myopathy may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine.", "entity": "Renal Aminoacidurias", "aliases": "Aminoaciduria Renal Aminoacidurias", "definition": "A group of inherited kidney disorders characterized by the abnormally elevated levels of AMINO ACIDS in URINE. Genetic mutations of transport proteins result in the defective reabsorption of free amino acids at the PROXIMAL RENAL TUBULES. Renal aminoaciduria are classified by the specific amino acid or acids involved.\n    ", "id": "MESH:D000608"}
{"mention": "tacrolimus", "mention_text": "Advances in the field of transplantation provide a better quality of life and allow more favorable conditions for growth and development in children. However, combinations of different therapeutic regimens require consideration of potential adverse reactions. We describe a 15-yr-old girl who had orthotopic liver transplantation because of Wilson's disease. Tacrolimus, MMF, and steroids were given as immunosuppressant. Lamivudine was added because of de nova hepatitis B infection during her follow-up. Three yr after transplantation she developed renal Fanconi syndrome with severe metabolic acidosis, hypophosphatemia, glycosuria, and aminoaciduria. Although tacrolimus was suspected to be the cause of late post-transplant renal acidosis and was replaced by sirolimus, acidosis, and electrolyte imbalance got worse. Proximal muscle weakness has developed during her follow-up. Fanconi syndrome, as well as myopathy, is well recognized in patients with mitochondrial disorders and caused by depletion of mtDNA. We suggest that our patient's tubular dysfunction and myopathy may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "acidosis", "mention_text": "Advances in the field of transplantation provide a better quality of life and allow more favorable conditions for growth and development in children. However, combinations of different therapeutic regimens require consideration of potential adverse reactions. We describe a 15-yr-old girl who had orthotopic liver transplantation because of Wilson's disease. Tacrolimus, MMF, and steroids were given as immunosuppressant. Lamivudine was added because of de nova hepatitis B infection during her follow-up. Three yr after transplantation she developed renal Fanconi syndrome with severe metabolic acidosis, hypophosphatemia, glycosuria, and aminoaciduria. Although tacrolimus was suspected to be the cause of late post-transplant renal acidosis and was replaced by sirolimus, acidosis, and electrolyte imbalance got worse. Proximal muscle weakness has developed during her follow-up. Fanconi syndrome, as well as myopathy, is well recognized in patients with mitochondrial disorders and caused by depletion of mtDNA. We suggest that our patient's tubular dysfunction and myopathy may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine.", "entity": "Acidosis", "aliases": "Acidoses Metabolic Acidosis", "definition": "A pathologic condition of acid accumulation or depletion of base in the body. The two main types are RESPIRATORY ACIDOSIS and metabolic acidosis, due to metabolic acid build up.\n    ", "id": "MESH:D000138"}
{"mention": "sirolimus", "mention_text": "Advances in the field of transplantation provide a better quality of life and allow more favorable conditions for growth and development in children. However, combinations of different therapeutic regimens require consideration of potential adverse reactions. We describe a 15-yr-old girl who had orthotopic liver transplantation because of Wilson's disease. Tacrolimus, MMF, and steroids were given as immunosuppressant. Lamivudine was added because of de nova hepatitis B infection during her follow-up. Three yr after transplantation she developed renal Fanconi syndrome with severe metabolic acidosis, hypophosphatemia, glycosuria, and aminoaciduria. Although tacrolimus was suspected to be the cause of late post-transplant renal acidosis and was replaced by sirolimus, acidosis, and electrolyte imbalance got worse. Proximal muscle weakness has developed during her follow-up. Fanconi syndrome, as well as myopathy, is well recognized in patients with mitochondrial disorders and caused by depletion of mtDNA. We suggest that our patient's tubular dysfunction and myopathy may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine.", "entity": "Sirolimus", "aliases": "AY 22 989 22-989 22989 I 2190A I-2190A I2190A Rapamune Rapamycin Sirolimus Wyeth Brand of", "definition": "A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.\n    ", "id": "MESH:D020123"}
{"mention": "muscle weakness", "mention_text": "Advances in the field of transplantation provide a better quality of life and allow more favorable conditions for growth and development in children. However, combinations of different therapeutic regimens require consideration of potential adverse reactions. We describe a 15-yr-old girl who had orthotopic liver transplantation because of Wilson's disease. Tacrolimus, MMF, and steroids were given as immunosuppressant. Lamivudine was added because of de nova hepatitis B infection during her follow-up. Three yr after transplantation she developed renal Fanconi syndrome with severe metabolic acidosis, hypophosphatemia, glycosuria, and aminoaciduria. Although tacrolimus was suspected to be the cause of late post-transplant renal acidosis and was replaced by sirolimus, acidosis, and electrolyte imbalance got worse. Proximal muscle weakness has developed during her follow-up. Fanconi syndrome, as well as myopathy, is well recognized in patients with mitochondrial disorders and caused by depletion of mtDNA. We suggest that our patient's tubular dysfunction and myopathy may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine.", "entity": "Muscle Weakness", "aliases": "Muscle Weakness Weaknesses Muscular", "definition": "A vague complaint of debility, fatigue, or exhaustion attributable to weakness of various muscles. The weakness can be characterized as subacute or chronic, often progressive, and is a manifestation of many muscle and neuromuscular diseases. (From Wyngaarden et al., Cecil Textbook of Medicine, 19th ed, p2251)\n    ", "id": "MESH:D018908"}
{"mention": "Fanconi syndrome", "mention_text": "Advances in the field of transplantation provide a better quality of life and allow more favorable conditions for growth and development in children. However, combinations of different therapeutic regimens require consideration of potential adverse reactions. We describe a 15-yr-old girl who had orthotopic liver transplantation because of Wilson's disease. Tacrolimus, MMF, and steroids were given as immunosuppressant. Lamivudine was added because of de nova hepatitis B infection during her follow-up. Three yr after transplantation she developed renal Fanconi syndrome with severe metabolic acidosis, hypophosphatemia, glycosuria, and aminoaciduria. Although tacrolimus was suspected to be the cause of late post-transplant renal acidosis and was replaced by sirolimus, acidosis, and electrolyte imbalance got worse. Proximal muscle weakness has developed during her follow-up. Fanconi syndrome, as well as myopathy, is well recognized in patients with mitochondrial disorders and caused by depletion of mtDNA. We suggest that our patient's tubular dysfunction and myopathy may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine.", "entity": "Fanconi Syndrome", "aliases": "Adult Fanconi Syndrome Bickel De Toni-Debre-Fanconi Diabete Pseudo-Phlorizin Diabetes Renotubular with Intestinal Malabsorption and Galactose Intolerance without Cystinosis Renal Type Glycogenosis Fanconi-Bickel Syndromes Glycogen Storage Disease XI Hepatic Amino Aciduria Glucosuria Nephropathy Hepatorenal Idiopathic Lignac Lignac-Fanconi Luder Sheldon Luder-Sheldon Neonatal Primary Proximal Tubular Dysfunction Pseudo Phlorizin", "definition": "A hereditary or acquired form of generalized dysfunction of the PROXIMAL KIDNEY TUBULE without primary involvement of the KIDNEY GLOMERULUS. It is usually characterized by the tubular wasting of nutrients and salts (GLUCOSE; AMINO ACIDS; PHOSPHATES; and BICARBONATES) resulting in HYPOKALEMIA; ACIDOSIS; HYPERCALCIURIA; and PROTEINURIA.\n    ", "id": "MESH:D005198"}
{"mention": "myopathy", "mention_text": "Advances in the field of transplantation provide a better quality of life and allow more favorable conditions for growth and development in children. However, combinations of different therapeutic regimens require consideration of potential adverse reactions. We describe a 15-yr-old girl who had orthotopic liver transplantation because of Wilson's disease. Tacrolimus, MMF, and steroids were given as immunosuppressant. Lamivudine was added because of de nova hepatitis B infection during her follow-up. Three yr after transplantation she developed renal Fanconi syndrome with severe metabolic acidosis, hypophosphatemia, glycosuria, and aminoaciduria. Although tacrolimus was suspected to be the cause of late post-transplant renal acidosis and was replaced by sirolimus, acidosis, and electrolyte imbalance got worse. Proximal muscle weakness has developed during her follow-up. Fanconi syndrome, as well as myopathy, is well recognized in patients with mitochondrial disorders and caused by depletion of mtDNA. We suggest that our patient's tubular dysfunction and myopathy may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine.", "entity": "Muscular Diseases", "aliases": "Muscle Disorder Disorders Muscular Disease Diseases Myopathic Condition Conditions Myopathies Myopathy", "definition": "Acquired, familial, and congenital disorders of SKELETAL MUSCLE and SMOOTH MUSCLE.\n    ", "id": "MESH:D009135"}
{"mention": "mitochondrial disorders", "mention_text": "Advances in the field of transplantation provide a better quality of life and allow more favorable conditions for growth and development in children. However, combinations of different therapeutic regimens require consideration of potential adverse reactions. We describe a 15-yr-old girl who had orthotopic liver transplantation because of Wilson's disease. Tacrolimus, MMF, and steroids were given as immunosuppressant. Lamivudine was added because of de nova hepatitis B infection during her follow-up. Three yr after transplantation she developed renal Fanconi syndrome with severe metabolic acidosis, hypophosphatemia, glycosuria, and aminoaciduria. Although tacrolimus was suspected to be the cause of late post-transplant renal acidosis and was replaced by sirolimus, acidosis, and electrolyte imbalance got worse. Proximal muscle weakness has developed during her follow-up. Fanconi syndrome, as well as myopathy, is well recognized in patients with mitochondrial disorders and caused by depletion of mtDNA. We suggest that our patient's tubular dysfunction and myopathy may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine.", "entity": "Mitochondrial Diseases", "aliases": "Deficiencies Oxidative Phosphorylation Respiratory Chain Deficiency Disease Mitochondrial Disorder Disorders Electron Transport Diseases", "definition": "Diseases caused by abnormal function of the MITOCHONDRIA. They may be caused by mutations, acquired or inherited, in mitochondrial DNA or in nuclear genes that code for mitochondrial components. They may also be the result of acquired mitochondria dysfunction due to adverse effects of drugs, infections, or other environmental causes.\n    ", "id": "MESH:D028361"}
{"mention": "tubular dysfunction", "mention_text": "Advances in the field of transplantation provide a better quality of life and allow more favorable conditions for growth and development in children. However, combinations of different therapeutic regimens require consideration of potential adverse reactions. We describe a 15-yr-old girl who had orthotopic liver transplantation because of Wilson's disease. Tacrolimus, MMF, and steroids were given as immunosuppressant. Lamivudine was added because of de nova hepatitis B infection during her follow-up. Three yr after transplantation she developed renal Fanconi syndrome with severe metabolic acidosis, hypophosphatemia, glycosuria, and aminoaciduria. Although tacrolimus was suspected to be the cause of late post-transplant renal acidosis and was replaced by sirolimus, acidosis, and electrolyte imbalance got worse. Proximal muscle weakness has developed during her follow-up. Fanconi syndrome, as well as myopathy, is well recognized in patients with mitochondrial disorders and caused by depletion of mtDNA. We suggest that our patient's tubular dysfunction and myopathy may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine.", "entity": "Fanconi Syndrome", "aliases": "Adult Fanconi Syndrome Bickel De Toni-Debre-Fanconi Diabete Pseudo-Phlorizin Diabetes Renotubular with Intestinal Malabsorption and Galactose Intolerance without Cystinosis Renal Type Glycogenosis Fanconi-Bickel Syndromes Glycogen Storage Disease XI Hepatic Amino Aciduria Glucosuria Nephropathy Hepatorenal Idiopathic Lignac Lignac-Fanconi Luder Sheldon Luder-Sheldon Neonatal Primary Proximal Tubular Dysfunction Pseudo Phlorizin", "definition": "A hereditary or acquired form of generalized dysfunction of the PROXIMAL KIDNEY TUBULE without primary involvement of the KIDNEY GLOMERULUS. It is usually characterized by the tubular wasting of nutrients and salts (GLUCOSE; AMINO ACIDS; PHOSPHATES; and BICARBONATES) resulting in HYPOKALEMIA; ACIDOSIS; HYPERCALCIURIA; and PROTEINURIA.\n    ", "id": "MESH:D005198"}
{"mention": "mitochondrial dysfunction", "mention_text": "Advances in the field of transplantation provide a better quality of life and allow more favorable conditions for growth and development in children. However, combinations of different therapeutic regimens require consideration of potential adverse reactions. We describe a 15-yr-old girl who had orthotopic liver transplantation because of Wilson's disease. Tacrolimus, MMF, and steroids were given as immunosuppressant. Lamivudine was added because of de nova hepatitis B infection during her follow-up. Three yr after transplantation she developed renal Fanconi syndrome with severe metabolic acidosis, hypophosphatemia, glycosuria, and aminoaciduria. Although tacrolimus was suspected to be the cause of late post-transplant renal acidosis and was replaced by sirolimus, acidosis, and electrolyte imbalance got worse. Proximal muscle weakness has developed during her follow-up. Fanconi syndrome, as well as myopathy, is well recognized in patients with mitochondrial disorders and caused by depletion of mtDNA. We suggest that our patient's tubular dysfunction and myopathy may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine.", "entity": "Mitochondrial Diseases", "aliases": "Deficiencies Oxidative Phosphorylation Respiratory Chain Deficiency Disease Mitochondrial Disorder Disorders Electron Transport Diseases", "definition": "Diseases caused by abnormal function of the MITOCHONDRIA. They may be caused by mutations, acquired or inherited, in mitochondrial DNA or in nuclear genes that code for mitochondrial components. They may also be the result of acquired mitochondria dysfunction due to adverse effects of drugs, infections, or other environmental causes.\n    ", "id": "MESH:D028361"}
{"mention": "lamivudine", "mention_text": "Advances in the field of transplantation provide a better quality of life and allow more favorable conditions for growth and development in children. However, combinations of different therapeutic regimens require consideration of potential adverse reactions. We describe a 15-yr-old girl who had orthotopic liver transplantation because of Wilson's disease. Tacrolimus, MMF, and steroids were given as immunosuppressant. Lamivudine was added because of de nova hepatitis B infection during her follow-up. Three yr after transplantation she developed renal Fanconi syndrome with severe metabolic acidosis, hypophosphatemia, glycosuria, and aminoaciduria. Although tacrolimus was suspected to be the cause of late post-transplant renal acidosis and was replaced by sirolimus, acidosis, and electrolyte imbalance got worse. Proximal muscle weakness has developed during her follow-up. Fanconi syndrome, as well as myopathy, is well recognized in patients with mitochondrial disorders and caused by depletion of mtDNA. We suggest that our patient's tubular dysfunction and myopathy may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine.", "entity": "Lamivudine", "aliases": "2',3' Dideoxy 3' thiacytidine 2',3'-Dideoxy-3'-thiacytidine 3TC BCH 189 BCH-189 BCH189 Epivir GR-109714X GR109714X Lamivudine (2S-cis)-Isomer", "definition": "A reverse transcriptase inhibitor and ZALCITABINE analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease.\n    ", "id": "MESH:D019259"}
{"mention": "thioperamide", "mention_text": "Antipsychotic-like profile of thioperamide, a selective H3-receptor antagonist in mice.", "entity": "thioperamide", "aliases": "MR 12842 MR-12842 N-cyclohexy-4-(imidazol-4-yl)-1-piperidinecarbothioamide thioperamide", "definition": "", "id": "MESH:C052075"}
{"mention": "schizophrenia", "mention_text": "Experimental and clinical evidence points to a role of central histaminergic system in the pathogenesis of schizophrenia. The present study was designed to study the effect of histamine H(3)-receptor ligands on neuroleptic-induced catalepsy, apomorphine-induced climbing behavior and amphetamine-induced locomotor activities in mice. Catalepsy was induced by haloperidol (2 mg/kg p.o.), while apomorphine (1.5 mg/kg s.c.) and amphetamine (2 mg/kg s.c.) were used for studying climbing behavior and locomotor activities, respectively. (R)-alpha-methylhistamine (RAMH) (5 microg i.c.v.) and thioperamide (THP) (15 mg/kg i.p.), per se did not cause catalepsy. Administration of THP (3.75, 7.5 and 15 mg/kg i.p.) 1 h prior to haloperidol resulted in a dose-dependent increase in the catalepsy times (P < 0.05). However, pretreatment with RAMH significantly reversed such an effect of THP (15 mg/kg i.p.). RAMH per se showed significant reduction in locomotor time, distance traveled and average speed but THP (15 mg/kg i.p.) per se had no effect on these parameters. On amphetamine-induced hyperactivity, THP (3.75 and 7.5 mg/kg i.p.) reduced locomotor time, distance traveled and average speed (P < 0.05). Pretreatment with RAMH (5 microg i.c.v.) could partially reverse such effects of THP (3.75 mg/kg i.p.). Climbing behavior induced by apomorphine was reduced in animals treated with THP. Such an effect was, however, reversed in presence of RAMH. THP exhibited an antipsychotic-like profile by potentiating haloperidol-induced catalepsy, reducing amphetamine-induced hyperactivity and reducing apomorphine-induced climbing in mice. Such effects of THP were reversed by RAMH indicating the involvement of histamine H(3)-receptors. Findings suggest a potential for H(3)-receptor antagonists in improving the refractory cases of schizophrenia.", "entity": "Schizophrenia", "aliases": "Dementia Praecox Disorder Schizophrenic Disorders Schizophrenia Schizophrenias", "definition": "A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior.\n    ", "id": "MESH:D012559"}
{"mention": "histamine", "mention_text": "Experimental and clinical evidence points to a role of central histaminergic system in the pathogenesis of schizophrenia. The present study was designed to study the effect of histamine H(3)-receptor ligands on neuroleptic-induced catalepsy, apomorphine-induced climbing behavior and amphetamine-induced locomotor activities in mice. Catalepsy was induced by haloperidol (2 mg/kg p.o.), while apomorphine (1.5 mg/kg s.c.) and amphetamine (2 mg/kg s.c.) were used for studying climbing behavior and locomotor activities, respectively. (R)-alpha-methylhistamine (RAMH) (5 microg i.c.v.) and thioperamide (THP) (15 mg/kg i.p.), per se did not cause catalepsy. Administration of THP (3.75, 7.5 and 15 mg/kg i.p.) 1 h prior to haloperidol resulted in a dose-dependent increase in the catalepsy times (P < 0.05). However, pretreatment with RAMH significantly reversed such an effect of THP (15 mg/kg i.p.). RAMH per se showed significant reduction in locomotor time, distance traveled and average speed but THP (15 mg/kg i.p.) per se had no effect on these parameters. On amphetamine-induced hyperactivity, THP (3.75 and 7.5 mg/kg i.p.) reduced locomotor time, distance traveled and average speed (P < 0.05). Pretreatment with RAMH (5 microg i.c.v.) could partially reverse such effects of THP (3.75 mg/kg i.p.). Climbing behavior induced by apomorphine was reduced in animals treated with THP. Such an effect was, however, reversed in presence of RAMH. THP exhibited an antipsychotic-like profile by potentiating haloperidol-induced catalepsy, reducing amphetamine-induced hyperactivity and reducing apomorphine-induced climbing in mice. Such effects of THP were reversed by RAMH indicating the involvement of histamine H(3)-receptors. Findings suggest a potential for H(3)-receptor antagonists in improving the refractory cases of schizophrenia.", "entity": "Histamine", "aliases": "Ceplene Dihydrochloride Histamine Hydrochloride Peremin", "definition": "An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.\n    ", "id": "MESH:D006632"}
{"mention": "catalepsy", "mention_text": "Experimental and clinical evidence points to a role of central histaminergic system in the pathogenesis of schizophrenia. The present study was designed to study the effect of histamine H(3)-receptor ligands on neuroleptic-induced catalepsy, apomorphine-induced climbing behavior and amphetamine-induced locomotor activities in mice. Catalepsy was induced by haloperidol (2 mg/kg p.o.), while apomorphine (1.5 mg/kg s.c.) and amphetamine (2 mg/kg s.c.) were used for studying climbing behavior and locomotor activities, respectively. (R)-alpha-methylhistamine (RAMH) (5 microg i.c.v.) and thioperamide (THP) (15 mg/kg i.p.), per se did not cause catalepsy. Administration of THP (3.75, 7.5 and 15 mg/kg i.p.) 1 h prior to haloperidol resulted in a dose-dependent increase in the catalepsy times (P < 0.05). However, pretreatment with RAMH significantly reversed such an effect of THP (15 mg/kg i.p.). RAMH per se showed significant reduction in locomotor time, distance traveled and average speed but THP (15 mg/kg i.p.) per se had no effect on these parameters. On amphetamine-induced hyperactivity, THP (3.75 and 7.5 mg/kg i.p.) reduced locomotor time, distance traveled and average speed (P < 0.05). Pretreatment with RAMH (5 microg i.c.v.) could partially reverse such effects of THP (3.75 mg/kg i.p.). Climbing behavior induced by apomorphine was reduced in animals treated with THP. Such an effect was, however, reversed in presence of RAMH. THP exhibited an antipsychotic-like profile by potentiating haloperidol-induced catalepsy, reducing amphetamine-induced hyperactivity and reducing apomorphine-induced climbing in mice. Such effects of THP were reversed by RAMH indicating the involvement of histamine H(3)-receptors. Findings suggest a potential for H(3)-receptor antagonists in improving the refractory cases of schizophrenia.", "entity": "Catalepsy", "aliases": "Anochlesia Anochlesias Catalepsies Catalepsy Cerea Flexibilitas Flexibilities Waxy Flexibility", "definition": "A condition characterized by inactivity, decreased responsiveness to stimuli, and a tendency to maintain an immobile posture. The limbs tend to remain in whatever position they are placed (waxy flexibility). Catalepsy may be associated with PSYCHOTIC DISORDERS (e.g., SCHIZOPHRENIA, CATATONIC), nervous system drug toxicity, and other conditions.\n    ", "id": "MESH:D002375"}
{"mention": "apomorphine", "mention_text": "Experimental and clinical evidence points to a role of central histaminergic system in the pathogenesis of schizophrenia. The present study was designed to study the effect of histamine H(3)-receptor ligands on neuroleptic-induced catalepsy, apomorphine-induced climbing behavior and amphetamine-induced locomotor activities in mice. Catalepsy was induced by haloperidol (2 mg/kg p.o.), while apomorphine (1.5 mg/kg s.c.) and amphetamine (2 mg/kg s.c.) were used for studying climbing behavior and locomotor activities, respectively. (R)-alpha-methylhistamine (RAMH) (5 microg i.c.v.) and thioperamide (THP) (15 mg/kg i.p.), per se did not cause catalepsy. Administration of THP (3.75, 7.5 and 15 mg/kg i.p.) 1 h prior to haloperidol resulted in a dose-dependent increase in the catalepsy times (P < 0.05). However, pretreatment with RAMH significantly reversed such an effect of THP (15 mg/kg i.p.). RAMH per se showed significant reduction in locomotor time, distance traveled and average speed but THP (15 mg/kg i.p.) per se had no effect on these parameters. On amphetamine-induced hyperactivity, THP (3.75 and 7.5 mg/kg i.p.) reduced locomotor time, distance traveled and average speed (P < 0.05). Pretreatment with RAMH (5 microg i.c.v.) could partially reverse such effects of THP (3.75 mg/kg i.p.). Climbing behavior induced by apomorphine was reduced in animals treated with THP. Such an effect was, however, reversed in presence of RAMH. THP exhibited an antipsychotic-like profile by potentiating haloperidol-induced catalepsy, reducing amphetamine-induced hyperactivity and reducing apomorphine-induced climbing in mice. Such effects of THP were reversed by RAMH indicating the involvement of histamine H(3)-receptors. Findings suggest a potential for H(3)-receptor antagonists in improving the refractory cases of schizophrenia.", "entity": "Apomorphine", "aliases": "Aguettant Brand of Apomorphine Hydrochloride Anhydrous Apokinon Apomorphin Teclapharm Apomorphin-Teclapharm ApomorphinTeclapharm Chloride Hemihydrate Britaject Britannia", "definition": "A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use.\n    ", "id": "MESH:D001058"}
{"mention": "amphetamine", "mention_text": "Experimental and clinical evidence points to a role of central histaminergic system in the pathogenesis of schizophrenia. The present study was designed to study the effect of histamine H(3)-receptor ligands on neuroleptic-induced catalepsy, apomorphine-induced climbing behavior and amphetamine-induced locomotor activities in mice. Catalepsy was induced by haloperidol (2 mg/kg p.o.), while apomorphine (1.5 mg/kg s.c.) and amphetamine (2 mg/kg s.c.) were used for studying climbing behavior and locomotor activities, respectively. (R)-alpha-methylhistamine (RAMH) (5 microg i.c.v.) and thioperamide (THP) (15 mg/kg i.p.), per se did not cause catalepsy. Administration of THP (3.75, 7.5 and 15 mg/kg i.p.) 1 h prior to haloperidol resulted in a dose-dependent increase in the catalepsy times (P < 0.05). However, pretreatment with RAMH significantly reversed such an effect of THP (15 mg/kg i.p.). RAMH per se showed significant reduction in locomotor time, distance traveled and average speed but THP (15 mg/kg i.p.) per se had no effect on these parameters. On amphetamine-induced hyperactivity, THP (3.75 and 7.5 mg/kg i.p.) reduced locomotor time, distance traveled and average speed (P < 0.05). Pretreatment with RAMH (5 microg i.c.v.) could partially reverse such effects of THP (3.75 mg/kg i.p.). Climbing behavior induced by apomorphine was reduced in animals treated with THP. Such an effect was, however, reversed in presence of RAMH. THP exhibited an antipsychotic-like profile by potentiating haloperidol-induced catalepsy, reducing amphetamine-induced hyperactivity and reducing apomorphine-induced climbing in mice. Such effects of THP were reversed by RAMH indicating the involvement of histamine H(3)-receptors. Findings suggest a potential for H(3)-receptor antagonists in improving the refractory cases of schizophrenia.", "entity": "Amphetamine", "aliases": "Amfetamine Amphetamine Sulfate (2:1) Centramina Desoxynorephedrin Fenamine Levoamphetamine Miquel Brand of Mydrial Phenamine Phenopromin Thyramine l l-Amphetamine levo levo-Amphetamine", "definition": "A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE.\n    ", "id": "MESH:D000661"}
{"mention": "Catalepsy", "mention_text": "Experimental and clinical evidence points to a role of central histaminergic system in the pathogenesis of schizophrenia. The present study was designed to study the effect of histamine H(3)-receptor ligands on neuroleptic-induced catalepsy, apomorphine-induced climbing behavior and amphetamine-induced locomotor activities in mice. Catalepsy was induced by haloperidol (2 mg/kg p.o.), while apomorphine (1.5 mg/kg s.c.) and amphetamine (2 mg/kg s.c.) were used for studying climbing behavior and locomotor activities, respectively. (R)-alpha-methylhistamine (RAMH) (5 microg i.c.v.) and thioperamide (THP) (15 mg/kg i.p.), per se did not cause catalepsy. Administration of THP (3.75, 7.5 and 15 mg/kg i.p.) 1 h prior to haloperidol resulted in a dose-dependent increase in the catalepsy times (P < 0.05). However, pretreatment with RAMH significantly reversed such an effect of THP (15 mg/kg i.p.). RAMH per se showed significant reduction in locomotor time, distance traveled and average speed but THP (15 mg/kg i.p.) per se had no effect on these parameters. On amphetamine-induced hyperactivity, THP (3.75 and 7.5 mg/kg i.p.) reduced locomotor time, distance traveled and average speed (P < 0.05). Pretreatment with RAMH (5 microg i.c.v.) could partially reverse such effects of THP (3.75 mg/kg i.p.). Climbing behavior induced by apomorphine was reduced in animals treated with THP. Such an effect was, however, reversed in presence of RAMH. THP exhibited an antipsychotic-like profile by potentiating haloperidol-induced catalepsy, reducing amphetamine-induced hyperactivity and reducing apomorphine-induced climbing in mice. Such effects of THP were reversed by RAMH indicating the involvement of histamine H(3)-receptors. Findings suggest a potential for H(3)-receptor antagonists in improving the refractory cases of schizophrenia.", "entity": "Catalepsy", "aliases": "Anochlesia Anochlesias Catalepsies Catalepsy Cerea Flexibilitas Flexibilities Waxy Flexibility", "definition": "A condition characterized by inactivity, decreased responsiveness to stimuli, and a tendency to maintain an immobile posture. The limbs tend to remain in whatever position they are placed (waxy flexibility). Catalepsy may be associated with PSYCHOTIC DISORDERS (e.g., SCHIZOPHRENIA, CATATONIC), nervous system drug toxicity, and other conditions.\n    ", "id": "MESH:D002375"}
{"mention": "haloperidol", "mention_text": "Experimental and clinical evidence points to a role of central histaminergic system in the pathogenesis of schizophrenia. The present study was designed to study the effect of histamine H(3)-receptor ligands on neuroleptic-induced catalepsy, apomorphine-induced climbing behavior and amphetamine-induced locomotor activities in mice. Catalepsy was induced by haloperidol (2 mg/kg p.o.), while apomorphine (1.5 mg/kg s.c.) and amphetamine (2 mg/kg s.c.) were used for studying climbing behavior and locomotor activities, respectively. (R)-alpha-methylhistamine (RAMH) (5 microg i.c.v.) and thioperamide (THP) (15 mg/kg i.p.), per se did not cause catalepsy. Administration of THP (3.75, 7.5 and 15 mg/kg i.p.) 1 h prior to haloperidol resulted in a dose-dependent increase in the catalepsy times (P < 0.05). However, pretreatment with RAMH significantly reversed such an effect of THP (15 mg/kg i.p.). RAMH per se showed significant reduction in locomotor time, distance traveled and average speed but THP (15 mg/kg i.p.) per se had no effect on these parameters. On amphetamine-induced hyperactivity, THP (3.75 and 7.5 mg/kg i.p.) reduced locomotor time, distance traveled and average speed (P < 0.05). Pretreatment with RAMH (5 microg i.c.v.) could partially reverse such effects of THP (3.75 mg/kg i.p.). Climbing behavior induced by apomorphine was reduced in animals treated with THP. Such an effect was, however, reversed in presence of RAMH. THP exhibited an antipsychotic-like profile by potentiating haloperidol-induced catalepsy, reducing amphetamine-induced hyperactivity and reducing apomorphine-induced climbing in mice. Such effects of THP were reversed by RAMH indicating the involvement of histamine H(3)-receptors. Findings suggest a potential for H(3)-receptor antagonists in improving the refractory cases of schizophrenia.", "entity": "Haloperidol", "aliases": "Haldol Haloperidol", "definition": "A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)\n    ", "id": "MESH:D006220"}
{"mention": "(R)-alpha-methylhistamine", "mention_text": "Experimental and clinical evidence points to a role of central histaminergic system in the pathogenesis of schizophrenia. The present study was designed to study the effect of histamine H(3)-receptor ligands on neuroleptic-induced catalepsy, apomorphine-induced climbing behavior and amphetamine-induced locomotor activities in mice. Catalepsy was induced by haloperidol (2 mg/kg p.o.), while apomorphine (1.5 mg/kg s.c.) and amphetamine (2 mg/kg s.c.) were used for studying climbing behavior and locomotor activities, respectively. (R)-alpha-methylhistamine (RAMH) (5 microg i.c.v.) and thioperamide (THP) (15 mg/kg i.p.), per se did not cause catalepsy. Administration of THP (3.75, 7.5 and 15 mg/kg i.p.) 1 h prior to haloperidol resulted in a dose-dependent increase in the catalepsy times (P < 0.05). However, pretreatment with RAMH significantly reversed such an effect of THP (15 mg/kg i.p.). RAMH per se showed significant reduction in locomotor time, distance traveled and average speed but THP (15 mg/kg i.p.) per se had no effect on these parameters. On amphetamine-induced hyperactivity, THP (3.75 and 7.5 mg/kg i.p.) reduced locomotor time, distance traveled and average speed (P < 0.05). Pretreatment with RAMH (5 microg i.c.v.) could partially reverse such effects of THP (3.75 mg/kg i.p.). Climbing behavior induced by apomorphine was reduced in animals treated with THP. Such an effect was, however, reversed in presence of RAMH. THP exhibited an antipsychotic-like profile by potentiating haloperidol-induced catalepsy, reducing amphetamine-induced hyperactivity and reducing apomorphine-induced climbing in mice. Such effects of THP were reversed by RAMH indicating the involvement of histamine H(3)-receptors. Findings suggest a potential for H(3)-receptor antagonists in improving the refractory cases of schizophrenia.", "entity": "alpha-methylhistamine", "aliases": "alpha-methylhistamine dihydrochloride (R)-isomer (S)-isomer", "definition": "", "id": "MESH:C069357"}
{"mention": "RAMH", "mention_text": "Experimental and clinical evidence points to a role of central histaminergic system in the pathogenesis of schizophrenia. The present study was designed to study the effect of histamine H(3)-receptor ligands on neuroleptic-induced catalepsy, apomorphine-induced climbing behavior and amphetamine-induced locomotor activities in mice. Catalepsy was induced by haloperidol (2 mg/kg p.o.), while apomorphine (1.5 mg/kg s.c.) and amphetamine (2 mg/kg s.c.) were used for studying climbing behavior and locomotor activities, respectively. (R)-alpha-methylhistamine (RAMH) (5 microg i.c.v.) and thioperamide (THP) (15 mg/kg i.p.), per se did not cause catalepsy. Administration of THP (3.75, 7.5 and 15 mg/kg i.p.) 1 h prior to haloperidol resulted in a dose-dependent increase in the catalepsy times (P < 0.05). However, pretreatment with RAMH significantly reversed such an effect of THP (15 mg/kg i.p.). RAMH per se showed significant reduction in locomotor time, distance traveled and average speed but THP (15 mg/kg i.p.) per se had no effect on these parameters. On amphetamine-induced hyperactivity, THP (3.75 and 7.5 mg/kg i.p.) reduced locomotor time, distance traveled and average speed (P < 0.05). Pretreatment with RAMH (5 microg i.c.v.) could partially reverse such effects of THP (3.75 mg/kg i.p.). Climbing behavior induced by apomorphine was reduced in animals treated with THP. Such an effect was, however, reversed in presence of RAMH. THP exhibited an antipsychotic-like profile by potentiating haloperidol-induced catalepsy, reducing amphetamine-induced hyperactivity and reducing apomorphine-induced climbing in mice. Such effects of THP were reversed by RAMH indicating the involvement of histamine H(3)-receptors. Findings suggest a potential for H(3)-receptor antagonists in improving the refractory cases of schizophrenia.", "entity": "alpha-methylhistamine", "aliases": "alpha-methylhistamine dihydrochloride (R)-isomer (S)-isomer", "definition": "", "id": "MESH:C069357"}
{"mention": "thioperamide", "mention_text": "Experimental and clinical evidence points to a role of central histaminergic system in the pathogenesis of schizophrenia. The present study was designed to study the effect of histamine H(3)-receptor ligands on neuroleptic-induced catalepsy, apomorphine-induced climbing behavior and amphetamine-induced locomotor activities in mice. Catalepsy was induced by haloperidol (2 mg/kg p.o.), while apomorphine (1.5 mg/kg s.c.) and amphetamine (2 mg/kg s.c.) were used for studying climbing behavior and locomotor activities, respectively. (R)-alpha-methylhistamine (RAMH) (5 microg i.c.v.) and thioperamide (THP) (15 mg/kg i.p.), per se did not cause catalepsy. Administration of THP (3.75, 7.5 and 15 mg/kg i.p.) 1 h prior to haloperidol resulted in a dose-dependent increase in the catalepsy times (P < 0.05). However, pretreatment with RAMH significantly reversed such an effect of THP (15 mg/kg i.p.). RAMH per se showed significant reduction in locomotor time, distance traveled and average speed but THP (15 mg/kg i.p.) per se had no effect on these parameters. On amphetamine-induced hyperactivity, THP (3.75 and 7.5 mg/kg i.p.) reduced locomotor time, distance traveled and average speed (P < 0.05). Pretreatment with RAMH (5 microg i.c.v.) could partially reverse such effects of THP (3.75 mg/kg i.p.). Climbing behavior induced by apomorphine was reduced in animals treated with THP. Such an effect was, however, reversed in presence of RAMH. THP exhibited an antipsychotic-like profile by potentiating haloperidol-induced catalepsy, reducing amphetamine-induced hyperactivity and reducing apomorphine-induced climbing in mice. Such effects of THP were reversed by RAMH indicating the involvement of histamine H(3)-receptors. Findings suggest a potential for H(3)-receptor antagonists in improving the refractory cases of schizophrenia.", "entity": "thioperamide", "aliases": "MR 12842 MR-12842 N-cyclohexy-4-(imidazol-4-yl)-1-piperidinecarbothioamide thioperamide", "definition": "", "id": "MESH:C052075"}
{"mention": "THP", "mention_text": "Experimental and clinical evidence points to a role of central histaminergic system in the pathogenesis of schizophrenia. The present study was designed to study the effect of histamine H(3)-receptor ligands on neuroleptic-induced catalepsy, apomorphine-induced climbing behavior and amphetamine-induced locomotor activities in mice. Catalepsy was induced by haloperidol (2 mg/kg p.o.), while apomorphine (1.5 mg/kg s.c.) and amphetamine (2 mg/kg s.c.) were used for studying climbing behavior and locomotor activities, respectively. (R)-alpha-methylhistamine (RAMH) (5 microg i.c.v.) and thioperamide (THP) (15 mg/kg i.p.), per se did not cause catalepsy. Administration of THP (3.75, 7.5 and 15 mg/kg i.p.) 1 h prior to haloperidol resulted in a dose-dependent increase in the catalepsy times (P < 0.05). However, pretreatment with RAMH significantly reversed such an effect of THP (15 mg/kg i.p.). RAMH per se showed significant reduction in locomotor time, distance traveled and average speed but THP (15 mg/kg i.p.) per se had no effect on these parameters. On amphetamine-induced hyperactivity, THP (3.75 and 7.5 mg/kg i.p.) reduced locomotor time, distance traveled and average speed (P < 0.05). Pretreatment with RAMH (5 microg i.c.v.) could partially reverse such effects of THP (3.75 mg/kg i.p.). Climbing behavior induced by apomorphine was reduced in animals treated with THP. Such an effect was, however, reversed in presence of RAMH. THP exhibited an antipsychotic-like profile by potentiating haloperidol-induced catalepsy, reducing amphetamine-induced hyperactivity and reducing apomorphine-induced climbing in mice. Such effects of THP were reversed by RAMH indicating the involvement of histamine H(3)-receptors. Findings suggest a potential for H(3)-receptor antagonists in improving the refractory cases of schizophrenia.", "entity": "thioperamide", "aliases": "MR 12842 MR-12842 N-cyclohexy-4-(imidazol-4-yl)-1-piperidinecarbothioamide thioperamide", "definition": "", "id": "MESH:C052075"}
{"mention": "hyperactivity", "mention_text": "Experimental and clinical evidence points to a role of central histaminergic system in the pathogenesis of schizophrenia. The present study was designed to study the effect of histamine H(3)-receptor ligands on neuroleptic-induced catalepsy, apomorphine-induced climbing behavior and amphetamine-induced locomotor activities in mice. Catalepsy was induced by haloperidol (2 mg/kg p.o.), while apomorphine (1.5 mg/kg s.c.) and amphetamine (2 mg/kg s.c.) were used for studying climbing behavior and locomotor activities, respectively. (R)-alpha-methylhistamine (RAMH) (5 microg i.c.v.) and thioperamide (THP) (15 mg/kg i.p.), per se did not cause catalepsy. Administration of THP (3.75, 7.5 and 15 mg/kg i.p.) 1 h prior to haloperidol resulted in a dose-dependent increase in the catalepsy times (P < 0.05). However, pretreatment with RAMH significantly reversed such an effect of THP (15 mg/kg i.p.). RAMH per se showed significant reduction in locomotor time, distance traveled and average speed but THP (15 mg/kg i.p.) per se had no effect on these parameters. On amphetamine-induced hyperactivity, THP (3.75 and 7.5 mg/kg i.p.) reduced locomotor time, distance traveled and average speed (P < 0.05). Pretreatment with RAMH (5 microg i.c.v.) could partially reverse such effects of THP (3.75 mg/kg i.p.). Climbing behavior induced by apomorphine was reduced in animals treated with THP. Such an effect was, however, reversed in presence of RAMH. THP exhibited an antipsychotic-like profile by potentiating haloperidol-induced catalepsy, reducing amphetamine-induced hyperactivity and reducing apomorphine-induced climbing in mice. Such effects of THP were reversed by RAMH indicating the involvement of histamine H(3)-receptors. Findings suggest a potential for H(3)-receptor antagonists in improving the refractory cases of schizophrenia.", "entity": "Hyperkinesis", "aliases": "Generalized Hyperkinesia Hyperkinesias Hyperactivity Motor Hyperkinesis Hyperkinetic Movement Movements", "definition": "Excessive movement of muscles of the body as a whole, which may be associated with organic or psychological disorders.\n    ", "id": "MESH:D006948"}
{"mention": "propafenone", "mention_text": "Transient platypnea-orthodeoxia-like syndrome induced by propafenone overdose in a young woman with Ebstein's anomaly.", "entity": "Propafenone", "aliases": "Abbott Brand of Propafenone Hydrochloride Aliud Alpharma Apo-Propafenone Apotex Arythmol Azupharma Baxarytmon Cuxafenon Fenoprain Hexal Juta Jutanorm Kendrick Knoll Merck dura Nistaken Norfenon Pintoform Prolecofen Propafenon AL Minden (R)-Isomer (S)-Isomer (+-)-Isomer Propamerck Q-Pharm Rythmol Rytmo-Puren Rytmogenat Rytmonorm SA 79 SA-79 SA79 TAD", "definition": "An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity.\n    ", "id": "MESH:D011405"}
{"mention": "overdose", "mention_text": "Transient platypnea-orthodeoxia-like syndrome induced by propafenone overdose in a young woman with Ebstein's anomaly.", "entity": "Drug Overdose", "aliases": "Drug Overdose Overdoses", "definition": "Accidental or deliberate use of a medication or street drug in excess of normal dosage.\n    ", "id": "MESH:D062787"}
{"mention": "Ebstein's anomaly", "mention_text": "Transient platypnea-orthodeoxia-like syndrome induced by propafenone overdose in a young woman with Ebstein's anomaly.", "entity": "Ebstein Anomaly", "aliases": "Anomaly Ebstein Ebstein's Malformation Familial Ebsteins", "definition": "A congenital heart defect characterized by downward or apical displacement of the TRICUSPID VALVE, usually with the septal and posterior leaflets being attached to the wall of the RIGHT VENTRICLE. It is characterized by a huge RIGHT ATRIUM and a small and less effective right ventricle.\n    ", "id": "MESH:D004437"}
{"mention": "Ebstein's anomaly", "mention_text": "In this report we describe the case of a 37-year-old white woman with Ebstein's anomaly, who developed a rare syndrome called platypnea-orthodeoxia, characterized by massive right-to-left interatrial shunting with transient profound hypoxia and cyanosis. This shunt of blood via a patent foramen ovale occurred in the presence of a normal pulmonary artery pressure, and was probably precipitated by a propafenone overdose. This drug caused biventricular dysfunction, due to its negative inotropic effect, and hypotension, due to its peripheral vasodilatory effect. These effects gave rise to an increase in the right atrial pressure and a decrease in the left one with a consequent stretching of the foramen ovale and the creation of massive right-to-left shunting. In our case this interatrial shunt was very accurately detected at bubble contrast echocardiography.", "entity": "Ebstein Anomaly", "aliases": "Anomaly Ebstein Ebstein's Malformation Familial Ebsteins", "definition": "A congenital heart defect characterized by downward or apical displacement of the TRICUSPID VALVE, usually with the septal and posterior leaflets being attached to the wall of the RIGHT VENTRICLE. It is characterized by a huge RIGHT ATRIUM and a small and less effective right ventricle.\n    ", "id": "MESH:D004437"}
{"mention": "hypoxia", "mention_text": "In this report we describe the case of a 37-year-old white woman with Ebstein's anomaly, who developed a rare syndrome called platypnea-orthodeoxia, characterized by massive right-to-left interatrial shunting with transient profound hypoxia and cyanosis. This shunt of blood via a patent foramen ovale occurred in the presence of a normal pulmonary artery pressure, and was probably precipitated by a propafenone overdose. This drug caused biventricular dysfunction, due to its negative inotropic effect, and hypotension, due to its peripheral vasodilatory effect. These effects gave rise to an increase in the right atrial pressure and a decrease in the left one with a consequent stretching of the foramen ovale and the creation of massive right-to-left shunting. In our case this interatrial shunt was very accurately detected at bubble contrast echocardiography.", "entity": "Anoxia", "aliases": "Anoxemia Anoxemias Anoxia Anoxias Deficiencies Oxygen Deficiency Hypoxemia Hypoxemias Hypoxia Hypoxias", "definition": "Relatively complete absence of oxygen in one or more tissues.\n    ", "id": "MESH:D000860"}
{"mention": "cyanosis", "mention_text": "In this report we describe the case of a 37-year-old white woman with Ebstein's anomaly, who developed a rare syndrome called platypnea-orthodeoxia, characterized by massive right-to-left interatrial shunting with transient profound hypoxia and cyanosis. This shunt of blood via a patent foramen ovale occurred in the presence of a normal pulmonary artery pressure, and was probably precipitated by a propafenone overdose. This drug caused biventricular dysfunction, due to its negative inotropic effect, and hypotension, due to its peripheral vasodilatory effect. These effects gave rise to an increase in the right atrial pressure and a decrease in the left one with a consequent stretching of the foramen ovale and the creation of massive right-to-left shunting. In our case this interatrial shunt was very accurately detected at bubble contrast echocardiography.", "entity": "Cyanosis", "aliases": "Cyanoses Cyanosis", "definition": "A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule.\n    ", "id": "MESH:D003490"}
{"mention": "patent foramen ovale", "mention_text": "In this report we describe the case of a 37-year-old white woman with Ebstein's anomaly, who developed a rare syndrome called platypnea-orthodeoxia, characterized by massive right-to-left interatrial shunting with transient profound hypoxia and cyanosis. This shunt of blood via a patent foramen ovale occurred in the presence of a normal pulmonary artery pressure, and was probably precipitated by a propafenone overdose. This drug caused biventricular dysfunction, due to its negative inotropic effect, and hypotension, due to its peripheral vasodilatory effect. These effects gave rise to an increase in the right atrial pressure and a decrease in the left one with a consequent stretching of the foramen ovale and the creation of massive right-to-left shunting. In our case this interatrial shunt was very accurately detected at bubble contrast echocardiography.", "entity": "Foramen Ovale, Patent", "aliases": "Foramen Ovale Patent Oval", "definition": "A condition in which the FORAMEN OVALE in the ATRIAL SEPTUM fails to close shortly after birth. This results in abnormal communications between the two upper chambers of the heart. An isolated patent ovale foramen without other structural heart defects is usually of no hemodynamic significance.\n    ", "id": "MESH:D054092"}
{"mention": "propafenone", "mention_text": "In this report we describe the case of a 37-year-old white woman with Ebstein's anomaly, who developed a rare syndrome called platypnea-orthodeoxia, characterized by massive right-to-left interatrial shunting with transient profound hypoxia and cyanosis. This shunt of blood via a patent foramen ovale occurred in the presence of a normal pulmonary artery pressure, and was probably precipitated by a propafenone overdose. This drug caused biventricular dysfunction, due to its negative inotropic effect, and hypotension, due to its peripheral vasodilatory effect. These effects gave rise to an increase in the right atrial pressure and a decrease in the left one with a consequent stretching of the foramen ovale and the creation of massive right-to-left shunting. In our case this interatrial shunt was very accurately detected at bubble contrast echocardiography.", "entity": "Propafenone", "aliases": "Abbott Brand of Propafenone Hydrochloride Aliud Alpharma Apo-Propafenone Apotex Arythmol Azupharma Baxarytmon Cuxafenon Fenoprain Hexal Juta Jutanorm Kendrick Knoll Merck dura Nistaken Norfenon Pintoform Prolecofen Propafenon AL Minden (R)-Isomer (S)-Isomer (+-)-Isomer Propamerck Q-Pharm Rythmol Rytmo-Puren Rytmogenat Rytmonorm SA 79 SA-79 SA79 TAD", "definition": "An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity.\n    ", "id": "MESH:D011405"}
{"mention": "overdose", "mention_text": "In this report we describe the case of a 37-year-old white woman with Ebstein's anomaly, who developed a rare syndrome called platypnea-orthodeoxia, characterized by massive right-to-left interatrial shunting with transient profound hypoxia and cyanosis. This shunt of blood via a patent foramen ovale occurred in the presence of a normal pulmonary artery pressure, and was probably precipitated by a propafenone overdose. This drug caused biventricular dysfunction, due to its negative inotropic effect, and hypotension, due to its peripheral vasodilatory effect. These effects gave rise to an increase in the right atrial pressure and a decrease in the left one with a consequent stretching of the foramen ovale and the creation of massive right-to-left shunting. In our case this interatrial shunt was very accurately detected at bubble contrast echocardiography.", "entity": "Drug Overdose", "aliases": "Drug Overdose Overdoses", "definition": "Accidental or deliberate use of a medication or street drug in excess of normal dosage.\n    ", "id": "MESH:D062787"}
{"mention": "biventricular dysfunction", "mention_text": "In this report we describe the case of a 37-year-old white woman with Ebstein's anomaly, who developed a rare syndrome called platypnea-orthodeoxia, characterized by massive right-to-left interatrial shunting with transient profound hypoxia and cyanosis. This shunt of blood via a patent foramen ovale occurred in the presence of a normal pulmonary artery pressure, and was probably precipitated by a propafenone overdose. This drug caused biventricular dysfunction, due to its negative inotropic effect, and hypotension, due to its peripheral vasodilatory effect. These effects gave rise to an increase in the right atrial pressure and a decrease in the left one with a consequent stretching of the foramen ovale and the creation of massive right-to-left shunting. In our case this interatrial shunt was very accurately detected at bubble contrast echocardiography.", "entity": "Ventricular Dysfunction", "aliases": "Dysfunction Ventricular Dysfunctions", "definition": "A condition in which HEART VENTRICLES exhibit impaired function.\n    ", "id": "MESH:D018754"}
{"mention": "hypotension", "mention_text": "In this report we describe the case of a 37-year-old white woman with Ebstein's anomaly, who developed a rare syndrome called platypnea-orthodeoxia, characterized by massive right-to-left interatrial shunting with transient profound hypoxia and cyanosis. This shunt of blood via a patent foramen ovale occurred in the presence of a normal pulmonary artery pressure, and was probably precipitated by a propafenone overdose. This drug caused biventricular dysfunction, due to its negative inotropic effect, and hypotension, due to its peripheral vasodilatory effect. These effects gave rise to an increase in the right atrial pressure and a decrease in the left one with a consequent stretching of the foramen ovale and the creation of massive right-to-left shunting. In our case this interatrial shunt was very accurately detected at bubble contrast echocardiography.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "cisplatin", "mention_text": "A Phase II trial of cisplatin plus WR-2721 (amifostine) for metastatic breast carcinoma: an Eastern Cooperative Oncology Group Study (E8188).", "entity": "Cisplatin", "aliases": "Biocisplatinum Cisplatin Diamminodichloride Platinum Dichlorodiammineplatinum NSC-119875 Platidiam Platino Platinol cis Diamminedichloroplatinum cis-Diamminedichloroplatinum cis-Diamminedichloroplatinum(II) cis-Dichlorodiammineplatinum(II) cis-Platinum", "definition": "An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.\n    ", "id": "MESH:D002945"}
{"mention": "WR-2721", "mention_text": "A Phase II trial of cisplatin plus WR-2721 (amifostine) for metastatic breast carcinoma: an Eastern Cooperative Oncology Group Study (E8188).", "entity": "Amifostine", "aliases": "APAETP Alza Brand of Amifostine Anhydrous Disodium Salt Essex Lilly Monohydrate Monohydrochloride Schering-Plough Trihydrate Aminopropyl Aminoethylthiophosphate Aminopropylaminoethylthiophosphate Aminopropylaminoethylthiophosphoric Acid Ethiofos Ethyol Gammaphos NSC 296961 NSC-296961 NSC296961 S-(N-(3-Aminopropyl)-2-aminoethyl)thiophosphoric Schering Plough US Bioscience WR 2721 WR-2721 WR2721 YM 08310 YM-08310 YM08310", "definition": "A phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia.\n    ", "id": "MESH:D004999"}
{"mention": "amifostine", "mention_text": "A Phase II trial of cisplatin plus WR-2721 (amifostine) for metastatic breast carcinoma: an Eastern Cooperative Oncology Group Study (E8188).", "entity": "Amifostine", "aliases": "APAETP Alza Brand of Amifostine Anhydrous Disodium Salt Essex Lilly Monohydrate Monohydrochloride Schering-Plough Trihydrate Aminopropyl Aminoethylthiophosphate Aminopropylaminoethylthiophosphate Aminopropylaminoethylthiophosphoric Acid Ethiofos Ethyol Gammaphos NSC 296961 NSC-296961 NSC296961 S-(N-(3-Aminopropyl)-2-aminoethyl)thiophosphoric Schering Plough US Bioscience WR 2721 WR-2721 WR2721 YM 08310 YM-08310 YM08310", "definition": "A phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia.\n    ", "id": "MESH:D004999"}
{"mention": "breast carcinoma", "mention_text": "A Phase II trial of cisplatin plus WR-2721 (amifostine) for metastatic breast carcinoma: an Eastern Cooperative Oncology Group Study (E8188).", "entity": "Breast Neoplasms", "aliases": "Breast Cancer Carcinoma Neoplasm Neoplasms Tumor Tumors of the Human Mammary Carcinomas Malignant", "definition": "Tumors or cancer of the human BREAST.\n    ", "id": "MESH:D001943"}
{"mention": "Cisplatin", "mention_text": "BACKGROUND: Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60-120 mg/m2 of cisplatin is administered every 3-4 weeks. Although a dose-response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS: A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg/m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg/m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS: Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS: The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial.", "entity": "Cisplatin", "aliases": "Biocisplatinum Cisplatin Diamminodichloride Platinum Dichlorodiammineplatinum NSC-119875 Platidiam Platino Platinol cis Diamminedichloroplatinum cis-Diamminedichloroplatinum cis-Diamminedichloroplatinum(II) cis-Dichlorodiammineplatinum(II) cis-Platinum", "definition": "An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.\n    ", "id": "MESH:D002945"}
{"mention": "breast carcinoma", "mention_text": "BACKGROUND: Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60-120 mg/m2 of cisplatin is administered every 3-4 weeks. Although a dose-response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS: A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg/m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg/m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS: Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS: The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial.", "entity": "Breast Neoplasms", "aliases": "Breast Cancer Carcinoma Neoplasm Neoplasms Tumor Tumors of the Human Mammary Carcinomas Malignant", "definition": "Tumors or cancer of the human BREAST.\n    ", "id": "MESH:D001943"}
{"mention": "cisplatin", "mention_text": "BACKGROUND: Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60-120 mg/m2 of cisplatin is administered every 3-4 weeks. Although a dose-response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS: A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg/m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg/m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS: Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS: The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial.", "entity": "Cisplatin", "aliases": "Biocisplatinum Cisplatin Diamminodichloride Platinum Dichlorodiammineplatinum NSC-119875 Platidiam Platino Platinol cis Diamminedichloroplatinum cis-Diamminedichloroplatinum cis-Diamminedichloroplatinum(II) cis-Dichlorodiammineplatinum(II) cis-Platinum", "definition": "An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.\n    ", "id": "MESH:D002945"}
{"mention": "toxicities", "mention_text": "BACKGROUND: Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60-120 mg/m2 of cisplatin is administered every 3-4 weeks. Although a dose-response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS: A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg/m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg/m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS: Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS: The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "nephrotoxicity", "mention_text": "BACKGROUND: Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60-120 mg/m2 of cisplatin is administered every 3-4 weeks. Although a dose-response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS: A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg/m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg/m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS: Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS: The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "ototoxicity", "mention_text": "BACKGROUND: Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60-120 mg/m2 of cisplatin is administered every 3-4 weeks. Although a dose-response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS: A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg/m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg/m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS: Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS: The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial.", "entity": "Hearing Disorders", "aliases": "Distorted Hearing Dysacusis Disorder Disorders Paracousis Paracusis", "definition": "Conditions that impair the transmission of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways.\n    ", "id": "MESH:D006311"}
{"mention": "neurotoxicity", "mention_text": "BACKGROUND: Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60-120 mg/m2 of cisplatin is administered every 3-4 weeks. Although a dose-response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS: A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg/m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg/m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS: Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS: The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "WR-2721", "mention_text": "BACKGROUND: Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60-120 mg/m2 of cisplatin is administered every 3-4 weeks. Although a dose-response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS: A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg/m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg/m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS: Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS: The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial.", "entity": "Amifostine", "aliases": "APAETP Alza Brand of Amifostine Anhydrous Disodium Salt Essex Lilly Monohydrate Monohydrochloride Schering-Plough Trihydrate Aminopropyl Aminoethylthiophosphate Aminopropylaminoethylthiophosphate Aminopropylaminoethylthiophosphoric Acid Ethiofos Ethyol Gammaphos NSC 296961 NSC-296961 NSC296961 S-(N-(3-Aminopropyl)-2-aminoethyl)thiophosphoric Schering Plough US Bioscience WR 2721 WR-2721 WR2721 YM 08310 YM-08310 YM08310", "definition": "A phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia.\n    ", "id": "MESH:D004999"}
{"mention": "amifostine", "mention_text": "BACKGROUND: Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60-120 mg/m2 of cisplatin is administered every 3-4 weeks. Although a dose-response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS: A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg/m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg/m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS: Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS: The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial.", "entity": "Amifostine", "aliases": "APAETP Alza Brand of Amifostine Anhydrous Disodium Salt Essex Lilly Monohydrate Monohydrochloride Schering-Plough Trihydrate Aminopropyl Aminoethylthiophosphate Aminopropylaminoethylthiophosphate Aminopropylaminoethylthiophosphoric Acid Ethiofos Ethyol Gammaphos NSC 296961 NSC-296961 NSC296961 S-(N-(3-Aminopropyl)-2-aminoethyl)thiophosphoric Schering Plough US Bioscience WR 2721 WR-2721 WR2721 YM 08310 YM-08310 YM08310", "definition": "A phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia.\n    ", "id": "MESH:D004999"}
{"mention": "Amifostine", "mention_text": "BACKGROUND: Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60-120 mg/m2 of cisplatin is administered every 3-4 weeks. Although a dose-response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS: A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg/m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg/m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS: Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS: The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial.", "entity": "Amifostine", "aliases": "APAETP Alza Brand of Amifostine Anhydrous Disodium Salt Essex Lilly Monohydrate Monohydrochloride Schering-Plough Trihydrate Aminopropyl Aminoethylthiophosphate Aminopropylaminoethylthiophosphate Aminopropylaminoethylthiophosphoric Acid Ethiofos Ethyol Gammaphos NSC 296961 NSC-296961 NSC296961 S-(N-(3-Aminopropyl)-2-aminoethyl)thiophosphoric Schering Plough US Bioscience WR 2721 WR-2721 WR2721 YM 08310 YM-08310 YM08310", "definition": "A phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia.\n    ", "id": "MESH:D004999"}
{"mention": "alkylating agents", "mention_text": "BACKGROUND: Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60-120 mg/m2 of cisplatin is administered every 3-4 weeks. Although a dose-response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS: A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg/m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg/m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS: Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS: The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial.", "entity": "Alkylating Agents", "aliases": "Agents Alkylating Alkylators", "definition": "Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases.\n    ", "id": "MESH:D000477"}
{"mention": "neuropathy", "mention_text": "BACKGROUND: Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60-120 mg/m2 of cisplatin is administered every 3-4 weeks. Although a dose-response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS: A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg/m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg/m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS: Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS: The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "mannitol", "mention_text": "BACKGROUND: Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60-120 mg/m2 of cisplatin is administered every 3-4 weeks. Although a dose-response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS: A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg/m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg/m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS: Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS: The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial.", "entity": "Mannitol", "aliases": "(L)-Mannitol Mannitol Osmitrol Osmofundin", "definition": "A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity.\n    ", "id": "MESH:D008353"}
{"mention": "Neurologic toxicity", "mention_text": "BACKGROUND: Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60-120 mg/m2 of cisplatin is administered every 3-4 weeks. Although a dose-response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS: A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg/m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg/m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS: Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS: The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "tumor", "mention_text": "BACKGROUND: Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60-120 mg/m2 of cisplatin is administered every 3-4 weeks. Although a dose-response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS: A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg/m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg/m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS: Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS: The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "toxicity", "mention_text": "BACKGROUND: Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60-120 mg/m2 of cisplatin is administered every 3-4 weeks. Although a dose-response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS: A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg/m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg/m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS: Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS: The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "Warfarin", "mention_text": "Warfarin-induced iliopsoas hemorrhage with subsequent femoral nerve palsy.", "entity": "Warfarin", "aliases": "4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one Aldo Brand of Warfarin Sodium Aldocumar Antigen Apo-Warfarin Apotex Bailly Boots Bristol-Myers Squibb Coumadin Coumadine Estedi Gen-Warfarin Genpharm Goldshield Marevan Potassium Tedicumar Warfant", "definition": "An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.\n    ", "id": "MESH:D014859"}
{"mention": "hemorrhage", "mention_text": "Warfarin-induced iliopsoas hemorrhage with subsequent femoral nerve palsy.", "entity": "Hemorrhage", "aliases": "Bleeding Hemorrhage Hemorrhages", "definition": "Bleeding or escape of blood from a vessel.\n    ", "id": "MESH:D006470"}
{"mention": "femoral nerve palsy", "mention_text": "Warfarin-induced iliopsoas hemorrhage with subsequent femoral nerve palsy.", "entity": "Femoral Neuropathy", "aliases": "Femoral Mononeuropathies Mononeuropathy Nerve Disease Diseases Neuritis Neuropathies Neuropathy", "definition": "Disease involving the femoral nerve. The femoral nerve may be injured by ISCHEMIA (e.g., in association with DIABETIC NEUROPATHIES), nerve compression, trauma, COLLAGEN DISEASES, and other disease processes. Clinical features include MUSCLE WEAKNESS or PARALYSIS of hip flexion and knee extension, ATROPHY of the QUADRICEPS MUSCLE, reduced or absent patellar reflex, and impaired sensation over the anterior and medial thigh.\n    ", "id": "MESH:D020428"}
{"mention": "warfarin", "mention_text": "We present the case of a 28-year-old man on chronic warfarin therapy who sustained a minor muscle tear and developed increasing pain and a flexure contracture of the right hip. Surgical exploration revealed an iliopsoas hematoma and femoral nerve entrapment, resulting in a femoral nerve palsy and partial loss of quadriceps functions. Anticoagulant-induced femoral nerve palsy represents the most common form of warfarin-induced peripheral neuropathy; it is characterized by severe pain in the inguinal region, varying degrees of motor and sensory impairment, and flexure contracture of the involved extremity.", "entity": "Warfarin", "aliases": "4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one Aldo Brand of Warfarin Sodium Aldocumar Antigen Apo-Warfarin Apotex Bailly Boots Bristol-Myers Squibb Coumadin Coumadine Estedi Gen-Warfarin Genpharm Goldshield Marevan Potassium Tedicumar Warfant", "definition": "An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.\n    ", "id": "MESH:D014859"}
{"mention": "muscle tear", "mention_text": "We present the case of a 28-year-old man on chronic warfarin therapy who sustained a minor muscle tear and developed increasing pain and a flexure contracture of the right hip. Surgical exploration revealed an iliopsoas hematoma and femoral nerve entrapment, resulting in a femoral nerve palsy and partial loss of quadriceps functions. Anticoagulant-induced femoral nerve palsy represents the most common form of warfarin-induced peripheral neuropathy; it is characterized by severe pain in the inguinal region, varying degrees of motor and sensory impairment, and flexure contracture of the involved extremity.", "entity": "Muscular Diseases", "aliases": "Muscle Disorder Disorders Muscular Disease Diseases Myopathic Condition Conditions Myopathies Myopathy", "definition": "Acquired, familial, and congenital disorders of SKELETAL MUSCLE and SMOOTH MUSCLE.\n    ", "id": "MESH:D009135"}
{"mention": "pain", "mention_text": "We present the case of a 28-year-old man on chronic warfarin therapy who sustained a minor muscle tear and developed increasing pain and a flexure contracture of the right hip. Surgical exploration revealed an iliopsoas hematoma and femoral nerve entrapment, resulting in a femoral nerve palsy and partial loss of quadriceps functions. Anticoagulant-induced femoral nerve palsy represents the most common form of warfarin-induced peripheral neuropathy; it is characterized by severe pain in the inguinal region, varying degrees of motor and sensory impairment, and flexure contracture of the involved extremity.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "contracture", "mention_text": "We present the case of a 28-year-old man on chronic warfarin therapy who sustained a minor muscle tear and developed increasing pain and a flexure contracture of the right hip. Surgical exploration revealed an iliopsoas hematoma and femoral nerve entrapment, resulting in a femoral nerve palsy and partial loss of quadriceps functions. Anticoagulant-induced femoral nerve palsy represents the most common form of warfarin-induced peripheral neuropathy; it is characterized by severe pain in the inguinal region, varying degrees of motor and sensory impairment, and flexure contracture of the involved extremity.", "entity": "Contracture", "aliases": "Contracture Contractures", "definition": "Prolonged shortening of the muscle or other soft tissue around a joint, preventing movement of the joint.\n    ", "id": "MESH:D003286"}
{"mention": "hematoma", "mention_text": "We present the case of a 28-year-old man on chronic warfarin therapy who sustained a minor muscle tear and developed increasing pain and a flexure contracture of the right hip. Surgical exploration revealed an iliopsoas hematoma and femoral nerve entrapment, resulting in a femoral nerve palsy and partial loss of quadriceps functions. Anticoagulant-induced femoral nerve palsy represents the most common form of warfarin-induced peripheral neuropathy; it is characterized by severe pain in the inguinal region, varying degrees of motor and sensory impairment, and flexure contracture of the involved extremity.", "entity": "Hematoma", "aliases": "Hematoma Hematomas", "definition": "A collection of blood outside the BLOOD VESSELS. Hematoma can be localized in an organ, space, or tissue.\n    ", "id": "MESH:D006406"}
{"mention": "nerve entrapment", "mention_text": "We present the case of a 28-year-old man on chronic warfarin therapy who sustained a minor muscle tear and developed increasing pain and a flexure contracture of the right hip. Surgical exploration revealed an iliopsoas hematoma and femoral nerve entrapment, resulting in a femoral nerve palsy and partial loss of quadriceps functions. Anticoagulant-induced femoral nerve palsy represents the most common form of warfarin-induced peripheral neuropathy; it is characterized by severe pain in the inguinal region, varying degrees of motor and sensory impairment, and flexure contracture of the involved extremity.", "entity": "Nerve Compression Syndromes", "aliases": "Compression Syndrome Nerve Syndromes Entrapment Neuropathies Entrapments External Internal Neuropathy", "definition": "Mechanical compression of nerves or nerve roots from internal or external causes. These may result in a conduction block to nerve impulses (due to MYELIN SHEATH dysfunction) or axonal loss. The nerve and nerve sheath injuries may be caused by ISCHEMIA; INFLAMMATION; or a direct mechanical effect.\n    ", "id": "MESH:D009408"}
{"mention": "femoral nerve palsy", "mention_text": "We present the case of a 28-year-old man on chronic warfarin therapy who sustained a minor muscle tear and developed increasing pain and a flexure contracture of the right hip. Surgical exploration revealed an iliopsoas hematoma and femoral nerve entrapment, resulting in a femoral nerve palsy and partial loss of quadriceps functions. Anticoagulant-induced femoral nerve palsy represents the most common form of warfarin-induced peripheral neuropathy; it is characterized by severe pain in the inguinal region, varying degrees of motor and sensory impairment, and flexure contracture of the involved extremity.", "entity": "Femoral Neuropathy", "aliases": "Femoral Mononeuropathies Mononeuropathy Nerve Disease Diseases Neuritis Neuropathies Neuropathy", "definition": "Disease involving the femoral nerve. The femoral nerve may be injured by ISCHEMIA (e.g., in association with DIABETIC NEUROPATHIES), nerve compression, trauma, COLLAGEN DISEASES, and other disease processes. Clinical features include MUSCLE WEAKNESS or PARALYSIS of hip flexion and knee extension, ATROPHY of the QUADRICEPS MUSCLE, reduced or absent patellar reflex, and impaired sensation over the anterior and medial thigh.\n    ", "id": "MESH:D020428"}
{"mention": "partial loss of quadriceps functions", "mention_text": "We present the case of a 28-year-old man on chronic warfarin therapy who sustained a minor muscle tear and developed increasing pain and a flexure contracture of the right hip. Surgical exploration revealed an iliopsoas hematoma and femoral nerve entrapment, resulting in a femoral nerve palsy and partial loss of quadriceps functions. Anticoagulant-induced femoral nerve palsy represents the most common form of warfarin-induced peripheral neuropathy; it is characterized by severe pain in the inguinal region, varying degrees of motor and sensory impairment, and flexure contracture of the involved extremity.", "entity": "Muscular Diseases", "aliases": "Muscle Disorder Disorders Muscular Disease Diseases Myopathic Condition Conditions Myopathies Myopathy", "definition": "Acquired, familial, and congenital disorders of SKELETAL MUSCLE and SMOOTH MUSCLE.\n    ", "id": "MESH:D009135"}
{"mention": "peripheral neuropathy", "mention_text": "We present the case of a 28-year-old man on chronic warfarin therapy who sustained a minor muscle tear and developed increasing pain and a flexure contracture of the right hip. Surgical exploration revealed an iliopsoas hematoma and femoral nerve entrapment, resulting in a femoral nerve palsy and partial loss of quadriceps functions. Anticoagulant-induced femoral nerve palsy represents the most common form of warfarin-induced peripheral neuropathy; it is characterized by severe pain in the inguinal region, varying degrees of motor and sensory impairment, and flexure contracture of the involved extremity.", "entity": "Peripheral Nervous System Diseases", "aliases": "Nerve Disease Peripheral Diseases Neuropathy PNS (Peripheral Nervous System) System Disorders Neuropathies", "definition": "Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.\n    ", "id": "MESH:D010523"}
{"mention": "motor and sensory impairment", "mention_text": "We present the case of a 28-year-old man on chronic warfarin therapy who sustained a minor muscle tear and developed increasing pain and a flexure contracture of the right hip. Surgical exploration revealed an iliopsoas hematoma and femoral nerve entrapment, resulting in a femoral nerve palsy and partial loss of quadriceps functions. Anticoagulant-induced femoral nerve palsy represents the most common form of warfarin-induced peripheral neuropathy; it is characterized by severe pain in the inguinal region, varying degrees of motor and sensory impairment, and flexure contracture of the involved extremity.", "entity": "Hereditary Sensory and Motor Neuropathy", "aliases": "CMT4f Charcot Marie Tooth Disease Type 3 Charcot-Marie-Tooth Demyelinating 4f Dejerine Sottas Neuropathy Syndrome Dejerine-Sottas Hypertrophic HMSN III IIIs VII VIIs HMSN3 Herditary Sensory and Motor Hereditary Neuropathies of", "definition": "A group of slowly progressive inherited disorders affecting motor and sensory peripheral nerves. Subtypes include HMSNs I-VII. HMSN I and II both refer to CHARCOT-MARIE-TOOTH DISEASE. HMSN III refers to hypertrophic neuropathy of infancy. HMSN IV refers to REFSUM DISEASE. HMSN V refers to a condition marked by a hereditary motor and sensory neuropathy associated with spastic paraplegia (see SPASTIC PARAPLEGIA, HEREDITARY). HMSN VI refers to HMSN associated with an inherited optic atrophy (OPTIC ATROPHIES, HEREDITARY), and HMSN VII refers to HMSN associated with retinitis pigmentosa. (From Adams et al., Principles of Neurology, 6th ed, p1343)\n    ", "id": "MESH:D015417"}
{"mention": "Myasthenia gravis", "mention_text": "Myasthenia gravis caused by penicillamine and chloroquine therapy for rheumatoid arthritis.", "entity": "Myasthenia Gravis", "aliases": "Generalized Myasthenia Gravis Ocular", "definition": "A disorder of neuromuscular transmission characterized by weakness of cranial and skeletal muscles. Autoantibodies directed against acetylcholine receptors damage the motor endplate portion of the NEUROMUSCULAR JUNCTION, impairing the transmission of impulses to skeletal muscles. Clinical manifestations may include diplopia, ptosis, and weakness of facial, bulbar, respiratory, and proximal limb muscles. The disease may remain limited to the ocular muscles. THYMOMA is commonly associated with this condition. (Adams et al., Principles of Neurology, 6th ed, p1459)\n    ", "id": "MESH:D009157"}
{"mention": "penicillamine", "mention_text": "Myasthenia gravis caused by penicillamine and chloroquine therapy for rheumatoid arthritis.", "entity": "Penicillamine", "aliases": "Copper Penicillaminate Cuprenil Cuprimine D 3 Mercaptovaline Penicillamine D-3-Mercaptovaline D-Penicillamine Dimethylcysteine Metalcaptase beta,beta beta,beta-Dimethylcysteine", "definition": "3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease.\n    ", "id": "MESH:D010396"}
{"mention": "chloroquine", "mention_text": "Myasthenia gravis caused by penicillamine and chloroquine therapy for rheumatoid arthritis.", "entity": "Chloroquine", "aliases": "Aralen Arechine Arequin Chingamin Chlorochin Chloroquine Sulfate Sulphate Khingamin Nivaquine", "definition": "The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses.\n    ", "id": "MESH:D002738"}
{"mention": "rheumatoid arthritis", "mention_text": "Myasthenia gravis caused by penicillamine and chloroquine therapy for rheumatoid arthritis.", "entity": "Arthritis, Rheumatoid", "aliases": "Arthritis Rheumatoid", "definition": "A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.\n    ", "id": "MESH:D001172"}
{"mention": "myasthenia gravis", "mention_text": "We have described a unique patient who had reversible and dose-related myasthenia gravis after penicillamine and chloroquine therapy for rheumatoid arthritis. Although acetylcholine receptor antibodies were not detectable, the time course was consistent with an autoimmune process.", "entity": "Myasthenia Gravis", "aliases": "Generalized Myasthenia Gravis Ocular", "definition": "A disorder of neuromuscular transmission characterized by weakness of cranial and skeletal muscles. Autoantibodies directed against acetylcholine receptors damage the motor endplate portion of the NEUROMUSCULAR JUNCTION, impairing the transmission of impulses to skeletal muscles. Clinical manifestations may include diplopia, ptosis, and weakness of facial, bulbar, respiratory, and proximal limb muscles. The disease may remain limited to the ocular muscles. THYMOMA is commonly associated with this condition. (Adams et al., Principles of Neurology, 6th ed, p1459)\n    ", "id": "MESH:D009157"}
{"mention": "penicillamine", "mention_text": "We have described a unique patient who had reversible and dose-related myasthenia gravis after penicillamine and chloroquine therapy for rheumatoid arthritis. Although acetylcholine receptor antibodies were not detectable, the time course was consistent with an autoimmune process.", "entity": "Penicillamine", "aliases": "Copper Penicillaminate Cuprenil Cuprimine D 3 Mercaptovaline Penicillamine D-3-Mercaptovaline D-Penicillamine Dimethylcysteine Metalcaptase beta,beta beta,beta-Dimethylcysteine", "definition": "3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease.\n    ", "id": "MESH:D010396"}
{"mention": "chloroquine", "mention_text": "We have described a unique patient who had reversible and dose-related myasthenia gravis after penicillamine and chloroquine therapy for rheumatoid arthritis. Although acetylcholine receptor antibodies were not detectable, the time course was consistent with an autoimmune process.", "entity": "Chloroquine", "aliases": "Aralen Arechine Arequin Chingamin Chlorochin Chloroquine Sulfate Sulphate Khingamin Nivaquine", "definition": "The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses.\n    ", "id": "MESH:D002738"}
{"mention": "rheumatoid arthritis", "mention_text": "We have described a unique patient who had reversible and dose-related myasthenia gravis after penicillamine and chloroquine therapy for rheumatoid arthritis. Although acetylcholine receptor antibodies were not detectable, the time course was consistent with an autoimmune process.", "entity": "Arthritis, Rheumatoid", "aliases": "Arthritis Rheumatoid", "definition": "A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.\n    ", "id": "MESH:D001172"}
{"mention": "acetylcholine", "mention_text": "We have described a unique patient who had reversible and dose-related myasthenia gravis after penicillamine and chloroquine therapy for rheumatoid arthritis. Although acetylcholine receptor antibodies were not detectable, the time course was consistent with an autoimmune process.", "entity": "Acetylcholine", "aliases": "2-(Acetyloxy)-N,N,N-trimethylethanaminium Acetilcolina Cusi Acetylcholine Bromide Chloride Fluoride Hydroxide Iodide L Tartrate L-Tartrate Perchlorate Picrate (1:1) Sulfate Alcon Brand of Bournonville Bromoacetylcholine Chloroacetylcholine Ciba Vision Iolab Miochol", "definition": "A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.\n    ", "id": "MESH:D000109"}
{"mention": "Nephrotoxicity", "mention_text": "Nephrotoxicity of combined cephalothin-gentamicin regimen.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "cephalothin", "mention_text": "Nephrotoxicity of combined cephalothin-gentamicin regimen.", "entity": "Cephalothin", "aliases": "Cefalotin Cefalotina Normon Sodica Spaly Ceftina Cephalothin Monosodium Salt Sodium Galen Brand of Keflin Lilly Seffin", "definition": "A cephalosporin antibiotic.\n    ", "id": "MESH:D002512"}
{"mention": "gentamicin", "mention_text": "Nephrotoxicity of combined cephalothin-gentamicin regimen.", "entity": "Gentamicins", "aliases": "G Myticin G-Myticin GMyticin Garamycin Gentacycol Gentamicin Sulfate (USP) Gentamicins Gentamycin Gentamycins Gentavet Genticin", "definition": "A complex of closely related aminoglycosides obtained from MICROMONOSPORA purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit PROTEIN BIOSYNTHESIS.\n    ", "id": "MESH:D005839"}
{"mention": "acute tubular necrosis", "mention_text": "Two patients developed acute tubular necrosis, characterized clinically by acute oliguric renal failure, while they were receiving a combination of cephalothin sodium and gentamicin sulfate therapy. Patients who are given this drug regimen should be observed very carefully for early signs of nephrotoxicity. High doses of this antibiotic combination should be avoided especially in elderly patients. Patients with renal insufficiency should not be given this regimen.", "entity": "Kidney Tubular Necrosis, Acute", "aliases": "Acute Kidney Tubular Necrosis Lower Nephron Nephroses Nephrosis", "definition": "Acute kidney failure resulting from destruction of EPITHELIAL CELLS of the KIDNEY TUBULES. It is commonly attributed to exposure to toxic agents or renal ISCHEMIA following severe TRAUMA.\n    ", "id": "MESH:D007683"}
{"mention": "oliguric", "mention_text": "Two patients developed acute tubular necrosis, characterized clinically by acute oliguric renal failure, while they were receiving a combination of cephalothin sodium and gentamicin sulfate therapy. Patients who are given this drug regimen should be observed very carefully for early signs of nephrotoxicity. High doses of this antibiotic combination should be avoided especially in elderly patients. Patients with renal insufficiency should not be given this regimen.", "entity": "Oliguria", "aliases": "Oliguria Oligurias", "definition": "Decreased URINE output that is below the normal range. Oliguria can be defined as urine output of less than or equal to 0.5 or 1 ml/kg/hr depending on the age.\n    ", "id": "MESH:D009846"}
{"mention": "renal failure", "mention_text": "Two patients developed acute tubular necrosis, characterized clinically by acute oliguric renal failure, while they were receiving a combination of cephalothin sodium and gentamicin sulfate therapy. Patients who are given this drug regimen should be observed very carefully for early signs of nephrotoxicity. High doses of this antibiotic combination should be avoided especially in elderly patients. Patients with renal insufficiency should not be given this regimen.", "entity": "Renal Insufficiency", "aliases": "Failure Kidney Renal Failures Insufficiency Insufficiencies", "definition": "Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.\n    ", "id": "MESH:D051437"}
{"mention": "cephalothin sodium", "mention_text": "Two patients developed acute tubular necrosis, characterized clinically by acute oliguric renal failure, while they were receiving a combination of cephalothin sodium and gentamicin sulfate therapy. Patients who are given this drug regimen should be observed very carefully for early signs of nephrotoxicity. High doses of this antibiotic combination should be avoided especially in elderly patients. Patients with renal insufficiency should not be given this regimen.", "entity": "Cephalothin", "aliases": "Cefalotin Cefalotina Normon Sodica Spaly Ceftina Cephalothin Monosodium Salt Sodium Galen Brand of Keflin Lilly Seffin", "definition": "A cephalosporin antibiotic.\n    ", "id": "MESH:D002512"}
{"mention": "gentamicin sulfate", "mention_text": "Two patients developed acute tubular necrosis, characterized clinically by acute oliguric renal failure, while they were receiving a combination of cephalothin sodium and gentamicin sulfate therapy. Patients who are given this drug regimen should be observed very carefully for early signs of nephrotoxicity. High doses of this antibiotic combination should be avoided especially in elderly patients. Patients with renal insufficiency should not be given this regimen.", "entity": "Gentamicins", "aliases": "G Myticin G-Myticin GMyticin Garamycin Gentacycol Gentamicin Sulfate (USP) Gentamicins Gentamycin Gentamycins Gentavet Genticin", "definition": "A complex of closely related aminoglycosides obtained from MICROMONOSPORA purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit PROTEIN BIOSYNTHESIS.\n    ", "id": "MESH:D005839"}
{"mention": "nephrotoxicity", "mention_text": "Two patients developed acute tubular necrosis, characterized clinically by acute oliguric renal failure, while they were receiving a combination of cephalothin sodium and gentamicin sulfate therapy. Patients who are given this drug regimen should be observed very carefully for early signs of nephrotoxicity. High doses of this antibiotic combination should be avoided especially in elderly patients. Patients with renal insufficiency should not be given this regimen.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "renal insufficiency", "mention_text": "Two patients developed acute tubular necrosis, characterized clinically by acute oliguric renal failure, while they were receiving a combination of cephalothin sodium and gentamicin sulfate therapy. Patients who are given this drug regimen should be observed very carefully for early signs of nephrotoxicity. High doses of this antibiotic combination should be avoided especially in elderly patients. Patients with renal insufficiency should not be given this regimen.", "entity": "Renal Insufficiency", "aliases": "Failure Kidney Renal Failures Insufficiency Insufficiencies", "definition": "Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.\n    ", "id": "MESH:D051437"}
{"mention": "dementia", "mention_text": "Components of lemon essential oil attenuate dementia induced by scopolamine.", "entity": "Dementia", "aliases": "Amentia Amentias Dementia Familial Dementias Senile Paranoid", "definition": "An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness.\n    ", "id": "MESH:D003704"}
{"mention": "scopolamine", "mention_text": "Components of lemon essential oil attenuate dementia induced by scopolamine.", "entity": "Scopolamine Hydrobromide", "aliases": "Alcon Brand of Scopolamine Hydrobromide Boro Scopol Boro-Scopol BoroScopol Bull Cooper Hamilton Hope Hyoscine Inibisa Isopto Kwells Novartis Consumer Health Renaudin Roche Scoburen Scopace Scopoderm TTS Transderm Scop V Transderm-V Travacalm HO Vorigeno Winzer Borate", "definition": "An alkaloid from SOLANACEAE, especially DATURA and SCOPOLIA. Scopolamine and its quaternary derivatives act as antimuscarinics like ATROPINE, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in URINARY INCONTINENCE, in MOTION SICKNESS, as an antispasmodic, and as a mydriatic and cycloplegic.\n    ", "id": "MESH:D012601"}
{"mention": "dementia", "mention_text": "The anti-dementia effects of s-limonene and s-perillyl alcohol were observed using the passive avoidance test (PA) and the open field habituation test (OFH). These lemon essential oils showed strong ability to improve memory impaired by scopolamine; however, s-perillyl alcohol relieved the deficit of associative memory in PA only, and did not improve non-associative memory significantly in OFH. Analysis of neurotransmitter concentration in some brain regions on the test day showed that dopamine concentration of the vehicle/scopolamine group was significantly lower than that of the vehicle/vehicle group, but this phenomenon was reversed when s-limonene or s-perillyl alcohol were administered before the injection of scopolamine. Simultaneously, we found that these two lemon essential oil components could inhibit acetylcholinesterase activity in vitro using the Ellman method.", "entity": "Dementia", "aliases": "Amentia Amentias Dementia Familial Dementias Senile Paranoid", "definition": "An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness.\n    ", "id": "MESH:D003704"}
{"mention": "s-limonene", "mention_text": "The anti-dementia effects of s-limonene and s-perillyl alcohol were observed using the passive avoidance test (PA) and the open field habituation test (OFH). These lemon essential oils showed strong ability to improve memory impaired by scopolamine; however, s-perillyl alcohol relieved the deficit of associative memory in PA only, and did not improve non-associative memory significantly in OFH. Analysis of neurotransmitter concentration in some brain regions on the test day showed that dopamine concentration of the vehicle/scopolamine group was significantly lower than that of the vehicle/vehicle group, but this phenomenon was reversed when s-limonene or s-perillyl alcohol were administered before the injection of scopolamine. Simultaneously, we found that these two lemon essential oil components could inhibit acetylcholinesterase activity in vitro using the Ellman method.", "entity": "limonene", "aliases": "(+)-limonene (-)-limonene (4S)-1-methyl-4-isopropenylcyclohex-1-ene (D)-limonene 1-methyl-4-(1-methylethenyl)cyclohexene 4-mentha-1,8-diene AISA 5203-L (+)limonene d-limonene dipentene limonene (+-)-isomer (R)-isomer (S)-isomer", "definition": "", "id": "MESH:C008281"}
{"mention": "s-perillyl alcohol", "mention_text": "The anti-dementia effects of s-limonene and s-perillyl alcohol were observed using the passive avoidance test (PA) and the open field habituation test (OFH). These lemon essential oils showed strong ability to improve memory impaired by scopolamine; however, s-perillyl alcohol relieved the deficit of associative memory in PA only, and did not improve non-associative memory significantly in OFH. Analysis of neurotransmitter concentration in some brain regions on the test day showed that dopamine concentration of the vehicle/scopolamine group was significantly lower than that of the vehicle/vehicle group, but this phenomenon was reversed when s-limonene or s-perillyl alcohol were administered before the injection of scopolamine. Simultaneously, we found that these two lemon essential oil components could inhibit acetylcholinesterase activity in vitro using the Ellman method.", "entity": "perilla alcohol", "aliases": "4-isopropenyl-cyclohex-1-ene-1-methanol NSC 641066 cyclohex-1-ene-1-methanol 4(1-methylethenyl) dihydrocuminyl alcohol p-mentha-1,8-dien-7-ol perilla (R)-isomer (S)-isomer perillyl", "definition": "", "id": "MESH:C032208"}
{"mention": "memory impaired", "mention_text": "The anti-dementia effects of s-limonene and s-perillyl alcohol were observed using the passive avoidance test (PA) and the open field habituation test (OFH). These lemon essential oils showed strong ability to improve memory impaired by scopolamine; however, s-perillyl alcohol relieved the deficit of associative memory in PA only, and did not improve non-associative memory significantly in OFH. Analysis of neurotransmitter concentration in some brain regions on the test day showed that dopamine concentration of the vehicle/scopolamine group was significantly lower than that of the vehicle/vehicle group, but this phenomenon was reversed when s-limonene or s-perillyl alcohol were administered before the injection of scopolamine. Simultaneously, we found that these two lemon essential oil components could inhibit acetylcholinesterase activity in vitro using the Ellman method.", "entity": "Memory Disorders", "aliases": "Age Related Memory Disorders Age-Related Disorder Cognitive Retention Deficit Deficits Semantic Spatial Loss Losses", "definition": "Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions.\n    ", "id": "MESH:D008569"}
{"mention": "scopolamine", "mention_text": "The anti-dementia effects of s-limonene and s-perillyl alcohol were observed using the passive avoidance test (PA) and the open field habituation test (OFH). These lemon essential oils showed strong ability to improve memory impaired by scopolamine; however, s-perillyl alcohol relieved the deficit of associative memory in PA only, and did not improve non-associative memory significantly in OFH. Analysis of neurotransmitter concentration in some brain regions on the test day showed that dopamine concentration of the vehicle/scopolamine group was significantly lower than that of the vehicle/vehicle group, but this phenomenon was reversed when s-limonene or s-perillyl alcohol were administered before the injection of scopolamine. Simultaneously, we found that these two lemon essential oil components could inhibit acetylcholinesterase activity in vitro using the Ellman method.", "entity": "Scopolamine Hydrobromide", "aliases": "Alcon Brand of Scopolamine Hydrobromide Boro Scopol Boro-Scopol BoroScopol Bull Cooper Hamilton Hope Hyoscine Inibisa Isopto Kwells Novartis Consumer Health Renaudin Roche Scoburen Scopace Scopoderm TTS Transderm Scop V Transderm-V Travacalm HO Vorigeno Winzer Borate", "definition": "An alkaloid from SOLANACEAE, especially DATURA and SCOPOLIA. Scopolamine and its quaternary derivatives act as antimuscarinics like ATROPINE, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in URINARY INCONTINENCE, in MOTION SICKNESS, as an antispasmodic, and as a mydriatic and cycloplegic.\n    ", "id": "MESH:D012601"}
{"mention": "deficit of associative memory", "mention_text": "The anti-dementia effects of s-limonene and s-perillyl alcohol were observed using the passive avoidance test (PA) and the open field habituation test (OFH). These lemon essential oils showed strong ability to improve memory impaired by scopolamine; however, s-perillyl alcohol relieved the deficit of associative memory in PA only, and did not improve non-associative memory significantly in OFH. Analysis of neurotransmitter concentration in some brain regions on the test day showed that dopamine concentration of the vehicle/scopolamine group was significantly lower than that of the vehicle/vehicle group, but this phenomenon was reversed when s-limonene or s-perillyl alcohol were administered before the injection of scopolamine. Simultaneously, we found that these two lemon essential oil components could inhibit acetylcholinesterase activity in vitro using the Ellman method.", "entity": "Memory Disorders", "aliases": "Age Related Memory Disorders Age-Related Disorder Cognitive Retention Deficit Deficits Semantic Spatial Loss Losses", "definition": "Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions.\n    ", "id": "MESH:D008569"}
{"mention": "dopamine", "mention_text": "The anti-dementia effects of s-limonene and s-perillyl alcohol were observed using the passive avoidance test (PA) and the open field habituation test (OFH). These lemon essential oils showed strong ability to improve memory impaired by scopolamine; however, s-perillyl alcohol relieved the deficit of associative memory in PA only, and did not improve non-associative memory significantly in OFH. Analysis of neurotransmitter concentration in some brain regions on the test day showed that dopamine concentration of the vehicle/scopolamine group was significantly lower than that of the vehicle/vehicle group, but this phenomenon was reversed when s-limonene or s-perillyl alcohol were administered before the injection of scopolamine. Simultaneously, we found that these two lemon essential oil components could inhibit acetylcholinesterase activity in vitro using the Ellman method.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "Ro4368554", "mention_text": "The selective 5-HT6 receptor antagonist Ro4368554 restores memory performance in cholinergic and serotonergic models of memory deficiency in the rat.", "entity": "Ro4368554", "aliases": "3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole Ro4368554", "definition": "", "id": "MESH:C507242"}
{"mention": "memory deficiency", "mention_text": "The selective 5-HT6 receptor antagonist Ro4368554 restores memory performance in cholinergic and serotonergic models of memory deficiency in the rat.", "entity": "Memory Disorders", "aliases": "Age Related Memory Disorders Age-Related Disorder Cognitive Retention Deficit Deficits Semantic Spatial Loss Losses", "definition": "Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions.\n    ", "id": "MESH:D008569"}
{"mention": "serotonin", "mention_text": "Antagonists at serotonin type 6 (5-HT(6)) receptors show activity in models of learning and memory. Although the underlying mechanism(s) are not well understood, these effects may involve an increase in acetylcholine (ACh) levels. The present study sought to characterize the cognitive-enhancing effects of the 5-HT(6) antagonist Ro4368554 (3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole) in a rat object recognition task employing a cholinergic (scopolamine pretreatment) and a serotonergic- (tryptophan (TRP) depletion) deficient model, and compared its pattern of action with that of the acetylcholinesterase inhibitor metrifonate. Initial testing in a time-dependent forgetting task employing a 24-h delay between training and testing showed that metrifonate improved object recognition (at 10 and 30 mg/kg, p.o.), whereas Ro4368554 was inactive. Both, Ro4368554 (3 and 10 mg/kg, intraperitoneally (i.p.)) and metrifonate (10 mg/kg, p.o., respectively) reversed memory deficits induced by scopolamine and TRP depletion (10 mg/kg, i.p., and 3 mg/kg, p.o., respectively). In conclusion, although Ro4368554 did not improve a time-related retention deficit, it reversed a cholinergic and a serotonergic memory deficit, suggesting that both mechanisms may be involved in the facilitation of object memory by Ro4368554 and, possibly, other 5-HT(6) receptor antagonists.", "entity": "Serotonin", "aliases": "3-(2-Aminoethyl)-1H-indol-5-ol 5 Hydroxytryptamine 5-HT 5-Hydroxytryptamine Enteramine Hippophaine Serotonin", "definition": "A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.\n    ", "id": "MESH:D012701"}
{"mention": "5-HT", "mention_text": "Antagonists at serotonin type 6 (5-HT(6)) receptors show activity in models of learning and memory. Although the underlying mechanism(s) are not well understood, these effects may involve an increase in acetylcholine (ACh) levels. The present study sought to characterize the cognitive-enhancing effects of the 5-HT(6) antagonist Ro4368554 (3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole) in a rat object recognition task employing a cholinergic (scopolamine pretreatment) and a serotonergic- (tryptophan (TRP) depletion) deficient model, and compared its pattern of action with that of the acetylcholinesterase inhibitor metrifonate. Initial testing in a time-dependent forgetting task employing a 24-h delay between training and testing showed that metrifonate improved object recognition (at 10 and 30 mg/kg, p.o.), whereas Ro4368554 was inactive. Both, Ro4368554 (3 and 10 mg/kg, intraperitoneally (i.p.)) and metrifonate (10 mg/kg, p.o., respectively) reversed memory deficits induced by scopolamine and TRP depletion (10 mg/kg, i.p., and 3 mg/kg, p.o., respectively). In conclusion, although Ro4368554 did not improve a time-related retention deficit, it reversed a cholinergic and a serotonergic memory deficit, suggesting that both mechanisms may be involved in the facilitation of object memory by Ro4368554 and, possibly, other 5-HT(6) receptor antagonists.", "entity": "Serotonin", "aliases": "3-(2-Aminoethyl)-1H-indol-5-ol 5 Hydroxytryptamine 5-HT 5-Hydroxytryptamine Enteramine Hippophaine Serotonin", "definition": "A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.\n    ", "id": "MESH:D012701"}
{"mention": "acetylcholine", "mention_text": "Antagonists at serotonin type 6 (5-HT(6)) receptors show activity in models of learning and memory. Although the underlying mechanism(s) are not well understood, these effects may involve an increase in acetylcholine (ACh) levels. The present study sought to characterize the cognitive-enhancing effects of the 5-HT(6) antagonist Ro4368554 (3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole) in a rat object recognition task employing a cholinergic (scopolamine pretreatment) and a serotonergic- (tryptophan (TRP) depletion) deficient model, and compared its pattern of action with that of the acetylcholinesterase inhibitor metrifonate. Initial testing in a time-dependent forgetting task employing a 24-h delay between training and testing showed that metrifonate improved object recognition (at 10 and 30 mg/kg, p.o.), whereas Ro4368554 was inactive. Both, Ro4368554 (3 and 10 mg/kg, intraperitoneally (i.p.)) and metrifonate (10 mg/kg, p.o., respectively) reversed memory deficits induced by scopolamine and TRP depletion (10 mg/kg, i.p., and 3 mg/kg, p.o., respectively). In conclusion, although Ro4368554 did not improve a time-related retention deficit, it reversed a cholinergic and a serotonergic memory deficit, suggesting that both mechanisms may be involved in the facilitation of object memory by Ro4368554 and, possibly, other 5-HT(6) receptor antagonists.", "entity": "Acetylcholine", "aliases": "2-(Acetyloxy)-N,N,N-trimethylethanaminium Acetilcolina Cusi Acetylcholine Bromide Chloride Fluoride Hydroxide Iodide L Tartrate L-Tartrate Perchlorate Picrate (1:1) Sulfate Alcon Brand of Bournonville Bromoacetylcholine Chloroacetylcholine Ciba Vision Iolab Miochol", "definition": "A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.\n    ", "id": "MESH:D000109"}
{"mention": "ACh", "mention_text": "Antagonists at serotonin type 6 (5-HT(6)) receptors show activity in models of learning and memory. Although the underlying mechanism(s) are not well understood, these effects may involve an increase in acetylcholine (ACh) levels. The present study sought to characterize the cognitive-enhancing effects of the 5-HT(6) antagonist Ro4368554 (3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole) in a rat object recognition task employing a cholinergic (scopolamine pretreatment) and a serotonergic- (tryptophan (TRP) depletion) deficient model, and compared its pattern of action with that of the acetylcholinesterase inhibitor metrifonate. Initial testing in a time-dependent forgetting task employing a 24-h delay between training and testing showed that metrifonate improved object recognition (at 10 and 30 mg/kg, p.o.), whereas Ro4368554 was inactive. Both, Ro4368554 (3 and 10 mg/kg, intraperitoneally (i.p.)) and metrifonate (10 mg/kg, p.o., respectively) reversed memory deficits induced by scopolamine and TRP depletion (10 mg/kg, i.p., and 3 mg/kg, p.o., respectively). In conclusion, although Ro4368554 did not improve a time-related retention deficit, it reversed a cholinergic and a serotonergic memory deficit, suggesting that both mechanisms may be involved in the facilitation of object memory by Ro4368554 and, possibly, other 5-HT(6) receptor antagonists.", "entity": "Acetylcholine", "aliases": "2-(Acetyloxy)-N,N,N-trimethylethanaminium Acetilcolina Cusi Acetylcholine Bromide Chloride Fluoride Hydroxide Iodide L Tartrate L-Tartrate Perchlorate Picrate (1:1) Sulfate Alcon Brand of Bournonville Bromoacetylcholine Chloroacetylcholine Ciba Vision Iolab Miochol", "definition": "A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.\n    ", "id": "MESH:D000109"}
{"mention": "Ro4368554", "mention_text": "Antagonists at serotonin type 6 (5-HT(6)) receptors show activity in models of learning and memory. Although the underlying mechanism(s) are not well understood, these effects may involve an increase in acetylcholine (ACh) levels. The present study sought to characterize the cognitive-enhancing effects of the 5-HT(6) antagonist Ro4368554 (3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole) in a rat object recognition task employing a cholinergic (scopolamine pretreatment) and a serotonergic- (tryptophan (TRP) depletion) deficient model, and compared its pattern of action with that of the acetylcholinesterase inhibitor metrifonate. Initial testing in a time-dependent forgetting task employing a 24-h delay between training and testing showed that metrifonate improved object recognition (at 10 and 30 mg/kg, p.o.), whereas Ro4368554 was inactive. Both, Ro4368554 (3 and 10 mg/kg, intraperitoneally (i.p.)) and metrifonate (10 mg/kg, p.o., respectively) reversed memory deficits induced by scopolamine and TRP depletion (10 mg/kg, i.p., and 3 mg/kg, p.o., respectively). In conclusion, although Ro4368554 did not improve a time-related retention deficit, it reversed a cholinergic and a serotonergic memory deficit, suggesting that both mechanisms may be involved in the facilitation of object memory by Ro4368554 and, possibly, other 5-HT(6) receptor antagonists.", "entity": "Ro4368554", "aliases": "3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole Ro4368554", "definition": "", "id": "MESH:C507242"}
{"mention": "3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole", "mention_text": "Antagonists at serotonin type 6 (5-HT(6)) receptors show activity in models of learning and memory. Although the underlying mechanism(s) are not well understood, these effects may involve an increase in acetylcholine (ACh) levels. The present study sought to characterize the cognitive-enhancing effects of the 5-HT(6) antagonist Ro4368554 (3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole) in a rat object recognition task employing a cholinergic (scopolamine pretreatment) and a serotonergic- (tryptophan (TRP) depletion) deficient model, and compared its pattern of action with that of the acetylcholinesterase inhibitor metrifonate. Initial testing in a time-dependent forgetting task employing a 24-h delay between training and testing showed that metrifonate improved object recognition (at 10 and 30 mg/kg, p.o.), whereas Ro4368554 was inactive. Both, Ro4368554 (3 and 10 mg/kg, intraperitoneally (i.p.)) and metrifonate (10 mg/kg, p.o., respectively) reversed memory deficits induced by scopolamine and TRP depletion (10 mg/kg, i.p., and 3 mg/kg, p.o., respectively). In conclusion, although Ro4368554 did not improve a time-related retention deficit, it reversed a cholinergic and a serotonergic memory deficit, suggesting that both mechanisms may be involved in the facilitation of object memory by Ro4368554 and, possibly, other 5-HT(6) receptor antagonists.", "entity": "Ro4368554", "aliases": "3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole Ro4368554", "definition": "", "id": "MESH:C507242"}
{"mention": "scopolamine", "mention_text": "Antagonists at serotonin type 6 (5-HT(6)) receptors show activity in models of learning and memory. Although the underlying mechanism(s) are not well understood, these effects may involve an increase in acetylcholine (ACh) levels. The present study sought to characterize the cognitive-enhancing effects of the 5-HT(6) antagonist Ro4368554 (3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole) in a rat object recognition task employing a cholinergic (scopolamine pretreatment) and a serotonergic- (tryptophan (TRP) depletion) deficient model, and compared its pattern of action with that of the acetylcholinesterase inhibitor metrifonate. Initial testing in a time-dependent forgetting task employing a 24-h delay between training and testing showed that metrifonate improved object recognition (at 10 and 30 mg/kg, p.o.), whereas Ro4368554 was inactive. Both, Ro4368554 (3 and 10 mg/kg, intraperitoneally (i.p.)) and metrifonate (10 mg/kg, p.o., respectively) reversed memory deficits induced by scopolamine and TRP depletion (10 mg/kg, i.p., and 3 mg/kg, p.o., respectively). In conclusion, although Ro4368554 did not improve a time-related retention deficit, it reversed a cholinergic and a serotonergic memory deficit, suggesting that both mechanisms may be involved in the facilitation of object memory by Ro4368554 and, possibly, other 5-HT(6) receptor antagonists.", "entity": "Scopolamine Hydrobromide", "aliases": "Alcon Brand of Scopolamine Hydrobromide Boro Scopol Boro-Scopol BoroScopol Bull Cooper Hamilton Hope Hyoscine Inibisa Isopto Kwells Novartis Consumer Health Renaudin Roche Scoburen Scopace Scopoderm TTS Transderm Scop V Transderm-V Travacalm HO Vorigeno Winzer Borate", "definition": "An alkaloid from SOLANACEAE, especially DATURA and SCOPOLIA. Scopolamine and its quaternary derivatives act as antimuscarinics like ATROPINE, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in URINARY INCONTINENCE, in MOTION SICKNESS, as an antispasmodic, and as a mydriatic and cycloplegic.\n    ", "id": "MESH:D012601"}
{"mention": "tryptophan", "mention_text": "Antagonists at serotonin type 6 (5-HT(6)) receptors show activity in models of learning and memory. Although the underlying mechanism(s) are not well understood, these effects may involve an increase in acetylcholine (ACh) levels. The present study sought to characterize the cognitive-enhancing effects of the 5-HT(6) antagonist Ro4368554 (3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole) in a rat object recognition task employing a cholinergic (scopolamine pretreatment) and a serotonergic- (tryptophan (TRP) depletion) deficient model, and compared its pattern of action with that of the acetylcholinesterase inhibitor metrifonate. Initial testing in a time-dependent forgetting task employing a 24-h delay between training and testing showed that metrifonate improved object recognition (at 10 and 30 mg/kg, p.o.), whereas Ro4368554 was inactive. Both, Ro4368554 (3 and 10 mg/kg, intraperitoneally (i.p.)) and metrifonate (10 mg/kg, p.o., respectively) reversed memory deficits induced by scopolamine and TRP depletion (10 mg/kg, i.p., and 3 mg/kg, p.o., respectively). In conclusion, although Ro4368554 did not improve a time-related retention deficit, it reversed a cholinergic and a serotonergic memory deficit, suggesting that both mechanisms may be involved in the facilitation of object memory by Ro4368554 and, possibly, other 5-HT(6) receptor antagonists.", "entity": "Tryptophan", "aliases": "Ardeydorm Ardeypharm Brand of Tryptophan Ardeytropin ICN Kalma L ratiopharm L-Tryptophan L-Tryptophan-ratiopharm Levotryptophan Lyphan Merck Naturruhe Niddapharm Optimax PMS PMS-Tryptophan Pharmascience Ratiopharm Trofan Tryptacin Tryptan Metabolism Alterations Upsher-Smith esparma ratio ratio-Tryptophan", "definition": "An essential amino acid that is necessary for normal growth in infants and for NITROGEN balance in adults. It is a precursor of INDOLE ALKALOIDS in plants. It is a precursor of SEROTONIN (hence its use as an antidepressant and sleep aid). It can be a precursor to NIACIN, albeit inefficiently, in mammals.\n    ", "id": "MESH:D014364"}
{"mention": "TRP", "mention_text": "Antagonists at serotonin type 6 (5-HT(6)) receptors show activity in models of learning and memory. Although the underlying mechanism(s) are not well understood, these effects may involve an increase in acetylcholine (ACh) levels. The present study sought to characterize the cognitive-enhancing effects of the 5-HT(6) antagonist Ro4368554 (3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole) in a rat object recognition task employing a cholinergic (scopolamine pretreatment) and a serotonergic- (tryptophan (TRP) depletion) deficient model, and compared its pattern of action with that of the acetylcholinesterase inhibitor metrifonate. Initial testing in a time-dependent forgetting task employing a 24-h delay between training and testing showed that metrifonate improved object recognition (at 10 and 30 mg/kg, p.o.), whereas Ro4368554 was inactive. Both, Ro4368554 (3 and 10 mg/kg, intraperitoneally (i.p.)) and metrifonate (10 mg/kg, p.o., respectively) reversed memory deficits induced by scopolamine and TRP depletion (10 mg/kg, i.p., and 3 mg/kg, p.o., respectively). In conclusion, although Ro4368554 did not improve a time-related retention deficit, it reversed a cholinergic and a serotonergic memory deficit, suggesting that both mechanisms may be involved in the facilitation of object memory by Ro4368554 and, possibly, other 5-HT(6) receptor antagonists.", "entity": "Tryptophan", "aliases": "Ardeydorm Ardeypharm Brand of Tryptophan Ardeytropin ICN Kalma L ratiopharm L-Tryptophan L-Tryptophan-ratiopharm Levotryptophan Lyphan Merck Naturruhe Niddapharm Optimax PMS PMS-Tryptophan Pharmascience Ratiopharm Trofan Tryptacin Tryptan Metabolism Alterations Upsher-Smith esparma ratio ratio-Tryptophan", "definition": "An essential amino acid that is necessary for normal growth in infants and for NITROGEN balance in adults. It is a precursor of INDOLE ALKALOIDS in plants. It is a precursor of SEROTONIN (hence its use as an antidepressant and sleep aid). It can be a precursor to NIACIN, albeit inefficiently, in mammals.\n    ", "id": "MESH:D014364"}
{"mention": "metrifonate", "mention_text": "Antagonists at serotonin type 6 (5-HT(6)) receptors show activity in models of learning and memory. Although the underlying mechanism(s) are not well understood, these effects may involve an increase in acetylcholine (ACh) levels. The present study sought to characterize the cognitive-enhancing effects of the 5-HT(6) antagonist Ro4368554 (3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole) in a rat object recognition task employing a cholinergic (scopolamine pretreatment) and a serotonergic- (tryptophan (TRP) depletion) deficient model, and compared its pattern of action with that of the acetylcholinesterase inhibitor metrifonate. Initial testing in a time-dependent forgetting task employing a 24-h delay between training and testing showed that metrifonate improved object recognition (at 10 and 30 mg/kg, p.o.), whereas Ro4368554 was inactive. Both, Ro4368554 (3 and 10 mg/kg, intraperitoneally (i.p.)) and metrifonate (10 mg/kg, p.o., respectively) reversed memory deficits induced by scopolamine and TRP depletion (10 mg/kg, i.p., and 3 mg/kg, p.o., respectively). In conclusion, although Ro4368554 did not improve a time-related retention deficit, it reversed a cholinergic and a serotonergic memory deficit, suggesting that both mechanisms may be involved in the facilitation of object memory by Ro4368554 and, possibly, other 5-HT(6) receptor antagonists.", "entity": "Trichlorfon", "aliases": "Bilarcil Chlorofos Chlorophos Dipterex Dylox Foschlor Metrifonate Metriphonate Neguvon Ricifon Trichlorfon Trichlorphon", "definition": "An organochlorophosphate cholinesterase inhibitor that is used as an insecticide for the control of flies and roaches. It is also used in anthelmintic compositions for animals. (From Merck, 11th ed)\n    ", "id": "MESH:D014236"}
{"mention": "memory deficits", "mention_text": "Antagonists at serotonin type 6 (5-HT(6)) receptors show activity in models of learning and memory. Although the underlying mechanism(s) are not well understood, these effects may involve an increase in acetylcholine (ACh) levels. The present study sought to characterize the cognitive-enhancing effects of the 5-HT(6) antagonist Ro4368554 (3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole) in a rat object recognition task employing a cholinergic (scopolamine pretreatment) and a serotonergic- (tryptophan (TRP) depletion) deficient model, and compared its pattern of action with that of the acetylcholinesterase inhibitor metrifonate. Initial testing in a time-dependent forgetting task employing a 24-h delay between training and testing showed that metrifonate improved object recognition (at 10 and 30 mg/kg, p.o.), whereas Ro4368554 was inactive. Both, Ro4368554 (3 and 10 mg/kg, intraperitoneally (i.p.)) and metrifonate (10 mg/kg, p.o., respectively) reversed memory deficits induced by scopolamine and TRP depletion (10 mg/kg, i.p., and 3 mg/kg, p.o., respectively). In conclusion, although Ro4368554 did not improve a time-related retention deficit, it reversed a cholinergic and a serotonergic memory deficit, suggesting that both mechanisms may be involved in the facilitation of object memory by Ro4368554 and, possibly, other 5-HT(6) receptor antagonists.", "entity": "Memory Disorders", "aliases": "Age Related Memory Disorders Age-Related Disorder Cognitive Retention Deficit Deficits Semantic Spatial Loss Losses", "definition": "Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions.\n    ", "id": "MESH:D008569"}
{"mention": "memory deficit", "mention_text": "Antagonists at serotonin type 6 (5-HT(6)) receptors show activity in models of learning and memory. Although the underlying mechanism(s) are not well understood, these effects may involve an increase in acetylcholine (ACh) levels. The present study sought to characterize the cognitive-enhancing effects of the 5-HT(6) antagonist Ro4368554 (3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole) in a rat object recognition task employing a cholinergic (scopolamine pretreatment) and a serotonergic- (tryptophan (TRP) depletion) deficient model, and compared its pattern of action with that of the acetylcholinesterase inhibitor metrifonate. Initial testing in a time-dependent forgetting task employing a 24-h delay between training and testing showed that metrifonate improved object recognition (at 10 and 30 mg/kg, p.o.), whereas Ro4368554 was inactive. Both, Ro4368554 (3 and 10 mg/kg, intraperitoneally (i.p.)) and metrifonate (10 mg/kg, p.o., respectively) reversed memory deficits induced by scopolamine and TRP depletion (10 mg/kg, i.p., and 3 mg/kg, p.o., respectively). In conclusion, although Ro4368554 did not improve a time-related retention deficit, it reversed a cholinergic and a serotonergic memory deficit, suggesting that both mechanisms may be involved in the facilitation of object memory by Ro4368554 and, possibly, other 5-HT(6) receptor antagonists.", "entity": "Memory Disorders", "aliases": "Age Related Memory Disorders Age-Related Disorder Cognitive Retention Deficit Deficits Semantic Spatial Loss Losses", "definition": "Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions.\n    ", "id": "MESH:D008569"}
{"mention": "atrial fibrillation", "mention_text": "Lone atrial fibrillation associated with creatine monohydrate supplementation.", "entity": "Atrial Fibrillation", "aliases": "Atrial Fibrillation Fibrillations Auricular Familial", "definition": "Abnormal cardiac rhythm that is characterized by rapid, uncoordinated firing of electrical impulses in the upper chambers of the heart (HEART ATRIA). In such case, blood cannot be effectively pumped into the lower chambers of the heart (HEART VENTRICLES). It is caused by abnormal impulse generation.\n    ", "id": "MESH:D001281"}
{"mention": "creatine", "mention_text": "Lone atrial fibrillation associated with creatine monohydrate supplementation.", "entity": "Creatine", "aliases": "Creatine", "definition": "An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as CREATININE in the urine.\n    ", "id": "MESH:D003401"}
{"mention": "Atrial fibrillation", "mention_text": "Atrial fibrillation in young patients without structural heart disease is rare. Therefore, when the arrhythmia is present in this population, reversible causes must be identified and resolved. Thyroid disorders, illicit drug or stimulant use, and acute alcohol intoxication are among these causes. We report the case of a 30-year-old Caucasian man who came to the emergency department in atrial fibrillation with rapid ventricular response. His medical history was unremarkable, except for minor fractures of the fingers and foot. Thyroid-stimulating hormone, magnesium, and potassium levels were within normal limits, urine drug screen was negative, and alcohol use was denied. However, when the patient was questioned about use of herbal products and supplements, the use of creatine monohydrate was revealed. The patient was admitted to the hospital, anticoagulated with unfractionated heparin, and given intravenous diltiazem for rate control and intravenous amiodarone for rate and rhythm control. When discharged less than 24 hours later, he was receiving metoprolol and aspirin, with follow-up plans for echocardiography and nuclear imaging to assess perfusion. Exogenous creatine is used by athletes to theoretically improve exercise performance. Vegetarians may also take creatine to replace what they are not consuming from meat, fish, and other animal products. Previous anecdotal reports have linked creatine to the development of arrhythmia. Clinicians must be diligent when interviewing patients about their drug therapy histories and include questions about their use of herbal products and dietary supplements. In addition, it is important to report adverse effects associated with frequently consumed supplements and herbal products to the Food and Drug Administration and in the literature.", "entity": "Atrial Fibrillation", "aliases": "Atrial Fibrillation Fibrillations Auricular Familial", "definition": "Abnormal cardiac rhythm that is characterized by rapid, uncoordinated firing of electrical impulses in the upper chambers of the heart (HEART ATRIA). In such case, blood cannot be effectively pumped into the lower chambers of the heart (HEART VENTRICLES). It is caused by abnormal impulse generation.\n    ", "id": "MESH:D001281"}
{"mention": "heart disease", "mention_text": "Atrial fibrillation in young patients without structural heart disease is rare. Therefore, when the arrhythmia is present in this population, reversible causes must be identified and resolved. Thyroid disorders, illicit drug or stimulant use, and acute alcohol intoxication are among these causes. We report the case of a 30-year-old Caucasian man who came to the emergency department in atrial fibrillation with rapid ventricular response. His medical history was unremarkable, except for minor fractures of the fingers and foot. Thyroid-stimulating hormone, magnesium, and potassium levels were within normal limits, urine drug screen was negative, and alcohol use was denied. However, when the patient was questioned about use of herbal products and supplements, the use of creatine monohydrate was revealed. The patient was admitted to the hospital, anticoagulated with unfractionated heparin, and given intravenous diltiazem for rate control and intravenous amiodarone for rate and rhythm control. When discharged less than 24 hours later, he was receiving metoprolol and aspirin, with follow-up plans for echocardiography and nuclear imaging to assess perfusion. Exogenous creatine is used by athletes to theoretically improve exercise performance. Vegetarians may also take creatine to replace what they are not consuming from meat, fish, and other animal products. Previous anecdotal reports have linked creatine to the development of arrhythmia. Clinicians must be diligent when interviewing patients about their drug therapy histories and include questions about their use of herbal products and dietary supplements. In addition, it is important to report adverse effects associated with frequently consumed supplements and herbal products to the Food and Drug Administration and in the literature.", "entity": "Heart Diseases", "aliases": "Cardiac Disease Diseases Heart", "definition": "Pathological conditions involving the HEART including its structural and functional abnormalities.\n    ", "id": "MESH:D006331"}
{"mention": "arrhythmia", "mention_text": "Atrial fibrillation in young patients without structural heart disease is rare. Therefore, when the arrhythmia is present in this population, reversible causes must be identified and resolved. Thyroid disorders, illicit drug or stimulant use, and acute alcohol intoxication are among these causes. We report the case of a 30-year-old Caucasian man who came to the emergency department in atrial fibrillation with rapid ventricular response. His medical history was unremarkable, except for minor fractures of the fingers and foot. Thyroid-stimulating hormone, magnesium, and potassium levels were within normal limits, urine drug screen was negative, and alcohol use was denied. However, when the patient was questioned about use of herbal products and supplements, the use of creatine monohydrate was revealed. The patient was admitted to the hospital, anticoagulated with unfractionated heparin, and given intravenous diltiazem for rate control and intravenous amiodarone for rate and rhythm control. When discharged less than 24 hours later, he was receiving metoprolol and aspirin, with follow-up plans for echocardiography and nuclear imaging to assess perfusion. Exogenous creatine is used by athletes to theoretically improve exercise performance. Vegetarians may also take creatine to replace what they are not consuming from meat, fish, and other animal products. Previous anecdotal reports have linked creatine to the development of arrhythmia. Clinicians must be diligent when interviewing patients about their drug therapy histories and include questions about their use of herbal products and dietary supplements. In addition, it is important to report adverse effects associated with frequently consumed supplements and herbal products to the Food and Drug Administration and in the literature.", "entity": "Arrhythmias, Cardiac", "aliases": "Arrhythmia Cardiac Arrhythmias Arrythmia Dysrhythmia", "definition": "Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.\n    ", "id": "MESH:D001145"}
{"mention": "Thyroid disorders", "mention_text": "Atrial fibrillation in young patients without structural heart disease is rare. Therefore, when the arrhythmia is present in this population, reversible causes must be identified and resolved. Thyroid disorders, illicit drug or stimulant use, and acute alcohol intoxication are among these causes. We report the case of a 30-year-old Caucasian man who came to the emergency department in atrial fibrillation with rapid ventricular response. His medical history was unremarkable, except for minor fractures of the fingers and foot. Thyroid-stimulating hormone, magnesium, and potassium levels were within normal limits, urine drug screen was negative, and alcohol use was denied. However, when the patient was questioned about use of herbal products and supplements, the use of creatine monohydrate was revealed. The patient was admitted to the hospital, anticoagulated with unfractionated heparin, and given intravenous diltiazem for rate control and intravenous amiodarone for rate and rhythm control. When discharged less than 24 hours later, he was receiving metoprolol and aspirin, with follow-up plans for echocardiography and nuclear imaging to assess perfusion. Exogenous creatine is used by athletes to theoretically improve exercise performance. Vegetarians may also take creatine to replace what they are not consuming from meat, fish, and other animal products. Previous anecdotal reports have linked creatine to the development of arrhythmia. Clinicians must be diligent when interviewing patients about their drug therapy histories and include questions about their use of herbal products and dietary supplements. In addition, it is important to report adverse effects associated with frequently consumed supplements and herbal products to the Food and Drug Administration and in the literature.", "entity": "Thyroid Diseases", "aliases": "Disease Thyroid Diseases", "definition": "Pathological processes involving the THYROID GLAND.\n    ", "id": "MESH:D013959"}
{"mention": "acute alcohol intoxication", "mention_text": "Atrial fibrillation in young patients without structural heart disease is rare. Therefore, when the arrhythmia is present in this population, reversible causes must be identified and resolved. Thyroid disorders, illicit drug or stimulant use, and acute alcohol intoxication are among these causes. We report the case of a 30-year-old Caucasian man who came to the emergency department in atrial fibrillation with rapid ventricular response. His medical history was unremarkable, except for minor fractures of the fingers and foot. Thyroid-stimulating hormone, magnesium, and potassium levels were within normal limits, urine drug screen was negative, and alcohol use was denied. However, when the patient was questioned about use of herbal products and supplements, the use of creatine monohydrate was revealed. The patient was admitted to the hospital, anticoagulated with unfractionated heparin, and given intravenous diltiazem for rate control and intravenous amiodarone for rate and rhythm control. When discharged less than 24 hours later, he was receiving metoprolol and aspirin, with follow-up plans for echocardiography and nuclear imaging to assess perfusion. Exogenous creatine is used by athletes to theoretically improve exercise performance. Vegetarians may also take creatine to replace what they are not consuming from meat, fish, and other animal products. Previous anecdotal reports have linked creatine to the development of arrhythmia. Clinicians must be diligent when interviewing patients about their drug therapy histories and include questions about their use of herbal products and dietary supplements. In addition, it is important to report adverse effects associated with frequently consumed supplements and herbal products to the Food and Drug Administration and in the literature.", "entity": "Alcoholic Intoxication", "aliases": "Alcoholic Intoxication Drunkenness Drunkennesses", "definition": "An acute brain syndrome which results from the excessive ingestion of ETHANOL or ALCOHOLIC BEVERAGES.\n    ", "id": "MESH:D000435"}
{"mention": "atrial fibrillation", "mention_text": "Atrial fibrillation in young patients without structural heart disease is rare. Therefore, when the arrhythmia is present in this population, reversible causes must be identified and resolved. Thyroid disorders, illicit drug or stimulant use, and acute alcohol intoxication are among these causes. We report the case of a 30-year-old Caucasian man who came to the emergency department in atrial fibrillation with rapid ventricular response. His medical history was unremarkable, except for minor fractures of the fingers and foot. Thyroid-stimulating hormone, magnesium, and potassium levels were within normal limits, urine drug screen was negative, and alcohol use was denied. However, when the patient was questioned about use of herbal products and supplements, the use of creatine monohydrate was revealed. The patient was admitted to the hospital, anticoagulated with unfractionated heparin, and given intravenous diltiazem for rate control and intravenous amiodarone for rate and rhythm control. When discharged less than 24 hours later, he was receiving metoprolol and aspirin, with follow-up plans for echocardiography and nuclear imaging to assess perfusion. Exogenous creatine is used by athletes to theoretically improve exercise performance. Vegetarians may also take creatine to replace what they are not consuming from meat, fish, and other animal products. Previous anecdotal reports have linked creatine to the development of arrhythmia. Clinicians must be diligent when interviewing patients about their drug therapy histories and include questions about their use of herbal products and dietary supplements. In addition, it is important to report adverse effects associated with frequently consumed supplements and herbal products to the Food and Drug Administration and in the literature.", "entity": "Atrial Fibrillation", "aliases": "Atrial Fibrillation Fibrillations Auricular Familial", "definition": "Abnormal cardiac rhythm that is characterized by rapid, uncoordinated firing of electrical impulses in the upper chambers of the heart (HEART ATRIA). In such case, blood cannot be effectively pumped into the lower chambers of the heart (HEART VENTRICLES). It is caused by abnormal impulse generation.\n    ", "id": "MESH:D001281"}
{"mention": "fractures", "mention_text": "Atrial fibrillation in young patients without structural heart disease is rare. Therefore, when the arrhythmia is present in this population, reversible causes must be identified and resolved. Thyroid disorders, illicit drug or stimulant use, and acute alcohol intoxication are among these causes. We report the case of a 30-year-old Caucasian man who came to the emergency department in atrial fibrillation with rapid ventricular response. His medical history was unremarkable, except for minor fractures of the fingers and foot. Thyroid-stimulating hormone, magnesium, and potassium levels were within normal limits, urine drug screen was negative, and alcohol use was denied. However, when the patient was questioned about use of herbal products and supplements, the use of creatine monohydrate was revealed. The patient was admitted to the hospital, anticoagulated with unfractionated heparin, and given intravenous diltiazem for rate control and intravenous amiodarone for rate and rhythm control. When discharged less than 24 hours later, he was receiving metoprolol and aspirin, with follow-up plans for echocardiography and nuclear imaging to assess perfusion. Exogenous creatine is used by athletes to theoretically improve exercise performance. Vegetarians may also take creatine to replace what they are not consuming from meat, fish, and other animal products. Previous anecdotal reports have linked creatine to the development of arrhythmia. Clinicians must be diligent when interviewing patients about their drug therapy histories and include questions about their use of herbal products and dietary supplements. In addition, it is important to report adverse effects associated with frequently consumed supplements and herbal products to the Food and Drug Administration and in the literature.", "entity": "Fractures, Bone", "aliases": "Bone Fracture Fractures Broken Bones", "definition": "Breaks in bones.\n    ", "id": "MESH:D050723"}
{"mention": "magnesium", "mention_text": "Atrial fibrillation in young patients without structural heart disease is rare. Therefore, when the arrhythmia is present in this population, reversible causes must be identified and resolved. Thyroid disorders, illicit drug or stimulant use, and acute alcohol intoxication are among these causes. We report the case of a 30-year-old Caucasian man who came to the emergency department in atrial fibrillation with rapid ventricular response. His medical history was unremarkable, except for minor fractures of the fingers and foot. Thyroid-stimulating hormone, magnesium, and potassium levels were within normal limits, urine drug screen was negative, and alcohol use was denied. However, when the patient was questioned about use of herbal products and supplements, the use of creatine monohydrate was revealed. The patient was admitted to the hospital, anticoagulated with unfractionated heparin, and given intravenous diltiazem for rate control and intravenous amiodarone for rate and rhythm control. When discharged less than 24 hours later, he was receiving metoprolol and aspirin, with follow-up plans for echocardiography and nuclear imaging to assess perfusion. Exogenous creatine is used by athletes to theoretically improve exercise performance. Vegetarians may also take creatine to replace what they are not consuming from meat, fish, and other animal products. Previous anecdotal reports have linked creatine to the development of arrhythmia. Clinicians must be diligent when interviewing patients about their drug therapy histories and include questions about their use of herbal products and dietary supplements. In addition, it is important to report adverse effects associated with frequently consumed supplements and herbal products to the Food and Drug Administration and in the literature.", "entity": "Magnesium", "aliases": "Magnesium", "definition": "A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.\n    ", "id": "MESH:D008274"}
{"mention": "potassium", "mention_text": "Atrial fibrillation in young patients without structural heart disease is rare. Therefore, when the arrhythmia is present in this population, reversible causes must be identified and resolved. Thyroid disorders, illicit drug or stimulant use, and acute alcohol intoxication are among these causes. We report the case of a 30-year-old Caucasian man who came to the emergency department in atrial fibrillation with rapid ventricular response. His medical history was unremarkable, except for minor fractures of the fingers and foot. Thyroid-stimulating hormone, magnesium, and potassium levels were within normal limits, urine drug screen was negative, and alcohol use was denied. However, when the patient was questioned about use of herbal products and supplements, the use of creatine monohydrate was revealed. The patient was admitted to the hospital, anticoagulated with unfractionated heparin, and given intravenous diltiazem for rate control and intravenous amiodarone for rate and rhythm control. When discharged less than 24 hours later, he was receiving metoprolol and aspirin, with follow-up plans for echocardiography and nuclear imaging to assess perfusion. Exogenous creatine is used by athletes to theoretically improve exercise performance. Vegetarians may also take creatine to replace what they are not consuming from meat, fish, and other animal products. Previous anecdotal reports have linked creatine to the development of arrhythmia. Clinicians must be diligent when interviewing patients about their drug therapy histories and include questions about their use of herbal products and dietary supplements. In addition, it is important to report adverse effects associated with frequently consumed supplements and herbal products to the Food and Drug Administration and in the literature.", "entity": "Potassium", "aliases": "Potassium", "definition": "An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.\n    ", "id": "MESH:D011188"}
{"mention": "alcohol", "mention_text": "Atrial fibrillation in young patients without structural heart disease is rare. Therefore, when the arrhythmia is present in this population, reversible causes must be identified and resolved. Thyroid disorders, illicit drug or stimulant use, and acute alcohol intoxication are among these causes. We report the case of a 30-year-old Caucasian man who came to the emergency department in atrial fibrillation with rapid ventricular response. His medical history was unremarkable, except for minor fractures of the fingers and foot. Thyroid-stimulating hormone, magnesium, and potassium levels were within normal limits, urine drug screen was negative, and alcohol use was denied. However, when the patient was questioned about use of herbal products and supplements, the use of creatine monohydrate was revealed. The patient was admitted to the hospital, anticoagulated with unfractionated heparin, and given intravenous diltiazem for rate control and intravenous amiodarone for rate and rhythm control. When discharged less than 24 hours later, he was receiving metoprolol and aspirin, with follow-up plans for echocardiography and nuclear imaging to assess perfusion. Exogenous creatine is used by athletes to theoretically improve exercise performance. Vegetarians may also take creatine to replace what they are not consuming from meat, fish, and other animal products. Previous anecdotal reports have linked creatine to the development of arrhythmia. Clinicians must be diligent when interviewing patients about their drug therapy histories and include questions about their use of herbal products and dietary supplements. In addition, it is important to report adverse effects associated with frequently consumed supplements and herbal products to the Food and Drug Administration and in the literature.", "entity": "Ethanol", "aliases": "Absolute Alcohol Ethyl Grain Ethanol", "definition": "A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.\n    ", "id": "MESH:D000431"}
{"mention": "creatine", "mention_text": "Atrial fibrillation in young patients without structural heart disease is rare. Therefore, when the arrhythmia is present in this population, reversible causes must be identified and resolved. Thyroid disorders, illicit drug or stimulant use, and acute alcohol intoxication are among these causes. We report the case of a 30-year-old Caucasian man who came to the emergency department in atrial fibrillation with rapid ventricular response. His medical history was unremarkable, except for minor fractures of the fingers and foot. Thyroid-stimulating hormone, magnesium, and potassium levels were within normal limits, urine drug screen was negative, and alcohol use was denied. However, when the patient was questioned about use of herbal products and supplements, the use of creatine monohydrate was revealed. The patient was admitted to the hospital, anticoagulated with unfractionated heparin, and given intravenous diltiazem for rate control and intravenous amiodarone for rate and rhythm control. When discharged less than 24 hours later, he was receiving metoprolol and aspirin, with follow-up plans for echocardiography and nuclear imaging to assess perfusion. Exogenous creatine is used by athletes to theoretically improve exercise performance. Vegetarians may also take creatine to replace what they are not consuming from meat, fish, and other animal products. Previous anecdotal reports have linked creatine to the development of arrhythmia. Clinicians must be diligent when interviewing patients about their drug therapy histories and include questions about their use of herbal products and dietary supplements. In addition, it is important to report adverse effects associated with frequently consumed supplements and herbal products to the Food and Drug Administration and in the literature.", "entity": "Creatine", "aliases": "Creatine", "definition": "An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as CREATININE in the urine.\n    ", "id": "MESH:D003401"}
{"mention": "heparin", "mention_text": "Atrial fibrillation in young patients without structural heart disease is rare. Therefore, when the arrhythmia is present in this population, reversible causes must be identified and resolved. Thyroid disorders, illicit drug or stimulant use, and acute alcohol intoxication are among these causes. We report the case of a 30-year-old Caucasian man who came to the emergency department in atrial fibrillation with rapid ventricular response. His medical history was unremarkable, except for minor fractures of the fingers and foot. Thyroid-stimulating hormone, magnesium, and potassium levels were within normal limits, urine drug screen was negative, and alcohol use was denied. However, when the patient was questioned about use of herbal products and supplements, the use of creatine monohydrate was revealed. The patient was admitted to the hospital, anticoagulated with unfractionated heparin, and given intravenous diltiazem for rate control and intravenous amiodarone for rate and rhythm control. When discharged less than 24 hours later, he was receiving metoprolol and aspirin, with follow-up plans for echocardiography and nuclear imaging to assess perfusion. Exogenous creatine is used by athletes to theoretically improve exercise performance. Vegetarians may also take creatine to replace what they are not consuming from meat, fish, and other animal products. Previous anecdotal reports have linked creatine to the development of arrhythmia. Clinicians must be diligent when interviewing patients about their drug therapy histories and include questions about their use of herbal products and dietary supplements. In addition, it is important to report adverse effects associated with frequently consumed supplements and herbal products to the Food and Drug Administration and in the literature.", "entity": "Heparin", "aliases": "Heparin Sodium Unfractionated Heparinic Acid Liquaemin alpha alpha-Heparin", "definition": "A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.\n    ", "id": "MESH:D006493"}
{"mention": "diltiazem", "mention_text": "Atrial fibrillation in young patients without structural heart disease is rare. Therefore, when the arrhythmia is present in this population, reversible causes must be identified and resolved. Thyroid disorders, illicit drug or stimulant use, and acute alcohol intoxication are among these causes. We report the case of a 30-year-old Caucasian man who came to the emergency department in atrial fibrillation with rapid ventricular response. His medical history was unremarkable, except for minor fractures of the fingers and foot. Thyroid-stimulating hormone, magnesium, and potassium levels were within normal limits, urine drug screen was negative, and alcohol use was denied. However, when the patient was questioned about use of herbal products and supplements, the use of creatine monohydrate was revealed. The patient was admitted to the hospital, anticoagulated with unfractionated heparin, and given intravenous diltiazem for rate control and intravenous amiodarone for rate and rhythm control. When discharged less than 24 hours later, he was receiving metoprolol and aspirin, with follow-up plans for echocardiography and nuclear imaging to assess perfusion. Exogenous creatine is used by athletes to theoretically improve exercise performance. Vegetarians may also take creatine to replace what they are not consuming from meat, fish, and other animal products. Previous anecdotal reports have linked creatine to the development of arrhythmia. Clinicians must be diligent when interviewing patients about their drug therapy histories and include questions about their use of herbal products and dietary supplements. In addition, it is important to report adverse effects associated with frequently consumed supplements and herbal products to the Food and Drug Administration and in the literature.", "entity": "Diltiazem", "aliases": "Aldizem Biovail Brand of Diltiazem Hydrochloride CRD 401 CRD-401 CRD401 Cardil Cardizem Dilacor XR Dilren Malate Dilzem Tiazac Watson Pharmaceuticals Diltazem", "definition": "A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of CALCIUM ion on membrane functions.\n    ", "id": "MESH:D004110"}
{"mention": "amiodarone", "mention_text": "Atrial fibrillation in young patients without structural heart disease is rare. Therefore, when the arrhythmia is present in this population, reversible causes must be identified and resolved. Thyroid disorders, illicit drug or stimulant use, and acute alcohol intoxication are among these causes. We report the case of a 30-year-old Caucasian man who came to the emergency department in atrial fibrillation with rapid ventricular response. His medical history was unremarkable, except for minor fractures of the fingers and foot. Thyroid-stimulating hormone, magnesium, and potassium levels were within normal limits, urine drug screen was negative, and alcohol use was denied. However, when the patient was questioned about use of herbal products and supplements, the use of creatine monohydrate was revealed. The patient was admitted to the hospital, anticoagulated with unfractionated heparin, and given intravenous diltiazem for rate control and intravenous amiodarone for rate and rhythm control. When discharged less than 24 hours later, he was receiving metoprolol and aspirin, with follow-up plans for echocardiography and nuclear imaging to assess perfusion. Exogenous creatine is used by athletes to theoretically improve exercise performance. Vegetarians may also take creatine to replace what they are not consuming from meat, fish, and other animal products. Previous anecdotal reports have linked creatine to the development of arrhythmia. Clinicians must be diligent when interviewing patients about their drug therapy histories and include questions about their use of herbal products and dietary supplements. In addition, it is important to report adverse effects associated with frequently consumed supplements and herbal products to the Food and Drug Administration and in the literature.", "entity": "Amiodarone", "aliases": "ASTA Medica Brand of Amiodarone Hydrochloride Alphapharm Amiobeta Amiodarex Amiodarona Amiohexal Aratac Armstrong Berenguer Infale Betapharm Braxan Corbionax Cordarex Cordarone G Gam Hexal Kordaron L 3428 L-3428 L3428 Leurquin Ortacrone Pharma Investi Rytmarone SKF 33134 A 33134-A 33134A Sanofi Winthrop Tachydaron Trangorex Wyeth", "definition": "An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.\n    ", "id": "MESH:D000638"}
{"mention": "metoprolol", "mention_text": "Atrial fibrillation in young patients without structural heart disease is rare. Therefore, when the arrhythmia is present in this population, reversible causes must be identified and resolved. Thyroid disorders, illicit drug or stimulant use, and acute alcohol intoxication are among these causes. We report the case of a 30-year-old Caucasian man who came to the emergency department in atrial fibrillation with rapid ventricular response. His medical history was unremarkable, except for minor fractures of the fingers and foot. Thyroid-stimulating hormone, magnesium, and potassium levels were within normal limits, urine drug screen was negative, and alcohol use was denied. However, when the patient was questioned about use of herbal products and supplements, the use of creatine monohydrate was revealed. The patient was admitted to the hospital, anticoagulated with unfractionated heparin, and given intravenous diltiazem for rate control and intravenous amiodarone for rate and rhythm control. When discharged less than 24 hours later, he was receiving metoprolol and aspirin, with follow-up plans for echocardiography and nuclear imaging to assess perfusion. Exogenous creatine is used by athletes to theoretically improve exercise performance. Vegetarians may also take creatine to replace what they are not consuming from meat, fish, and other animal products. Previous anecdotal reports have linked creatine to the development of arrhythmia. Clinicians must be diligent when interviewing patients about their drug therapy histories and include questions about their use of herbal products and dietary supplements. In addition, it is important to report adverse effects associated with frequently consumed supplements and herbal products to the Food and Drug Administration and in the literature.", "entity": "Metoprolol", "aliases": "AstraZeneca Brand of Metaoprolol Tartrate Seloken Beloc Duriles Beloc-Duriles BelocDuriles Betaloc Astra Betaloc-Astra BetalocAstra Betalok CGP 2175 CGP-2175 CGP2175 H 93 26 93-26 9326 Leiras Metoprolol Succinate or Metoprolol Lopressor Novartis Metprolol Spesicor Spesikor", "definition": "A selective adrenergic beta-1 blocking agent that is commonly used to treat ANGINA PECTORIS; HYPERTENSION; and CARDIAC ARRHYTHMIAS.\n    ", "id": "MESH:D008790"}
{"mention": "aspirin", "mention_text": "Atrial fibrillation in young patients without structural heart disease is rare. Therefore, when the arrhythmia is present in this population, reversible causes must be identified and resolved. Thyroid disorders, illicit drug or stimulant use, and acute alcohol intoxication are among these causes. We report the case of a 30-year-old Caucasian man who came to the emergency department in atrial fibrillation with rapid ventricular response. His medical history was unremarkable, except for minor fractures of the fingers and foot. Thyroid-stimulating hormone, magnesium, and potassium levels were within normal limits, urine drug screen was negative, and alcohol use was denied. However, when the patient was questioned about use of herbal products and supplements, the use of creatine monohydrate was revealed. The patient was admitted to the hospital, anticoagulated with unfractionated heparin, and given intravenous diltiazem for rate control and intravenous amiodarone for rate and rhythm control. When discharged less than 24 hours later, he was receiving metoprolol and aspirin, with follow-up plans for echocardiography and nuclear imaging to assess perfusion. Exogenous creatine is used by athletes to theoretically improve exercise performance. Vegetarians may also take creatine to replace what they are not consuming from meat, fish, and other animal products. Previous anecdotal reports have linked creatine to the development of arrhythmia. Clinicians must be diligent when interviewing patients about their drug therapy histories and include questions about their use of herbal products and dietary supplements. In addition, it is important to report adverse effects associated with frequently consumed supplements and herbal products to the Food and Drug Administration and in the literature.", "entity": "Aspirin", "aliases": "2-(Acetyloxy)benzoic Acid Acetylsalicylic Acetysal Acylpyrin Aloxiprimum Aspirin Colfarit Dispril Easprin Ecotrin Endosprin Magnecyl Micristin Polopirin Polopiryna Solprin Solupsan Zorprin", "definition": "The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)\n    ", "id": "MESH:D001241"}
{"mention": "toxicity", "mention_text": "Comparison of developmental toxicity of selective and non-selective cyclooxygenase-2 inhibitors in CRL:(WI)WUBR Wistar rats--DFU and piroxicam study.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "DFU", "mention_text": "Comparison of developmental toxicity of selective and non-selective cyclooxygenase-2 inhibitors in CRL:(WI)WUBR Wistar rats--DFU and piroxicam study.", "entity": "5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanone", "aliases": "5,5-DFU 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanone DFU-5,5", "definition": "", "id": "MESH:C106876"}
{"mention": "piroxicam", "mention_text": "Comparison of developmental toxicity of selective and non-selective cyclooxygenase-2 inhibitors in CRL:(WI)WUBR Wistar rats--DFU and piroxicam study.", "entity": "Piroxicam", "aliases": "CP 16171 CP-16171 CP16171 Feldene Piroxicam", "definition": "A cyclooxygenase inhibiting, non-steroidal anti-inflammatory agent (NSAID) that is well established in treating rheumatoid arthritis and osteoarthritis and used for musculoskeletal disorders, dysmenorrhea, and postoperative pain. Its long half-life enables it to be administered once daily.\n    ", "id": "MESH:D010894"}
{"mention": "toxicity", "mention_text": "BACKGROUND: Cyclooxygenase (COX) inhibitors are one of the most often ingested drugs during pregnancy. Unlike general toxicity data, their prenatal toxic effects were not extensively studied before. The aim of the experiment was to evaluate the developmental toxicity of the non-selective (piroxicam) and selective (DFU; 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanon) COX-2 inhibitors. METHODS: Drugs were separately, orally once daily dosed to pregnant rats from day 8 to 21 (GD1=plug day). Doses were set at 0.3, 3.0 and 30.0mg/kg for piroxicam and 0.2, 2.0 and 20.0mg/kg for DFU. Fetuses were delivered on GD 21 and routinely examined. Comprehensive clinical and developmental measurements were done. The pooled statistical analysis for ventricular septal (VSD) and midline (MD) defects was performed for rat fetuses exposed to piroxicam, selective and non-selective COX-2 inhibitor based on present and historic data. RESULTS: Maternal toxicity, intrauterine growth retardation, and increase of external and skeletal variations were found in rats treated with the highest dose of piroxicam. Decrease of fetal length was the only signs of the DFU developmental toxicity observed in pups exposed to the highest compound dose. Lack of teratogenicity was found in piroxicam and DFU-exposed groups. Prenatal exposure to non-selective COX inhibitors increases the risk of VSD and MD when compared to historic control but not with selective COX-2 inhibitors. CONCLUSION: Both selective and non-selective COX-2 inhibitors were toxic for rats fetuses when administered in the highest dose. Unlike DFU, piroxicam was also highly toxic to the dams. Prenatal exposure to selective COX-2 inhibitors does not increase the risk of ventricular septal and midline defects in rat when compared to non-selective drugs and historic control.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "piroxicam", "mention_text": "BACKGROUND: Cyclooxygenase (COX) inhibitors are one of the most often ingested drugs during pregnancy. Unlike general toxicity data, their prenatal toxic effects were not extensively studied before. The aim of the experiment was to evaluate the developmental toxicity of the non-selective (piroxicam) and selective (DFU; 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanon) COX-2 inhibitors. METHODS: Drugs were separately, orally once daily dosed to pregnant rats from day 8 to 21 (GD1=plug day). Doses were set at 0.3, 3.0 and 30.0mg/kg for piroxicam and 0.2, 2.0 and 20.0mg/kg for DFU. Fetuses were delivered on GD 21 and routinely examined. Comprehensive clinical and developmental measurements were done. The pooled statistical analysis for ventricular septal (VSD) and midline (MD) defects was performed for rat fetuses exposed to piroxicam, selective and non-selective COX-2 inhibitor based on present and historic data. RESULTS: Maternal toxicity, intrauterine growth retardation, and increase of external and skeletal variations were found in rats treated with the highest dose of piroxicam. Decrease of fetal length was the only signs of the DFU developmental toxicity observed in pups exposed to the highest compound dose. Lack of teratogenicity was found in piroxicam and DFU-exposed groups. Prenatal exposure to non-selective COX inhibitors increases the risk of VSD and MD when compared to historic control but not with selective COX-2 inhibitors. CONCLUSION: Both selective and non-selective COX-2 inhibitors were toxic for rats fetuses when administered in the highest dose. Unlike DFU, piroxicam was also highly toxic to the dams. Prenatal exposure to selective COX-2 inhibitors does not increase the risk of ventricular septal and midline defects in rat when compared to non-selective drugs and historic control.", "entity": "Piroxicam", "aliases": "CP 16171 CP-16171 CP16171 Feldene Piroxicam", "definition": "A cyclooxygenase inhibiting, non-steroidal anti-inflammatory agent (NSAID) that is well established in treating rheumatoid arthritis and osteoarthritis and used for musculoskeletal disorders, dysmenorrhea, and postoperative pain. Its long half-life enables it to be administered once daily.\n    ", "id": "MESH:D010894"}
{"mention": "DFU", "mention_text": "BACKGROUND: Cyclooxygenase (COX) inhibitors are one of the most often ingested drugs during pregnancy. Unlike general toxicity data, their prenatal toxic effects were not extensively studied before. The aim of the experiment was to evaluate the developmental toxicity of the non-selective (piroxicam) and selective (DFU; 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanon) COX-2 inhibitors. METHODS: Drugs were separately, orally once daily dosed to pregnant rats from day 8 to 21 (GD1=plug day). Doses were set at 0.3, 3.0 and 30.0mg/kg for piroxicam and 0.2, 2.0 and 20.0mg/kg for DFU. Fetuses were delivered on GD 21 and routinely examined. Comprehensive clinical and developmental measurements were done. The pooled statistical analysis for ventricular septal (VSD) and midline (MD) defects was performed for rat fetuses exposed to piroxicam, selective and non-selective COX-2 inhibitor based on present and historic data. RESULTS: Maternal toxicity, intrauterine growth retardation, and increase of external and skeletal variations were found in rats treated with the highest dose of piroxicam. Decrease of fetal length was the only signs of the DFU developmental toxicity observed in pups exposed to the highest compound dose. Lack of teratogenicity was found in piroxicam and DFU-exposed groups. Prenatal exposure to non-selective COX inhibitors increases the risk of VSD and MD when compared to historic control but not with selective COX-2 inhibitors. CONCLUSION: Both selective and non-selective COX-2 inhibitors were toxic for rats fetuses when administered in the highest dose. Unlike DFU, piroxicam was also highly toxic to the dams. Prenatal exposure to selective COX-2 inhibitors does not increase the risk of ventricular septal and midline defects in rat when compared to non-selective drugs and historic control.", "entity": "5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanone", "aliases": "5,5-DFU 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanone DFU-5,5", "definition": "", "id": "MESH:C106876"}
{"mention": "5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanon", "mention_text": "BACKGROUND: Cyclooxygenase (COX) inhibitors are one of the most often ingested drugs during pregnancy. Unlike general toxicity data, their prenatal toxic effects were not extensively studied before. The aim of the experiment was to evaluate the developmental toxicity of the non-selective (piroxicam) and selective (DFU; 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanon) COX-2 inhibitors. METHODS: Drugs were separately, orally once daily dosed to pregnant rats from day 8 to 21 (GD1=plug day). Doses were set at 0.3, 3.0 and 30.0mg/kg for piroxicam and 0.2, 2.0 and 20.0mg/kg for DFU. Fetuses were delivered on GD 21 and routinely examined. Comprehensive clinical and developmental measurements were done. The pooled statistical analysis for ventricular septal (VSD) and midline (MD) defects was performed for rat fetuses exposed to piroxicam, selective and non-selective COX-2 inhibitor based on present and historic data. RESULTS: Maternal toxicity, intrauterine growth retardation, and increase of external and skeletal variations were found in rats treated with the highest dose of piroxicam. Decrease of fetal length was the only signs of the DFU developmental toxicity observed in pups exposed to the highest compound dose. Lack of teratogenicity was found in piroxicam and DFU-exposed groups. Prenatal exposure to non-selective COX inhibitors increases the risk of VSD and MD when compared to historic control but not with selective COX-2 inhibitors. CONCLUSION: Both selective and non-selective COX-2 inhibitors were toxic for rats fetuses when administered in the highest dose. Unlike DFU, piroxicam was also highly toxic to the dams. Prenatal exposure to selective COX-2 inhibitors does not increase the risk of ventricular septal and midline defects in rat when compared to non-selective drugs and historic control.", "entity": "5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanone", "aliases": "5,5-DFU 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanone DFU-5,5", "definition": "", "id": "MESH:C106876"}
{"mention": "midline (MD) defects", "mention_text": "BACKGROUND: Cyclooxygenase (COX) inhibitors are one of the most often ingested drugs during pregnancy. Unlike general toxicity data, their prenatal toxic effects were not extensively studied before. The aim of the experiment was to evaluate the developmental toxicity of the non-selective (piroxicam) and selective (DFU; 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanon) COX-2 inhibitors. METHODS: Drugs were separately, orally once daily dosed to pregnant rats from day 8 to 21 (GD1=plug day). Doses were set at 0.3, 3.0 and 30.0mg/kg for piroxicam and 0.2, 2.0 and 20.0mg/kg for DFU. Fetuses were delivered on GD 21 and routinely examined. Comprehensive clinical and developmental measurements were done. The pooled statistical analysis for ventricular septal (VSD) and midline (MD) defects was performed for rat fetuses exposed to piroxicam, selective and non-selective COX-2 inhibitor based on present and historic data. RESULTS: Maternal toxicity, intrauterine growth retardation, and increase of external and skeletal variations were found in rats treated with the highest dose of piroxicam. Decrease of fetal length was the only signs of the DFU developmental toxicity observed in pups exposed to the highest compound dose. Lack of teratogenicity was found in piroxicam and DFU-exposed groups. Prenatal exposure to non-selective COX inhibitors increases the risk of VSD and MD when compared to historic control but not with selective COX-2 inhibitors. CONCLUSION: Both selective and non-selective COX-2 inhibitors were toxic for rats fetuses when administered in the highest dose. Unlike DFU, piroxicam was also highly toxic to the dams. Prenatal exposure to selective COX-2 inhibitors does not increase the risk of ventricular septal and midline defects in rat when compared to non-selective drugs and historic control.", "entity": "Neural Tube Defects", "aliases": "Acrania Acranias Craniorachischises Craniorachischisis Cyst Neurenteric Neuroenteric Cysts Defect Neural Tube Defects Developmental Diastematomyelia Diastematomyelias Dysraphism Occult Spinal Dysraphisms Exencephalies Exencephaly Iniencephalies Iniencephaly Myelodysplasia Cord Myelodysplasias Sequence Tethered Syndrome Syndromes", "definition": "Congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy generally occurring between days 18-29 of gestation. Ectodermal and mesodermal malformations (mainly involving the skull and vertebrae) may occur as a result of defects of neural tube closure. (From Joynt, Clinical Neurology, 1992, Ch55, pp31-41)\n    ", "id": "MESH:D009436"}
{"mention": "intrauterine growth retardation", "mention_text": "BACKGROUND: Cyclooxygenase (COX) inhibitors are one of the most often ingested drugs during pregnancy. Unlike general toxicity data, their prenatal toxic effects were not extensively studied before. The aim of the experiment was to evaluate the developmental toxicity of the non-selective (piroxicam) and selective (DFU; 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanon) COX-2 inhibitors. METHODS: Drugs were separately, orally once daily dosed to pregnant rats from day 8 to 21 (GD1=plug day). Doses were set at 0.3, 3.0 and 30.0mg/kg for piroxicam and 0.2, 2.0 and 20.0mg/kg for DFU. Fetuses were delivered on GD 21 and routinely examined. Comprehensive clinical and developmental measurements were done. The pooled statistical analysis for ventricular septal (VSD) and midline (MD) defects was performed for rat fetuses exposed to piroxicam, selective and non-selective COX-2 inhibitor based on present and historic data. RESULTS: Maternal toxicity, intrauterine growth retardation, and increase of external and skeletal variations were found in rats treated with the highest dose of piroxicam. Decrease of fetal length was the only signs of the DFU developmental toxicity observed in pups exposed to the highest compound dose. Lack of teratogenicity was found in piroxicam and DFU-exposed groups. Prenatal exposure to non-selective COX inhibitors increases the risk of VSD and MD when compared to historic control but not with selective COX-2 inhibitors. CONCLUSION: Both selective and non-selective COX-2 inhibitors were toxic for rats fetuses when administered in the highest dose. Unlike DFU, piroxicam was also highly toxic to the dams. Prenatal exposure to selective COX-2 inhibitors does not increase the risk of ventricular septal and midline defects in rat when compared to non-selective drugs and historic control.", "entity": "Fetal Growth Retardation", "aliases": "Fetal Growth Retardation Intrauterine IUGR", "definition": "The failure of a FETUS to attain its expected FETAL GROWTH at any GESTATIONAL AGE.\n    ", "id": "MESH:D005317"}
{"mention": "increase of external and skeletal variations", "mention_text": "BACKGROUND: Cyclooxygenase (COX) inhibitors are one of the most often ingested drugs during pregnancy. Unlike general toxicity data, their prenatal toxic effects were not extensively studied before. The aim of the experiment was to evaluate the developmental toxicity of the non-selective (piroxicam) and selective (DFU; 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanon) COX-2 inhibitors. METHODS: Drugs were separately, orally once daily dosed to pregnant rats from day 8 to 21 (GD1=plug day). Doses were set at 0.3, 3.0 and 30.0mg/kg for piroxicam and 0.2, 2.0 and 20.0mg/kg for DFU. Fetuses were delivered on GD 21 and routinely examined. Comprehensive clinical and developmental measurements were done. The pooled statistical analysis for ventricular septal (VSD) and midline (MD) defects was performed for rat fetuses exposed to piroxicam, selective and non-selective COX-2 inhibitor based on present and historic data. RESULTS: Maternal toxicity, intrauterine growth retardation, and increase of external and skeletal variations were found in rats treated with the highest dose of piroxicam. Decrease of fetal length was the only signs of the DFU developmental toxicity observed in pups exposed to the highest compound dose. Lack of teratogenicity was found in piroxicam and DFU-exposed groups. Prenatal exposure to non-selective COX inhibitors increases the risk of VSD and MD when compared to historic control but not with selective COX-2 inhibitors. CONCLUSION: Both selective and non-selective COX-2 inhibitors were toxic for rats fetuses when administered in the highest dose. Unlike DFU, piroxicam was also highly toxic to the dams. Prenatal exposure to selective COX-2 inhibitors does not increase the risk of ventricular septal and midline defects in rat when compared to non-selective drugs and historic control.", "entity": "Musculoskeletal Abnormalities", "aliases": "Abnormalities Musculoskeletal Abnormality", "definition": "Congenital structural abnormalities and deformities of the musculoskeletal system.\n    ", "id": "MESH:D009139"}
{"mention": "midline defects", "mention_text": "BACKGROUND: Cyclooxygenase (COX) inhibitors are one of the most often ingested drugs during pregnancy. Unlike general toxicity data, their prenatal toxic effects were not extensively studied before. The aim of the experiment was to evaluate the developmental toxicity of the non-selective (piroxicam) and selective (DFU; 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanon) COX-2 inhibitors. METHODS: Drugs were separately, orally once daily dosed to pregnant rats from day 8 to 21 (GD1=plug day). Doses were set at 0.3, 3.0 and 30.0mg/kg for piroxicam and 0.2, 2.0 and 20.0mg/kg for DFU. Fetuses were delivered on GD 21 and routinely examined. Comprehensive clinical and developmental measurements were done. The pooled statistical analysis for ventricular septal (VSD) and midline (MD) defects was performed for rat fetuses exposed to piroxicam, selective and non-selective COX-2 inhibitor based on present and historic data. RESULTS: Maternal toxicity, intrauterine growth retardation, and increase of external and skeletal variations were found in rats treated with the highest dose of piroxicam. Decrease of fetal length was the only signs of the DFU developmental toxicity observed in pups exposed to the highest compound dose. Lack of teratogenicity was found in piroxicam and DFU-exposed groups. Prenatal exposure to non-selective COX inhibitors increases the risk of VSD and MD when compared to historic control but not with selective COX-2 inhibitors. CONCLUSION: Both selective and non-selective COX-2 inhibitors were toxic for rats fetuses when administered in the highest dose. Unlike DFU, piroxicam was also highly toxic to the dams. Prenatal exposure to selective COX-2 inhibitors does not increase the risk of ventricular septal and midline defects in rat when compared to non-selective drugs and historic control.", "entity": "Neural Tube Defects", "aliases": "Acrania Acranias Craniorachischises Craniorachischisis Cyst Neurenteric Neuroenteric Cysts Defect Neural Tube Defects Developmental Diastematomyelia Diastematomyelias Dysraphism Occult Spinal Dysraphisms Exencephalies Exencephaly Iniencephalies Iniencephaly Myelodysplasia Cord Myelodysplasias Sequence Tethered Syndrome Syndromes", "definition": "Congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy generally occurring between days 18-29 of gestation. Ectodermal and mesodermal malformations (mainly involving the skull and vertebrae) may occur as a result of defects of neural tube closure. (From Joynt, Clinical Neurology, 1992, Ch55, pp31-41)\n    ", "id": "MESH:D009436"}
{"mention": "steroids", "mention_text": "Protective efficacy of neuroactive steroids against cocaine kindled-seizures in mice.", "entity": "Steroids", "aliases": "Catatoxic Steroids", "definition": "A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)\n    ", "id": "MESH:D013256"}
{"mention": "cocaine", "mention_text": "Protective efficacy of neuroactive steroids against cocaine kindled-seizures in mice.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "seizures", "mention_text": "Protective efficacy of neuroactive steroids against cocaine kindled-seizures in mice.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "steroids", "mention_text": "Neuroactive steroids demonstrate pharmacological actions that have relevance for a host of neurological and psychiatric disorders. They offer protection against seizures in a range of models and seem to inhibit certain stages of drug dependence in preclinical assessments. The present study was designed to evaluate two endogenous and one synthetic neuroactive steroid that positively modulate the gamma-aminobutyric acid (GABA(A)) receptor against the increase in sensitivity to the convulsant effects of cocaine engendered by repeated cocaine administration (seizure kindling). Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) and ganaxolone (a synthetic derivative of allopregnanolone 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) were tested for their ability to suppress the expression (anticonvulsant effect) and development (antiepileptogenic effect) of cocaine-kindled seizures in male, Swiss-Webster mice. Kindled seizures were induced by daily administration of 60 mg/kg cocaine for 5 days. All of these positive GABA(A) modulators suppressed the expression of kindled seizures, whereas only allopregnanolone and ganaxolone inhibited the development of kindling. Allopregnanolone and pregnanolone, but not ganaxolone, also reduced cumulative lethality associated with kindling. These findings demonstrate that some neuroactive steroids attenuate convulsant and sensitizing properties of cocaine and add to a growing literature on their potential use in the modulation of effects of drugs of abuse.", "entity": "Steroids", "aliases": "Catatoxic Steroids", "definition": "A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)\n    ", "id": "MESH:D013256"}
{"mention": "psychiatric disorders", "mention_text": "Neuroactive steroids demonstrate pharmacological actions that have relevance for a host of neurological and psychiatric disorders. They offer protection against seizures in a range of models and seem to inhibit certain stages of drug dependence in preclinical assessments. The present study was designed to evaluate two endogenous and one synthetic neuroactive steroid that positively modulate the gamma-aminobutyric acid (GABA(A)) receptor against the increase in sensitivity to the convulsant effects of cocaine engendered by repeated cocaine administration (seizure kindling). Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) and ganaxolone (a synthetic derivative of allopregnanolone 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) were tested for their ability to suppress the expression (anticonvulsant effect) and development (antiepileptogenic effect) of cocaine-kindled seizures in male, Swiss-Webster mice. Kindled seizures were induced by daily administration of 60 mg/kg cocaine for 5 days. All of these positive GABA(A) modulators suppressed the expression of kindled seizures, whereas only allopregnanolone and ganaxolone inhibited the development of kindling. Allopregnanolone and pregnanolone, but not ganaxolone, also reduced cumulative lethality associated with kindling. These findings demonstrate that some neuroactive steroids attenuate convulsant and sensitizing properties of cocaine and add to a growing literature on their potential use in the modulation of effects of drugs of abuse.", "entity": "Mental Disorders", "aliases": "Behavior Disorders Diagnosis Psychiatric Disorder Mental", "definition": "Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.\n    ", "id": "MESH:D001523"}
{"mention": "seizures", "mention_text": "Neuroactive steroids demonstrate pharmacological actions that have relevance for a host of neurological and psychiatric disorders. They offer protection against seizures in a range of models and seem to inhibit certain stages of drug dependence in preclinical assessments. The present study was designed to evaluate two endogenous and one synthetic neuroactive steroid that positively modulate the gamma-aminobutyric acid (GABA(A)) receptor against the increase in sensitivity to the convulsant effects of cocaine engendered by repeated cocaine administration (seizure kindling). Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) and ganaxolone (a synthetic derivative of allopregnanolone 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) were tested for their ability to suppress the expression (anticonvulsant effect) and development (antiepileptogenic effect) of cocaine-kindled seizures in male, Swiss-Webster mice. Kindled seizures were induced by daily administration of 60 mg/kg cocaine for 5 days. All of these positive GABA(A) modulators suppressed the expression of kindled seizures, whereas only allopregnanolone and ganaxolone inhibited the development of kindling. Allopregnanolone and pregnanolone, but not ganaxolone, also reduced cumulative lethality associated with kindling. These findings demonstrate that some neuroactive steroids attenuate convulsant and sensitizing properties of cocaine and add to a growing literature on their potential use in the modulation of effects of drugs of abuse.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "drug dependence", "mention_text": "Neuroactive steroids demonstrate pharmacological actions that have relevance for a host of neurological and psychiatric disorders. They offer protection against seizures in a range of models and seem to inhibit certain stages of drug dependence in preclinical assessments. The present study was designed to evaluate two endogenous and one synthetic neuroactive steroid that positively modulate the gamma-aminobutyric acid (GABA(A)) receptor against the increase in sensitivity to the convulsant effects of cocaine engendered by repeated cocaine administration (seizure kindling). Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) and ganaxolone (a synthetic derivative of allopregnanolone 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) were tested for their ability to suppress the expression (anticonvulsant effect) and development (antiepileptogenic effect) of cocaine-kindled seizures in male, Swiss-Webster mice. Kindled seizures were induced by daily administration of 60 mg/kg cocaine for 5 days. All of these positive GABA(A) modulators suppressed the expression of kindled seizures, whereas only allopregnanolone and ganaxolone inhibited the development of kindling. Allopregnanolone and pregnanolone, but not ganaxolone, also reduced cumulative lethality associated with kindling. These findings demonstrate that some neuroactive steroids attenuate convulsant and sensitizing properties of cocaine and add to a growing literature on their potential use in the modulation of effects of drugs of abuse.", "entity": "Substance-Related Disorders", "aliases": "Abuse Drug Substance Abuses Addiction Dependence Disorder Use Habituation Disorders Organic Mental Induced Substance-Induced Substance-Related", "definition": "Disorders related to substance abuse.\n    ", "id": "MESH:D019966"}
{"mention": "steroid", "mention_text": "Neuroactive steroids demonstrate pharmacological actions that have relevance for a host of neurological and psychiatric disorders. They offer protection against seizures in a range of models and seem to inhibit certain stages of drug dependence in preclinical assessments. The present study was designed to evaluate two endogenous and one synthetic neuroactive steroid that positively modulate the gamma-aminobutyric acid (GABA(A)) receptor against the increase in sensitivity to the convulsant effects of cocaine engendered by repeated cocaine administration (seizure kindling). Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) and ganaxolone (a synthetic derivative of allopregnanolone 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) were tested for their ability to suppress the expression (anticonvulsant effect) and development (antiepileptogenic effect) of cocaine-kindled seizures in male, Swiss-Webster mice. Kindled seizures were induced by daily administration of 60 mg/kg cocaine for 5 days. All of these positive GABA(A) modulators suppressed the expression of kindled seizures, whereas only allopregnanolone and ganaxolone inhibited the development of kindling. Allopregnanolone and pregnanolone, but not ganaxolone, also reduced cumulative lethality associated with kindling. These findings demonstrate that some neuroactive steroids attenuate convulsant and sensitizing properties of cocaine and add to a growing literature on their potential use in the modulation of effects of drugs of abuse.", "entity": "Steroids", "aliases": "Catatoxic Steroids", "definition": "A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)\n    ", "id": "MESH:D013256"}
{"mention": "gamma-aminobutyric acid", "mention_text": "Neuroactive steroids demonstrate pharmacological actions that have relevance for a host of neurological and psychiatric disorders. They offer protection against seizures in a range of models and seem to inhibit certain stages of drug dependence in preclinical assessments. The present study was designed to evaluate two endogenous and one synthetic neuroactive steroid that positively modulate the gamma-aminobutyric acid (GABA(A)) receptor against the increase in sensitivity to the convulsant effects of cocaine engendered by repeated cocaine administration (seizure kindling). Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) and ganaxolone (a synthetic derivative of allopregnanolone 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) were tested for their ability to suppress the expression (anticonvulsant effect) and development (antiepileptogenic effect) of cocaine-kindled seizures in male, Swiss-Webster mice. Kindled seizures were induced by daily administration of 60 mg/kg cocaine for 5 days. All of these positive GABA(A) modulators suppressed the expression of kindled seizures, whereas only allopregnanolone and ganaxolone inhibited the development of kindling. Allopregnanolone and pregnanolone, but not ganaxolone, also reduced cumulative lethality associated with kindling. These findings demonstrate that some neuroactive steroids attenuate convulsant and sensitizing properties of cocaine and add to a growing literature on their potential use in the modulation of effects of drugs of abuse.", "entity": "gamma-Aminobutyric Acid", "aliases": "4 Aminobutanoic Acid Aminobutyric 4-Aminobutanoic 4-Aminobutyric Hydrochloride gamma-Aminobutyric Aminalon Aminalone GABA Lithium Gammalon gamma Monolithium Salt Monosodium Calcium (2:1) Zinc", "definition": "The most common inhibitory neurotransmitter in the central nervous system.\n    ", "id": "MESH:D005680"}
{"mention": "GABA", "mention_text": "Neuroactive steroids demonstrate pharmacological actions that have relevance for a host of neurological and psychiatric disorders. They offer protection against seizures in a range of models and seem to inhibit certain stages of drug dependence in preclinical assessments. The present study was designed to evaluate two endogenous and one synthetic neuroactive steroid that positively modulate the gamma-aminobutyric acid (GABA(A)) receptor against the increase in sensitivity to the convulsant effects of cocaine engendered by repeated cocaine administration (seizure kindling). Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) and ganaxolone (a synthetic derivative of allopregnanolone 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) were tested for their ability to suppress the expression (anticonvulsant effect) and development (antiepileptogenic effect) of cocaine-kindled seizures in male, Swiss-Webster mice. Kindled seizures were induced by daily administration of 60 mg/kg cocaine for 5 days. All of these positive GABA(A) modulators suppressed the expression of kindled seizures, whereas only allopregnanolone and ganaxolone inhibited the development of kindling. Allopregnanolone and pregnanolone, but not ganaxolone, also reduced cumulative lethality associated with kindling. These findings demonstrate that some neuroactive steroids attenuate convulsant and sensitizing properties of cocaine and add to a growing literature on their potential use in the modulation of effects of drugs of abuse.", "entity": "gamma-Aminobutyric Acid", "aliases": "4 Aminobutanoic Acid Aminobutyric 4-Aminobutanoic 4-Aminobutyric Hydrochloride gamma-Aminobutyric Aminalon Aminalone GABA Lithium Gammalon gamma Monolithium Salt Monosodium Calcium (2:1) Zinc", "definition": "The most common inhibitory neurotransmitter in the central nervous system.\n    ", "id": "MESH:D005680"}
{"mention": "cocaine", "mention_text": "Neuroactive steroids demonstrate pharmacological actions that have relevance for a host of neurological and psychiatric disorders. They offer protection against seizures in a range of models and seem to inhibit certain stages of drug dependence in preclinical assessments. The present study was designed to evaluate two endogenous and one synthetic neuroactive steroid that positively modulate the gamma-aminobutyric acid (GABA(A)) receptor against the increase in sensitivity to the convulsant effects of cocaine engendered by repeated cocaine administration (seizure kindling). Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) and ganaxolone (a synthetic derivative of allopregnanolone 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) were tested for their ability to suppress the expression (anticonvulsant effect) and development (antiepileptogenic effect) of cocaine-kindled seizures in male, Swiss-Webster mice. Kindled seizures were induced by daily administration of 60 mg/kg cocaine for 5 days. All of these positive GABA(A) modulators suppressed the expression of kindled seizures, whereas only allopregnanolone and ganaxolone inhibited the development of kindling. Allopregnanolone and pregnanolone, but not ganaxolone, also reduced cumulative lethality associated with kindling. These findings demonstrate that some neuroactive steroids attenuate convulsant and sensitizing properties of cocaine and add to a growing literature on their potential use in the modulation of effects of drugs of abuse.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "seizure", "mention_text": "Neuroactive steroids demonstrate pharmacological actions that have relevance for a host of neurological and psychiatric disorders. They offer protection against seizures in a range of models and seem to inhibit certain stages of drug dependence in preclinical assessments. The present study was designed to evaluate two endogenous and one synthetic neuroactive steroid that positively modulate the gamma-aminobutyric acid (GABA(A)) receptor against the increase in sensitivity to the convulsant effects of cocaine engendered by repeated cocaine administration (seizure kindling). Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) and ganaxolone (a synthetic derivative of allopregnanolone 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) were tested for their ability to suppress the expression (anticonvulsant effect) and development (antiepileptogenic effect) of cocaine-kindled seizures in male, Swiss-Webster mice. Kindled seizures were induced by daily administration of 60 mg/kg cocaine for 5 days. All of these positive GABA(A) modulators suppressed the expression of kindled seizures, whereas only allopregnanolone and ganaxolone inhibited the development of kindling. Allopregnanolone and pregnanolone, but not ganaxolone, also reduced cumulative lethality associated with kindling. These findings demonstrate that some neuroactive steroids attenuate convulsant and sensitizing properties of cocaine and add to a growing literature on their potential use in the modulation of effects of drugs of abuse.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "Allopregnanolone", "mention_text": "Neuroactive steroids demonstrate pharmacological actions that have relevance for a host of neurological and psychiatric disorders. They offer protection against seizures in a range of models and seem to inhibit certain stages of drug dependence in preclinical assessments. The present study was designed to evaluate two endogenous and one synthetic neuroactive steroid that positively modulate the gamma-aminobutyric acid (GABA(A)) receptor against the increase in sensitivity to the convulsant effects of cocaine engendered by repeated cocaine administration (seizure kindling). Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) and ganaxolone (a synthetic derivative of allopregnanolone 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) were tested for their ability to suppress the expression (anticonvulsant effect) and development (antiepileptogenic effect) of cocaine-kindled seizures in male, Swiss-Webster mice. Kindled seizures were induced by daily administration of 60 mg/kg cocaine for 5 days. All of these positive GABA(A) modulators suppressed the expression of kindled seizures, whereas only allopregnanolone and ganaxolone inhibited the development of kindling. Allopregnanolone and pregnanolone, but not ganaxolone, also reduced cumulative lethality associated with kindling. These findings demonstrate that some neuroactive steroids attenuate convulsant and sensitizing properties of cocaine and add to a growing literature on their potential use in the modulation of effects of drugs of abuse.", "entity": "Pregnanolone", "aliases": "3 Hydroxypregnan 20 one alpha Hydroxy 5 alpha pregnan beta Tetrahydroprogesterone beta-Tetrahydroprogesterone alpha-Hydroxy-5 alpha-pregnan-20-one beta-pregnan-20-one 3-Hydroxypregnan-20-one 3beta 5alpha 3beta-Hydroxy-5alpha-pregnan-20-one Allopregnan ol Allopregnan-3 beta-ol-20-one Allopregnanolone Eltanolone Epipregnanolone Pregnan 3alpha Pregnan-3alpha-ol-20-one Pregnanolone (3alpha)-isomer (3alpha 5beta 17-alpha)-isomer (3alpha,5alpha)-isomer (3alpha,5beta)-isomer (3beta)-isomer (3beta 5alph", "definition": "A pregnane found in the urine of pregnant women and sows. It has anesthetic, hypnotic, and sedative properties.\n    ", "id": "MESH:D011280"}
{"mention": "3alpha-hydroxy-5alpha-pregnan-20-one", "mention_text": "Neuroactive steroids demonstrate pharmacological actions that have relevance for a host of neurological and psychiatric disorders. They offer protection against seizures in a range of models and seem to inhibit certain stages of drug dependence in preclinical assessments. The present study was designed to evaluate two endogenous and one synthetic neuroactive steroid that positively modulate the gamma-aminobutyric acid (GABA(A)) receptor against the increase in sensitivity to the convulsant effects of cocaine engendered by repeated cocaine administration (seizure kindling). Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) and ganaxolone (a synthetic derivative of allopregnanolone 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) were tested for their ability to suppress the expression (anticonvulsant effect) and development (antiepileptogenic effect) of cocaine-kindled seizures in male, Swiss-Webster mice. Kindled seizures were induced by daily administration of 60 mg/kg cocaine for 5 days. All of these positive GABA(A) modulators suppressed the expression of kindled seizures, whereas only allopregnanolone and ganaxolone inhibited the development of kindling. Allopregnanolone and pregnanolone, but not ganaxolone, also reduced cumulative lethality associated with kindling. These findings demonstrate that some neuroactive steroids attenuate convulsant and sensitizing properties of cocaine and add to a growing literature on their potential use in the modulation of effects of drugs of abuse.", "entity": "Pregnanolone", "aliases": "3 Hydroxypregnan 20 one alpha Hydroxy 5 alpha pregnan beta Tetrahydroprogesterone beta-Tetrahydroprogesterone alpha-Hydroxy-5 alpha-pregnan-20-one beta-pregnan-20-one 3-Hydroxypregnan-20-one 3beta 5alpha 3beta-Hydroxy-5alpha-pregnan-20-one Allopregnan ol Allopregnan-3 beta-ol-20-one Allopregnanolone Eltanolone Epipregnanolone Pregnan 3alpha Pregnan-3alpha-ol-20-one Pregnanolone (3alpha)-isomer (3alpha 5beta 17-alpha)-isomer (3alpha,5alpha)-isomer (3alpha,5beta)-isomer (3beta)-isomer (3beta 5alph", "definition": "A pregnane found in the urine of pregnant women and sows. It has anesthetic, hypnotic, and sedative properties.\n    ", "id": "MESH:D011280"}
{"mention": "pregnanolone", "mention_text": "Neuroactive steroids demonstrate pharmacological actions that have relevance for a host of neurological and psychiatric disorders. They offer protection against seizures in a range of models and seem to inhibit certain stages of drug dependence in preclinical assessments. The present study was designed to evaluate two endogenous and one synthetic neuroactive steroid that positively modulate the gamma-aminobutyric acid (GABA(A)) receptor against the increase in sensitivity to the convulsant effects of cocaine engendered by repeated cocaine administration (seizure kindling). Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) and ganaxolone (a synthetic derivative of allopregnanolone 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) were tested for their ability to suppress the expression (anticonvulsant effect) and development (antiepileptogenic effect) of cocaine-kindled seizures in male, Swiss-Webster mice. Kindled seizures were induced by daily administration of 60 mg/kg cocaine for 5 days. All of these positive GABA(A) modulators suppressed the expression of kindled seizures, whereas only allopregnanolone and ganaxolone inhibited the development of kindling. Allopregnanolone and pregnanolone, but not ganaxolone, also reduced cumulative lethality associated with kindling. These findings demonstrate that some neuroactive steroids attenuate convulsant and sensitizing properties of cocaine and add to a growing literature on their potential use in the modulation of effects of drugs of abuse.", "entity": "Pregnanolone", "aliases": "3 Hydroxypregnan 20 one alpha Hydroxy 5 alpha pregnan beta Tetrahydroprogesterone beta-Tetrahydroprogesterone alpha-Hydroxy-5 alpha-pregnan-20-one beta-pregnan-20-one 3-Hydroxypregnan-20-one 3beta 5alpha 3beta-Hydroxy-5alpha-pregnan-20-one Allopregnan ol Allopregnan-3 beta-ol-20-one Allopregnanolone Eltanolone Epipregnanolone Pregnan 3alpha Pregnan-3alpha-ol-20-one Pregnanolone (3alpha)-isomer (3alpha 5beta 17-alpha)-isomer (3alpha,5alpha)-isomer (3alpha,5beta)-isomer (3beta)-isomer (3beta 5alph", "definition": "A pregnane found in the urine of pregnant women and sows. It has anesthetic, hypnotic, and sedative properties.\n    ", "id": "MESH:D011280"}
{"mention": "3alpha-hydroxy-5beta-pregnan-20-one", "mention_text": "Neuroactive steroids demonstrate pharmacological actions that have relevance for a host of neurological and psychiatric disorders. They offer protection against seizures in a range of models and seem to inhibit certain stages of drug dependence in preclinical assessments. The present study was designed to evaluate two endogenous and one synthetic neuroactive steroid that positively modulate the gamma-aminobutyric acid (GABA(A)) receptor against the increase in sensitivity to the convulsant effects of cocaine engendered by repeated cocaine administration (seizure kindling). Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) and ganaxolone (a synthetic derivative of allopregnanolone 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) were tested for their ability to suppress the expression (anticonvulsant effect) and development (antiepileptogenic effect) of cocaine-kindled seizures in male, Swiss-Webster mice. Kindled seizures were induced by daily administration of 60 mg/kg cocaine for 5 days. All of these positive GABA(A) modulators suppressed the expression of kindled seizures, whereas only allopregnanolone and ganaxolone inhibited the development of kindling. Allopregnanolone and pregnanolone, but not ganaxolone, also reduced cumulative lethality associated with kindling. These findings demonstrate that some neuroactive steroids attenuate convulsant and sensitizing properties of cocaine and add to a growing literature on their potential use in the modulation of effects of drugs of abuse.", "entity": "Pregnanolone", "aliases": "3 Hydroxypregnan 20 one alpha Hydroxy 5 alpha pregnan beta Tetrahydroprogesterone beta-Tetrahydroprogesterone alpha-Hydroxy-5 alpha-pregnan-20-one beta-pregnan-20-one 3-Hydroxypregnan-20-one 3beta 5alpha 3beta-Hydroxy-5alpha-pregnan-20-one Allopregnan ol Allopregnan-3 beta-ol-20-one Allopregnanolone Eltanolone Epipregnanolone Pregnan 3alpha Pregnan-3alpha-ol-20-one Pregnanolone (3alpha)-isomer (3alpha 5beta 17-alpha)-isomer (3alpha,5alpha)-isomer (3alpha,5beta)-isomer (3beta)-isomer (3beta 5alph", "definition": "A pregnane found in the urine of pregnant women and sows. It has anesthetic, hypnotic, and sedative properties.\n    ", "id": "MESH:D011280"}
{"mention": "ganaxolone", "mention_text": "Neuroactive steroids demonstrate pharmacological actions that have relevance for a host of neurological and psychiatric disorders. They offer protection against seizures in a range of models and seem to inhibit certain stages of drug dependence in preclinical assessments. The present study was designed to evaluate two endogenous and one synthetic neuroactive steroid that positively modulate the gamma-aminobutyric acid (GABA(A)) receptor against the increase in sensitivity to the convulsant effects of cocaine engendered by repeated cocaine administration (seizure kindling). Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) and ganaxolone (a synthetic derivative of allopregnanolone 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) were tested for their ability to suppress the expression (anticonvulsant effect) and development (antiepileptogenic effect) of cocaine-kindled seizures in male, Swiss-Webster mice. Kindled seizures were induced by daily administration of 60 mg/kg cocaine for 5 days. All of these positive GABA(A) modulators suppressed the expression of kindled seizures, whereas only allopregnanolone and ganaxolone inhibited the development of kindling. Allopregnanolone and pregnanolone, but not ganaxolone, also reduced cumulative lethality associated with kindling. These findings demonstrate that some neuroactive steroids attenuate convulsant and sensitizing properties of cocaine and add to a growing literature on their potential use in the modulation of effects of drugs of abuse.", "entity": "ganaxolone", "aliases": "3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one CCD 1042 CCD-1042 ganaxolone", "definition": "", "id": "MESH:C105051"}
{"mention": "allopregnanolone", "mention_text": "Neuroactive steroids demonstrate pharmacological actions that have relevance for a host of neurological and psychiatric disorders. They offer protection against seizures in a range of models and seem to inhibit certain stages of drug dependence in preclinical assessments. The present study was designed to evaluate two endogenous and one synthetic neuroactive steroid that positively modulate the gamma-aminobutyric acid (GABA(A)) receptor against the increase in sensitivity to the convulsant effects of cocaine engendered by repeated cocaine administration (seizure kindling). Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) and ganaxolone (a synthetic derivative of allopregnanolone 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) were tested for their ability to suppress the expression (anticonvulsant effect) and development (antiepileptogenic effect) of cocaine-kindled seizures in male, Swiss-Webster mice. Kindled seizures were induced by daily administration of 60 mg/kg cocaine for 5 days. All of these positive GABA(A) modulators suppressed the expression of kindled seizures, whereas only allopregnanolone and ganaxolone inhibited the development of kindling. Allopregnanolone and pregnanolone, but not ganaxolone, also reduced cumulative lethality associated with kindling. These findings demonstrate that some neuroactive steroids attenuate convulsant and sensitizing properties of cocaine and add to a growing literature on their potential use in the modulation of effects of drugs of abuse.", "entity": "Pregnanolone", "aliases": "3 Hydroxypregnan 20 one alpha Hydroxy 5 alpha pregnan beta Tetrahydroprogesterone beta-Tetrahydroprogesterone alpha-Hydroxy-5 alpha-pregnan-20-one beta-pregnan-20-one 3-Hydroxypregnan-20-one 3beta 5alpha 3beta-Hydroxy-5alpha-pregnan-20-one Allopregnan ol Allopregnan-3 beta-ol-20-one Allopregnanolone Eltanolone Epipregnanolone Pregnan 3alpha Pregnan-3alpha-ol-20-one Pregnanolone (3alpha)-isomer (3alpha 5beta 17-alpha)-isomer (3alpha,5alpha)-isomer (3alpha,5beta)-isomer (3beta)-isomer (3beta 5alph", "definition": "A pregnane found in the urine of pregnant women and sows. It has anesthetic, hypnotic, and sedative properties.\n    ", "id": "MESH:D011280"}
{"mention": "3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one", "mention_text": "Neuroactive steroids demonstrate pharmacological actions that have relevance for a host of neurological and psychiatric disorders. They offer protection against seizures in a range of models and seem to inhibit certain stages of drug dependence in preclinical assessments. The present study was designed to evaluate two endogenous and one synthetic neuroactive steroid that positively modulate the gamma-aminobutyric acid (GABA(A)) receptor against the increase in sensitivity to the convulsant effects of cocaine engendered by repeated cocaine administration (seizure kindling). Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) and ganaxolone (a synthetic derivative of allopregnanolone 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) were tested for their ability to suppress the expression (anticonvulsant effect) and development (antiepileptogenic effect) of cocaine-kindled seizures in male, Swiss-Webster mice. Kindled seizures were induced by daily administration of 60 mg/kg cocaine for 5 days. All of these positive GABA(A) modulators suppressed the expression of kindled seizures, whereas only allopregnanolone and ganaxolone inhibited the development of kindling. Allopregnanolone and pregnanolone, but not ganaxolone, also reduced cumulative lethality associated with kindling. These findings demonstrate that some neuroactive steroids attenuate convulsant and sensitizing properties of cocaine and add to a growing literature on their potential use in the modulation of effects of drugs of abuse.", "entity": "ganaxolone", "aliases": "3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one CCD 1042 CCD-1042 ganaxolone", "definition": "", "id": "MESH:C105051"}
{"mention": "cyclosporine A", "mention_text": "Kidney function and morphology after short-term combination therapy with cyclosporine A, tacrolimus and sirolimus in the rat.", "entity": "Cyclosporine", "aliases": "Ciclosporin CsA Neoral CsA-Neoral CsANeoral CyA NOF CyA-NOF Cyclosporin A Cyclosporine OL 27 400 27-400 27400 Sandimmun Sandimmune", "definition": "A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).\n    ", "id": "MESH:D016572"}
{"mention": "tacrolimus", "mention_text": "Kidney function and morphology after short-term combination therapy with cyclosporine A, tacrolimus and sirolimus in the rat.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "sirolimus", "mention_text": "Kidney function and morphology after short-term combination therapy with cyclosporine A, tacrolimus and sirolimus in the rat.", "entity": "Sirolimus", "aliases": "AY 22 989 22-989 22989 I 2190A I-2190A I2190A Rapamune Rapamycin Sirolimus Wyeth Brand of", "definition": "A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.\n    ", "id": "MESH:D020123"}
{"mention": "Sirolimus", "mention_text": "BACKGROUND: Sirolimus (SRL) may supplement calcineurin inhibitors in clinical organ transplantation. These are nephrotoxic, but SRL seems to act differently displaying only minor nephrotoxic effects, although this question is still open. In a number of treatment protocols where SRL was combined with a calcineurin inhibitor indications of a synergistic nephrotoxic effect were described. The aim of this study was to examine further the renal function, including morphological analysis of the kidneys of male Sprague-Dawley rats treated with either cyclosporine A (CsA), tacrolimus (FK506) or SRL as monotherapies or in different combinations. METHODS: For a period of 2 weeks, CsA 15 mg/kg/day (given orally), FK506 3.0 mg/kg/day (given orally) or SRL 0.4 mg/kg/day (given intraperitoneally) was administered once a day as these doses have earlier been found to achieve a significant immunosuppressive effect in Sprague-Dawley rats. In the 'conscious catheterized rat' model, the glomerular filtration rate (GFR) was measured as the clearance of Cr(EDTA). The morphological analysis of the kidneys included a semi-quantitative scoring system analysing the degree of striped fibrosis, subcapsular fibrosis and the number of basophilic tubules, plus an additional stereological analysis of the total grade of fibrosis in the cortex stained with Sirius Red. RESULTS: CsA, FK506 and SRL all significantly decreased the GFR. A further deterioration was seen when CsA was combined with either FK506 or SRL, whereas the GFR remained unchanged in the group treated with FK506 plus SRL when compared with treatment with any of the single substances. The morphological changes presented a similar pattern. The semi-quantitative scoring was significantly worst in the group treated with CsA plus SRL (P<0.001 compared with controls) and the analysis of the total grade of fibrosis also showed the highest proportion in the same group and was significantly different from controls (P<0.02). The FK506 plus SRL combination showed only a marginally higher degree of fibrosis as compared with controls (P=0.05). CONCLUSION: This rat study demonstrated a synergistic nephrotoxic effect of CsA plus SRL, whereas FK506 plus SRL was better tolerated.", "entity": "Sirolimus", "aliases": "AY 22 989 22-989 22989 I 2190A I-2190A I2190A Rapamune Rapamycin Sirolimus Wyeth Brand of", "definition": "A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.\n    ", "id": "MESH:D020123"}
{"mention": "SRL", "mention_text": "BACKGROUND: Sirolimus (SRL) may supplement calcineurin inhibitors in clinical organ transplantation. These are nephrotoxic, but SRL seems to act differently displaying only minor nephrotoxic effects, although this question is still open. In a number of treatment protocols where SRL was combined with a calcineurin inhibitor indications of a synergistic nephrotoxic effect were described. The aim of this study was to examine further the renal function, including morphological analysis of the kidneys of male Sprague-Dawley rats treated with either cyclosporine A (CsA), tacrolimus (FK506) or SRL as monotherapies or in different combinations. METHODS: For a period of 2 weeks, CsA 15 mg/kg/day (given orally), FK506 3.0 mg/kg/day (given orally) or SRL 0.4 mg/kg/day (given intraperitoneally) was administered once a day as these doses have earlier been found to achieve a significant immunosuppressive effect in Sprague-Dawley rats. In the 'conscious catheterized rat' model, the glomerular filtration rate (GFR) was measured as the clearance of Cr(EDTA). The morphological analysis of the kidneys included a semi-quantitative scoring system analysing the degree of striped fibrosis, subcapsular fibrosis and the number of basophilic tubules, plus an additional stereological analysis of the total grade of fibrosis in the cortex stained with Sirius Red. RESULTS: CsA, FK506 and SRL all significantly decreased the GFR. A further deterioration was seen when CsA was combined with either FK506 or SRL, whereas the GFR remained unchanged in the group treated with FK506 plus SRL when compared with treatment with any of the single substances. The morphological changes presented a similar pattern. The semi-quantitative scoring was significantly worst in the group treated with CsA plus SRL (P<0.001 compared with controls) and the analysis of the total grade of fibrosis also showed the highest proportion in the same group and was significantly different from controls (P<0.02). The FK506 plus SRL combination showed only a marginally higher degree of fibrosis as compared with controls (P=0.05). CONCLUSION: This rat study demonstrated a synergistic nephrotoxic effect of CsA plus SRL, whereas FK506 plus SRL was better tolerated.", "entity": "Sirolimus", "aliases": "AY 22 989 22-989 22989 I 2190A I-2190A I2190A Rapamune Rapamycin Sirolimus Wyeth Brand of", "definition": "A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.\n    ", "id": "MESH:D020123"}
{"mention": "nephrotoxic", "mention_text": "BACKGROUND: Sirolimus (SRL) may supplement calcineurin inhibitors in clinical organ transplantation. These are nephrotoxic, but SRL seems to act differently displaying only minor nephrotoxic effects, although this question is still open. In a number of treatment protocols where SRL was combined with a calcineurin inhibitor indications of a synergistic nephrotoxic effect were described. The aim of this study was to examine further the renal function, including morphological analysis of the kidneys of male Sprague-Dawley rats treated with either cyclosporine A (CsA), tacrolimus (FK506) or SRL as monotherapies or in different combinations. METHODS: For a period of 2 weeks, CsA 15 mg/kg/day (given orally), FK506 3.0 mg/kg/day (given orally) or SRL 0.4 mg/kg/day (given intraperitoneally) was administered once a day as these doses have earlier been found to achieve a significant immunosuppressive effect in Sprague-Dawley rats. In the 'conscious catheterized rat' model, the glomerular filtration rate (GFR) was measured as the clearance of Cr(EDTA). The morphological analysis of the kidneys included a semi-quantitative scoring system analysing the degree of striped fibrosis, subcapsular fibrosis and the number of basophilic tubules, plus an additional stereological analysis of the total grade of fibrosis in the cortex stained with Sirius Red. RESULTS: CsA, FK506 and SRL all significantly decreased the GFR. A further deterioration was seen when CsA was combined with either FK506 or SRL, whereas the GFR remained unchanged in the group treated with FK506 plus SRL when compared with treatment with any of the single substances. The morphological changes presented a similar pattern. The semi-quantitative scoring was significantly worst in the group treated with CsA plus SRL (P<0.001 compared with controls) and the analysis of the total grade of fibrosis also showed the highest proportion in the same group and was significantly different from controls (P<0.02). The FK506 plus SRL combination showed only a marginally higher degree of fibrosis as compared with controls (P=0.05). CONCLUSION: This rat study demonstrated a synergistic nephrotoxic effect of CsA plus SRL, whereas FK506 plus SRL was better tolerated.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "cyclosporine A", "mention_text": "BACKGROUND: Sirolimus (SRL) may supplement calcineurin inhibitors in clinical organ transplantation. These are nephrotoxic, but SRL seems to act differently displaying only minor nephrotoxic effects, although this question is still open. In a number of treatment protocols where SRL was combined with a calcineurin inhibitor indications of a synergistic nephrotoxic effect were described. The aim of this study was to examine further the renal function, including morphological analysis of the kidneys of male Sprague-Dawley rats treated with either cyclosporine A (CsA), tacrolimus (FK506) or SRL as monotherapies or in different combinations. METHODS: For a period of 2 weeks, CsA 15 mg/kg/day (given orally), FK506 3.0 mg/kg/day (given orally) or SRL 0.4 mg/kg/day (given intraperitoneally) was administered once a day as these doses have earlier been found to achieve a significant immunosuppressive effect in Sprague-Dawley rats. In the 'conscious catheterized rat' model, the glomerular filtration rate (GFR) was measured as the clearance of Cr(EDTA). The morphological analysis of the kidneys included a semi-quantitative scoring system analysing the degree of striped fibrosis, subcapsular fibrosis and the number of basophilic tubules, plus an additional stereological analysis of the total grade of fibrosis in the cortex stained with Sirius Red. RESULTS: CsA, FK506 and SRL all significantly decreased the GFR. A further deterioration was seen when CsA was combined with either FK506 or SRL, whereas the GFR remained unchanged in the group treated with FK506 plus SRL when compared with treatment with any of the single substances. The morphological changes presented a similar pattern. The semi-quantitative scoring was significantly worst in the group treated with CsA plus SRL (P<0.001 compared with controls) and the analysis of the total grade of fibrosis also showed the highest proportion in the same group and was significantly different from controls (P<0.02). The FK506 plus SRL combination showed only a marginally higher degree of fibrosis as compared with controls (P=0.05). CONCLUSION: This rat study demonstrated a synergistic nephrotoxic effect of CsA plus SRL, whereas FK506 plus SRL was better tolerated.", "entity": "Cyclosporine", "aliases": "Ciclosporin CsA Neoral CsA-Neoral CsANeoral CyA NOF CyA-NOF Cyclosporin A Cyclosporine OL 27 400 27-400 27400 Sandimmun Sandimmune", "definition": "A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).\n    ", "id": "MESH:D016572"}
{"mention": "CsA", "mention_text": "BACKGROUND: Sirolimus (SRL) may supplement calcineurin inhibitors in clinical organ transplantation. These are nephrotoxic, but SRL seems to act differently displaying only minor nephrotoxic effects, although this question is still open. In a number of treatment protocols where SRL was combined with a calcineurin inhibitor indications of a synergistic nephrotoxic effect were described. The aim of this study was to examine further the renal function, including morphological analysis of the kidneys of male Sprague-Dawley rats treated with either cyclosporine A (CsA), tacrolimus (FK506) or SRL as monotherapies or in different combinations. METHODS: For a period of 2 weeks, CsA 15 mg/kg/day (given orally), FK506 3.0 mg/kg/day (given orally) or SRL 0.4 mg/kg/day (given intraperitoneally) was administered once a day as these doses have earlier been found to achieve a significant immunosuppressive effect in Sprague-Dawley rats. In the 'conscious catheterized rat' model, the glomerular filtration rate (GFR) was measured as the clearance of Cr(EDTA). The morphological analysis of the kidneys included a semi-quantitative scoring system analysing the degree of striped fibrosis, subcapsular fibrosis and the number of basophilic tubules, plus an additional stereological analysis of the total grade of fibrosis in the cortex stained with Sirius Red. RESULTS: CsA, FK506 and SRL all significantly decreased the GFR. A further deterioration was seen when CsA was combined with either FK506 or SRL, whereas the GFR remained unchanged in the group treated with FK506 plus SRL when compared with treatment with any of the single substances. The morphological changes presented a similar pattern. The semi-quantitative scoring was significantly worst in the group treated with CsA plus SRL (P<0.001 compared with controls) and the analysis of the total grade of fibrosis also showed the highest proportion in the same group and was significantly different from controls (P<0.02). The FK506 plus SRL combination showed only a marginally higher degree of fibrosis as compared with controls (P=0.05). CONCLUSION: This rat study demonstrated a synergistic nephrotoxic effect of CsA plus SRL, whereas FK506 plus SRL was better tolerated.", "entity": "Cyclosporine", "aliases": "Ciclosporin CsA Neoral CsA-Neoral CsANeoral CyA NOF CyA-NOF Cyclosporin A Cyclosporine OL 27 400 27-400 27400 Sandimmun Sandimmune", "definition": "A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).\n    ", "id": "MESH:D016572"}
{"mention": "tacrolimus", "mention_text": "BACKGROUND: Sirolimus (SRL) may supplement calcineurin inhibitors in clinical organ transplantation. These are nephrotoxic, but SRL seems to act differently displaying only minor nephrotoxic effects, although this question is still open. In a number of treatment protocols where SRL was combined with a calcineurin inhibitor indications of a synergistic nephrotoxic effect were described. The aim of this study was to examine further the renal function, including morphological analysis of the kidneys of male Sprague-Dawley rats treated with either cyclosporine A (CsA), tacrolimus (FK506) or SRL as monotherapies or in different combinations. METHODS: For a period of 2 weeks, CsA 15 mg/kg/day (given orally), FK506 3.0 mg/kg/day (given orally) or SRL 0.4 mg/kg/day (given intraperitoneally) was administered once a day as these doses have earlier been found to achieve a significant immunosuppressive effect in Sprague-Dawley rats. In the 'conscious catheterized rat' model, the glomerular filtration rate (GFR) was measured as the clearance of Cr(EDTA). The morphological analysis of the kidneys included a semi-quantitative scoring system analysing the degree of striped fibrosis, subcapsular fibrosis and the number of basophilic tubules, plus an additional stereological analysis of the total grade of fibrosis in the cortex stained with Sirius Red. RESULTS: CsA, FK506 and SRL all significantly decreased the GFR. A further deterioration was seen when CsA was combined with either FK506 or SRL, whereas the GFR remained unchanged in the group treated with FK506 plus SRL when compared with treatment with any of the single substances. The morphological changes presented a similar pattern. The semi-quantitative scoring was significantly worst in the group treated with CsA plus SRL (P<0.001 compared with controls) and the analysis of the total grade of fibrosis also showed the highest proportion in the same group and was significantly different from controls (P<0.02). The FK506 plus SRL combination showed only a marginally higher degree of fibrosis as compared with controls (P=0.05). CONCLUSION: This rat study demonstrated a synergistic nephrotoxic effect of CsA plus SRL, whereas FK506 plus SRL was better tolerated.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "FK506", "mention_text": "BACKGROUND: Sirolimus (SRL) may supplement calcineurin inhibitors in clinical organ transplantation. These are nephrotoxic, but SRL seems to act differently displaying only minor nephrotoxic effects, although this question is still open. In a number of treatment protocols where SRL was combined with a calcineurin inhibitor indications of a synergistic nephrotoxic effect were described. The aim of this study was to examine further the renal function, including morphological analysis of the kidneys of male Sprague-Dawley rats treated with either cyclosporine A (CsA), tacrolimus (FK506) or SRL as monotherapies or in different combinations. METHODS: For a period of 2 weeks, CsA 15 mg/kg/day (given orally), FK506 3.0 mg/kg/day (given orally) or SRL 0.4 mg/kg/day (given intraperitoneally) was administered once a day as these doses have earlier been found to achieve a significant immunosuppressive effect in Sprague-Dawley rats. In the 'conscious catheterized rat' model, the glomerular filtration rate (GFR) was measured as the clearance of Cr(EDTA). The morphological analysis of the kidneys included a semi-quantitative scoring system analysing the degree of striped fibrosis, subcapsular fibrosis and the number of basophilic tubules, plus an additional stereological analysis of the total grade of fibrosis in the cortex stained with Sirius Red. RESULTS: CsA, FK506 and SRL all significantly decreased the GFR. A further deterioration was seen when CsA was combined with either FK506 or SRL, whereas the GFR remained unchanged in the group treated with FK506 plus SRL when compared with treatment with any of the single substances. The morphological changes presented a similar pattern. The semi-quantitative scoring was significantly worst in the group treated with CsA plus SRL (P<0.001 compared with controls) and the analysis of the total grade of fibrosis also showed the highest proportion in the same group and was significantly different from controls (P<0.02). The FK506 plus SRL combination showed only a marginally higher degree of fibrosis as compared with controls (P=0.05). CONCLUSION: This rat study demonstrated a synergistic nephrotoxic effect of CsA plus SRL, whereas FK506 plus SRL was better tolerated.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "fibrosis", "mention_text": "BACKGROUND: Sirolimus (SRL) may supplement calcineurin inhibitors in clinical organ transplantation. These are nephrotoxic, but SRL seems to act differently displaying only minor nephrotoxic effects, although this question is still open. In a number of treatment protocols where SRL was combined with a calcineurin inhibitor indications of a synergistic nephrotoxic effect were described. The aim of this study was to examine further the renal function, including morphological analysis of the kidneys of male Sprague-Dawley rats treated with either cyclosporine A (CsA), tacrolimus (FK506) or SRL as monotherapies or in different combinations. METHODS: For a period of 2 weeks, CsA 15 mg/kg/day (given orally), FK506 3.0 mg/kg/day (given orally) or SRL 0.4 mg/kg/day (given intraperitoneally) was administered once a day as these doses have earlier been found to achieve a significant immunosuppressive effect in Sprague-Dawley rats. In the 'conscious catheterized rat' model, the glomerular filtration rate (GFR) was measured as the clearance of Cr(EDTA). The morphological analysis of the kidneys included a semi-quantitative scoring system analysing the degree of striped fibrosis, subcapsular fibrosis and the number of basophilic tubules, plus an additional stereological analysis of the total grade of fibrosis in the cortex stained with Sirius Red. RESULTS: CsA, FK506 and SRL all significantly decreased the GFR. A further deterioration was seen when CsA was combined with either FK506 or SRL, whereas the GFR remained unchanged in the group treated with FK506 plus SRL when compared with treatment with any of the single substances. The morphological changes presented a similar pattern. The semi-quantitative scoring was significantly worst in the group treated with CsA plus SRL (P<0.001 compared with controls) and the analysis of the total grade of fibrosis also showed the highest proportion in the same group and was significantly different from controls (P<0.02). The FK506 plus SRL combination showed only a marginally higher degree of fibrosis as compared with controls (P=0.05). CONCLUSION: This rat study demonstrated a synergistic nephrotoxic effect of CsA plus SRL, whereas FK506 plus SRL was better tolerated.", "entity": "Fibrosis", "aliases": "Cirrhosis Fibroses Fibrosis", "definition": "Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.\n    ", "id": "MESH:D005355"}
{"mention": "fucoidan", "mention_text": "Effect of fucoidan treatment on collagenase-induced intracerebral hemorrhage in rats.", "entity": "fucoidan", "aliases": "fucan sulfate Hor-1 fucoidan fucoidin sulfated fucans", "definition": "", "id": "MESH:C007789"}
{"mention": "intracerebral hemorrhage", "mention_text": "Effect of fucoidan treatment on collagenase-induced intracerebral hemorrhage in rats.", "entity": "Cerebral Hemorrhage", "aliases": "Brain Hemorrhage Cerebral Hemorrhages Parenchymal Cerebrum Intracerebral", "definition": "Bleeding into one or both CEREBRAL HEMISPHERES including the BASAL GANGLIA and the CEREBRAL CORTEX. It is often associated with HYPERTENSION and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D002543"}
{"mention": "brain damage", "mention_text": "Inflammatory cells are postulated to mediate some of the brain damage following ischemic stroke. Intracerebral hemorrhage is associated with more inflammation than ischemic stroke. We tested the sulfated polysaccharide fucoidan, which has been reported to reduce inflammatory brain damage, in a rat model of intracerebral hemorrhage induced by injection of bacterial collagenase into the caudate nucleus. Rats were treated with seven day intravenous infusion of fucoidan (30 micrograms h-1) or vehicle. The hematoma was assessed in vivo by magnetic resonance imaging. Motor behavior, passive avoidance, and skilled forelimb function were tested repeatedly for six weeks. Fucoidan-treated rats exhibited evidence of impaired blood clotting and hemodilution, had larger hematomas, and tended to have less inflammation in the vicinity of the hematoma after three days. They showed significantly more rapid improvement of motor function in the first week following hemorrhage and better memory retention in the passive avoidance test. Acute white matter edema and eventual neuronal loss in the striatum adjacent to the hematoma did not differ between the two groups. Investigation of more specific anti-inflammatory agents and hemodiluting agents are warranted in intracerebral hemorrhage.", "entity": "Brain Damage, Chronic", "aliases": "Brain Damage Chronic Encephalopathy", "definition": "A condition characterized by long-standing brain dysfunction or damage, usually of three months duration or longer. Potential etiologies include BRAIN INFARCTION; certain NEURODEGENERATIVE DISORDERS; CRANIOCEREBRAL TRAUMA; ANOXIA, BRAIN; ENCEPHALITIS; certain NEUROTOXICITY SYNDROMES; metabolic disorders (see BRAIN DISEASES, METABOLIC); and other conditions.\n    ", "id": "MESH:D001925"}
{"mention": "ischemic stroke", "mention_text": "Inflammatory cells are postulated to mediate some of the brain damage following ischemic stroke. Intracerebral hemorrhage is associated with more inflammation than ischemic stroke. We tested the sulfated polysaccharide fucoidan, which has been reported to reduce inflammatory brain damage, in a rat model of intracerebral hemorrhage induced by injection of bacterial collagenase into the caudate nucleus. Rats were treated with seven day intravenous infusion of fucoidan (30 micrograms h-1) or vehicle. The hematoma was assessed in vivo by magnetic resonance imaging. Motor behavior, passive avoidance, and skilled forelimb function were tested repeatedly for six weeks. Fucoidan-treated rats exhibited evidence of impaired blood clotting and hemodilution, had larger hematomas, and tended to have less inflammation in the vicinity of the hematoma after three days. They showed significantly more rapid improvement of motor function in the first week following hemorrhage and better memory retention in the passive avoidance test. Acute white matter edema and eventual neuronal loss in the striatum adjacent to the hematoma did not differ between the two groups. Investigation of more specific anti-inflammatory agents and hemodiluting agents are warranted in intracerebral hemorrhage.", "entity": "Cerebral Infarction", "aliases": "Anterior Choroidal Artery Infarction Cerebral Left Hemisphere Right Infarctions Subcortical Posterior", "definition": "The formation of an area of NECROSIS in the CEREBRUM caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., INFARCTION, ANTERIOR CEREBRAL ARTERY), and etiology (e.g., embolic infarction).\n    ", "id": "MESH:D002544"}
{"mention": "Intracerebral hemorrhage", "mention_text": "Inflammatory cells are postulated to mediate some of the brain damage following ischemic stroke. Intracerebral hemorrhage is associated with more inflammation than ischemic stroke. We tested the sulfated polysaccharide fucoidan, which has been reported to reduce inflammatory brain damage, in a rat model of intracerebral hemorrhage induced by injection of bacterial collagenase into the caudate nucleus. Rats were treated with seven day intravenous infusion of fucoidan (30 micrograms h-1) or vehicle. The hematoma was assessed in vivo by magnetic resonance imaging. Motor behavior, passive avoidance, and skilled forelimb function were tested repeatedly for six weeks. Fucoidan-treated rats exhibited evidence of impaired blood clotting and hemodilution, had larger hematomas, and tended to have less inflammation in the vicinity of the hematoma after three days. They showed significantly more rapid improvement of motor function in the first week following hemorrhage and better memory retention in the passive avoidance test. Acute white matter edema and eventual neuronal loss in the striatum adjacent to the hematoma did not differ between the two groups. Investigation of more specific anti-inflammatory agents and hemodiluting agents are warranted in intracerebral hemorrhage.", "entity": "Cerebral Hemorrhage", "aliases": "Brain Hemorrhage Cerebral Hemorrhages Parenchymal Cerebrum Intracerebral", "definition": "Bleeding into one or both CEREBRAL HEMISPHERES including the BASAL GANGLIA and the CEREBRAL CORTEX. It is often associated with HYPERTENSION and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D002543"}
{"mention": "inflammation", "mention_text": "Inflammatory cells are postulated to mediate some of the brain damage following ischemic stroke. Intracerebral hemorrhage is associated with more inflammation than ischemic stroke. We tested the sulfated polysaccharide fucoidan, which has been reported to reduce inflammatory brain damage, in a rat model of intracerebral hemorrhage induced by injection of bacterial collagenase into the caudate nucleus. Rats were treated with seven day intravenous infusion of fucoidan (30 micrograms h-1) or vehicle. The hematoma was assessed in vivo by magnetic resonance imaging. Motor behavior, passive avoidance, and skilled forelimb function were tested repeatedly for six weeks. Fucoidan-treated rats exhibited evidence of impaired blood clotting and hemodilution, had larger hematomas, and tended to have less inflammation in the vicinity of the hematoma after three days. They showed significantly more rapid improvement of motor function in the first week following hemorrhage and better memory retention in the passive avoidance test. Acute white matter edema and eventual neuronal loss in the striatum adjacent to the hematoma did not differ between the two groups. Investigation of more specific anti-inflammatory agents and hemodiluting agents are warranted in intracerebral hemorrhage.", "entity": "Inflammation", "aliases": "Inflammation Inflammations", "definition": "A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.\n    ", "id": "MESH:D007249"}
{"mention": "fucoidan", "mention_text": "Inflammatory cells are postulated to mediate some of the brain damage following ischemic stroke. Intracerebral hemorrhage is associated with more inflammation than ischemic stroke. We tested the sulfated polysaccharide fucoidan, which has been reported to reduce inflammatory brain damage, in a rat model of intracerebral hemorrhage induced by injection of bacterial collagenase into the caudate nucleus. Rats were treated with seven day intravenous infusion of fucoidan (30 micrograms h-1) or vehicle. The hematoma was assessed in vivo by magnetic resonance imaging. Motor behavior, passive avoidance, and skilled forelimb function were tested repeatedly for six weeks. Fucoidan-treated rats exhibited evidence of impaired blood clotting and hemodilution, had larger hematomas, and tended to have less inflammation in the vicinity of the hematoma after three days. They showed significantly more rapid improvement of motor function in the first week following hemorrhage and better memory retention in the passive avoidance test. Acute white matter edema and eventual neuronal loss in the striatum adjacent to the hematoma did not differ between the two groups. Investigation of more specific anti-inflammatory agents and hemodiluting agents are warranted in intracerebral hemorrhage.", "entity": "fucoidan", "aliases": "fucan sulfate Hor-1 fucoidan fucoidin sulfated fucans", "definition": "", "id": "MESH:C007789"}
{"mention": "intracerebral hemorrhage", "mention_text": "Inflammatory cells are postulated to mediate some of the brain damage following ischemic stroke. Intracerebral hemorrhage is associated with more inflammation than ischemic stroke. We tested the sulfated polysaccharide fucoidan, which has been reported to reduce inflammatory brain damage, in a rat model of intracerebral hemorrhage induced by injection of bacterial collagenase into the caudate nucleus. Rats were treated with seven day intravenous infusion of fucoidan (30 micrograms h-1) or vehicle. The hematoma was assessed in vivo by magnetic resonance imaging. Motor behavior, passive avoidance, and skilled forelimb function were tested repeatedly for six weeks. Fucoidan-treated rats exhibited evidence of impaired blood clotting and hemodilution, had larger hematomas, and tended to have less inflammation in the vicinity of the hematoma after three days. They showed significantly more rapid improvement of motor function in the first week following hemorrhage and better memory retention in the passive avoidance test. Acute white matter edema and eventual neuronal loss in the striatum adjacent to the hematoma did not differ between the two groups. Investigation of more specific anti-inflammatory agents and hemodiluting agents are warranted in intracerebral hemorrhage.", "entity": "Cerebral Hemorrhage", "aliases": "Brain Hemorrhage Cerebral Hemorrhages Parenchymal Cerebrum Intracerebral", "definition": "Bleeding into one or both CEREBRAL HEMISPHERES including the BASAL GANGLIA and the CEREBRAL CORTEX. It is often associated with HYPERTENSION and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D002543"}
{"mention": "hematoma", "mention_text": "Inflammatory cells are postulated to mediate some of the brain damage following ischemic stroke. Intracerebral hemorrhage is associated with more inflammation than ischemic stroke. We tested the sulfated polysaccharide fucoidan, which has been reported to reduce inflammatory brain damage, in a rat model of intracerebral hemorrhage induced by injection of bacterial collagenase into the caudate nucleus. Rats were treated with seven day intravenous infusion of fucoidan (30 micrograms h-1) or vehicle. The hematoma was assessed in vivo by magnetic resonance imaging. Motor behavior, passive avoidance, and skilled forelimb function were tested repeatedly for six weeks. Fucoidan-treated rats exhibited evidence of impaired blood clotting and hemodilution, had larger hematomas, and tended to have less inflammation in the vicinity of the hematoma after three days. They showed significantly more rapid improvement of motor function in the first week following hemorrhage and better memory retention in the passive avoidance test. Acute white matter edema and eventual neuronal loss in the striatum adjacent to the hematoma did not differ between the two groups. Investigation of more specific anti-inflammatory agents and hemodiluting agents are warranted in intracerebral hemorrhage.", "entity": "Hematoma", "aliases": "Hematoma Hematomas", "definition": "A collection of blood outside the BLOOD VESSELS. Hematoma can be localized in an organ, space, or tissue.\n    ", "id": "MESH:D006406"}
{"mention": "Fucoidan", "mention_text": "Inflammatory cells are postulated to mediate some of the brain damage following ischemic stroke. Intracerebral hemorrhage is associated with more inflammation than ischemic stroke. We tested the sulfated polysaccharide fucoidan, which has been reported to reduce inflammatory brain damage, in a rat model of intracerebral hemorrhage induced by injection of bacterial collagenase into the caudate nucleus. Rats were treated with seven day intravenous infusion of fucoidan (30 micrograms h-1) or vehicle. The hematoma was assessed in vivo by magnetic resonance imaging. Motor behavior, passive avoidance, and skilled forelimb function were tested repeatedly for six weeks. Fucoidan-treated rats exhibited evidence of impaired blood clotting and hemodilution, had larger hematomas, and tended to have less inflammation in the vicinity of the hematoma after three days. They showed significantly more rapid improvement of motor function in the first week following hemorrhage and better memory retention in the passive avoidance test. Acute white matter edema and eventual neuronal loss in the striatum adjacent to the hematoma did not differ between the two groups. Investigation of more specific anti-inflammatory agents and hemodiluting agents are warranted in intracerebral hemorrhage.", "entity": "fucoidan", "aliases": "fucan sulfate Hor-1 fucoidan fucoidin sulfated fucans", "definition": "", "id": "MESH:C007789"}
{"mention": "impaired blood clotting", "mention_text": "Inflammatory cells are postulated to mediate some of the brain damage following ischemic stroke. Intracerebral hemorrhage is associated with more inflammation than ischemic stroke. We tested the sulfated polysaccharide fucoidan, which has been reported to reduce inflammatory brain damage, in a rat model of intracerebral hemorrhage induced by injection of bacterial collagenase into the caudate nucleus. Rats were treated with seven day intravenous infusion of fucoidan (30 micrograms h-1) or vehicle. The hematoma was assessed in vivo by magnetic resonance imaging. Motor behavior, passive avoidance, and skilled forelimb function were tested repeatedly for six weeks. Fucoidan-treated rats exhibited evidence of impaired blood clotting and hemodilution, had larger hematomas, and tended to have less inflammation in the vicinity of the hematoma after three days. They showed significantly more rapid improvement of motor function in the first week following hemorrhage and better memory retention in the passive avoidance test. Acute white matter edema and eventual neuronal loss in the striatum adjacent to the hematoma did not differ between the two groups. Investigation of more specific anti-inflammatory agents and hemodiluting agents are warranted in intracerebral hemorrhage.", "entity": "Hemostatic Disorders", "aliases": "Disorder Vascular Hemostatic Disorders", "definition": "Pathological processes involving the integrity of blood circulation. Hemostasis depends on the integrity of BLOOD VESSELS, blood fluidity, and BLOOD COAGULATION. Majority of the hemostatic disorders are caused by disruption of the normal interaction between the VASCULAR ENDOTHELIUM, the plasma proteins (including BLOOD COAGULATION FACTORS), and PLATELETS.\n    ", "id": "MESH:D020141"}
{"mention": "hemodilution", "mention_text": "Inflammatory cells are postulated to mediate some of the brain damage following ischemic stroke. Intracerebral hemorrhage is associated with more inflammation than ischemic stroke. We tested the sulfated polysaccharide fucoidan, which has been reported to reduce inflammatory brain damage, in a rat model of intracerebral hemorrhage induced by injection of bacterial collagenase into the caudate nucleus. Rats were treated with seven day intravenous infusion of fucoidan (30 micrograms h-1) or vehicle. The hematoma was assessed in vivo by magnetic resonance imaging. Motor behavior, passive avoidance, and skilled forelimb function were tested repeatedly for six weeks. Fucoidan-treated rats exhibited evidence of impaired blood clotting and hemodilution, had larger hematomas, and tended to have less inflammation in the vicinity of the hematoma after three days. They showed significantly more rapid improvement of motor function in the first week following hemorrhage and better memory retention in the passive avoidance test. Acute white matter edema and eventual neuronal loss in the striatum adjacent to the hematoma did not differ between the two groups. Investigation of more specific anti-inflammatory agents and hemodiluting agents are warranted in intracerebral hemorrhage.", "entity": "Hemostatic Disorders", "aliases": "Disorder Vascular Hemostatic Disorders", "definition": "Pathological processes involving the integrity of blood circulation. Hemostasis depends on the integrity of BLOOD VESSELS, blood fluidity, and BLOOD COAGULATION. Majority of the hemostatic disorders are caused by disruption of the normal interaction between the VASCULAR ENDOTHELIUM, the plasma proteins (including BLOOD COAGULATION FACTORS), and PLATELETS.\n    ", "id": "MESH:D020141"}
{"mention": "hematomas", "mention_text": "Inflammatory cells are postulated to mediate some of the brain damage following ischemic stroke. Intracerebral hemorrhage is associated with more inflammation than ischemic stroke. We tested the sulfated polysaccharide fucoidan, which has been reported to reduce inflammatory brain damage, in a rat model of intracerebral hemorrhage induced by injection of bacterial collagenase into the caudate nucleus. Rats were treated with seven day intravenous infusion of fucoidan (30 micrograms h-1) or vehicle. The hematoma was assessed in vivo by magnetic resonance imaging. Motor behavior, passive avoidance, and skilled forelimb function were tested repeatedly for six weeks. Fucoidan-treated rats exhibited evidence of impaired blood clotting and hemodilution, had larger hematomas, and tended to have less inflammation in the vicinity of the hematoma after three days. They showed significantly more rapid improvement of motor function in the first week following hemorrhage and better memory retention in the passive avoidance test. Acute white matter edema and eventual neuronal loss in the striatum adjacent to the hematoma did not differ between the two groups. Investigation of more specific anti-inflammatory agents and hemodiluting agents are warranted in intracerebral hemorrhage.", "entity": "Hematoma", "aliases": "Hematoma Hematomas", "definition": "A collection of blood outside the BLOOD VESSELS. Hematoma can be localized in an organ, space, or tissue.\n    ", "id": "MESH:D006406"}
{"mention": "hemorrhage", "mention_text": "Inflammatory cells are postulated to mediate some of the brain damage following ischemic stroke. Intracerebral hemorrhage is associated with more inflammation than ischemic stroke. We tested the sulfated polysaccharide fucoidan, which has been reported to reduce inflammatory brain damage, in a rat model of intracerebral hemorrhage induced by injection of bacterial collagenase into the caudate nucleus. Rats were treated with seven day intravenous infusion of fucoidan (30 micrograms h-1) or vehicle. The hematoma was assessed in vivo by magnetic resonance imaging. Motor behavior, passive avoidance, and skilled forelimb function were tested repeatedly for six weeks. Fucoidan-treated rats exhibited evidence of impaired blood clotting and hemodilution, had larger hematomas, and tended to have less inflammation in the vicinity of the hematoma after three days. They showed significantly more rapid improvement of motor function in the first week following hemorrhage and better memory retention in the passive avoidance test. Acute white matter edema and eventual neuronal loss in the striatum adjacent to the hematoma did not differ between the two groups. Investigation of more specific anti-inflammatory agents and hemodiluting agents are warranted in intracerebral hemorrhage.", "entity": "Hemorrhage", "aliases": "Bleeding Hemorrhage Hemorrhages", "definition": "Bleeding or escape of blood from a vessel.\n    ", "id": "MESH:D006470"}
{"mention": "white matter edema", "mention_text": "Inflammatory cells are postulated to mediate some of the brain damage following ischemic stroke. Intracerebral hemorrhage is associated with more inflammation than ischemic stroke. We tested the sulfated polysaccharide fucoidan, which has been reported to reduce inflammatory brain damage, in a rat model of intracerebral hemorrhage induced by injection of bacterial collagenase into the caudate nucleus. Rats were treated with seven day intravenous infusion of fucoidan (30 micrograms h-1) or vehicle. The hematoma was assessed in vivo by magnetic resonance imaging. Motor behavior, passive avoidance, and skilled forelimb function were tested repeatedly for six weeks. Fucoidan-treated rats exhibited evidence of impaired blood clotting and hemodilution, had larger hematomas, and tended to have less inflammation in the vicinity of the hematoma after three days. They showed significantly more rapid improvement of motor function in the first week following hemorrhage and better memory retention in the passive avoidance test. Acute white matter edema and eventual neuronal loss in the striatum adjacent to the hematoma did not differ between the two groups. Investigation of more specific anti-inflammatory agents and hemodiluting agents are warranted in intracerebral hemorrhage.", "entity": "Brain Edema", "aliases": "Brain Edema Cytotoxic Vasogenic Swelling Swellings Cerebral Edemas Intracranial", "definition": "Increased intracellular or extracellular fluid in brain tissue. Cytotoxic brain edema (swelling due to increased intracellular fluid) is indicative of a disturbance in cell metabolism, and is commonly associated with hypoxic or ischemic injuries (see HYPOXIA, BRAIN). An increase in extracellular fluid may be caused by increased brain capillary permeability (vasogenic edema), an osmotic gradient, local blockages in interstitial fluid pathways, or by obstruction of CSF flow (e.g., obstructive HYDROCEPHALUS). (From Childs Nerv Syst 1992 Sep; 8(6):301-6)\n    ", "id": "MESH:D001929"}
{"mention": "neuronal loss", "mention_text": "Inflammatory cells are postulated to mediate some of the brain damage following ischemic stroke. Intracerebral hemorrhage is associated with more inflammation than ischemic stroke. We tested the sulfated polysaccharide fucoidan, which has been reported to reduce inflammatory brain damage, in a rat model of intracerebral hemorrhage induced by injection of bacterial collagenase into the caudate nucleus. Rats were treated with seven day intravenous infusion of fucoidan (30 micrograms h-1) or vehicle. The hematoma was assessed in vivo by magnetic resonance imaging. Motor behavior, passive avoidance, and skilled forelimb function were tested repeatedly for six weeks. Fucoidan-treated rats exhibited evidence of impaired blood clotting and hemodilution, had larger hematomas, and tended to have less inflammation in the vicinity of the hematoma after three days. They showed significantly more rapid improvement of motor function in the first week following hemorrhage and better memory retention in the passive avoidance test. Acute white matter edema and eventual neuronal loss in the striatum adjacent to the hematoma did not differ between the two groups. Investigation of more specific anti-inflammatory agents and hemodiluting agents are warranted in intracerebral hemorrhage.", "entity": "Nerve Degeneration", "aliases": "Degeneration Nerve Neuron Degenerations", "definition": "Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.\n    ", "id": "MESH:D009410"}
{"mention": "Paracetamol", "mention_text": "Paracetamol-associated coma, metabolic acidosis, renal and hepatic failure.", "entity": "Acetaminophen", "aliases": "APAP Acamol Acephen Acetaco Acetamidophenol Acetaminophen Acetominophen Algotropyl Anacin 3 Anacin-3 Anacin3 Datril Hydroxyacetanilide N-(4-Hydroxyphenyl)acetanilide N-Acetyl-p-aminophenol Panadol Paracetamol Tylenol p-Acetamidophenol p-Hydroxyacetanilide", "definition": "Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.\n    ", "id": "MESH:D000082"}
{"mention": "coma", "mention_text": "Paracetamol-associated coma, metabolic acidosis, renal and hepatic failure.", "entity": "Coma", "aliases": "Coma Comas Comatose Pseudocoma Pseudocomas", "definition": "A profound state of unconsciousness associated with depressed cerebral activity from which the individual cannot be aroused. Coma generally occurs when there is dysfunction or injury involving both cerebral hemispheres or the brain stem RETICULAR FORMATION.\n    ", "id": "MESH:D003128"}
{"mention": "metabolic acidosis", "mention_text": "Paracetamol-associated coma, metabolic acidosis, renal and hepatic failure.", "entity": "Acidosis", "aliases": "Acidoses Metabolic Acidosis", "definition": "A pathologic condition of acid accumulation or depletion of base in the body. The two main types are RESPIRATORY ACIDOSIS and metabolic acidosis, due to metabolic acid build up.\n    ", "id": "MESH:D000138"}
{"mention": "hepatic failure", "mention_text": "Paracetamol-associated coma, metabolic acidosis, renal and hepatic failure.", "entity": "Liver Failure", "aliases": "Hepatic Failure Liver", "definition": "Severe inability of the LIVER to perform its normal metabolic functions, as evidenced by severe JAUNDICE and abnormal serum levels of AMMONIA; BILIRUBIN; ALKALINE PHOSPHATASE; ASPARTATE AMINOTRANSFERASE; LACTATE DEHYDROGENASES; and albumin/globulin ratio. (Blakiston's Gould Medical Dictionary, 4th ed)\n    ", "id": "MESH:D017093"}
{"mention": "metabolic acidosis", "mention_text": "A case of metabolic acidosis, acute renal failure and hepatic failure following paracetamol ingestion is presented. The diagnostic difficulty at presentation is highlighted. Continuous arteriovenous haemofiltration proved a valuable means of maintaining fluid and electrolyte balance. The patient recovered.", "entity": "Acidosis", "aliases": "Acidoses Metabolic Acidosis", "definition": "A pathologic condition of acid accumulation or depletion of base in the body. The two main types are RESPIRATORY ACIDOSIS and metabolic acidosis, due to metabolic acid build up.\n    ", "id": "MESH:D000138"}
{"mention": "acute renal failure", "mention_text": "A case of metabolic acidosis, acute renal failure and hepatic failure following paracetamol ingestion is presented. The diagnostic difficulty at presentation is highlighted. Continuous arteriovenous haemofiltration proved a valuable means of maintaining fluid and electrolyte balance. The patient recovered.", "entity": "Acute Kidney Injury", "aliases": "Acute Kidney Failure Failures Injuries Injury Insufficiencies Insufficiency Renal", "definition": "Abrupt reduction in kidney function. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions.\n    ", "id": "MESH:D058186"}
{"mention": "paracetamol", "mention_text": "A case of metabolic acidosis, acute renal failure and hepatic failure following paracetamol ingestion is presented. The diagnostic difficulty at presentation is highlighted. Continuous arteriovenous haemofiltration proved a valuable means of maintaining fluid and electrolyte balance. The patient recovered.", "entity": "Acetaminophen", "aliases": "APAP Acamol Acephen Acetaco Acetamidophenol Acetaminophen Acetominophen Algotropyl Anacin 3 Anacin-3 Anacin3 Datril Hydroxyacetanilide N-(4-Hydroxyphenyl)acetanilide N-Acetyl-p-aminophenol Panadol Paracetamol Tylenol p-Acetamidophenol p-Hydroxyacetanilide", "definition": "Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.\n    ", "id": "MESH:D000082"}
{"mention": "ketoconazole", "mention_text": "Hepatic reactions associated with ketoconazole in the United Kingdom.", "entity": "Ketoconazole", "aliases": "Janssen Brand of Ketoconazole Nizoral R 41400 R-41400 R41,400 R41400", "definition": "Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.\n    ", "id": "MESH:D007654"}
{"mention": "Ketoconazole", "mention_text": "Ketoconazole was introduced in the United Kingdom in 1981. By November 1984 the Committee on Safety of Medicines had received 82 reports of possible hepatotoxicity associated with the drug, including five deaths. An analysis of the 75 cases that had been adequately followed up suggested that 16, including three deaths, were probably related to treatment with the drug. Of the remainder, 48 were possibly related to treatment, five were unlikely to be so, and six were unclassifiable. The mean age of patients in the 16 probable cases was 57.9, with hepatotoxicity being more common in women. The average duration of treatment before the onset of jaundice was 61 days. None of these well validated cases occurred within the first 10 days after treatment. The results of serum liver function tests suggested hepatocellular injury in 10 (63%); the rest showed a mixed pattern. In contrast, the results of histological examination of the liver often showed evidence of cholestasis. The characteristics of the 48 patients in the possible cases were similar. Allergic manifestations such as rash and eosinophilia were rare. Hepatitis was usually reversible when treatment was stopped, with the results of liver function tests returning to normal after an average of 3.1 months. In two of the three deaths probably associated with ketoconazole treatment the drug had been continued after the onset of jaundice and other symptoms of hepatitis. Clinical and biochemical monitoring at regular intervals for evidence of hepatitis is advised during long term treatment with ketoconazole to prevent possible serious hepatic injury.", "entity": "Ketoconazole", "aliases": "Janssen Brand of Ketoconazole Nizoral R 41400 R-41400 R41,400 R41400", "definition": "Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.\n    ", "id": "MESH:D007654"}
{"mention": "hepatotoxicity", "mention_text": "Ketoconazole was introduced in the United Kingdom in 1981. By November 1984 the Committee on Safety of Medicines had received 82 reports of possible hepatotoxicity associated with the drug, including five deaths. An analysis of the 75 cases that had been adequately followed up suggested that 16, including three deaths, were probably related to treatment with the drug. Of the remainder, 48 were possibly related to treatment, five were unlikely to be so, and six were unclassifiable. The mean age of patients in the 16 probable cases was 57.9, with hepatotoxicity being more common in women. The average duration of treatment before the onset of jaundice was 61 days. None of these well validated cases occurred within the first 10 days after treatment. The results of serum liver function tests suggested hepatocellular injury in 10 (63%); the rest showed a mixed pattern. In contrast, the results of histological examination of the liver often showed evidence of cholestasis. The characteristics of the 48 patients in the possible cases were similar. Allergic manifestations such as rash and eosinophilia were rare. Hepatitis was usually reversible when treatment was stopped, with the results of liver function tests returning to normal after an average of 3.1 months. In two of the three deaths probably associated with ketoconazole treatment the drug had been continued after the onset of jaundice and other symptoms of hepatitis. Clinical and biochemical monitoring at regular intervals for evidence of hepatitis is advised during long term treatment with ketoconazole to prevent possible serious hepatic injury.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "deaths", "mention_text": "Ketoconazole was introduced in the United Kingdom in 1981. By November 1984 the Committee on Safety of Medicines had received 82 reports of possible hepatotoxicity associated with the drug, including five deaths. An analysis of the 75 cases that had been adequately followed up suggested that 16, including three deaths, were probably related to treatment with the drug. Of the remainder, 48 were possibly related to treatment, five were unlikely to be so, and six were unclassifiable. The mean age of patients in the 16 probable cases was 57.9, with hepatotoxicity being more common in women. The average duration of treatment before the onset of jaundice was 61 days. None of these well validated cases occurred within the first 10 days after treatment. The results of serum liver function tests suggested hepatocellular injury in 10 (63%); the rest showed a mixed pattern. In contrast, the results of histological examination of the liver often showed evidence of cholestasis. The characteristics of the 48 patients in the possible cases were similar. Allergic manifestations such as rash and eosinophilia were rare. Hepatitis was usually reversible when treatment was stopped, with the results of liver function tests returning to normal after an average of 3.1 months. In two of the three deaths probably associated with ketoconazole treatment the drug had been continued after the onset of jaundice and other symptoms of hepatitis. Clinical and biochemical monitoring at regular intervals for evidence of hepatitis is advised during long term treatment with ketoconazole to prevent possible serious hepatic injury.", "entity": "Death", "aliases": "Cardiac Death Determination of Near-Death Experience", "definition": "Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.\n    ", "id": "MESH:D003643"}
{"mention": "jaundice", "mention_text": "Ketoconazole was introduced in the United Kingdom in 1981. By November 1984 the Committee on Safety of Medicines had received 82 reports of possible hepatotoxicity associated with the drug, including five deaths. An analysis of the 75 cases that had been adequately followed up suggested that 16, including three deaths, were probably related to treatment with the drug. Of the remainder, 48 were possibly related to treatment, five were unlikely to be so, and six were unclassifiable. The mean age of patients in the 16 probable cases was 57.9, with hepatotoxicity being more common in women. The average duration of treatment before the onset of jaundice was 61 days. None of these well validated cases occurred within the first 10 days after treatment. The results of serum liver function tests suggested hepatocellular injury in 10 (63%); the rest showed a mixed pattern. In contrast, the results of histological examination of the liver often showed evidence of cholestasis. The characteristics of the 48 patients in the possible cases were similar. Allergic manifestations such as rash and eosinophilia were rare. Hepatitis was usually reversible when treatment was stopped, with the results of liver function tests returning to normal after an average of 3.1 months. In two of the three deaths probably associated with ketoconazole treatment the drug had been continued after the onset of jaundice and other symptoms of hepatitis. Clinical and biochemical monitoring at regular intervals for evidence of hepatitis is advised during long term treatment with ketoconazole to prevent possible serious hepatic injury.", "entity": "Jaundice", "aliases": "Hemolytic Jaundice Jaundices Icterus", "definition": "A clinical manifestation of HYPERBILIRUBINEMIA, characterized by the yellowish staining of the SKIN; MUCOUS MEMBRANE; and SCLERA. Clinical jaundice usually is a sign of LIVER dysfunction.\n    ", "id": "MESH:D007565"}
{"mention": "hepatocellular injury", "mention_text": "Ketoconazole was introduced in the United Kingdom in 1981. By November 1984 the Committee on Safety of Medicines had received 82 reports of possible hepatotoxicity associated with the drug, including five deaths. An analysis of the 75 cases that had been adequately followed up suggested that 16, including three deaths, were probably related to treatment with the drug. Of the remainder, 48 were possibly related to treatment, five were unlikely to be so, and six were unclassifiable. The mean age of patients in the 16 probable cases was 57.9, with hepatotoxicity being more common in women. The average duration of treatment before the onset of jaundice was 61 days. None of these well validated cases occurred within the first 10 days after treatment. The results of serum liver function tests suggested hepatocellular injury in 10 (63%); the rest showed a mixed pattern. In contrast, the results of histological examination of the liver often showed evidence of cholestasis. The characteristics of the 48 patients in the possible cases were similar. Allergic manifestations such as rash and eosinophilia were rare. Hepatitis was usually reversible when treatment was stopped, with the results of liver function tests returning to normal after an average of 3.1 months. In two of the three deaths probably associated with ketoconazole treatment the drug had been continued after the onset of jaundice and other symptoms of hepatitis. Clinical and biochemical monitoring at regular intervals for evidence of hepatitis is advised during long term treatment with ketoconazole to prevent possible serious hepatic injury.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "cholestasis", "mention_text": "Ketoconazole was introduced in the United Kingdom in 1981. By November 1984 the Committee on Safety of Medicines had received 82 reports of possible hepatotoxicity associated with the drug, including five deaths. An analysis of the 75 cases that had been adequately followed up suggested that 16, including three deaths, were probably related to treatment with the drug. Of the remainder, 48 were possibly related to treatment, five were unlikely to be so, and six were unclassifiable. The mean age of patients in the 16 probable cases was 57.9, with hepatotoxicity being more common in women. The average duration of treatment before the onset of jaundice was 61 days. None of these well validated cases occurred within the first 10 days after treatment. The results of serum liver function tests suggested hepatocellular injury in 10 (63%); the rest showed a mixed pattern. In contrast, the results of histological examination of the liver often showed evidence of cholestasis. The characteristics of the 48 patients in the possible cases were similar. Allergic manifestations such as rash and eosinophilia were rare. Hepatitis was usually reversible when treatment was stopped, with the results of liver function tests returning to normal after an average of 3.1 months. In two of the three deaths probably associated with ketoconazole treatment the drug had been continued after the onset of jaundice and other symptoms of hepatitis. Clinical and biochemical monitoring at regular intervals for evidence of hepatitis is advised during long term treatment with ketoconazole to prevent possible serious hepatic injury.", "entity": "Cholestasis", "aliases": "Bile Duct Obstruction Obstructions Biliary Stases Stasis Cholestases Cholestasis", "definition": "Impairment of bile flow due to obstruction in small bile ducts (INTRAHEPATIC CHOLESTASIS) or obstruction in large bile ducts (EXTRAHEPATIC CHOLESTASIS).\n    ", "id": "MESH:D002779"}
{"mention": "rash", "mention_text": "Ketoconazole was introduced in the United Kingdom in 1981. By November 1984 the Committee on Safety of Medicines had received 82 reports of possible hepatotoxicity associated with the drug, including five deaths. An analysis of the 75 cases that had been adequately followed up suggested that 16, including three deaths, were probably related to treatment with the drug. Of the remainder, 48 were possibly related to treatment, five were unlikely to be so, and six were unclassifiable. The mean age of patients in the 16 probable cases was 57.9, with hepatotoxicity being more common in women. The average duration of treatment before the onset of jaundice was 61 days. None of these well validated cases occurred within the first 10 days after treatment. The results of serum liver function tests suggested hepatocellular injury in 10 (63%); the rest showed a mixed pattern. In contrast, the results of histological examination of the liver often showed evidence of cholestasis. The characteristics of the 48 patients in the possible cases were similar. Allergic manifestations such as rash and eosinophilia were rare. Hepatitis was usually reversible when treatment was stopped, with the results of liver function tests returning to normal after an average of 3.1 months. In two of the three deaths probably associated with ketoconazole treatment the drug had been continued after the onset of jaundice and other symptoms of hepatitis. Clinical and biochemical monitoring at regular intervals for evidence of hepatitis is advised during long term treatment with ketoconazole to prevent possible serious hepatic injury.", "entity": "Exanthema", "aliases": "Exanthem Exanthema Rash Skin", "definition": "Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke's disease), fifth (ERYTHEMA INFECTIOSUM), and sixth (EXANTHEMA SUBITUM) numeric designations survive as occasional synonyms in current terminology.\n    ", "id": "MESH:D005076"}
{"mention": "eosinophilia", "mention_text": "Ketoconazole was introduced in the United Kingdom in 1981. By November 1984 the Committee on Safety of Medicines had received 82 reports of possible hepatotoxicity associated with the drug, including five deaths. An analysis of the 75 cases that had been adequately followed up suggested that 16, including three deaths, were probably related to treatment with the drug. Of the remainder, 48 were possibly related to treatment, five were unlikely to be so, and six were unclassifiable. The mean age of patients in the 16 probable cases was 57.9, with hepatotoxicity being more common in women. The average duration of treatment before the onset of jaundice was 61 days. None of these well validated cases occurred within the first 10 days after treatment. The results of serum liver function tests suggested hepatocellular injury in 10 (63%); the rest showed a mixed pattern. In contrast, the results of histological examination of the liver often showed evidence of cholestasis. The characteristics of the 48 patients in the possible cases were similar. Allergic manifestations such as rash and eosinophilia were rare. Hepatitis was usually reversible when treatment was stopped, with the results of liver function tests returning to normal after an average of 3.1 months. In two of the three deaths probably associated with ketoconazole treatment the drug had been continued after the onset of jaundice and other symptoms of hepatitis. Clinical and biochemical monitoring at regular intervals for evidence of hepatitis is advised during long term treatment with ketoconazole to prevent possible serious hepatic injury.", "entity": "Eosinophilia", "aliases": "Eosinophilia Tropical Eosinophilias", "definition": "Abnormal increase of EOSINOPHILS in the blood, tissues or organs.\n    ", "id": "MESH:D004802"}
{"mention": "Hepatitis", "mention_text": "Ketoconazole was introduced in the United Kingdom in 1981. By November 1984 the Committee on Safety of Medicines had received 82 reports of possible hepatotoxicity associated with the drug, including five deaths. An analysis of the 75 cases that had been adequately followed up suggested that 16, including three deaths, were probably related to treatment with the drug. Of the remainder, 48 were possibly related to treatment, five were unlikely to be so, and six were unclassifiable. The mean age of patients in the 16 probable cases was 57.9, with hepatotoxicity being more common in women. The average duration of treatment before the onset of jaundice was 61 days. None of these well validated cases occurred within the first 10 days after treatment. The results of serum liver function tests suggested hepatocellular injury in 10 (63%); the rest showed a mixed pattern. In contrast, the results of histological examination of the liver often showed evidence of cholestasis. The characteristics of the 48 patients in the possible cases were similar. Allergic manifestations such as rash and eosinophilia were rare. Hepatitis was usually reversible when treatment was stopped, with the results of liver function tests returning to normal after an average of 3.1 months. In two of the three deaths probably associated with ketoconazole treatment the drug had been continued after the onset of jaundice and other symptoms of hepatitis. Clinical and biochemical monitoring at regular intervals for evidence of hepatitis is advised during long term treatment with ketoconazole to prevent possible serious hepatic injury.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "ketoconazole", "mention_text": "Ketoconazole was introduced in the United Kingdom in 1981. By November 1984 the Committee on Safety of Medicines had received 82 reports of possible hepatotoxicity associated with the drug, including five deaths. An analysis of the 75 cases that had been adequately followed up suggested that 16, including three deaths, were probably related to treatment with the drug. Of the remainder, 48 were possibly related to treatment, five were unlikely to be so, and six were unclassifiable. The mean age of patients in the 16 probable cases was 57.9, with hepatotoxicity being more common in women. The average duration of treatment before the onset of jaundice was 61 days. None of these well validated cases occurred within the first 10 days after treatment. The results of serum liver function tests suggested hepatocellular injury in 10 (63%); the rest showed a mixed pattern. In contrast, the results of histological examination of the liver often showed evidence of cholestasis. The characteristics of the 48 patients in the possible cases were similar. Allergic manifestations such as rash and eosinophilia were rare. Hepatitis was usually reversible when treatment was stopped, with the results of liver function tests returning to normal after an average of 3.1 months. In two of the three deaths probably associated with ketoconazole treatment the drug had been continued after the onset of jaundice and other symptoms of hepatitis. Clinical and biochemical monitoring at regular intervals for evidence of hepatitis is advised during long term treatment with ketoconazole to prevent possible serious hepatic injury.", "entity": "Ketoconazole", "aliases": "Janssen Brand of Ketoconazole Nizoral R 41400 R-41400 R41,400 R41400", "definition": "Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.\n    ", "id": "MESH:D007654"}
{"mention": "hepatitis", "mention_text": "Ketoconazole was introduced in the United Kingdom in 1981. By November 1984 the Committee on Safety of Medicines had received 82 reports of possible hepatotoxicity associated with the drug, including five deaths. An analysis of the 75 cases that had been adequately followed up suggested that 16, including three deaths, were probably related to treatment with the drug. Of the remainder, 48 were possibly related to treatment, five were unlikely to be so, and six were unclassifiable. The mean age of patients in the 16 probable cases was 57.9, with hepatotoxicity being more common in women. The average duration of treatment before the onset of jaundice was 61 days. None of these well validated cases occurred within the first 10 days after treatment. The results of serum liver function tests suggested hepatocellular injury in 10 (63%); the rest showed a mixed pattern. In contrast, the results of histological examination of the liver often showed evidence of cholestasis. The characteristics of the 48 patients in the possible cases were similar. Allergic manifestations such as rash and eosinophilia were rare. Hepatitis was usually reversible when treatment was stopped, with the results of liver function tests returning to normal after an average of 3.1 months. In two of the three deaths probably associated with ketoconazole treatment the drug had been continued after the onset of jaundice and other symptoms of hepatitis. Clinical and biochemical monitoring at regular intervals for evidence of hepatitis is advised during long term treatment with ketoconazole to prevent possible serious hepatic injury.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "hepatic injury", "mention_text": "Ketoconazole was introduced in the United Kingdom in 1981. By November 1984 the Committee on Safety of Medicines had received 82 reports of possible hepatotoxicity associated with the drug, including five deaths. An analysis of the 75 cases that had been adequately followed up suggested that 16, including three deaths, were probably related to treatment with the drug. Of the remainder, 48 were possibly related to treatment, five were unlikely to be so, and six were unclassifiable. The mean age of patients in the 16 probable cases was 57.9, with hepatotoxicity being more common in women. The average duration of treatment before the onset of jaundice was 61 days. None of these well validated cases occurred within the first 10 days after treatment. The results of serum liver function tests suggested hepatocellular injury in 10 (63%); the rest showed a mixed pattern. In contrast, the results of histological examination of the liver often showed evidence of cholestasis. The characteristics of the 48 patients in the possible cases were similar. Allergic manifestations such as rash and eosinophilia were rare. Hepatitis was usually reversible when treatment was stopped, with the results of liver function tests returning to normal after an average of 3.1 months. In two of the three deaths probably associated with ketoconazole treatment the drug had been continued after the onset of jaundice and other symptoms of hepatitis. Clinical and biochemical monitoring at regular intervals for evidence of hepatitis is advised during long term treatment with ketoconazole to prevent possible serious hepatic injury.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "prostaglandin E1", "mention_text": "Combined effects of prolonged prostaglandin E1-induced hypotension and haemodilution on human hepatic function.", "entity": "Alprostadil", "aliases": "Abbott Brand of Alprostadil Allphar Astra AstraZeneca Caverject Edex Hoyer Janssen Lipo PGE1 Lipo-PGE1 Minprog Muse PGE1alpha Paladin Pharmacia 1 2 Prostaglandin E1 E1alpha Prostavasin Prostin VR Prostine Schwarz Pharma Sugiran Vasaprostan Viridal Vivus", "definition": "A potent vasodilator agent that increases peripheral blood flow.\n    ", "id": "MESH:D000527"}
{"mention": "hypotension", "mention_text": "Combined effects of prolonged prostaglandin E1-induced hypotension and haemodilution on human hepatic function.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "haemodilution", "mention_text": "Combined effects of prolonged prostaglandin E1-induced hypotension and haemodilution on human hepatic function.", "entity": "Hemostatic Disorders", "aliases": "Disorder Vascular Hemostatic Disorders", "definition": "Pathological processes involving the integrity of blood circulation. Hemostasis depends on the integrity of BLOOD VESSELS, blood fluidity, and BLOOD COAGULATION. Majority of the hemostatic disorders are caused by disruption of the normal interaction between the VASCULAR ENDOTHELIUM, the plasma proteins (including BLOOD COAGULATION FACTORS), and PLATELETS.\n    ", "id": "MESH:D020141"}
{"mention": "prostaglandin E1", "mention_text": "Combined effects of prolonged prostaglandin E1 (PGE1)-induced hypotension and haemodilution on hepatic function were studied in 30 patients undergoing hip surgery. The patients were randomly allocated to one of three groups; those in group A (n = 10) were subjected to controlled hypotension alone, those in group B (n = 10) to haemodilution alone and those in group C (n = 10) to both controlled hypotension and haemodilution. Haemodilution in groups B and C was produced by withdrawing approximately 1000 mL of blood and replacing it with the same amount of dextran solution, and final haematocrit values were 21 or 22%. Controlled hypotension in groups A and C was induced with PGE1 to maintain mean arterial blood pressure at 55 mmHg for 180 min. Measurements included arterial ketone body ratio (AKBR, aceto-acetate/3-hydroxybutyrate) and clinical hepatic function parameters. AKBR and biological hepatic function tests showed no change throughout the time course in groups A and B. In group C, AKBR showed a significant decrease at 120 min (-40%) and at 180 min (-49%) after the start of hypotension and at 60 min (-32%) after recovery of normotension, and SGOT, SGPT, LDH and total bilirubin showed significant increases after operation. The results suggest that a prolonged combination of more than 120 min of PGE1-induced hypotension and moderate haemodilution would cause impairment of hepatic function.", "entity": "Alprostadil", "aliases": "Abbott Brand of Alprostadil Allphar Astra AstraZeneca Caverject Edex Hoyer Janssen Lipo PGE1 Lipo-PGE1 Minprog Muse PGE1alpha Paladin Pharmacia 1 2 Prostaglandin E1 E1alpha Prostavasin Prostin VR Prostine Schwarz Pharma Sugiran Vasaprostan Viridal Vivus", "definition": "A potent vasodilator agent that increases peripheral blood flow.\n    ", "id": "MESH:D000527"}
{"mention": "PGE1", "mention_text": "Combined effects of prolonged prostaglandin E1 (PGE1)-induced hypotension and haemodilution on hepatic function were studied in 30 patients undergoing hip surgery. The patients were randomly allocated to one of three groups; those in group A (n = 10) were subjected to controlled hypotension alone, those in group B (n = 10) to haemodilution alone and those in group C (n = 10) to both controlled hypotension and haemodilution. Haemodilution in groups B and C was produced by withdrawing approximately 1000 mL of blood and replacing it with the same amount of dextran solution, and final haematocrit values were 21 or 22%. Controlled hypotension in groups A and C was induced with PGE1 to maintain mean arterial blood pressure at 55 mmHg for 180 min. Measurements included arterial ketone body ratio (AKBR, aceto-acetate/3-hydroxybutyrate) and clinical hepatic function parameters. AKBR and biological hepatic function tests showed no change throughout the time course in groups A and B. In group C, AKBR showed a significant decrease at 120 min (-40%) and at 180 min (-49%) after the start of hypotension and at 60 min (-32%) after recovery of normotension, and SGOT, SGPT, LDH and total bilirubin showed significant increases after operation. The results suggest that a prolonged combination of more than 120 min of PGE1-induced hypotension and moderate haemodilution would cause impairment of hepatic function.", "entity": "Alprostadil", "aliases": "Abbott Brand of Alprostadil Allphar Astra AstraZeneca Caverject Edex Hoyer Janssen Lipo PGE1 Lipo-PGE1 Minprog Muse PGE1alpha Paladin Pharmacia 1 2 Prostaglandin E1 E1alpha Prostavasin Prostin VR Prostine Schwarz Pharma Sugiran Vasaprostan Viridal Vivus", "definition": "A potent vasodilator agent that increases peripheral blood flow.\n    ", "id": "MESH:D000527"}
{"mention": "hypotension", "mention_text": "Combined effects of prolonged prostaglandin E1 (PGE1)-induced hypotension and haemodilution on hepatic function were studied in 30 patients undergoing hip surgery. The patients were randomly allocated to one of three groups; those in group A (n = 10) were subjected to controlled hypotension alone, those in group B (n = 10) to haemodilution alone and those in group C (n = 10) to both controlled hypotension and haemodilution. Haemodilution in groups B and C was produced by withdrawing approximately 1000 mL of blood and replacing it with the same amount of dextran solution, and final haematocrit values were 21 or 22%. Controlled hypotension in groups A and C was induced with PGE1 to maintain mean arterial blood pressure at 55 mmHg for 180 min. Measurements included arterial ketone body ratio (AKBR, aceto-acetate/3-hydroxybutyrate) and clinical hepatic function parameters. AKBR and biological hepatic function tests showed no change throughout the time course in groups A and B. In group C, AKBR showed a significant decrease at 120 min (-40%) and at 180 min (-49%) after the start of hypotension and at 60 min (-32%) after recovery of normotension, and SGOT, SGPT, LDH and total bilirubin showed significant increases after operation. The results suggest that a prolonged combination of more than 120 min of PGE1-induced hypotension and moderate haemodilution would cause impairment of hepatic function.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "haemodilution", "mention_text": "Combined effects of prolonged prostaglandin E1 (PGE1)-induced hypotension and haemodilution on hepatic function were studied in 30 patients undergoing hip surgery. The patients were randomly allocated to one of three groups; those in group A (n = 10) were subjected to controlled hypotension alone, those in group B (n = 10) to haemodilution alone and those in group C (n = 10) to both controlled hypotension and haemodilution. Haemodilution in groups B and C was produced by withdrawing approximately 1000 mL of blood and replacing it with the same amount of dextran solution, and final haematocrit values were 21 or 22%. Controlled hypotension in groups A and C was induced with PGE1 to maintain mean arterial blood pressure at 55 mmHg for 180 min. Measurements included arterial ketone body ratio (AKBR, aceto-acetate/3-hydroxybutyrate) and clinical hepatic function parameters. AKBR and biological hepatic function tests showed no change throughout the time course in groups A and B. In group C, AKBR showed a significant decrease at 120 min (-40%) and at 180 min (-49%) after the start of hypotension and at 60 min (-32%) after recovery of normotension, and SGOT, SGPT, LDH and total bilirubin showed significant increases after operation. The results suggest that a prolonged combination of more than 120 min of PGE1-induced hypotension and moderate haemodilution would cause impairment of hepatic function.", "entity": "Hemostatic Disorders", "aliases": "Disorder Vascular Hemostatic Disorders", "definition": "Pathological processes involving the integrity of blood circulation. Hemostasis depends on the integrity of BLOOD VESSELS, blood fluidity, and BLOOD COAGULATION. Majority of the hemostatic disorders are caused by disruption of the normal interaction between the VASCULAR ENDOTHELIUM, the plasma proteins (including BLOOD COAGULATION FACTORS), and PLATELETS.\n    ", "id": "MESH:D020141"}
{"mention": "Haemodilution", "mention_text": "Combined effects of prolonged prostaglandin E1 (PGE1)-induced hypotension and haemodilution on hepatic function were studied in 30 patients undergoing hip surgery. The patients were randomly allocated to one of three groups; those in group A (n = 10) were subjected to controlled hypotension alone, those in group B (n = 10) to haemodilution alone and those in group C (n = 10) to both controlled hypotension and haemodilution. Haemodilution in groups B and C was produced by withdrawing approximately 1000 mL of blood and replacing it with the same amount of dextran solution, and final haematocrit values were 21 or 22%. Controlled hypotension in groups A and C was induced with PGE1 to maintain mean arterial blood pressure at 55 mmHg for 180 min. Measurements included arterial ketone body ratio (AKBR, aceto-acetate/3-hydroxybutyrate) and clinical hepatic function parameters. AKBR and biological hepatic function tests showed no change throughout the time course in groups A and B. In group C, AKBR showed a significant decrease at 120 min (-40%) and at 180 min (-49%) after the start of hypotension and at 60 min (-32%) after recovery of normotension, and SGOT, SGPT, LDH and total bilirubin showed significant increases after operation. The results suggest that a prolonged combination of more than 120 min of PGE1-induced hypotension and moderate haemodilution would cause impairment of hepatic function.", "entity": "Hemostatic Disorders", "aliases": "Disorder Vascular Hemostatic Disorders", "definition": "Pathological processes involving the integrity of blood circulation. Hemostasis depends on the integrity of BLOOD VESSELS, blood fluidity, and BLOOD COAGULATION. Majority of the hemostatic disorders are caused by disruption of the normal interaction between the VASCULAR ENDOTHELIUM, the plasma proteins (including BLOOD COAGULATION FACTORS), and PLATELETS.\n    ", "id": "MESH:D020141"}
{"mention": "dextran", "mention_text": "Combined effects of prolonged prostaglandin E1 (PGE1)-induced hypotension and haemodilution on hepatic function were studied in 30 patients undergoing hip surgery. The patients were randomly allocated to one of three groups; those in group A (n = 10) were subjected to controlled hypotension alone, those in group B (n = 10) to haemodilution alone and those in group C (n = 10) to both controlled hypotension and haemodilution. Haemodilution in groups B and C was produced by withdrawing approximately 1000 mL of blood and replacing it with the same amount of dextran solution, and final haematocrit values were 21 or 22%. Controlled hypotension in groups A and C was induced with PGE1 to maintain mean arterial blood pressure at 55 mmHg for 180 min. Measurements included arterial ketone body ratio (AKBR, aceto-acetate/3-hydroxybutyrate) and clinical hepatic function parameters. AKBR and biological hepatic function tests showed no change throughout the time course in groups A and B. In group C, AKBR showed a significant decrease at 120 min (-40%) and at 180 min (-49%) after the start of hypotension and at 60 min (-32%) after recovery of normotension, and SGOT, SGPT, LDH and total bilirubin showed significant increases after operation. The results suggest that a prolonged combination of more than 120 min of PGE1-induced hypotension and moderate haemodilution would cause impairment of hepatic function.", "entity": "Dextrans", "aliases": "Dextran 40 40000 70 75 80 B 1355 S B-1355 B-1355-S B1355 B512 Derivatives M T 500 T-40 T-500 Dextrans Hemodex Hyskon Infukoll Macrodex Polyglucin Promit Rheodextran Rheoisodex Rheomacrodex Rheopolyglucin Rondex Saviosol", "definition": "A group of glucose polymers made by certain bacteria. Dextrans are used therapeutically as plasma volume expanders and anticoagulants. They are also commonly used in biological experimentation and in industry for a wide variety of purposes.\n    ", "id": "MESH:D003911"}
{"mention": "aceto-acetate", "mention_text": "Combined effects of prolonged prostaglandin E1 (PGE1)-induced hypotension and haemodilution on hepatic function were studied in 30 patients undergoing hip surgery. The patients were randomly allocated to one of three groups; those in group A (n = 10) were subjected to controlled hypotension alone, those in group B (n = 10) to haemodilution alone and those in group C (n = 10) to both controlled hypotension and haemodilution. Haemodilution in groups B and C was produced by withdrawing approximately 1000 mL of blood and replacing it with the same amount of dextran solution, and final haematocrit values were 21 or 22%. Controlled hypotension in groups A and C was induced with PGE1 to maintain mean arterial blood pressure at 55 mmHg for 180 min. Measurements included arterial ketone body ratio (AKBR, aceto-acetate/3-hydroxybutyrate) and clinical hepatic function parameters. AKBR and biological hepatic function tests showed no change throughout the time course in groups A and B. In group C, AKBR showed a significant decrease at 120 min (-40%) and at 180 min (-49%) after the start of hypotension and at 60 min (-32%) after recovery of normotension, and SGOT, SGPT, LDH and total bilirubin showed significant increases after operation. The results suggest that a prolonged combination of more than 120 min of PGE1-induced hypotension and moderate haemodilution would cause impairment of hepatic function.", "entity": "acetoacetic acid", "aliases": "3-ketobutyrate 3-oxobutyric acid acetoacetate acetoacetic calcium salt lithium sodium oxobutyrate", "definition": "", "id": "MESH:C016635"}
{"mention": "3-hydroxybutyrate", "mention_text": "Combined effects of prolonged prostaglandin E1 (PGE1)-induced hypotension and haemodilution on hepatic function were studied in 30 patients undergoing hip surgery. The patients were randomly allocated to one of three groups; those in group A (n = 10) were subjected to controlled hypotension alone, those in group B (n = 10) to haemodilution alone and those in group C (n = 10) to both controlled hypotension and haemodilution. Haemodilution in groups B and C was produced by withdrawing approximately 1000 mL of blood and replacing it with the same amount of dextran solution, and final haematocrit values were 21 or 22%. Controlled hypotension in groups A and C was induced with PGE1 to maintain mean arterial blood pressure at 55 mmHg for 180 min. Measurements included arterial ketone body ratio (AKBR, aceto-acetate/3-hydroxybutyrate) and clinical hepatic function parameters. AKBR and biological hepatic function tests showed no change throughout the time course in groups A and B. In group C, AKBR showed a significant decrease at 120 min (-40%) and at 180 min (-49%) after the start of hypotension and at 60 min (-32%) after recovery of normotension, and SGOT, SGPT, LDH and total bilirubin showed significant increases after operation. The results suggest that a prolonged combination of more than 120 min of PGE1-induced hypotension and moderate haemodilution would cause impairment of hepatic function.", "entity": "3-Hydroxybutyric Acid", "aliases": "(+/-)-3-Hydroxybutyric Acid 3 Hydroxybutyrate Hydroxybutyric 3-Hydroxybutyrate 3-Hydroxybutyric beta beta-Hydroxybutyrate beta-Hydroxybutyric", "definition": "BUTYRIC ACID substituted in the beta or 3 position. It is one of the ketone bodies produced in the liver.\n    ", "id": "MESH:D020155"}
{"mention": "bilirubin", "mention_text": "Combined effects of prolonged prostaglandin E1 (PGE1)-induced hypotension and haemodilution on hepatic function were studied in 30 patients undergoing hip surgery. The patients were randomly allocated to one of three groups; those in group A (n = 10) were subjected to controlled hypotension alone, those in group B (n = 10) to haemodilution alone and those in group C (n = 10) to both controlled hypotension and haemodilution. Haemodilution in groups B and C was produced by withdrawing approximately 1000 mL of blood and replacing it with the same amount of dextran solution, and final haematocrit values were 21 or 22%. Controlled hypotension in groups A and C was induced with PGE1 to maintain mean arterial blood pressure at 55 mmHg for 180 min. Measurements included arterial ketone body ratio (AKBR, aceto-acetate/3-hydroxybutyrate) and clinical hepatic function parameters. AKBR and biological hepatic function tests showed no change throughout the time course in groups A and B. In group C, AKBR showed a significant decrease at 120 min (-40%) and at 180 min (-49%) after the start of hypotension and at 60 min (-32%) after recovery of normotension, and SGOT, SGPT, LDH and total bilirubin showed significant increases after operation. The results suggest that a prolonged combination of more than 120 min of PGE1-induced hypotension and moderate haemodilution would cause impairment of hepatic function.", "entity": "Bilirubin", "aliases": "Bilirubin IX alpha (15E)-Isomer (4E)-Isomer (4E,15E)-Isomer Calcium Salt Disodium Monosodium Bilirubinate Hematoidin delta delta-Bilirubin", "definition": "A bile pigment that is a degradation product of HEME.\n    ", "id": "MESH:D001663"}
{"mention": "impairment of hepatic function", "mention_text": "Combined effects of prolonged prostaglandin E1 (PGE1)-induced hypotension and haemodilution on hepatic function were studied in 30 patients undergoing hip surgery. The patients were randomly allocated to one of three groups; those in group A (n = 10) were subjected to controlled hypotension alone, those in group B (n = 10) to haemodilution alone and those in group C (n = 10) to both controlled hypotension and haemodilution. Haemodilution in groups B and C was produced by withdrawing approximately 1000 mL of blood and replacing it with the same amount of dextran solution, and final haematocrit values were 21 or 22%. Controlled hypotension in groups A and C was induced with PGE1 to maintain mean arterial blood pressure at 55 mmHg for 180 min. Measurements included arterial ketone body ratio (AKBR, aceto-acetate/3-hydroxybutyrate) and clinical hepatic function parameters. AKBR and biological hepatic function tests showed no change throughout the time course in groups A and B. In group C, AKBR showed a significant decrease at 120 min (-40%) and at 180 min (-49%) after the start of hypotension and at 60 min (-32%) after recovery of normotension, and SGOT, SGPT, LDH and total bilirubin showed significant increases after operation. The results suggest that a prolonged combination of more than 120 min of PGE1-induced hypotension and moderate haemodilution would cause impairment of hepatic function.", "entity": "Liver Diseases", "aliases": "Disease Liver Diseases Dysfunction Dysfunctions", "definition": "Pathological processes of the LIVER.\n    ", "id": "MESH:D008107"}
{"mention": "Levodopa", "mention_text": "Levodopa-induced dyskinesias in patients with Parkinson's disease: filling the bench-to-bedside gap.", "entity": "Levodopa", "aliases": "3 Hydroxy L tyrosine 3-Hydroxy-L-tyrosine Dopaflex Dopar 3,4 Dihydroxyphenylalanine Dopa L-3,4-Dihydroxyphenylalanine L-Dopa Larodopa Levodopa Levopa Medphano Brand of Roberts Roche", "definition": "The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.\n    ", "id": "MESH:D007980"}
{"mention": "dyskinesias", "mention_text": "Levodopa-induced dyskinesias in patients with Parkinson's disease: filling the bench-to-bedside gap.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "Parkinson's disease", "mention_text": "Levodopa-induced dyskinesias in patients with Parkinson's disease: filling the bench-to-bedside gap.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "Levodopa", "mention_text": "Levodopa is the most effective drug for the treatment of Parkinson's disease. However, the long-term use of this dopamine precursor is complicated by highly disabling fluctuations and dyskinesias. Although preclinical and clinical findings suggest pulsatile stimulation of striatal postsynaptic receptors as a key mechanism underlying levodopa-induced dyskinesias, their pathogenesis is still unclear. In recent years, evidence from animal models of Parkinson's disease has provided important information to understand the effect of specific receptor and post-receptor molecular mechanisms underlying the development of dyskinetic movements. Recent preclinical and clinical data from promising lines of research focus on the differential role of presynaptic versus postsynaptic mechanisms, dopamine receptor subtypes, ionotropic and metabotropic glutamate receptors, and non-dopaminergic neurotransmitter systems in the pathophysiology of levodopa-induced dyskinesias.", "entity": "Levodopa", "aliases": "3 Hydroxy L tyrosine 3-Hydroxy-L-tyrosine Dopaflex Dopar 3,4 Dihydroxyphenylalanine Dopa L-3,4-Dihydroxyphenylalanine L-Dopa Larodopa Levodopa Levopa Medphano Brand of Roberts Roche", "definition": "The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.\n    ", "id": "MESH:D007980"}
{"mention": "Parkinson's disease", "mention_text": "Levodopa is the most effective drug for the treatment of Parkinson's disease. However, the long-term use of this dopamine precursor is complicated by highly disabling fluctuations and dyskinesias. Although preclinical and clinical findings suggest pulsatile stimulation of striatal postsynaptic receptors as a key mechanism underlying levodopa-induced dyskinesias, their pathogenesis is still unclear. In recent years, evidence from animal models of Parkinson's disease has provided important information to understand the effect of specific receptor and post-receptor molecular mechanisms underlying the development of dyskinetic movements. Recent preclinical and clinical data from promising lines of research focus on the differential role of presynaptic versus postsynaptic mechanisms, dopamine receptor subtypes, ionotropic and metabotropic glutamate receptors, and non-dopaminergic neurotransmitter systems in the pathophysiology of levodopa-induced dyskinesias.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "dopamine", "mention_text": "Levodopa is the most effective drug for the treatment of Parkinson's disease. However, the long-term use of this dopamine precursor is complicated by highly disabling fluctuations and dyskinesias. Although preclinical and clinical findings suggest pulsatile stimulation of striatal postsynaptic receptors as a key mechanism underlying levodopa-induced dyskinesias, their pathogenesis is still unclear. In recent years, evidence from animal models of Parkinson's disease has provided important information to understand the effect of specific receptor and post-receptor molecular mechanisms underlying the development of dyskinetic movements. Recent preclinical and clinical data from promising lines of research focus on the differential role of presynaptic versus postsynaptic mechanisms, dopamine receptor subtypes, ionotropic and metabotropic glutamate receptors, and non-dopaminergic neurotransmitter systems in the pathophysiology of levodopa-induced dyskinesias.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "dyskinesias", "mention_text": "Levodopa is the most effective drug for the treatment of Parkinson's disease. However, the long-term use of this dopamine precursor is complicated by highly disabling fluctuations and dyskinesias. Although preclinical and clinical findings suggest pulsatile stimulation of striatal postsynaptic receptors as a key mechanism underlying levodopa-induced dyskinesias, their pathogenesis is still unclear. In recent years, evidence from animal models of Parkinson's disease has provided important information to understand the effect of specific receptor and post-receptor molecular mechanisms underlying the development of dyskinetic movements. Recent preclinical and clinical data from promising lines of research focus on the differential role of presynaptic versus postsynaptic mechanisms, dopamine receptor subtypes, ionotropic and metabotropic glutamate receptors, and non-dopaminergic neurotransmitter systems in the pathophysiology of levodopa-induced dyskinesias.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "levodopa", "mention_text": "Levodopa is the most effective drug for the treatment of Parkinson's disease. However, the long-term use of this dopamine precursor is complicated by highly disabling fluctuations and dyskinesias. Although preclinical and clinical findings suggest pulsatile stimulation of striatal postsynaptic receptors as a key mechanism underlying levodopa-induced dyskinesias, their pathogenesis is still unclear. In recent years, evidence from animal models of Parkinson's disease has provided important information to understand the effect of specific receptor and post-receptor molecular mechanisms underlying the development of dyskinetic movements. Recent preclinical and clinical data from promising lines of research focus on the differential role of presynaptic versus postsynaptic mechanisms, dopamine receptor subtypes, ionotropic and metabotropic glutamate receptors, and non-dopaminergic neurotransmitter systems in the pathophysiology of levodopa-induced dyskinesias.", "entity": "Levodopa", "aliases": "3 Hydroxy L tyrosine 3-Hydroxy-L-tyrosine Dopaflex Dopar 3,4 Dihydroxyphenylalanine Dopa L-3,4-Dihydroxyphenylalanine L-Dopa Larodopa Levodopa Levopa Medphano Brand of Roberts Roche", "definition": "The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.\n    ", "id": "MESH:D007980"}
{"mention": "dyskinetic movements", "mention_text": "Levodopa is the most effective drug for the treatment of Parkinson's disease. However, the long-term use of this dopamine precursor is complicated by highly disabling fluctuations and dyskinesias. Although preclinical and clinical findings suggest pulsatile stimulation of striatal postsynaptic receptors as a key mechanism underlying levodopa-induced dyskinesias, their pathogenesis is still unclear. In recent years, evidence from animal models of Parkinson's disease has provided important information to understand the effect of specific receptor and post-receptor molecular mechanisms underlying the development of dyskinetic movements. Recent preclinical and clinical data from promising lines of research focus on the differential role of presynaptic versus postsynaptic mechanisms, dopamine receptor subtypes, ionotropic and metabotropic glutamate receptors, and non-dopaminergic neurotransmitter systems in the pathophysiology of levodopa-induced dyskinesias.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "glutamate", "mention_text": "Levodopa is the most effective drug for the treatment of Parkinson's disease. However, the long-term use of this dopamine precursor is complicated by highly disabling fluctuations and dyskinesias. Although preclinical and clinical findings suggest pulsatile stimulation of striatal postsynaptic receptors as a key mechanism underlying levodopa-induced dyskinesias, their pathogenesis is still unclear. In recent years, evidence from animal models of Parkinson's disease has provided important information to understand the effect of specific receptor and post-receptor molecular mechanisms underlying the development of dyskinetic movements. Recent preclinical and clinical data from promising lines of research focus on the differential role of presynaptic versus postsynaptic mechanisms, dopamine receptor subtypes, ionotropic and metabotropic glutamate receptors, and non-dopaminergic neurotransmitter systems in the pathophysiology of levodopa-induced dyskinesias.", "entity": "Glutamic Acid", "aliases": "Aluminum L Glutamate L-Glutamate D D-Glutamate Potassium Glutamic Acid (D)-Isomer L-Glutamic", "definition": "A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.\n    ", "id": "MESH:D018698"}
{"mention": "seizures", "mention_text": "Prevention of seizures and reorganization of hippocampal functions by transplantation of bone marrow cells in the acute phase of experimental epilepsy.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "epilepsy", "mention_text": "Prevention of seizures and reorganization of hippocampal functions by transplantation of bone marrow cells in the acute phase of experimental epilepsy.", "entity": "Epilepsy", "aliases": "Aura Auras Awakening Epilepsy Cryptogenic Epilepsies Epileptic Seizure Seizures Disorder Disorders Single", "definition": "A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313)\n    ", "id": "MESH:D004827"}
{"mention": "epilepsy", "mention_text": "In this study, we investigated the therapeutic potential of bone marrow mononuclear cells (BMCs) in a model of epilepsy induced by pilocarpine in rats. BMCs obtained from green fluorescent protein (GFP) transgenic mice or rats were transplanted intravenously after induction of status epilepticus (SE). Spontaneous recurrent seizures (SRS) were monitored using Racine's seizure severity scale. All of the rats in the saline-treated epileptic control group developed SRS, whereas none of the BMC-treated epileptic animals had seizures in the short term (15 days after transplantation), regardless of the BMC source. Over the long-term chronic phase (120 days after transplantation), only 25% of BMC-treated epileptic animals had seizures, but with a lower frequency and duration compared to the epileptic control group. The density of hippocampal neurons in the brains of animals treated with BMCs was markedly preserved. At hippocampal Schaeffer collateral-CA1 synapses, long-term potentiation was preserved in BMC-transplanted rats compared to epileptic controls. The donor-derived GFP(+) cells were rarely found in the brains of transplanted epileptic rats. In conclusion, treatment with BMCs can prevent the development of chronic seizures, reduce neuronal loss, and influence the reorganization of the hippocampal neuronal network.", "entity": "Epilepsy", "aliases": "Aura Auras Awakening Epilepsy Cryptogenic Epilepsies Epileptic Seizure Seizures Disorder Disorders Single", "definition": "A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313)\n    ", "id": "MESH:D004827"}
{"mention": "pilocarpine", "mention_text": "In this study, we investigated the therapeutic potential of bone marrow mononuclear cells (BMCs) in a model of epilepsy induced by pilocarpine in rats. BMCs obtained from green fluorescent protein (GFP) transgenic mice or rats were transplanted intravenously after induction of status epilepticus (SE). Spontaneous recurrent seizures (SRS) were monitored using Racine's seizure severity scale. All of the rats in the saline-treated epileptic control group developed SRS, whereas none of the BMC-treated epileptic animals had seizures in the short term (15 days after transplantation), regardless of the BMC source. Over the long-term chronic phase (120 days after transplantation), only 25% of BMC-treated epileptic animals had seizures, but with a lower frequency and duration compared to the epileptic control group. The density of hippocampal neurons in the brains of animals treated with BMCs was markedly preserved. At hippocampal Schaeffer collateral-CA1 synapses, long-term potentiation was preserved in BMC-transplanted rats compared to epileptic controls. The donor-derived GFP(+) cells were rarely found in the brains of transplanted epileptic rats. In conclusion, treatment with BMCs can prevent the development of chronic seizures, reduce neuronal loss, and influence the reorganization of the hippocampal neuronal network.", "entity": "Pilocarpine", "aliases": "Hydrochloride Pilocarpine Isopilocarpine Isoptocarpine Nitrate Ocusert Mononitrate (3S-cis)-Isomer Monohydrochloride Salagen", "definition": "A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma.\n    ", "id": "MESH:D010862"}
{"mention": "status epilepticus", "mention_text": "In this study, we investigated the therapeutic potential of bone marrow mononuclear cells (BMCs) in a model of epilepsy induced by pilocarpine in rats. BMCs obtained from green fluorescent protein (GFP) transgenic mice or rats were transplanted intravenously after induction of status epilepticus (SE). Spontaneous recurrent seizures (SRS) were monitored using Racine's seizure severity scale. All of the rats in the saline-treated epileptic control group developed SRS, whereas none of the BMC-treated epileptic animals had seizures in the short term (15 days after transplantation), regardless of the BMC source. Over the long-term chronic phase (120 days after transplantation), only 25% of BMC-treated epileptic animals had seizures, but with a lower frequency and duration compared to the epileptic control group. The density of hippocampal neurons in the brains of animals treated with BMCs was markedly preserved. At hippocampal Schaeffer collateral-CA1 synapses, long-term potentiation was preserved in BMC-transplanted rats compared to epileptic controls. The donor-derived GFP(+) cells were rarely found in the brains of transplanted epileptic rats. In conclusion, treatment with BMCs can prevent the development of chronic seizures, reduce neuronal loss, and influence the reorganization of the hippocampal neuronal network.", "entity": "Status Epilepticus", "aliases": "Absence Status Complex Partial Epilepticus Electrographic Generalized Convulsive Grand Mal Non Non-Convulsive Petit Simple Subclinical", "definition": "A prolonged seizure or seizures repeated frequently enough to prevent recovery between episodes occurring over a period of 20-30 minutes. The most common subtype is generalized tonic-clonic status epilepticus, a potentially fatal condition associated with neuronal injury and respiratory and metabolic dysfunction. Nonconvulsive forms include petit mal status and complex partial status, which may manifest as behavioral disturbances. Simple partial status epilepticus consists of persistent motor, sensory, or autonomic seizures that do not impair cognition (see also EPILEPSIA PARTIALIS CONTINUA). Subclinical status epilepticus generally refers to seizures occurring in an unresponsive or comatose individual in the absence of overt signs of seizure activity. (From N Engl J Med 1998 Apr 2;338(14):970-6; Neurologia 1997 Dec;12 Suppl 6:25-30)\n    ", "id": "MESH:D013226"}
{"mention": "SE", "mention_text": "In this study, we investigated the therapeutic potential of bone marrow mononuclear cells (BMCs) in a model of epilepsy induced by pilocarpine in rats. BMCs obtained from green fluorescent protein (GFP) transgenic mice or rats were transplanted intravenously after induction of status epilepticus (SE). Spontaneous recurrent seizures (SRS) were monitored using Racine's seizure severity scale. All of the rats in the saline-treated epileptic control group developed SRS, whereas none of the BMC-treated epileptic animals had seizures in the short term (15 days after transplantation), regardless of the BMC source. Over the long-term chronic phase (120 days after transplantation), only 25% of BMC-treated epileptic animals had seizures, but with a lower frequency and duration compared to the epileptic control group. The density of hippocampal neurons in the brains of animals treated with BMCs was markedly preserved. At hippocampal Schaeffer collateral-CA1 synapses, long-term potentiation was preserved in BMC-transplanted rats compared to epileptic controls. The donor-derived GFP(+) cells were rarely found in the brains of transplanted epileptic rats. In conclusion, treatment with BMCs can prevent the development of chronic seizures, reduce neuronal loss, and influence the reorganization of the hippocampal neuronal network.", "entity": "Status Epilepticus", "aliases": "Absence Status Complex Partial Epilepticus Electrographic Generalized Convulsive Grand Mal Non Non-Convulsive Petit Simple Subclinical", "definition": "A prolonged seizure or seizures repeated frequently enough to prevent recovery between episodes occurring over a period of 20-30 minutes. The most common subtype is generalized tonic-clonic status epilepticus, a potentially fatal condition associated with neuronal injury and respiratory and metabolic dysfunction. Nonconvulsive forms include petit mal status and complex partial status, which may manifest as behavioral disturbances. Simple partial status epilepticus consists of persistent motor, sensory, or autonomic seizures that do not impair cognition (see also EPILEPSIA PARTIALIS CONTINUA). Subclinical status epilepticus generally refers to seizures occurring in an unresponsive or comatose individual in the absence of overt signs of seizure activity. (From N Engl J Med 1998 Apr 2;338(14):970-6; Neurologia 1997 Dec;12 Suppl 6:25-30)\n    ", "id": "MESH:D013226"}
{"mention": "seizure", "mention_text": "In this study, we investigated the therapeutic potential of bone marrow mononuclear cells (BMCs) in a model of epilepsy induced by pilocarpine in rats. BMCs obtained from green fluorescent protein (GFP) transgenic mice or rats were transplanted intravenously after induction of status epilepticus (SE). Spontaneous recurrent seizures (SRS) were monitored using Racine's seizure severity scale. All of the rats in the saline-treated epileptic control group developed SRS, whereas none of the BMC-treated epileptic animals had seizures in the short term (15 days after transplantation), regardless of the BMC source. Over the long-term chronic phase (120 days after transplantation), only 25% of BMC-treated epileptic animals had seizures, but with a lower frequency and duration compared to the epileptic control group. The density of hippocampal neurons in the brains of animals treated with BMCs was markedly preserved. At hippocampal Schaeffer collateral-CA1 synapses, long-term potentiation was preserved in BMC-transplanted rats compared to epileptic controls. The donor-derived GFP(+) cells were rarely found in the brains of transplanted epileptic rats. In conclusion, treatment with BMCs can prevent the development of chronic seizures, reduce neuronal loss, and influence the reorganization of the hippocampal neuronal network.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "epileptic", "mention_text": "In this study, we investigated the therapeutic potential of bone marrow mononuclear cells (BMCs) in a model of epilepsy induced by pilocarpine in rats. BMCs obtained from green fluorescent protein (GFP) transgenic mice or rats were transplanted intravenously after induction of status epilepticus (SE). Spontaneous recurrent seizures (SRS) were monitored using Racine's seizure severity scale. All of the rats in the saline-treated epileptic control group developed SRS, whereas none of the BMC-treated epileptic animals had seizures in the short term (15 days after transplantation), regardless of the BMC source. Over the long-term chronic phase (120 days after transplantation), only 25% of BMC-treated epileptic animals had seizures, but with a lower frequency and duration compared to the epileptic control group. The density of hippocampal neurons in the brains of animals treated with BMCs was markedly preserved. At hippocampal Schaeffer collateral-CA1 synapses, long-term potentiation was preserved in BMC-transplanted rats compared to epileptic controls. The donor-derived GFP(+) cells were rarely found in the brains of transplanted epileptic rats. In conclusion, treatment with BMCs can prevent the development of chronic seizures, reduce neuronal loss, and influence the reorganization of the hippocampal neuronal network.", "entity": "Epilepsy", "aliases": "Aura Auras Awakening Epilepsy Cryptogenic Epilepsies Epileptic Seizure Seizures Disorder Disorders Single", "definition": "A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313)\n    ", "id": "MESH:D004827"}
{"mention": "seizures", "mention_text": "In this study, we investigated the therapeutic potential of bone marrow mononuclear cells (BMCs) in a model of epilepsy induced by pilocarpine in rats. BMCs obtained from green fluorescent protein (GFP) transgenic mice or rats were transplanted intravenously after induction of status epilepticus (SE). Spontaneous recurrent seizures (SRS) were monitored using Racine's seizure severity scale. All of the rats in the saline-treated epileptic control group developed SRS, whereas none of the BMC-treated epileptic animals had seizures in the short term (15 days after transplantation), regardless of the BMC source. Over the long-term chronic phase (120 days after transplantation), only 25% of BMC-treated epileptic animals had seizures, but with a lower frequency and duration compared to the epileptic control group. The density of hippocampal neurons in the brains of animals treated with BMCs was markedly preserved. At hippocampal Schaeffer collateral-CA1 synapses, long-term potentiation was preserved in BMC-transplanted rats compared to epileptic controls. The donor-derived GFP(+) cells were rarely found in the brains of transplanted epileptic rats. In conclusion, treatment with BMCs can prevent the development of chronic seizures, reduce neuronal loss, and influence the reorganization of the hippocampal neuronal network.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "neuronal loss", "mention_text": "In this study, we investigated the therapeutic potential of bone marrow mononuclear cells (BMCs) in a model of epilepsy induced by pilocarpine in rats. BMCs obtained from green fluorescent protein (GFP) transgenic mice or rats were transplanted intravenously after induction of status epilepticus (SE). Spontaneous recurrent seizures (SRS) were monitored using Racine's seizure severity scale. All of the rats in the saline-treated epileptic control group developed SRS, whereas none of the BMC-treated epileptic animals had seizures in the short term (15 days after transplantation), regardless of the BMC source. Over the long-term chronic phase (120 days after transplantation), only 25% of BMC-treated epileptic animals had seizures, but with a lower frequency and duration compared to the epileptic control group. The density of hippocampal neurons in the brains of animals treated with BMCs was markedly preserved. At hippocampal Schaeffer collateral-CA1 synapses, long-term potentiation was preserved in BMC-transplanted rats compared to epileptic controls. The donor-derived GFP(+) cells were rarely found in the brains of transplanted epileptic rats. In conclusion, treatment with BMCs can prevent the development of chronic seizures, reduce neuronal loss, and influence the reorganization of the hippocampal neuronal network.", "entity": "Nerve Degeneration", "aliases": "Degeneration Nerve Neuron Degenerations", "definition": "Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.\n    ", "id": "MESH:D009410"}
{"mention": "salvianolic acid A", "mention_text": "Cardioprotective effect of salvianolic acid A on isoproterenol-induced myocardial infarction in rats.", "entity": "salvianolic acid A", "aliases": "salvianolic acid A", "definition": "", "id": "MESH:C066201"}
{"mention": "isoproterenol", "mention_text": "Cardioprotective effect of salvianolic acid A on isoproterenol-induced myocardial infarction in rats.", "entity": "Isoproterenol", "aliases": "4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol Euspiran Hydrochloride Isoproterenol Isadrin Isadrine Isoprenaline Isopropyl Noradrenaline Isopropylarterenol Isopropylnoradrenaline Isopropylnorepinephrine Sulfate Isuprel Izadrin Norisodrine Novodrin", "definition": "Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.\n    ", "id": "MESH:D007545"}
{"mention": "myocardial infarction", "mention_text": "Cardioprotective effect of salvianolic acid A on isoproterenol-induced myocardial infarction in rats.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "salvianolic acid A", "mention_text": "The present study was designed to evaluate the cardioprotective potential of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. Hemodynamic parameters and lead II electrocardiograph were monitored and recorded continuously. Cardiac marker enzymes and antioxidative parameters in serum and heart tissues were measured. Assay for mitochondrial respiratory function and histopathological examination of heart tissues were performed. Isoproterenol-treated rats showed significant increases in the levels of lactate dehydrogenase, aspartate transaminase, creatine kinase and malondialdehyde and significant decreases in the activities of superoxide dismutase, catalase and glutathione peroxidase in serum and heart. These rats also showed declines in left ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, and elevation of left ventricular end-diastolic pressure and ST-segment. In addition, mitochondrial respiratory dysfunction characterized by decreased respiratory control ratio and ADP/O was observed in isoproterenol-treated rats. Administration of salvianolic acid A for a period of 8 days significantly attenuated isoproterenol-induced cardiac dysfunction and myocardial injury and improved mitochondrial respiratory function. The protective role of salvianolic acid A against isoproterenol-induced myocardial damage was further confirmed by histopathological examination. The results of our study suggest that salvianolic acid A possessing antioxidant activity has a significant protective effect against isoproterenol-induced myocardial infarction.", "entity": "salvianolic acid A", "aliases": "salvianolic acid A", "definition": "", "id": "MESH:C066201"}
{"mention": "isoproterenol", "mention_text": "The present study was designed to evaluate the cardioprotective potential of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. Hemodynamic parameters and lead II electrocardiograph were monitored and recorded continuously. Cardiac marker enzymes and antioxidative parameters in serum and heart tissues were measured. Assay for mitochondrial respiratory function and histopathological examination of heart tissues were performed. Isoproterenol-treated rats showed significant increases in the levels of lactate dehydrogenase, aspartate transaminase, creatine kinase and malondialdehyde and significant decreases in the activities of superoxide dismutase, catalase and glutathione peroxidase in serum and heart. These rats also showed declines in left ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, and elevation of left ventricular end-diastolic pressure and ST-segment. In addition, mitochondrial respiratory dysfunction characterized by decreased respiratory control ratio and ADP/O was observed in isoproterenol-treated rats. Administration of salvianolic acid A for a period of 8 days significantly attenuated isoproterenol-induced cardiac dysfunction and myocardial injury and improved mitochondrial respiratory function. The protective role of salvianolic acid A against isoproterenol-induced myocardial damage was further confirmed by histopathological examination. The results of our study suggest that salvianolic acid A possessing antioxidant activity has a significant protective effect against isoproterenol-induced myocardial infarction.", "entity": "Isoproterenol", "aliases": "4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol Euspiran Hydrochloride Isoproterenol Isadrin Isadrine Isoprenaline Isopropyl Noradrenaline Isopropylarterenol Isopropylnoradrenaline Isopropylnorepinephrine Sulfate Isuprel Izadrin Norisodrine Novodrin", "definition": "Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.\n    ", "id": "MESH:D007545"}
{"mention": "myocardial infarction", "mention_text": "The present study was designed to evaluate the cardioprotective potential of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. Hemodynamic parameters and lead II electrocardiograph were monitored and recorded continuously. Cardiac marker enzymes and antioxidative parameters in serum and heart tissues were measured. Assay for mitochondrial respiratory function and histopathological examination of heart tissues were performed. Isoproterenol-treated rats showed significant increases in the levels of lactate dehydrogenase, aspartate transaminase, creatine kinase and malondialdehyde and significant decreases in the activities of superoxide dismutase, catalase and glutathione peroxidase in serum and heart. These rats also showed declines in left ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, and elevation of left ventricular end-diastolic pressure and ST-segment. In addition, mitochondrial respiratory dysfunction characterized by decreased respiratory control ratio and ADP/O was observed in isoproterenol-treated rats. Administration of salvianolic acid A for a period of 8 days significantly attenuated isoproterenol-induced cardiac dysfunction and myocardial injury and improved mitochondrial respiratory function. The protective role of salvianolic acid A against isoproterenol-induced myocardial damage was further confirmed by histopathological examination. The results of our study suggest that salvianolic acid A possessing antioxidant activity has a significant protective effect against isoproterenol-induced myocardial infarction.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "Isoproterenol", "mention_text": "The present study was designed to evaluate the cardioprotective potential of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. Hemodynamic parameters and lead II electrocardiograph were monitored and recorded continuously. Cardiac marker enzymes and antioxidative parameters in serum and heart tissues were measured. Assay for mitochondrial respiratory function and histopathological examination of heart tissues were performed. Isoproterenol-treated rats showed significant increases in the levels of lactate dehydrogenase, aspartate transaminase, creatine kinase and malondialdehyde and significant decreases in the activities of superoxide dismutase, catalase and glutathione peroxidase in serum and heart. These rats also showed declines in left ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, and elevation of left ventricular end-diastolic pressure and ST-segment. In addition, mitochondrial respiratory dysfunction characterized by decreased respiratory control ratio and ADP/O was observed in isoproterenol-treated rats. Administration of salvianolic acid A for a period of 8 days significantly attenuated isoproterenol-induced cardiac dysfunction and myocardial injury and improved mitochondrial respiratory function. The protective role of salvianolic acid A against isoproterenol-induced myocardial damage was further confirmed by histopathological examination. The results of our study suggest that salvianolic acid A possessing antioxidant activity has a significant protective effect against isoproterenol-induced myocardial infarction.", "entity": "Isoproterenol", "aliases": "4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol Euspiran Hydrochloride Isoproterenol Isadrin Isadrine Isoprenaline Isopropyl Noradrenaline Isopropylarterenol Isopropylnoradrenaline Isopropylnorepinephrine Sulfate Isuprel Izadrin Norisodrine Novodrin", "definition": "Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.\n    ", "id": "MESH:D007545"}
{"mention": "lactate", "mention_text": "The present study was designed to evaluate the cardioprotective potential of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. Hemodynamic parameters and lead II electrocardiograph were monitored and recorded continuously. Cardiac marker enzymes and antioxidative parameters in serum and heart tissues were measured. Assay for mitochondrial respiratory function and histopathological examination of heart tissues were performed. Isoproterenol-treated rats showed significant increases in the levels of lactate dehydrogenase, aspartate transaminase, creatine kinase and malondialdehyde and significant decreases in the activities of superoxide dismutase, catalase and glutathione peroxidase in serum and heart. These rats also showed declines in left ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, and elevation of left ventricular end-diastolic pressure and ST-segment. In addition, mitochondrial respiratory dysfunction characterized by decreased respiratory control ratio and ADP/O was observed in isoproterenol-treated rats. Administration of salvianolic acid A for a period of 8 days significantly attenuated isoproterenol-induced cardiac dysfunction and myocardial injury and improved mitochondrial respiratory function. The protective role of salvianolic acid A against isoproterenol-induced myocardial damage was further confirmed by histopathological examination. The results of our study suggest that salvianolic acid A possessing antioxidant activity has a significant protective effect against isoproterenol-induced myocardial infarction.", "entity": "Lactic Acid", "aliases": "2 Hydroxypropanoic Acid Hydroxypropionic 2-Hydroxypropanoic 2-Hydroxypropionic Ammonium Lactate D Lactic D-Lactic L L-Lactic Propanoic 2-Hydroxy- (2R)- (2S)- Sarcolactic", "definition": "A normal intermediate in the fermentation (oxidation, metabolism) of sugar. The concentrated form is used internally to prevent gastrointestinal fermentation. (From Stedman, 26th ed)\n    ", "id": "MESH:D019344"}
{"mention": "aspartate", "mention_text": "The present study was designed to evaluate the cardioprotective potential of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. Hemodynamic parameters and lead II electrocardiograph were monitored and recorded continuously. Cardiac marker enzymes and antioxidative parameters in serum and heart tissues were measured. Assay for mitochondrial respiratory function and histopathological examination of heart tissues were performed. Isoproterenol-treated rats showed significant increases in the levels of lactate dehydrogenase, aspartate transaminase, creatine kinase and malondialdehyde and significant decreases in the activities of superoxide dismutase, catalase and glutathione peroxidase in serum and heart. These rats also showed declines in left ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, and elevation of left ventricular end-diastolic pressure and ST-segment. In addition, mitochondrial respiratory dysfunction characterized by decreased respiratory control ratio and ADP/O was observed in isoproterenol-treated rats. Administration of salvianolic acid A for a period of 8 days significantly attenuated isoproterenol-induced cardiac dysfunction and myocardial injury and improved mitochondrial respiratory function. The protective role of salvianolic acid A against isoproterenol-induced myocardial damage was further confirmed by histopathological examination. The results of our study suggest that salvianolic acid A possessing antioxidant activity has a significant protective effect against isoproterenol-induced myocardial infarction.", "entity": "Aspartic Acid", "aliases": "(+-)-Aspartic Acid (R,S)-Aspartic Ammonium Aspartate Magnesium Hydrochloride Calcium Dipotassium Disodium Monopotassium Monosodium Potassium Sodium Aspartic Salt Hydrobromide (1:1) Trihydrate (2:1) Magnesium-Potassium (2:1:2) L L-Aspartate L-Aspartic Magnesiocard Mg 5 Longoral Mg-5-Longoral Mg5Longoral", "definition": "One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.\n    ", "id": "MESH:D001224"}
{"mention": "creatine", "mention_text": "The present study was designed to evaluate the cardioprotective potential of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. Hemodynamic parameters and lead II electrocardiograph were monitored and recorded continuously. Cardiac marker enzymes and antioxidative parameters in serum and heart tissues were measured. Assay for mitochondrial respiratory function and histopathological examination of heart tissues were performed. Isoproterenol-treated rats showed significant increases in the levels of lactate dehydrogenase, aspartate transaminase, creatine kinase and malondialdehyde and significant decreases in the activities of superoxide dismutase, catalase and glutathione peroxidase in serum and heart. These rats also showed declines in left ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, and elevation of left ventricular end-diastolic pressure and ST-segment. In addition, mitochondrial respiratory dysfunction characterized by decreased respiratory control ratio and ADP/O was observed in isoproterenol-treated rats. Administration of salvianolic acid A for a period of 8 days significantly attenuated isoproterenol-induced cardiac dysfunction and myocardial injury and improved mitochondrial respiratory function. The protective role of salvianolic acid A against isoproterenol-induced myocardial damage was further confirmed by histopathological examination. The results of our study suggest that salvianolic acid A possessing antioxidant activity has a significant protective effect against isoproterenol-induced myocardial infarction.", "entity": "Creatine", "aliases": "Creatine", "definition": "An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as CREATININE in the urine.\n    ", "id": "MESH:D003401"}
{"mention": "malondialdehyde", "mention_text": "The present study was designed to evaluate the cardioprotective potential of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. Hemodynamic parameters and lead II electrocardiograph were monitored and recorded continuously. Cardiac marker enzymes and antioxidative parameters in serum and heart tissues were measured. Assay for mitochondrial respiratory function and histopathological examination of heart tissues were performed. Isoproterenol-treated rats showed significant increases in the levels of lactate dehydrogenase, aspartate transaminase, creatine kinase and malondialdehyde and significant decreases in the activities of superoxide dismutase, catalase and glutathione peroxidase in serum and heart. These rats also showed declines in left ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, and elevation of left ventricular end-diastolic pressure and ST-segment. In addition, mitochondrial respiratory dysfunction characterized by decreased respiratory control ratio and ADP/O was observed in isoproterenol-treated rats. Administration of salvianolic acid A for a period of 8 days significantly attenuated isoproterenol-induced cardiac dysfunction and myocardial injury and improved mitochondrial respiratory function. The protective role of salvianolic acid A against isoproterenol-induced myocardial damage was further confirmed by histopathological examination. The results of our study suggest that salvianolic acid A possessing antioxidant activity has a significant protective effect against isoproterenol-induced myocardial infarction.", "entity": "Malondialdehyde", "aliases": "Malonaldehyde Malondialdehyde Sodium Malonylaldehyde Malonyldialdehyde Propanedial", "definition": "The dialdehyde of malonic acid.\n    ", "id": "MESH:D008315"}
{"mention": "superoxide", "mention_text": "The present study was designed to evaluate the cardioprotective potential of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. Hemodynamic parameters and lead II electrocardiograph were monitored and recorded continuously. Cardiac marker enzymes and antioxidative parameters in serum and heart tissues were measured. Assay for mitochondrial respiratory function and histopathological examination of heart tissues were performed. Isoproterenol-treated rats showed significant increases in the levels of lactate dehydrogenase, aspartate transaminase, creatine kinase and malondialdehyde and significant decreases in the activities of superoxide dismutase, catalase and glutathione peroxidase in serum and heart. These rats also showed declines in left ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, and elevation of left ventricular end-diastolic pressure and ST-segment. In addition, mitochondrial respiratory dysfunction characterized by decreased respiratory control ratio and ADP/O was observed in isoproterenol-treated rats. Administration of salvianolic acid A for a period of 8 days significantly attenuated isoproterenol-induced cardiac dysfunction and myocardial injury and improved mitochondrial respiratory function. The protective role of salvianolic acid A against isoproterenol-induced myocardial damage was further confirmed by histopathological examination. The results of our study suggest that salvianolic acid A possessing antioxidant activity has a significant protective effect against isoproterenol-induced myocardial infarction.", "entity": "Superoxides", "aliases": "Superoxide Anion Radical Superoxides", "definition": "Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides.\n    ", "id": "MESH:D013481"}
{"mention": "glutathione", "mention_text": "The present study was designed to evaluate the cardioprotective potential of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. Hemodynamic parameters and lead II electrocardiograph were monitored and recorded continuously. Cardiac marker enzymes and antioxidative parameters in serum and heart tissues were measured. Assay for mitochondrial respiratory function and histopathological examination of heart tissues were performed. Isoproterenol-treated rats showed significant increases in the levels of lactate dehydrogenase, aspartate transaminase, creatine kinase and malondialdehyde and significant decreases in the activities of superoxide dismutase, catalase and glutathione peroxidase in serum and heart. These rats also showed declines in left ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, and elevation of left ventricular end-diastolic pressure and ST-segment. In addition, mitochondrial respiratory dysfunction characterized by decreased respiratory control ratio and ADP/O was observed in isoproterenol-treated rats. Administration of salvianolic acid A for a period of 8 days significantly attenuated isoproterenol-induced cardiac dysfunction and myocardial injury and improved mitochondrial respiratory function. The protective role of salvianolic acid A against isoproterenol-induced myocardial damage was further confirmed by histopathological examination. The results of our study suggest that salvianolic acid A possessing antioxidant activity has a significant protective effect against isoproterenol-induced myocardial infarction.", "entity": "Glutathione", "aliases": "Glutathione Reduced gamma L Glu L Cys Gly Glutamyl Cysteinylglycine gamma-L-Glu-L-Cys-Gly gamma-L-Glutamyl-L-Cysteinylglycine", "definition": "A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.\n    ", "id": "MESH:D005978"}
{"mention": "respiratory dysfunction", "mention_text": "The present study was designed to evaluate the cardioprotective potential of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. Hemodynamic parameters and lead II electrocardiograph were monitored and recorded continuously. Cardiac marker enzymes and antioxidative parameters in serum and heart tissues were measured. Assay for mitochondrial respiratory function and histopathological examination of heart tissues were performed. Isoproterenol-treated rats showed significant increases in the levels of lactate dehydrogenase, aspartate transaminase, creatine kinase and malondialdehyde and significant decreases in the activities of superoxide dismutase, catalase and glutathione peroxidase in serum and heart. These rats also showed declines in left ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, and elevation of left ventricular end-diastolic pressure and ST-segment. In addition, mitochondrial respiratory dysfunction characterized by decreased respiratory control ratio and ADP/O was observed in isoproterenol-treated rats. Administration of salvianolic acid A for a period of 8 days significantly attenuated isoproterenol-induced cardiac dysfunction and myocardial injury and improved mitochondrial respiratory function. The protective role of salvianolic acid A against isoproterenol-induced myocardial damage was further confirmed by histopathological examination. The results of our study suggest that salvianolic acid A possessing antioxidant activity has a significant protective effect against isoproterenol-induced myocardial infarction.", "entity": "Respiratory Insufficiency", "aliases": "Depressions Ventilatory Respiratory Depression Failure Insufficiency", "definition": "Failure to adequately provide oxygen to cells of the body and to remove excess carbon dioxide from them. (Stedman, 25th ed)\n    ", "id": "MESH:D012131"}
{"mention": "ADP", "mention_text": "The present study was designed to evaluate the cardioprotective potential of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. Hemodynamic parameters and lead II electrocardiograph were monitored and recorded continuously. Cardiac marker enzymes and antioxidative parameters in serum and heart tissues were measured. Assay for mitochondrial respiratory function and histopathological examination of heart tissues were performed. Isoproterenol-treated rats showed significant increases in the levels of lactate dehydrogenase, aspartate transaminase, creatine kinase and malondialdehyde and significant decreases in the activities of superoxide dismutase, catalase and glutathione peroxidase in serum and heart. These rats also showed declines in left ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, and elevation of left ventricular end-diastolic pressure and ST-segment. In addition, mitochondrial respiratory dysfunction characterized by decreased respiratory control ratio and ADP/O was observed in isoproterenol-treated rats. Administration of salvianolic acid A for a period of 8 days significantly attenuated isoproterenol-induced cardiac dysfunction and myocardial injury and improved mitochondrial respiratory function. The protective role of salvianolic acid A against isoproterenol-induced myocardial damage was further confirmed by histopathological examination. The results of our study suggest that salvianolic acid A possessing antioxidant activity has a significant protective effect against isoproterenol-induced myocardial infarction.", "entity": "Adenosine Diphosphate", "aliases": "5'-Pyrophosphate Adenosine ADP Magnesium 5' Pyrophosphate Diphosphate MgADP", "definition": "Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.\n    ", "id": "MESH:D000244"}
{"mention": "cardiac dysfunction", "mention_text": "The present study was designed to evaluate the cardioprotective potential of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. Hemodynamic parameters and lead II electrocardiograph were monitored and recorded continuously. Cardiac marker enzymes and antioxidative parameters in serum and heart tissues were measured. Assay for mitochondrial respiratory function and histopathological examination of heart tissues were performed. Isoproterenol-treated rats showed significant increases in the levels of lactate dehydrogenase, aspartate transaminase, creatine kinase and malondialdehyde and significant decreases in the activities of superoxide dismutase, catalase and glutathione peroxidase in serum and heart. These rats also showed declines in left ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, and elevation of left ventricular end-diastolic pressure and ST-segment. In addition, mitochondrial respiratory dysfunction characterized by decreased respiratory control ratio and ADP/O was observed in isoproterenol-treated rats. Administration of salvianolic acid A for a period of 8 days significantly attenuated isoproterenol-induced cardiac dysfunction and myocardial injury and improved mitochondrial respiratory function. The protective role of salvianolic acid A against isoproterenol-induced myocardial damage was further confirmed by histopathological examination. The results of our study suggest that salvianolic acid A possessing antioxidant activity has a significant protective effect against isoproterenol-induced myocardial infarction.", "entity": "Heart Diseases", "aliases": "Cardiac Disease Diseases Heart", "definition": "Pathological conditions involving the HEART including its structural and functional abnormalities.\n    ", "id": "MESH:D006331"}
{"mention": "myocardial injury", "mention_text": "The present study was designed to evaluate the cardioprotective potential of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. Hemodynamic parameters and lead II electrocardiograph were monitored and recorded continuously. Cardiac marker enzymes and antioxidative parameters in serum and heart tissues were measured. Assay for mitochondrial respiratory function and histopathological examination of heart tissues were performed. Isoproterenol-treated rats showed significant increases in the levels of lactate dehydrogenase, aspartate transaminase, creatine kinase and malondialdehyde and significant decreases in the activities of superoxide dismutase, catalase and glutathione peroxidase in serum and heart. These rats also showed declines in left ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, and elevation of left ventricular end-diastolic pressure and ST-segment. In addition, mitochondrial respiratory dysfunction characterized by decreased respiratory control ratio and ADP/O was observed in isoproterenol-treated rats. Administration of salvianolic acid A for a period of 8 days significantly attenuated isoproterenol-induced cardiac dysfunction and myocardial injury and improved mitochondrial respiratory function. The protective role of salvianolic acid A against isoproterenol-induced myocardial damage was further confirmed by histopathological examination. The results of our study suggest that salvianolic acid A possessing antioxidant activity has a significant protective effect against isoproterenol-induced myocardial infarction.", "entity": "Cardiomyopathies", "aliases": "Cardiomyopathies Primary Secondary Cardiomyopathy Disease Myocardial Diseases Myocardiopathies Myocardiopathy", "definition": "A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).\n    ", "id": "MESH:D009202"}
{"mention": "myocardial damage", "mention_text": "The present study was designed to evaluate the cardioprotective potential of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. Hemodynamic parameters and lead II electrocardiograph were monitored and recorded continuously. Cardiac marker enzymes and antioxidative parameters in serum and heart tissues were measured. Assay for mitochondrial respiratory function and histopathological examination of heart tissues were performed. Isoproterenol-treated rats showed significant increases in the levels of lactate dehydrogenase, aspartate transaminase, creatine kinase and malondialdehyde and significant decreases in the activities of superoxide dismutase, catalase and glutathione peroxidase in serum and heart. These rats also showed declines in left ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, and elevation of left ventricular end-diastolic pressure and ST-segment. In addition, mitochondrial respiratory dysfunction characterized by decreased respiratory control ratio and ADP/O was observed in isoproterenol-treated rats. Administration of salvianolic acid A for a period of 8 days significantly attenuated isoproterenol-induced cardiac dysfunction and myocardial injury and improved mitochondrial respiratory function. The protective role of salvianolic acid A against isoproterenol-induced myocardial damage was further confirmed by histopathological examination. The results of our study suggest that salvianolic acid A possessing antioxidant activity has a significant protective effect against isoproterenol-induced myocardial infarction.", "entity": "Cardiomyopathies", "aliases": "Cardiomyopathies Primary Secondary Cardiomyopathy Disease Myocardial Diseases Myocardiopathies Myocardiopathy", "definition": "A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).\n    ", "id": "MESH:D009202"}
{"mention": "N-(2-propylpentanoyl)urea", "mention_text": "Acute effects of N-(2-propylpentanoyl)urea on hippocampal amino acid neurotransmitters in pilocarpine-induced seizure in rats.", "entity": "N-(2-propylpentanoyl)urea", "aliases": "N-(2-propylpentanoyl)urea VPU compound valproyl urea", "definition": "", "id": "MESH:C108761"}
{"mention": "amino acid", "mention_text": "Acute effects of N-(2-propylpentanoyl)urea on hippocampal amino acid neurotransmitters in pilocarpine-induced seizure in rats.", "entity": "Amino Acids", "aliases": "Acids Amino", "definition": "Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.\n    ", "id": "MESH:D000596"}
{"mention": "pilocarpine", "mention_text": "Acute effects of N-(2-propylpentanoyl)urea on hippocampal amino acid neurotransmitters in pilocarpine-induced seizure in rats.", "entity": "Pilocarpine", "aliases": "Hydrochloride Pilocarpine Isopilocarpine Isoptocarpine Nitrate Ocusert Mononitrate (3S-cis)-Isomer Monohydrochloride Salagen", "definition": "A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma.\n    ", "id": "MESH:D010862"}
{"mention": "seizure", "mention_text": "Acute effects of N-(2-propylpentanoyl)urea on hippocampal amino acid neurotransmitters in pilocarpine-induced seizure in rats.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "amino acid", "mention_text": "The present study aimed to investigate the anticonvulsant activity as well as the effects on the level of hippocampal amino acid neurotransmitters (glutamate, aspartate, glycine and GABA) of N-(2-propylpentanoyl)urea (VPU) in comparison to its parent compound, valproic acid (VPA). VPU was more potent than VPA, exhibiting the median effective dose (ED(50)) of 49 mg/kg in protecting rats against pilocarpine-induced seizure whereas the corresponding value for VPA was 322 mg/kg. In vivo microdialysis demonstrated that an intraperitoneal administration of pilocarpine induced a pronounced increment of hippocampal glutamate and aspartate whereas no significant change was observed on the level of glycine and GABA. Pretreatment with either VPU (50 and 100 mg/kg) or VPA (300 and 600 mg/kg) completely abolished pilocarpine-evoked increases in extracellular glutamate and aspartate. In addition, a statistically significant reduction was also observed on the level of GABA and glycine but less than a drastic reduction of glutamate and aspartate level. Based on the finding that VPU and VPA could protect the animals against pilocarpine-induced seizure it is suggested that the reduction of inhibitory amino acid neurotransmitters was comparatively minor and offset by a pronounced reduction of glutamate and aspartate. Therefore, like VPA, the finding that VPU could drastically reduce pilocarpine-induced increases in glutamate and aspartate should account, at least partly, for its anticonvulsant activity observed in pilocarpine-induced seizure in experimental animals. Some other mechanism than those being reported herein should be further investigated.", "entity": "Amino Acids", "aliases": "Acids Amino", "definition": "Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.\n    ", "id": "MESH:D000596"}
{"mention": "glutamate", "mention_text": "The present study aimed to investigate the anticonvulsant activity as well as the effects on the level of hippocampal amino acid neurotransmitters (glutamate, aspartate, glycine and GABA) of N-(2-propylpentanoyl)urea (VPU) in comparison to its parent compound, valproic acid (VPA). VPU was more potent than VPA, exhibiting the median effective dose (ED(50)) of 49 mg/kg in protecting rats against pilocarpine-induced seizure whereas the corresponding value for VPA was 322 mg/kg. In vivo microdialysis demonstrated that an intraperitoneal administration of pilocarpine induced a pronounced increment of hippocampal glutamate and aspartate whereas no significant change was observed on the level of glycine and GABA. Pretreatment with either VPU (50 and 100 mg/kg) or VPA (300 and 600 mg/kg) completely abolished pilocarpine-evoked increases in extracellular glutamate and aspartate. In addition, a statistically significant reduction was also observed on the level of GABA and glycine but less than a drastic reduction of glutamate and aspartate level. Based on the finding that VPU and VPA could protect the animals against pilocarpine-induced seizure it is suggested that the reduction of inhibitory amino acid neurotransmitters was comparatively minor and offset by a pronounced reduction of glutamate and aspartate. Therefore, like VPA, the finding that VPU could drastically reduce pilocarpine-induced increases in glutamate and aspartate should account, at least partly, for its anticonvulsant activity observed in pilocarpine-induced seizure in experimental animals. Some other mechanism than those being reported herein should be further investigated.", "entity": "Glutamic Acid", "aliases": "Aluminum L Glutamate L-Glutamate D D-Glutamate Potassium Glutamic Acid (D)-Isomer L-Glutamic", "definition": "A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.\n    ", "id": "MESH:D018698"}
{"mention": "aspartate", "mention_text": "The present study aimed to investigate the anticonvulsant activity as well as the effects on the level of hippocampal amino acid neurotransmitters (glutamate, aspartate, glycine and GABA) of N-(2-propylpentanoyl)urea (VPU) in comparison to its parent compound, valproic acid (VPA). VPU was more potent than VPA, exhibiting the median effective dose (ED(50)) of 49 mg/kg in protecting rats against pilocarpine-induced seizure whereas the corresponding value for VPA was 322 mg/kg. In vivo microdialysis demonstrated that an intraperitoneal administration of pilocarpine induced a pronounced increment of hippocampal glutamate and aspartate whereas no significant change was observed on the level of glycine and GABA. Pretreatment with either VPU (50 and 100 mg/kg) or VPA (300 and 600 mg/kg) completely abolished pilocarpine-evoked increases in extracellular glutamate and aspartate. In addition, a statistically significant reduction was also observed on the level of GABA and glycine but less than a drastic reduction of glutamate and aspartate level. Based on the finding that VPU and VPA could protect the animals against pilocarpine-induced seizure it is suggested that the reduction of inhibitory amino acid neurotransmitters was comparatively minor and offset by a pronounced reduction of glutamate and aspartate. Therefore, like VPA, the finding that VPU could drastically reduce pilocarpine-induced increases in glutamate and aspartate should account, at least partly, for its anticonvulsant activity observed in pilocarpine-induced seizure in experimental animals. Some other mechanism than those being reported herein should be further investigated.", "entity": "Aspartic Acid", "aliases": "(+-)-Aspartic Acid (R,S)-Aspartic Ammonium Aspartate Magnesium Hydrochloride Calcium Dipotassium Disodium Monopotassium Monosodium Potassium Sodium Aspartic Salt Hydrobromide (1:1) Trihydrate (2:1) Magnesium-Potassium (2:1:2) L L-Aspartate L-Aspartic Magnesiocard Mg 5 Longoral Mg-5-Longoral Mg5Longoral", "definition": "One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.\n    ", "id": "MESH:D001224"}
{"mention": "glycine", "mention_text": "The present study aimed to investigate the anticonvulsant activity as well as the effects on the level of hippocampal amino acid neurotransmitters (glutamate, aspartate, glycine and GABA) of N-(2-propylpentanoyl)urea (VPU) in comparison to its parent compound, valproic acid (VPA). VPU was more potent than VPA, exhibiting the median effective dose (ED(50)) of 49 mg/kg in protecting rats against pilocarpine-induced seizure whereas the corresponding value for VPA was 322 mg/kg. In vivo microdialysis demonstrated that an intraperitoneal administration of pilocarpine induced a pronounced increment of hippocampal glutamate and aspartate whereas no significant change was observed on the level of glycine and GABA. Pretreatment with either VPU (50 and 100 mg/kg) or VPA (300 and 600 mg/kg) completely abolished pilocarpine-evoked increases in extracellular glutamate and aspartate. In addition, a statistically significant reduction was also observed on the level of GABA and glycine but less than a drastic reduction of glutamate and aspartate level. Based on the finding that VPU and VPA could protect the animals against pilocarpine-induced seizure it is suggested that the reduction of inhibitory amino acid neurotransmitters was comparatively minor and offset by a pronounced reduction of glutamate and aspartate. Therefore, like VPA, the finding that VPU could drastically reduce pilocarpine-induced increases in glutamate and aspartate should account, at least partly, for its anticonvulsant activity observed in pilocarpine-induced seizure in experimental animals. Some other mechanism than those being reported herein should be further investigated.", "entity": "Glycine", "aliases": "Acid Aminoacetic Calcium Salt Glycine Cobalt Copper Carbonate (1:1) Monosodium (2:1) Monolithium Monopotassium Hydrochloride Phosphate Sulfate (3:1) Monoammonium Monopotasssium Sodium Hydrogen", "definition": "A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter.\n    ", "id": "MESH:D005998"}
{"mention": "GABA", "mention_text": "The present study aimed to investigate the anticonvulsant activity as well as the effects on the level of hippocampal amino acid neurotransmitters (glutamate, aspartate, glycine and GABA) of N-(2-propylpentanoyl)urea (VPU) in comparison to its parent compound, valproic acid (VPA). VPU was more potent than VPA, exhibiting the median effective dose (ED(50)) of 49 mg/kg in protecting rats against pilocarpine-induced seizure whereas the corresponding value for VPA was 322 mg/kg. In vivo microdialysis demonstrated that an intraperitoneal administration of pilocarpine induced a pronounced increment of hippocampal glutamate and aspartate whereas no significant change was observed on the level of glycine and GABA. Pretreatment with either VPU (50 and 100 mg/kg) or VPA (300 and 600 mg/kg) completely abolished pilocarpine-evoked increases in extracellular glutamate and aspartate. In addition, a statistically significant reduction was also observed on the level of GABA and glycine but less than a drastic reduction of glutamate and aspartate level. Based on the finding that VPU and VPA could protect the animals against pilocarpine-induced seizure it is suggested that the reduction of inhibitory amino acid neurotransmitters was comparatively minor and offset by a pronounced reduction of glutamate and aspartate. Therefore, like VPA, the finding that VPU could drastically reduce pilocarpine-induced increases in glutamate and aspartate should account, at least partly, for its anticonvulsant activity observed in pilocarpine-induced seizure in experimental animals. Some other mechanism than those being reported herein should be further investigated.", "entity": "gamma-Aminobutyric Acid", "aliases": "4 Aminobutanoic Acid Aminobutyric 4-Aminobutanoic 4-Aminobutyric Hydrochloride gamma-Aminobutyric Aminalon Aminalone GABA Lithium Gammalon gamma Monolithium Salt Monosodium Calcium (2:1) Zinc", "definition": "The most common inhibitory neurotransmitter in the central nervous system.\n    ", "id": "MESH:D005680"}
{"mention": "N-(2-propylpentanoyl)urea", "mention_text": "The present study aimed to investigate the anticonvulsant activity as well as the effects on the level of hippocampal amino acid neurotransmitters (glutamate, aspartate, glycine and GABA) of N-(2-propylpentanoyl)urea (VPU) in comparison to its parent compound, valproic acid (VPA). VPU was more potent than VPA, exhibiting the median effective dose (ED(50)) of 49 mg/kg in protecting rats against pilocarpine-induced seizure whereas the corresponding value for VPA was 322 mg/kg. In vivo microdialysis demonstrated that an intraperitoneal administration of pilocarpine induced a pronounced increment of hippocampal glutamate and aspartate whereas no significant change was observed on the level of glycine and GABA. Pretreatment with either VPU (50 and 100 mg/kg) or VPA (300 and 600 mg/kg) completely abolished pilocarpine-evoked increases in extracellular glutamate and aspartate. In addition, a statistically significant reduction was also observed on the level of GABA and glycine but less than a drastic reduction of glutamate and aspartate level. Based on the finding that VPU and VPA could protect the animals against pilocarpine-induced seizure it is suggested that the reduction of inhibitory amino acid neurotransmitters was comparatively minor and offset by a pronounced reduction of glutamate and aspartate. Therefore, like VPA, the finding that VPU could drastically reduce pilocarpine-induced increases in glutamate and aspartate should account, at least partly, for its anticonvulsant activity observed in pilocarpine-induced seizure in experimental animals. Some other mechanism than those being reported herein should be further investigated.", "entity": "N-(2-propylpentanoyl)urea", "aliases": "N-(2-propylpentanoyl)urea VPU compound valproyl urea", "definition": "", "id": "MESH:C108761"}
{"mention": "VPU", "mention_text": "The present study aimed to investigate the anticonvulsant activity as well as the effects on the level of hippocampal amino acid neurotransmitters (glutamate, aspartate, glycine and GABA) of N-(2-propylpentanoyl)urea (VPU) in comparison to its parent compound, valproic acid (VPA). VPU was more potent than VPA, exhibiting the median effective dose (ED(50)) of 49 mg/kg in protecting rats against pilocarpine-induced seizure whereas the corresponding value for VPA was 322 mg/kg. In vivo microdialysis demonstrated that an intraperitoneal administration of pilocarpine induced a pronounced increment of hippocampal glutamate and aspartate whereas no significant change was observed on the level of glycine and GABA. Pretreatment with either VPU (50 and 100 mg/kg) or VPA (300 and 600 mg/kg) completely abolished pilocarpine-evoked increases in extracellular glutamate and aspartate. In addition, a statistically significant reduction was also observed on the level of GABA and glycine but less than a drastic reduction of glutamate and aspartate level. Based on the finding that VPU and VPA could protect the animals against pilocarpine-induced seizure it is suggested that the reduction of inhibitory amino acid neurotransmitters was comparatively minor and offset by a pronounced reduction of glutamate and aspartate. Therefore, like VPA, the finding that VPU could drastically reduce pilocarpine-induced increases in glutamate and aspartate should account, at least partly, for its anticonvulsant activity observed in pilocarpine-induced seizure in experimental animals. Some other mechanism than those being reported herein should be further investigated.", "entity": "N-(2-propylpentanoyl)urea", "aliases": "N-(2-propylpentanoyl)urea VPU compound valproyl urea", "definition": "", "id": "MESH:C108761"}
{"mention": "valproic acid", "mention_text": "The present study aimed to investigate the anticonvulsant activity as well as the effects on the level of hippocampal amino acid neurotransmitters (glutamate, aspartate, glycine and GABA) of N-(2-propylpentanoyl)urea (VPU) in comparison to its parent compound, valproic acid (VPA). VPU was more potent than VPA, exhibiting the median effective dose (ED(50)) of 49 mg/kg in protecting rats against pilocarpine-induced seizure whereas the corresponding value for VPA was 322 mg/kg. In vivo microdialysis demonstrated that an intraperitoneal administration of pilocarpine induced a pronounced increment of hippocampal glutamate and aspartate whereas no significant change was observed on the level of glycine and GABA. Pretreatment with either VPU (50 and 100 mg/kg) or VPA (300 and 600 mg/kg) completely abolished pilocarpine-evoked increases in extracellular glutamate and aspartate. In addition, a statistically significant reduction was also observed on the level of GABA and glycine but less than a drastic reduction of glutamate and aspartate level. Based on the finding that VPU and VPA could protect the animals against pilocarpine-induced seizure it is suggested that the reduction of inhibitory amino acid neurotransmitters was comparatively minor and offset by a pronounced reduction of glutamate and aspartate. Therefore, like VPA, the finding that VPU could drastically reduce pilocarpine-induced increases in glutamate and aspartate should account, at least partly, for its anticonvulsant activity observed in pilocarpine-induced seizure in experimental animals. Some other mechanism than those being reported herein should be further investigated.", "entity": "Valproic Acid", "aliases": "2 Propylpentanoic Acid 2-Propylpentanoic Acetate Dipropyl Propylisopropylacetic Valproic Calcium Valproate Convulsofin Depakene Depakine Depakote Divalproex Sodium Ergenyl Magnesium Semisodium Salt (2:1) Vupral", "definition": "A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.\n    ", "id": "MESH:D014635"}
{"mention": "VPA", "mention_text": "The present study aimed to investigate the anticonvulsant activity as well as the effects on the level of hippocampal amino acid neurotransmitters (glutamate, aspartate, glycine and GABA) of N-(2-propylpentanoyl)urea (VPU) in comparison to its parent compound, valproic acid (VPA). VPU was more potent than VPA, exhibiting the median effective dose (ED(50)) of 49 mg/kg in protecting rats against pilocarpine-induced seizure whereas the corresponding value for VPA was 322 mg/kg. In vivo microdialysis demonstrated that an intraperitoneal administration of pilocarpine induced a pronounced increment of hippocampal glutamate and aspartate whereas no significant change was observed on the level of glycine and GABA. Pretreatment with either VPU (50 and 100 mg/kg) or VPA (300 and 600 mg/kg) completely abolished pilocarpine-evoked increases in extracellular glutamate and aspartate. In addition, a statistically significant reduction was also observed on the level of GABA and glycine but less than a drastic reduction of glutamate and aspartate level. Based on the finding that VPU and VPA could protect the animals against pilocarpine-induced seizure it is suggested that the reduction of inhibitory amino acid neurotransmitters was comparatively minor and offset by a pronounced reduction of glutamate and aspartate. Therefore, like VPA, the finding that VPU could drastically reduce pilocarpine-induced increases in glutamate and aspartate should account, at least partly, for its anticonvulsant activity observed in pilocarpine-induced seizure in experimental animals. Some other mechanism than those being reported herein should be further investigated.", "entity": "Valproic Acid", "aliases": "2 Propylpentanoic Acid 2-Propylpentanoic Acetate Dipropyl Propylisopropylacetic Valproic Calcium Valproate Convulsofin Depakene Depakine Depakote Divalproex Sodium Ergenyl Magnesium Semisodium Salt (2:1) Vupral", "definition": "A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.\n    ", "id": "MESH:D014635"}
{"mention": "pilocarpine", "mention_text": "The present study aimed to investigate the anticonvulsant activity as well as the effects on the level of hippocampal amino acid neurotransmitters (glutamate, aspartate, glycine and GABA) of N-(2-propylpentanoyl)urea (VPU) in comparison to its parent compound, valproic acid (VPA). VPU was more potent than VPA, exhibiting the median effective dose (ED(50)) of 49 mg/kg in protecting rats against pilocarpine-induced seizure whereas the corresponding value for VPA was 322 mg/kg. In vivo microdialysis demonstrated that an intraperitoneal administration of pilocarpine induced a pronounced increment of hippocampal glutamate and aspartate whereas no significant change was observed on the level of glycine and GABA. Pretreatment with either VPU (50 and 100 mg/kg) or VPA (300 and 600 mg/kg) completely abolished pilocarpine-evoked increases in extracellular glutamate and aspartate. In addition, a statistically significant reduction was also observed on the level of GABA and glycine but less than a drastic reduction of glutamate and aspartate level. Based on the finding that VPU and VPA could protect the animals against pilocarpine-induced seizure it is suggested that the reduction of inhibitory amino acid neurotransmitters was comparatively minor and offset by a pronounced reduction of glutamate and aspartate. Therefore, like VPA, the finding that VPU could drastically reduce pilocarpine-induced increases in glutamate and aspartate should account, at least partly, for its anticonvulsant activity observed in pilocarpine-induced seizure in experimental animals. Some other mechanism than those being reported herein should be further investigated.", "entity": "Pilocarpine", "aliases": "Hydrochloride Pilocarpine Isopilocarpine Isoptocarpine Nitrate Ocusert Mononitrate (3S-cis)-Isomer Monohydrochloride Salagen", "definition": "A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma.\n    ", "id": "MESH:D010862"}
{"mention": "seizure", "mention_text": "The present study aimed to investigate the anticonvulsant activity as well as the effects on the level of hippocampal amino acid neurotransmitters (glutamate, aspartate, glycine and GABA) of N-(2-propylpentanoyl)urea (VPU) in comparison to its parent compound, valproic acid (VPA). VPU was more potent than VPA, exhibiting the median effective dose (ED(50)) of 49 mg/kg in protecting rats against pilocarpine-induced seizure whereas the corresponding value for VPA was 322 mg/kg. In vivo microdialysis demonstrated that an intraperitoneal administration of pilocarpine induced a pronounced increment of hippocampal glutamate and aspartate whereas no significant change was observed on the level of glycine and GABA. Pretreatment with either VPU (50 and 100 mg/kg) or VPA (300 and 600 mg/kg) completely abolished pilocarpine-evoked increases in extracellular glutamate and aspartate. In addition, a statistically significant reduction was also observed on the level of GABA and glycine but less than a drastic reduction of glutamate and aspartate level. Based on the finding that VPU and VPA could protect the animals against pilocarpine-induced seizure it is suggested that the reduction of inhibitory amino acid neurotransmitters was comparatively minor and offset by a pronounced reduction of glutamate and aspartate. Therefore, like VPA, the finding that VPU could drastically reduce pilocarpine-induced increases in glutamate and aspartate should account, at least partly, for its anticonvulsant activity observed in pilocarpine-induced seizure in experimental animals. Some other mechanism than those being reported herein should be further investigated.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "hepatitis", "mention_text": "Acute hepatitis attack after exposure to telithromycin.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "telithromycin", "mention_text": "Acute hepatitis attack after exposure to telithromycin.", "entity": "telithromycin", "aliases": "HMR 3647 HMR-3647 HMR3647 Ketek RU 66647 RU-66647 telithromycin", "definition": "", "id": "MESH:C106791"}
{"mention": "hepatotoxicity", "mention_text": "INTRODUCTION: Antibiotic-associated hepatotoxicity is rare. With widespread use of antimicrobial agents, however, hepatic injury occurs frequently, and among adverse drug reactions, idiosyncratic reactions are the most serious. CASE SUMMARY: A 25-year-old male patient, with a height of 175 cm and weight of 72 kg presented to Marmara University Hospital Emergency Department, Istanbul, Turkey, with 5 days' history of jaundice, malaise, nausea, and vomiting. He had been prescribed telithromycin 400 mg/d PO to treat an upper respiratory tract infection 7 days prior. Admission laboratory tests were as follows: alanine aminotransferase, 67 U/L (reference range, 10-37 U/L); aspartate aminotransferase, 98 U/L (10-40 U/L); alkaline phosphatase, 513 U/L (0-270 U/L); gamma-glutamyltransferase, 32 U/L (7-49 U/L); amylase, 46 U/L (0-220 U/L); total bilirubin, 20.1 mg/dL (0.2-1.0 mg/dL); direct bilirubin, 14.8 mg/dL (0-0.3 mg/dL); and albumin, 4.7 mg/dL (3.5-5.4 mg/dL). No toxin, alcohol, or other drugs were reported. The patient had suffered a previous episode of \"acute hepatitis of unknown origin,\" that occurred after telithromycin usage. Both incidents occurred within a year. DISCUSSION: Telithromycin is the first of the ketolide antibacterials to receive US Food and Drug Administration approval for clinical use. It has been associated with infrequent and usually reversible severe hepatic dysfunction. Based on a score of 8 on the Naranjo adverse drug reaction probability scale, telithromycin was the probable cause of acute hepatitis in this patient, and pathological findings suggested drug-induced toxic hepatitis. Recurrence of hepatitis attack might have been avoided if the initial incident had been communicated to the attending physician who prescribed telithromycin the second time. CONCLUSION: Here we report a case of acute hepatitis probably associated with the administration of telithromycin.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "hepatic injury", "mention_text": "INTRODUCTION: Antibiotic-associated hepatotoxicity is rare. With widespread use of antimicrobial agents, however, hepatic injury occurs frequently, and among adverse drug reactions, idiosyncratic reactions are the most serious. CASE SUMMARY: A 25-year-old male patient, with a height of 175 cm and weight of 72 kg presented to Marmara University Hospital Emergency Department, Istanbul, Turkey, with 5 days' history of jaundice, malaise, nausea, and vomiting. He had been prescribed telithromycin 400 mg/d PO to treat an upper respiratory tract infection 7 days prior. Admission laboratory tests were as follows: alanine aminotransferase, 67 U/L (reference range, 10-37 U/L); aspartate aminotransferase, 98 U/L (10-40 U/L); alkaline phosphatase, 513 U/L (0-270 U/L); gamma-glutamyltransferase, 32 U/L (7-49 U/L); amylase, 46 U/L (0-220 U/L); total bilirubin, 20.1 mg/dL (0.2-1.0 mg/dL); direct bilirubin, 14.8 mg/dL (0-0.3 mg/dL); and albumin, 4.7 mg/dL (3.5-5.4 mg/dL). No toxin, alcohol, or other drugs were reported. The patient had suffered a previous episode of \"acute hepatitis of unknown origin,\" that occurred after telithromycin usage. Both incidents occurred within a year. DISCUSSION: Telithromycin is the first of the ketolide antibacterials to receive US Food and Drug Administration approval for clinical use. It has been associated with infrequent and usually reversible severe hepatic dysfunction. Based on a score of 8 on the Naranjo adverse drug reaction probability scale, telithromycin was the probable cause of acute hepatitis in this patient, and pathological findings suggested drug-induced toxic hepatitis. Recurrence of hepatitis attack might have been avoided if the initial incident had been communicated to the attending physician who prescribed telithromycin the second time. CONCLUSION: Here we report a case of acute hepatitis probably associated with the administration of telithromycin.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "adverse drug reactions", "mention_text": "INTRODUCTION: Antibiotic-associated hepatotoxicity is rare. With widespread use of antimicrobial agents, however, hepatic injury occurs frequently, and among adverse drug reactions, idiosyncratic reactions are the most serious. CASE SUMMARY: A 25-year-old male patient, with a height of 175 cm and weight of 72 kg presented to Marmara University Hospital Emergency Department, Istanbul, Turkey, with 5 days' history of jaundice, malaise, nausea, and vomiting. He had been prescribed telithromycin 400 mg/d PO to treat an upper respiratory tract infection 7 days prior. Admission laboratory tests were as follows: alanine aminotransferase, 67 U/L (reference range, 10-37 U/L); aspartate aminotransferase, 98 U/L (10-40 U/L); alkaline phosphatase, 513 U/L (0-270 U/L); gamma-glutamyltransferase, 32 U/L (7-49 U/L); amylase, 46 U/L (0-220 U/L); total bilirubin, 20.1 mg/dL (0.2-1.0 mg/dL); direct bilirubin, 14.8 mg/dL (0-0.3 mg/dL); and albumin, 4.7 mg/dL (3.5-5.4 mg/dL). No toxin, alcohol, or other drugs were reported. The patient had suffered a previous episode of \"acute hepatitis of unknown origin,\" that occurred after telithromycin usage. Both incidents occurred within a year. DISCUSSION: Telithromycin is the first of the ketolide antibacterials to receive US Food and Drug Administration approval for clinical use. It has been associated with infrequent and usually reversible severe hepatic dysfunction. Based on a score of 8 on the Naranjo adverse drug reaction probability scale, telithromycin was the probable cause of acute hepatitis in this patient, and pathological findings suggested drug-induced toxic hepatitis. Recurrence of hepatitis attack might have been avoided if the initial incident had been communicated to the attending physician who prescribed telithromycin the second time. CONCLUSION: Here we report a case of acute hepatitis probably associated with the administration of telithromycin.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "jaundice", "mention_text": "INTRODUCTION: Antibiotic-associated hepatotoxicity is rare. With widespread use of antimicrobial agents, however, hepatic injury occurs frequently, and among adverse drug reactions, idiosyncratic reactions are the most serious. CASE SUMMARY: A 25-year-old male patient, with a height of 175 cm and weight of 72 kg presented to Marmara University Hospital Emergency Department, Istanbul, Turkey, with 5 days' history of jaundice, malaise, nausea, and vomiting. He had been prescribed telithromycin 400 mg/d PO to treat an upper respiratory tract infection 7 days prior. Admission laboratory tests were as follows: alanine aminotransferase, 67 U/L (reference range, 10-37 U/L); aspartate aminotransferase, 98 U/L (10-40 U/L); alkaline phosphatase, 513 U/L (0-270 U/L); gamma-glutamyltransferase, 32 U/L (7-49 U/L); amylase, 46 U/L (0-220 U/L); total bilirubin, 20.1 mg/dL (0.2-1.0 mg/dL); direct bilirubin, 14.8 mg/dL (0-0.3 mg/dL); and albumin, 4.7 mg/dL (3.5-5.4 mg/dL). No toxin, alcohol, or other drugs were reported. The patient had suffered a previous episode of \"acute hepatitis of unknown origin,\" that occurred after telithromycin usage. Both incidents occurred within a year. DISCUSSION: Telithromycin is the first of the ketolide antibacterials to receive US Food and Drug Administration approval for clinical use. It has been associated with infrequent and usually reversible severe hepatic dysfunction. Based on a score of 8 on the Naranjo adverse drug reaction probability scale, telithromycin was the probable cause of acute hepatitis in this patient, and pathological findings suggested drug-induced toxic hepatitis. Recurrence of hepatitis attack might have been avoided if the initial incident had been communicated to the attending physician who prescribed telithromycin the second time. CONCLUSION: Here we report a case of acute hepatitis probably associated with the administration of telithromycin.", "entity": "Jaundice", "aliases": "Hemolytic Jaundice Jaundices Icterus", "definition": "A clinical manifestation of HYPERBILIRUBINEMIA, characterized by the yellowish staining of the SKIN; MUCOUS MEMBRANE; and SCLERA. Clinical jaundice usually is a sign of LIVER dysfunction.\n    ", "id": "MESH:D007565"}
{"mention": "nausea", "mention_text": "INTRODUCTION: Antibiotic-associated hepatotoxicity is rare. With widespread use of antimicrobial agents, however, hepatic injury occurs frequently, and among adverse drug reactions, idiosyncratic reactions are the most serious. CASE SUMMARY: A 25-year-old male patient, with a height of 175 cm and weight of 72 kg presented to Marmara University Hospital Emergency Department, Istanbul, Turkey, with 5 days' history of jaundice, malaise, nausea, and vomiting. He had been prescribed telithromycin 400 mg/d PO to treat an upper respiratory tract infection 7 days prior. Admission laboratory tests were as follows: alanine aminotransferase, 67 U/L (reference range, 10-37 U/L); aspartate aminotransferase, 98 U/L (10-40 U/L); alkaline phosphatase, 513 U/L (0-270 U/L); gamma-glutamyltransferase, 32 U/L (7-49 U/L); amylase, 46 U/L (0-220 U/L); total bilirubin, 20.1 mg/dL (0.2-1.0 mg/dL); direct bilirubin, 14.8 mg/dL (0-0.3 mg/dL); and albumin, 4.7 mg/dL (3.5-5.4 mg/dL). No toxin, alcohol, or other drugs were reported. The patient had suffered a previous episode of \"acute hepatitis of unknown origin,\" that occurred after telithromycin usage. Both incidents occurred within a year. DISCUSSION: Telithromycin is the first of the ketolide antibacterials to receive US Food and Drug Administration approval for clinical use. It has been associated with infrequent and usually reversible severe hepatic dysfunction. Based on a score of 8 on the Naranjo adverse drug reaction probability scale, telithromycin was the probable cause of acute hepatitis in this patient, and pathological findings suggested drug-induced toxic hepatitis. Recurrence of hepatitis attack might have been avoided if the initial incident had been communicated to the attending physician who prescribed telithromycin the second time. CONCLUSION: Here we report a case of acute hepatitis probably associated with the administration of telithromycin.", "entity": "Nausea", "aliases": "Nausea", "definition": "An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.\n    ", "id": "MESH:D009325"}
{"mention": "vomiting", "mention_text": "INTRODUCTION: Antibiotic-associated hepatotoxicity is rare. With widespread use of antimicrobial agents, however, hepatic injury occurs frequently, and among adverse drug reactions, idiosyncratic reactions are the most serious. CASE SUMMARY: A 25-year-old male patient, with a height of 175 cm and weight of 72 kg presented to Marmara University Hospital Emergency Department, Istanbul, Turkey, with 5 days' history of jaundice, malaise, nausea, and vomiting. He had been prescribed telithromycin 400 mg/d PO to treat an upper respiratory tract infection 7 days prior. Admission laboratory tests were as follows: alanine aminotransferase, 67 U/L (reference range, 10-37 U/L); aspartate aminotransferase, 98 U/L (10-40 U/L); alkaline phosphatase, 513 U/L (0-270 U/L); gamma-glutamyltransferase, 32 U/L (7-49 U/L); amylase, 46 U/L (0-220 U/L); total bilirubin, 20.1 mg/dL (0.2-1.0 mg/dL); direct bilirubin, 14.8 mg/dL (0-0.3 mg/dL); and albumin, 4.7 mg/dL (3.5-5.4 mg/dL). No toxin, alcohol, or other drugs were reported. The patient had suffered a previous episode of \"acute hepatitis of unknown origin,\" that occurred after telithromycin usage. Both incidents occurred within a year. DISCUSSION: Telithromycin is the first of the ketolide antibacterials to receive US Food and Drug Administration approval for clinical use. It has been associated with infrequent and usually reversible severe hepatic dysfunction. Based on a score of 8 on the Naranjo adverse drug reaction probability scale, telithromycin was the probable cause of acute hepatitis in this patient, and pathological findings suggested drug-induced toxic hepatitis. Recurrence of hepatitis attack might have been avoided if the initial incident had been communicated to the attending physician who prescribed telithromycin the second time. CONCLUSION: Here we report a case of acute hepatitis probably associated with the administration of telithromycin.", "entity": "Vomiting", "aliases": "Emesis Vomiting", "definition": "The forcible expulsion of the contents of the STOMACH through the MOUTH.\n    ", "id": "MESH:D014839"}
{"mention": "telithromycin", "mention_text": "INTRODUCTION: Antibiotic-associated hepatotoxicity is rare. With widespread use of antimicrobial agents, however, hepatic injury occurs frequently, and among adverse drug reactions, idiosyncratic reactions are the most serious. CASE SUMMARY: A 25-year-old male patient, with a height of 175 cm and weight of 72 kg presented to Marmara University Hospital Emergency Department, Istanbul, Turkey, with 5 days' history of jaundice, malaise, nausea, and vomiting. He had been prescribed telithromycin 400 mg/d PO to treat an upper respiratory tract infection 7 days prior. Admission laboratory tests were as follows: alanine aminotransferase, 67 U/L (reference range, 10-37 U/L); aspartate aminotransferase, 98 U/L (10-40 U/L); alkaline phosphatase, 513 U/L (0-270 U/L); gamma-glutamyltransferase, 32 U/L (7-49 U/L); amylase, 46 U/L (0-220 U/L); total bilirubin, 20.1 mg/dL (0.2-1.0 mg/dL); direct bilirubin, 14.8 mg/dL (0-0.3 mg/dL); and albumin, 4.7 mg/dL (3.5-5.4 mg/dL). No toxin, alcohol, or other drugs were reported. The patient had suffered a previous episode of \"acute hepatitis of unknown origin,\" that occurred after telithromycin usage. Both incidents occurred within a year. DISCUSSION: Telithromycin is the first of the ketolide antibacterials to receive US Food and Drug Administration approval for clinical use. It has been associated with infrequent and usually reversible severe hepatic dysfunction. Based on a score of 8 on the Naranjo adverse drug reaction probability scale, telithromycin was the probable cause of acute hepatitis in this patient, and pathological findings suggested drug-induced toxic hepatitis. Recurrence of hepatitis attack might have been avoided if the initial incident had been communicated to the attending physician who prescribed telithromycin the second time. CONCLUSION: Here we report a case of acute hepatitis probably associated with the administration of telithromycin.", "entity": "telithromycin", "aliases": "HMR 3647 HMR-3647 HMR3647 Ketek RU 66647 RU-66647 telithromycin", "definition": "", "id": "MESH:C106791"}
{"mention": "upper respiratory tract infection", "mention_text": "INTRODUCTION: Antibiotic-associated hepatotoxicity is rare. With widespread use of antimicrobial agents, however, hepatic injury occurs frequently, and among adverse drug reactions, idiosyncratic reactions are the most serious. CASE SUMMARY: A 25-year-old male patient, with a height of 175 cm and weight of 72 kg presented to Marmara University Hospital Emergency Department, Istanbul, Turkey, with 5 days' history of jaundice, malaise, nausea, and vomiting. He had been prescribed telithromycin 400 mg/d PO to treat an upper respiratory tract infection 7 days prior. Admission laboratory tests were as follows: alanine aminotransferase, 67 U/L (reference range, 10-37 U/L); aspartate aminotransferase, 98 U/L (10-40 U/L); alkaline phosphatase, 513 U/L (0-270 U/L); gamma-glutamyltransferase, 32 U/L (7-49 U/L); amylase, 46 U/L (0-220 U/L); total bilirubin, 20.1 mg/dL (0.2-1.0 mg/dL); direct bilirubin, 14.8 mg/dL (0-0.3 mg/dL); and albumin, 4.7 mg/dL (3.5-5.4 mg/dL). No toxin, alcohol, or other drugs were reported. The patient had suffered a previous episode of \"acute hepatitis of unknown origin,\" that occurred after telithromycin usage. Both incidents occurred within a year. DISCUSSION: Telithromycin is the first of the ketolide antibacterials to receive US Food and Drug Administration approval for clinical use. It has been associated with infrequent and usually reversible severe hepatic dysfunction. Based on a score of 8 on the Naranjo adverse drug reaction probability scale, telithromycin was the probable cause of acute hepatitis in this patient, and pathological findings suggested drug-induced toxic hepatitis. Recurrence of hepatitis attack might have been avoided if the initial incident had been communicated to the attending physician who prescribed telithromycin the second time. CONCLUSION: Here we report a case of acute hepatitis probably associated with the administration of telithromycin.", "entity": "Respiratory Tract Infections", "aliases": "Infection Respiratory Tract Infections Upper", "definition": "Invasion of the host RESPIRATORY SYSTEM by microorganisms, usually leading to pathological processes or diseases.\n    ", "id": "MESH:D012141"}
{"mention": "alanine", "mention_text": "INTRODUCTION: Antibiotic-associated hepatotoxicity is rare. With widespread use of antimicrobial agents, however, hepatic injury occurs frequently, and among adverse drug reactions, idiosyncratic reactions are the most serious. CASE SUMMARY: A 25-year-old male patient, with a height of 175 cm and weight of 72 kg presented to Marmara University Hospital Emergency Department, Istanbul, Turkey, with 5 days' history of jaundice, malaise, nausea, and vomiting. He had been prescribed telithromycin 400 mg/d PO to treat an upper respiratory tract infection 7 days prior. Admission laboratory tests were as follows: alanine aminotransferase, 67 U/L (reference range, 10-37 U/L); aspartate aminotransferase, 98 U/L (10-40 U/L); alkaline phosphatase, 513 U/L (0-270 U/L); gamma-glutamyltransferase, 32 U/L (7-49 U/L); amylase, 46 U/L (0-220 U/L); total bilirubin, 20.1 mg/dL (0.2-1.0 mg/dL); direct bilirubin, 14.8 mg/dL (0-0.3 mg/dL); and albumin, 4.7 mg/dL (3.5-5.4 mg/dL). No toxin, alcohol, or other drugs were reported. The patient had suffered a previous episode of \"acute hepatitis of unknown origin,\" that occurred after telithromycin usage. Both incidents occurred within a year. DISCUSSION: Telithromycin is the first of the ketolide antibacterials to receive US Food and Drug Administration approval for clinical use. It has been associated with infrequent and usually reversible severe hepatic dysfunction. Based on a score of 8 on the Naranjo adverse drug reaction probability scale, telithromycin was the probable cause of acute hepatitis in this patient, and pathological findings suggested drug-induced toxic hepatitis. Recurrence of hepatitis attack might have been avoided if the initial incident had been communicated to the attending physician who prescribed telithromycin the second time. CONCLUSION: Here we report a case of acute hepatitis probably associated with the administration of telithromycin.", "entity": "Alanine", "aliases": "Abufène Alanine Doms-Adrian Brand L Isomer L-Isomer Doms Adrian of L-Alanine", "definition": "A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases IMMUNITY, and provides energy for muscle tissue, BRAIN, and the CENTRAL NERVOUS SYSTEM.\n    ", "id": "MESH:D000409"}
{"mention": "aspartate", "mention_text": "INTRODUCTION: Antibiotic-associated hepatotoxicity is rare. With widespread use of antimicrobial agents, however, hepatic injury occurs frequently, and among adverse drug reactions, idiosyncratic reactions are the most serious. CASE SUMMARY: A 25-year-old male patient, with a height of 175 cm and weight of 72 kg presented to Marmara University Hospital Emergency Department, Istanbul, Turkey, with 5 days' history of jaundice, malaise, nausea, and vomiting. He had been prescribed telithromycin 400 mg/d PO to treat an upper respiratory tract infection 7 days prior. Admission laboratory tests were as follows: alanine aminotransferase, 67 U/L (reference range, 10-37 U/L); aspartate aminotransferase, 98 U/L (10-40 U/L); alkaline phosphatase, 513 U/L (0-270 U/L); gamma-glutamyltransferase, 32 U/L (7-49 U/L); amylase, 46 U/L (0-220 U/L); total bilirubin, 20.1 mg/dL (0.2-1.0 mg/dL); direct bilirubin, 14.8 mg/dL (0-0.3 mg/dL); and albumin, 4.7 mg/dL (3.5-5.4 mg/dL). No toxin, alcohol, or other drugs were reported. The patient had suffered a previous episode of \"acute hepatitis of unknown origin,\" that occurred after telithromycin usage. Both incidents occurred within a year. DISCUSSION: Telithromycin is the first of the ketolide antibacterials to receive US Food and Drug Administration approval for clinical use. It has been associated with infrequent and usually reversible severe hepatic dysfunction. Based on a score of 8 on the Naranjo adverse drug reaction probability scale, telithromycin was the probable cause of acute hepatitis in this patient, and pathological findings suggested drug-induced toxic hepatitis. Recurrence of hepatitis attack might have been avoided if the initial incident had been communicated to the attending physician who prescribed telithromycin the second time. CONCLUSION: Here we report a case of acute hepatitis probably associated with the administration of telithromycin.", "entity": "Aspartic Acid", "aliases": "(+-)-Aspartic Acid (R,S)-Aspartic Ammonium Aspartate Magnesium Hydrochloride Calcium Dipotassium Disodium Monopotassium Monosodium Potassium Sodium Aspartic Salt Hydrobromide (1:1) Trihydrate (2:1) Magnesium-Potassium (2:1:2) L L-Aspartate L-Aspartic Magnesiocard Mg 5 Longoral Mg-5-Longoral Mg5Longoral", "definition": "One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.\n    ", "id": "MESH:D001224"}
{"mention": "bilirubin", "mention_text": "INTRODUCTION: Antibiotic-associated hepatotoxicity is rare. With widespread use of antimicrobial agents, however, hepatic injury occurs frequently, and among adverse drug reactions, idiosyncratic reactions are the most serious. CASE SUMMARY: A 25-year-old male patient, with a height of 175 cm and weight of 72 kg presented to Marmara University Hospital Emergency Department, Istanbul, Turkey, with 5 days' history of jaundice, malaise, nausea, and vomiting. He had been prescribed telithromycin 400 mg/d PO to treat an upper respiratory tract infection 7 days prior. Admission laboratory tests were as follows: alanine aminotransferase, 67 U/L (reference range, 10-37 U/L); aspartate aminotransferase, 98 U/L (10-40 U/L); alkaline phosphatase, 513 U/L (0-270 U/L); gamma-glutamyltransferase, 32 U/L (7-49 U/L); amylase, 46 U/L (0-220 U/L); total bilirubin, 20.1 mg/dL (0.2-1.0 mg/dL); direct bilirubin, 14.8 mg/dL (0-0.3 mg/dL); and albumin, 4.7 mg/dL (3.5-5.4 mg/dL). No toxin, alcohol, or other drugs were reported. The patient had suffered a previous episode of \"acute hepatitis of unknown origin,\" that occurred after telithromycin usage. Both incidents occurred within a year. DISCUSSION: Telithromycin is the first of the ketolide antibacterials to receive US Food and Drug Administration approval for clinical use. It has been associated with infrequent and usually reversible severe hepatic dysfunction. Based on a score of 8 on the Naranjo adverse drug reaction probability scale, telithromycin was the probable cause of acute hepatitis in this patient, and pathological findings suggested drug-induced toxic hepatitis. Recurrence of hepatitis attack might have been avoided if the initial incident had been communicated to the attending physician who prescribed telithromycin the second time. CONCLUSION: Here we report a case of acute hepatitis probably associated with the administration of telithromycin.", "entity": "Bilirubin", "aliases": "Bilirubin IX alpha (15E)-Isomer (4E)-Isomer (4E,15E)-Isomer Calcium Salt Disodium Monosodium Bilirubinate Hematoidin delta delta-Bilirubin", "definition": "A bile pigment that is a degradation product of HEME.\n    ", "id": "MESH:D001663"}
{"mention": "alcohol", "mention_text": "INTRODUCTION: Antibiotic-associated hepatotoxicity is rare. With widespread use of antimicrobial agents, however, hepatic injury occurs frequently, and among adverse drug reactions, idiosyncratic reactions are the most serious. CASE SUMMARY: A 25-year-old male patient, with a height of 175 cm and weight of 72 kg presented to Marmara University Hospital Emergency Department, Istanbul, Turkey, with 5 days' history of jaundice, malaise, nausea, and vomiting. He had been prescribed telithromycin 400 mg/d PO to treat an upper respiratory tract infection 7 days prior. Admission laboratory tests were as follows: alanine aminotransferase, 67 U/L (reference range, 10-37 U/L); aspartate aminotransferase, 98 U/L (10-40 U/L); alkaline phosphatase, 513 U/L (0-270 U/L); gamma-glutamyltransferase, 32 U/L (7-49 U/L); amylase, 46 U/L (0-220 U/L); total bilirubin, 20.1 mg/dL (0.2-1.0 mg/dL); direct bilirubin, 14.8 mg/dL (0-0.3 mg/dL); and albumin, 4.7 mg/dL (3.5-5.4 mg/dL). No toxin, alcohol, or other drugs were reported. The patient had suffered a previous episode of \"acute hepatitis of unknown origin,\" that occurred after telithromycin usage. Both incidents occurred within a year. DISCUSSION: Telithromycin is the first of the ketolide antibacterials to receive US Food and Drug Administration approval for clinical use. It has been associated with infrequent and usually reversible severe hepatic dysfunction. Based on a score of 8 on the Naranjo adverse drug reaction probability scale, telithromycin was the probable cause of acute hepatitis in this patient, and pathological findings suggested drug-induced toxic hepatitis. Recurrence of hepatitis attack might have been avoided if the initial incident had been communicated to the attending physician who prescribed telithromycin the second time. CONCLUSION: Here we report a case of acute hepatitis probably associated with the administration of telithromycin.", "entity": "Ethanol", "aliases": "Absolute Alcohol Ethyl Grain Ethanol", "definition": "A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.\n    ", "id": "MESH:D000431"}
{"mention": "hepatitis", "mention_text": "INTRODUCTION: Antibiotic-associated hepatotoxicity is rare. With widespread use of antimicrobial agents, however, hepatic injury occurs frequently, and among adverse drug reactions, idiosyncratic reactions are the most serious. CASE SUMMARY: A 25-year-old male patient, with a height of 175 cm and weight of 72 kg presented to Marmara University Hospital Emergency Department, Istanbul, Turkey, with 5 days' history of jaundice, malaise, nausea, and vomiting. He had been prescribed telithromycin 400 mg/d PO to treat an upper respiratory tract infection 7 days prior. Admission laboratory tests were as follows: alanine aminotransferase, 67 U/L (reference range, 10-37 U/L); aspartate aminotransferase, 98 U/L (10-40 U/L); alkaline phosphatase, 513 U/L (0-270 U/L); gamma-glutamyltransferase, 32 U/L (7-49 U/L); amylase, 46 U/L (0-220 U/L); total bilirubin, 20.1 mg/dL (0.2-1.0 mg/dL); direct bilirubin, 14.8 mg/dL (0-0.3 mg/dL); and albumin, 4.7 mg/dL (3.5-5.4 mg/dL). No toxin, alcohol, or other drugs were reported. The patient had suffered a previous episode of \"acute hepatitis of unknown origin,\" that occurred after telithromycin usage. Both incidents occurred within a year. DISCUSSION: Telithromycin is the first of the ketolide antibacterials to receive US Food and Drug Administration approval for clinical use. It has been associated with infrequent and usually reversible severe hepatic dysfunction. Based on a score of 8 on the Naranjo adverse drug reaction probability scale, telithromycin was the probable cause of acute hepatitis in this patient, and pathological findings suggested drug-induced toxic hepatitis. Recurrence of hepatitis attack might have been avoided if the initial incident had been communicated to the attending physician who prescribed telithromycin the second time. CONCLUSION: Here we report a case of acute hepatitis probably associated with the administration of telithromycin.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "Telithromycin", "mention_text": "INTRODUCTION: Antibiotic-associated hepatotoxicity is rare. With widespread use of antimicrobial agents, however, hepatic injury occurs frequently, and among adverse drug reactions, idiosyncratic reactions are the most serious. CASE SUMMARY: A 25-year-old male patient, with a height of 175 cm and weight of 72 kg presented to Marmara University Hospital Emergency Department, Istanbul, Turkey, with 5 days' history of jaundice, malaise, nausea, and vomiting. He had been prescribed telithromycin 400 mg/d PO to treat an upper respiratory tract infection 7 days prior. Admission laboratory tests were as follows: alanine aminotransferase, 67 U/L (reference range, 10-37 U/L); aspartate aminotransferase, 98 U/L (10-40 U/L); alkaline phosphatase, 513 U/L (0-270 U/L); gamma-glutamyltransferase, 32 U/L (7-49 U/L); amylase, 46 U/L (0-220 U/L); total bilirubin, 20.1 mg/dL (0.2-1.0 mg/dL); direct bilirubin, 14.8 mg/dL (0-0.3 mg/dL); and albumin, 4.7 mg/dL (3.5-5.4 mg/dL). No toxin, alcohol, or other drugs were reported. The patient had suffered a previous episode of \"acute hepatitis of unknown origin,\" that occurred after telithromycin usage. Both incidents occurred within a year. DISCUSSION: Telithromycin is the first of the ketolide antibacterials to receive US Food and Drug Administration approval for clinical use. It has been associated with infrequent and usually reversible severe hepatic dysfunction. Based on a score of 8 on the Naranjo adverse drug reaction probability scale, telithromycin was the probable cause of acute hepatitis in this patient, and pathological findings suggested drug-induced toxic hepatitis. Recurrence of hepatitis attack might have been avoided if the initial incident had been communicated to the attending physician who prescribed telithromycin the second time. CONCLUSION: Here we report a case of acute hepatitis probably associated with the administration of telithromycin.", "entity": "telithromycin", "aliases": "HMR 3647 HMR-3647 HMR3647 Ketek RU 66647 RU-66647 telithromycin", "definition": "", "id": "MESH:C106791"}
{"mention": "hepatic dysfunction", "mention_text": "INTRODUCTION: Antibiotic-associated hepatotoxicity is rare. With widespread use of antimicrobial agents, however, hepatic injury occurs frequently, and among adverse drug reactions, idiosyncratic reactions are the most serious. CASE SUMMARY: A 25-year-old male patient, with a height of 175 cm and weight of 72 kg presented to Marmara University Hospital Emergency Department, Istanbul, Turkey, with 5 days' history of jaundice, malaise, nausea, and vomiting. He had been prescribed telithromycin 400 mg/d PO to treat an upper respiratory tract infection 7 days prior. Admission laboratory tests were as follows: alanine aminotransferase, 67 U/L (reference range, 10-37 U/L); aspartate aminotransferase, 98 U/L (10-40 U/L); alkaline phosphatase, 513 U/L (0-270 U/L); gamma-glutamyltransferase, 32 U/L (7-49 U/L); amylase, 46 U/L (0-220 U/L); total bilirubin, 20.1 mg/dL (0.2-1.0 mg/dL); direct bilirubin, 14.8 mg/dL (0-0.3 mg/dL); and albumin, 4.7 mg/dL (3.5-5.4 mg/dL). No toxin, alcohol, or other drugs were reported. The patient had suffered a previous episode of \"acute hepatitis of unknown origin,\" that occurred after telithromycin usage. Both incidents occurred within a year. DISCUSSION: Telithromycin is the first of the ketolide antibacterials to receive US Food and Drug Administration approval for clinical use. It has been associated with infrequent and usually reversible severe hepatic dysfunction. Based on a score of 8 on the Naranjo adverse drug reaction probability scale, telithromycin was the probable cause of acute hepatitis in this patient, and pathological findings suggested drug-induced toxic hepatitis. Recurrence of hepatitis attack might have been avoided if the initial incident had been communicated to the attending physician who prescribed telithromycin the second time. CONCLUSION: Here we report a case of acute hepatitis probably associated with the administration of telithromycin.", "entity": "Liver Diseases", "aliases": "Disease Liver Diseases Dysfunction Dysfunctions", "definition": "Pathological processes of the LIVER.\n    ", "id": "MESH:D008107"}
{"mention": "adverse drug reaction", "mention_text": "INTRODUCTION: Antibiotic-associated hepatotoxicity is rare. With widespread use of antimicrobial agents, however, hepatic injury occurs frequently, and among adverse drug reactions, idiosyncratic reactions are the most serious. CASE SUMMARY: A 25-year-old male patient, with a height of 175 cm and weight of 72 kg presented to Marmara University Hospital Emergency Department, Istanbul, Turkey, with 5 days' history of jaundice, malaise, nausea, and vomiting. He had been prescribed telithromycin 400 mg/d PO to treat an upper respiratory tract infection 7 days prior. Admission laboratory tests were as follows: alanine aminotransferase, 67 U/L (reference range, 10-37 U/L); aspartate aminotransferase, 98 U/L (10-40 U/L); alkaline phosphatase, 513 U/L (0-270 U/L); gamma-glutamyltransferase, 32 U/L (7-49 U/L); amylase, 46 U/L (0-220 U/L); total bilirubin, 20.1 mg/dL (0.2-1.0 mg/dL); direct bilirubin, 14.8 mg/dL (0-0.3 mg/dL); and albumin, 4.7 mg/dL (3.5-5.4 mg/dL). No toxin, alcohol, or other drugs were reported. The patient had suffered a previous episode of \"acute hepatitis of unknown origin,\" that occurred after telithromycin usage. Both incidents occurred within a year. DISCUSSION: Telithromycin is the first of the ketolide antibacterials to receive US Food and Drug Administration approval for clinical use. It has been associated with infrequent and usually reversible severe hepatic dysfunction. Based on a score of 8 on the Naranjo adverse drug reaction probability scale, telithromycin was the probable cause of acute hepatitis in this patient, and pathological findings suggested drug-induced toxic hepatitis. Recurrence of hepatitis attack might have been avoided if the initial incident had been communicated to the attending physician who prescribed telithromycin the second time. CONCLUSION: Here we report a case of acute hepatitis probably associated with the administration of telithromycin.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "toxic hepatitis", "mention_text": "INTRODUCTION: Antibiotic-associated hepatotoxicity is rare. With widespread use of antimicrobial agents, however, hepatic injury occurs frequently, and among adverse drug reactions, idiosyncratic reactions are the most serious. CASE SUMMARY: A 25-year-old male patient, with a height of 175 cm and weight of 72 kg presented to Marmara University Hospital Emergency Department, Istanbul, Turkey, with 5 days' history of jaundice, malaise, nausea, and vomiting. He had been prescribed telithromycin 400 mg/d PO to treat an upper respiratory tract infection 7 days prior. Admission laboratory tests were as follows: alanine aminotransferase, 67 U/L (reference range, 10-37 U/L); aspartate aminotransferase, 98 U/L (10-40 U/L); alkaline phosphatase, 513 U/L (0-270 U/L); gamma-glutamyltransferase, 32 U/L (7-49 U/L); amylase, 46 U/L (0-220 U/L); total bilirubin, 20.1 mg/dL (0.2-1.0 mg/dL); direct bilirubin, 14.8 mg/dL (0-0.3 mg/dL); and albumin, 4.7 mg/dL (3.5-5.4 mg/dL). No toxin, alcohol, or other drugs were reported. The patient had suffered a previous episode of \"acute hepatitis of unknown origin,\" that occurred after telithromycin usage. Both incidents occurred within a year. DISCUSSION: Telithromycin is the first of the ketolide antibacterials to receive US Food and Drug Administration approval for clinical use. It has been associated with infrequent and usually reversible severe hepatic dysfunction. Based on a score of 8 on the Naranjo adverse drug reaction probability scale, telithromycin was the probable cause of acute hepatitis in this patient, and pathological findings suggested drug-induced toxic hepatitis. Recurrence of hepatitis attack might have been avoided if the initial incident had been communicated to the attending physician who prescribed telithromycin the second time. CONCLUSION: Here we report a case of acute hepatitis probably associated with the administration of telithromycin.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "Spironolactone", "mention_text": "Spironolactone-induced renal insufficiency and hyperkalemia in patients with heart failure.", "entity": "Spironolactone", "aliases": "Aldactone A Alphapharm Brand of Spironolactone Alpharma Alter Aquareduct Ashbourne Azupharma Cardel Dexo Espironolactona Mundogen Flumach Frumikal Generosan Hormosan Jenapharm Jenaspiron Mayoly-Spindler Merck dura Novo Spiroton Novo-Spiroton NovoSpiroton Novopharm Pfizer Pharmafrid Practon Roche SC 9420 SC-9420 SC9420 Searle Spiractin Spiro L.U.T. Spirobeta Spirogamma Spirolactone Spirolang Spirono Isis Spirono-Isis Spironone Spirospare Veroshpiron Verospiron Verospirone Wörwag betapharm ct Arzn", "definition": "A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p827)\n    ", "id": "MESH:D013148"}
{"mention": "renal insufficiency", "mention_text": "Spironolactone-induced renal insufficiency and hyperkalemia in patients with heart failure.", "entity": "Renal Insufficiency", "aliases": "Failure Kidney Renal Failures Insufficiency Insufficiencies", "definition": "Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.\n    ", "id": "MESH:D051437"}
{"mention": "hyperkalemia", "mention_text": "Spironolactone-induced renal insufficiency and hyperkalemia in patients with heart failure.", "entity": "Hyperkalemia", "aliases": "Hyperkalemia Hyperkalemias Hyperpotassemia Hyperpotassemias", "definition": "Abnormally high potassium concentration in the blood, most often due to defective renal excretion. It is characterized clinically by electrocardiographic abnormalities (elevated T waves and depressed P waves, and eventually by atrial asystole). In severe cases, weakness and flaccid paralysis may occur. (Dorland, 27th ed)\n    ", "id": "MESH:D006947"}
{"mention": "heart failure", "mention_text": "Spironolactone-induced renal insufficiency and hyperkalemia in patients with heart failure.", "entity": "Heart Failure", "aliases": "Cardiac Failure Congestive Heart Decompensation Left Sided Left-Sided Right Right-Sided Myocardial", "definition": "A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.\n    ", "id": "MESH:D006333"}
{"mention": "spironolactone", "mention_text": "BACKGROUND: A previous randomized controlled trial evaluating the use of spironolactone in heart failure patients reported a low risk of hyperkalemia (2%) and renal insufficiency (0%). Because treatments for heart failure have changed since the benefits of spironolactone were reported, the prevalence of these complications may differ in current clinical practice. We therefore sought to determine the prevalence and clinical associations of hyperkalemia and renal insufficiency in heart failure patients treated with spironolactone. METHODS: We performed a case control study of heart failure patients treated with spironolactone in our clinical practice. Cases were patients who developed hyperkalemia (K(+) >5.0 mEq/L) or renal insufficiency (Cr >or=2.5 mg/dL), and they were compared to 2 randomly selected controls per case. Clinical characteristics, medications, and serum chemistries at baseline and follow-up time periods were compared. RESULTS: Sixty-seven of 926 patients (7.2%) required discontinuation of spironolactone due to hyperkalemia (n = 33) or renal failure (n = 34). Patients who developed hyperkalemia were older and more likely to have diabetes, had higher baseline serum potassium levels and lower baseline potassium supplement doses, and were more likely to be treated with beta-blockers than controls (n = 134). Patients who developed renal insufficiency had lower baseline body weight and higher baseline serum creatinine, required higher doses of loop diuretics, and were more likely to be treated with thiazide diuretics than controls. CONCLUSIONS: Spironolactone-induced hyperkalemia and renal insufficiency are more common in our clinical experience than reported previously. This difference is explained by patient comorbidities and more frequent use of beta-blockers.", "entity": "Spironolactone", "aliases": "Aldactone A Alphapharm Brand of Spironolactone Alpharma Alter Aquareduct Ashbourne Azupharma Cardel Dexo Espironolactona Mundogen Flumach Frumikal Generosan Hormosan Jenapharm Jenaspiron Mayoly-Spindler Merck dura Novo Spiroton Novo-Spiroton NovoSpiroton Novopharm Pfizer Pharmafrid Practon Roche SC 9420 SC-9420 SC9420 Searle Spiractin Spiro L.U.T. Spirobeta Spirogamma Spirolactone Spirolang Spirono Isis Spirono-Isis Spironone Spirospare Veroshpiron Verospiron Verospirone Wörwag betapharm ct Arzn", "definition": "A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p827)\n    ", "id": "MESH:D013148"}
{"mention": "heart failure", "mention_text": "BACKGROUND: A previous randomized controlled trial evaluating the use of spironolactone in heart failure patients reported a low risk of hyperkalemia (2%) and renal insufficiency (0%). Because treatments for heart failure have changed since the benefits of spironolactone were reported, the prevalence of these complications may differ in current clinical practice. We therefore sought to determine the prevalence and clinical associations of hyperkalemia and renal insufficiency in heart failure patients treated with spironolactone. METHODS: We performed a case control study of heart failure patients treated with spironolactone in our clinical practice. Cases were patients who developed hyperkalemia (K(+) >5.0 mEq/L) or renal insufficiency (Cr >or=2.5 mg/dL), and they were compared to 2 randomly selected controls per case. Clinical characteristics, medications, and serum chemistries at baseline and follow-up time periods were compared. RESULTS: Sixty-seven of 926 patients (7.2%) required discontinuation of spironolactone due to hyperkalemia (n = 33) or renal failure (n = 34). Patients who developed hyperkalemia were older and more likely to have diabetes, had higher baseline serum potassium levels and lower baseline potassium supplement doses, and were more likely to be treated with beta-blockers than controls (n = 134). Patients who developed renal insufficiency had lower baseline body weight and higher baseline serum creatinine, required higher doses of loop diuretics, and were more likely to be treated with thiazide diuretics than controls. CONCLUSIONS: Spironolactone-induced hyperkalemia and renal insufficiency are more common in our clinical experience than reported previously. This difference is explained by patient comorbidities and more frequent use of beta-blockers.", "entity": "Heart Failure", "aliases": "Cardiac Failure Congestive Heart Decompensation Left Sided Left-Sided Right Right-Sided Myocardial", "definition": "A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.\n    ", "id": "MESH:D006333"}
{"mention": "hyperkalemia", "mention_text": "BACKGROUND: A previous randomized controlled trial evaluating the use of spironolactone in heart failure patients reported a low risk of hyperkalemia (2%) and renal insufficiency (0%). Because treatments for heart failure have changed since the benefits of spironolactone were reported, the prevalence of these complications may differ in current clinical practice. We therefore sought to determine the prevalence and clinical associations of hyperkalemia and renal insufficiency in heart failure patients treated with spironolactone. METHODS: We performed a case control study of heart failure patients treated with spironolactone in our clinical practice. Cases were patients who developed hyperkalemia (K(+) >5.0 mEq/L) or renal insufficiency (Cr >or=2.5 mg/dL), and they were compared to 2 randomly selected controls per case. Clinical characteristics, medications, and serum chemistries at baseline and follow-up time periods were compared. RESULTS: Sixty-seven of 926 patients (7.2%) required discontinuation of spironolactone due to hyperkalemia (n = 33) or renal failure (n = 34). Patients who developed hyperkalemia were older and more likely to have diabetes, had higher baseline serum potassium levels and lower baseline potassium supplement doses, and were more likely to be treated with beta-blockers than controls (n = 134). Patients who developed renal insufficiency had lower baseline body weight and higher baseline serum creatinine, required higher doses of loop diuretics, and were more likely to be treated with thiazide diuretics than controls. CONCLUSIONS: Spironolactone-induced hyperkalemia and renal insufficiency are more common in our clinical experience than reported previously. This difference is explained by patient comorbidities and more frequent use of beta-blockers.", "entity": "Hyperkalemia", "aliases": "Hyperkalemia Hyperkalemias Hyperpotassemia Hyperpotassemias", "definition": "Abnormally high potassium concentration in the blood, most often due to defective renal excretion. It is characterized clinically by electrocardiographic abnormalities (elevated T waves and depressed P waves, and eventually by atrial asystole). In severe cases, weakness and flaccid paralysis may occur. (Dorland, 27th ed)\n    ", "id": "MESH:D006947"}
{"mention": "renal insufficiency", "mention_text": "BACKGROUND: A previous randomized controlled trial evaluating the use of spironolactone in heart failure patients reported a low risk of hyperkalemia (2%) and renal insufficiency (0%). Because treatments for heart failure have changed since the benefits of spironolactone were reported, the prevalence of these complications may differ in current clinical practice. We therefore sought to determine the prevalence and clinical associations of hyperkalemia and renal insufficiency in heart failure patients treated with spironolactone. METHODS: We performed a case control study of heart failure patients treated with spironolactone in our clinical practice. Cases were patients who developed hyperkalemia (K(+) >5.0 mEq/L) or renal insufficiency (Cr >or=2.5 mg/dL), and they were compared to 2 randomly selected controls per case. Clinical characteristics, medications, and serum chemistries at baseline and follow-up time periods were compared. RESULTS: Sixty-seven of 926 patients (7.2%) required discontinuation of spironolactone due to hyperkalemia (n = 33) or renal failure (n = 34). Patients who developed hyperkalemia were older and more likely to have diabetes, had higher baseline serum potassium levels and lower baseline potassium supplement doses, and were more likely to be treated with beta-blockers than controls (n = 134). Patients who developed renal insufficiency had lower baseline body weight and higher baseline serum creatinine, required higher doses of loop diuretics, and were more likely to be treated with thiazide diuretics than controls. CONCLUSIONS: Spironolactone-induced hyperkalemia and renal insufficiency are more common in our clinical experience than reported previously. This difference is explained by patient comorbidities and more frequent use of beta-blockers.", "entity": "Renal Insufficiency", "aliases": "Failure Kidney Renal Failures Insufficiency Insufficiencies", "definition": "Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.\n    ", "id": "MESH:D051437"}
{"mention": "K", "mention_text": "BACKGROUND: A previous randomized controlled trial evaluating the use of spironolactone in heart failure patients reported a low risk of hyperkalemia (2%) and renal insufficiency (0%). Because treatments for heart failure have changed since the benefits of spironolactone were reported, the prevalence of these complications may differ in current clinical practice. We therefore sought to determine the prevalence and clinical associations of hyperkalemia and renal insufficiency in heart failure patients treated with spironolactone. METHODS: We performed a case control study of heart failure patients treated with spironolactone in our clinical practice. Cases were patients who developed hyperkalemia (K(+) >5.0 mEq/L) or renal insufficiency (Cr >or=2.5 mg/dL), and they were compared to 2 randomly selected controls per case. Clinical characteristics, medications, and serum chemistries at baseline and follow-up time periods were compared. RESULTS: Sixty-seven of 926 patients (7.2%) required discontinuation of spironolactone due to hyperkalemia (n = 33) or renal failure (n = 34). Patients who developed hyperkalemia were older and more likely to have diabetes, had higher baseline serum potassium levels and lower baseline potassium supplement doses, and were more likely to be treated with beta-blockers than controls (n = 134). Patients who developed renal insufficiency had lower baseline body weight and higher baseline serum creatinine, required higher doses of loop diuretics, and were more likely to be treated with thiazide diuretics than controls. CONCLUSIONS: Spironolactone-induced hyperkalemia and renal insufficiency are more common in our clinical experience than reported previously. This difference is explained by patient comorbidities and more frequent use of beta-blockers.", "entity": "Potassium", "aliases": "Potassium", "definition": "An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.\n    ", "id": "MESH:D011188"}
{"mention": "Cr", "mention_text": "BACKGROUND: A previous randomized controlled trial evaluating the use of spironolactone in heart failure patients reported a low risk of hyperkalemia (2%) and renal insufficiency (0%). Because treatments for heart failure have changed since the benefits of spironolactone were reported, the prevalence of these complications may differ in current clinical practice. We therefore sought to determine the prevalence and clinical associations of hyperkalemia and renal insufficiency in heart failure patients treated with spironolactone. METHODS: We performed a case control study of heart failure patients treated with spironolactone in our clinical practice. Cases were patients who developed hyperkalemia (K(+) >5.0 mEq/L) or renal insufficiency (Cr >or=2.5 mg/dL), and they were compared to 2 randomly selected controls per case. Clinical characteristics, medications, and serum chemistries at baseline and follow-up time periods were compared. RESULTS: Sixty-seven of 926 patients (7.2%) required discontinuation of spironolactone due to hyperkalemia (n = 33) or renal failure (n = 34). Patients who developed hyperkalemia were older and more likely to have diabetes, had higher baseline serum potassium levels and lower baseline potassium supplement doses, and were more likely to be treated with beta-blockers than controls (n = 134). Patients who developed renal insufficiency had lower baseline body weight and higher baseline serum creatinine, required higher doses of loop diuretics, and were more likely to be treated with thiazide diuretics than controls. CONCLUSIONS: Spironolactone-induced hyperkalemia and renal insufficiency are more common in our clinical experience than reported previously. This difference is explained by patient comorbidities and more frequent use of beta-blockers.", "entity": "Chromium", "aliases": "Chromium", "definition": "A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens.\n    ", "id": "MESH:D002857"}
{"mention": "renal failure", "mention_text": "BACKGROUND: A previous randomized controlled trial evaluating the use of spironolactone in heart failure patients reported a low risk of hyperkalemia (2%) and renal insufficiency (0%). Because treatments for heart failure have changed since the benefits of spironolactone were reported, the prevalence of these complications may differ in current clinical practice. We therefore sought to determine the prevalence and clinical associations of hyperkalemia and renal insufficiency in heart failure patients treated with spironolactone. METHODS: We performed a case control study of heart failure patients treated with spironolactone in our clinical practice. Cases were patients who developed hyperkalemia (K(+) >5.0 mEq/L) or renal insufficiency (Cr >or=2.5 mg/dL), and they were compared to 2 randomly selected controls per case. Clinical characteristics, medications, and serum chemistries at baseline and follow-up time periods were compared. RESULTS: Sixty-seven of 926 patients (7.2%) required discontinuation of spironolactone due to hyperkalemia (n = 33) or renal failure (n = 34). Patients who developed hyperkalemia were older and more likely to have diabetes, had higher baseline serum potassium levels and lower baseline potassium supplement doses, and were more likely to be treated with beta-blockers than controls (n = 134). Patients who developed renal insufficiency had lower baseline body weight and higher baseline serum creatinine, required higher doses of loop diuretics, and were more likely to be treated with thiazide diuretics than controls. CONCLUSIONS: Spironolactone-induced hyperkalemia and renal insufficiency are more common in our clinical experience than reported previously. This difference is explained by patient comorbidities and more frequent use of beta-blockers.", "entity": "Renal Insufficiency", "aliases": "Failure Kidney Renal Failures Insufficiency Insufficiencies", "definition": "Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.\n    ", "id": "MESH:D051437"}
{"mention": "diabetes", "mention_text": "BACKGROUND: A previous randomized controlled trial evaluating the use of spironolactone in heart failure patients reported a low risk of hyperkalemia (2%) and renal insufficiency (0%). Because treatments for heart failure have changed since the benefits of spironolactone were reported, the prevalence of these complications may differ in current clinical practice. We therefore sought to determine the prevalence and clinical associations of hyperkalemia and renal insufficiency in heart failure patients treated with spironolactone. METHODS: We performed a case control study of heart failure patients treated with spironolactone in our clinical practice. Cases were patients who developed hyperkalemia (K(+) >5.0 mEq/L) or renal insufficiency (Cr >or=2.5 mg/dL), and they were compared to 2 randomly selected controls per case. Clinical characteristics, medications, and serum chemistries at baseline and follow-up time periods were compared. RESULTS: Sixty-seven of 926 patients (7.2%) required discontinuation of spironolactone due to hyperkalemia (n = 33) or renal failure (n = 34). Patients who developed hyperkalemia were older and more likely to have diabetes, had higher baseline serum potassium levels and lower baseline potassium supplement doses, and were more likely to be treated with beta-blockers than controls (n = 134). Patients who developed renal insufficiency had lower baseline body weight and higher baseline serum creatinine, required higher doses of loop diuretics, and were more likely to be treated with thiazide diuretics than controls. CONCLUSIONS: Spironolactone-induced hyperkalemia and renal insufficiency are more common in our clinical experience than reported previously. This difference is explained by patient comorbidities and more frequent use of beta-blockers.", "entity": "Diabetes Mellitus", "aliases": "Diabetes Mellitus", "definition": "A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.\n    ", "id": "MESH:D003920"}
{"mention": "potassium", "mention_text": "BACKGROUND: A previous randomized controlled trial evaluating the use of spironolactone in heart failure patients reported a low risk of hyperkalemia (2%) and renal insufficiency (0%). Because treatments for heart failure have changed since the benefits of spironolactone were reported, the prevalence of these complications may differ in current clinical practice. We therefore sought to determine the prevalence and clinical associations of hyperkalemia and renal insufficiency in heart failure patients treated with spironolactone. METHODS: We performed a case control study of heart failure patients treated with spironolactone in our clinical practice. Cases were patients who developed hyperkalemia (K(+) >5.0 mEq/L) or renal insufficiency (Cr >or=2.5 mg/dL), and they were compared to 2 randomly selected controls per case. Clinical characteristics, medications, and serum chemistries at baseline and follow-up time periods were compared. RESULTS: Sixty-seven of 926 patients (7.2%) required discontinuation of spironolactone due to hyperkalemia (n = 33) or renal failure (n = 34). Patients who developed hyperkalemia were older and more likely to have diabetes, had higher baseline serum potassium levels and lower baseline potassium supplement doses, and were more likely to be treated with beta-blockers than controls (n = 134). Patients who developed renal insufficiency had lower baseline body weight and higher baseline serum creatinine, required higher doses of loop diuretics, and were more likely to be treated with thiazide diuretics than controls. CONCLUSIONS: Spironolactone-induced hyperkalemia and renal insufficiency are more common in our clinical experience than reported previously. This difference is explained by patient comorbidities and more frequent use of beta-blockers.", "entity": "Potassium", "aliases": "Potassium", "definition": "An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.\n    ", "id": "MESH:D011188"}
{"mention": "creatinine", "mention_text": "BACKGROUND: A previous randomized controlled trial evaluating the use of spironolactone in heart failure patients reported a low risk of hyperkalemia (2%) and renal insufficiency (0%). Because treatments for heart failure have changed since the benefits of spironolactone were reported, the prevalence of these complications may differ in current clinical practice. We therefore sought to determine the prevalence and clinical associations of hyperkalemia and renal insufficiency in heart failure patients treated with spironolactone. METHODS: We performed a case control study of heart failure patients treated with spironolactone in our clinical practice. Cases were patients who developed hyperkalemia (K(+) >5.0 mEq/L) or renal insufficiency (Cr >or=2.5 mg/dL), and they were compared to 2 randomly selected controls per case. Clinical characteristics, medications, and serum chemistries at baseline and follow-up time periods were compared. RESULTS: Sixty-seven of 926 patients (7.2%) required discontinuation of spironolactone due to hyperkalemia (n = 33) or renal failure (n = 34). Patients who developed hyperkalemia were older and more likely to have diabetes, had higher baseline serum potassium levels and lower baseline potassium supplement doses, and were more likely to be treated with beta-blockers than controls (n = 134). Patients who developed renal insufficiency had lower baseline body weight and higher baseline serum creatinine, required higher doses of loop diuretics, and were more likely to be treated with thiazide diuretics than controls. CONCLUSIONS: Spironolactone-induced hyperkalemia and renal insufficiency are more common in our clinical experience than reported previously. This difference is explained by patient comorbidities and more frequent use of beta-blockers.", "entity": "Creatinine", "aliases": "Creatinine Sulfate Salt Krebiozen", "definition": "", "id": "MESH:D003404"}
{"mention": "thiazide", "mention_text": "BACKGROUND: A previous randomized controlled trial evaluating the use of spironolactone in heart failure patients reported a low risk of hyperkalemia (2%) and renal insufficiency (0%). Because treatments for heart failure have changed since the benefits of spironolactone were reported, the prevalence of these complications may differ in current clinical practice. We therefore sought to determine the prevalence and clinical associations of hyperkalemia and renal insufficiency in heart failure patients treated with spironolactone. METHODS: We performed a case control study of heart failure patients treated with spironolactone in our clinical practice. Cases were patients who developed hyperkalemia (K(+) >5.0 mEq/L) or renal insufficiency (Cr >or=2.5 mg/dL), and they were compared to 2 randomly selected controls per case. Clinical characteristics, medications, and serum chemistries at baseline and follow-up time periods were compared. RESULTS: Sixty-seven of 926 patients (7.2%) required discontinuation of spironolactone due to hyperkalemia (n = 33) or renal failure (n = 34). Patients who developed hyperkalemia were older and more likely to have diabetes, had higher baseline serum potassium levels and lower baseline potassium supplement doses, and were more likely to be treated with beta-blockers than controls (n = 134). Patients who developed renal insufficiency had lower baseline body weight and higher baseline serum creatinine, required higher doses of loop diuretics, and were more likely to be treated with thiazide diuretics than controls. CONCLUSIONS: Spironolactone-induced hyperkalemia and renal insufficiency are more common in our clinical experience than reported previously. This difference is explained by patient comorbidities and more frequent use of beta-blockers.", "entity": "Thiazides", "aliases": "Thiazides", "definition": "Heterocyclic compounds with SULFUR and NITROGEN in the ring. This term commonly refers to the BENZOTHIADIAZINES that inhibit SODIUM-POTASSIUM-CHLORIDE SYMPORTERS and are used as DIURETICS.\n    ", "id": "MESH:D049971"}
{"mention": "Spironolactone", "mention_text": "BACKGROUND: A previous randomized controlled trial evaluating the use of spironolactone in heart failure patients reported a low risk of hyperkalemia (2%) and renal insufficiency (0%). Because treatments for heart failure have changed since the benefits of spironolactone were reported, the prevalence of these complications may differ in current clinical practice. We therefore sought to determine the prevalence and clinical associations of hyperkalemia and renal insufficiency in heart failure patients treated with spironolactone. METHODS: We performed a case control study of heart failure patients treated with spironolactone in our clinical practice. Cases were patients who developed hyperkalemia (K(+) >5.0 mEq/L) or renal insufficiency (Cr >or=2.5 mg/dL), and they were compared to 2 randomly selected controls per case. Clinical characteristics, medications, and serum chemistries at baseline and follow-up time periods were compared. RESULTS: Sixty-seven of 926 patients (7.2%) required discontinuation of spironolactone due to hyperkalemia (n = 33) or renal failure (n = 34). Patients who developed hyperkalemia were older and more likely to have diabetes, had higher baseline serum potassium levels and lower baseline potassium supplement doses, and were more likely to be treated with beta-blockers than controls (n = 134). Patients who developed renal insufficiency had lower baseline body weight and higher baseline serum creatinine, required higher doses of loop diuretics, and were more likely to be treated with thiazide diuretics than controls. CONCLUSIONS: Spironolactone-induced hyperkalemia and renal insufficiency are more common in our clinical experience than reported previously. This difference is explained by patient comorbidities and more frequent use of beta-blockers.", "entity": "Spironolactone", "aliases": "Aldactone A Alphapharm Brand of Spironolactone Alpharma Alter Aquareduct Ashbourne Azupharma Cardel Dexo Espironolactona Mundogen Flumach Frumikal Generosan Hormosan Jenapharm Jenaspiron Mayoly-Spindler Merck dura Novo Spiroton Novo-Spiroton NovoSpiroton Novopharm Pfizer Pharmafrid Practon Roche SC 9420 SC-9420 SC9420 Searle Spiractin Spiro L.U.T. Spirobeta Spirogamma Spirolactone Spirolang Spirono Isis Spirono-Isis Spironone Spirospare Veroshpiron Verospiron Verospirone Wörwag betapharm ct Arzn", "definition": "A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p827)\n    ", "id": "MESH:D013148"}
{"mention": "End-stage renal disease", "mention_text": "End-stage renal disease (ESRD) after orthotopic liver transplantation (OLTX) using calcineurin-based immunotherapy: risk of development and treatment.", "entity": "Kidney Failure, Chronic", "aliases": "Chronic Kidney Failure Renal Disease End-Stage ESRD End Stage", "definition": "The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.\n    ", "id": "MESH:D007676"}
{"mention": "ESRD", "mention_text": "End-stage renal disease (ESRD) after orthotopic liver transplantation (OLTX) using calcineurin-based immunotherapy: risk of development and treatment.", "entity": "Kidney Failure, Chronic", "aliases": "Chronic Kidney Failure Renal Disease End-Stage ESRD End Stage", "definition": "The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.\n    ", "id": "MESH:D007676"}
{"mention": "cyclosporine", "mention_text": "BACKGROUND: The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their use in orthotopic liver transplantation (OLTX) has dramatically improved success rates. Recently, however, we have had an increase of patients who are presenting after OLTX with end-stage renal disease (ESRD). This retrospective study examines the incidence and treatment of ESRD and chronic renal failure (CRF) in OLTX patients. METHODS: Patients receiving an OLTX only from June 1985 through December of 1994 who survived 6 months postoperatively were studied (n=834). Our prospectively collected database was the source of information. Patients were divided into three groups: Controls, no CRF or ESRD, n=748; CRF, sustained serum creatinine >2.5 mg/dl, n=41; and ESRD, n=45. Groups were compared for preoperative laboratory variables, diagnosis, postoperative variables, survival, type of ESRD therapy, and survival from onset of ESRD. RESULTS: At 13 years after OLTX, the incidence of severe renal dysfunction was 18.1% (CRF 8.6% and ESRD 9.5%). Compared with control patients, CRF and ESRD patients had higher preoperative serum creatinine levels, a greater percentage of patients with hepatorenal syndrome, higher percentage requirement for dialysis in the first 3 months postoperatively, and a higher 1-year serum creatinine. Multivariate stepwise logistic regression analysis using preoperative and postoperative variables identified that an increase of serum creatinine compared with average at 1 year, 3 months, and 4 weeks postoperatively were independent risk factors for the development of CRF or ESRD with odds ratios of 2.6, 2.2, and 1.6, respectively. Overall survival from the time of OLTX was not significantly different among groups, but by year 13, the survival of the patients who had ESRD was only 28.2% compared with 54.6% in the control group. Patients developing ESRD had a 6-year survival after onset of ESRD of 27% for the patients receiving hemodialysis versus 71.4% for the patients developing ESRD who subsequently received kidney transplants. CONCLUSIONS: Patients who are more than 10 years post-OLTX have CRF and ESRD at a high rate. The development of ESRD decreases survival, particularly in those patients treated with dialysis only. Patients who develop ESRD have a higher preoperative and 1-year serum creatinine and are more likely to have hepatorenal syndrome. However, an increase of serum creatinine at various times postoperatively is more predictive of the development of CRF or ESRD. New strategies for long-term immunosuppression may be needed to decrease this complication.", "entity": "Cyclosporine", "aliases": "Ciclosporin CsA Neoral CsA-Neoral CsANeoral CyA NOF CyA-NOF Cyclosporin A Cyclosporine OL 27 400 27-400 27400 Sandimmun Sandimmune", "definition": "A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).\n    ", "id": "MESH:D016572"}
{"mention": "tacrolimus", "mention_text": "BACKGROUND: The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their use in orthotopic liver transplantation (OLTX) has dramatically improved success rates. Recently, however, we have had an increase of patients who are presenting after OLTX with end-stage renal disease (ESRD). This retrospective study examines the incidence and treatment of ESRD and chronic renal failure (CRF) in OLTX patients. METHODS: Patients receiving an OLTX only from June 1985 through December of 1994 who survived 6 months postoperatively were studied (n=834). Our prospectively collected database was the source of information. Patients were divided into three groups: Controls, no CRF or ESRD, n=748; CRF, sustained serum creatinine >2.5 mg/dl, n=41; and ESRD, n=45. Groups were compared for preoperative laboratory variables, diagnosis, postoperative variables, survival, type of ESRD therapy, and survival from onset of ESRD. RESULTS: At 13 years after OLTX, the incidence of severe renal dysfunction was 18.1% (CRF 8.6% and ESRD 9.5%). Compared with control patients, CRF and ESRD patients had higher preoperative serum creatinine levels, a greater percentage of patients with hepatorenal syndrome, higher percentage requirement for dialysis in the first 3 months postoperatively, and a higher 1-year serum creatinine. Multivariate stepwise logistic regression analysis using preoperative and postoperative variables identified that an increase of serum creatinine compared with average at 1 year, 3 months, and 4 weeks postoperatively were independent risk factors for the development of CRF or ESRD with odds ratios of 2.6, 2.2, and 1.6, respectively. Overall survival from the time of OLTX was not significantly different among groups, but by year 13, the survival of the patients who had ESRD was only 28.2% compared with 54.6% in the control group. Patients developing ESRD had a 6-year survival after onset of ESRD of 27% for the patients receiving hemodialysis versus 71.4% for the patients developing ESRD who subsequently received kidney transplants. CONCLUSIONS: Patients who are more than 10 years post-OLTX have CRF and ESRD at a high rate. The development of ESRD decreases survival, particularly in those patients treated with dialysis only. Patients who develop ESRD have a higher preoperative and 1-year serum creatinine and are more likely to have hepatorenal syndrome. However, an increase of serum creatinine at various times postoperatively is more predictive of the development of CRF or ESRD. New strategies for long-term immunosuppression may be needed to decrease this complication.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "nephrotoxic", "mention_text": "BACKGROUND: The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their use in orthotopic liver transplantation (OLTX) has dramatically improved success rates. Recently, however, we have had an increase of patients who are presenting after OLTX with end-stage renal disease (ESRD). This retrospective study examines the incidence and treatment of ESRD and chronic renal failure (CRF) in OLTX patients. METHODS: Patients receiving an OLTX only from June 1985 through December of 1994 who survived 6 months postoperatively were studied (n=834). Our prospectively collected database was the source of information. Patients were divided into three groups: Controls, no CRF or ESRD, n=748; CRF, sustained serum creatinine >2.5 mg/dl, n=41; and ESRD, n=45. Groups were compared for preoperative laboratory variables, diagnosis, postoperative variables, survival, type of ESRD therapy, and survival from onset of ESRD. RESULTS: At 13 years after OLTX, the incidence of severe renal dysfunction was 18.1% (CRF 8.6% and ESRD 9.5%). Compared with control patients, CRF and ESRD patients had higher preoperative serum creatinine levels, a greater percentage of patients with hepatorenal syndrome, higher percentage requirement for dialysis in the first 3 months postoperatively, and a higher 1-year serum creatinine. Multivariate stepwise logistic regression analysis using preoperative and postoperative variables identified that an increase of serum creatinine compared with average at 1 year, 3 months, and 4 weeks postoperatively were independent risk factors for the development of CRF or ESRD with odds ratios of 2.6, 2.2, and 1.6, respectively. Overall survival from the time of OLTX was not significantly different among groups, but by year 13, the survival of the patients who had ESRD was only 28.2% compared with 54.6% in the control group. Patients developing ESRD had a 6-year survival after onset of ESRD of 27% for the patients receiving hemodialysis versus 71.4% for the patients developing ESRD who subsequently received kidney transplants. CONCLUSIONS: Patients who are more than 10 years post-OLTX have CRF and ESRD at a high rate. The development of ESRD decreases survival, particularly in those patients treated with dialysis only. Patients who develop ESRD have a higher preoperative and 1-year serum creatinine and are more likely to have hepatorenal syndrome. However, an increase of serum creatinine at various times postoperatively is more predictive of the development of CRF or ESRD. New strategies for long-term immunosuppression may be needed to decrease this complication.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "end-stage renal disease", "mention_text": "BACKGROUND: The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their use in orthotopic liver transplantation (OLTX) has dramatically improved success rates. Recently, however, we have had an increase of patients who are presenting after OLTX with end-stage renal disease (ESRD). This retrospective study examines the incidence and treatment of ESRD and chronic renal failure (CRF) in OLTX patients. METHODS: Patients receiving an OLTX only from June 1985 through December of 1994 who survived 6 months postoperatively were studied (n=834). Our prospectively collected database was the source of information. Patients were divided into three groups: Controls, no CRF or ESRD, n=748; CRF, sustained serum creatinine >2.5 mg/dl, n=41; and ESRD, n=45. Groups were compared for preoperative laboratory variables, diagnosis, postoperative variables, survival, type of ESRD therapy, and survival from onset of ESRD. RESULTS: At 13 years after OLTX, the incidence of severe renal dysfunction was 18.1% (CRF 8.6% and ESRD 9.5%). Compared with control patients, CRF and ESRD patients had higher preoperative serum creatinine levels, a greater percentage of patients with hepatorenal syndrome, higher percentage requirement for dialysis in the first 3 months postoperatively, and a higher 1-year serum creatinine. Multivariate stepwise logistic regression analysis using preoperative and postoperative variables identified that an increase of serum creatinine compared with average at 1 year, 3 months, and 4 weeks postoperatively were independent risk factors for the development of CRF or ESRD with odds ratios of 2.6, 2.2, and 1.6, respectively. Overall survival from the time of OLTX was not significantly different among groups, but by year 13, the survival of the patients who had ESRD was only 28.2% compared with 54.6% in the control group. Patients developing ESRD had a 6-year survival after onset of ESRD of 27% for the patients receiving hemodialysis versus 71.4% for the patients developing ESRD who subsequently received kidney transplants. CONCLUSIONS: Patients who are more than 10 years post-OLTX have CRF and ESRD at a high rate. The development of ESRD decreases survival, particularly in those patients treated with dialysis only. Patients who develop ESRD have a higher preoperative and 1-year serum creatinine and are more likely to have hepatorenal syndrome. However, an increase of serum creatinine at various times postoperatively is more predictive of the development of CRF or ESRD. New strategies for long-term immunosuppression may be needed to decrease this complication.", "entity": "Kidney Failure, Chronic", "aliases": "Chronic Kidney Failure Renal Disease End-Stage ESRD End Stage", "definition": "The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.\n    ", "id": "MESH:D007676"}
{"mention": "ESRD", "mention_text": "BACKGROUND: The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their use in orthotopic liver transplantation (OLTX) has dramatically improved success rates. Recently, however, we have had an increase of patients who are presenting after OLTX with end-stage renal disease (ESRD). This retrospective study examines the incidence and treatment of ESRD and chronic renal failure (CRF) in OLTX patients. METHODS: Patients receiving an OLTX only from June 1985 through December of 1994 who survived 6 months postoperatively were studied (n=834). Our prospectively collected database was the source of information. Patients were divided into three groups: Controls, no CRF or ESRD, n=748; CRF, sustained serum creatinine >2.5 mg/dl, n=41; and ESRD, n=45. Groups were compared for preoperative laboratory variables, diagnosis, postoperative variables, survival, type of ESRD therapy, and survival from onset of ESRD. RESULTS: At 13 years after OLTX, the incidence of severe renal dysfunction was 18.1% (CRF 8.6% and ESRD 9.5%). Compared with control patients, CRF and ESRD patients had higher preoperative serum creatinine levels, a greater percentage of patients with hepatorenal syndrome, higher percentage requirement for dialysis in the first 3 months postoperatively, and a higher 1-year serum creatinine. Multivariate stepwise logistic regression analysis using preoperative and postoperative variables identified that an increase of serum creatinine compared with average at 1 year, 3 months, and 4 weeks postoperatively were independent risk factors for the development of CRF or ESRD with odds ratios of 2.6, 2.2, and 1.6, respectively. Overall survival from the time of OLTX was not significantly different among groups, but by year 13, the survival of the patients who had ESRD was only 28.2% compared with 54.6% in the control group. Patients developing ESRD had a 6-year survival after onset of ESRD of 27% for the patients receiving hemodialysis versus 71.4% for the patients developing ESRD who subsequently received kidney transplants. CONCLUSIONS: Patients who are more than 10 years post-OLTX have CRF and ESRD at a high rate. The development of ESRD decreases survival, particularly in those patients treated with dialysis only. Patients who develop ESRD have a higher preoperative and 1-year serum creatinine and are more likely to have hepatorenal syndrome. However, an increase of serum creatinine at various times postoperatively is more predictive of the development of CRF or ESRD. New strategies for long-term immunosuppression may be needed to decrease this complication.", "entity": "Kidney Failure, Chronic", "aliases": "Chronic Kidney Failure Renal Disease End-Stage ESRD End Stage", "definition": "The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.\n    ", "id": "MESH:D007676"}
{"mention": "chronic renal failure", "mention_text": "BACKGROUND: The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their use in orthotopic liver transplantation (OLTX) has dramatically improved success rates. Recently, however, we have had an increase of patients who are presenting after OLTX with end-stage renal disease (ESRD). This retrospective study examines the incidence and treatment of ESRD and chronic renal failure (CRF) in OLTX patients. METHODS: Patients receiving an OLTX only from June 1985 through December of 1994 who survived 6 months postoperatively were studied (n=834). Our prospectively collected database was the source of information. Patients were divided into three groups: Controls, no CRF or ESRD, n=748; CRF, sustained serum creatinine >2.5 mg/dl, n=41; and ESRD, n=45. Groups were compared for preoperative laboratory variables, diagnosis, postoperative variables, survival, type of ESRD therapy, and survival from onset of ESRD. RESULTS: At 13 years after OLTX, the incidence of severe renal dysfunction was 18.1% (CRF 8.6% and ESRD 9.5%). Compared with control patients, CRF and ESRD patients had higher preoperative serum creatinine levels, a greater percentage of patients with hepatorenal syndrome, higher percentage requirement for dialysis in the first 3 months postoperatively, and a higher 1-year serum creatinine. Multivariate stepwise logistic regression analysis using preoperative and postoperative variables identified that an increase of serum creatinine compared with average at 1 year, 3 months, and 4 weeks postoperatively were independent risk factors for the development of CRF or ESRD with odds ratios of 2.6, 2.2, and 1.6, respectively. Overall survival from the time of OLTX was not significantly different among groups, but by year 13, the survival of the patients who had ESRD was only 28.2% compared with 54.6% in the control group. Patients developing ESRD had a 6-year survival after onset of ESRD of 27% for the patients receiving hemodialysis versus 71.4% for the patients developing ESRD who subsequently received kidney transplants. CONCLUSIONS: Patients who are more than 10 years post-OLTX have CRF and ESRD at a high rate. The development of ESRD decreases survival, particularly in those patients treated with dialysis only. Patients who develop ESRD have a higher preoperative and 1-year serum creatinine and are more likely to have hepatorenal syndrome. However, an increase of serum creatinine at various times postoperatively is more predictive of the development of CRF or ESRD. New strategies for long-term immunosuppression may be needed to decrease this complication.", "entity": "Kidney Failure, Chronic", "aliases": "Chronic Kidney Failure Renal Disease End-Stage ESRD End Stage", "definition": "The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.\n    ", "id": "MESH:D007676"}
{"mention": "CRF", "mention_text": "BACKGROUND: The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their use in orthotopic liver transplantation (OLTX) has dramatically improved success rates. Recently, however, we have had an increase of patients who are presenting after OLTX with end-stage renal disease (ESRD). This retrospective study examines the incidence and treatment of ESRD and chronic renal failure (CRF) in OLTX patients. METHODS: Patients receiving an OLTX only from June 1985 through December of 1994 who survived 6 months postoperatively were studied (n=834). Our prospectively collected database was the source of information. Patients were divided into three groups: Controls, no CRF or ESRD, n=748; CRF, sustained serum creatinine >2.5 mg/dl, n=41; and ESRD, n=45. Groups were compared for preoperative laboratory variables, diagnosis, postoperative variables, survival, type of ESRD therapy, and survival from onset of ESRD. RESULTS: At 13 years after OLTX, the incidence of severe renal dysfunction was 18.1% (CRF 8.6% and ESRD 9.5%). Compared with control patients, CRF and ESRD patients had higher preoperative serum creatinine levels, a greater percentage of patients with hepatorenal syndrome, higher percentage requirement for dialysis in the first 3 months postoperatively, and a higher 1-year serum creatinine. Multivariate stepwise logistic regression analysis using preoperative and postoperative variables identified that an increase of serum creatinine compared with average at 1 year, 3 months, and 4 weeks postoperatively were independent risk factors for the development of CRF or ESRD with odds ratios of 2.6, 2.2, and 1.6, respectively. Overall survival from the time of OLTX was not significantly different among groups, but by year 13, the survival of the patients who had ESRD was only 28.2% compared with 54.6% in the control group. Patients developing ESRD had a 6-year survival after onset of ESRD of 27% for the patients receiving hemodialysis versus 71.4% for the patients developing ESRD who subsequently received kidney transplants. CONCLUSIONS: Patients who are more than 10 years post-OLTX have CRF and ESRD at a high rate. The development of ESRD decreases survival, particularly in those patients treated with dialysis only. Patients who develop ESRD have a higher preoperative and 1-year serum creatinine and are more likely to have hepatorenal syndrome. However, an increase of serum creatinine at various times postoperatively is more predictive of the development of CRF or ESRD. New strategies for long-term immunosuppression may be needed to decrease this complication.", "entity": "Kidney Failure, Chronic", "aliases": "Chronic Kidney Failure Renal Disease End-Stage ESRD End Stage", "definition": "The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.\n    ", "id": "MESH:D007676"}
{"mention": "creatinine", "mention_text": "BACKGROUND: The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their use in orthotopic liver transplantation (OLTX) has dramatically improved success rates. Recently, however, we have had an increase of patients who are presenting after OLTX with end-stage renal disease (ESRD). This retrospective study examines the incidence and treatment of ESRD and chronic renal failure (CRF) in OLTX patients. METHODS: Patients receiving an OLTX only from June 1985 through December of 1994 who survived 6 months postoperatively were studied (n=834). Our prospectively collected database was the source of information. Patients were divided into three groups: Controls, no CRF or ESRD, n=748; CRF, sustained serum creatinine >2.5 mg/dl, n=41; and ESRD, n=45. Groups were compared for preoperative laboratory variables, diagnosis, postoperative variables, survival, type of ESRD therapy, and survival from onset of ESRD. RESULTS: At 13 years after OLTX, the incidence of severe renal dysfunction was 18.1% (CRF 8.6% and ESRD 9.5%). Compared with control patients, CRF and ESRD patients had higher preoperative serum creatinine levels, a greater percentage of patients with hepatorenal syndrome, higher percentage requirement for dialysis in the first 3 months postoperatively, and a higher 1-year serum creatinine. Multivariate stepwise logistic regression analysis using preoperative and postoperative variables identified that an increase of serum creatinine compared with average at 1 year, 3 months, and 4 weeks postoperatively were independent risk factors for the development of CRF or ESRD with odds ratios of 2.6, 2.2, and 1.6, respectively. Overall survival from the time of OLTX was not significantly different among groups, but by year 13, the survival of the patients who had ESRD was only 28.2% compared with 54.6% in the control group. Patients developing ESRD had a 6-year survival after onset of ESRD of 27% for the patients receiving hemodialysis versus 71.4% for the patients developing ESRD who subsequently received kidney transplants. CONCLUSIONS: Patients who are more than 10 years post-OLTX have CRF and ESRD at a high rate. The development of ESRD decreases survival, particularly in those patients treated with dialysis only. Patients who develop ESRD have a higher preoperative and 1-year serum creatinine and are more likely to have hepatorenal syndrome. However, an increase of serum creatinine at various times postoperatively is more predictive of the development of CRF or ESRD. New strategies for long-term immunosuppression may be needed to decrease this complication.", "entity": "Creatinine", "aliases": "Creatinine Sulfate Salt Krebiozen", "definition": "", "id": "MESH:D003404"}
{"mention": "renal dysfunction", "mention_text": "BACKGROUND: The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their use in orthotopic liver transplantation (OLTX) has dramatically improved success rates. Recently, however, we have had an increase of patients who are presenting after OLTX with end-stage renal disease (ESRD). This retrospective study examines the incidence and treatment of ESRD and chronic renal failure (CRF) in OLTX patients. METHODS: Patients receiving an OLTX only from June 1985 through December of 1994 who survived 6 months postoperatively were studied (n=834). Our prospectively collected database was the source of information. Patients were divided into three groups: Controls, no CRF or ESRD, n=748; CRF, sustained serum creatinine >2.5 mg/dl, n=41; and ESRD, n=45. Groups were compared for preoperative laboratory variables, diagnosis, postoperative variables, survival, type of ESRD therapy, and survival from onset of ESRD. RESULTS: At 13 years after OLTX, the incidence of severe renal dysfunction was 18.1% (CRF 8.6% and ESRD 9.5%). Compared with control patients, CRF and ESRD patients had higher preoperative serum creatinine levels, a greater percentage of patients with hepatorenal syndrome, higher percentage requirement for dialysis in the first 3 months postoperatively, and a higher 1-year serum creatinine. Multivariate stepwise logistic regression analysis using preoperative and postoperative variables identified that an increase of serum creatinine compared with average at 1 year, 3 months, and 4 weeks postoperatively were independent risk factors for the development of CRF or ESRD with odds ratios of 2.6, 2.2, and 1.6, respectively. Overall survival from the time of OLTX was not significantly different among groups, but by year 13, the survival of the patients who had ESRD was only 28.2% compared with 54.6% in the control group. Patients developing ESRD had a 6-year survival after onset of ESRD of 27% for the patients receiving hemodialysis versus 71.4% for the patients developing ESRD who subsequently received kidney transplants. CONCLUSIONS: Patients who are more than 10 years post-OLTX have CRF and ESRD at a high rate. The development of ESRD decreases survival, particularly in those patients treated with dialysis only. Patients who develop ESRD have a higher preoperative and 1-year serum creatinine and are more likely to have hepatorenal syndrome. However, an increase of serum creatinine at various times postoperatively is more predictive of the development of CRF or ESRD. New strategies for long-term immunosuppression may be needed to decrease this complication.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "hepatorenal syndrome", "mention_text": "BACKGROUND: The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their use in orthotopic liver transplantation (OLTX) has dramatically improved success rates. Recently, however, we have had an increase of patients who are presenting after OLTX with end-stage renal disease (ESRD). This retrospective study examines the incidence and treatment of ESRD and chronic renal failure (CRF) in OLTX patients. METHODS: Patients receiving an OLTX only from June 1985 through December of 1994 who survived 6 months postoperatively were studied (n=834). Our prospectively collected database was the source of information. Patients were divided into three groups: Controls, no CRF or ESRD, n=748; CRF, sustained serum creatinine >2.5 mg/dl, n=41; and ESRD, n=45. Groups were compared for preoperative laboratory variables, diagnosis, postoperative variables, survival, type of ESRD therapy, and survival from onset of ESRD. RESULTS: At 13 years after OLTX, the incidence of severe renal dysfunction was 18.1% (CRF 8.6% and ESRD 9.5%). Compared with control patients, CRF and ESRD patients had higher preoperative serum creatinine levels, a greater percentage of patients with hepatorenal syndrome, higher percentage requirement for dialysis in the first 3 months postoperatively, and a higher 1-year serum creatinine. Multivariate stepwise logistic regression analysis using preoperative and postoperative variables identified that an increase of serum creatinine compared with average at 1 year, 3 months, and 4 weeks postoperatively were independent risk factors for the development of CRF or ESRD with odds ratios of 2.6, 2.2, and 1.6, respectively. Overall survival from the time of OLTX was not significantly different among groups, but by year 13, the survival of the patients who had ESRD was only 28.2% compared with 54.6% in the control group. Patients developing ESRD had a 6-year survival after onset of ESRD of 27% for the patients receiving hemodialysis versus 71.4% for the patients developing ESRD who subsequently received kidney transplants. CONCLUSIONS: Patients who are more than 10 years post-OLTX have CRF and ESRD at a high rate. The development of ESRD decreases survival, particularly in those patients treated with dialysis only. Patients who develop ESRD have a higher preoperative and 1-year serum creatinine and are more likely to have hepatorenal syndrome. However, an increase of serum creatinine at various times postoperatively is more predictive of the development of CRF or ESRD. New strategies for long-term immunosuppression may be needed to decrease this complication.", "entity": "Hepatorenal Syndrome", "aliases": "Hepatorenal Syndrome", "definition": "Functional KIDNEY FAILURE in patients with liver disease, usually LIVER CIRRHOSIS or portal hypertension (HYPERTENSION, PORTAL), and in the absence of intrinsic renal disease or kidney abnormality. It is characterized by intense renal vasculature constriction, reduced renal blood flow, OLIGURIA, and sodium retention.\n    ", "id": "MESH:D006530"}
{"mention": "nimodipine", "mention_text": "Effect of intravenous nimodipine on blood pressure and outcome after acute stroke.", "entity": "Nimodipine", "aliases": "9736 Bay e Admon Almirall Brand of Nimodipine Alpharma Andromaco Bayer Bayvit Nimodipino Brainal Calnit Cantabria Elan Esteve Hexal Nimodipin Kenesil Modus ISIS Nimodipin-ISIS NimodipinISIS Nimotop Nymalize Remontal Vita", "definition": "A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure.\n    ", "id": "MESH:D009553"}
{"mention": "acute stroke", "mention_text": "Effect of intravenous nimodipine on blood pressure and outcome after acute stroke.", "entity": "Stroke", "aliases": "Acute Cerebrovascular Accident Accidents Stroke Strokes Apoplexy Brain Vascular CVA (Cerebrovascular Accident) CVAs Cerebral", "definition": "A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)\n    ", "id": "MESH:D020521"}
{"mention": "Nimodipine", "mention_text": "BACKGROUND AND PURPOSE: The Intravenous Nimodipine West European Stroke Trial (INWEST) found a correlation between nimodipine-induced reduction in blood pressure (BP) and an unfavorable outcome in acute stroke. We sought to confirm this correlation with and without adjustment for prognostic variables and to investigate outcome in subgroups with increasing levels of BP reduction. METHODS: Patients with a clinical diagnosis of ischemic stroke (within 24 hours) were consecutively allocated to receive placebo (n=100), 1 mg/h (low-dose) nimodipine (n=101), or 2 mg/h (high-dose) nimodipine (n=94). The correlation between average BP change during the first 2 days and the outcome at day 21 was analyzed. RESULTS: Two hundred sixty-five patients were included in this analysis (n=92, 93, and 80 for placebo, low dose, and high dose, respectively). Nimodipine treatment resulted in a statistically significant reduction in systolic BP (SBP) and diastolic BP (DBP) from baseline compared with placebo during the first few days. In multivariate analysis, a significant correlation between DBP reduction and worsening of the neurological score was found for the high-dose group (beta=0.49, P=0. 048). Patients with a DBP reduction of > or =20% in the high-dose group had a significantly increased adjusted OR for the compound outcome variable death or dependency (Barthel Index <60) (n/N=25/26, OR 10. 16, 95% CI 1.02 to 101.74) and death alone (n/N=9/26, OR 4.336, 95% CI 1.131 16.619) compared with all placebo patients (n/N=62/92 and 14/92, respectively). There was no correlation between SBP change and outcome. CONCLUSIONS: DBP, but not SBP, reduction was associated with neurological worsening after the intravenous administration of high-dose nimodipine after acute stroke. For low-dose nimodipine, the results were not conclusive. These results do not confirm or exclude a neuroprotective property of nimodipine.", "entity": "Nimodipine", "aliases": "9736 Bay e Admon Almirall Brand of Nimodipine Alpharma Andromaco Bayer Bayvit Nimodipino Brainal Calnit Cantabria Elan Esteve Hexal Nimodipin Kenesil Modus ISIS Nimodipin-ISIS NimodipinISIS Nimotop Nymalize Remontal Vita", "definition": "A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure.\n    ", "id": "MESH:D009553"}
{"mention": "Stroke", "mention_text": "BACKGROUND AND PURPOSE: The Intravenous Nimodipine West European Stroke Trial (INWEST) found a correlation between nimodipine-induced reduction in blood pressure (BP) and an unfavorable outcome in acute stroke. We sought to confirm this correlation with and without adjustment for prognostic variables and to investigate outcome in subgroups with increasing levels of BP reduction. METHODS: Patients with a clinical diagnosis of ischemic stroke (within 24 hours) were consecutively allocated to receive placebo (n=100), 1 mg/h (low-dose) nimodipine (n=101), or 2 mg/h (high-dose) nimodipine (n=94). The correlation between average BP change during the first 2 days and the outcome at day 21 was analyzed. RESULTS: Two hundred sixty-five patients were included in this analysis (n=92, 93, and 80 for placebo, low dose, and high dose, respectively). Nimodipine treatment resulted in a statistically significant reduction in systolic BP (SBP) and diastolic BP (DBP) from baseline compared with placebo during the first few days. In multivariate analysis, a significant correlation between DBP reduction and worsening of the neurological score was found for the high-dose group (beta=0.49, P=0. 048). Patients with a DBP reduction of > or =20% in the high-dose group had a significantly increased adjusted OR for the compound outcome variable death or dependency (Barthel Index <60) (n/N=25/26, OR 10. 16, 95% CI 1.02 to 101.74) and death alone (n/N=9/26, OR 4.336, 95% CI 1.131 16.619) compared with all placebo patients (n/N=62/92 and 14/92, respectively). There was no correlation between SBP change and outcome. CONCLUSIONS: DBP, but not SBP, reduction was associated with neurological worsening after the intravenous administration of high-dose nimodipine after acute stroke. For low-dose nimodipine, the results were not conclusive. These results do not confirm or exclude a neuroprotective property of nimodipine.", "entity": "Stroke", "aliases": "Acute Cerebrovascular Accident Accidents Stroke Strokes Apoplexy Brain Vascular CVA (Cerebrovascular Accident) CVAs Cerebral", "definition": "A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)\n    ", "id": "MESH:D020521"}
{"mention": "nimodipine", "mention_text": "BACKGROUND AND PURPOSE: The Intravenous Nimodipine West European Stroke Trial (INWEST) found a correlation between nimodipine-induced reduction in blood pressure (BP) and an unfavorable outcome in acute stroke. We sought to confirm this correlation with and without adjustment for prognostic variables and to investigate outcome in subgroups with increasing levels of BP reduction. METHODS: Patients with a clinical diagnosis of ischemic stroke (within 24 hours) were consecutively allocated to receive placebo (n=100), 1 mg/h (low-dose) nimodipine (n=101), or 2 mg/h (high-dose) nimodipine (n=94). The correlation between average BP change during the first 2 days and the outcome at day 21 was analyzed. RESULTS: Two hundred sixty-five patients were included in this analysis (n=92, 93, and 80 for placebo, low dose, and high dose, respectively). Nimodipine treatment resulted in a statistically significant reduction in systolic BP (SBP) and diastolic BP (DBP) from baseline compared with placebo during the first few days. In multivariate analysis, a significant correlation between DBP reduction and worsening of the neurological score was found for the high-dose group (beta=0.49, P=0. 048). Patients with a DBP reduction of > or =20% in the high-dose group had a significantly increased adjusted OR for the compound outcome variable death or dependency (Barthel Index <60) (n/N=25/26, OR 10. 16, 95% CI 1.02 to 101.74) and death alone (n/N=9/26, OR 4.336, 95% CI 1.131 16.619) compared with all placebo patients (n/N=62/92 and 14/92, respectively). There was no correlation between SBP change and outcome. CONCLUSIONS: DBP, but not SBP, reduction was associated with neurological worsening after the intravenous administration of high-dose nimodipine after acute stroke. For low-dose nimodipine, the results were not conclusive. These results do not confirm or exclude a neuroprotective property of nimodipine.", "entity": "Nimodipine", "aliases": "9736 Bay e Admon Almirall Brand of Nimodipine Alpharma Andromaco Bayer Bayvit Nimodipino Brainal Calnit Cantabria Elan Esteve Hexal Nimodipin Kenesil Modus ISIS Nimodipin-ISIS NimodipinISIS Nimotop Nymalize Remontal Vita", "definition": "A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure.\n    ", "id": "MESH:D009553"}
{"mention": "reduction in blood pressure", "mention_text": "BACKGROUND AND PURPOSE: The Intravenous Nimodipine West European Stroke Trial (INWEST) found a correlation between nimodipine-induced reduction in blood pressure (BP) and an unfavorable outcome in acute stroke. We sought to confirm this correlation with and without adjustment for prognostic variables and to investigate outcome in subgroups with increasing levels of BP reduction. METHODS: Patients with a clinical diagnosis of ischemic stroke (within 24 hours) were consecutively allocated to receive placebo (n=100), 1 mg/h (low-dose) nimodipine (n=101), or 2 mg/h (high-dose) nimodipine (n=94). The correlation between average BP change during the first 2 days and the outcome at day 21 was analyzed. RESULTS: Two hundred sixty-five patients were included in this analysis (n=92, 93, and 80 for placebo, low dose, and high dose, respectively). Nimodipine treatment resulted in a statistically significant reduction in systolic BP (SBP) and diastolic BP (DBP) from baseline compared with placebo during the first few days. In multivariate analysis, a significant correlation between DBP reduction and worsening of the neurological score was found for the high-dose group (beta=0.49, P=0. 048). Patients with a DBP reduction of > or =20% in the high-dose group had a significantly increased adjusted OR for the compound outcome variable death or dependency (Barthel Index <60) (n/N=25/26, OR 10. 16, 95% CI 1.02 to 101.74) and death alone (n/N=9/26, OR 4.336, 95% CI 1.131 16.619) compared with all placebo patients (n/N=62/92 and 14/92, respectively). There was no correlation between SBP change and outcome. CONCLUSIONS: DBP, but not SBP, reduction was associated with neurological worsening after the intravenous administration of high-dose nimodipine after acute stroke. For low-dose nimodipine, the results were not conclusive. These results do not confirm or exclude a neuroprotective property of nimodipine.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "acute stroke", "mention_text": "BACKGROUND AND PURPOSE: The Intravenous Nimodipine West European Stroke Trial (INWEST) found a correlation between nimodipine-induced reduction in blood pressure (BP) and an unfavorable outcome in acute stroke. We sought to confirm this correlation with and without adjustment for prognostic variables and to investigate outcome in subgroups with increasing levels of BP reduction. METHODS: Patients with a clinical diagnosis of ischemic stroke (within 24 hours) were consecutively allocated to receive placebo (n=100), 1 mg/h (low-dose) nimodipine (n=101), or 2 mg/h (high-dose) nimodipine (n=94). The correlation between average BP change during the first 2 days and the outcome at day 21 was analyzed. RESULTS: Two hundred sixty-five patients were included in this analysis (n=92, 93, and 80 for placebo, low dose, and high dose, respectively). Nimodipine treatment resulted in a statistically significant reduction in systolic BP (SBP) and diastolic BP (DBP) from baseline compared with placebo during the first few days. In multivariate analysis, a significant correlation between DBP reduction and worsening of the neurological score was found for the high-dose group (beta=0.49, P=0. 048). Patients with a DBP reduction of > or =20% in the high-dose group had a significantly increased adjusted OR for the compound outcome variable death or dependency (Barthel Index <60) (n/N=25/26, OR 10. 16, 95% CI 1.02 to 101.74) and death alone (n/N=9/26, OR 4.336, 95% CI 1.131 16.619) compared with all placebo patients (n/N=62/92 and 14/92, respectively). There was no correlation between SBP change and outcome. CONCLUSIONS: DBP, but not SBP, reduction was associated with neurological worsening after the intravenous administration of high-dose nimodipine after acute stroke. For low-dose nimodipine, the results were not conclusive. These results do not confirm or exclude a neuroprotective property of nimodipine.", "entity": "Stroke", "aliases": "Acute Cerebrovascular Accident Accidents Stroke Strokes Apoplexy Brain Vascular CVA (Cerebrovascular Accident) CVAs Cerebral", "definition": "A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)\n    ", "id": "MESH:D020521"}
{"mention": "BP reduction", "mention_text": "BACKGROUND AND PURPOSE: The Intravenous Nimodipine West European Stroke Trial (INWEST) found a correlation between nimodipine-induced reduction in blood pressure (BP) and an unfavorable outcome in acute stroke. We sought to confirm this correlation with and without adjustment for prognostic variables and to investigate outcome in subgroups with increasing levels of BP reduction. METHODS: Patients with a clinical diagnosis of ischemic stroke (within 24 hours) were consecutively allocated to receive placebo (n=100), 1 mg/h (low-dose) nimodipine (n=101), or 2 mg/h (high-dose) nimodipine (n=94). The correlation between average BP change during the first 2 days and the outcome at day 21 was analyzed. RESULTS: Two hundred sixty-five patients were included in this analysis (n=92, 93, and 80 for placebo, low dose, and high dose, respectively). Nimodipine treatment resulted in a statistically significant reduction in systolic BP (SBP) and diastolic BP (DBP) from baseline compared with placebo during the first few days. In multivariate analysis, a significant correlation between DBP reduction and worsening of the neurological score was found for the high-dose group (beta=0.49, P=0. 048). Patients with a DBP reduction of > or =20% in the high-dose group had a significantly increased adjusted OR for the compound outcome variable death or dependency (Barthel Index <60) (n/N=25/26, OR 10. 16, 95% CI 1.02 to 101.74) and death alone (n/N=9/26, OR 4.336, 95% CI 1.131 16.619) compared with all placebo patients (n/N=62/92 and 14/92, respectively). There was no correlation between SBP change and outcome. CONCLUSIONS: DBP, but not SBP, reduction was associated with neurological worsening after the intravenous administration of high-dose nimodipine after acute stroke. For low-dose nimodipine, the results were not conclusive. These results do not confirm or exclude a neuroprotective property of nimodipine.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "ischemic stroke", "mention_text": "BACKGROUND AND PURPOSE: The Intravenous Nimodipine West European Stroke Trial (INWEST) found a correlation between nimodipine-induced reduction in blood pressure (BP) and an unfavorable outcome in acute stroke. We sought to confirm this correlation with and without adjustment for prognostic variables and to investigate outcome in subgroups with increasing levels of BP reduction. METHODS: Patients with a clinical diagnosis of ischemic stroke (within 24 hours) were consecutively allocated to receive placebo (n=100), 1 mg/h (low-dose) nimodipine (n=101), or 2 mg/h (high-dose) nimodipine (n=94). The correlation between average BP change during the first 2 days and the outcome at day 21 was analyzed. RESULTS: Two hundred sixty-five patients were included in this analysis (n=92, 93, and 80 for placebo, low dose, and high dose, respectively). Nimodipine treatment resulted in a statistically significant reduction in systolic BP (SBP) and diastolic BP (DBP) from baseline compared with placebo during the first few days. In multivariate analysis, a significant correlation between DBP reduction and worsening of the neurological score was found for the high-dose group (beta=0.49, P=0. 048). Patients with a DBP reduction of > or =20% in the high-dose group had a significantly increased adjusted OR for the compound outcome variable death or dependency (Barthel Index <60) (n/N=25/26, OR 10. 16, 95% CI 1.02 to 101.74) and death alone (n/N=9/26, OR 4.336, 95% CI 1.131 16.619) compared with all placebo patients (n/N=62/92 and 14/92, respectively). There was no correlation between SBP change and outcome. CONCLUSIONS: DBP, but not SBP, reduction was associated with neurological worsening after the intravenous administration of high-dose nimodipine after acute stroke. For low-dose nimodipine, the results were not conclusive. These results do not confirm or exclude a neuroprotective property of nimodipine.", "entity": "Cerebral Infarction", "aliases": "Anterior Choroidal Artery Infarction Cerebral Left Hemisphere Right Infarctions Subcortical Posterior", "definition": "The formation of an area of NECROSIS in the CEREBRUM caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., INFARCTION, ANTERIOR CEREBRAL ARTERY), and etiology (e.g., embolic infarction).\n    ", "id": "MESH:D002544"}
{"mention": "reduction in systolic BP", "mention_text": "BACKGROUND AND PURPOSE: The Intravenous Nimodipine West European Stroke Trial (INWEST) found a correlation between nimodipine-induced reduction in blood pressure (BP) and an unfavorable outcome in acute stroke. We sought to confirm this correlation with and without adjustment for prognostic variables and to investigate outcome in subgroups with increasing levels of BP reduction. METHODS: Patients with a clinical diagnosis of ischemic stroke (within 24 hours) were consecutively allocated to receive placebo (n=100), 1 mg/h (low-dose) nimodipine (n=101), or 2 mg/h (high-dose) nimodipine (n=94). The correlation between average BP change during the first 2 days and the outcome at day 21 was analyzed. RESULTS: Two hundred sixty-five patients were included in this analysis (n=92, 93, and 80 for placebo, low dose, and high dose, respectively). Nimodipine treatment resulted in a statistically significant reduction in systolic BP (SBP) and diastolic BP (DBP) from baseline compared with placebo during the first few days. In multivariate analysis, a significant correlation between DBP reduction and worsening of the neurological score was found for the high-dose group (beta=0.49, P=0. 048). Patients with a DBP reduction of > or =20% in the high-dose group had a significantly increased adjusted OR for the compound outcome variable death or dependency (Barthel Index <60) (n/N=25/26, OR 10. 16, 95% CI 1.02 to 101.74) and death alone (n/N=9/26, OR 4.336, 95% CI 1.131 16.619) compared with all placebo patients (n/N=62/92 and 14/92, respectively). There was no correlation between SBP change and outcome. CONCLUSIONS: DBP, but not SBP, reduction was associated with neurological worsening after the intravenous administration of high-dose nimodipine after acute stroke. For low-dose nimodipine, the results were not conclusive. These results do not confirm or exclude a neuroprotective property of nimodipine.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "DBP reduction", "mention_text": "BACKGROUND AND PURPOSE: The Intravenous Nimodipine West European Stroke Trial (INWEST) found a correlation between nimodipine-induced reduction in blood pressure (BP) and an unfavorable outcome in acute stroke. We sought to confirm this correlation with and without adjustment for prognostic variables and to investigate outcome in subgroups with increasing levels of BP reduction. METHODS: Patients with a clinical diagnosis of ischemic stroke (within 24 hours) were consecutively allocated to receive placebo (n=100), 1 mg/h (low-dose) nimodipine (n=101), or 2 mg/h (high-dose) nimodipine (n=94). The correlation between average BP change during the first 2 days and the outcome at day 21 was analyzed. RESULTS: Two hundred sixty-five patients were included in this analysis (n=92, 93, and 80 for placebo, low dose, and high dose, respectively). Nimodipine treatment resulted in a statistically significant reduction in systolic BP (SBP) and diastolic BP (DBP) from baseline compared with placebo during the first few days. In multivariate analysis, a significant correlation between DBP reduction and worsening of the neurological score was found for the high-dose group (beta=0.49, P=0. 048). Patients with a DBP reduction of > or =20% in the high-dose group had a significantly increased adjusted OR for the compound outcome variable death or dependency (Barthel Index <60) (n/N=25/26, OR 10. 16, 95% CI 1.02 to 101.74) and death alone (n/N=9/26, OR 4.336, 95% CI 1.131 16.619) compared with all placebo patients (n/N=62/92 and 14/92, respectively). There was no correlation between SBP change and outcome. CONCLUSIONS: DBP, but not SBP, reduction was associated with neurological worsening after the intravenous administration of high-dose nimodipine after acute stroke. For low-dose nimodipine, the results were not conclusive. These results do not confirm or exclude a neuroprotective property of nimodipine.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "death", "mention_text": "BACKGROUND AND PURPOSE: The Intravenous Nimodipine West European Stroke Trial (INWEST) found a correlation between nimodipine-induced reduction in blood pressure (BP) and an unfavorable outcome in acute stroke. We sought to confirm this correlation with and without adjustment for prognostic variables and to investigate outcome in subgroups with increasing levels of BP reduction. METHODS: Patients with a clinical diagnosis of ischemic stroke (within 24 hours) were consecutively allocated to receive placebo (n=100), 1 mg/h (low-dose) nimodipine (n=101), or 2 mg/h (high-dose) nimodipine (n=94). The correlation between average BP change during the first 2 days and the outcome at day 21 was analyzed. RESULTS: Two hundred sixty-five patients were included in this analysis (n=92, 93, and 80 for placebo, low dose, and high dose, respectively). Nimodipine treatment resulted in a statistically significant reduction in systolic BP (SBP) and diastolic BP (DBP) from baseline compared with placebo during the first few days. In multivariate analysis, a significant correlation between DBP reduction and worsening of the neurological score was found for the high-dose group (beta=0.49, P=0. 048). Patients with a DBP reduction of > or =20% in the high-dose group had a significantly increased adjusted OR for the compound outcome variable death or dependency (Barthel Index <60) (n/N=25/26, OR 10. 16, 95% CI 1.02 to 101.74) and death alone (n/N=9/26, OR 4.336, 95% CI 1.131 16.619) compared with all placebo patients (n/N=62/92 and 14/92, respectively). There was no correlation between SBP change and outcome. CONCLUSIONS: DBP, but not SBP, reduction was associated with neurological worsening after the intravenous administration of high-dose nimodipine after acute stroke. For low-dose nimodipine, the results were not conclusive. These results do not confirm or exclude a neuroprotective property of nimodipine.", "entity": "Death", "aliases": "Cardiac Death Determination of Near-Death Experience", "definition": "Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.\n    ", "id": "MESH:D003643"}
{"mention": "Transient neurologic symptoms", "mention_text": "Transient neurologic symptoms after spinal anesthesia: a lower incidence with prilocaine and bupivacaine than with lidocaine.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "prilocaine", "mention_text": "Transient neurologic symptoms after spinal anesthesia: a lower incidence with prilocaine and bupivacaine than with lidocaine.", "entity": "Prilocaine", "aliases": "Astra Brand of Prilocaine Hydrochloride AstraZeneca Citanest Octapressin Delvet Inibsa Parnell Propitocaine Xylonest", "definition": "A local anesthetic that is similar pharmacologically to LIDOCAINE. Currently, it is used most often for infiltration anesthesia in dentistry.\n    ", "id": "MESH:D011318"}
{"mention": "bupivacaine", "mention_text": "Transient neurologic symptoms after spinal anesthesia: a lower incidence with prilocaine and bupivacaine than with lidocaine.", "entity": "Bupivacaine", "aliases": "1-Butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide Abbott Brand of Bupivacaine Hydrochloride Anhydrous Astra AstraZeneca Aventis Braun Bupivacaina Bupivacain Janapharm RPR Bupivacain-RPR Carbonate Monohydrochloride Monohydrate Buvacaina Carbostesin Dolanaest Inibsa Jenapharm Marcain Marcaine Pisa Sensorcaine Strathmann Svedocain Sin Vasoconstr", "definition": "A widely used local anesthetic agent.\n    ", "id": "MESH:D002045"}
{"mention": "lidocaine", "mention_text": "Transient neurologic symptoms after spinal anesthesia: a lower incidence with prilocaine and bupivacaine than with lidocaine.", "entity": "Lidocaine", "aliases": "2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide 2-2EtN-2MePhAcN Astrazeneca Brand of Lidocaine Dalcaine Jenapharm Lidocanine Hydrochloride Carbonate (2:1) Hydrocarbonate Monoacetate Monohydrochloride Monohydrate Sulfate (1:1) Lignocaine Novocol Octocaine Strathmann Xylesthesin Xylocaine Xylocitin Xyloneural", "definition": "A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.\n    ", "id": "MESH:D008012"}
{"mention": "transient neurologic symptoms", "mention_text": "BACKGROUND: Recent evidence suggests that transient neurologic symptoms (TNSs) frequently follow lidocaine spinal anesthesia but are infrequent with bupivacaine. However, identification of a short-acting local anesthetic to substitute for lidocaine for brief surgical procedures remains an important goal. Prilocaine is an amide local anesthetic with a duration of action similar to that of lidocaine. Accordingly, the present, prospective double-blind study compares prilocaine with lidocaine and bupivacaine with respect to duration of action and relative risk of TNSs. METHODS: Ninety patients classified as American Society of Anesthesiologists physical status I or II who were scheduled for short gynecologic procedures under spinal anesthesia were randomly allocated to receive 2.5 ml 2% lidocaine in 7.5% glucose, 2% prilocaine in 7.5% glucose, or 0.5% bupivacaine in 7.5% glucose. All solutions were provided in blinded vials by the hospital pharmacy. Details of spinal puncture, extension and regression of spinal block, and the times to reach discharge criteria were noted. In the evening of postoperative day 1, patients were evaluated for TNSs by a physician unaware of the drug administered and the details of the anesthetic procedure. RESULTS: Nine of 30 patients receiving lidocaine experienced TNSs, 1 of 30 patients receiving prilocaine (P = 0.03) had them, and none of 30 patients receiving bupivacaine had TNSs. Times to ambulate and to void were similar after lidocaine and prilocaine (150 vs. 165 min and 238 vs. 253 min, respectively) but prolonged after bupivacaine (200 and 299 min, respectively; P < 0.05). CONCLUSIONS: Prilocaine may be preferable to lidocaine for short surgical procedures because it has a similar duration of action but a lower incidence of TNSs.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "TNSs", "mention_text": "BACKGROUND: Recent evidence suggests that transient neurologic symptoms (TNSs) frequently follow lidocaine spinal anesthesia but are infrequent with bupivacaine. However, identification of a short-acting local anesthetic to substitute for lidocaine for brief surgical procedures remains an important goal. Prilocaine is an amide local anesthetic with a duration of action similar to that of lidocaine. Accordingly, the present, prospective double-blind study compares prilocaine with lidocaine and bupivacaine with respect to duration of action and relative risk of TNSs. METHODS: Ninety patients classified as American Society of Anesthesiologists physical status I or II who were scheduled for short gynecologic procedures under spinal anesthesia were randomly allocated to receive 2.5 ml 2% lidocaine in 7.5% glucose, 2% prilocaine in 7.5% glucose, or 0.5% bupivacaine in 7.5% glucose. All solutions were provided in blinded vials by the hospital pharmacy. Details of spinal puncture, extension and regression of spinal block, and the times to reach discharge criteria were noted. In the evening of postoperative day 1, patients were evaluated for TNSs by a physician unaware of the drug administered and the details of the anesthetic procedure. RESULTS: Nine of 30 patients receiving lidocaine experienced TNSs, 1 of 30 patients receiving prilocaine (P = 0.03) had them, and none of 30 patients receiving bupivacaine had TNSs. Times to ambulate and to void were similar after lidocaine and prilocaine (150 vs. 165 min and 238 vs. 253 min, respectively) but prolonged after bupivacaine (200 and 299 min, respectively; P < 0.05). CONCLUSIONS: Prilocaine may be preferable to lidocaine for short surgical procedures because it has a similar duration of action but a lower incidence of TNSs.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "lidocaine", "mention_text": "BACKGROUND: Recent evidence suggests that transient neurologic symptoms (TNSs) frequently follow lidocaine spinal anesthesia but are infrequent with bupivacaine. However, identification of a short-acting local anesthetic to substitute for lidocaine for brief surgical procedures remains an important goal. Prilocaine is an amide local anesthetic with a duration of action similar to that of lidocaine. Accordingly, the present, prospective double-blind study compares prilocaine with lidocaine and bupivacaine with respect to duration of action and relative risk of TNSs. METHODS: Ninety patients classified as American Society of Anesthesiologists physical status I or II who were scheduled for short gynecologic procedures under spinal anesthesia were randomly allocated to receive 2.5 ml 2% lidocaine in 7.5% glucose, 2% prilocaine in 7.5% glucose, or 0.5% bupivacaine in 7.5% glucose. All solutions were provided in blinded vials by the hospital pharmacy. Details of spinal puncture, extension and regression of spinal block, and the times to reach discharge criteria were noted. In the evening of postoperative day 1, patients were evaluated for TNSs by a physician unaware of the drug administered and the details of the anesthetic procedure. RESULTS: Nine of 30 patients receiving lidocaine experienced TNSs, 1 of 30 patients receiving prilocaine (P = 0.03) had them, and none of 30 patients receiving bupivacaine had TNSs. Times to ambulate and to void were similar after lidocaine and prilocaine (150 vs. 165 min and 238 vs. 253 min, respectively) but prolonged after bupivacaine (200 and 299 min, respectively; P < 0.05). CONCLUSIONS: Prilocaine may be preferable to lidocaine for short surgical procedures because it has a similar duration of action but a lower incidence of TNSs.", "entity": "Lidocaine", "aliases": "2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide 2-2EtN-2MePhAcN Astrazeneca Brand of Lidocaine Dalcaine Jenapharm Lidocanine Hydrochloride Carbonate (2:1) Hydrocarbonate Monoacetate Monohydrochloride Monohydrate Sulfate (1:1) Lignocaine Novocol Octocaine Strathmann Xylesthesin Xylocaine Xylocitin Xyloneural", "definition": "A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.\n    ", "id": "MESH:D008012"}
{"mention": "bupivacaine", "mention_text": "BACKGROUND: Recent evidence suggests that transient neurologic symptoms (TNSs) frequently follow lidocaine spinal anesthesia but are infrequent with bupivacaine. However, identification of a short-acting local anesthetic to substitute for lidocaine for brief surgical procedures remains an important goal. Prilocaine is an amide local anesthetic with a duration of action similar to that of lidocaine. Accordingly, the present, prospective double-blind study compares prilocaine with lidocaine and bupivacaine with respect to duration of action and relative risk of TNSs. METHODS: Ninety patients classified as American Society of Anesthesiologists physical status I or II who were scheduled for short gynecologic procedures under spinal anesthesia were randomly allocated to receive 2.5 ml 2% lidocaine in 7.5% glucose, 2% prilocaine in 7.5% glucose, or 0.5% bupivacaine in 7.5% glucose. All solutions were provided in blinded vials by the hospital pharmacy. Details of spinal puncture, extension and regression of spinal block, and the times to reach discharge criteria were noted. In the evening of postoperative day 1, patients were evaluated for TNSs by a physician unaware of the drug administered and the details of the anesthetic procedure. RESULTS: Nine of 30 patients receiving lidocaine experienced TNSs, 1 of 30 patients receiving prilocaine (P = 0.03) had them, and none of 30 patients receiving bupivacaine had TNSs. Times to ambulate and to void were similar after lidocaine and prilocaine (150 vs. 165 min and 238 vs. 253 min, respectively) but prolonged after bupivacaine (200 and 299 min, respectively; P < 0.05). CONCLUSIONS: Prilocaine may be preferable to lidocaine for short surgical procedures because it has a similar duration of action but a lower incidence of TNSs.", "entity": "Bupivacaine", "aliases": "1-Butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide Abbott Brand of Bupivacaine Hydrochloride Anhydrous Astra AstraZeneca Aventis Braun Bupivacaina Bupivacain Janapharm RPR Bupivacain-RPR Carbonate Monohydrochloride Monohydrate Buvacaina Carbostesin Dolanaest Inibsa Jenapharm Marcain Marcaine Pisa Sensorcaine Strathmann Svedocain Sin Vasoconstr", "definition": "A widely used local anesthetic agent.\n    ", "id": "MESH:D002045"}
{"mention": "Prilocaine", "mention_text": "BACKGROUND: Recent evidence suggests that transient neurologic symptoms (TNSs) frequently follow lidocaine spinal anesthesia but are infrequent with bupivacaine. However, identification of a short-acting local anesthetic to substitute for lidocaine for brief surgical procedures remains an important goal. Prilocaine is an amide local anesthetic with a duration of action similar to that of lidocaine. Accordingly, the present, prospective double-blind study compares prilocaine with lidocaine and bupivacaine with respect to duration of action and relative risk of TNSs. METHODS: Ninety patients classified as American Society of Anesthesiologists physical status I or II who were scheduled for short gynecologic procedures under spinal anesthesia were randomly allocated to receive 2.5 ml 2% lidocaine in 7.5% glucose, 2% prilocaine in 7.5% glucose, or 0.5% bupivacaine in 7.5% glucose. All solutions were provided in blinded vials by the hospital pharmacy. Details of spinal puncture, extension and regression of spinal block, and the times to reach discharge criteria were noted. In the evening of postoperative day 1, patients were evaluated for TNSs by a physician unaware of the drug administered and the details of the anesthetic procedure. RESULTS: Nine of 30 patients receiving lidocaine experienced TNSs, 1 of 30 patients receiving prilocaine (P = 0.03) had them, and none of 30 patients receiving bupivacaine had TNSs. Times to ambulate and to void were similar after lidocaine and prilocaine (150 vs. 165 min and 238 vs. 253 min, respectively) but prolonged after bupivacaine (200 and 299 min, respectively; P < 0.05). CONCLUSIONS: Prilocaine may be preferable to lidocaine for short surgical procedures because it has a similar duration of action but a lower incidence of TNSs.", "entity": "Prilocaine", "aliases": "Astra Brand of Prilocaine Hydrochloride AstraZeneca Citanest Octapressin Delvet Inibsa Parnell Propitocaine Xylonest", "definition": "A local anesthetic that is similar pharmacologically to LIDOCAINE. Currently, it is used most often for infiltration anesthesia in dentistry.\n    ", "id": "MESH:D011318"}
{"mention": "prilocaine", "mention_text": "BACKGROUND: Recent evidence suggests that transient neurologic symptoms (TNSs) frequently follow lidocaine spinal anesthesia but are infrequent with bupivacaine. However, identification of a short-acting local anesthetic to substitute for lidocaine for brief surgical procedures remains an important goal. Prilocaine is an amide local anesthetic with a duration of action similar to that of lidocaine. Accordingly, the present, prospective double-blind study compares prilocaine with lidocaine and bupivacaine with respect to duration of action and relative risk of TNSs. METHODS: Ninety patients classified as American Society of Anesthesiologists physical status I or II who were scheduled for short gynecologic procedures under spinal anesthesia were randomly allocated to receive 2.5 ml 2% lidocaine in 7.5% glucose, 2% prilocaine in 7.5% glucose, or 0.5% bupivacaine in 7.5% glucose. All solutions were provided in blinded vials by the hospital pharmacy. Details of spinal puncture, extension and regression of spinal block, and the times to reach discharge criteria were noted. In the evening of postoperative day 1, patients were evaluated for TNSs by a physician unaware of the drug administered and the details of the anesthetic procedure. RESULTS: Nine of 30 patients receiving lidocaine experienced TNSs, 1 of 30 patients receiving prilocaine (P = 0.03) had them, and none of 30 patients receiving bupivacaine had TNSs. Times to ambulate and to void were similar after lidocaine and prilocaine (150 vs. 165 min and 238 vs. 253 min, respectively) but prolonged after bupivacaine (200 and 299 min, respectively; P < 0.05). CONCLUSIONS: Prilocaine may be preferable to lidocaine for short surgical procedures because it has a similar duration of action but a lower incidence of TNSs.", "entity": "Prilocaine", "aliases": "Astra Brand of Prilocaine Hydrochloride AstraZeneca Citanest Octapressin Delvet Inibsa Parnell Propitocaine Xylonest", "definition": "A local anesthetic that is similar pharmacologically to LIDOCAINE. Currently, it is used most often for infiltration anesthesia in dentistry.\n    ", "id": "MESH:D011318"}
{"mention": "glucose", "mention_text": "BACKGROUND: Recent evidence suggests that transient neurologic symptoms (TNSs) frequently follow lidocaine spinal anesthesia but are infrequent with bupivacaine. However, identification of a short-acting local anesthetic to substitute for lidocaine for brief surgical procedures remains an important goal. Prilocaine is an amide local anesthetic with a duration of action similar to that of lidocaine. Accordingly, the present, prospective double-blind study compares prilocaine with lidocaine and bupivacaine with respect to duration of action and relative risk of TNSs. METHODS: Ninety patients classified as American Society of Anesthesiologists physical status I or II who were scheduled for short gynecologic procedures under spinal anesthesia were randomly allocated to receive 2.5 ml 2% lidocaine in 7.5% glucose, 2% prilocaine in 7.5% glucose, or 0.5% bupivacaine in 7.5% glucose. All solutions were provided in blinded vials by the hospital pharmacy. Details of spinal puncture, extension and regression of spinal block, and the times to reach discharge criteria were noted. In the evening of postoperative day 1, patients were evaluated for TNSs by a physician unaware of the drug administered and the details of the anesthetic procedure. RESULTS: Nine of 30 patients receiving lidocaine experienced TNSs, 1 of 30 patients receiving prilocaine (P = 0.03) had them, and none of 30 patients receiving bupivacaine had TNSs. Times to ambulate and to void were similar after lidocaine and prilocaine (150 vs. 165 min and 238 vs. 253 min, respectively) but prolonged after bupivacaine (200 and 299 min, respectively; P < 0.05). CONCLUSIONS: Prilocaine may be preferable to lidocaine for short surgical procedures because it has a similar duration of action but a lower incidence of TNSs.", "entity": "Glucose", "aliases": "Anhydrous Dextrose D Glucose D-Glucose Monohydrate (DL)-Isomer (L)-Isomer (alpha-D)-Isomer (beta-D)-Isomer L L-Glucose", "definition": "A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.\n    ", "id": "MESH:D005947"}
{"mention": "nicotine", "mention_text": "The role of nicotine in smoking-related cardiovascular disease.", "entity": "Nicotine", "aliases": "Bitartrate Nicotine Tartrate", "definition": "Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.\n    ", "id": "MESH:D009538"}
{"mention": "cardiovascular disease", "mention_text": "The role of nicotine in smoking-related cardiovascular disease.", "entity": "Cardiovascular Diseases", "aliases": "Cardiovascular Disease Diseases", "definition": "Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.\n    ", "id": "MESH:D002318"}
{"mention": "Nicotine", "mention_text": "Nicotine activates the sympathetic nervous system and in this way could contribute to cardiovascular disease. Animal studies and mechanistic studies indicate that nicotine could play a role in accelerating atherosclerosis, but evidence among humans is too inadequate to be definitive about such an effect. Almost certainly, nicotine via its hemodynamic effects contributes to acute cardiovascular events, although current evidence suggests that the effects of nicotine are much less important than are the prothrombotic effects of cigarette smoking or the effects of carbon monoxide. Nicotine does not appear to enhance thrombosis among humans. Clinical studies of pipe smokers and people using transdermal nicotine support the idea that toxins other than nicotine are the most important causes of acute cardiovascular events. Finally, the dose response for cardiovascular events of nicotine appears to be flat, suggesting that if nicotine is involved, adverse effects might be seen with relatively low-level cigarette exposures.", "entity": "Nicotine", "aliases": "Bitartrate Nicotine Tartrate", "definition": "Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.\n    ", "id": "MESH:D009538"}
{"mention": "cardiovascular disease", "mention_text": "Nicotine activates the sympathetic nervous system and in this way could contribute to cardiovascular disease. Animal studies and mechanistic studies indicate that nicotine could play a role in accelerating atherosclerosis, but evidence among humans is too inadequate to be definitive about such an effect. Almost certainly, nicotine via its hemodynamic effects contributes to acute cardiovascular events, although current evidence suggests that the effects of nicotine are much less important than are the prothrombotic effects of cigarette smoking or the effects of carbon monoxide. Nicotine does not appear to enhance thrombosis among humans. Clinical studies of pipe smokers and people using transdermal nicotine support the idea that toxins other than nicotine are the most important causes of acute cardiovascular events. Finally, the dose response for cardiovascular events of nicotine appears to be flat, suggesting that if nicotine is involved, adverse effects might be seen with relatively low-level cigarette exposures.", "entity": "Cardiovascular Diseases", "aliases": "Cardiovascular Disease Diseases", "definition": "Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.\n    ", "id": "MESH:D002318"}
{"mention": "nicotine", "mention_text": "Nicotine activates the sympathetic nervous system and in this way could contribute to cardiovascular disease. Animal studies and mechanistic studies indicate that nicotine could play a role in accelerating atherosclerosis, but evidence among humans is too inadequate to be definitive about such an effect. Almost certainly, nicotine via its hemodynamic effects contributes to acute cardiovascular events, although current evidence suggests that the effects of nicotine are much less important than are the prothrombotic effects of cigarette smoking or the effects of carbon monoxide. Nicotine does not appear to enhance thrombosis among humans. Clinical studies of pipe smokers and people using transdermal nicotine support the idea that toxins other than nicotine are the most important causes of acute cardiovascular events. Finally, the dose response for cardiovascular events of nicotine appears to be flat, suggesting that if nicotine is involved, adverse effects might be seen with relatively low-level cigarette exposures.", "entity": "Nicotine", "aliases": "Bitartrate Nicotine Tartrate", "definition": "Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.\n    ", "id": "MESH:D009538"}
{"mention": "atherosclerosis", "mention_text": "Nicotine activates the sympathetic nervous system and in this way could contribute to cardiovascular disease. Animal studies and mechanistic studies indicate that nicotine could play a role in accelerating atherosclerosis, but evidence among humans is too inadequate to be definitive about such an effect. Almost certainly, nicotine via its hemodynamic effects contributes to acute cardiovascular events, although current evidence suggests that the effects of nicotine are much less important than are the prothrombotic effects of cigarette smoking or the effects of carbon monoxide. Nicotine does not appear to enhance thrombosis among humans. Clinical studies of pipe smokers and people using transdermal nicotine support the idea that toxins other than nicotine are the most important causes of acute cardiovascular events. Finally, the dose response for cardiovascular events of nicotine appears to be flat, suggesting that if nicotine is involved, adverse effects might be seen with relatively low-level cigarette exposures.", "entity": "Atherosclerosis", "aliases": "Atherogenesis Atheroscleroses Atherosclerosis", "definition": "A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA.\n    ", "id": "MESH:D050197"}
{"mention": "carbon monoxide", "mention_text": "Nicotine activates the sympathetic nervous system and in this way could contribute to cardiovascular disease. Animal studies and mechanistic studies indicate that nicotine could play a role in accelerating atherosclerosis, but evidence among humans is too inadequate to be definitive about such an effect. Almost certainly, nicotine via its hemodynamic effects contributes to acute cardiovascular events, although current evidence suggests that the effects of nicotine are much less important than are the prothrombotic effects of cigarette smoking or the effects of carbon monoxide. Nicotine does not appear to enhance thrombosis among humans. Clinical studies of pipe smokers and people using transdermal nicotine support the idea that toxins other than nicotine are the most important causes of acute cardiovascular events. Finally, the dose response for cardiovascular events of nicotine appears to be flat, suggesting that if nicotine is involved, adverse effects might be seen with relatively low-level cigarette exposures.", "entity": "Carbon Monoxide", "aliases": "Carbon Monoxide", "definition": "Carbon monoxide (CO). A poisonous colorless, odorless, tasteless gas. It combines with hemoglobin to form carboxyhemoglobin, which has no oxygen carrying capacity. The resultant oxygen deprivation causes headache, dizziness, decreased pulse and respiratory rates, unconsciousness, and death. (From Merck Index, 11th ed)\n    ", "id": "MESH:D002248"}
{"mention": "thrombosis", "mention_text": "Nicotine activates the sympathetic nervous system and in this way could contribute to cardiovascular disease. Animal studies and mechanistic studies indicate that nicotine could play a role in accelerating atherosclerosis, but evidence among humans is too inadequate to be definitive about such an effect. Almost certainly, nicotine via its hemodynamic effects contributes to acute cardiovascular events, although current evidence suggests that the effects of nicotine are much less important than are the prothrombotic effects of cigarette smoking or the effects of carbon monoxide. Nicotine does not appear to enhance thrombosis among humans. Clinical studies of pipe smokers and people using transdermal nicotine support the idea that toxins other than nicotine are the most important causes of acute cardiovascular events. Finally, the dose response for cardiovascular events of nicotine appears to be flat, suggesting that if nicotine is involved, adverse effects might be seen with relatively low-level cigarette exposures.", "entity": "Thrombosis", "aliases": "Thromboses Thrombosis Thrombus", "definition": "Formation and development of a thrombus or blood clot in the blood vessel.\n    ", "id": "MESH:D013927"}
{"mention": "Seizure", "mention_text": "Seizure resulting from a venlafaxine overdose.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "venlafaxine", "mention_text": "Seizure resulting from a venlafaxine overdose.", "entity": "venlafaxine", "aliases": "1-(2-(dimethylamino)-1-(4-methoxyphenyl)ethyl)cyclohexanol HCl Cyclohexanol 1-(2-(dimethylamino)-1-(4-methoxyphenyl)ethyl)- hydrochloride Dobupal Efexor Effexor Trevilor Vandral Wy 45030 Wy-45,030 Wy-45030 sila-venlafaxine venlafaxine", "definition": "", "id": "MESH:C047426"}
{"mention": "overdose", "mention_text": "Seizure resulting from a venlafaxine overdose.", "entity": "Drug Overdose", "aliases": "Drug Overdose Overdoses", "definition": "Accidental or deliberate use of a medication or street drug in excess of normal dosage.\n    ", "id": "MESH:D062787"}
{"mention": "venlafaxine", "mention_text": "OBJECTIVE: To report a case of venlafaxine overdose. CASE SUMMARY: A 40-year-old woman with major depression took an overdose of venlafaxine in an apparent suicide attempt. After the ingestion of 26 venlafaxine 50-mg tablets, the patient experienced a witnessed generalized seizure. She was admitted to the medical intensive care unit, venlafaxine was discontinued, and no further sequelae were seen. DISCUSSION: To our knowledge, this is the first reported case of venlafaxine overdose that resulted in a generalized seizure. Based on nonoverdose pharmacokinetics and pharmacodynamics of venlafaxine and the potential risks of available interventions, no emergent therapy was instituted. CONCLUSIONS: The venlafaxine overdose in our patient resulted in a single episode of generalized seizure but elicited no further sequelae.", "entity": "venlafaxine", "aliases": "1-(2-(dimethylamino)-1-(4-methoxyphenyl)ethyl)cyclohexanol HCl Cyclohexanol 1-(2-(dimethylamino)-1-(4-methoxyphenyl)ethyl)- hydrochloride Dobupal Efexor Effexor Trevilor Vandral Wy 45030 Wy-45,030 Wy-45030 sila-venlafaxine venlafaxine", "definition": "", "id": "MESH:C047426"}
{"mention": "overdose", "mention_text": "OBJECTIVE: To report a case of venlafaxine overdose. CASE SUMMARY: A 40-year-old woman with major depression took an overdose of venlafaxine in an apparent suicide attempt. After the ingestion of 26 venlafaxine 50-mg tablets, the patient experienced a witnessed generalized seizure. She was admitted to the medical intensive care unit, venlafaxine was discontinued, and no further sequelae were seen. DISCUSSION: To our knowledge, this is the first reported case of venlafaxine overdose that resulted in a generalized seizure. Based on nonoverdose pharmacokinetics and pharmacodynamics of venlafaxine and the potential risks of available interventions, no emergent therapy was instituted. CONCLUSIONS: The venlafaxine overdose in our patient resulted in a single episode of generalized seizure but elicited no further sequelae.", "entity": "Drug Overdose", "aliases": "Drug Overdose Overdoses", "definition": "Accidental or deliberate use of a medication or street drug in excess of normal dosage.\n    ", "id": "MESH:D062787"}
{"mention": "major depression", "mention_text": "OBJECTIVE: To report a case of venlafaxine overdose. CASE SUMMARY: A 40-year-old woman with major depression took an overdose of venlafaxine in an apparent suicide attempt. After the ingestion of 26 venlafaxine 50-mg tablets, the patient experienced a witnessed generalized seizure. She was admitted to the medical intensive care unit, venlafaxine was discontinued, and no further sequelae were seen. DISCUSSION: To our knowledge, this is the first reported case of venlafaxine overdose that resulted in a generalized seizure. Based on nonoverdose pharmacokinetics and pharmacodynamics of venlafaxine and the potential risks of available interventions, no emergent therapy was instituted. CONCLUSIONS: The venlafaxine overdose in our patient resulted in a single episode of generalized seizure but elicited no further sequelae.", "entity": "Depressive Disorder, Major", "aliases": "Depression Involutional Depressive Disorder Major Disorders Melancholia Psychoses Psychosis Paraphrenia", "definition": "Marked depression appearing in the involution period and characterized by hallucinations, delusions, paranoia, and agitation.\n    ", "id": "MESH:D003865"}
{"mention": "seizure", "mention_text": "OBJECTIVE: To report a case of venlafaxine overdose. CASE SUMMARY: A 40-year-old woman with major depression took an overdose of venlafaxine in an apparent suicide attempt. After the ingestion of 26 venlafaxine 50-mg tablets, the patient experienced a witnessed generalized seizure. She was admitted to the medical intensive care unit, venlafaxine was discontinued, and no further sequelae were seen. DISCUSSION: To our knowledge, this is the first reported case of venlafaxine overdose that resulted in a generalized seizure. Based on nonoverdose pharmacokinetics and pharmacodynamics of venlafaxine and the potential risks of available interventions, no emergent therapy was instituted. CONCLUSIONS: The venlafaxine overdose in our patient resulted in a single episode of generalized seizure but elicited no further sequelae.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "nifedipine", "mention_text": "Effect of nifedipine on renal function in liver transplant recipients receiving tacrolimus.", "entity": "Nifedipine", "aliases": "AWD Pharma Brand of Nifedipine Adalat Adcock Ingram BAY a 1040 BAY-a-1040 BAYa1040 Bay Bay-1040 Bay1040 Bayer Cordipin Cordipine Corinfar Fenigidin KRKA Korinfar Monohydrochloride Nifangin GTIS Orion Pfizer Nifedipine-GTIS Procardia XL Vascard", "definition": "A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.\n    ", "id": "MESH:D009543"}
{"mention": "tacrolimus", "mention_text": "Effect of nifedipine on renal function in liver transplant recipients receiving tacrolimus.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "nifedipine", "mention_text": "The effect of nifedipine on renal function in liver transplant recipients who were receiving tacrolimus was evaluated between January 1992 and January 1996. Two groups of patients receiving tacrolimus were compared over a period of 1 year, one group comprising hypertensive patients who were receiving nifedipine, and the other comprising nonhypertensive patients not receiving nifedipine. The time from transplant to baseline was similar in all patients. Nifedipine significantly improved kidney function as indicated by a significant lowering of serum creatinine levels at 6 and 12 months. The observed positive impact of nifedipine on reducing the nephrotoxicity associated with tacrolimus in liver transplant recipients should be an important factor in selecting an agent to treat hypertension in this population.", "entity": "Nifedipine", "aliases": "AWD Pharma Brand of Nifedipine Adalat Adcock Ingram BAY a 1040 BAY-a-1040 BAYa1040 Bay Bay-1040 Bay1040 Bayer Cordipin Cordipine Corinfar Fenigidin KRKA Korinfar Monohydrochloride Nifangin GTIS Orion Pfizer Nifedipine-GTIS Procardia XL Vascard", "definition": "A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.\n    ", "id": "MESH:D009543"}
{"mention": "tacrolimus", "mention_text": "The effect of nifedipine on renal function in liver transplant recipients who were receiving tacrolimus was evaluated between January 1992 and January 1996. Two groups of patients receiving tacrolimus were compared over a period of 1 year, one group comprising hypertensive patients who were receiving nifedipine, and the other comprising nonhypertensive patients not receiving nifedipine. The time from transplant to baseline was similar in all patients. Nifedipine significantly improved kidney function as indicated by a significant lowering of serum creatinine levels at 6 and 12 months. The observed positive impact of nifedipine on reducing the nephrotoxicity associated with tacrolimus in liver transplant recipients should be an important factor in selecting an agent to treat hypertension in this population.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "hypertensive", "mention_text": "The effect of nifedipine on renal function in liver transplant recipients who were receiving tacrolimus was evaluated between January 1992 and January 1996. Two groups of patients receiving tacrolimus were compared over a period of 1 year, one group comprising hypertensive patients who were receiving nifedipine, and the other comprising nonhypertensive patients not receiving nifedipine. The time from transplant to baseline was similar in all patients. Nifedipine significantly improved kidney function as indicated by a significant lowering of serum creatinine levels at 6 and 12 months. The observed positive impact of nifedipine on reducing the nephrotoxicity associated with tacrolimus in liver transplant recipients should be an important factor in selecting an agent to treat hypertension in this population.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "Nifedipine", "mention_text": "The effect of nifedipine on renal function in liver transplant recipients who were receiving tacrolimus was evaluated between January 1992 and January 1996. Two groups of patients receiving tacrolimus were compared over a period of 1 year, one group comprising hypertensive patients who were receiving nifedipine, and the other comprising nonhypertensive patients not receiving nifedipine. The time from transplant to baseline was similar in all patients. Nifedipine significantly improved kidney function as indicated by a significant lowering of serum creatinine levels at 6 and 12 months. The observed positive impact of nifedipine on reducing the nephrotoxicity associated with tacrolimus in liver transplant recipients should be an important factor in selecting an agent to treat hypertension in this population.", "entity": "Nifedipine", "aliases": "AWD Pharma Brand of Nifedipine Adalat Adcock Ingram BAY a 1040 BAY-a-1040 BAYa1040 Bay Bay-1040 Bay1040 Bayer Cordipin Cordipine Corinfar Fenigidin KRKA Korinfar Monohydrochloride Nifangin GTIS Orion Pfizer Nifedipine-GTIS Procardia XL Vascard", "definition": "A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.\n    ", "id": "MESH:D009543"}
{"mention": "creatinine", "mention_text": "The effect of nifedipine on renal function in liver transplant recipients who were receiving tacrolimus was evaluated between January 1992 and January 1996. Two groups of patients receiving tacrolimus were compared over a period of 1 year, one group comprising hypertensive patients who were receiving nifedipine, and the other comprising nonhypertensive patients not receiving nifedipine. The time from transplant to baseline was similar in all patients. Nifedipine significantly improved kidney function as indicated by a significant lowering of serum creatinine levels at 6 and 12 months. The observed positive impact of nifedipine on reducing the nephrotoxicity associated with tacrolimus in liver transplant recipients should be an important factor in selecting an agent to treat hypertension in this population.", "entity": "Creatinine", "aliases": "Creatinine Sulfate Salt Krebiozen", "definition": "", "id": "MESH:D003404"}
{"mention": "nephrotoxicity", "mention_text": "The effect of nifedipine on renal function in liver transplant recipients who were receiving tacrolimus was evaluated between January 1992 and January 1996. Two groups of patients receiving tacrolimus were compared over a period of 1 year, one group comprising hypertensive patients who were receiving nifedipine, and the other comprising nonhypertensive patients not receiving nifedipine. The time from transplant to baseline was similar in all patients. Nifedipine significantly improved kidney function as indicated by a significant lowering of serum creatinine levels at 6 and 12 months. The observed positive impact of nifedipine on reducing the nephrotoxicity associated with tacrolimus in liver transplant recipients should be an important factor in selecting an agent to treat hypertension in this population.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "hypertension", "mention_text": "The effect of nifedipine on renal function in liver transplant recipients who were receiving tacrolimus was evaluated between January 1992 and January 1996. Two groups of patients receiving tacrolimus were compared over a period of 1 year, one group comprising hypertensive patients who were receiving nifedipine, and the other comprising nonhypertensive patients not receiving nifedipine. The time from transplant to baseline was similar in all patients. Nifedipine significantly improved kidney function as indicated by a significant lowering of serum creatinine levels at 6 and 12 months. The observed positive impact of nifedipine on reducing the nephrotoxicity associated with tacrolimus in liver transplant recipients should be an important factor in selecting an agent to treat hypertension in this population.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "Sinus arrest", "mention_text": "Sinus arrest associated with continuous-infusion cimetidine.", "entity": "Sinus Arrest, Cardiac", "aliases": "Cardiac Sinus Arrest Arrests Pause Pauses", "definition": "The omission of atrial activation that is caused by transient cessation of impulse generation at the SINOATRIAL NODE. It is characterized by a prolonged pause without P wave in an ELECTROCARDIOGRAM. Sinus arrest has been associated with sleep apnea (REM SLEEP-RELATED SINUS ARREST).\n    ", "id": "MESH:D054138"}
{"mention": "cimetidine", "mention_text": "Sinus arrest associated with continuous-infusion cimetidine.", "entity": "Cimetidine", "aliases": "Altramet Biomet Biomet400 Cimetidine HCl Hydrochloride Eureceptor Histodil N-Cyano-N'-methyl-N''-(2-(((5-methyl-1H-imidazol-4-yl)methyl)thio)ethyl)guanidine SK&F 92334 SK&F-92334 SK&F92334 SKF SKF-92334 SKF92334 Tagamet", "definition": "A histamine congener, it competitively inhibits HISTAMINE binding to HISTAMINE H2 RECEPTORS. Cimetidine has a range of pharmacological actions. It inhibits GASTRIC ACID secretion, as well as PEPSIN and GASTRIN output.\n    ", "id": "MESH:D002927"}
{"mention": "cimetidine", "mention_text": "The administration of intermittent intravenous infusions of cimetidine is infrequently associated with the development of bradyarrhythmias. A 40-year-old man with leukemia and no history of cardiac disease developed recurrent, brief episodes of apparent sinus arrest while receiving continuous-infusion cimetidine 50 mg/hour. The arrhythmias were temporally related to cimetidine administration, disappeared after dechallenge, and did not recur during ranitidine treatment. This is the first reported case of sinus arrest associated with continuous-infusion cimetidine.", "entity": "Cimetidine", "aliases": "Altramet Biomet Biomet400 Cimetidine HCl Hydrochloride Eureceptor Histodil N-Cyano-N'-methyl-N''-(2-(((5-methyl-1H-imidazol-4-yl)methyl)thio)ethyl)guanidine SK&F 92334 SK&F-92334 SK&F92334 SKF SKF-92334 SKF92334 Tagamet", "definition": "A histamine congener, it competitively inhibits HISTAMINE binding to HISTAMINE H2 RECEPTORS. Cimetidine has a range of pharmacological actions. It inhibits GASTRIC ACID secretion, as well as PEPSIN and GASTRIN output.\n    ", "id": "MESH:D002927"}
{"mention": "bradyarrhythmias", "mention_text": "The administration of intermittent intravenous infusions of cimetidine is infrequently associated with the development of bradyarrhythmias. A 40-year-old man with leukemia and no history of cardiac disease developed recurrent, brief episodes of apparent sinus arrest while receiving continuous-infusion cimetidine 50 mg/hour. The arrhythmias were temporally related to cimetidine administration, disappeared after dechallenge, and did not recur during ranitidine treatment. This is the first reported case of sinus arrest associated with continuous-infusion cimetidine.", "entity": "Bradycardia", "aliases": "Bradyarrhythmia Bradyarrhythmias Bradycardia Bradycardias", "definition": "Cardiac arrhythmias that are characterized by excessively slow HEART RATE, usually below 50 beats per minute in human adults. They can be classified broadly into SINOATRIAL NODE dysfunction and ATRIOVENTRICULAR BLOCK.\n    ", "id": "MESH:D001919"}
{"mention": "leukemia", "mention_text": "The administration of intermittent intravenous infusions of cimetidine is infrequently associated with the development of bradyarrhythmias. A 40-year-old man with leukemia and no history of cardiac disease developed recurrent, brief episodes of apparent sinus arrest while receiving continuous-infusion cimetidine 50 mg/hour. The arrhythmias were temporally related to cimetidine administration, disappeared after dechallenge, and did not recur during ranitidine treatment. This is the first reported case of sinus arrest associated with continuous-infusion cimetidine.", "entity": "Leukemia", "aliases": "Leucocythaemia Leucocythaemias Leucocythemia Leucocythemias Leukemia Leukemias", "definition": "A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006)\n    ", "id": "MESH:D007938"}
{"mention": "cardiac disease", "mention_text": "The administration of intermittent intravenous infusions of cimetidine is infrequently associated with the development of bradyarrhythmias. A 40-year-old man with leukemia and no history of cardiac disease developed recurrent, brief episodes of apparent sinus arrest while receiving continuous-infusion cimetidine 50 mg/hour. The arrhythmias were temporally related to cimetidine administration, disappeared after dechallenge, and did not recur during ranitidine treatment. This is the first reported case of sinus arrest associated with continuous-infusion cimetidine.", "entity": "Heart Diseases", "aliases": "Cardiac Disease Diseases Heart", "definition": "Pathological conditions involving the HEART including its structural and functional abnormalities.\n    ", "id": "MESH:D006331"}
{"mention": "sinus arrest", "mention_text": "The administration of intermittent intravenous infusions of cimetidine is infrequently associated with the development of bradyarrhythmias. A 40-year-old man with leukemia and no history of cardiac disease developed recurrent, brief episodes of apparent sinus arrest while receiving continuous-infusion cimetidine 50 mg/hour. The arrhythmias were temporally related to cimetidine administration, disappeared after dechallenge, and did not recur during ranitidine treatment. This is the first reported case of sinus arrest associated with continuous-infusion cimetidine.", "entity": "Sinus Arrest, Cardiac", "aliases": "Cardiac Sinus Arrest Arrests Pause Pauses", "definition": "The omission of atrial activation that is caused by transient cessation of impulse generation at the SINOATRIAL NODE. It is characterized by a prolonged pause without P wave in an ELECTROCARDIOGRAM. Sinus arrest has been associated with sleep apnea (REM SLEEP-RELATED SINUS ARREST).\n    ", "id": "MESH:D054138"}
{"mention": "arrhythmias", "mention_text": "The administration of intermittent intravenous infusions of cimetidine is infrequently associated with the development of bradyarrhythmias. A 40-year-old man with leukemia and no history of cardiac disease developed recurrent, brief episodes of apparent sinus arrest while receiving continuous-infusion cimetidine 50 mg/hour. The arrhythmias were temporally related to cimetidine administration, disappeared after dechallenge, and did not recur during ranitidine treatment. This is the first reported case of sinus arrest associated with continuous-infusion cimetidine.", "entity": "Arrhythmias, Cardiac", "aliases": "Arrhythmia Cardiac Arrhythmias Arrythmia Dysrhythmia", "definition": "Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.\n    ", "id": "MESH:D001145"}
{"mention": "ranitidine", "mention_text": "The administration of intermittent intravenous infusions of cimetidine is infrequently associated with the development of bradyarrhythmias. A 40-year-old man with leukemia and no history of cardiac disease developed recurrent, brief episodes of apparent sinus arrest while receiving continuous-infusion cimetidine 50 mg/hour. The arrhythmias were temporally related to cimetidine administration, disappeared after dechallenge, and did not recur during ranitidine treatment. This is the first reported case of sinus arrest associated with continuous-infusion cimetidine.", "entity": "Ranitidine", "aliases": "AH 19065 AH-19065 AH19065 Biotidin Hydrochloride Ranitidine N (2-(((5-((Dimethylamino)methyl)-2-furanyl)methyl)thio)ethyl)-N'-methyl-2-nitro-1,1-ethenediamine Ranisen Ranitidin Sostril Zantac Zantic", "definition": "A non-imidazole blocker of those histamine receptors that mediate gastric secretion (H2 receptors). It is used to treat gastrointestinal ulcers.\n    ", "id": "MESH:D011899"}
{"mention": "gall bladder stones", "mention_text": "Composition of gall bladder stones associated with octreotide: response to oral ursodeoxycholic acid.", "entity": "Gallstones", "aliases": "Biliary Calculi Common Bile Duct Gall Stones Gallstones Stone Gallstone", "definition": "Solid crystalline precipitates in the BILIARY TRACT, usually formed in the GALLBLADDER, resulting in the condition of CHOLELITHIASIS. Gallstones, derived from the BILE, consist mainly of calcium, cholesterol, or bilirubin.\n    ", "id": "MESH:D042882"}
{"mention": "octreotide", "mention_text": "Composition of gall bladder stones associated with octreotide: response to oral ursodeoxycholic acid.", "entity": "Octreotide", "aliases": "Compound 201 995 201-995 201995 Octreotide Acetate Salt SAN SM SMS Sandostatin Sandostatine Sandoz", "definition": "A potent, long-acting synthetic SOMATOSTATIN octapeptide analog that inhibits secretion of GROWTH HORMONE and is used to treat hormone-secreting tumors; DIABETES MELLITUS; HYPOTENSION, ORTHOSTATIC; HYPERINSULINISM; hypergastrinemia; and small bowel fistula.\n    ", "id": "MESH:D015282"}
{"mention": "ursodeoxycholic acid", "mention_text": "Composition of gall bladder stones associated with octreotide: response to oral ursodeoxycholic acid.", "entity": "Ursodeoxycholic Acid", "aliases": "3 alpha,7 beta Dihydroxy 5 beta cholan 24 oic Acid beta-Dihydroxy-5 beta-cholan-24-oic Deoxyursocholic Ursacholic Ursodeoxycholic Antigen Brand of Aventis Axcan CP Cholit-Ursan Cholofalk Delursan Destolit Estedi Falk Farmasa Galen Heumann Niddapharm Norgine Orphan Provalis Sanofi Synthelabo Sodium Ursodeoxycholate Tramedico Urdox Urso Ursobilane Ursochol Ursodiol Ursofalk Ursogal Ursolite Ursolvan Vita Zambon", "definition": "An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.\n    ", "id": "MESH:D014580"}
{"mention": "Octreotide", "mention_text": "Octreotide, an effective treatment for acromegaly, induces gall bladder stones in 13-60% of patients. Because knowledge of stone composition is essential for studies of their pathogenesis, treatment, and prevention, this was investigated by direct and indirect methods in 14 octreotide treated acromegalic patients with gall stones. Chemical analysis of gall stones retrieved at cholecystectomy from two patients, showed that they contained 71% and 87% cholesterol by weight. In the remaining 12 patients, localised computed tomography of the gall bladder showed that eight had stones with maximum attenuation scores of < 100 Hounsfield units (values of < 100 HU predict cholesterol rich, dissolvable stones). Gall bladder bile was obtained by ultrasound guided, fine needle puncture from six patients. All six patients had supersaturated bile (mean (SEM) cholesterol saturation index of 1.19 (0.08) (range 1.01-1.53)) and all had abnormally rapid cholesterol microcrystal nucleation times (< 4 days (range 1-4)), whilst in four, the bile contained cholesterol microcrystals immediately after sampling. Of the 12 patients considered for oral ursodeoxycholic acid (UDCA) treatment, two had a blocked cystic duct and were not started on UDCA while one was lost to follow up. After one year of treatment, five of the remaining nine patients showed either partial (n = 3) or complete (n = 2) gall stone dissolution, suggesting that their stones were cholesterol rich. This corresponds, by actuarial (life table) analysis, to a combined gall stone dissolution rate of 58.3 (15.9%). In conclusion, octreotide induced gall stones are generally small, multiple, and cholesterol rich although, in common with spontaneous gall stone disease, at presentation some patients will have a blocked cystic duct and some gall stones containing calcium.", "entity": "Octreotide", "aliases": "Compound 201 995 201-995 201995 Octreotide Acetate Salt SAN SM SMS Sandostatin Sandostatine Sandoz", "definition": "A potent, long-acting synthetic SOMATOSTATIN octapeptide analog that inhibits secretion of GROWTH HORMONE and is used to treat hormone-secreting tumors; DIABETES MELLITUS; HYPOTENSION, ORTHOSTATIC; HYPERINSULINISM; hypergastrinemia; and small bowel fistula.\n    ", "id": "MESH:D015282"}
{"mention": "acromegaly", "mention_text": "Octreotide, an effective treatment for acromegaly, induces gall bladder stones in 13-60% of patients. Because knowledge of stone composition is essential for studies of their pathogenesis, treatment, and prevention, this was investigated by direct and indirect methods in 14 octreotide treated acromegalic patients with gall stones. Chemical analysis of gall stones retrieved at cholecystectomy from two patients, showed that they contained 71% and 87% cholesterol by weight. In the remaining 12 patients, localised computed tomography of the gall bladder showed that eight had stones with maximum attenuation scores of < 100 Hounsfield units (values of < 100 HU predict cholesterol rich, dissolvable stones). Gall bladder bile was obtained by ultrasound guided, fine needle puncture from six patients. All six patients had supersaturated bile (mean (SEM) cholesterol saturation index of 1.19 (0.08) (range 1.01-1.53)) and all had abnormally rapid cholesterol microcrystal nucleation times (< 4 days (range 1-4)), whilst in four, the bile contained cholesterol microcrystals immediately after sampling. Of the 12 patients considered for oral ursodeoxycholic acid (UDCA) treatment, two had a blocked cystic duct and were not started on UDCA while one was lost to follow up. After one year of treatment, five of the remaining nine patients showed either partial (n = 3) or complete (n = 2) gall stone dissolution, suggesting that their stones were cholesterol rich. This corresponds, by actuarial (life table) analysis, to a combined gall stone dissolution rate of 58.3 (15.9%). In conclusion, octreotide induced gall stones are generally small, multiple, and cholesterol rich although, in common with spontaneous gall stone disease, at presentation some patients will have a blocked cystic duct and some gall stones containing calcium.", "entity": "Acromegaly", "aliases": "Acromegaly Hypersecretion Syndrome Somatotropin (Acromegaly) Syndromes Inappropriate GH Secretion Growth Hormone", "definition": "A condition caused by prolonged exposure to excessive HUMAN GROWTH HORMONE in adults. It is characterized by bony enlargement of the FACE; lower jaw (PROGNATHISM); hands; FEET; HEAD; and THORAX. The most common etiology is a GROWTH HORMONE-SECRETING PITUITARY ADENOMA. (From Joynt, Clinical Neurology, 1992, Ch36, pp79-80)\n    ", "id": "MESH:D000172"}
{"mention": "gall bladder stones", "mention_text": "Octreotide, an effective treatment for acromegaly, induces gall bladder stones in 13-60% of patients. Because knowledge of stone composition is essential for studies of their pathogenesis, treatment, and prevention, this was investigated by direct and indirect methods in 14 octreotide treated acromegalic patients with gall stones. Chemical analysis of gall stones retrieved at cholecystectomy from two patients, showed that they contained 71% and 87% cholesterol by weight. In the remaining 12 patients, localised computed tomography of the gall bladder showed that eight had stones with maximum attenuation scores of < 100 Hounsfield units (values of < 100 HU predict cholesterol rich, dissolvable stones). Gall bladder bile was obtained by ultrasound guided, fine needle puncture from six patients. All six patients had supersaturated bile (mean (SEM) cholesterol saturation index of 1.19 (0.08) (range 1.01-1.53)) and all had abnormally rapid cholesterol microcrystal nucleation times (< 4 days (range 1-4)), whilst in four, the bile contained cholesterol microcrystals immediately after sampling. Of the 12 patients considered for oral ursodeoxycholic acid (UDCA) treatment, two had a blocked cystic duct and were not started on UDCA while one was lost to follow up. After one year of treatment, five of the remaining nine patients showed either partial (n = 3) or complete (n = 2) gall stone dissolution, suggesting that their stones were cholesterol rich. This corresponds, by actuarial (life table) analysis, to a combined gall stone dissolution rate of 58.3 (15.9%). In conclusion, octreotide induced gall stones are generally small, multiple, and cholesterol rich although, in common with spontaneous gall stone disease, at presentation some patients will have a blocked cystic duct and some gall stones containing calcium.", "entity": "Gallstones", "aliases": "Biliary Calculi Common Bile Duct Gall Stones Gallstones Stone Gallstone", "definition": "Solid crystalline precipitates in the BILIARY TRACT, usually formed in the GALLBLADDER, resulting in the condition of CHOLELITHIASIS. Gallstones, derived from the BILE, consist mainly of calcium, cholesterol, or bilirubin.\n    ", "id": "MESH:D042882"}
{"mention": "octreotide", "mention_text": "Octreotide, an effective treatment for acromegaly, induces gall bladder stones in 13-60% of patients. Because knowledge of stone composition is essential for studies of their pathogenesis, treatment, and prevention, this was investigated by direct and indirect methods in 14 octreotide treated acromegalic patients with gall stones. Chemical analysis of gall stones retrieved at cholecystectomy from two patients, showed that they contained 71% and 87% cholesterol by weight. In the remaining 12 patients, localised computed tomography of the gall bladder showed that eight had stones with maximum attenuation scores of < 100 Hounsfield units (values of < 100 HU predict cholesterol rich, dissolvable stones). Gall bladder bile was obtained by ultrasound guided, fine needle puncture from six patients. All six patients had supersaturated bile (mean (SEM) cholesterol saturation index of 1.19 (0.08) (range 1.01-1.53)) and all had abnormally rapid cholesterol microcrystal nucleation times (< 4 days (range 1-4)), whilst in four, the bile contained cholesterol microcrystals immediately after sampling. Of the 12 patients considered for oral ursodeoxycholic acid (UDCA) treatment, two had a blocked cystic duct and were not started on UDCA while one was lost to follow up. After one year of treatment, five of the remaining nine patients showed either partial (n = 3) or complete (n = 2) gall stone dissolution, suggesting that their stones were cholesterol rich. This corresponds, by actuarial (life table) analysis, to a combined gall stone dissolution rate of 58.3 (15.9%). In conclusion, octreotide induced gall stones are generally small, multiple, and cholesterol rich although, in common with spontaneous gall stone disease, at presentation some patients will have a blocked cystic duct and some gall stones containing calcium.", "entity": "Octreotide", "aliases": "Compound 201 995 201-995 201995 Octreotide Acetate Salt SAN SM SMS Sandostatin Sandostatine Sandoz", "definition": "A potent, long-acting synthetic SOMATOSTATIN octapeptide analog that inhibits secretion of GROWTH HORMONE and is used to treat hormone-secreting tumors; DIABETES MELLITUS; HYPOTENSION, ORTHOSTATIC; HYPERINSULINISM; hypergastrinemia; and small bowel fistula.\n    ", "id": "MESH:D015282"}
{"mention": "acromegalic", "mention_text": "Octreotide, an effective treatment for acromegaly, induces gall bladder stones in 13-60% of patients. Because knowledge of stone composition is essential for studies of their pathogenesis, treatment, and prevention, this was investigated by direct and indirect methods in 14 octreotide treated acromegalic patients with gall stones. Chemical analysis of gall stones retrieved at cholecystectomy from two patients, showed that they contained 71% and 87% cholesterol by weight. In the remaining 12 patients, localised computed tomography of the gall bladder showed that eight had stones with maximum attenuation scores of < 100 Hounsfield units (values of < 100 HU predict cholesterol rich, dissolvable stones). Gall bladder bile was obtained by ultrasound guided, fine needle puncture from six patients. All six patients had supersaturated bile (mean (SEM) cholesterol saturation index of 1.19 (0.08) (range 1.01-1.53)) and all had abnormally rapid cholesterol microcrystal nucleation times (< 4 days (range 1-4)), whilst in four, the bile contained cholesterol microcrystals immediately after sampling. Of the 12 patients considered for oral ursodeoxycholic acid (UDCA) treatment, two had a blocked cystic duct and were not started on UDCA while one was lost to follow up. After one year of treatment, five of the remaining nine patients showed either partial (n = 3) or complete (n = 2) gall stone dissolution, suggesting that their stones were cholesterol rich. This corresponds, by actuarial (life table) analysis, to a combined gall stone dissolution rate of 58.3 (15.9%). In conclusion, octreotide induced gall stones are generally small, multiple, and cholesterol rich although, in common with spontaneous gall stone disease, at presentation some patients will have a blocked cystic duct and some gall stones containing calcium.", "entity": "Acromegaly", "aliases": "Acromegaly Hypersecretion Syndrome Somatotropin (Acromegaly) Syndromes Inappropriate GH Secretion Growth Hormone", "definition": "A condition caused by prolonged exposure to excessive HUMAN GROWTH HORMONE in adults. It is characterized by bony enlargement of the FACE; lower jaw (PROGNATHISM); hands; FEET; HEAD; and THORAX. The most common etiology is a GROWTH HORMONE-SECRETING PITUITARY ADENOMA. (From Joynt, Clinical Neurology, 1992, Ch36, pp79-80)\n    ", "id": "MESH:D000172"}
{"mention": "gall stones", "mention_text": "Octreotide, an effective treatment for acromegaly, induces gall bladder stones in 13-60% of patients. Because knowledge of stone composition is essential for studies of their pathogenesis, treatment, and prevention, this was investigated by direct and indirect methods in 14 octreotide treated acromegalic patients with gall stones. Chemical analysis of gall stones retrieved at cholecystectomy from two patients, showed that they contained 71% and 87% cholesterol by weight. In the remaining 12 patients, localised computed tomography of the gall bladder showed that eight had stones with maximum attenuation scores of < 100 Hounsfield units (values of < 100 HU predict cholesterol rich, dissolvable stones). Gall bladder bile was obtained by ultrasound guided, fine needle puncture from six patients. All six patients had supersaturated bile (mean (SEM) cholesterol saturation index of 1.19 (0.08) (range 1.01-1.53)) and all had abnormally rapid cholesterol microcrystal nucleation times (< 4 days (range 1-4)), whilst in four, the bile contained cholesterol microcrystals immediately after sampling. Of the 12 patients considered for oral ursodeoxycholic acid (UDCA) treatment, two had a blocked cystic duct and were not started on UDCA while one was lost to follow up. After one year of treatment, five of the remaining nine patients showed either partial (n = 3) or complete (n = 2) gall stone dissolution, suggesting that their stones were cholesterol rich. This corresponds, by actuarial (life table) analysis, to a combined gall stone dissolution rate of 58.3 (15.9%). In conclusion, octreotide induced gall stones are generally small, multiple, and cholesterol rich although, in common with spontaneous gall stone disease, at presentation some patients will have a blocked cystic duct and some gall stones containing calcium.", "entity": "Gallstones", "aliases": "Biliary Calculi Common Bile Duct Gall Stones Gallstones Stone Gallstone", "definition": "Solid crystalline precipitates in the BILIARY TRACT, usually formed in the GALLBLADDER, resulting in the condition of CHOLELITHIASIS. Gallstones, derived from the BILE, consist mainly of calcium, cholesterol, or bilirubin.\n    ", "id": "MESH:D042882"}
{"mention": "cholesterol", "mention_text": "Octreotide, an effective treatment for acromegaly, induces gall bladder stones in 13-60% of patients. Because knowledge of stone composition is essential for studies of their pathogenesis, treatment, and prevention, this was investigated by direct and indirect methods in 14 octreotide treated acromegalic patients with gall stones. Chemical analysis of gall stones retrieved at cholecystectomy from two patients, showed that they contained 71% and 87% cholesterol by weight. In the remaining 12 patients, localised computed tomography of the gall bladder showed that eight had stones with maximum attenuation scores of < 100 Hounsfield units (values of < 100 HU predict cholesterol rich, dissolvable stones). Gall bladder bile was obtained by ultrasound guided, fine needle puncture from six patients. All six patients had supersaturated bile (mean (SEM) cholesterol saturation index of 1.19 (0.08) (range 1.01-1.53)) and all had abnormally rapid cholesterol microcrystal nucleation times (< 4 days (range 1-4)), whilst in four, the bile contained cholesterol microcrystals immediately after sampling. Of the 12 patients considered for oral ursodeoxycholic acid (UDCA) treatment, two had a blocked cystic duct and were not started on UDCA while one was lost to follow up. After one year of treatment, five of the remaining nine patients showed either partial (n = 3) or complete (n = 2) gall stone dissolution, suggesting that their stones were cholesterol rich. This corresponds, by actuarial (life table) analysis, to a combined gall stone dissolution rate of 58.3 (15.9%). In conclusion, octreotide induced gall stones are generally small, multiple, and cholesterol rich although, in common with spontaneous gall stone disease, at presentation some patients will have a blocked cystic duct and some gall stones containing calcium.", "entity": "Cholesterol", "aliases": "Cholesterol Epicholesterol", "definition": "The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.\n    ", "id": "MESH:D002784"}
{"mention": "ursodeoxycholic acid", "mention_text": "Octreotide, an effective treatment for acromegaly, induces gall bladder stones in 13-60% of patients. Because knowledge of stone composition is essential for studies of their pathogenesis, treatment, and prevention, this was investigated by direct and indirect methods in 14 octreotide treated acromegalic patients with gall stones. Chemical analysis of gall stones retrieved at cholecystectomy from two patients, showed that they contained 71% and 87% cholesterol by weight. In the remaining 12 patients, localised computed tomography of the gall bladder showed that eight had stones with maximum attenuation scores of < 100 Hounsfield units (values of < 100 HU predict cholesterol rich, dissolvable stones). Gall bladder bile was obtained by ultrasound guided, fine needle puncture from six patients. All six patients had supersaturated bile (mean (SEM) cholesterol saturation index of 1.19 (0.08) (range 1.01-1.53)) and all had abnormally rapid cholesterol microcrystal nucleation times (< 4 days (range 1-4)), whilst in four, the bile contained cholesterol microcrystals immediately after sampling. Of the 12 patients considered for oral ursodeoxycholic acid (UDCA) treatment, two had a blocked cystic duct and were not started on UDCA while one was lost to follow up. After one year of treatment, five of the remaining nine patients showed either partial (n = 3) or complete (n = 2) gall stone dissolution, suggesting that their stones were cholesterol rich. This corresponds, by actuarial (life table) analysis, to a combined gall stone dissolution rate of 58.3 (15.9%). In conclusion, octreotide induced gall stones are generally small, multiple, and cholesterol rich although, in common with spontaneous gall stone disease, at presentation some patients will have a blocked cystic duct and some gall stones containing calcium.", "entity": "Ursodeoxycholic Acid", "aliases": "3 alpha,7 beta Dihydroxy 5 beta cholan 24 oic Acid beta-Dihydroxy-5 beta-cholan-24-oic Deoxyursocholic Ursacholic Ursodeoxycholic Antigen Brand of Aventis Axcan CP Cholit-Ursan Cholofalk Delursan Destolit Estedi Falk Farmasa Galen Heumann Niddapharm Norgine Orphan Provalis Sanofi Synthelabo Sodium Ursodeoxycholate Tramedico Urdox Urso Ursobilane Ursochol Ursodiol Ursofalk Ursogal Ursolite Ursolvan Vita Zambon", "definition": "An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.\n    ", "id": "MESH:D014580"}
{"mention": "UDCA", "mention_text": "Octreotide, an effective treatment for acromegaly, induces gall bladder stones in 13-60% of patients. Because knowledge of stone composition is essential for studies of their pathogenesis, treatment, and prevention, this was investigated by direct and indirect methods in 14 octreotide treated acromegalic patients with gall stones. Chemical analysis of gall stones retrieved at cholecystectomy from two patients, showed that they contained 71% and 87% cholesterol by weight. In the remaining 12 patients, localised computed tomography of the gall bladder showed that eight had stones with maximum attenuation scores of < 100 Hounsfield units (values of < 100 HU predict cholesterol rich, dissolvable stones). Gall bladder bile was obtained by ultrasound guided, fine needle puncture from six patients. All six patients had supersaturated bile (mean (SEM) cholesterol saturation index of 1.19 (0.08) (range 1.01-1.53)) and all had abnormally rapid cholesterol microcrystal nucleation times (< 4 days (range 1-4)), whilst in four, the bile contained cholesterol microcrystals immediately after sampling. Of the 12 patients considered for oral ursodeoxycholic acid (UDCA) treatment, two had a blocked cystic duct and were not started on UDCA while one was lost to follow up. After one year of treatment, five of the remaining nine patients showed either partial (n = 3) or complete (n = 2) gall stone dissolution, suggesting that their stones were cholesterol rich. This corresponds, by actuarial (life table) analysis, to a combined gall stone dissolution rate of 58.3 (15.9%). In conclusion, octreotide induced gall stones are generally small, multiple, and cholesterol rich although, in common with spontaneous gall stone disease, at presentation some patients will have a blocked cystic duct and some gall stones containing calcium.", "entity": "Ursodeoxycholic Acid", "aliases": "3 alpha,7 beta Dihydroxy 5 beta cholan 24 oic Acid beta-Dihydroxy-5 beta-cholan-24-oic Deoxyursocholic Ursacholic Ursodeoxycholic Antigen Brand of Aventis Axcan CP Cholit-Ursan Cholofalk Delursan Destolit Estedi Falk Farmasa Galen Heumann Niddapharm Norgine Orphan Provalis Sanofi Synthelabo Sodium Ursodeoxycholate Tramedico Urdox Urso Ursobilane Ursochol Ursodiol Ursofalk Ursogal Ursolite Ursolvan Vita Zambon", "definition": "An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.\n    ", "id": "MESH:D014580"}
{"mention": "gall stone", "mention_text": "Octreotide, an effective treatment for acromegaly, induces gall bladder stones in 13-60% of patients. Because knowledge of stone composition is essential for studies of their pathogenesis, treatment, and prevention, this was investigated by direct and indirect methods in 14 octreotide treated acromegalic patients with gall stones. Chemical analysis of gall stones retrieved at cholecystectomy from two patients, showed that they contained 71% and 87% cholesterol by weight. In the remaining 12 patients, localised computed tomography of the gall bladder showed that eight had stones with maximum attenuation scores of < 100 Hounsfield units (values of < 100 HU predict cholesterol rich, dissolvable stones). Gall bladder bile was obtained by ultrasound guided, fine needle puncture from six patients. All six patients had supersaturated bile (mean (SEM) cholesterol saturation index of 1.19 (0.08) (range 1.01-1.53)) and all had abnormally rapid cholesterol microcrystal nucleation times (< 4 days (range 1-4)), whilst in four, the bile contained cholesterol microcrystals immediately after sampling. Of the 12 patients considered for oral ursodeoxycholic acid (UDCA) treatment, two had a blocked cystic duct and were not started on UDCA while one was lost to follow up. After one year of treatment, five of the remaining nine patients showed either partial (n = 3) or complete (n = 2) gall stone dissolution, suggesting that their stones were cholesterol rich. This corresponds, by actuarial (life table) analysis, to a combined gall stone dissolution rate of 58.3 (15.9%). In conclusion, octreotide induced gall stones are generally small, multiple, and cholesterol rich although, in common with spontaneous gall stone disease, at presentation some patients will have a blocked cystic duct and some gall stones containing calcium.", "entity": "Gallstones", "aliases": "Biliary Calculi Common Bile Duct Gall Stones Gallstones Stone Gallstone", "definition": "Solid crystalline precipitates in the BILIARY TRACT, usually formed in the GALLBLADDER, resulting in the condition of CHOLELITHIASIS. Gallstones, derived from the BILE, consist mainly of calcium, cholesterol, or bilirubin.\n    ", "id": "MESH:D042882"}
{"mention": "gall stone disease", "mention_text": "Octreotide, an effective treatment for acromegaly, induces gall bladder stones in 13-60% of patients. Because knowledge of stone composition is essential for studies of their pathogenesis, treatment, and prevention, this was investigated by direct and indirect methods in 14 octreotide treated acromegalic patients with gall stones. Chemical analysis of gall stones retrieved at cholecystectomy from two patients, showed that they contained 71% and 87% cholesterol by weight. In the remaining 12 patients, localised computed tomography of the gall bladder showed that eight had stones with maximum attenuation scores of < 100 Hounsfield units (values of < 100 HU predict cholesterol rich, dissolvable stones). Gall bladder bile was obtained by ultrasound guided, fine needle puncture from six patients. All six patients had supersaturated bile (mean (SEM) cholesterol saturation index of 1.19 (0.08) (range 1.01-1.53)) and all had abnormally rapid cholesterol microcrystal nucleation times (< 4 days (range 1-4)), whilst in four, the bile contained cholesterol microcrystals immediately after sampling. Of the 12 patients considered for oral ursodeoxycholic acid (UDCA) treatment, two had a blocked cystic duct and were not started on UDCA while one was lost to follow up. After one year of treatment, five of the remaining nine patients showed either partial (n = 3) or complete (n = 2) gall stone dissolution, suggesting that their stones were cholesterol rich. This corresponds, by actuarial (life table) analysis, to a combined gall stone dissolution rate of 58.3 (15.9%). In conclusion, octreotide induced gall stones are generally small, multiple, and cholesterol rich although, in common with spontaneous gall stone disease, at presentation some patients will have a blocked cystic duct and some gall stones containing calcium.", "entity": "Gallstones", "aliases": "Biliary Calculi Common Bile Duct Gall Stones Gallstones Stone Gallstone", "definition": "Solid crystalline precipitates in the BILIARY TRACT, usually formed in the GALLBLADDER, resulting in the condition of CHOLELITHIASIS. Gallstones, derived from the BILE, consist mainly of calcium, cholesterol, or bilirubin.\n    ", "id": "MESH:D042882"}
{"mention": "calcium", "mention_text": "Octreotide, an effective treatment for acromegaly, induces gall bladder stones in 13-60% of patients. Because knowledge of stone composition is essential for studies of their pathogenesis, treatment, and prevention, this was investigated by direct and indirect methods in 14 octreotide treated acromegalic patients with gall stones. Chemical analysis of gall stones retrieved at cholecystectomy from two patients, showed that they contained 71% and 87% cholesterol by weight. In the remaining 12 patients, localised computed tomography of the gall bladder showed that eight had stones with maximum attenuation scores of < 100 Hounsfield units (values of < 100 HU predict cholesterol rich, dissolvable stones). Gall bladder bile was obtained by ultrasound guided, fine needle puncture from six patients. All six patients had supersaturated bile (mean (SEM) cholesterol saturation index of 1.19 (0.08) (range 1.01-1.53)) and all had abnormally rapid cholesterol microcrystal nucleation times (< 4 days (range 1-4)), whilst in four, the bile contained cholesterol microcrystals immediately after sampling. Of the 12 patients considered for oral ursodeoxycholic acid (UDCA) treatment, two had a blocked cystic duct and were not started on UDCA while one was lost to follow up. After one year of treatment, five of the remaining nine patients showed either partial (n = 3) or complete (n = 2) gall stone dissolution, suggesting that their stones were cholesterol rich. This corresponds, by actuarial (life table) analysis, to a combined gall stone dissolution rate of 58.3 (15.9%). In conclusion, octreotide induced gall stones are generally small, multiple, and cholesterol rich although, in common with spontaneous gall stone disease, at presentation some patients will have a blocked cystic duct and some gall stones containing calcium.", "entity": "Calcium", "aliases": "Blood Coagulation Factor IV Calcium", "definition": "A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.\n    ", "id": "MESH:D002118"}
{"mention": "Cardiovascular complications", "mention_text": "Cardiovascular complications associated with terbutaline treatment for preterm labor.", "entity": "Cardiovascular Diseases", "aliases": "Cardiovascular Disease Diseases", "definition": "Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.\n    ", "id": "MESH:D002318"}
{"mention": "terbutaline", "mention_text": "Cardiovascular complications associated with terbutaline treatment for preterm labor.", "entity": "Terbutaline", "aliases": "Aliud Brand of Terbutaline Sulfate Alpharma Arubendol Asthmoprotect AstraZeneca Azupharma Brethaire Brethine Bricanyl SA Butaliret Butalitab Contimit Dermapharm Estedi Fatol Hexal Hoechst KWD 2019 KWD-2019 KWD2019 Kendrick Lagap Lindopharm Monovent Novartis Stadapharm Taziken Tedipulmo Terbasmin Terbul Terbutalin AL Stada ratiopharm Terbutalin-ratiopharm Terbuturmant ct Arzneimittel ct-Arzneimittel pharma-stern terbutalin von", "definition": "A selective beta-2 adrenergic agonist used as a bronchodilator and tocolytic.\n    ", "id": "MESH:D013726"}
{"mention": "preterm labor", "mention_text": "Cardiovascular complications associated with terbutaline treatment for preterm labor.", "entity": "Obstetric Labor, Premature", "aliases": "Labor Premature Obstetric Preterm", "definition": "Onset of OBSTETRIC LABOR before term (TERM BIRTH) but usually after the FETUS has become viable. In humans, it occurs sometime during the 29th through 38th week of PREGNANCY. TOCOLYSIS inhibits premature labor and can prevent the BIRTH of premature infants (INFANT, PREMATURE).\n    ", "id": "MESH:D007752"}
{"mention": "cardiovascular complications", "mention_text": "Severe cardiovascular complications occurred in eight of 160 patients treated with terbutaline for preterm labor. Associated corticosteroid therapy and twin gestations appear to be predisposing factors. Potential mechanisms of the pathophysiology are briefly discussed.", "entity": "Cardiovascular Diseases", "aliases": "Cardiovascular Disease Diseases", "definition": "Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.\n    ", "id": "MESH:D002318"}
{"mention": "terbutaline", "mention_text": "Severe cardiovascular complications occurred in eight of 160 patients treated with terbutaline for preterm labor. Associated corticosteroid therapy and twin gestations appear to be predisposing factors. Potential mechanisms of the pathophysiology are briefly discussed.", "entity": "Terbutaline", "aliases": "Aliud Brand of Terbutaline Sulfate Alpharma Arubendol Asthmoprotect AstraZeneca Azupharma Brethaire Brethine Bricanyl SA Butaliret Butalitab Contimit Dermapharm Estedi Fatol Hexal Hoechst KWD 2019 KWD-2019 KWD2019 Kendrick Lagap Lindopharm Monovent Novartis Stadapharm Taziken Tedipulmo Terbasmin Terbul Terbutalin AL Stada ratiopharm Terbutalin-ratiopharm Terbuturmant ct Arzneimittel ct-Arzneimittel pharma-stern terbutalin von", "definition": "A selective beta-2 adrenergic agonist used as a bronchodilator and tocolytic.\n    ", "id": "MESH:D013726"}
{"mention": "preterm labor", "mention_text": "Severe cardiovascular complications occurred in eight of 160 patients treated with terbutaline for preterm labor. Associated corticosteroid therapy and twin gestations appear to be predisposing factors. Potential mechanisms of the pathophysiology are briefly discussed.", "entity": "Obstetric Labor, Premature", "aliases": "Labor Premature Obstetric Preterm", "definition": "Onset of OBSTETRIC LABOR before term (TERM BIRTH) but usually after the FETUS has become viable. In humans, it occurs sometime during the 29th through 38th week of PREGNANCY. TOCOLYSIS inhibits premature labor and can prevent the BIRTH of premature infants (INFANT, PREMATURE).\n    ", "id": "MESH:D007752"}
{"mention": "2-chloroprocaine-CE", "mention_text": "Neurologic effects of subarachnoid administration of 2-chloroprocaine-CE, bupivacaine, and low pH normal saline in dogs.", "entity": "chloroprocaine", "aliases": "2-chloroprocaine Nesacaine MPF chlor-procaine chloroprocaine hydrochloride", "definition": "", "id": "MESH:C004616"}
{"mention": "bupivacaine", "mention_text": "Neurologic effects of subarachnoid administration of 2-chloroprocaine-CE, bupivacaine, and low pH normal saline in dogs.", "entity": "Bupivacaine", "aliases": "1-Butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide Abbott Brand of Bupivacaine Hydrochloride Anhydrous Astra AstraZeneca Aventis Braun Bupivacaina Bupivacain Janapharm RPR Bupivacain-RPR Carbonate Monohydrochloride Monohydrate Buvacaina Carbostesin Dolanaest Inibsa Jenapharm Marcain Marcaine Pisa Sensorcaine Strathmann Svedocain Sin Vasoconstr", "definition": "A widely used local anesthetic agent.\n    ", "id": "MESH:D002045"}
{"mention": "2-chloroprocaine-CE", "mention_text": "The purpose of this study was to evaluate the neurologic consequences of deliberate subarachnoid injection of large volumes of 2-chloroprocaine-CE in experimental animals. The possible role of low pH as well as total volume as potential factors in causing neurotoxicity was evaluated. The 65 dogs in the study received injections in the subarachnoid space as follows: 6 to 8 ml of bupivacaine (N = 15), 2-chloroprocaine-CE (N = 20), low pH normal saline (pH 3.0) (N = 20), or normal saline (N = 10). Of the 20 animals that received subarachnoid injection of 2-chloroprocaine-CE seven (35%) developed hind-limb paralysis. None of the animals that received bupivacaine, normal saline, or normal saline titrated to a pH 3.0 developed hind-limb paralysis. Of the 15 spinal cords of the animals that received 2-chloroprocaine-CE, 13 showed subpial necrosis; the nerve roots and subarachnoid vessels were normal. The spinal cords of the animals that received bupivacaine, low pH normal saline (pH 3.0), or normal saline did not show abnormal findings.", "entity": "chloroprocaine", "aliases": "2-chloroprocaine Nesacaine MPF chlor-procaine chloroprocaine hydrochloride", "definition": "", "id": "MESH:C004616"}
{"mention": "neurotoxicity", "mention_text": "The purpose of this study was to evaluate the neurologic consequences of deliberate subarachnoid injection of large volumes of 2-chloroprocaine-CE in experimental animals. The possible role of low pH as well as total volume as potential factors in causing neurotoxicity was evaluated. The 65 dogs in the study received injections in the subarachnoid space as follows: 6 to 8 ml of bupivacaine (N = 15), 2-chloroprocaine-CE (N = 20), low pH normal saline (pH 3.0) (N = 20), or normal saline (N = 10). Of the 20 animals that received subarachnoid injection of 2-chloroprocaine-CE seven (35%) developed hind-limb paralysis. None of the animals that received bupivacaine, normal saline, or normal saline titrated to a pH 3.0 developed hind-limb paralysis. Of the 15 spinal cords of the animals that received 2-chloroprocaine-CE, 13 showed subpial necrosis; the nerve roots and subarachnoid vessels were normal. The spinal cords of the animals that received bupivacaine, low pH normal saline (pH 3.0), or normal saline did not show abnormal findings.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "bupivacaine", "mention_text": "The purpose of this study was to evaluate the neurologic consequences of deliberate subarachnoid injection of large volumes of 2-chloroprocaine-CE in experimental animals. The possible role of low pH as well as total volume as potential factors in causing neurotoxicity was evaluated. The 65 dogs in the study received injections in the subarachnoid space as follows: 6 to 8 ml of bupivacaine (N = 15), 2-chloroprocaine-CE (N = 20), low pH normal saline (pH 3.0) (N = 20), or normal saline (N = 10). Of the 20 animals that received subarachnoid injection of 2-chloroprocaine-CE seven (35%) developed hind-limb paralysis. None of the animals that received bupivacaine, normal saline, or normal saline titrated to a pH 3.0 developed hind-limb paralysis. Of the 15 spinal cords of the animals that received 2-chloroprocaine-CE, 13 showed subpial necrosis; the nerve roots and subarachnoid vessels were normal. The spinal cords of the animals that received bupivacaine, low pH normal saline (pH 3.0), or normal saline did not show abnormal findings.", "entity": "Bupivacaine", "aliases": "1-Butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide Abbott Brand of Bupivacaine Hydrochloride Anhydrous Astra AstraZeneca Aventis Braun Bupivacaina Bupivacain Janapharm RPR Bupivacain-RPR Carbonate Monohydrochloride Monohydrate Buvacaina Carbostesin Dolanaest Inibsa Jenapharm Marcain Marcaine Pisa Sensorcaine Strathmann Svedocain Sin Vasoconstr", "definition": "A widely used local anesthetic agent.\n    ", "id": "MESH:D002045"}
{"mention": "paralysis", "mention_text": "The purpose of this study was to evaluate the neurologic consequences of deliberate subarachnoid injection of large volumes of 2-chloroprocaine-CE in experimental animals. The possible role of low pH as well as total volume as potential factors in causing neurotoxicity was evaluated. The 65 dogs in the study received injections in the subarachnoid space as follows: 6 to 8 ml of bupivacaine (N = 15), 2-chloroprocaine-CE (N = 20), low pH normal saline (pH 3.0) (N = 20), or normal saline (N = 10). Of the 20 animals that received subarachnoid injection of 2-chloroprocaine-CE seven (35%) developed hind-limb paralysis. None of the animals that received bupivacaine, normal saline, or normal saline titrated to a pH 3.0 developed hind-limb paralysis. Of the 15 spinal cords of the animals that received 2-chloroprocaine-CE, 13 showed subpial necrosis; the nerve roots and subarachnoid vessels were normal. The spinal cords of the animals that received bupivacaine, low pH normal saline (pH 3.0), or normal saline did not show abnormal findings.", "entity": "Paralysis", "aliases": "Palsies Palsy Paralyses Paralysis Todd Todd's Plegia Plegias Todds", "definition": "A general term most often used to describe severe or complete loss of muscle strength due to motor system disease from the level of the cerebral cortex to the muscle fiber. This term may also occasionally refer to a loss of sensory function. (From Adams et al., Principles of Neurology, 6th ed, p45)\n    ", "id": "MESH:D010243"}
{"mention": "subpial necrosis", "mention_text": "The purpose of this study was to evaluate the neurologic consequences of deliberate subarachnoid injection of large volumes of 2-chloroprocaine-CE in experimental animals. The possible role of low pH as well as total volume as potential factors in causing neurotoxicity was evaluated. The 65 dogs in the study received injections in the subarachnoid space as follows: 6 to 8 ml of bupivacaine (N = 15), 2-chloroprocaine-CE (N = 20), low pH normal saline (pH 3.0) (N = 20), or normal saline (N = 10). Of the 20 animals that received subarachnoid injection of 2-chloroprocaine-CE seven (35%) developed hind-limb paralysis. None of the animals that received bupivacaine, normal saline, or normal saline titrated to a pH 3.0 developed hind-limb paralysis. Of the 15 spinal cords of the animals that received 2-chloroprocaine-CE, 13 showed subpial necrosis; the nerve roots and subarachnoid vessels were normal. The spinal cords of the animals that received bupivacaine, low pH normal saline (pH 3.0), or normal saline did not show abnormal findings.", "entity": "Spinal Cord Diseases", "aliases": "Myelopathies Myelopathy Spinal Cord Disease Diseases Disorder Disorders", "definition": "Pathologic conditions which feature SPINAL CORD damage or dysfunction, including disorders involving the meninges and perimeningeal spaces surrounding the spinal cord. Traumatic injuries, vascular diseases, infections, and inflammatory/autoimmune processes may affect the spinal cord.\n    ", "id": "MESH:D013118"}
{"mention": "adriamycin", "mention_text": "Early adjuvant adriamycin in superficial bladder carcinoma.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "bladder carcinoma", "mention_text": "Early adjuvant adriamycin in superficial bladder carcinoma.", "entity": "Urinary Bladder Neoplasms", "aliases": "Bladder Cancer Cancers Neoplasm Neoplasms Tumor Tumors of the Urinary Malignant", "definition": "Tumors or cancer of the URINARY BLADDER.\n    ", "id": "MESH:D001749"}
{"mention": "carcinoma", "mention_text": "Early adjuvant adriamycin in superficial bladder carcinoma.", "entity": "Carcinoma", "aliases": "Anaplastic Carcinoma Carcinomas Spindle Cell Spindle-Cell Undifferentiated Carcinomatoses Carcinomatosis Epithelial Neoplasm Malignant Neoplasms Tumor Tumors Epithelioma Epitheliomas", "definition": "A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm but is often wrongly used as a synonym for \"cancer.\" (From Dorland, 27th ed)\n    ", "id": "MESH:D002277"}
{"mention": "carcinoma of the bladder", "mention_text": "A multicenter study was performed in 110 patients with superficial transitional cell carcinoma of the bladder. Adriamycin (50 mg/50 ml) was administered intravesically within 24 h after transurethral resection of TA-T1 (O-A) bladder tumors. Instillation was repeated twice during the first week, then weekly during the first month and afterwards monthly for 1 year. The tolerance was evaluated in these 110 patients, and 29 patients presented with local side-effects. In 24 of these patients chemical cystitis was severe enough for them to drop out of the study. No systemic side-effects were observed. Recurrence was studied in 82 evaluable patients after 1 year of follow-up and in 72 patients followed for 2-3 years (mean 32 months). Of the 82 patients studied after 1 year, 23 had primary and 59 recurrent disease. Of the 82 evaluable patients, 50 did not show any recurrence after 1 year (61%), while 32 presented with one or more recurrences (39%). Of these recurrences, 27 were T1 tumors while five progressed to more highly invasive lesions. In patients that were free of recurrence during the first year, 80% remained tumor-free during the 2- to 3-year follow-up period. Of the patients developing one or more recurrences during the first year, only 50% presented with further recurrence once the instillations were stopped. The beneficial effect of Adriamycin appears obvious and might be related to the drug itself, the early and repeated instillations after TUR, or both.", "entity": "Urinary Bladder Neoplasms", "aliases": "Bladder Cancer Cancers Neoplasm Neoplasms Tumor Tumors of the Urinary Malignant", "definition": "Tumors or cancer of the URINARY BLADDER.\n    ", "id": "MESH:D001749"}
{"mention": "carcinoma", "mention_text": "A multicenter study was performed in 110 patients with superficial transitional cell carcinoma of the bladder. Adriamycin (50 mg/50 ml) was administered intravesically within 24 h after transurethral resection of TA-T1 (O-A) bladder tumors. Instillation was repeated twice during the first week, then weekly during the first month and afterwards monthly for 1 year. The tolerance was evaluated in these 110 patients, and 29 patients presented with local side-effects. In 24 of these patients chemical cystitis was severe enough for them to drop out of the study. No systemic side-effects were observed. Recurrence was studied in 82 evaluable patients after 1 year of follow-up and in 72 patients followed for 2-3 years (mean 32 months). Of the 82 patients studied after 1 year, 23 had primary and 59 recurrent disease. Of the 82 evaluable patients, 50 did not show any recurrence after 1 year (61%), while 32 presented with one or more recurrences (39%). Of these recurrences, 27 were T1 tumors while five progressed to more highly invasive lesions. In patients that were free of recurrence during the first year, 80% remained tumor-free during the 2- to 3-year follow-up period. Of the patients developing one or more recurrences during the first year, only 50% presented with further recurrence once the instillations were stopped. The beneficial effect of Adriamycin appears obvious and might be related to the drug itself, the early and repeated instillations after TUR, or both.", "entity": "Carcinoma", "aliases": "Anaplastic Carcinoma Carcinomas Spindle Cell Spindle-Cell Undifferentiated Carcinomatoses Carcinomatosis Epithelial Neoplasm Malignant Neoplasms Tumor Tumors Epithelioma Epitheliomas", "definition": "A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm but is often wrongly used as a synonym for \"cancer.\" (From Dorland, 27th ed)\n    ", "id": "MESH:D002277"}
{"mention": "Adriamycin", "mention_text": "A multicenter study was performed in 110 patients with superficial transitional cell carcinoma of the bladder. Adriamycin (50 mg/50 ml) was administered intravesically within 24 h after transurethral resection of TA-T1 (O-A) bladder tumors. Instillation was repeated twice during the first week, then weekly during the first month and afterwards monthly for 1 year. The tolerance was evaluated in these 110 patients, and 29 patients presented with local side-effects. In 24 of these patients chemical cystitis was severe enough for them to drop out of the study. No systemic side-effects were observed. Recurrence was studied in 82 evaluable patients after 1 year of follow-up and in 72 patients followed for 2-3 years (mean 32 months). Of the 82 patients studied after 1 year, 23 had primary and 59 recurrent disease. Of the 82 evaluable patients, 50 did not show any recurrence after 1 year (61%), while 32 presented with one or more recurrences (39%). Of these recurrences, 27 were T1 tumors while five progressed to more highly invasive lesions. In patients that were free of recurrence during the first year, 80% remained tumor-free during the 2- to 3-year follow-up period. Of the patients developing one or more recurrences during the first year, only 50% presented with further recurrence once the instillations were stopped. The beneficial effect of Adriamycin appears obvious and might be related to the drug itself, the early and repeated instillations after TUR, or both.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "bladder tumors", "mention_text": "A multicenter study was performed in 110 patients with superficial transitional cell carcinoma of the bladder. Adriamycin (50 mg/50 ml) was administered intravesically within 24 h after transurethral resection of TA-T1 (O-A) bladder tumors. Instillation was repeated twice during the first week, then weekly during the first month and afterwards monthly for 1 year. The tolerance was evaluated in these 110 patients, and 29 patients presented with local side-effects. In 24 of these patients chemical cystitis was severe enough for them to drop out of the study. No systemic side-effects were observed. Recurrence was studied in 82 evaluable patients after 1 year of follow-up and in 72 patients followed for 2-3 years (mean 32 months). Of the 82 patients studied after 1 year, 23 had primary and 59 recurrent disease. Of the 82 evaluable patients, 50 did not show any recurrence after 1 year (61%), while 32 presented with one or more recurrences (39%). Of these recurrences, 27 were T1 tumors while five progressed to more highly invasive lesions. In patients that were free of recurrence during the first year, 80% remained tumor-free during the 2- to 3-year follow-up period. Of the patients developing one or more recurrences during the first year, only 50% presented with further recurrence once the instillations were stopped. The beneficial effect of Adriamycin appears obvious and might be related to the drug itself, the early and repeated instillations after TUR, or both.", "entity": "Urinary Bladder Neoplasms", "aliases": "Bladder Cancer Cancers Neoplasm Neoplasms Tumor Tumors of the Urinary Malignant", "definition": "Tumors or cancer of the URINARY BLADDER.\n    ", "id": "MESH:D001749"}
{"mention": "cystitis", "mention_text": "A multicenter study was performed in 110 patients with superficial transitional cell carcinoma of the bladder. Adriamycin (50 mg/50 ml) was administered intravesically within 24 h after transurethral resection of TA-T1 (O-A) bladder tumors. Instillation was repeated twice during the first week, then weekly during the first month and afterwards monthly for 1 year. The tolerance was evaluated in these 110 patients, and 29 patients presented with local side-effects. In 24 of these patients chemical cystitis was severe enough for them to drop out of the study. No systemic side-effects were observed. Recurrence was studied in 82 evaluable patients after 1 year of follow-up and in 72 patients followed for 2-3 years (mean 32 months). Of the 82 patients studied after 1 year, 23 had primary and 59 recurrent disease. Of the 82 evaluable patients, 50 did not show any recurrence after 1 year (61%), while 32 presented with one or more recurrences (39%). Of these recurrences, 27 were T1 tumors while five progressed to more highly invasive lesions. In patients that were free of recurrence during the first year, 80% remained tumor-free during the 2- to 3-year follow-up period. Of the patients developing one or more recurrences during the first year, only 50% presented with further recurrence once the instillations were stopped. The beneficial effect of Adriamycin appears obvious and might be related to the drug itself, the early and repeated instillations after TUR, or both.", "entity": "Cystitis", "aliases": "Cystitides Cystitis", "definition": "Inflammation of the URINARY BLADDER, either from bacterial or non-bacterial causes. Cystitis is usually associated with painful urination (dysuria), increased frequency, urgency, and suprapubic pain.\n    ", "id": "MESH:D003556"}
{"mention": "tumors", "mention_text": "A multicenter study was performed in 110 patients with superficial transitional cell carcinoma of the bladder. Adriamycin (50 mg/50 ml) was administered intravesically within 24 h after transurethral resection of TA-T1 (O-A) bladder tumors. Instillation was repeated twice during the first week, then weekly during the first month and afterwards monthly for 1 year. The tolerance was evaluated in these 110 patients, and 29 patients presented with local side-effects. In 24 of these patients chemical cystitis was severe enough for them to drop out of the study. No systemic side-effects were observed. Recurrence was studied in 82 evaluable patients after 1 year of follow-up and in 72 patients followed for 2-3 years (mean 32 months). Of the 82 patients studied after 1 year, 23 had primary and 59 recurrent disease. Of the 82 evaluable patients, 50 did not show any recurrence after 1 year (61%), while 32 presented with one or more recurrences (39%). Of these recurrences, 27 were T1 tumors while five progressed to more highly invasive lesions. In patients that were free of recurrence during the first year, 80% remained tumor-free during the 2- to 3-year follow-up period. Of the patients developing one or more recurrences during the first year, only 50% presented with further recurrence once the instillations were stopped. The beneficial effect of Adriamycin appears obvious and might be related to the drug itself, the early and repeated instillations after TUR, or both.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "tumor", "mention_text": "A multicenter study was performed in 110 patients with superficial transitional cell carcinoma of the bladder. Adriamycin (50 mg/50 ml) was administered intravesically within 24 h after transurethral resection of TA-T1 (O-A) bladder tumors. Instillation was repeated twice during the first week, then weekly during the first month and afterwards monthly for 1 year. The tolerance was evaluated in these 110 patients, and 29 patients presented with local side-effects. In 24 of these patients chemical cystitis was severe enough for them to drop out of the study. No systemic side-effects were observed. Recurrence was studied in 82 evaluable patients after 1 year of follow-up and in 72 patients followed for 2-3 years (mean 32 months). Of the 82 patients studied after 1 year, 23 had primary and 59 recurrent disease. Of the 82 evaluable patients, 50 did not show any recurrence after 1 year (61%), while 32 presented with one or more recurrences (39%). Of these recurrences, 27 were T1 tumors while five progressed to more highly invasive lesions. In patients that were free of recurrence during the first year, 80% remained tumor-free during the 2- to 3-year follow-up period. Of the patients developing one or more recurrences during the first year, only 50% presented with further recurrence once the instillations were stopped. The beneficial effect of Adriamycin appears obvious and might be related to the drug itself, the early and repeated instillations after TUR, or both.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "Hyperkalemia", "mention_text": "Hyperkalemia associated with sulindac therapy.", "entity": "Hyperkalemia", "aliases": "Hyperkalemia Hyperkalemias Hyperpotassemia Hyperpotassemias", "definition": "Abnormally high potassium concentration in the blood, most often due to defective renal excretion. It is characterized clinically by electrocardiographic abnormalities (elevated T waves and depressed P waves, and eventually by atrial asystole). In severe cases, weakness and flaccid paralysis may occur. (Dorland, 27th ed)\n    ", "id": "MESH:D006947"}
{"mention": "sulindac", "mention_text": "Hyperkalemia associated with sulindac therapy.", "entity": "Sulindac", "aliases": "Aclin Alphapharm Brand of Sulindac Apo Sulin Apo-Sulin Apotex Arthrobid Arthrocine Cahill May Roberts Chemia Chibret Clinoril Copal Kenalin Kendrick Klinoril MK 231 MK-231 MK231 Merck Sharp & Dohme Novo Sundac Novo-Sundac Novopharm Nu Pharm Nu-Pharm Nu-Sulindac Sulindal", "definition": "A sulfinylindene derivative prodrug whose sulfinyl moiety is converted in vivo to an active NSAID analgesic. Specifically, the prodrug is converted by liver enzymes to a sulfide which is excreted in the bile and then reabsorbed from the intestine. This helps to maintain constant blood levels with reduced gastrointestinal side effects.\n    ", "id": "MESH:D013467"}
{"mention": "Hyperkalemia", "mention_text": "Hyperkalemia has recently been recognized as a complication of nonsteroidal antiinflammatory agents (NSAID) such as indomethacin. Several recent studies have stressed the renal sparing features of sulindac, owing to its lack of interference with renal prostacyclin synthesis. We describe 4 patients in whom hyperkalemia ranging from 6.1 to 6.9 mEq/l developed within 3 to 8 days of sulindac administration. In all of them normal serum potassium levels reached within 2 to 4 days of stopping sulindac. As no other medications known to effect serum potassium had been given concomitantly, this course of events is suggestive of a cause-and-effect relationship between sulindac and hyperkalemia. These observations indicate that initial hopes that sulindac may not be associated with the adverse renal effects of other NSAID are probably not justified.", "entity": "Hyperkalemia", "aliases": "Hyperkalemia Hyperkalemias Hyperpotassemia Hyperpotassemias", "definition": "Abnormally high potassium concentration in the blood, most often due to defective renal excretion. It is characterized clinically by electrocardiographic abnormalities (elevated T waves and depressed P waves, and eventually by atrial asystole). In severe cases, weakness and flaccid paralysis may occur. (Dorland, 27th ed)\n    ", "id": "MESH:D006947"}
{"mention": "indomethacin", "mention_text": "Hyperkalemia has recently been recognized as a complication of nonsteroidal antiinflammatory agents (NSAID) such as indomethacin. Several recent studies have stressed the renal sparing features of sulindac, owing to its lack of interference with renal prostacyclin synthesis. We describe 4 patients in whom hyperkalemia ranging from 6.1 to 6.9 mEq/l developed within 3 to 8 days of sulindac administration. In all of them normal serum potassium levels reached within 2 to 4 days of stopping sulindac. As no other medications known to effect serum potassium had been given concomitantly, this course of events is suggestive of a cause-and-effect relationship between sulindac and hyperkalemia. These observations indicate that initial hopes that sulindac may not be associated with the adverse renal effects of other NSAID are probably not justified.", "entity": "Indomethacin", "aliases": "Amuno Hydrochloride Indomethacin Indocid Indocin Indomet 140 Indometacin Metindol Osmosin", "definition": "A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes.\n    ", "id": "MESH:D007213"}
{"mention": "sulindac", "mention_text": "Hyperkalemia has recently been recognized as a complication of nonsteroidal antiinflammatory agents (NSAID) such as indomethacin. Several recent studies have stressed the renal sparing features of sulindac, owing to its lack of interference with renal prostacyclin synthesis. We describe 4 patients in whom hyperkalemia ranging from 6.1 to 6.9 mEq/l developed within 3 to 8 days of sulindac administration. In all of them normal serum potassium levels reached within 2 to 4 days of stopping sulindac. As no other medications known to effect serum potassium had been given concomitantly, this course of events is suggestive of a cause-and-effect relationship between sulindac and hyperkalemia. These observations indicate that initial hopes that sulindac may not be associated with the adverse renal effects of other NSAID are probably not justified.", "entity": "Sulindac", "aliases": "Aclin Alphapharm Brand of Sulindac Apo Sulin Apo-Sulin Apotex Arthrobid Arthrocine Cahill May Roberts Chemia Chibret Clinoril Copal Kenalin Kendrick Klinoril MK 231 MK-231 MK231 Merck Sharp & Dohme Novo Sundac Novo-Sundac Novopharm Nu Pharm Nu-Pharm Nu-Sulindac Sulindal", "definition": "A sulfinylindene derivative prodrug whose sulfinyl moiety is converted in vivo to an active NSAID analgesic. Specifically, the prodrug is converted by liver enzymes to a sulfide which is excreted in the bile and then reabsorbed from the intestine. This helps to maintain constant blood levels with reduced gastrointestinal side effects.\n    ", "id": "MESH:D013467"}
{"mention": "prostacyclin", "mention_text": "Hyperkalemia has recently been recognized as a complication of nonsteroidal antiinflammatory agents (NSAID) such as indomethacin. Several recent studies have stressed the renal sparing features of sulindac, owing to its lack of interference with renal prostacyclin synthesis. We describe 4 patients in whom hyperkalemia ranging from 6.1 to 6.9 mEq/l developed within 3 to 8 days of sulindac administration. In all of them normal serum potassium levels reached within 2 to 4 days of stopping sulindac. As no other medications known to effect serum potassium had been given concomitantly, this course of events is suggestive of a cause-and-effect relationship between sulindac and hyperkalemia. These observations indicate that initial hopes that sulindac may not be associated with the adverse renal effects of other NSAID are probably not justified.", "entity": "Epoprostenol", "aliases": "Epoprostanol Epoprostenol Sodium Salt (5Z,9alpha,11alpha,13E,15S)-Isomer Flolan PGI2 PGX Prostacyclin Prostaglandin I(2) I2", "definition": "A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY).\n    ", "id": "MESH:D011464"}
{"mention": "hyperkalemia", "mention_text": "Hyperkalemia has recently been recognized as a complication of nonsteroidal antiinflammatory agents (NSAID) such as indomethacin. Several recent studies have stressed the renal sparing features of sulindac, owing to its lack of interference with renal prostacyclin synthesis. We describe 4 patients in whom hyperkalemia ranging from 6.1 to 6.9 mEq/l developed within 3 to 8 days of sulindac administration. In all of them normal serum potassium levels reached within 2 to 4 days of stopping sulindac. As no other medications known to effect serum potassium had been given concomitantly, this course of events is suggestive of a cause-and-effect relationship between sulindac and hyperkalemia. These observations indicate that initial hopes that sulindac may not be associated with the adverse renal effects of other NSAID are probably not justified.", "entity": "Hyperkalemia", "aliases": "Hyperkalemia Hyperkalemias Hyperpotassemia Hyperpotassemias", "definition": "Abnormally high potassium concentration in the blood, most often due to defective renal excretion. It is characterized clinically by electrocardiographic abnormalities (elevated T waves and depressed P waves, and eventually by atrial asystole). In severe cases, weakness and flaccid paralysis may occur. (Dorland, 27th ed)\n    ", "id": "MESH:D006947"}
{"mention": "potassium", "mention_text": "Hyperkalemia has recently been recognized as a complication of nonsteroidal antiinflammatory agents (NSAID) such as indomethacin. Several recent studies have stressed the renal sparing features of sulindac, owing to its lack of interference with renal prostacyclin synthesis. We describe 4 patients in whom hyperkalemia ranging from 6.1 to 6.9 mEq/l developed within 3 to 8 days of sulindac administration. In all of them normal serum potassium levels reached within 2 to 4 days of stopping sulindac. As no other medications known to effect serum potassium had been given concomitantly, this course of events is suggestive of a cause-and-effect relationship between sulindac and hyperkalemia. These observations indicate that initial hopes that sulindac may not be associated with the adverse renal effects of other NSAID are probably not justified.", "entity": "Potassium", "aliases": "Potassium", "definition": "An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.\n    ", "id": "MESH:D011188"}
{"mention": "Ventricular tachyarrhythmias", "mention_text": "Ventricular tachyarrhythmias during cesarean section after ritodrine therapy: interaction with anesthetics.", "entity": "Ventricular Fibrillation", "aliases": "Fibrillation Ventricular Fibrillations", "definition": "A potentially lethal cardiac arrhythmia that is characterized by uncoordinated extremely rapid firing of electrical impulses (400-600/min) in HEART VENTRICLES. Such asynchronous ventricular quivering or fibrillation prevents any effective cardiac output and results in unconsciousness (SYNCOPE). It is one of the major electrocardiographic patterns seen with CARDIAC ARREST.\n    ", "id": "MESH:D014693"}
{"mention": "ritodrine", "mention_text": "Ventricular tachyarrhythmias during cesarean section after ritodrine therapy: interaction with anesthetics.", "entity": "Ritodrine", "aliases": "Astra Brand of Ritodrine Hydrochloride DU 21220 DU-21220 DU21220 Janssen Pre Par Pre-Par PrePar Solvay Yutopar", "definition": "An adrenergic beta-2 agonist used to control PREMATURE LABOR.\n    ", "id": "MESH:D012312"}
{"mention": "ritodrine", "mention_text": "This case illustrates that patients receiving ritodrine for preterm labor may risk interactions between the residual betamimetic effects of ritodrine and the effects of anesthetics during cesarean section. Such interactions may result in serious cardiovascular complications even after cessation of an infusion of ritodrine. Preoperative assessment should focus on cardiovascular status and serum potassium level. Delaying induction of anesthesia should be considered whenever possible. Careful fluid administration and cautious use of titrated doses of ephedrine are advised. After delivery of the infant, there should be no contraindication to the use of an alpha-adrenergic vasopressor such as phenylephrine to treat hypotensive patients with tachycardia.", "entity": "Ritodrine", "aliases": "Astra Brand of Ritodrine Hydrochloride DU 21220 DU-21220 DU21220 Janssen Pre Par Pre-Par PrePar Solvay Yutopar", "definition": "An adrenergic beta-2 agonist used to control PREMATURE LABOR.\n    ", "id": "MESH:D012312"}
{"mention": "preterm labor", "mention_text": "This case illustrates that patients receiving ritodrine for preterm labor may risk interactions between the residual betamimetic effects of ritodrine and the effects of anesthetics during cesarean section. Such interactions may result in serious cardiovascular complications even after cessation of an infusion of ritodrine. Preoperative assessment should focus on cardiovascular status and serum potassium level. Delaying induction of anesthesia should be considered whenever possible. Careful fluid administration and cautious use of titrated doses of ephedrine are advised. After delivery of the infant, there should be no contraindication to the use of an alpha-adrenergic vasopressor such as phenylephrine to treat hypotensive patients with tachycardia.", "entity": "Obstetric Labor, Premature", "aliases": "Labor Premature Obstetric Preterm", "definition": "Onset of OBSTETRIC LABOR before term (TERM BIRTH) but usually after the FETUS has become viable. In humans, it occurs sometime during the 29th through 38th week of PREGNANCY. TOCOLYSIS inhibits premature labor and can prevent the BIRTH of premature infants (INFANT, PREMATURE).\n    ", "id": "MESH:D007752"}
{"mention": "cardiovascular complications", "mention_text": "This case illustrates that patients receiving ritodrine for preterm labor may risk interactions between the residual betamimetic effects of ritodrine and the effects of anesthetics during cesarean section. Such interactions may result in serious cardiovascular complications even after cessation of an infusion of ritodrine. Preoperative assessment should focus on cardiovascular status and serum potassium level. Delaying induction of anesthesia should be considered whenever possible. Careful fluid administration and cautious use of titrated doses of ephedrine are advised. After delivery of the infant, there should be no contraindication to the use of an alpha-adrenergic vasopressor such as phenylephrine to treat hypotensive patients with tachycardia.", "entity": "Cardiovascular Diseases", "aliases": "Cardiovascular Disease Diseases", "definition": "Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.\n    ", "id": "MESH:D002318"}
{"mention": "potassium", "mention_text": "This case illustrates that patients receiving ritodrine for preterm labor may risk interactions between the residual betamimetic effects of ritodrine and the effects of anesthetics during cesarean section. Such interactions may result in serious cardiovascular complications even after cessation of an infusion of ritodrine. Preoperative assessment should focus on cardiovascular status and serum potassium level. Delaying induction of anesthesia should be considered whenever possible. Careful fluid administration and cautious use of titrated doses of ephedrine are advised. After delivery of the infant, there should be no contraindication to the use of an alpha-adrenergic vasopressor such as phenylephrine to treat hypotensive patients with tachycardia.", "entity": "Potassium", "aliases": "Potassium", "definition": "An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.\n    ", "id": "MESH:D011188"}
{"mention": "ephedrine", "mention_text": "This case illustrates that patients receiving ritodrine for preterm labor may risk interactions between the residual betamimetic effects of ritodrine and the effects of anesthetics during cesarean section. Such interactions may result in serious cardiovascular complications even after cessation of an infusion of ritodrine. Preoperative assessment should focus on cardiovascular status and serum potassium level. Delaying induction of anesthesia should be considered whenever possible. Careful fluid administration and cautious use of titrated doses of ephedrine are advised. After delivery of the infant, there should be no contraindication to the use of an alpha-adrenergic vasopressor such as phenylephrine to treat hypotensive patients with tachycardia.", "entity": "Ephedrine", "aliases": "Ephedrine Erythro Isomer Hydrochloride Renaudin Sulfate of Brand Sal Phedrine Sal-Phedrine SalPhedrine Wendt", "definition": "A phenethylamine found in EPHEDRA SINICA. PSEUDOEPHEDRINE is an isomer. It is an alpha- and beta-adrenergic agonist that may also enhance release of norepinephrine. It has been used for asthma, heart failure, rhinitis, and urinary incontinence, and for its central nervous system stimulatory effects in the treatment of narcolepsy and depression. It has become less extensively used with the advent of more selective agonists.\n    ", "id": "MESH:D004809"}
{"mention": "phenylephrine", "mention_text": "This case illustrates that patients receiving ritodrine for preterm labor may risk interactions between the residual betamimetic effects of ritodrine and the effects of anesthetics during cesarean section. Such interactions may result in serious cardiovascular complications even after cessation of an infusion of ritodrine. Preoperative assessment should focus on cardiovascular status and serum potassium level. Delaying induction of anesthesia should be considered whenever possible. Careful fluid administration and cautious use of titrated doses of ephedrine are advised. After delivery of the infant, there should be no contraindication to the use of an alpha-adrenergic vasopressor such as phenylephrine to treat hypotensive patients with tachycardia.", "entity": "Phenylephrine", "aliases": "(R)-3-Hydroxy-alpha-((methylamino)methyl)benzenemethanol Metaoxedrin Metasympatol Mezaton Neo Synephrine Neo-Synephrine Neosynephrine Phenylephrine Hydrochloride Tannate", "definition": "An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.\n    ", "id": "MESH:D010656"}
{"mention": "hypotensive", "mention_text": "This case illustrates that patients receiving ritodrine for preterm labor may risk interactions between the residual betamimetic effects of ritodrine and the effects of anesthetics during cesarean section. Such interactions may result in serious cardiovascular complications even after cessation of an infusion of ritodrine. Preoperative assessment should focus on cardiovascular status and serum potassium level. Delaying induction of anesthesia should be considered whenever possible. Careful fluid administration and cautious use of titrated doses of ephedrine are advised. After delivery of the infant, there should be no contraindication to the use of an alpha-adrenergic vasopressor such as phenylephrine to treat hypotensive patients with tachycardia.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "tachycardia", "mention_text": "This case illustrates that patients receiving ritodrine for preterm labor may risk interactions between the residual betamimetic effects of ritodrine and the effects of anesthetics during cesarean section. Such interactions may result in serious cardiovascular complications even after cessation of an infusion of ritodrine. Preoperative assessment should focus on cardiovascular status and serum potassium level. Delaying induction of anesthesia should be considered whenever possible. Careful fluid administration and cautious use of titrated doses of ephedrine are advised. After delivery of the infant, there should be no contraindication to the use of an alpha-adrenergic vasopressor such as phenylephrine to treat hypotensive patients with tachycardia.", "entity": "Tachycardia", "aliases": "Tachyarrhythmia Tachyarrhythmias Tachycardia Tachycardias", "definition": "Abnormally rapid heartbeat, usually with a HEART RATE above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia.\n    ", "id": "MESH:D013610"}
{"mention": "estrogen", "mention_text": "Immunohistochemical, electron microscopic and morphometric studies of estrogen-induced rat prolactinomas after bromocriptine treatment.", "entity": "Estrogens", "aliases": "Agents Estrogenic Agonists Estrogen Receptor Compounds Effects Effect Estrogens", "definition": "Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds.\n    ", "id": "MESH:D004967"}
{"mention": "prolactinomas", "mention_text": "Immunohistochemical, electron microscopic and morphometric studies of estrogen-induced rat prolactinomas after bromocriptine treatment.", "entity": "Prolactinoma", "aliases": "Adenoma Lactotroph Prolactin-Secreting Pituitary Adenomas Macroprolactinoma Macroprolactinomas Microprolactinoma Microprolactinomas PRL Secreting PRL-Secreting Prolactin Prolactin-Producing Producing Prolactinoma Familial Prolactinomas", "definition": "A pituitary adenoma which secretes PROLACTIN, leading to HYPERPROLACTINEMIA. Clinical manifestations include AMENORRHEA; GALACTORRHEA; IMPOTENCE; HEADACHE; visual disturbances; and CEREBROSPINAL FLUID RHINORRHEA.\n    ", "id": "MESH:D015175"}
{"mention": "bromocriptine", "mention_text": "Immunohistochemical, electron microscopic and morphometric studies of estrogen-induced rat prolactinomas after bromocriptine treatment.", "entity": "Bromocriptine", "aliases": "2 Bromo alpha ergocryptine ergokryptine Bromoergocryptine Mesylate Methanesulfonate Bromoergokryptine 2-Bromo-alpha-ergocryptine 2-Bromo-alpha-ergokryptine 2-Bromoergocryptine 2-Bromoergokryptine Bromocriptin Bromocriptine Bromocryptin CB 154 CB-154 CB154 Parlodel", "definition": "A semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion.\n    ", "id": "MESH:D001971"}
{"mention": "bromocriptine", "mention_text": "To clarify the effects of bromocriptine on prolactinoma cells in vivo, immunohistochemical, ultrastructural and morphometrical analyses were applied to estrogen-induced rat prolactinoma cells 1 h and 6 h after injection of bromocriptine (3 mg/kg of body weight). One h after treatment, serum prolactin levels decreased markedly. Electron microscopy disclosed many secretory granules, slightly distorted rough endoplasmic reticulum, and partially dilated Golgi cisternae in the prolactinoma cells. Morphometric analysis revealed that the volume density of secretory granules increased, while the volume density of cytoplasmic microtubules decreased. These findings suggest that lowered serum prolactin levels in the early phase of bromocriptine treatment may result from an impaired secretion of prolactin due to decreasing numbers of cytoplasmic microtubules. At 6 h after injection, serum prolactin levels were still considerably lower than in controls. The prolactinoma cells at this time were well granulated, with vesiculated rough endoplasmic reticulum and markedly dilated Golgi cisternae. Electron microscopical immunohistochemistry revealed positive reaction products noted on the secretory granules, Golgi cisternae, and endoplasmic reticulum of the untreated rat prolactinoma cells. However, only secretory granules showed the positive reaction products for prolactin 6 h after bromocriptine treatment of the adenoma cells. An increase in the volume density of secretory granules and a decrease in the volume densities of rough endoplasmic reticulum and microtubules was determined by morphometric analysis, suggesting that bromocriptine inhibits protein synthesis as well as bringing about a disturbance of the prolactin secretion.", "entity": "Bromocriptine", "aliases": "2 Bromo alpha ergocryptine ergokryptine Bromoergocryptine Mesylate Methanesulfonate Bromoergokryptine 2-Bromo-alpha-ergocryptine 2-Bromo-alpha-ergokryptine 2-Bromoergocryptine 2-Bromoergokryptine Bromocriptin Bromocriptine Bromocryptin CB 154 CB-154 CB154 Parlodel", "definition": "A semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion.\n    ", "id": "MESH:D001971"}
{"mention": "prolactinoma", "mention_text": "To clarify the effects of bromocriptine on prolactinoma cells in vivo, immunohistochemical, ultrastructural and morphometrical analyses were applied to estrogen-induced rat prolactinoma cells 1 h and 6 h after injection of bromocriptine (3 mg/kg of body weight). One h after treatment, serum prolactin levels decreased markedly. Electron microscopy disclosed many secretory granules, slightly distorted rough endoplasmic reticulum, and partially dilated Golgi cisternae in the prolactinoma cells. Morphometric analysis revealed that the volume density of secretory granules increased, while the volume density of cytoplasmic microtubules decreased. These findings suggest that lowered serum prolactin levels in the early phase of bromocriptine treatment may result from an impaired secretion of prolactin due to decreasing numbers of cytoplasmic microtubules. At 6 h after injection, serum prolactin levels were still considerably lower than in controls. The prolactinoma cells at this time were well granulated, with vesiculated rough endoplasmic reticulum and markedly dilated Golgi cisternae. Electron microscopical immunohistochemistry revealed positive reaction products noted on the secretory granules, Golgi cisternae, and endoplasmic reticulum of the untreated rat prolactinoma cells. However, only secretory granules showed the positive reaction products for prolactin 6 h after bromocriptine treatment of the adenoma cells. An increase in the volume density of secretory granules and a decrease in the volume densities of rough endoplasmic reticulum and microtubules was determined by morphometric analysis, suggesting that bromocriptine inhibits protein synthesis as well as bringing about a disturbance of the prolactin secretion.", "entity": "Prolactinoma", "aliases": "Adenoma Lactotroph Prolactin-Secreting Pituitary Adenomas Macroprolactinoma Macroprolactinomas Microprolactinoma Microprolactinomas PRL Secreting PRL-Secreting Prolactin Prolactin-Producing Producing Prolactinoma Familial Prolactinomas", "definition": "A pituitary adenoma which secretes PROLACTIN, leading to HYPERPROLACTINEMIA. Clinical manifestations include AMENORRHEA; GALACTORRHEA; IMPOTENCE; HEADACHE; visual disturbances; and CEREBROSPINAL FLUID RHINORRHEA.\n    ", "id": "MESH:D015175"}
{"mention": "estrogen", "mention_text": "To clarify the effects of bromocriptine on prolactinoma cells in vivo, immunohistochemical, ultrastructural and morphometrical analyses were applied to estrogen-induced rat prolactinoma cells 1 h and 6 h after injection of bromocriptine (3 mg/kg of body weight). One h after treatment, serum prolactin levels decreased markedly. Electron microscopy disclosed many secretory granules, slightly distorted rough endoplasmic reticulum, and partially dilated Golgi cisternae in the prolactinoma cells. Morphometric analysis revealed that the volume density of secretory granules increased, while the volume density of cytoplasmic microtubules decreased. These findings suggest that lowered serum prolactin levels in the early phase of bromocriptine treatment may result from an impaired secretion of prolactin due to decreasing numbers of cytoplasmic microtubules. At 6 h after injection, serum prolactin levels were still considerably lower than in controls. The prolactinoma cells at this time were well granulated, with vesiculated rough endoplasmic reticulum and markedly dilated Golgi cisternae. Electron microscopical immunohistochemistry revealed positive reaction products noted on the secretory granules, Golgi cisternae, and endoplasmic reticulum of the untreated rat prolactinoma cells. However, only secretory granules showed the positive reaction products for prolactin 6 h after bromocriptine treatment of the adenoma cells. An increase in the volume density of secretory granules and a decrease in the volume densities of rough endoplasmic reticulum and microtubules was determined by morphometric analysis, suggesting that bromocriptine inhibits protein synthesis as well as bringing about a disturbance of the prolactin secretion.", "entity": "Estrogens", "aliases": "Agents Estrogenic Agonists Estrogen Receptor Compounds Effects Effect Estrogens", "definition": "Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds.\n    ", "id": "MESH:D004967"}
{"mention": "adenoma", "mention_text": "To clarify the effects of bromocriptine on prolactinoma cells in vivo, immunohistochemical, ultrastructural and morphometrical analyses were applied to estrogen-induced rat prolactinoma cells 1 h and 6 h after injection of bromocriptine (3 mg/kg of body weight). One h after treatment, serum prolactin levels decreased markedly. Electron microscopy disclosed many secretory granules, slightly distorted rough endoplasmic reticulum, and partially dilated Golgi cisternae in the prolactinoma cells. Morphometric analysis revealed that the volume density of secretory granules increased, while the volume density of cytoplasmic microtubules decreased. These findings suggest that lowered serum prolactin levels in the early phase of bromocriptine treatment may result from an impaired secretion of prolactin due to decreasing numbers of cytoplasmic microtubules. At 6 h after injection, serum prolactin levels were still considerably lower than in controls. The prolactinoma cells at this time were well granulated, with vesiculated rough endoplasmic reticulum and markedly dilated Golgi cisternae. Electron microscopical immunohistochemistry revealed positive reaction products noted on the secretory granules, Golgi cisternae, and endoplasmic reticulum of the untreated rat prolactinoma cells. However, only secretory granules showed the positive reaction products for prolactin 6 h after bromocriptine treatment of the adenoma cells. An increase in the volume density of secretory granules and a decrease in the volume densities of rough endoplasmic reticulum and microtubules was determined by morphometric analysis, suggesting that bromocriptine inhibits protein synthesis as well as bringing about a disturbance of the prolactin secretion.", "entity": "Adenoma", "aliases": "Adenoma Basal Cell Follicular Microcystic Monomorphic Papillary Trabecular Adenomas", "definition": "A benign epithelial tumor with a glandular organization.\n    ", "id": "MESH:D000236"}
{"mention": "prednisolone", "mention_text": "On two paradoxical side-effects of prednisolone in rats, ribosomal RNA biosyntheses, and a mechanism of action.", "entity": "Prednisolone", "aliases": "Di Adreson F Di-Adreson-F DiAdresonF Predate Prednisolone Predonine", "definition": "A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states.\n    ", "id": "MESH:D011239"}
{"mention": "Liver enlargement", "mention_text": "Liver enlargement and muscle wastage occurred in Wistar rats following the subcutaneous administration of prednisolone. In the liver both the content of RNA and the biosynthesis of ribosomal RNA increased while both the RNA content and ribosomal RNA biosynthesis were reduced in the gastrocnemius muscle. It is suggested that the drug acted in a selective and tissue-specific manner to enhance ribosomal RNA synthesis in the liver and depress such synthesis in the muscle. This view supports the contention that the liver and muscle are independent sites of prednisolone action.", "entity": "Hepatomegaly", "aliases": "Enlarged Liver Hepatomegaly", "definition": "Enlargement of the liver.\n    ", "id": "MESH:D006529"}
{"mention": "muscle wastage", "mention_text": "Liver enlargement and muscle wastage occurred in Wistar rats following the subcutaneous administration of prednisolone. In the liver both the content of RNA and the biosynthesis of ribosomal RNA increased while both the RNA content and ribosomal RNA biosynthesis were reduced in the gastrocnemius muscle. It is suggested that the drug acted in a selective and tissue-specific manner to enhance ribosomal RNA synthesis in the liver and depress such synthesis in the muscle. This view supports the contention that the liver and muscle are independent sites of prednisolone action.", "entity": "Muscular Atrophy", "aliases": "Atrophies Muscle Muscular Neurogenic Neurotrophic Atrophy", "definition": "Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation.\n    ", "id": "MESH:D009133"}
{"mention": "prednisolone", "mention_text": "Liver enlargement and muscle wastage occurred in Wistar rats following the subcutaneous administration of prednisolone. In the liver both the content of RNA and the biosynthesis of ribosomal RNA increased while both the RNA content and ribosomal RNA biosynthesis were reduced in the gastrocnemius muscle. It is suggested that the drug acted in a selective and tissue-specific manner to enhance ribosomal RNA synthesis in the liver and depress such synthesis in the muscle. This view supports the contention that the liver and muscle are independent sites of prednisolone action.", "entity": "Prednisolone", "aliases": "Di Adreson F Di-Adreson-F DiAdresonF Predate Prednisolone Predonine", "definition": "A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states.\n    ", "id": "MESH:D011239"}
{"mention": "midazolam", "mention_text": "Possible intramuscular midazolam-associated cardiorespiratory arrest and death.", "entity": "Midazolam", "aliases": "Dormicum Hydrochloride Midazolam Maleate Ro 21 3981 21-3981 213981 Versed", "definition": "A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH.\n    ", "id": "MESH:D008874"}
{"mention": "cardiorespiratory arrest", "mention_text": "Possible intramuscular midazolam-associated cardiorespiratory arrest and death.", "entity": "Heart Arrest", "aliases": "Arrest Cardiac Cardiopulmonary Heart Asystole Asystoles", "definition": "Cessation of heart beat or MYOCARDIAL CONTRACTION. If it is treated within a few minutes, heart arrest can be reversed in most cases to normal cardiac rhythm and effective circulation.\n    ", "id": "MESH:D006323"}
{"mention": "death", "mention_text": "Possible intramuscular midazolam-associated cardiorespiratory arrest and death.", "entity": "Death", "aliases": "Cardiac Death Determination of Near-Death Experience", "definition": "Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.\n    ", "id": "MESH:D003643"}
{"mention": "Midazolam hydrochloride", "mention_text": "Midazolam hydrochloride is commonly used for dental or endoscopic procedures. Although generally consisted safe when given intramuscularly, intravenous administration is known to cause respiratory and cardiovascular depression. This report describes the first published case of cardiorespiratory arrest and death associated with intramuscular administration of midazolam. Information regarding midazolam use is reviewed to provide recommendation for safe administration.", "entity": "Midazolam", "aliases": "Dormicum Hydrochloride Midazolam Maleate Ro 21 3981 21-3981 213981 Versed", "definition": "A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH.\n    ", "id": "MESH:D008874"}
{"mention": "cardiovascular depression", "mention_text": "Midazolam hydrochloride is commonly used for dental or endoscopic procedures. Although generally consisted safe when given intramuscularly, intravenous administration is known to cause respiratory and cardiovascular depression. This report describes the first published case of cardiorespiratory arrest and death associated with intramuscular administration of midazolam. Information regarding midazolam use is reviewed to provide recommendation for safe administration.", "entity": "Cardiovascular Diseases", "aliases": "Cardiovascular Disease Diseases", "definition": "Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.\n    ", "id": "MESH:D002318"}
{"mention": "cardiorespiratory arrest", "mention_text": "Midazolam hydrochloride is commonly used for dental or endoscopic procedures. Although generally consisted safe when given intramuscularly, intravenous administration is known to cause respiratory and cardiovascular depression. This report describes the first published case of cardiorespiratory arrest and death associated with intramuscular administration of midazolam. Information regarding midazolam use is reviewed to provide recommendation for safe administration.", "entity": "Heart Arrest", "aliases": "Arrest Cardiac Cardiopulmonary Heart Asystole Asystoles", "definition": "Cessation of heart beat or MYOCARDIAL CONTRACTION. If it is treated within a few minutes, heart arrest can be reversed in most cases to normal cardiac rhythm and effective circulation.\n    ", "id": "MESH:D006323"}
{"mention": "death", "mention_text": "Midazolam hydrochloride is commonly used for dental or endoscopic procedures. Although generally consisted safe when given intramuscularly, intravenous administration is known to cause respiratory and cardiovascular depression. This report describes the first published case of cardiorespiratory arrest and death associated with intramuscular administration of midazolam. Information regarding midazolam use is reviewed to provide recommendation for safe administration.", "entity": "Death", "aliases": "Cardiac Death Determination of Near-Death Experience", "definition": "Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.\n    ", "id": "MESH:D003643"}
{"mention": "midazolam", "mention_text": "Midazolam hydrochloride is commonly used for dental or endoscopic procedures. Although generally consisted safe when given intramuscularly, intravenous administration is known to cause respiratory and cardiovascular depression. This report describes the first published case of cardiorespiratory arrest and death associated with intramuscular administration of midazolam. Information regarding midazolam use is reviewed to provide recommendation for safe administration.", "entity": "Midazolam", "aliases": "Dormicum Hydrochloride Midazolam Maleate Ro 21 3981 21-3981 213981 Versed", "definition": "A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH.\n    ", "id": "MESH:D008874"}
{"mention": "epilepsy", "mention_text": "Serial epilepsy caused by levodopa/carbidopa administration in two patients on hemodialysis.", "entity": "Epilepsy", "aliases": "Aura Auras Awakening Epilepsy Cryptogenic Epilepsies Epileptic Seizure Seizures Disorder Disorders Single", "definition": "A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313)\n    ", "id": "MESH:D004827"}
{"mention": "levodopa/carbidopa", "mention_text": "Serial epilepsy caused by levodopa/carbidopa administration in two patients on hemodialysis.", "entity": "carbidopa, levodopa drug combination", "aliases": "Grifoparkin IPX066 Nacom Nakom Parcopa Sinemet CR CR4 carbidopa - levodopa drug combination duodopa tidomed", "definition": "", "id": "MESH:C009265"}
{"mention": "chronic renal failure", "mention_text": "Two patients with similar clinical features are presented: both patients had chronic renal failure, on hemodialysis for many years but recently begun on a high-flux dialyzer; both had been receiving a carbidopa/levodopa preparation; and both had the onset of hallucinosis and recurrent seizures, which were refractory to anticonvulsants. The first patient died without a diagnosis; the second patient had a dramatic recovery following the administration of vitamin B6. Neither patient was considered to have a renal state sufficiently severe enough to explain their presentation.", "entity": "Kidney Failure, Chronic", "aliases": "Chronic Kidney Failure Renal Disease End-Stage ESRD End Stage", "definition": "The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.\n    ", "id": "MESH:D007676"}
{"mention": "carbidopa/levodopa", "mention_text": "Two patients with similar clinical features are presented: both patients had chronic renal failure, on hemodialysis for many years but recently begun on a high-flux dialyzer; both had been receiving a carbidopa/levodopa preparation; and both had the onset of hallucinosis and recurrent seizures, which were refractory to anticonvulsants. The first patient died without a diagnosis; the second patient had a dramatic recovery following the administration of vitamin B6. Neither patient was considered to have a renal state sufficiently severe enough to explain their presentation.", "entity": "carbidopa, levodopa drug combination", "aliases": "Grifoparkin IPX066 Nacom Nakom Parcopa Sinemet CR CR4 carbidopa - levodopa drug combination duodopa tidomed", "definition": "", "id": "MESH:C009265"}
{"mention": "hallucinosis", "mention_text": "Two patients with similar clinical features are presented: both patients had chronic renal failure, on hemodialysis for many years but recently begun on a high-flux dialyzer; both had been receiving a carbidopa/levodopa preparation; and both had the onset of hallucinosis and recurrent seizures, which were refractory to anticonvulsants. The first patient died without a diagnosis; the second patient had a dramatic recovery following the administration of vitamin B6. Neither patient was considered to have a renal state sufficiently severe enough to explain their presentation.", "entity": "Mental Disorders", "aliases": "Behavior Disorders Diagnosis Psychiatric Disorder Mental", "definition": "Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.\n    ", "id": "MESH:D001523"}
{"mention": "seizures", "mention_text": "Two patients with similar clinical features are presented: both patients had chronic renal failure, on hemodialysis for many years but recently begun on a high-flux dialyzer; both had been receiving a carbidopa/levodopa preparation; and both had the onset of hallucinosis and recurrent seizures, which were refractory to anticonvulsants. The first patient died without a diagnosis; the second patient had a dramatic recovery following the administration of vitamin B6. Neither patient was considered to have a renal state sufficiently severe enough to explain their presentation.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "vitamin B6", "mention_text": "Two patients with similar clinical features are presented: both patients had chronic renal failure, on hemodialysis for many years but recently begun on a high-flux dialyzer; both had been receiving a carbidopa/levodopa preparation; and both had the onset of hallucinosis and recurrent seizures, which were refractory to anticonvulsants. The first patient died without a diagnosis; the second patient had a dramatic recovery following the administration of vitamin B6. Neither patient was considered to have a renal state sufficiently severe enough to explain their presentation.", "entity": "Vitamin B 6", "aliases": "Vitamin B 6 B6", "definition": "VITAMIN B 6 refers to several PICOLINES (especially PYRIDOXINE; PYRIDOXAL; & PYRIDOXAMINE) that are efficiently converted by the body to PYRIDOXAL PHOSPHATE which is a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, and aminolevulinic acid. During transamination of amino acids, pyridoxal phosphate is transiently converted into PYRIDOXAMINE phosphate. Although pyridoxine and Vitamin B 6 are still frequently used as synonyms, especially by medical researchers, this practice is erroneous and sometimes misleading (EE Snell; Ann NY Acad Sci, vol 585 pg 1, 1990). Most of vitamin B6 is eventually degraded to PYRIDOXIC ACID and excreted in the urine.\n    ", "id": "MESH:D025101"}
{"mention": "L-alpha-glyceryl-phosphorylcholine", "mention_text": "Effect of L-alpha-glyceryl-phosphorylcholine on amnesia caused by scopolamine.", "entity": "Glycerylphosphorylcholine", "aliases": "3-Phosphocholine Glycerol Alfoscerate Choline Alphoscerate Glycerophosphate 3 Phosphocholine Glycerophosphorylcholine Glycerylphosphorylcholine L alpha L-alpha-Glycerylphosphorylcholine", "definition": "A component of PHOSPHATIDYLCHOLINES or LECITHINS, in which the two hydroxy groups of GLYCEROL are esterified with fatty acids. (From Stedman, 26th ed) It counteracts the effects of urea on enzymes and other macromolecules.\n    ", "id": "MESH:D005997"}
{"mention": "amnesia", "mention_text": "Effect of L-alpha-glyceryl-phosphorylcholine on amnesia caused by scopolamine.", "entity": "Amnesia", "aliases": "Amnesia Memory Loss Dissociative Global Hysterical Tactile Temporary Amnesia-Memory Losses Amnesias Amnestic State States", "definition": "Pathologic partial or complete loss of the ability to recall past experiences (AMNESIA, RETROGRADE) or to form new memories (AMNESIA, ANTEROGRADE). This condition may be of organic or psychologic origin. Organic forms of amnesia are usually associated with dysfunction of the DIENCEPHALON or HIPPOCAMPUS. (From Adams et al., Principles of Neurology, 6th ed, pp426-7)\n    ", "id": "MESH:D000647"}
{"mention": "scopolamine", "mention_text": "Effect of L-alpha-glyceryl-phosphorylcholine on amnesia caused by scopolamine.", "entity": "Scopolamine Hydrobromide", "aliases": "Alcon Brand of Scopolamine Hydrobromide Boro Scopol Boro-Scopol BoroScopol Bull Cooper Hamilton Hope Hyoscine Inibisa Isopto Kwells Novartis Consumer Health Renaudin Roche Scoburen Scopace Scopoderm TTS Transderm Scop V Transderm-V Travacalm HO Vorigeno Winzer Borate", "definition": "An alkaloid from SOLANACEAE, especially DATURA and SCOPOLIA. Scopolamine and its quaternary derivatives act as antimuscarinics like ATROPINE, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in URINARY INCONTINENCE, in MOTION SICKNESS, as an antispasmodic, and as a mydriatic and cycloplegic.\n    ", "id": "MESH:D012601"}
{"mention": "L-alpha-glycerylphosphorylcholine", "mention_text": "The present study was carried out to test the effects of L-alpha-glycerylphosphorylcholine (L-alpha-GFC) on memory impairment induced by scopolamine in man. Thirty-two healthy young volunteers were randomly allocated to four different groups. They were given a ten day pretreatment with either L-alpha-GFC or placebo, p.o., and on the eleventh day either scopolamine or placebo, i.m. Before and 0.5, 1, 2, 3, and 6 h after injection the subjects were given attention and mnemonic tests. The findings of this study indicate that the drug is able to antagonize impairment of attention and memory induced by scopolamine.", "entity": "Glycerylphosphorylcholine", "aliases": "3-Phosphocholine Glycerol Alfoscerate Choline Alphoscerate Glycerophosphate 3 Phosphocholine Glycerophosphorylcholine Glycerylphosphorylcholine L alpha L-alpha-Glycerylphosphorylcholine", "definition": "A component of PHOSPHATIDYLCHOLINES or LECITHINS, in which the two hydroxy groups of GLYCEROL are esterified with fatty acids. (From Stedman, 26th ed) It counteracts the effects of urea on enzymes and other macromolecules.\n    ", "id": "MESH:D005997"}
{"mention": "L-alpha-GFC", "mention_text": "The present study was carried out to test the effects of L-alpha-glycerylphosphorylcholine (L-alpha-GFC) on memory impairment induced by scopolamine in man. Thirty-two healthy young volunteers were randomly allocated to four different groups. They were given a ten day pretreatment with either L-alpha-GFC or placebo, p.o., and on the eleventh day either scopolamine or placebo, i.m. Before and 0.5, 1, 2, 3, and 6 h after injection the subjects were given attention and mnemonic tests. The findings of this study indicate that the drug is able to antagonize impairment of attention and memory induced by scopolamine.", "entity": "Glycerylphosphorylcholine", "aliases": "3-Phosphocholine Glycerol Alfoscerate Choline Alphoscerate Glycerophosphate 3 Phosphocholine Glycerophosphorylcholine Glycerylphosphorylcholine L alpha L-alpha-Glycerylphosphorylcholine", "definition": "A component of PHOSPHATIDYLCHOLINES or LECITHINS, in which the two hydroxy groups of GLYCEROL are esterified with fatty acids. (From Stedman, 26th ed) It counteracts the effects of urea on enzymes and other macromolecules.\n    ", "id": "MESH:D005997"}
{"mention": "memory impairment", "mention_text": "The present study was carried out to test the effects of L-alpha-glycerylphosphorylcholine (L-alpha-GFC) on memory impairment induced by scopolamine in man. Thirty-two healthy young volunteers were randomly allocated to four different groups. They were given a ten day pretreatment with either L-alpha-GFC or placebo, p.o., and on the eleventh day either scopolamine or placebo, i.m. Before and 0.5, 1, 2, 3, and 6 h after injection the subjects were given attention and mnemonic tests. The findings of this study indicate that the drug is able to antagonize impairment of attention and memory induced by scopolamine.", "entity": "Memory Disorders", "aliases": "Age Related Memory Disorders Age-Related Disorder Cognitive Retention Deficit Deficits Semantic Spatial Loss Losses", "definition": "Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions.\n    ", "id": "MESH:D008569"}
{"mention": "scopolamine", "mention_text": "The present study was carried out to test the effects of L-alpha-glycerylphosphorylcholine (L-alpha-GFC) on memory impairment induced by scopolamine in man. Thirty-two healthy young volunteers were randomly allocated to four different groups. They were given a ten day pretreatment with either L-alpha-GFC or placebo, p.o., and on the eleventh day either scopolamine or placebo, i.m. Before and 0.5, 1, 2, 3, and 6 h after injection the subjects were given attention and mnemonic tests. The findings of this study indicate that the drug is able to antagonize impairment of attention and memory induced by scopolamine.", "entity": "Scopolamine Hydrobromide", "aliases": "Alcon Brand of Scopolamine Hydrobromide Boro Scopol Boro-Scopol BoroScopol Bull Cooper Hamilton Hope Hyoscine Inibisa Isopto Kwells Novartis Consumer Health Renaudin Roche Scoburen Scopace Scopoderm TTS Transderm Scop V Transderm-V Travacalm HO Vorigeno Winzer Borate", "definition": "An alkaloid from SOLANACEAE, especially DATURA and SCOPOLIA. Scopolamine and its quaternary derivatives act as antimuscarinics like ATROPINE, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in URINARY INCONTINENCE, in MOTION SICKNESS, as an antispasmodic, and as a mydriatic and cycloplegic.\n    ", "id": "MESH:D012601"}
{"mention": "impairment of attention and memory", "mention_text": "The present study was carried out to test the effects of L-alpha-glycerylphosphorylcholine (L-alpha-GFC) on memory impairment induced by scopolamine in man. Thirty-two healthy young volunteers were randomly allocated to four different groups. They were given a ten day pretreatment with either L-alpha-GFC or placebo, p.o., and on the eleventh day either scopolamine or placebo, i.m. Before and 0.5, 1, 2, 3, and 6 h after injection the subjects were given attention and mnemonic tests. The findings of this study indicate that the drug is able to antagonize impairment of attention and memory induced by scopolamine.", "entity": "Memory Disorders", "aliases": "Age Related Memory Disorders Age-Related Disorder Cognitive Retention Deficit Deficits Semantic Spatial Loss Losses", "definition": "Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions.\n    ", "id": "MESH:D008569"}
{"mention": "Seizures", "mention_text": "Seizures induced by the cocaine metabolite benzoylecgonine in rats.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "cocaine", "mention_text": "Seizures induced by the cocaine metabolite benzoylecgonine in rats.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "benzoylecgonine", "mention_text": "Seizures induced by the cocaine metabolite benzoylecgonine in rats.", "entity": "benzoylecgonine", "aliases": "benzoyl ecgonine benzoylecgonine (1R-(2-endo,3-exo))-isomer", "definition": "", "id": "MESH:C005618"}
{"mention": "cocaine", "mention_text": "The half-life (t1/2) of cocaine is relatively short, but some of the consequences of its use, such as seizures and strokes, can occur hours after exposure. This led us to hypothesize that a metabolite of cocaine may be responsible for some of those delayed sequelae. We evaluated the potential of the major metabolite of cocaine, benzoylecgonine (BE), to cause seizures. Two separate equimolar doses (0.2 and 0.4 mumol) of either cocaine or BE were injected ventricularly in unanesthetized juvenile rats. Treated rats were then evaluated for incidence, latency, and seizure pattern or for locomotor activity in animals without seizures. BE-Induced seizures occurred more frequently and had significantly longer latencies than those induced by equimolar amounts of cocaine. Whereas cocaine-induced seizures were best characterized as brief, generalized, and tonic and resulted in death, those induced by BE were prolonged, often multiple and mixed in type, and rarely resulted in death. Electrical recordings from the hippocampus showed a rhythmic progression in EEG frequency and voltage with clinical seizure expression. BE-Injected rats that did not have seizures had significantly more locomotor activity than cocaine-injected animals without seizures. The finding that cocaine- and BE-induced seizures differ in several respects suggests more than one mechanism for cocaine-induced seizures and emphasizes the importance of a cocaine metabolite, BE.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "seizures", "mention_text": "The half-life (t1/2) of cocaine is relatively short, but some of the consequences of its use, such as seizures and strokes, can occur hours after exposure. This led us to hypothesize that a metabolite of cocaine may be responsible for some of those delayed sequelae. We evaluated the potential of the major metabolite of cocaine, benzoylecgonine (BE), to cause seizures. Two separate equimolar doses (0.2 and 0.4 mumol) of either cocaine or BE were injected ventricularly in unanesthetized juvenile rats. Treated rats were then evaluated for incidence, latency, and seizure pattern or for locomotor activity in animals without seizures. BE-Induced seizures occurred more frequently and had significantly longer latencies than those induced by equimolar amounts of cocaine. Whereas cocaine-induced seizures were best characterized as brief, generalized, and tonic and resulted in death, those induced by BE were prolonged, often multiple and mixed in type, and rarely resulted in death. Electrical recordings from the hippocampus showed a rhythmic progression in EEG frequency and voltage with clinical seizure expression. BE-Injected rats that did not have seizures had significantly more locomotor activity than cocaine-injected animals without seizures. The finding that cocaine- and BE-induced seizures differ in several respects suggests more than one mechanism for cocaine-induced seizures and emphasizes the importance of a cocaine metabolite, BE.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "strokes", "mention_text": "The half-life (t1/2) of cocaine is relatively short, but some of the consequences of its use, such as seizures and strokes, can occur hours after exposure. This led us to hypothesize that a metabolite of cocaine may be responsible for some of those delayed sequelae. We evaluated the potential of the major metabolite of cocaine, benzoylecgonine (BE), to cause seizures. Two separate equimolar doses (0.2 and 0.4 mumol) of either cocaine or BE were injected ventricularly in unanesthetized juvenile rats. Treated rats were then evaluated for incidence, latency, and seizure pattern or for locomotor activity in animals without seizures. BE-Induced seizures occurred more frequently and had significantly longer latencies than those induced by equimolar amounts of cocaine. Whereas cocaine-induced seizures were best characterized as brief, generalized, and tonic and resulted in death, those induced by BE were prolonged, often multiple and mixed in type, and rarely resulted in death. Electrical recordings from the hippocampus showed a rhythmic progression in EEG frequency and voltage with clinical seizure expression. BE-Injected rats that did not have seizures had significantly more locomotor activity than cocaine-injected animals without seizures. The finding that cocaine- and BE-induced seizures differ in several respects suggests more than one mechanism for cocaine-induced seizures and emphasizes the importance of a cocaine metabolite, BE.", "entity": "Stroke", "aliases": "Acute Cerebrovascular Accident Accidents Stroke Strokes Apoplexy Brain Vascular CVA (Cerebrovascular Accident) CVAs Cerebral", "definition": "A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)\n    ", "id": "MESH:D020521"}
{"mention": "benzoylecgonine", "mention_text": "The half-life (t1/2) of cocaine is relatively short, but some of the consequences of its use, such as seizures and strokes, can occur hours after exposure. This led us to hypothesize that a metabolite of cocaine may be responsible for some of those delayed sequelae. We evaluated the potential of the major metabolite of cocaine, benzoylecgonine (BE), to cause seizures. Two separate equimolar doses (0.2 and 0.4 mumol) of either cocaine or BE were injected ventricularly in unanesthetized juvenile rats. Treated rats were then evaluated for incidence, latency, and seizure pattern or for locomotor activity in animals without seizures. BE-Induced seizures occurred more frequently and had significantly longer latencies than those induced by equimolar amounts of cocaine. Whereas cocaine-induced seizures were best characterized as brief, generalized, and tonic and resulted in death, those induced by BE were prolonged, often multiple and mixed in type, and rarely resulted in death. Electrical recordings from the hippocampus showed a rhythmic progression in EEG frequency and voltage with clinical seizure expression. BE-Injected rats that did not have seizures had significantly more locomotor activity than cocaine-injected animals without seizures. The finding that cocaine- and BE-induced seizures differ in several respects suggests more than one mechanism for cocaine-induced seizures and emphasizes the importance of a cocaine metabolite, BE.", "entity": "benzoylecgonine", "aliases": "benzoyl ecgonine benzoylecgonine (1R-(2-endo,3-exo))-isomer", "definition": "", "id": "MESH:C005618"}
{"mention": "BE", "mention_text": "The half-life (t1/2) of cocaine is relatively short, but some of the consequences of its use, such as seizures and strokes, can occur hours after exposure. This led us to hypothesize that a metabolite of cocaine may be responsible for some of those delayed sequelae. We evaluated the potential of the major metabolite of cocaine, benzoylecgonine (BE), to cause seizures. Two separate equimolar doses (0.2 and 0.4 mumol) of either cocaine or BE were injected ventricularly in unanesthetized juvenile rats. Treated rats were then evaluated for incidence, latency, and seizure pattern or for locomotor activity in animals without seizures. BE-Induced seizures occurred more frequently and had significantly longer latencies than those induced by equimolar amounts of cocaine. Whereas cocaine-induced seizures were best characterized as brief, generalized, and tonic and resulted in death, those induced by BE were prolonged, often multiple and mixed in type, and rarely resulted in death. Electrical recordings from the hippocampus showed a rhythmic progression in EEG frequency and voltage with clinical seizure expression. BE-Injected rats that did not have seizures had significantly more locomotor activity than cocaine-injected animals without seizures. The finding that cocaine- and BE-induced seizures differ in several respects suggests more than one mechanism for cocaine-induced seizures and emphasizes the importance of a cocaine metabolite, BE.", "entity": "benzoylecgonine", "aliases": "benzoyl ecgonine benzoylecgonine (1R-(2-endo,3-exo))-isomer", "definition": "", "id": "MESH:C005618"}
{"mention": "seizure", "mention_text": "The half-life (t1/2) of cocaine is relatively short, but some of the consequences of its use, such as seizures and strokes, can occur hours after exposure. This led us to hypothesize that a metabolite of cocaine may be responsible for some of those delayed sequelae. We evaluated the potential of the major metabolite of cocaine, benzoylecgonine (BE), to cause seizures. Two separate equimolar doses (0.2 and 0.4 mumol) of either cocaine or BE were injected ventricularly in unanesthetized juvenile rats. Treated rats were then evaluated for incidence, latency, and seizure pattern or for locomotor activity in animals without seizures. BE-Induced seizures occurred more frequently and had significantly longer latencies than those induced by equimolar amounts of cocaine. Whereas cocaine-induced seizures were best characterized as brief, generalized, and tonic and resulted in death, those induced by BE were prolonged, often multiple and mixed in type, and rarely resulted in death. Electrical recordings from the hippocampus showed a rhythmic progression in EEG frequency and voltage with clinical seizure expression. BE-Injected rats that did not have seizures had significantly more locomotor activity than cocaine-injected animals without seizures. The finding that cocaine- and BE-induced seizures differ in several respects suggests more than one mechanism for cocaine-induced seizures and emphasizes the importance of a cocaine metabolite, BE.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "death", "mention_text": "The half-life (t1/2) of cocaine is relatively short, but some of the consequences of its use, such as seizures and strokes, can occur hours after exposure. This led us to hypothesize that a metabolite of cocaine may be responsible for some of those delayed sequelae. We evaluated the potential of the major metabolite of cocaine, benzoylecgonine (BE), to cause seizures. Two separate equimolar doses (0.2 and 0.4 mumol) of either cocaine or BE were injected ventricularly in unanesthetized juvenile rats. Treated rats were then evaluated for incidence, latency, and seizure pattern or for locomotor activity in animals without seizures. BE-Induced seizures occurred more frequently and had significantly longer latencies than those induced by equimolar amounts of cocaine. Whereas cocaine-induced seizures were best characterized as brief, generalized, and tonic and resulted in death, those induced by BE were prolonged, often multiple and mixed in type, and rarely resulted in death. Electrical recordings from the hippocampus showed a rhythmic progression in EEG frequency and voltage with clinical seizure expression. BE-Injected rats that did not have seizures had significantly more locomotor activity than cocaine-injected animals without seizures. The finding that cocaine- and BE-induced seizures differ in several respects suggests more than one mechanism for cocaine-induced seizures and emphasizes the importance of a cocaine metabolite, BE.", "entity": "Death", "aliases": "Cardiac Death Determination of Near-Death Experience", "definition": "Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.\n    ", "id": "MESH:D003643"}
{"mention": "amphetamine", "mention_text": "Protection against amphetamine-induced neurotoxicity toward striatal dopamine neurons in rodents by LY274614, an excitatory amino acid antagonist.", "entity": "Amphetamine", "aliases": "Amfetamine Amphetamine Sulfate (2:1) Centramina Desoxynorephedrin Fenamine Levoamphetamine Miquel Brand of Mydrial Phenamine Phenopromin Thyramine l l-Amphetamine levo levo-Amphetamine", "definition": "A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE.\n    ", "id": "MESH:D000661"}
{"mention": "neurotoxicity", "mention_text": "Protection against amphetamine-induced neurotoxicity toward striatal dopamine neurons in rodents by LY274614, an excitatory amino acid antagonist.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "dopamine", "mention_text": "Protection against amphetamine-induced neurotoxicity toward striatal dopamine neurons in rodents by LY274614, an excitatory amino acid antagonist.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "LY274614", "mention_text": "Protection against amphetamine-induced neurotoxicity toward striatal dopamine neurons in rodents by LY274614, an excitatory amino acid antagonist.", "entity": "LY 274614", "aliases": "LY 274614 LY-274614 LY274614", "definition": "", "id": "MESH:C070935"}
{"mention": "amino acid", "mention_text": "Protection against amphetamine-induced neurotoxicity toward striatal dopamine neurons in rodents by LY274614, an excitatory amino acid antagonist.", "entity": "Amino Acids", "aliases": "Acids Amino", "definition": "Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.\n    ", "id": "MESH:D000596"}
{"mention": "LY274614", "mention_text": "LY274614, 3SR,4aRS,6SR,8aRS-6-[phosphonomethyl]decahydr oisoquinoline-3- carboxylic acid, has been described as a potent antagonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Here its ability to antagonize the prolonged depletion of dopamine in the striatum by amphetamine in iprindole-treated rats is reported. A single 18.4 mg/kg (i.p.) dose of (+/-)-amphetamine hemisulfate, given to rats pretreated with iprindole, resulted in persistent depletion of dopamine in the striatum 1 week later. This prolonged depletion of dopamine in the striatum was antagonized by dizocilpine (MK-801, a non-competitive antagonist of NMDA receptors) or by LY274614 (a competitive antagonist of NMDA receptors). The protective effect of LY274614 was dose-dependent, being maximum at 10-40 mgkg (i.p.). A 10 mg/kg dose of LY274614 was effective in antagonizing the depletion of dopamine in the striatum, when given as long as 8 hr prior to amphetamine but not when given 24 hr prior to amphetamine. Depletion of dopamine in the striatum was also antagonized when LY274614 was given after the injection of amphetamine; LY274614 protected when given up to 4 hr after but not when given 8 or 24 hr after amphetamine. The prolonged depletion of dopamine in the striatum in mice, given multiple injections of methamphetamine, was also antagonized dose-dependently and completely by LY274614. The data strengthen the evidence that the neurotoxic effect of amphetamine and related compounds toward nigrostriatal dopamine neurons involves NMDA receptors and that LY274614 is an NMDA receptor antagonist with long-lasting in vivo effects in rats.", "entity": "LY 274614", "aliases": "LY 274614 LY-274614 LY274614", "definition": "", "id": "MESH:C070935"}
{"mention": "3SR,4aRS,6SR,8aRS-6-[phosphonomethyl]decahydr oisoquinoline-3- carboxylic acid", "mention_text": "LY274614, 3SR,4aRS,6SR,8aRS-6-[phosphonomethyl]decahydr oisoquinoline-3- carboxylic acid, has been described as a potent antagonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Here its ability to antagonize the prolonged depletion of dopamine in the striatum by amphetamine in iprindole-treated rats is reported. A single 18.4 mg/kg (i.p.) dose of (+/-)-amphetamine hemisulfate, given to rats pretreated with iprindole, resulted in persistent depletion of dopamine in the striatum 1 week later. This prolonged depletion of dopamine in the striatum was antagonized by dizocilpine (MK-801, a non-competitive antagonist of NMDA receptors) or by LY274614 (a competitive antagonist of NMDA receptors). The protective effect of LY274614 was dose-dependent, being maximum at 10-40 mgkg (i.p.). A 10 mg/kg dose of LY274614 was effective in antagonizing the depletion of dopamine in the striatum, when given as long as 8 hr prior to amphetamine but not when given 24 hr prior to amphetamine. Depletion of dopamine in the striatum was also antagonized when LY274614 was given after the injection of amphetamine; LY274614 protected when given up to 4 hr after but not when given 8 or 24 hr after amphetamine. The prolonged depletion of dopamine in the striatum in mice, given multiple injections of methamphetamine, was also antagonized dose-dependently and completely by LY274614. The data strengthen the evidence that the neurotoxic effect of amphetamine and related compounds toward nigrostriatal dopamine neurons involves NMDA receptors and that LY274614 is an NMDA receptor antagonist with long-lasting in vivo effects in rats.", "entity": "LY 274614", "aliases": "LY 274614 LY-274614 LY274614", "definition": "", "id": "MESH:C070935"}
{"mention": "N-methyl-D-aspartate", "mention_text": "LY274614, 3SR,4aRS,6SR,8aRS-6-[phosphonomethyl]decahydr oisoquinoline-3- carboxylic acid, has been described as a potent antagonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Here its ability to antagonize the prolonged depletion of dopamine in the striatum by amphetamine in iprindole-treated rats is reported. A single 18.4 mg/kg (i.p.) dose of (+/-)-amphetamine hemisulfate, given to rats pretreated with iprindole, resulted in persistent depletion of dopamine in the striatum 1 week later. This prolonged depletion of dopamine in the striatum was antagonized by dizocilpine (MK-801, a non-competitive antagonist of NMDA receptors) or by LY274614 (a competitive antagonist of NMDA receptors). The protective effect of LY274614 was dose-dependent, being maximum at 10-40 mgkg (i.p.). A 10 mg/kg dose of LY274614 was effective in antagonizing the depletion of dopamine in the striatum, when given as long as 8 hr prior to amphetamine but not when given 24 hr prior to amphetamine. Depletion of dopamine in the striatum was also antagonized when LY274614 was given after the injection of amphetamine; LY274614 protected when given up to 4 hr after but not when given 8 or 24 hr after amphetamine. The prolonged depletion of dopamine in the striatum in mice, given multiple injections of methamphetamine, was also antagonized dose-dependently and completely by LY274614. The data strengthen the evidence that the neurotoxic effect of amphetamine and related compounds toward nigrostriatal dopamine neurons involves NMDA receptors and that LY274614 is an NMDA receptor antagonist with long-lasting in vivo effects in rats.", "entity": "N-Methylaspartate", "aliases": "Acid N-Methyl-D-aspartic N Methyl D aspartate aspartic Methylaspartate N-Methyl-D-aspartate N-Methylaspartate NMDA", "definition": "An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).\n    ", "id": "MESH:D016202"}
{"mention": "NMDA", "mention_text": "LY274614, 3SR,4aRS,6SR,8aRS-6-[phosphonomethyl]decahydr oisoquinoline-3- carboxylic acid, has been described as a potent antagonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Here its ability to antagonize the prolonged depletion of dopamine in the striatum by amphetamine in iprindole-treated rats is reported. A single 18.4 mg/kg (i.p.) dose of (+/-)-amphetamine hemisulfate, given to rats pretreated with iprindole, resulted in persistent depletion of dopamine in the striatum 1 week later. This prolonged depletion of dopamine in the striatum was antagonized by dizocilpine (MK-801, a non-competitive antagonist of NMDA receptors) or by LY274614 (a competitive antagonist of NMDA receptors). The protective effect of LY274614 was dose-dependent, being maximum at 10-40 mgkg (i.p.). A 10 mg/kg dose of LY274614 was effective in antagonizing the depletion of dopamine in the striatum, when given as long as 8 hr prior to amphetamine but not when given 24 hr prior to amphetamine. Depletion of dopamine in the striatum was also antagonized when LY274614 was given after the injection of amphetamine; LY274614 protected when given up to 4 hr after but not when given 8 or 24 hr after amphetamine. The prolonged depletion of dopamine in the striatum in mice, given multiple injections of methamphetamine, was also antagonized dose-dependently and completely by LY274614. The data strengthen the evidence that the neurotoxic effect of amphetamine and related compounds toward nigrostriatal dopamine neurons involves NMDA receptors and that LY274614 is an NMDA receptor antagonist with long-lasting in vivo effects in rats.", "entity": "N-Methylaspartate", "aliases": "Acid N-Methyl-D-aspartic N Methyl D aspartate aspartic Methylaspartate N-Methyl-D-aspartate N-Methylaspartate NMDA", "definition": "An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).\n    ", "id": "MESH:D016202"}
{"mention": "glutamate", "mention_text": "LY274614, 3SR,4aRS,6SR,8aRS-6-[phosphonomethyl]decahydr oisoquinoline-3- carboxylic acid, has been described as a potent antagonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Here its ability to antagonize the prolonged depletion of dopamine in the striatum by amphetamine in iprindole-treated rats is reported. A single 18.4 mg/kg (i.p.) dose of (+/-)-amphetamine hemisulfate, given to rats pretreated with iprindole, resulted in persistent depletion of dopamine in the striatum 1 week later. This prolonged depletion of dopamine in the striatum was antagonized by dizocilpine (MK-801, a non-competitive antagonist of NMDA receptors) or by LY274614 (a competitive antagonist of NMDA receptors). The protective effect of LY274614 was dose-dependent, being maximum at 10-40 mgkg (i.p.). A 10 mg/kg dose of LY274614 was effective in antagonizing the depletion of dopamine in the striatum, when given as long as 8 hr prior to amphetamine but not when given 24 hr prior to amphetamine. Depletion of dopamine in the striatum was also antagonized when LY274614 was given after the injection of amphetamine; LY274614 protected when given up to 4 hr after but not when given 8 or 24 hr after amphetamine. The prolonged depletion of dopamine in the striatum in mice, given multiple injections of methamphetamine, was also antagonized dose-dependently and completely by LY274614. The data strengthen the evidence that the neurotoxic effect of amphetamine and related compounds toward nigrostriatal dopamine neurons involves NMDA receptors and that LY274614 is an NMDA receptor antagonist with long-lasting in vivo effects in rats.", "entity": "Glutamic Acid", "aliases": "Aluminum L Glutamate L-Glutamate D D-Glutamate Potassium Glutamic Acid (D)-Isomer L-Glutamic", "definition": "A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.\n    ", "id": "MESH:D018698"}
{"mention": "dopamine", "mention_text": "LY274614, 3SR,4aRS,6SR,8aRS-6-[phosphonomethyl]decahydr oisoquinoline-3- carboxylic acid, has been described as a potent antagonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Here its ability to antagonize the prolonged depletion of dopamine in the striatum by amphetamine in iprindole-treated rats is reported. A single 18.4 mg/kg (i.p.) dose of (+/-)-amphetamine hemisulfate, given to rats pretreated with iprindole, resulted in persistent depletion of dopamine in the striatum 1 week later. This prolonged depletion of dopamine in the striatum was antagonized by dizocilpine (MK-801, a non-competitive antagonist of NMDA receptors) or by LY274614 (a competitive antagonist of NMDA receptors). The protective effect of LY274614 was dose-dependent, being maximum at 10-40 mgkg (i.p.). A 10 mg/kg dose of LY274614 was effective in antagonizing the depletion of dopamine in the striatum, when given as long as 8 hr prior to amphetamine but not when given 24 hr prior to amphetamine. Depletion of dopamine in the striatum was also antagonized when LY274614 was given after the injection of amphetamine; LY274614 protected when given up to 4 hr after but not when given 8 or 24 hr after amphetamine. The prolonged depletion of dopamine in the striatum in mice, given multiple injections of methamphetamine, was also antagonized dose-dependently and completely by LY274614. The data strengthen the evidence that the neurotoxic effect of amphetamine and related compounds toward nigrostriatal dopamine neurons involves NMDA receptors and that LY274614 is an NMDA receptor antagonist with long-lasting in vivo effects in rats.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "amphetamine", "mention_text": "LY274614, 3SR,4aRS,6SR,8aRS-6-[phosphonomethyl]decahydr oisoquinoline-3- carboxylic acid, has been described as a potent antagonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Here its ability to antagonize the prolonged depletion of dopamine in the striatum by amphetamine in iprindole-treated rats is reported. A single 18.4 mg/kg (i.p.) dose of (+/-)-amphetamine hemisulfate, given to rats pretreated with iprindole, resulted in persistent depletion of dopamine in the striatum 1 week later. This prolonged depletion of dopamine in the striatum was antagonized by dizocilpine (MK-801, a non-competitive antagonist of NMDA receptors) or by LY274614 (a competitive antagonist of NMDA receptors). The protective effect of LY274614 was dose-dependent, being maximum at 10-40 mgkg (i.p.). A 10 mg/kg dose of LY274614 was effective in antagonizing the depletion of dopamine in the striatum, when given as long as 8 hr prior to amphetamine but not when given 24 hr prior to amphetamine. Depletion of dopamine in the striatum was also antagonized when LY274614 was given after the injection of amphetamine; LY274614 protected when given up to 4 hr after but not when given 8 or 24 hr after amphetamine. The prolonged depletion of dopamine in the striatum in mice, given multiple injections of methamphetamine, was also antagonized dose-dependently and completely by LY274614. The data strengthen the evidence that the neurotoxic effect of amphetamine and related compounds toward nigrostriatal dopamine neurons involves NMDA receptors and that LY274614 is an NMDA receptor antagonist with long-lasting in vivo effects in rats.", "entity": "Amphetamine", "aliases": "Amfetamine Amphetamine Sulfate (2:1) Centramina Desoxynorephedrin Fenamine Levoamphetamine Miquel Brand of Mydrial Phenamine Phenopromin Thyramine l l-Amphetamine levo levo-Amphetamine", "definition": "A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE.\n    ", "id": "MESH:D000661"}
{"mention": "iprindole", "mention_text": "LY274614, 3SR,4aRS,6SR,8aRS-6-[phosphonomethyl]decahydr oisoquinoline-3- carboxylic acid, has been described as a potent antagonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Here its ability to antagonize the prolonged depletion of dopamine in the striatum by amphetamine in iprindole-treated rats is reported. A single 18.4 mg/kg (i.p.) dose of (+/-)-amphetamine hemisulfate, given to rats pretreated with iprindole, resulted in persistent depletion of dopamine in the striatum 1 week later. This prolonged depletion of dopamine in the striatum was antagonized by dizocilpine (MK-801, a non-competitive antagonist of NMDA receptors) or by LY274614 (a competitive antagonist of NMDA receptors). The protective effect of LY274614 was dose-dependent, being maximum at 10-40 mgkg (i.p.). A 10 mg/kg dose of LY274614 was effective in antagonizing the depletion of dopamine in the striatum, when given as long as 8 hr prior to amphetamine but not when given 24 hr prior to amphetamine. Depletion of dopamine in the striatum was also antagonized when LY274614 was given after the injection of amphetamine; LY274614 protected when given up to 4 hr after but not when given 8 or 24 hr after amphetamine. The prolonged depletion of dopamine in the striatum in mice, given multiple injections of methamphetamine, was also antagonized dose-dependently and completely by LY274614. The data strengthen the evidence that the neurotoxic effect of amphetamine and related compounds toward nigrostriatal dopamine neurons involves NMDA receptors and that LY274614 is an NMDA receptor antagonist with long-lasting in vivo effects in rats.", "entity": "Iprindole", "aliases": "Iprindole", "definition": "A tricyclic antidepressant that has actions and uses similar to those of AMITRIPTYLINE, but has only weak antimuscarinic and sedative effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p257)\n    ", "id": "MESH:D007488"}
{"mention": "dizocilpine", "mention_text": "LY274614, 3SR,4aRS,6SR,8aRS-6-[phosphonomethyl]decahydr oisoquinoline-3- carboxylic acid, has been described as a potent antagonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Here its ability to antagonize the prolonged depletion of dopamine in the striatum by amphetamine in iprindole-treated rats is reported. A single 18.4 mg/kg (i.p.) dose of (+/-)-amphetamine hemisulfate, given to rats pretreated with iprindole, resulted in persistent depletion of dopamine in the striatum 1 week later. This prolonged depletion of dopamine in the striatum was antagonized by dizocilpine (MK-801, a non-competitive antagonist of NMDA receptors) or by LY274614 (a competitive antagonist of NMDA receptors). The protective effect of LY274614 was dose-dependent, being maximum at 10-40 mgkg (i.p.). A 10 mg/kg dose of LY274614 was effective in antagonizing the depletion of dopamine in the striatum, when given as long as 8 hr prior to amphetamine but not when given 24 hr prior to amphetamine. Depletion of dopamine in the striatum was also antagonized when LY274614 was given after the injection of amphetamine; LY274614 protected when given up to 4 hr after but not when given 8 or 24 hr after amphetamine. The prolonged depletion of dopamine in the striatum in mice, given multiple injections of methamphetamine, was also antagonized dose-dependently and completely by LY274614. The data strengthen the evidence that the neurotoxic effect of amphetamine and related compounds toward nigrostriatal dopamine neurons involves NMDA receptors and that LY274614 is an NMDA receptor antagonist with long-lasting in vivo effects in rats.", "entity": "Dizocilpine Maleate", "aliases": "Dizocilpine Maleate MK 801 MK-801 MK801", "definition": "A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects.\n    ", "id": "MESH:D016291"}
{"mention": "MK-801", "mention_text": "LY274614, 3SR,4aRS,6SR,8aRS-6-[phosphonomethyl]decahydr oisoquinoline-3- carboxylic acid, has been described as a potent antagonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Here its ability to antagonize the prolonged depletion of dopamine in the striatum by amphetamine in iprindole-treated rats is reported. A single 18.4 mg/kg (i.p.) dose of (+/-)-amphetamine hemisulfate, given to rats pretreated with iprindole, resulted in persistent depletion of dopamine in the striatum 1 week later. This prolonged depletion of dopamine in the striatum was antagonized by dizocilpine (MK-801, a non-competitive antagonist of NMDA receptors) or by LY274614 (a competitive antagonist of NMDA receptors). The protective effect of LY274614 was dose-dependent, being maximum at 10-40 mgkg (i.p.). A 10 mg/kg dose of LY274614 was effective in antagonizing the depletion of dopamine in the striatum, when given as long as 8 hr prior to amphetamine but not when given 24 hr prior to amphetamine. Depletion of dopamine in the striatum was also antagonized when LY274614 was given after the injection of amphetamine; LY274614 protected when given up to 4 hr after but not when given 8 or 24 hr after amphetamine. The prolonged depletion of dopamine in the striatum in mice, given multiple injections of methamphetamine, was also antagonized dose-dependently and completely by LY274614. The data strengthen the evidence that the neurotoxic effect of amphetamine and related compounds toward nigrostriatal dopamine neurons involves NMDA receptors and that LY274614 is an NMDA receptor antagonist with long-lasting in vivo effects in rats.", "entity": "Dizocilpine Maleate", "aliases": "Dizocilpine Maleate MK 801 MK-801 MK801", "definition": "A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects.\n    ", "id": "MESH:D016291"}
{"mention": "methamphetamine", "mention_text": "LY274614, 3SR,4aRS,6SR,8aRS-6-[phosphonomethyl]decahydr oisoquinoline-3- carboxylic acid, has been described as a potent antagonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Here its ability to antagonize the prolonged depletion of dopamine in the striatum by amphetamine in iprindole-treated rats is reported. A single 18.4 mg/kg (i.p.) dose of (+/-)-amphetamine hemisulfate, given to rats pretreated with iprindole, resulted in persistent depletion of dopamine in the striatum 1 week later. This prolonged depletion of dopamine in the striatum was antagonized by dizocilpine (MK-801, a non-competitive antagonist of NMDA receptors) or by LY274614 (a competitive antagonist of NMDA receptors). The protective effect of LY274614 was dose-dependent, being maximum at 10-40 mgkg (i.p.). A 10 mg/kg dose of LY274614 was effective in antagonizing the depletion of dopamine in the striatum, when given as long as 8 hr prior to amphetamine but not when given 24 hr prior to amphetamine. Depletion of dopamine in the striatum was also antagonized when LY274614 was given after the injection of amphetamine; LY274614 protected when given up to 4 hr after but not when given 8 or 24 hr after amphetamine. The prolonged depletion of dopamine in the striatum in mice, given multiple injections of methamphetamine, was also antagonized dose-dependently and completely by LY274614. The data strengthen the evidence that the neurotoxic effect of amphetamine and related compounds toward nigrostriatal dopamine neurons involves NMDA receptors and that LY274614 is an NMDA receptor antagonist with long-lasting in vivo effects in rats.", "entity": "Methamphetamine", "aliases": "Abbott Brand of Methamphetamine Hydrochloride Deoxyephedrine Desoxyephedrine Desoxyn Langly Madrine Metamfetamine Methylamphetamine N N-Methylamphetamine", "definition": "A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.\n    ", "id": "MESH:D008694"}
{"mention": "neurotoxic", "mention_text": "LY274614, 3SR,4aRS,6SR,8aRS-6-[phosphonomethyl]decahydr oisoquinoline-3- carboxylic acid, has been described as a potent antagonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Here its ability to antagonize the prolonged depletion of dopamine in the striatum by amphetamine in iprindole-treated rats is reported. A single 18.4 mg/kg (i.p.) dose of (+/-)-amphetamine hemisulfate, given to rats pretreated with iprindole, resulted in persistent depletion of dopamine in the striatum 1 week later. This prolonged depletion of dopamine in the striatum was antagonized by dizocilpine (MK-801, a non-competitive antagonist of NMDA receptors) or by LY274614 (a competitive antagonist of NMDA receptors). The protective effect of LY274614 was dose-dependent, being maximum at 10-40 mgkg (i.p.). A 10 mg/kg dose of LY274614 was effective in antagonizing the depletion of dopamine in the striatum, when given as long as 8 hr prior to amphetamine but not when given 24 hr prior to amphetamine. Depletion of dopamine in the striatum was also antagonized when LY274614 was given after the injection of amphetamine; LY274614 protected when given up to 4 hr after but not when given 8 or 24 hr after amphetamine. The prolonged depletion of dopamine in the striatum in mice, given multiple injections of methamphetamine, was also antagonized dose-dependently and completely by LY274614. The data strengthen the evidence that the neurotoxic effect of amphetamine and related compounds toward nigrostriatal dopamine neurons involves NMDA receptors and that LY274614 is an NMDA receptor antagonist with long-lasting in vivo effects in rats.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "pyridoxine", "mention_text": "Neonatal pyridoxine responsive convulsions due to isoniazid therapy.", "entity": "Pyridoxine", "aliases": "Pyridoxin Pyridoxine Hydrochloride Pyridoxol Rodex", "definition": "The 4-methanol form of VITAMIN B 6 which is converted to PYRIDOXAL PHOSPHATE which is a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. Although pyridoxine and Vitamin B 6 are still frequently used as synonyms, especially by medical researchers, this practice is erroneous and sometimes misleading (EE Snell; Ann NY Acad Sci, vol 585 pg 1, 1990).\n    ", "id": "MESH:D011736"}
{"mention": "convulsions", "mention_text": "Neonatal pyridoxine responsive convulsions due to isoniazid therapy.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "isoniazid", "mention_text": "Neonatal pyridoxine responsive convulsions due to isoniazid therapy.", "entity": "Isoniazid", "aliases": "Acid Vanillylidenehydrazide Isonicotinic Ftivazide Hydrazide Isonex Isoniazid Phthivazid Phthivazide Tubazide", "definition": "Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis.\n    ", "id": "MESH:D007538"}
{"mention": "isoniazid", "mention_text": "A 17-day-old infant on isoniazid therapy 13 mg/kg daily from birth because of maternal tuberculosis was admitted after 4 days of clonic fits. No underlying infective or biochemical cause could be found. The fits ceased within 4 hours of administering intramuscular pyridoxine, suggesting an aetiology of pyridoxine deficiency secondary to isoniazid medication.", "entity": "Isoniazid", "aliases": "Acid Vanillylidenehydrazide Isonicotinic Ftivazide Hydrazide Isonex Isoniazid Phthivazid Phthivazide Tubazide", "definition": "Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis.\n    ", "id": "MESH:D007538"}
{"mention": "tuberculosis", "mention_text": "A 17-day-old infant on isoniazid therapy 13 mg/kg daily from birth because of maternal tuberculosis was admitted after 4 days of clonic fits. No underlying infective or biochemical cause could be found. The fits ceased within 4 hours of administering intramuscular pyridoxine, suggesting an aetiology of pyridoxine deficiency secondary to isoniazid medication.", "entity": "Tuberculosis", "aliases": "Disease Koch's Kochs Koch Tuberculoses Tuberculosis", "definition": "Any of the infectious diseases of man and other animals caused by species of MYCOBACTERIUM.\n    ", "id": "MESH:D014376"}
{"mention": "clonic fits", "mention_text": "A 17-day-old infant on isoniazid therapy 13 mg/kg daily from birth because of maternal tuberculosis was admitted after 4 days of clonic fits. No underlying infective or biochemical cause could be found. The fits ceased within 4 hours of administering intramuscular pyridoxine, suggesting an aetiology of pyridoxine deficiency secondary to isoniazid medication.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "fits", "mention_text": "A 17-day-old infant on isoniazid therapy 13 mg/kg daily from birth because of maternal tuberculosis was admitted after 4 days of clonic fits. No underlying infective or biochemical cause could be found. The fits ceased within 4 hours of administering intramuscular pyridoxine, suggesting an aetiology of pyridoxine deficiency secondary to isoniazid medication.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "pyridoxine", "mention_text": "A 17-day-old infant on isoniazid therapy 13 mg/kg daily from birth because of maternal tuberculosis was admitted after 4 days of clonic fits. No underlying infective or biochemical cause could be found. The fits ceased within 4 hours of administering intramuscular pyridoxine, suggesting an aetiology of pyridoxine deficiency secondary to isoniazid medication.", "entity": "Pyridoxine", "aliases": "Pyridoxin Pyridoxine Hydrochloride Pyridoxol Rodex", "definition": "The 4-methanol form of VITAMIN B 6 which is converted to PYRIDOXAL PHOSPHATE which is a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. Although pyridoxine and Vitamin B 6 are still frequently used as synonyms, especially by medical researchers, this practice is erroneous and sometimes misleading (EE Snell; Ann NY Acad Sci, vol 585 pg 1, 1990).\n    ", "id": "MESH:D011736"}
{"mention": "phenylephrine", "mention_text": "Reversal by phenylephrine of the beneficial effects of intravenous nitroglycerin in patients with acute myocardial infarction.", "entity": "Phenylephrine", "aliases": "(R)-3-Hydroxy-alpha-((methylamino)methyl)benzenemethanol Metaoxedrin Metasympatol Mezaton Neo Synephrine Neo-Synephrine Neosynephrine Phenylephrine Hydrochloride Tannate", "definition": "An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.\n    ", "id": "MESH:D010656"}
{"mention": "nitroglycerin", "mention_text": "Reversal by phenylephrine of the beneficial effects of intravenous nitroglycerin in patients with acute myocardial infarction.", "entity": "Nitroglycerin", "aliases": "Anginine Dynamite Gilustenon Glyceryl Trinitrate Nitrangin Nitro Bid Dur Nitro-Bid Nitro-Dur NitroBid NitroDur Nitrocard Nitroderm TTS Nitroglycerin Nitroglyn Nitrol Nitrolan Nitrong Nitrospan Nitrostat Perlinganit Susadrin Sustac Sustak Sustonit Transderm Tridil Trinitrin Trinitrolong", "definition": "A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives.\n    ", "id": "MESH:D005996"}
{"mention": "acute myocardial infarction", "mention_text": "Reversal by phenylephrine of the beneficial effects of intravenous nitroglycerin in patients with acute myocardial infarction.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "Nitroglycerin", "mention_text": "Nitroglycerin has been shown to reduce ST-segment elevation during acute myocardial infarction, an effect potentiated in the dog by agents that reverse nitroglycerin-induced hypotension. Our study was designed to determine the effects of combined nitroglycerin and phenylephrine therapy. Ten patients with acute transmural myocardial infarctions received intravenous nitroglycerin, sufficient to reduce mean arterial pressure from 107 +/- 6 to 85 +/- 6 mm Hg (P less than 0.001), for 60 minutes. Left ventricular filling pressure decreased from 19 +/- 2 to 11 +/- 2 mm Hg (P less than 0.001). SigmaST, the sum of ST-segment elevations in 16 precordial leads, decreased (P less than 0.02) with intravenous nitroglycerin. Subsequent addition of phenylephrine infusion, sufficient to re-elevate mean arterial pressure to 106 +/- 4 mm Hg (P less than 0.001) for 30 minutes, increased left ventricular filling pressure to 17 +/- 2 mm Hg (P less than 0.05) and also significantly increased sigmaST (P less than 0.05). Our results suggest that addition of phenylephrine to nitroglycerin is not beneficial in the treatment of patients with acute myocardial infarction.", "entity": "Nitroglycerin", "aliases": "Anginine Dynamite Gilustenon Glyceryl Trinitrate Nitrangin Nitro Bid Dur Nitro-Bid Nitro-Dur NitroBid NitroDur Nitrocard Nitroderm TTS Nitroglycerin Nitroglyn Nitrol Nitrolan Nitrong Nitrospan Nitrostat Perlinganit Susadrin Sustac Sustak Sustonit Transderm Tridil Trinitrin Trinitrolong", "definition": "A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives.\n    ", "id": "MESH:D005996"}
{"mention": "acute myocardial infarction", "mention_text": "Nitroglycerin has been shown to reduce ST-segment elevation during acute myocardial infarction, an effect potentiated in the dog by agents that reverse nitroglycerin-induced hypotension. Our study was designed to determine the effects of combined nitroglycerin and phenylephrine therapy. Ten patients with acute transmural myocardial infarctions received intravenous nitroglycerin, sufficient to reduce mean arterial pressure from 107 +/- 6 to 85 +/- 6 mm Hg (P less than 0.001), for 60 minutes. Left ventricular filling pressure decreased from 19 +/- 2 to 11 +/- 2 mm Hg (P less than 0.001). SigmaST, the sum of ST-segment elevations in 16 precordial leads, decreased (P less than 0.02) with intravenous nitroglycerin. Subsequent addition of phenylephrine infusion, sufficient to re-elevate mean arterial pressure to 106 +/- 4 mm Hg (P less than 0.001) for 30 minutes, increased left ventricular filling pressure to 17 +/- 2 mm Hg (P less than 0.05) and also significantly increased sigmaST (P less than 0.05). Our results suggest that addition of phenylephrine to nitroglycerin is not beneficial in the treatment of patients with acute myocardial infarction.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "nitroglycerin", "mention_text": "Nitroglycerin has been shown to reduce ST-segment elevation during acute myocardial infarction, an effect potentiated in the dog by agents that reverse nitroglycerin-induced hypotension. Our study was designed to determine the effects of combined nitroglycerin and phenylephrine therapy. Ten patients with acute transmural myocardial infarctions received intravenous nitroglycerin, sufficient to reduce mean arterial pressure from 107 +/- 6 to 85 +/- 6 mm Hg (P less than 0.001), for 60 minutes. Left ventricular filling pressure decreased from 19 +/- 2 to 11 +/- 2 mm Hg (P less than 0.001). SigmaST, the sum of ST-segment elevations in 16 precordial leads, decreased (P less than 0.02) with intravenous nitroglycerin. Subsequent addition of phenylephrine infusion, sufficient to re-elevate mean arterial pressure to 106 +/- 4 mm Hg (P less than 0.001) for 30 minutes, increased left ventricular filling pressure to 17 +/- 2 mm Hg (P less than 0.05) and also significantly increased sigmaST (P less than 0.05). Our results suggest that addition of phenylephrine to nitroglycerin is not beneficial in the treatment of patients with acute myocardial infarction.", "entity": "Nitroglycerin", "aliases": "Anginine Dynamite Gilustenon Glyceryl Trinitrate Nitrangin Nitro Bid Dur Nitro-Bid Nitro-Dur NitroBid NitroDur Nitrocard Nitroderm TTS Nitroglycerin Nitroglyn Nitrol Nitrolan Nitrong Nitrospan Nitrostat Perlinganit Susadrin Sustac Sustak Sustonit Transderm Tridil Trinitrin Trinitrolong", "definition": "A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives.\n    ", "id": "MESH:D005996"}
{"mention": "hypotension", "mention_text": "Nitroglycerin has been shown to reduce ST-segment elevation during acute myocardial infarction, an effect potentiated in the dog by agents that reverse nitroglycerin-induced hypotension. Our study was designed to determine the effects of combined nitroglycerin and phenylephrine therapy. Ten patients with acute transmural myocardial infarctions received intravenous nitroglycerin, sufficient to reduce mean arterial pressure from 107 +/- 6 to 85 +/- 6 mm Hg (P less than 0.001), for 60 minutes. Left ventricular filling pressure decreased from 19 +/- 2 to 11 +/- 2 mm Hg (P less than 0.001). SigmaST, the sum of ST-segment elevations in 16 precordial leads, decreased (P less than 0.02) with intravenous nitroglycerin. Subsequent addition of phenylephrine infusion, sufficient to re-elevate mean arterial pressure to 106 +/- 4 mm Hg (P less than 0.001) for 30 minutes, increased left ventricular filling pressure to 17 +/- 2 mm Hg (P less than 0.05) and also significantly increased sigmaST (P less than 0.05). Our results suggest that addition of phenylephrine to nitroglycerin is not beneficial in the treatment of patients with acute myocardial infarction.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "phenylephrine", "mention_text": "Nitroglycerin has been shown to reduce ST-segment elevation during acute myocardial infarction, an effect potentiated in the dog by agents that reverse nitroglycerin-induced hypotension. Our study was designed to determine the effects of combined nitroglycerin and phenylephrine therapy. Ten patients with acute transmural myocardial infarctions received intravenous nitroglycerin, sufficient to reduce mean arterial pressure from 107 +/- 6 to 85 +/- 6 mm Hg (P less than 0.001), for 60 minutes. Left ventricular filling pressure decreased from 19 +/- 2 to 11 +/- 2 mm Hg (P less than 0.001). SigmaST, the sum of ST-segment elevations in 16 precordial leads, decreased (P less than 0.02) with intravenous nitroglycerin. Subsequent addition of phenylephrine infusion, sufficient to re-elevate mean arterial pressure to 106 +/- 4 mm Hg (P less than 0.001) for 30 minutes, increased left ventricular filling pressure to 17 +/- 2 mm Hg (P less than 0.05) and also significantly increased sigmaST (P less than 0.05). Our results suggest that addition of phenylephrine to nitroglycerin is not beneficial in the treatment of patients with acute myocardial infarction.", "entity": "Phenylephrine", "aliases": "(R)-3-Hydroxy-alpha-((methylamino)methyl)benzenemethanol Metaoxedrin Metasympatol Mezaton Neo Synephrine Neo-Synephrine Neosynephrine Phenylephrine Hydrochloride Tannate", "definition": "An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.\n    ", "id": "MESH:D010656"}
{"mention": "myocardial infarctions", "mention_text": "Nitroglycerin has been shown to reduce ST-segment elevation during acute myocardial infarction, an effect potentiated in the dog by agents that reverse nitroglycerin-induced hypotension. Our study was designed to determine the effects of combined nitroglycerin and phenylephrine therapy. Ten patients with acute transmural myocardial infarctions received intravenous nitroglycerin, sufficient to reduce mean arterial pressure from 107 +/- 6 to 85 +/- 6 mm Hg (P less than 0.001), for 60 minutes. Left ventricular filling pressure decreased from 19 +/- 2 to 11 +/- 2 mm Hg (P less than 0.001). SigmaST, the sum of ST-segment elevations in 16 precordial leads, decreased (P less than 0.02) with intravenous nitroglycerin. Subsequent addition of phenylephrine infusion, sufficient to re-elevate mean arterial pressure to 106 +/- 4 mm Hg (P less than 0.001) for 30 minutes, increased left ventricular filling pressure to 17 +/- 2 mm Hg (P less than 0.05) and also significantly increased sigmaST (P less than 0.05). Our results suggest that addition of phenylephrine to nitroglycerin is not beneficial in the treatment of patients with acute myocardial infarction.", "entity": "Myocardial Infarction", "aliases": "Cardiovascular Stroke Strokes Infarct Myocardial Infarction Infarctions Infarcts", "definition": "NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).\n    ", "id": "MESH:D009203"}
{"mention": "CaCl2", "mention_text": "Elevation of ADAM10, ADAM17, MMP-2 and MMP-9 expression with media degeneration features CaCl2-induced thoracic aortic aneurysm in a rat model.", "entity": "Calcium Chloride", "aliases": "Calcium Chloride Dihydrate Anhydrous", "definition": "A salt used to replenish calcium levels, as an acid-producing diuretic, and as an antidote for magnesium poisoning.\n    ", "id": "MESH:D002122"}
{"mention": "thoracic aortic aneurysm", "mention_text": "Elevation of ADAM10, ADAM17, MMP-2 and MMP-9 expression with media degeneration features CaCl2-induced thoracic aortic aneurysm in a rat model.", "entity": "Aortic Aneurysm, Thoracic", "aliases": "Aneurysm Thoracic Aortic Thoracoabdominal Aneurysms", "definition": "An abnormal balloon- or sac-like dilatation in the wall of the THORACIC AORTA. This proximal descending portion of aorta gives rise to the visceral and the parietal branches above the aortic hiatus at the diaphragm.\n    ", "id": "MESH:D017545"}
{"mention": "thoracic aortic aneurysm", "mention_text": "PURPOSE: This study was designed to establish a rat model of thoracic aortic aneurysm (TAA) by calcium chloride (CaCl(2))-induced arterial injury and to explore the potential role of a disintegrin and metalloproteinase (ADAM), matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) in TAA formation. METHODS: Thoracic aorta of male Sprague-Dawley rats was exposed to 0.5M CaCl(2) or normal saline (NaCl). After 12weeks, animals were euthanized, and CaCl(2)-treated, CaCl(2)-untreated (n=12) and NaCl-treated aortic segments (n=12) were collected for histological and molecular assessments. MMP-TIMP and ADAM mRNAs were semi-quantitatively analyzed and protein expressions were determined by immunohistochemistry. RESULTS: Despite similar external diameters among CaCl(2)-treated, non-CaCl(2)-treated and NaCl-treated segments, aneurymal alteration (n=6, 50%), media degeneration with regional disruption, fragmentation of elastic fiber, and increased collagen deposition (n=12, 100%) were demonstrated in CaCl(2)-treated segments. MMP-2, MMP-9, ADAM-10 and ADAM-17 mRNA levels were increased in CaCl(2)-treated segments (all p<0.01), with trends of elevation in CaCl(2)-untreated segments, as compared with NaCl-treated segments. Immunohistochemistry displayed significantly increased expressions of MMP-2, MMP-9, ADAM-10 and ADAM-17 (all p<0.01) in intima and media for CaCl(2)-treated segments. TIMP mRNA and tissue levels did not differ obviously among the three aortic segments. CONCLUSION: This study establishes a TAA model by periarterial CaCl(2) exposure in rats, and demonstrates a significant elevation of expression of MMP-2, MMP-9, ADAM10 and ADAM17 in the pathogenesis of vascular remodeling.", "entity": "Aortic Aneurysm, Thoracic", "aliases": "Aneurysm Thoracic Aortic Thoracoabdominal Aneurysms", "definition": "An abnormal balloon- or sac-like dilatation in the wall of the THORACIC AORTA. This proximal descending portion of aorta gives rise to the visceral and the parietal branches above the aortic hiatus at the diaphragm.\n    ", "id": "MESH:D017545"}
{"mention": "TAA", "mention_text": "PURPOSE: This study was designed to establish a rat model of thoracic aortic aneurysm (TAA) by calcium chloride (CaCl(2))-induced arterial injury and to explore the potential role of a disintegrin and metalloproteinase (ADAM), matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) in TAA formation. METHODS: Thoracic aorta of male Sprague-Dawley rats was exposed to 0.5M CaCl(2) or normal saline (NaCl). After 12weeks, animals were euthanized, and CaCl(2)-treated, CaCl(2)-untreated (n=12) and NaCl-treated aortic segments (n=12) were collected for histological and molecular assessments. MMP-TIMP and ADAM mRNAs were semi-quantitatively analyzed and protein expressions were determined by immunohistochemistry. RESULTS: Despite similar external diameters among CaCl(2)-treated, non-CaCl(2)-treated and NaCl-treated segments, aneurymal alteration (n=6, 50%), media degeneration with regional disruption, fragmentation of elastic fiber, and increased collagen deposition (n=12, 100%) were demonstrated in CaCl(2)-treated segments. MMP-2, MMP-9, ADAM-10 and ADAM-17 mRNA levels were increased in CaCl(2)-treated segments (all p<0.01), with trends of elevation in CaCl(2)-untreated segments, as compared with NaCl-treated segments. Immunohistochemistry displayed significantly increased expressions of MMP-2, MMP-9, ADAM-10 and ADAM-17 (all p<0.01) in intima and media for CaCl(2)-treated segments. TIMP mRNA and tissue levels did not differ obviously among the three aortic segments. CONCLUSION: This study establishes a TAA model by periarterial CaCl(2) exposure in rats, and demonstrates a significant elevation of expression of MMP-2, MMP-9, ADAM10 and ADAM17 in the pathogenesis of vascular remodeling.", "entity": "Aortic Aneurysm, Thoracic", "aliases": "Aneurysm Thoracic Aortic Thoracoabdominal Aneurysms", "definition": "An abnormal balloon- or sac-like dilatation in the wall of the THORACIC AORTA. This proximal descending portion of aorta gives rise to the visceral and the parietal branches above the aortic hiatus at the diaphragm.\n    ", "id": "MESH:D017545"}
{"mention": "calcium chloride", "mention_text": "PURPOSE: This study was designed to establish a rat model of thoracic aortic aneurysm (TAA) by calcium chloride (CaCl(2))-induced arterial injury and to explore the potential role of a disintegrin and metalloproteinase (ADAM), matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) in TAA formation. METHODS: Thoracic aorta of male Sprague-Dawley rats was exposed to 0.5M CaCl(2) or normal saline (NaCl). After 12weeks, animals were euthanized, and CaCl(2)-treated, CaCl(2)-untreated (n=12) and NaCl-treated aortic segments (n=12) were collected for histological and molecular assessments. MMP-TIMP and ADAM mRNAs were semi-quantitatively analyzed and protein expressions were determined by immunohistochemistry. RESULTS: Despite similar external diameters among CaCl(2)-treated, non-CaCl(2)-treated and NaCl-treated segments, aneurymal alteration (n=6, 50%), media degeneration with regional disruption, fragmentation of elastic fiber, and increased collagen deposition (n=12, 100%) were demonstrated in CaCl(2)-treated segments. MMP-2, MMP-9, ADAM-10 and ADAM-17 mRNA levels were increased in CaCl(2)-treated segments (all p<0.01), with trends of elevation in CaCl(2)-untreated segments, as compared with NaCl-treated segments. Immunohistochemistry displayed significantly increased expressions of MMP-2, MMP-9, ADAM-10 and ADAM-17 (all p<0.01) in intima and media for CaCl(2)-treated segments. TIMP mRNA and tissue levels did not differ obviously among the three aortic segments. CONCLUSION: This study establishes a TAA model by periarterial CaCl(2) exposure in rats, and demonstrates a significant elevation of expression of MMP-2, MMP-9, ADAM10 and ADAM17 in the pathogenesis of vascular remodeling.", "entity": "Calcium Chloride", "aliases": "Calcium Chloride Dihydrate Anhydrous", "definition": "A salt used to replenish calcium levels, as an acid-producing diuretic, and as an antidote for magnesium poisoning.\n    ", "id": "MESH:D002122"}
{"mention": "CaCl(2)", "mention_text": "PURPOSE: This study was designed to establish a rat model of thoracic aortic aneurysm (TAA) by calcium chloride (CaCl(2))-induced arterial injury and to explore the potential role of a disintegrin and metalloproteinase (ADAM), matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) in TAA formation. METHODS: Thoracic aorta of male Sprague-Dawley rats was exposed to 0.5M CaCl(2) or normal saline (NaCl). After 12weeks, animals were euthanized, and CaCl(2)-treated, CaCl(2)-untreated (n=12) and NaCl-treated aortic segments (n=12) were collected for histological and molecular assessments. MMP-TIMP and ADAM mRNAs were semi-quantitatively analyzed and protein expressions were determined by immunohistochemistry. RESULTS: Despite similar external diameters among CaCl(2)-treated, non-CaCl(2)-treated and NaCl-treated segments, aneurymal alteration (n=6, 50%), media degeneration with regional disruption, fragmentation of elastic fiber, and increased collagen deposition (n=12, 100%) were demonstrated in CaCl(2)-treated segments. MMP-2, MMP-9, ADAM-10 and ADAM-17 mRNA levels were increased in CaCl(2)-treated segments (all p<0.01), with trends of elevation in CaCl(2)-untreated segments, as compared with NaCl-treated segments. Immunohistochemistry displayed significantly increased expressions of MMP-2, MMP-9, ADAM-10 and ADAM-17 (all p<0.01) in intima and media for CaCl(2)-treated segments. TIMP mRNA and tissue levels did not differ obviously among the three aortic segments. CONCLUSION: This study establishes a TAA model by periarterial CaCl(2) exposure in rats, and demonstrates a significant elevation of expression of MMP-2, MMP-9, ADAM10 and ADAM17 in the pathogenesis of vascular remodeling.", "entity": "Calcium Chloride", "aliases": "Calcium Chloride Dihydrate Anhydrous", "definition": "A salt used to replenish calcium levels, as an acid-producing diuretic, and as an antidote for magnesium poisoning.\n    ", "id": "MESH:D002122"}
{"mention": "arterial injury", "mention_text": "PURPOSE: This study was designed to establish a rat model of thoracic aortic aneurysm (TAA) by calcium chloride (CaCl(2))-induced arterial injury and to explore the potential role of a disintegrin and metalloproteinase (ADAM), matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) in TAA formation. METHODS: Thoracic aorta of male Sprague-Dawley rats was exposed to 0.5M CaCl(2) or normal saline (NaCl). After 12weeks, animals were euthanized, and CaCl(2)-treated, CaCl(2)-untreated (n=12) and NaCl-treated aortic segments (n=12) were collected for histological and molecular assessments. MMP-TIMP and ADAM mRNAs were semi-quantitatively analyzed and protein expressions were determined by immunohistochemistry. RESULTS: Despite similar external diameters among CaCl(2)-treated, non-CaCl(2)-treated and NaCl-treated segments, aneurymal alteration (n=6, 50%), media degeneration with regional disruption, fragmentation of elastic fiber, and increased collagen deposition (n=12, 100%) were demonstrated in CaCl(2)-treated segments. MMP-2, MMP-9, ADAM-10 and ADAM-17 mRNA levels were increased in CaCl(2)-treated segments (all p<0.01), with trends of elevation in CaCl(2)-untreated segments, as compared with NaCl-treated segments. Immunohistochemistry displayed significantly increased expressions of MMP-2, MMP-9, ADAM-10 and ADAM-17 (all p<0.01) in intima and media for CaCl(2)-treated segments. TIMP mRNA and tissue levels did not differ obviously among the three aortic segments. CONCLUSION: This study establishes a TAA model by periarterial CaCl(2) exposure in rats, and demonstrates a significant elevation of expression of MMP-2, MMP-9, ADAM10 and ADAM17 in the pathogenesis of vascular remodeling.", "entity": "Vascular Diseases", "aliases": "Disease Vascular Diseases", "definition": "Pathological processes involving any of the BLOOD VESSELS in the cardiac or peripheral circulation. They include diseases of ARTERIES; VEINS; and rest of the vasculature system in the body.\n    ", "id": "MESH:D014652"}
{"mention": "NaCl", "mention_text": "PURPOSE: This study was designed to establish a rat model of thoracic aortic aneurysm (TAA) by calcium chloride (CaCl(2))-induced arterial injury and to explore the potential role of a disintegrin and metalloproteinase (ADAM), matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) in TAA formation. METHODS: Thoracic aorta of male Sprague-Dawley rats was exposed to 0.5M CaCl(2) or normal saline (NaCl). After 12weeks, animals were euthanized, and CaCl(2)-treated, CaCl(2)-untreated (n=12) and NaCl-treated aortic segments (n=12) were collected for histological and molecular assessments. MMP-TIMP and ADAM mRNAs were semi-quantitatively analyzed and protein expressions were determined by immunohistochemistry. RESULTS: Despite similar external diameters among CaCl(2)-treated, non-CaCl(2)-treated and NaCl-treated segments, aneurymal alteration (n=6, 50%), media degeneration with regional disruption, fragmentation of elastic fiber, and increased collagen deposition (n=12, 100%) were demonstrated in CaCl(2)-treated segments. MMP-2, MMP-9, ADAM-10 and ADAM-17 mRNA levels were increased in CaCl(2)-treated segments (all p<0.01), with trends of elevation in CaCl(2)-untreated segments, as compared with NaCl-treated segments. Immunohistochemistry displayed significantly increased expressions of MMP-2, MMP-9, ADAM-10 and ADAM-17 (all p<0.01) in intima and media for CaCl(2)-treated segments. TIMP mRNA and tissue levels did not differ obviously among the three aortic segments. CONCLUSION: This study establishes a TAA model by periarterial CaCl(2) exposure in rats, and demonstrates a significant elevation of expression of MMP-2, MMP-9, ADAM10 and ADAM17 in the pathogenesis of vascular remodeling.", "entity": "Sodium Chloride", "aliases": "Saline Solution Sodium Chloride (22)Na (24)NaCl", "definition": "A ubiquitous sodium salt that is commonly used to season food.\n    ", "id": "MESH:D012965"}
{"mention": "right heart failure", "mention_text": "Twenty-three hours after heart transplantation, life-threatening acute right heart failure was diagnosed in a patient requiring continuous venovenous hemodiafiltration (CVVHDF). Increasing doses of catecholamines, sedatives, and muscle relaxants administered through a central venous catheter were ineffective. However, a bolus of epinephrine injected through an alternative catheter provoked a hypertensive crisis. Thus, interference with the central venous infusion by the dialysis catheter was suspected. The catheters were changed, and hemodynamics stabilized at lower catecholamine doses. When the effects of IV drugs are inadequate in patients receiving CVVHDF, interference with adjacent catheters resulting in elimination of the drug by CVVHDF should be suspected.", "entity": "Heart Failure", "aliases": "Cardiac Failure Congestive Heart Decompensation Left Sided Left-Sided Right Right-Sided Myocardial", "definition": "A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.\n    ", "id": "MESH:D006333"}
{"mention": "catecholamines", "mention_text": "Twenty-three hours after heart transplantation, life-threatening acute right heart failure was diagnosed in a patient requiring continuous venovenous hemodiafiltration (CVVHDF). Increasing doses of catecholamines, sedatives, and muscle relaxants administered through a central venous catheter were ineffective. However, a bolus of epinephrine injected through an alternative catheter provoked a hypertensive crisis. Thus, interference with the central venous infusion by the dialysis catheter was suspected. The catheters were changed, and hemodynamics stabilized at lower catecholamine doses. When the effects of IV drugs are inadequate in patients receiving CVVHDF, interference with adjacent catheters resulting in elimination of the drug by CVVHDF should be suspected.", "entity": "Catecholamines", "aliases": "Catecholamines Sympathins", "definition": "A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine.\n    ", "id": "MESH:D002395"}
{"mention": "epinephrine", "mention_text": "Twenty-three hours after heart transplantation, life-threatening acute right heart failure was diagnosed in a patient requiring continuous venovenous hemodiafiltration (CVVHDF). Increasing doses of catecholamines, sedatives, and muscle relaxants administered through a central venous catheter were ineffective. However, a bolus of epinephrine injected through an alternative catheter provoked a hypertensive crisis. Thus, interference with the central venous infusion by the dialysis catheter was suspected. The catheters were changed, and hemodynamics stabilized at lower catecholamine doses. When the effects of IV drugs are inadequate in patients receiving CVVHDF, interference with adjacent catheters resulting in elimination of the drug by CVVHDF should be suspected.", "entity": "Epinephrine", "aliases": "4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-benzenediol Acetate Epinephrine Adrenaline Acid Tartrate Bitartrate Hydrochloride Allergan Brand of Epifrin Hydrogen Epitrate Lyophrin Medihaler-Epi", "definition": "The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.\n    ", "id": "MESH:D004837"}
{"mention": "hypertensive", "mention_text": "Twenty-three hours after heart transplantation, life-threatening acute right heart failure was diagnosed in a patient requiring continuous venovenous hemodiafiltration (CVVHDF). Increasing doses of catecholamines, sedatives, and muscle relaxants administered through a central venous catheter were ineffective. However, a bolus of epinephrine injected through an alternative catheter provoked a hypertensive crisis. Thus, interference with the central venous infusion by the dialysis catheter was suspected. The catheters were changed, and hemodynamics stabilized at lower catecholamine doses. When the effects of IV drugs are inadequate in patients receiving CVVHDF, interference with adjacent catheters resulting in elimination of the drug by CVVHDF should be suspected.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "catecholamine", "mention_text": "Twenty-three hours after heart transplantation, life-threatening acute right heart failure was diagnosed in a patient requiring continuous venovenous hemodiafiltration (CVVHDF). Increasing doses of catecholamines, sedatives, and muscle relaxants administered through a central venous catheter were ineffective. However, a bolus of epinephrine injected through an alternative catheter provoked a hypertensive crisis. Thus, interference with the central venous infusion by the dialysis catheter was suspected. The catheters were changed, and hemodynamics stabilized at lower catecholamine doses. When the effects of IV drugs are inadequate in patients receiving CVVHDF, interference with adjacent catheters resulting in elimination of the drug by CVVHDF should be suspected.", "entity": "Catecholamines", "aliases": "Catecholamines Sympathins", "definition": "A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine.\n    ", "id": "MESH:D002395"}
{"mention": "glutamate", "mention_text": "Long-term glutamate supplementation failed to protect against peripheral neurotoxicity of paclitaxel.", "entity": "Glutamic Acid", "aliases": "Aluminum L Glutamate L-Glutamate D D-Glutamate Potassium Glutamic Acid (D)-Isomer L-Glutamic", "definition": "A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.\n    ", "id": "MESH:D018698"}
{"mention": "peripheral neurotoxicity", "mention_text": "Long-term glutamate supplementation failed to protect against peripheral neurotoxicity of paclitaxel.", "entity": "Peripheral Nervous System Diseases", "aliases": "Nerve Disease Peripheral Diseases Neuropathy PNS (Peripheral Nervous System) System Disorders Neuropathies", "definition": "Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.\n    ", "id": "MESH:D010523"}
{"mention": "paclitaxel", "mention_text": "Long-term glutamate supplementation failed to protect against peripheral neurotoxicity of paclitaxel.", "entity": "Paclitaxel", "aliases": "7 epi Taxol 7-epi-Taxol Anzatax Bris Bristol-Myers Brand of Paclitaxel Squibb Bull Ivax Lemery NSC 125973 NSC-125973 NSC125973 Onxol (4 alpha)-Isomer Paxene Praxel A", "definition": "A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.\n    ", "id": "MESH:D017239"}
{"mention": "peripheral neuropathy", "mention_text": "Toxic peripheral neuropathy is still a significant limiting factor for chemotherapy with paclitaxel (PAC), although glutamate and its closely related amino acid glutamine were claimed to ameliorate PAC neurotoxicity. This pilot trial aimed to evaluate the role of glutamate supplementation for preventing PAC-induced peripheral neuropathy in a randomized, placebo-controlled, double-blinded clinical and electro-diagnostic study. Forty-three ovarian cancer patients were available for analysis following six cycles of the same PAC-containing regimen: 23 had been supplemented by glutamate all along the treatment period, at a daily dose of three times 500 mg (group G), and 20 had received a placebo (group P). Patients were evaluated by neurological examinations, questionnaires and sensory-motor nerve conduction studies. There was no significant difference in the frequency of signs or symptoms between the two groups although neurotoxicity symptoms presented mostly with lower scores of severity in group G. However, this difference reached statistical significance only with regard to reported pain sensation (P = 0.011). Also the frequency of abnormal electro-diagnostic findings showed similarity between the two groups (G: 7/23 = 30.4%; P: 6/20 = 30%). This pilot study leads to the conclusion that glutamate supplementation at the chosen regimen fails to protect against peripheral neurotoxicity of PAC.", "entity": "Peripheral Nervous System Diseases", "aliases": "Nerve Disease Peripheral Diseases Neuropathy PNS (Peripheral Nervous System) System Disorders Neuropathies", "definition": "Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.\n    ", "id": "MESH:D010523"}
{"mention": "paclitaxel", "mention_text": "Toxic peripheral neuropathy is still a significant limiting factor for chemotherapy with paclitaxel (PAC), although glutamate and its closely related amino acid glutamine were claimed to ameliorate PAC neurotoxicity. This pilot trial aimed to evaluate the role of glutamate supplementation for preventing PAC-induced peripheral neuropathy in a randomized, placebo-controlled, double-blinded clinical and electro-diagnostic study. Forty-three ovarian cancer patients were available for analysis following six cycles of the same PAC-containing regimen: 23 had been supplemented by glutamate all along the treatment period, at a daily dose of three times 500 mg (group G), and 20 had received a placebo (group P). Patients were evaluated by neurological examinations, questionnaires and sensory-motor nerve conduction studies. There was no significant difference in the frequency of signs or symptoms between the two groups although neurotoxicity symptoms presented mostly with lower scores of severity in group G. However, this difference reached statistical significance only with regard to reported pain sensation (P = 0.011). Also the frequency of abnormal electro-diagnostic findings showed similarity between the two groups (G: 7/23 = 30.4%; P: 6/20 = 30%). This pilot study leads to the conclusion that glutamate supplementation at the chosen regimen fails to protect against peripheral neurotoxicity of PAC.", "entity": "Paclitaxel", "aliases": "7 epi Taxol 7-epi-Taxol Anzatax Bris Bristol-Myers Brand of Paclitaxel Squibb Bull Ivax Lemery NSC 125973 NSC-125973 NSC125973 Onxol (4 alpha)-Isomer Paxene Praxel A", "definition": "A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.\n    ", "id": "MESH:D017239"}
{"mention": "PAC", "mention_text": "Toxic peripheral neuropathy is still a significant limiting factor for chemotherapy with paclitaxel (PAC), although glutamate and its closely related amino acid glutamine were claimed to ameliorate PAC neurotoxicity. This pilot trial aimed to evaluate the role of glutamate supplementation for preventing PAC-induced peripheral neuropathy in a randomized, placebo-controlled, double-blinded clinical and electro-diagnostic study. Forty-three ovarian cancer patients were available for analysis following six cycles of the same PAC-containing regimen: 23 had been supplemented by glutamate all along the treatment period, at a daily dose of three times 500 mg (group G), and 20 had received a placebo (group P). Patients were evaluated by neurological examinations, questionnaires and sensory-motor nerve conduction studies. There was no significant difference in the frequency of signs or symptoms between the two groups although neurotoxicity symptoms presented mostly with lower scores of severity in group G. However, this difference reached statistical significance only with regard to reported pain sensation (P = 0.011). Also the frequency of abnormal electro-diagnostic findings showed similarity between the two groups (G: 7/23 = 30.4%; P: 6/20 = 30%). This pilot study leads to the conclusion that glutamate supplementation at the chosen regimen fails to protect against peripheral neurotoxicity of PAC.", "entity": "Paclitaxel", "aliases": "7 epi Taxol 7-epi-Taxol Anzatax Bris Bristol-Myers Brand of Paclitaxel Squibb Bull Ivax Lemery NSC 125973 NSC-125973 NSC125973 Onxol (4 alpha)-Isomer Paxene Praxel A", "definition": "A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.\n    ", "id": "MESH:D017239"}
{"mention": "glutamate", "mention_text": "Toxic peripheral neuropathy is still a significant limiting factor for chemotherapy with paclitaxel (PAC), although glutamate and its closely related amino acid glutamine were claimed to ameliorate PAC neurotoxicity. This pilot trial aimed to evaluate the role of glutamate supplementation for preventing PAC-induced peripheral neuropathy in a randomized, placebo-controlled, double-blinded clinical and electro-diagnostic study. Forty-three ovarian cancer patients were available for analysis following six cycles of the same PAC-containing regimen: 23 had been supplemented by glutamate all along the treatment period, at a daily dose of three times 500 mg (group G), and 20 had received a placebo (group P). Patients were evaluated by neurological examinations, questionnaires and sensory-motor nerve conduction studies. There was no significant difference in the frequency of signs or symptoms between the two groups although neurotoxicity symptoms presented mostly with lower scores of severity in group G. However, this difference reached statistical significance only with regard to reported pain sensation (P = 0.011). Also the frequency of abnormal electro-diagnostic findings showed similarity between the two groups (G: 7/23 = 30.4%; P: 6/20 = 30%). This pilot study leads to the conclusion that glutamate supplementation at the chosen regimen fails to protect against peripheral neurotoxicity of PAC.", "entity": "Glutamic Acid", "aliases": "Aluminum L Glutamate L-Glutamate D D-Glutamate Potassium Glutamic Acid (D)-Isomer L-Glutamic", "definition": "A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.\n    ", "id": "MESH:D018698"}
{"mention": "amino acid", "mention_text": "Toxic peripheral neuropathy is still a significant limiting factor for chemotherapy with paclitaxel (PAC), although glutamate and its closely related amino acid glutamine were claimed to ameliorate PAC neurotoxicity. This pilot trial aimed to evaluate the role of glutamate supplementation for preventing PAC-induced peripheral neuropathy in a randomized, placebo-controlled, double-blinded clinical and electro-diagnostic study. Forty-three ovarian cancer patients were available for analysis following six cycles of the same PAC-containing regimen: 23 had been supplemented by glutamate all along the treatment period, at a daily dose of three times 500 mg (group G), and 20 had received a placebo (group P). Patients were evaluated by neurological examinations, questionnaires and sensory-motor nerve conduction studies. There was no significant difference in the frequency of signs or symptoms between the two groups although neurotoxicity symptoms presented mostly with lower scores of severity in group G. However, this difference reached statistical significance only with regard to reported pain sensation (P = 0.011). Also the frequency of abnormal electro-diagnostic findings showed similarity between the two groups (G: 7/23 = 30.4%; P: 6/20 = 30%). This pilot study leads to the conclusion that glutamate supplementation at the chosen regimen fails to protect against peripheral neurotoxicity of PAC.", "entity": "Amino Acids", "aliases": "Acids Amino", "definition": "Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.\n    ", "id": "MESH:D000596"}
{"mention": "glutamine", "mention_text": "Toxic peripheral neuropathy is still a significant limiting factor for chemotherapy with paclitaxel (PAC), although glutamate and its closely related amino acid glutamine were claimed to ameliorate PAC neurotoxicity. This pilot trial aimed to evaluate the role of glutamate supplementation for preventing PAC-induced peripheral neuropathy in a randomized, placebo-controlled, double-blinded clinical and electro-diagnostic study. Forty-three ovarian cancer patients were available for analysis following six cycles of the same PAC-containing regimen: 23 had been supplemented by glutamate all along the treatment period, at a daily dose of three times 500 mg (group G), and 20 had received a placebo (group P). Patients were evaluated by neurological examinations, questionnaires and sensory-motor nerve conduction studies. There was no significant difference in the frequency of signs or symptoms between the two groups although neurotoxicity symptoms presented mostly with lower scores of severity in group G. However, this difference reached statistical significance only with regard to reported pain sensation (P = 0.011). Also the frequency of abnormal electro-diagnostic findings showed similarity between the two groups (G: 7/23 = 30.4%; P: 6/20 = 30%). This pilot study leads to the conclusion that glutamate supplementation at the chosen regimen fails to protect against peripheral neurotoxicity of PAC.", "entity": "Glutamic Acid", "aliases": "Aluminum L Glutamate L-Glutamate D D-Glutamate Potassium Glutamic Acid (D)-Isomer L-Glutamic", "definition": "A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.\n    ", "id": "MESH:D018698"}
{"mention": "neurotoxicity", "mention_text": "Toxic peripheral neuropathy is still a significant limiting factor for chemotherapy with paclitaxel (PAC), although glutamate and its closely related amino acid glutamine were claimed to ameliorate PAC neurotoxicity. This pilot trial aimed to evaluate the role of glutamate supplementation for preventing PAC-induced peripheral neuropathy in a randomized, placebo-controlled, double-blinded clinical and electro-diagnostic study. Forty-three ovarian cancer patients were available for analysis following six cycles of the same PAC-containing regimen: 23 had been supplemented by glutamate all along the treatment period, at a daily dose of three times 500 mg (group G), and 20 had received a placebo (group P). Patients were evaluated by neurological examinations, questionnaires and sensory-motor nerve conduction studies. There was no significant difference in the frequency of signs or symptoms between the two groups although neurotoxicity symptoms presented mostly with lower scores of severity in group G. However, this difference reached statistical significance only with regard to reported pain sensation (P = 0.011). Also the frequency of abnormal electro-diagnostic findings showed similarity between the two groups (G: 7/23 = 30.4%; P: 6/20 = 30%). This pilot study leads to the conclusion that glutamate supplementation at the chosen regimen fails to protect against peripheral neurotoxicity of PAC.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "ovarian cancer", "mention_text": "Toxic peripheral neuropathy is still a significant limiting factor for chemotherapy with paclitaxel (PAC), although glutamate and its closely related amino acid glutamine were claimed to ameliorate PAC neurotoxicity. This pilot trial aimed to evaluate the role of glutamate supplementation for preventing PAC-induced peripheral neuropathy in a randomized, placebo-controlled, double-blinded clinical and electro-diagnostic study. Forty-three ovarian cancer patients were available for analysis following six cycles of the same PAC-containing regimen: 23 had been supplemented by glutamate all along the treatment period, at a daily dose of three times 500 mg (group G), and 20 had received a placebo (group P). Patients were evaluated by neurological examinations, questionnaires and sensory-motor nerve conduction studies. There was no significant difference in the frequency of signs or symptoms between the two groups although neurotoxicity symptoms presented mostly with lower scores of severity in group G. However, this difference reached statistical significance only with regard to reported pain sensation (P = 0.011). Also the frequency of abnormal electro-diagnostic findings showed similarity between the two groups (G: 7/23 = 30.4%; P: 6/20 = 30%). This pilot study leads to the conclusion that glutamate supplementation at the chosen regimen fails to protect against peripheral neurotoxicity of PAC.", "entity": "Ovarian Neoplasms", "aliases": "Cancer of Ovary the Ovarian Cancers Neoplasm Neoplasms", "definition": "Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.\n    ", "id": "MESH:D010051"}
{"mention": "pain", "mention_text": "Toxic peripheral neuropathy is still a significant limiting factor for chemotherapy with paclitaxel (PAC), although glutamate and its closely related amino acid glutamine were claimed to ameliorate PAC neurotoxicity. This pilot trial aimed to evaluate the role of glutamate supplementation for preventing PAC-induced peripheral neuropathy in a randomized, placebo-controlled, double-blinded clinical and electro-diagnostic study. Forty-three ovarian cancer patients were available for analysis following six cycles of the same PAC-containing regimen: 23 had been supplemented by glutamate all along the treatment period, at a daily dose of three times 500 mg (group G), and 20 had received a placebo (group P). Patients were evaluated by neurological examinations, questionnaires and sensory-motor nerve conduction studies. There was no significant difference in the frequency of signs or symptoms between the two groups although neurotoxicity symptoms presented mostly with lower scores of severity in group G. However, this difference reached statistical significance only with regard to reported pain sensation (P = 0.011). Also the frequency of abnormal electro-diagnostic findings showed similarity between the two groups (G: 7/23 = 30.4%; P: 6/20 = 30%). This pilot study leads to the conclusion that glutamate supplementation at the chosen regimen fails to protect against peripheral neurotoxicity of PAC.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "peripheral neurotoxicity", "mention_text": "Toxic peripheral neuropathy is still a significant limiting factor for chemotherapy with paclitaxel (PAC), although glutamate and its closely related amino acid glutamine were claimed to ameliorate PAC neurotoxicity. This pilot trial aimed to evaluate the role of glutamate supplementation for preventing PAC-induced peripheral neuropathy in a randomized, placebo-controlled, double-blinded clinical and electro-diagnostic study. Forty-three ovarian cancer patients were available for analysis following six cycles of the same PAC-containing regimen: 23 had been supplemented by glutamate all along the treatment period, at a daily dose of three times 500 mg (group G), and 20 had received a placebo (group P). Patients were evaluated by neurological examinations, questionnaires and sensory-motor nerve conduction studies. There was no significant difference in the frequency of signs or symptoms between the two groups although neurotoxicity symptoms presented mostly with lower scores of severity in group G. However, this difference reached statistical significance only with regard to reported pain sensation (P = 0.011). Also the frequency of abnormal electro-diagnostic findings showed similarity between the two groups (G: 7/23 = 30.4%; P: 6/20 = 30%). This pilot study leads to the conclusion that glutamate supplementation at the chosen regimen fails to protect against peripheral neurotoxicity of PAC.", "entity": "Peripheral Nervous System Diseases", "aliases": "Nerve Disease Peripheral Diseases Neuropathy PNS (Peripheral Nervous System) System Disorders Neuropathies", "definition": "Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.\n    ", "id": "MESH:D010523"}
{"mention": "pain", "mention_text": "Attentional modulation of perceived pain intensity in capsaicin-induced secondary hyperalgesia.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "capsaicin", "mention_text": "Attentional modulation of perceived pain intensity in capsaicin-induced secondary hyperalgesia.", "entity": "Capsaicin", "aliases": "8 Methyl N Vanillyl 6 Nonenamide 8-Methyl-N-Vanillyl-6-Nonenamide Alacan Brand of Capsaicin Antiphlogistine Rub A-535 Axsain Capsaicine Capsicum Farmaya Capsidol Capsin Capzasin Carter Horner Centrum Elan Flemming Gelcen Katrum Link Medicis NGX 4010 NGX-4010 NGX4010 Smaller Thompson Vinas Zacin Zostrix", "definition": "An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.\n    ", "id": "MESH:D002211"}
{"mention": "hyperalgesia", "mention_text": "Attentional modulation of perceived pain intensity in capsaicin-induced secondary hyperalgesia.", "entity": "Hyperalgesia", "aliases": "Allodynia Mechanical Tactile Thermal Allodynias Hyperalgesia Primary Secondary Hyperalgesias Hyperalgesic Sensations", "definition": "An increased sensation of pain or discomfort produced by mimimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve.\n    ", "id": "MESH:D006930"}
{"mention": "pain", "mention_text": "Perceived pain intensity is modulated by attention. However, it is not known that how pain intensity ratings are affected by attention in capsaicin-induced secondary hyperalgesia. Here we show that perceived pain intensity in secondary hyperalgesia is decreased when attention is distracted away from the painful pinprick stimulus with a visual task. Furthermore, it was found that the magnitude of attentional modulation in secondary hyperalgesia is very similar to that of capsaicin-untreated, control condition. Our findings, showing no interaction between capsaicin treatment and attentional modulation suggest that capsaicin-induced secondary hyperalgesia and attention might affect mechanical pain through independent mechanisms.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "capsaicin", "mention_text": "Perceived pain intensity is modulated by attention. However, it is not known that how pain intensity ratings are affected by attention in capsaicin-induced secondary hyperalgesia. Here we show that perceived pain intensity in secondary hyperalgesia is decreased when attention is distracted away from the painful pinprick stimulus with a visual task. Furthermore, it was found that the magnitude of attentional modulation in secondary hyperalgesia is very similar to that of capsaicin-untreated, control condition. Our findings, showing no interaction between capsaicin treatment and attentional modulation suggest that capsaicin-induced secondary hyperalgesia and attention might affect mechanical pain through independent mechanisms.", "entity": "Capsaicin", "aliases": "8 Methyl N Vanillyl 6 Nonenamide 8-Methyl-N-Vanillyl-6-Nonenamide Alacan Brand of Capsaicin Antiphlogistine Rub A-535 Axsain Capsaicine Capsicum Farmaya Capsidol Capsin Capzasin Carter Horner Centrum Elan Flemming Gelcen Katrum Link Medicis NGX 4010 NGX-4010 NGX4010 Smaller Thompson Vinas Zacin Zostrix", "definition": "An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.\n    ", "id": "MESH:D002211"}
{"mention": "hyperalgesia", "mention_text": "Perceived pain intensity is modulated by attention. However, it is not known that how pain intensity ratings are affected by attention in capsaicin-induced secondary hyperalgesia. Here we show that perceived pain intensity in secondary hyperalgesia is decreased when attention is distracted away from the painful pinprick stimulus with a visual task. Furthermore, it was found that the magnitude of attentional modulation in secondary hyperalgesia is very similar to that of capsaicin-untreated, control condition. Our findings, showing no interaction between capsaicin treatment and attentional modulation suggest that capsaicin-induced secondary hyperalgesia and attention might affect mechanical pain through independent mechanisms.", "entity": "Hyperalgesia", "aliases": "Allodynia Mechanical Tactile Thermal Allodynias Hyperalgesia Primary Secondary Hyperalgesias Hyperalgesic Sensations", "definition": "An increased sensation of pain or discomfort produced by mimimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve.\n    ", "id": "MESH:D006930"}
{"mention": "Testosterone", "mention_text": "Testosterone-dependent hypertension and upregulation of intrarenal angiotensinogen in Dahl salt-sensitive rats.", "entity": "Testosterone", "aliases": "17 beta Hydroxy 4 Androsten 3 one 8 alpha 17-beta-Hydroxy-4-Androsten-3-one 17-beta-Hydroxy-8 alpha-4-Androsten-3-one Isotestosterone 8-Isotestosterone AndroGel Androderm Andropatch Androtop AstraZeneca Brand of Testosterone Auxilium Pharmaceuticals Inc. Bartor CEPA Dr. Kade Faulding Ferring GlaxoSmithKline Hauck Histerone Ortho Paladin Pasadena Schering SmithKline Beecham Solvay Sterotate Sustanon Testim Testoderm Testolin Testopel Sulfate Ulmer Unimed Watson", "definition": "A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.\n    ", "id": "MESH:D013739"}
{"mention": "hypertension", "mention_text": "Testosterone-dependent hypertension and upregulation of intrarenal angiotensinogen in Dahl salt-sensitive rats.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "salt", "mention_text": "Testosterone-dependent hypertension and upregulation of intrarenal angiotensinogen in Dahl salt-sensitive rats.", "entity": "Sodium Chloride, Dietary", "aliases": "Chloride Dietary Sodium Salt Table", "definition": "Sodium chloride used in foods.\n    ", "id": "MESH:D017673"}
{"mention": "salt", "mention_text": "Blood pressure (BP) is more salt sensitive in men than in premenopausal women. In Dahl salt-sensitive rats (DS), high-salt (HS) diet increases BP more in males than females. In contrast to the systemic renin-angiotensin system, which is suppressed in response to HS in male DS, intrarenal angiotensinogen expression is increased, and intrarenal levels of ANG II are not suppressed. In this study, the hypothesis was tested that there is a sexual dimorphism in HS-induced upregulation of intrarenal angiotensinogen mediated by testosterone that also causes increases in BP and renal injury. On a low-salt (LS) diet, male DS had higher levels of intrarenal angiotensinogen mRNA than females. HS diet for 4 wk increased renal cortical angiotensinogen mRNA and protein only in male DS, which was prevented by castration. Ovariectomy of female DS had no effect on intrarenal angiotensinogen expression on either diet. Radiotelemetric BP was similar between males and castrated rats on LS diet. HS diet for 4 wk caused a progressive increase in BP, protein and albumin excretion, and glomerular sclerosis in male DS rats, which were attenuated by castration. Testosterone replacement in castrated DS rats increased BP, renal injury, and upregulation of renal angiotensinogen associated with HS diet. Testosterone contributes to the development of hypertension and renal injury in male DS rats on HS diet possibly through upregulation of the intrarenal renin-angiotensin system.", "entity": "Sodium Chloride, Dietary", "aliases": "Chloride Dietary Sodium Salt Table", "definition": "Sodium chloride used in foods.\n    ", "id": "MESH:D017673"}
{"mention": "angiotensin", "mention_text": "Blood pressure (BP) is more salt sensitive in men than in premenopausal women. In Dahl salt-sensitive rats (DS), high-salt (HS) diet increases BP more in males than females. In contrast to the systemic renin-angiotensin system, which is suppressed in response to HS in male DS, intrarenal angiotensinogen expression is increased, and intrarenal levels of ANG II are not suppressed. In this study, the hypothesis was tested that there is a sexual dimorphism in HS-induced upregulation of intrarenal angiotensinogen mediated by testosterone that also causes increases in BP and renal injury. On a low-salt (LS) diet, male DS had higher levels of intrarenal angiotensinogen mRNA than females. HS diet for 4 wk increased renal cortical angiotensinogen mRNA and protein only in male DS, which was prevented by castration. Ovariectomy of female DS had no effect on intrarenal angiotensinogen expression on either diet. Radiotelemetric BP was similar between males and castrated rats on LS diet. HS diet for 4 wk caused a progressive increase in BP, protein and albumin excretion, and glomerular sclerosis in male DS rats, which were attenuated by castration. Testosterone replacement in castrated DS rats increased BP, renal injury, and upregulation of renal angiotensinogen associated with HS diet. Testosterone contributes to the development of hypertension and renal injury in male DS rats on HS diet possibly through upregulation of the intrarenal renin-angiotensin system.", "entity": "Angiotensins", "aliases": "Angiotensin Angiotensins", "definition": "Oligopeptides which are important in the regulation of blood pressure (VASOCONSTRICTION) and fluid homeostasis via the RENIN-ANGIOTENSIN SYSTEM. These include angiotensins derived naturally from precursor ANGIOTENSINOGEN, and those synthesized.\n    ", "id": "MESH:D000809"}
{"mention": "testosterone", "mention_text": "Blood pressure (BP) is more salt sensitive in men than in premenopausal women. In Dahl salt-sensitive rats (DS), high-salt (HS) diet increases BP more in males than females. In contrast to the systemic renin-angiotensin system, which is suppressed in response to HS in male DS, intrarenal angiotensinogen expression is increased, and intrarenal levels of ANG II are not suppressed. In this study, the hypothesis was tested that there is a sexual dimorphism in HS-induced upregulation of intrarenal angiotensinogen mediated by testosterone that also causes increases in BP and renal injury. On a low-salt (LS) diet, male DS had higher levels of intrarenal angiotensinogen mRNA than females. HS diet for 4 wk increased renal cortical angiotensinogen mRNA and protein only in male DS, which was prevented by castration. Ovariectomy of female DS had no effect on intrarenal angiotensinogen expression on either diet. Radiotelemetric BP was similar between males and castrated rats on LS diet. HS diet for 4 wk caused a progressive increase in BP, protein and albumin excretion, and glomerular sclerosis in male DS rats, which were attenuated by castration. Testosterone replacement in castrated DS rats increased BP, renal injury, and upregulation of renal angiotensinogen associated with HS diet. Testosterone contributes to the development of hypertension and renal injury in male DS rats on HS diet possibly through upregulation of the intrarenal renin-angiotensin system.", "entity": "Testosterone", "aliases": "17 beta Hydroxy 4 Androsten 3 one 8 alpha 17-beta-Hydroxy-4-Androsten-3-one 17-beta-Hydroxy-8 alpha-4-Androsten-3-one Isotestosterone 8-Isotestosterone AndroGel Androderm Andropatch Androtop AstraZeneca Brand of Testosterone Auxilium Pharmaceuticals Inc. Bartor CEPA Dr. Kade Faulding Ferring GlaxoSmithKline Hauck Histerone Ortho Paladin Pasadena Schering SmithKline Beecham Solvay Sterotate Sustanon Testim Testoderm Testolin Testopel Sulfate Ulmer Unimed Watson", "definition": "A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.\n    ", "id": "MESH:D013739"}
{"mention": "renal injury", "mention_text": "Blood pressure (BP) is more salt sensitive in men than in premenopausal women. In Dahl salt-sensitive rats (DS), high-salt (HS) diet increases BP more in males than females. In contrast to the systemic renin-angiotensin system, which is suppressed in response to HS in male DS, intrarenal angiotensinogen expression is increased, and intrarenal levels of ANG II are not suppressed. In this study, the hypothesis was tested that there is a sexual dimorphism in HS-induced upregulation of intrarenal angiotensinogen mediated by testosterone that also causes increases in BP and renal injury. On a low-salt (LS) diet, male DS had higher levels of intrarenal angiotensinogen mRNA than females. HS diet for 4 wk increased renal cortical angiotensinogen mRNA and protein only in male DS, which was prevented by castration. Ovariectomy of female DS had no effect on intrarenal angiotensinogen expression on either diet. Radiotelemetric BP was similar between males and castrated rats on LS diet. HS diet for 4 wk caused a progressive increase in BP, protein and albumin excretion, and glomerular sclerosis in male DS rats, which were attenuated by castration. Testosterone replacement in castrated DS rats increased BP, renal injury, and upregulation of renal angiotensinogen associated with HS diet. Testosterone contributes to the development of hypertension and renal injury in male DS rats on HS diet possibly through upregulation of the intrarenal renin-angiotensin system.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "glomerular sclerosis", "mention_text": "Blood pressure (BP) is more salt sensitive in men than in premenopausal women. In Dahl salt-sensitive rats (DS), high-salt (HS) diet increases BP more in males than females. In contrast to the systemic renin-angiotensin system, which is suppressed in response to HS in male DS, intrarenal angiotensinogen expression is increased, and intrarenal levels of ANG II are not suppressed. In this study, the hypothesis was tested that there is a sexual dimorphism in HS-induced upregulation of intrarenal angiotensinogen mediated by testosterone that also causes increases in BP and renal injury. On a low-salt (LS) diet, male DS had higher levels of intrarenal angiotensinogen mRNA than females. HS diet for 4 wk increased renal cortical angiotensinogen mRNA and protein only in male DS, which was prevented by castration. Ovariectomy of female DS had no effect on intrarenal angiotensinogen expression on either diet. Radiotelemetric BP was similar between males and castrated rats on LS diet. HS diet for 4 wk caused a progressive increase in BP, protein and albumin excretion, and glomerular sclerosis in male DS rats, which were attenuated by castration. Testosterone replacement in castrated DS rats increased BP, renal injury, and upregulation of renal angiotensinogen associated with HS diet. Testosterone contributes to the development of hypertension and renal injury in male DS rats on HS diet possibly through upregulation of the intrarenal renin-angiotensin system.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "Testosterone", "mention_text": "Blood pressure (BP) is more salt sensitive in men than in premenopausal women. In Dahl salt-sensitive rats (DS), high-salt (HS) diet increases BP more in males than females. In contrast to the systemic renin-angiotensin system, which is suppressed in response to HS in male DS, intrarenal angiotensinogen expression is increased, and intrarenal levels of ANG II are not suppressed. In this study, the hypothesis was tested that there is a sexual dimorphism in HS-induced upregulation of intrarenal angiotensinogen mediated by testosterone that also causes increases in BP and renal injury. On a low-salt (LS) diet, male DS had higher levels of intrarenal angiotensinogen mRNA than females. HS diet for 4 wk increased renal cortical angiotensinogen mRNA and protein only in male DS, which was prevented by castration. Ovariectomy of female DS had no effect on intrarenal angiotensinogen expression on either diet. Radiotelemetric BP was similar between males and castrated rats on LS diet. HS diet for 4 wk caused a progressive increase in BP, protein and albumin excretion, and glomerular sclerosis in male DS rats, which were attenuated by castration. Testosterone replacement in castrated DS rats increased BP, renal injury, and upregulation of renal angiotensinogen associated with HS diet. Testosterone contributes to the development of hypertension and renal injury in male DS rats on HS diet possibly through upregulation of the intrarenal renin-angiotensin system.", "entity": "Testosterone", "aliases": "17 beta Hydroxy 4 Androsten 3 one 8 alpha 17-beta-Hydroxy-4-Androsten-3-one 17-beta-Hydroxy-8 alpha-4-Androsten-3-one Isotestosterone 8-Isotestosterone AndroGel Androderm Andropatch Androtop AstraZeneca Brand of Testosterone Auxilium Pharmaceuticals Inc. Bartor CEPA Dr. Kade Faulding Ferring GlaxoSmithKline Hauck Histerone Ortho Paladin Pasadena Schering SmithKline Beecham Solvay Sterotate Sustanon Testim Testoderm Testolin Testopel Sulfate Ulmer Unimed Watson", "definition": "A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.\n    ", "id": "MESH:D013739"}
{"mention": "hypertension", "mention_text": "Blood pressure (BP) is more salt sensitive in men than in premenopausal women. In Dahl salt-sensitive rats (DS), high-salt (HS) diet increases BP more in males than females. In contrast to the systemic renin-angiotensin system, which is suppressed in response to HS in male DS, intrarenal angiotensinogen expression is increased, and intrarenal levels of ANG II are not suppressed. In this study, the hypothesis was tested that there is a sexual dimorphism in HS-induced upregulation of intrarenal angiotensinogen mediated by testosterone that also causes increases in BP and renal injury. On a low-salt (LS) diet, male DS had higher levels of intrarenal angiotensinogen mRNA than females. HS diet for 4 wk increased renal cortical angiotensinogen mRNA and protein only in male DS, which was prevented by castration. Ovariectomy of female DS had no effect on intrarenal angiotensinogen expression on either diet. Radiotelemetric BP was similar between males and castrated rats on LS diet. HS diet for 4 wk caused a progressive increase in BP, protein and albumin excretion, and glomerular sclerosis in male DS rats, which were attenuated by castration. Testosterone replacement in castrated DS rats increased BP, renal injury, and upregulation of renal angiotensinogen associated with HS diet. Testosterone contributes to the development of hypertension and renal injury in male DS rats on HS diet possibly through upregulation of the intrarenal renin-angiotensin system.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "dopamine", "mention_text": "Prenatal protein deprivation alters dopamine-mediated behaviors and dopaminergic and glutamatergic receptor binding.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "schizophrenia", "mention_text": "Epidemiological evidence indicates that prenatal nutritional deprivation may increase the risk of schizophrenia. The goal of these studies was to use an animal model to examine the effects of prenatal protein deprivation on behaviors and receptor binding with relevance to schizophrenia. We report that prenatally protein deprived (PD) female rats showed an increased stereotypic response to apomorphine and an increased locomotor response to amphetamine in adulthood. These differences were not observed during puberty. No changes in haloperidol-induced catalepsy or MK-801-induced locomotion were seen following PD. In addition, PD female rats showed increased (3)H-MK-801 binding in the striatum and hippocampus, but not in the cortex. PD female rats also showed increased (3)H-haloperidol binding and decreased dopamine transporter binding in striatum. No statistically significant changes in behavior or receptor binding were found in PD males with the exception of increased (3)H-MK-801 binding in cortex. This animal model may be useful to explore the mechanisms by which prenatal nutritional deficiency enhances risk for schizophrenia in humans and may also have implications for developmental processes leading to differential sensitivity to drugs of abuse.", "entity": "Schizophrenia", "aliases": "Dementia Praecox Disorder Schizophrenic Disorders Schizophrenia Schizophrenias", "definition": "A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior.\n    ", "id": "MESH:D012559"}
{"mention": "apomorphine", "mention_text": "Epidemiological evidence indicates that prenatal nutritional deprivation may increase the risk of schizophrenia. The goal of these studies was to use an animal model to examine the effects of prenatal protein deprivation on behaviors and receptor binding with relevance to schizophrenia. We report that prenatally protein deprived (PD) female rats showed an increased stereotypic response to apomorphine and an increased locomotor response to amphetamine in adulthood. These differences were not observed during puberty. No changes in haloperidol-induced catalepsy or MK-801-induced locomotion were seen following PD. In addition, PD female rats showed increased (3)H-MK-801 binding in the striatum and hippocampus, but not in the cortex. PD female rats also showed increased (3)H-haloperidol binding and decreased dopamine transporter binding in striatum. No statistically significant changes in behavior or receptor binding were found in PD males with the exception of increased (3)H-MK-801 binding in cortex. This animal model may be useful to explore the mechanisms by which prenatal nutritional deficiency enhances risk for schizophrenia in humans and may also have implications for developmental processes leading to differential sensitivity to drugs of abuse.", "entity": "Apomorphine", "aliases": "Aguettant Brand of Apomorphine Hydrochloride Anhydrous Apokinon Apomorphin Teclapharm Apomorphin-Teclapharm ApomorphinTeclapharm Chloride Hemihydrate Britaject Britannia", "definition": "A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use.\n    ", "id": "MESH:D001058"}
{"mention": "amphetamine", "mention_text": "Epidemiological evidence indicates that prenatal nutritional deprivation may increase the risk of schizophrenia. The goal of these studies was to use an animal model to examine the effects of prenatal protein deprivation on behaviors and receptor binding with relevance to schizophrenia. We report that prenatally protein deprived (PD) female rats showed an increased stereotypic response to apomorphine and an increased locomotor response to amphetamine in adulthood. These differences were not observed during puberty. No changes in haloperidol-induced catalepsy or MK-801-induced locomotion were seen following PD. In addition, PD female rats showed increased (3)H-MK-801 binding in the striatum and hippocampus, but not in the cortex. PD female rats also showed increased (3)H-haloperidol binding and decreased dopamine transporter binding in striatum. No statistically significant changes in behavior or receptor binding were found in PD males with the exception of increased (3)H-MK-801 binding in cortex. This animal model may be useful to explore the mechanisms by which prenatal nutritional deficiency enhances risk for schizophrenia in humans and may also have implications for developmental processes leading to differential sensitivity to drugs of abuse.", "entity": "Amphetamine", "aliases": "Amfetamine Amphetamine Sulfate (2:1) Centramina Desoxynorephedrin Fenamine Levoamphetamine Miquel Brand of Mydrial Phenamine Phenopromin Thyramine l l-Amphetamine levo levo-Amphetamine", "definition": "A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE.\n    ", "id": "MESH:D000661"}
{"mention": "haloperidol", "mention_text": "Epidemiological evidence indicates that prenatal nutritional deprivation may increase the risk of schizophrenia. The goal of these studies was to use an animal model to examine the effects of prenatal protein deprivation on behaviors and receptor binding with relevance to schizophrenia. We report that prenatally protein deprived (PD) female rats showed an increased stereotypic response to apomorphine and an increased locomotor response to amphetamine in adulthood. These differences were not observed during puberty. No changes in haloperidol-induced catalepsy or MK-801-induced locomotion were seen following PD. In addition, PD female rats showed increased (3)H-MK-801 binding in the striatum and hippocampus, but not in the cortex. PD female rats also showed increased (3)H-haloperidol binding and decreased dopamine transporter binding in striatum. No statistically significant changes in behavior or receptor binding were found in PD males with the exception of increased (3)H-MK-801 binding in cortex. This animal model may be useful to explore the mechanisms by which prenatal nutritional deficiency enhances risk for schizophrenia in humans and may also have implications for developmental processes leading to differential sensitivity to drugs of abuse.", "entity": "Haloperidol", "aliases": "Haldol Haloperidol", "definition": "A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)\n    ", "id": "MESH:D006220"}
{"mention": "catalepsy", "mention_text": "Epidemiological evidence indicates that prenatal nutritional deprivation may increase the risk of schizophrenia. The goal of these studies was to use an animal model to examine the effects of prenatal protein deprivation on behaviors and receptor binding with relevance to schizophrenia. We report that prenatally protein deprived (PD) female rats showed an increased stereotypic response to apomorphine and an increased locomotor response to amphetamine in adulthood. These differences were not observed during puberty. No changes in haloperidol-induced catalepsy or MK-801-induced locomotion were seen following PD. In addition, PD female rats showed increased (3)H-MK-801 binding in the striatum and hippocampus, but not in the cortex. PD female rats also showed increased (3)H-haloperidol binding and decreased dopamine transporter binding in striatum. No statistically significant changes in behavior or receptor binding were found in PD males with the exception of increased (3)H-MK-801 binding in cortex. This animal model may be useful to explore the mechanisms by which prenatal nutritional deficiency enhances risk for schizophrenia in humans and may also have implications for developmental processes leading to differential sensitivity to drugs of abuse.", "entity": "Catalepsy", "aliases": "Anochlesia Anochlesias Catalepsies Catalepsy Cerea Flexibilitas Flexibilities Waxy Flexibility", "definition": "A condition characterized by inactivity, decreased responsiveness to stimuli, and a tendency to maintain an immobile posture. The limbs tend to remain in whatever position they are placed (waxy flexibility). Catalepsy may be associated with PSYCHOTIC DISORDERS (e.g., SCHIZOPHRENIA, CATATONIC), nervous system drug toxicity, and other conditions.\n    ", "id": "MESH:D002375"}
{"mention": "MK-801", "mention_text": "Epidemiological evidence indicates that prenatal nutritional deprivation may increase the risk of schizophrenia. The goal of these studies was to use an animal model to examine the effects of prenatal protein deprivation on behaviors and receptor binding with relevance to schizophrenia. We report that prenatally protein deprived (PD) female rats showed an increased stereotypic response to apomorphine and an increased locomotor response to amphetamine in adulthood. These differences were not observed during puberty. No changes in haloperidol-induced catalepsy or MK-801-induced locomotion were seen following PD. In addition, PD female rats showed increased (3)H-MK-801 binding in the striatum and hippocampus, but not in the cortex. PD female rats also showed increased (3)H-haloperidol binding and decreased dopamine transporter binding in striatum. No statistically significant changes in behavior or receptor binding were found in PD males with the exception of increased (3)H-MK-801 binding in cortex. This animal model may be useful to explore the mechanisms by which prenatal nutritional deficiency enhances risk for schizophrenia in humans and may also have implications for developmental processes leading to differential sensitivity to drugs of abuse.", "entity": "Dizocilpine Maleate", "aliases": "Dizocilpine Maleate MK 801 MK-801 MK801", "definition": "A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects.\n    ", "id": "MESH:D016291"}
{"mention": "H", "mention_text": "Epidemiological evidence indicates that prenatal nutritional deprivation may increase the risk of schizophrenia. The goal of these studies was to use an animal model to examine the effects of prenatal protein deprivation on behaviors and receptor binding with relevance to schizophrenia. We report that prenatally protein deprived (PD) female rats showed an increased stereotypic response to apomorphine and an increased locomotor response to amphetamine in adulthood. These differences were not observed during puberty. No changes in haloperidol-induced catalepsy or MK-801-induced locomotion were seen following PD. In addition, PD female rats showed increased (3)H-MK-801 binding in the striatum and hippocampus, but not in the cortex. PD female rats also showed increased (3)H-haloperidol binding and decreased dopamine transporter binding in striatum. No statistically significant changes in behavior or receptor binding were found in PD males with the exception of increased (3)H-MK-801 binding in cortex. This animal model may be useful to explore the mechanisms by which prenatal nutritional deficiency enhances risk for schizophrenia in humans and may also have implications for developmental processes leading to differential sensitivity to drugs of abuse.", "entity": "Hydrogen", "aliases": "Hydrogen", "definition": "The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight [1.00784; 1.00811]. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are PROTONS. Besides the common H1 isotope, hydrogen exists as the stable isotope DEUTERIUM and the unstable, radioactive isotope TRITIUM.\n    ", "id": "MESH:D006859"}
{"mention": "dopamine", "mention_text": "Epidemiological evidence indicates that prenatal nutritional deprivation may increase the risk of schizophrenia. The goal of these studies was to use an animal model to examine the effects of prenatal protein deprivation on behaviors and receptor binding with relevance to schizophrenia. We report that prenatally protein deprived (PD) female rats showed an increased stereotypic response to apomorphine and an increased locomotor response to amphetamine in adulthood. These differences were not observed during puberty. No changes in haloperidol-induced catalepsy or MK-801-induced locomotion were seen following PD. In addition, PD female rats showed increased (3)H-MK-801 binding in the striatum and hippocampus, but not in the cortex. PD female rats also showed increased (3)H-haloperidol binding and decreased dopamine transporter binding in striatum. No statistically significant changes in behavior or receptor binding were found in PD males with the exception of increased (3)H-MK-801 binding in cortex. This animal model may be useful to explore the mechanisms by which prenatal nutritional deficiency enhances risk for schizophrenia in humans and may also have implications for developmental processes leading to differential sensitivity to drugs of abuse.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "nutritional deficiency", "mention_text": "Epidemiological evidence indicates that prenatal nutritional deprivation may increase the risk of schizophrenia. The goal of these studies was to use an animal model to examine the effects of prenatal protein deprivation on behaviors and receptor binding with relevance to schizophrenia. We report that prenatally protein deprived (PD) female rats showed an increased stereotypic response to apomorphine and an increased locomotor response to amphetamine in adulthood. These differences were not observed during puberty. No changes in haloperidol-induced catalepsy or MK-801-induced locomotion were seen following PD. In addition, PD female rats showed increased (3)H-MK-801 binding in the striatum and hippocampus, but not in the cortex. PD female rats also showed increased (3)H-haloperidol binding and decreased dopamine transporter binding in striatum. No statistically significant changes in behavior or receptor binding were found in PD males with the exception of increased (3)H-MK-801 binding in cortex. This animal model may be useful to explore the mechanisms by which prenatal nutritional deficiency enhances risk for schizophrenia in humans and may also have implications for developmental processes leading to differential sensitivity to drugs of abuse.", "entity": "Malnutrition", "aliases": "Malnutrition Nutritional Deficiencies Deficiency Undernutrition", "definition": "An imbalanced nutritional status resulted from insufficient intake of nutrients to meet normal physiological requirement.\n    ", "id": "MESH:D044342"}
{"mention": "proteinuria", "mention_text": "mToR inhibitors-induced proteinuria: mechanisms, significance, and management.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "rapamycin", "mention_text": "Massive urinary protein excretion has been observed after conversion from calcineurin inhibitors to mammalian target of rapamycin (mToR) inhibitors, especially sirolimus, in renal transplant recipients with chronic allograft nephropathy. Because proteinuria is a major predictive factor of poor transplantation outcome, many studies focused on this adverse event during the past years. Whether proteinuria was due to sirolimus or only a consequence of calcineurin inhibitors withdrawal remained unsolved until high range proteinuria has been observed during sirolimus therapy in islet transplantation and in patients who received sirolimus de novo. Podocyte injury and focal segmental glomerulosclerosis have been related to mToR inhibition in some patients, but the pathways underlying these lesions remain hypothetic. We discuss herein the possible mechanisms and the significance of mToR blockade-induced proteinuria.", "entity": "Sirolimus", "aliases": "AY 22 989 22-989 22989 I 2190A I-2190A I2190A Rapamune Rapamycin Sirolimus Wyeth Brand of", "definition": "A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.\n    ", "id": "MESH:D020123"}
{"mention": "sirolimus", "mention_text": "Massive urinary protein excretion has been observed after conversion from calcineurin inhibitors to mammalian target of rapamycin (mToR) inhibitors, especially sirolimus, in renal transplant recipients with chronic allograft nephropathy. Because proteinuria is a major predictive factor of poor transplantation outcome, many studies focused on this adverse event during the past years. Whether proteinuria was due to sirolimus or only a consequence of calcineurin inhibitors withdrawal remained unsolved until high range proteinuria has been observed during sirolimus therapy in islet transplantation and in patients who received sirolimus de novo. Podocyte injury and focal segmental glomerulosclerosis have been related to mToR inhibition in some patients, but the pathways underlying these lesions remain hypothetic. We discuss herein the possible mechanisms and the significance of mToR blockade-induced proteinuria.", "entity": "Sirolimus", "aliases": "AY 22 989 22-989 22989 I 2190A I-2190A I2190A Rapamune Rapamycin Sirolimus Wyeth Brand of", "definition": "A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.\n    ", "id": "MESH:D020123"}
{"mention": "chronic allograft nephropathy", "mention_text": "Massive urinary protein excretion has been observed after conversion from calcineurin inhibitors to mammalian target of rapamycin (mToR) inhibitors, especially sirolimus, in renal transplant recipients with chronic allograft nephropathy. Because proteinuria is a major predictive factor of poor transplantation outcome, many studies focused on this adverse event during the past years. Whether proteinuria was due to sirolimus or only a consequence of calcineurin inhibitors withdrawal remained unsolved until high range proteinuria has been observed during sirolimus therapy in islet transplantation and in patients who received sirolimus de novo. Podocyte injury and focal segmental glomerulosclerosis have been related to mToR inhibition in some patients, but the pathways underlying these lesions remain hypothetic. We discuss herein the possible mechanisms and the significance of mToR blockade-induced proteinuria.", "entity": "Renal Insufficiency, Chronic", "aliases": "Chronic Kidney Disease Diseases Insufficiencies Insufficiency Renal", "definition": "Conditions in which the KIDNEYS perform below the normal level for more than three months. Chronic kidney insufficiency is classified by five stages according to the decline in GLOMERULAR FILTRATION RATE and the degree of kidney damage (as measured by the level of PROTEINURIA). The most severe form is the end-stage renal disease (CHRONIC KIDNEY FAILURE). (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002)\n    ", "id": "MESH:D051436"}
{"mention": "proteinuria", "mention_text": "Massive urinary protein excretion has been observed after conversion from calcineurin inhibitors to mammalian target of rapamycin (mToR) inhibitors, especially sirolimus, in renal transplant recipients with chronic allograft nephropathy. Because proteinuria is a major predictive factor of poor transplantation outcome, many studies focused on this adverse event during the past years. Whether proteinuria was due to sirolimus or only a consequence of calcineurin inhibitors withdrawal remained unsolved until high range proteinuria has been observed during sirolimus therapy in islet transplantation and in patients who received sirolimus de novo. Podocyte injury and focal segmental glomerulosclerosis have been related to mToR inhibition in some patients, but the pathways underlying these lesions remain hypothetic. We discuss herein the possible mechanisms and the significance of mToR blockade-induced proteinuria.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "glomerulosclerosis", "mention_text": "Massive urinary protein excretion has been observed after conversion from calcineurin inhibitors to mammalian target of rapamycin (mToR) inhibitors, especially sirolimus, in renal transplant recipients with chronic allograft nephropathy. Because proteinuria is a major predictive factor of poor transplantation outcome, many studies focused on this adverse event during the past years. Whether proteinuria was due to sirolimus or only a consequence of calcineurin inhibitors withdrawal remained unsolved until high range proteinuria has been observed during sirolimus therapy in islet transplantation and in patients who received sirolimus de novo. Podocyte injury and focal segmental glomerulosclerosis have been related to mToR inhibition in some patients, but the pathways underlying these lesions remain hypothetic. We discuss herein the possible mechanisms and the significance of mToR blockade-induced proteinuria.", "entity": "Glomerulonephritis", "aliases": "Bright Disease Glomerulonephritides Glomerulonephritis", "definition": "Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.\n    ", "id": "MESH:D005921"}
{"mention": "ribonucleic acid", "mention_text": "Hypothalamic prolactin receptor messenger ribonucleic acid levels, prolactin signaling, and hyperprolactinemic inhibition of pulsatile luteinizing hormone secretion are dependent on estradiol.", "entity": "RNA", "aliases": "Acid Ribonucleic Gene Products RNA Non Polyadenylated Non-Polyadenylated", "definition": "A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)\n    ", "id": "MESH:D012313"}
{"mention": "hyperprolactinemic", "mention_text": "Hypothalamic prolactin receptor messenger ribonucleic acid levels, prolactin signaling, and hyperprolactinemic inhibition of pulsatile luteinizing hormone secretion are dependent on estradiol.", "entity": "Hyperprolactinemia", "aliases": "Hyperprolactinaemia Hyperprolactinemia Hyperprolactinemias Hypersecretion Syndrome Prolactin Inappropriate Secretion", "definition": "Increased levels of PROLACTIN in the BLOOD, which may be associated with AMENORRHEA and GALACTORRHEA. Relatively common etiologies include PROLACTINOMA, medication effect, KIDNEY FAILURE, granulomatous diseases of the PITUITARY GLAND, and disorders which interfere with the hypothalamic inhibition of prolactin release. Ectopic (non-pituitary) production of prolactin may also occur. (From Joynt, Clinical Neurology, 1992, Ch36, pp77-8)\n    ", "id": "MESH:D006966"}
{"mention": "estradiol", "mention_text": "Hypothalamic prolactin receptor messenger ribonucleic acid levels, prolactin signaling, and hyperprolactinemic inhibition of pulsatile luteinizing hormone secretion are dependent on estradiol.", "entity": "Estradiol", "aliases": "17 beta Estradiol Oestradiol beta-Estradiol beta-Oestradiol Aerodiol Estrace Estraderm TTS alpha 17beta Anhydrous Hemihydrate (17 alpha)-Isomer Monohydrate Orion Brand (+-)-Isomer (-)-Isomer (16 alpha,17 beta)-Isomer (17-alpha)-Isomer (8 beta)-(+-)-Isomer (9 beta,17 Monosodium Salt Sodium Estradiol-17 Estradiol-17beta Novartis Pharmaceuticals of Ovocyclin Vivelle", "definition": "The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.\n    ", "id": "MESH:D004958"}
{"mention": "Hyperprolactinemia", "mention_text": "Hyperprolactinemia can reduce fertility and libido. Although central prolactin actions are thought to contribute to this, the mechanisms are poorly understood. We first tested whether chronic hyperprolactinemia inhibited two neuroendocrine parameters necessary for female fertility: pulsatile LH secretion and the estrogen-induced LH surge. Chronic hyperprolactinemia induced by the dopamine antagonist sulpiride caused a 40% reduction LH pulse frequency in ovariectomized rats, but only in the presence of chronic low levels of estradiol. Sulpiride did not affect the magnitude of a steroid-induced LH surge or the percentage of GnRH neurons activated during the surge. Estradiol is known to influence expression of the long form of prolactin receptors (PRL-R) and components of prolactin's signaling pathway. To test the hypothesis that estrogen increases PRL-R expression and sensitivity to prolactin, we next demonstrated that estradiol greatly augments prolactin-induced STAT5 activation. Lastly, we measured PRL-R and suppressor of cytokine signaling (SOCS-1 and -3 and CIS, which reflect the level of prolactin signaling) mRNAs in response to sulpiride and estradiol. Sulpiride induced only SOCS-1 in the medial preoptic area, where GnRH neurons are regulated, but in the arcuate nucleus and choroid plexus, PRL-R, SOCS-3, and CIS mRNA levels were also induced. Estradiol enhanced these effects on SOCS-3 and CIS. Interestingly, estradiol also induced PRL-R, SOCS-3, and CIS mRNA levels independently. These data show that GnRH pulse frequency is inhibited by chronic hyperprolactinemia in a steroid-dependent manner. They also provide evidence for estradiol-dependent and brain region-specific regulation of PRL-R expression and signaling responses by prolactin.", "entity": "Hyperprolactinemia", "aliases": "Hyperprolactinaemia Hyperprolactinemia Hyperprolactinemias Hypersecretion Syndrome Prolactin Inappropriate Secretion", "definition": "Increased levels of PROLACTIN in the BLOOD, which may be associated with AMENORRHEA and GALACTORRHEA. Relatively common etiologies include PROLACTINOMA, medication effect, KIDNEY FAILURE, granulomatous diseases of the PITUITARY GLAND, and disorders which interfere with the hypothalamic inhibition of prolactin release. Ectopic (non-pituitary) production of prolactin may also occur. (From Joynt, Clinical Neurology, 1992, Ch36, pp77-8)\n    ", "id": "MESH:D006966"}
{"mention": "hyperprolactinemia", "mention_text": "Hyperprolactinemia can reduce fertility and libido. Although central prolactin actions are thought to contribute to this, the mechanisms are poorly understood. We first tested whether chronic hyperprolactinemia inhibited two neuroendocrine parameters necessary for female fertility: pulsatile LH secretion and the estrogen-induced LH surge. Chronic hyperprolactinemia induced by the dopamine antagonist sulpiride caused a 40% reduction LH pulse frequency in ovariectomized rats, but only in the presence of chronic low levels of estradiol. Sulpiride did not affect the magnitude of a steroid-induced LH surge or the percentage of GnRH neurons activated during the surge. Estradiol is known to influence expression of the long form of prolactin receptors (PRL-R) and components of prolactin's signaling pathway. To test the hypothesis that estrogen increases PRL-R expression and sensitivity to prolactin, we next demonstrated that estradiol greatly augments prolactin-induced STAT5 activation. Lastly, we measured PRL-R and suppressor of cytokine signaling (SOCS-1 and -3 and CIS, which reflect the level of prolactin signaling) mRNAs in response to sulpiride and estradiol. Sulpiride induced only SOCS-1 in the medial preoptic area, where GnRH neurons are regulated, but in the arcuate nucleus and choroid plexus, PRL-R, SOCS-3, and CIS mRNA levels were also induced. Estradiol enhanced these effects on SOCS-3 and CIS. Interestingly, estradiol also induced PRL-R, SOCS-3, and CIS mRNA levels independently. These data show that GnRH pulse frequency is inhibited by chronic hyperprolactinemia in a steroid-dependent manner. They also provide evidence for estradiol-dependent and brain region-specific regulation of PRL-R expression and signaling responses by prolactin.", "entity": "Hyperprolactinemia", "aliases": "Hyperprolactinaemia Hyperprolactinemia Hyperprolactinemias Hypersecretion Syndrome Prolactin Inappropriate Secretion", "definition": "Increased levels of PROLACTIN in the BLOOD, which may be associated with AMENORRHEA and GALACTORRHEA. Relatively common etiologies include PROLACTINOMA, medication effect, KIDNEY FAILURE, granulomatous diseases of the PITUITARY GLAND, and disorders which interfere with the hypothalamic inhibition of prolactin release. Ectopic (non-pituitary) production of prolactin may also occur. (From Joynt, Clinical Neurology, 1992, Ch36, pp77-8)\n    ", "id": "MESH:D006966"}
{"mention": "estrogen", "mention_text": "Hyperprolactinemia can reduce fertility and libido. Although central prolactin actions are thought to contribute to this, the mechanisms are poorly understood. We first tested whether chronic hyperprolactinemia inhibited two neuroendocrine parameters necessary for female fertility: pulsatile LH secretion and the estrogen-induced LH surge. Chronic hyperprolactinemia induced by the dopamine antagonist sulpiride caused a 40% reduction LH pulse frequency in ovariectomized rats, but only in the presence of chronic low levels of estradiol. Sulpiride did not affect the magnitude of a steroid-induced LH surge or the percentage of GnRH neurons activated during the surge. Estradiol is known to influence expression of the long form of prolactin receptors (PRL-R) and components of prolactin's signaling pathway. To test the hypothesis that estrogen increases PRL-R expression and sensitivity to prolactin, we next demonstrated that estradiol greatly augments prolactin-induced STAT5 activation. Lastly, we measured PRL-R and suppressor of cytokine signaling (SOCS-1 and -3 and CIS, which reflect the level of prolactin signaling) mRNAs in response to sulpiride and estradiol. Sulpiride induced only SOCS-1 in the medial preoptic area, where GnRH neurons are regulated, but in the arcuate nucleus and choroid plexus, PRL-R, SOCS-3, and CIS mRNA levels were also induced. Estradiol enhanced these effects on SOCS-3 and CIS. Interestingly, estradiol also induced PRL-R, SOCS-3, and CIS mRNA levels independently. These data show that GnRH pulse frequency is inhibited by chronic hyperprolactinemia in a steroid-dependent manner. They also provide evidence for estradiol-dependent and brain region-specific regulation of PRL-R expression and signaling responses by prolactin.", "entity": "Estrogens", "aliases": "Agents Estrogenic Agonists Estrogen Receptor Compounds Effects Effect Estrogens", "definition": "Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds.\n    ", "id": "MESH:D004967"}
{"mention": "dopamine", "mention_text": "Hyperprolactinemia can reduce fertility and libido. Although central prolactin actions are thought to contribute to this, the mechanisms are poorly understood. We first tested whether chronic hyperprolactinemia inhibited two neuroendocrine parameters necessary for female fertility: pulsatile LH secretion and the estrogen-induced LH surge. Chronic hyperprolactinemia induced by the dopamine antagonist sulpiride caused a 40% reduction LH pulse frequency in ovariectomized rats, but only in the presence of chronic low levels of estradiol. Sulpiride did not affect the magnitude of a steroid-induced LH surge or the percentage of GnRH neurons activated during the surge. Estradiol is known to influence expression of the long form of prolactin receptors (PRL-R) and components of prolactin's signaling pathway. To test the hypothesis that estrogen increases PRL-R expression and sensitivity to prolactin, we next demonstrated that estradiol greatly augments prolactin-induced STAT5 activation. Lastly, we measured PRL-R and suppressor of cytokine signaling (SOCS-1 and -3 and CIS, which reflect the level of prolactin signaling) mRNAs in response to sulpiride and estradiol. Sulpiride induced only SOCS-1 in the medial preoptic area, where GnRH neurons are regulated, but in the arcuate nucleus and choroid plexus, PRL-R, SOCS-3, and CIS mRNA levels were also induced. Estradiol enhanced these effects on SOCS-3 and CIS. Interestingly, estradiol also induced PRL-R, SOCS-3, and CIS mRNA levels independently. These data show that GnRH pulse frequency is inhibited by chronic hyperprolactinemia in a steroid-dependent manner. They also provide evidence for estradiol-dependent and brain region-specific regulation of PRL-R expression and signaling responses by prolactin.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "sulpiride", "mention_text": "Hyperprolactinemia can reduce fertility and libido. Although central prolactin actions are thought to contribute to this, the mechanisms are poorly understood. We first tested whether chronic hyperprolactinemia inhibited two neuroendocrine parameters necessary for female fertility: pulsatile LH secretion and the estrogen-induced LH surge. Chronic hyperprolactinemia induced by the dopamine antagonist sulpiride caused a 40% reduction LH pulse frequency in ovariectomized rats, but only in the presence of chronic low levels of estradiol. Sulpiride did not affect the magnitude of a steroid-induced LH surge or the percentage of GnRH neurons activated during the surge. Estradiol is known to influence expression of the long form of prolactin receptors (PRL-R) and components of prolactin's signaling pathway. To test the hypothesis that estrogen increases PRL-R expression and sensitivity to prolactin, we next demonstrated that estradiol greatly augments prolactin-induced STAT5 activation. Lastly, we measured PRL-R and suppressor of cytokine signaling (SOCS-1 and -3 and CIS, which reflect the level of prolactin signaling) mRNAs in response to sulpiride and estradiol. Sulpiride induced only SOCS-1 in the medial preoptic area, where GnRH neurons are regulated, but in the arcuate nucleus and choroid plexus, PRL-R, SOCS-3, and CIS mRNA levels were also induced. Estradiol enhanced these effects on SOCS-3 and CIS. Interestingly, estradiol also induced PRL-R, SOCS-3, and CIS mRNA levels independently. These data show that GnRH pulse frequency is inhibited by chronic hyperprolactinemia in a steroid-dependent manner. They also provide evidence for estradiol-dependent and brain region-specific regulation of PRL-R expression and signaling responses by prolactin.", "entity": "Sulpiride", "aliases": "Aiglonyl Allphar Brand of Sulpiride Almirall Areu Arminol Centrum Deponerton Desisulpid Desitin Digton Dogmatil Dolmatil Dolorgiet Eglonyl Ekilid Erempharma Fumouzer Guastil Hennig Hexal Hoechst Hormosan Krewel Lebopride Meresa Pharmacia Pontiride Psicocen Psicofarma Rosemont Sanofi Synthelabo Sanofi-Synthelabo Spyfarma Sulp Sulperide Sulpitil Sulpivert Sulpor Synédil Tepavil Uriach Vertigo Vertigo-Meresa neogama vertigo vertigo-neogama", "definition": "A dopamine D2-receptor antagonist. It has been used therapeutically as an antidepressant, antipsychotic, and as a digestive aid. (From Merck Index, 11th ed)\n    ", "id": "MESH:D013469"}
{"mention": "estradiol", "mention_text": "Hyperprolactinemia can reduce fertility and libido. Although central prolactin actions are thought to contribute to this, the mechanisms are poorly understood. We first tested whether chronic hyperprolactinemia inhibited two neuroendocrine parameters necessary for female fertility: pulsatile LH secretion and the estrogen-induced LH surge. Chronic hyperprolactinemia induced by the dopamine antagonist sulpiride caused a 40% reduction LH pulse frequency in ovariectomized rats, but only in the presence of chronic low levels of estradiol. Sulpiride did not affect the magnitude of a steroid-induced LH surge or the percentage of GnRH neurons activated during the surge. Estradiol is known to influence expression of the long form of prolactin receptors (PRL-R) and components of prolactin's signaling pathway. To test the hypothesis that estrogen increases PRL-R expression and sensitivity to prolactin, we next demonstrated that estradiol greatly augments prolactin-induced STAT5 activation. Lastly, we measured PRL-R and suppressor of cytokine signaling (SOCS-1 and -3 and CIS, which reflect the level of prolactin signaling) mRNAs in response to sulpiride and estradiol. Sulpiride induced only SOCS-1 in the medial preoptic area, where GnRH neurons are regulated, but in the arcuate nucleus and choroid plexus, PRL-R, SOCS-3, and CIS mRNA levels were also induced. Estradiol enhanced these effects on SOCS-3 and CIS. Interestingly, estradiol also induced PRL-R, SOCS-3, and CIS mRNA levels independently. These data show that GnRH pulse frequency is inhibited by chronic hyperprolactinemia in a steroid-dependent manner. They also provide evidence for estradiol-dependent and brain region-specific regulation of PRL-R expression and signaling responses by prolactin.", "entity": "Estradiol", "aliases": "17 beta Estradiol Oestradiol beta-Estradiol beta-Oestradiol Aerodiol Estrace Estraderm TTS alpha 17beta Anhydrous Hemihydrate (17 alpha)-Isomer Monohydrate Orion Brand (+-)-Isomer (-)-Isomer (16 alpha,17 beta)-Isomer (17-alpha)-Isomer (8 beta)-(+-)-Isomer (9 beta,17 Monosodium Salt Sodium Estradiol-17 Estradiol-17beta Novartis Pharmaceuticals of Ovocyclin Vivelle", "definition": "The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.\n    ", "id": "MESH:D004958"}
{"mention": "Sulpiride", "mention_text": "Hyperprolactinemia can reduce fertility and libido. Although central prolactin actions are thought to contribute to this, the mechanisms are poorly understood. We first tested whether chronic hyperprolactinemia inhibited two neuroendocrine parameters necessary for female fertility: pulsatile LH secretion and the estrogen-induced LH surge. Chronic hyperprolactinemia induced by the dopamine antagonist sulpiride caused a 40% reduction LH pulse frequency in ovariectomized rats, but only in the presence of chronic low levels of estradiol. Sulpiride did not affect the magnitude of a steroid-induced LH surge or the percentage of GnRH neurons activated during the surge. Estradiol is known to influence expression of the long form of prolactin receptors (PRL-R) and components of prolactin's signaling pathway. To test the hypothesis that estrogen increases PRL-R expression and sensitivity to prolactin, we next demonstrated that estradiol greatly augments prolactin-induced STAT5 activation. Lastly, we measured PRL-R and suppressor of cytokine signaling (SOCS-1 and -3 and CIS, which reflect the level of prolactin signaling) mRNAs in response to sulpiride and estradiol. Sulpiride induced only SOCS-1 in the medial preoptic area, where GnRH neurons are regulated, but in the arcuate nucleus and choroid plexus, PRL-R, SOCS-3, and CIS mRNA levels were also induced. Estradiol enhanced these effects on SOCS-3 and CIS. Interestingly, estradiol also induced PRL-R, SOCS-3, and CIS mRNA levels independently. These data show that GnRH pulse frequency is inhibited by chronic hyperprolactinemia in a steroid-dependent manner. They also provide evidence for estradiol-dependent and brain region-specific regulation of PRL-R expression and signaling responses by prolactin.", "entity": "Sulpiride", "aliases": "Aiglonyl Allphar Brand of Sulpiride Almirall Areu Arminol Centrum Deponerton Desisulpid Desitin Digton Dogmatil Dolmatil Dolorgiet Eglonyl Ekilid Erempharma Fumouzer Guastil Hennig Hexal Hoechst Hormosan Krewel Lebopride Meresa Pharmacia Pontiride Psicocen Psicofarma Rosemont Sanofi Synthelabo Sanofi-Synthelabo Spyfarma Sulp Sulperide Sulpitil Sulpivert Sulpor Synédil Tepavil Uriach Vertigo Vertigo-Meresa neogama vertigo vertigo-neogama", "definition": "A dopamine D2-receptor antagonist. It has been used therapeutically as an antidepressant, antipsychotic, and as a digestive aid. (From Merck Index, 11th ed)\n    ", "id": "MESH:D013469"}
{"mention": "steroid", "mention_text": "Hyperprolactinemia can reduce fertility and libido. Although central prolactin actions are thought to contribute to this, the mechanisms are poorly understood. We first tested whether chronic hyperprolactinemia inhibited two neuroendocrine parameters necessary for female fertility: pulsatile LH secretion and the estrogen-induced LH surge. Chronic hyperprolactinemia induced by the dopamine antagonist sulpiride caused a 40% reduction LH pulse frequency in ovariectomized rats, but only in the presence of chronic low levels of estradiol. Sulpiride did not affect the magnitude of a steroid-induced LH surge or the percentage of GnRH neurons activated during the surge. Estradiol is known to influence expression of the long form of prolactin receptors (PRL-R) and components of prolactin's signaling pathway. To test the hypothesis that estrogen increases PRL-R expression and sensitivity to prolactin, we next demonstrated that estradiol greatly augments prolactin-induced STAT5 activation. Lastly, we measured PRL-R and suppressor of cytokine signaling (SOCS-1 and -3 and CIS, which reflect the level of prolactin signaling) mRNAs in response to sulpiride and estradiol. Sulpiride induced only SOCS-1 in the medial preoptic area, where GnRH neurons are regulated, but in the arcuate nucleus and choroid plexus, PRL-R, SOCS-3, and CIS mRNA levels were also induced. Estradiol enhanced these effects on SOCS-3 and CIS. Interestingly, estradiol also induced PRL-R, SOCS-3, and CIS mRNA levels independently. These data show that GnRH pulse frequency is inhibited by chronic hyperprolactinemia in a steroid-dependent manner. They also provide evidence for estradiol-dependent and brain region-specific regulation of PRL-R expression and signaling responses by prolactin.", "entity": "Steroids", "aliases": "Catatoxic Steroids", "definition": "A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)\n    ", "id": "MESH:D013256"}
{"mention": "Estradiol", "mention_text": "Hyperprolactinemia can reduce fertility and libido. Although central prolactin actions are thought to contribute to this, the mechanisms are poorly understood. We first tested whether chronic hyperprolactinemia inhibited two neuroendocrine parameters necessary for female fertility: pulsatile LH secretion and the estrogen-induced LH surge. Chronic hyperprolactinemia induced by the dopamine antagonist sulpiride caused a 40% reduction LH pulse frequency in ovariectomized rats, but only in the presence of chronic low levels of estradiol. Sulpiride did not affect the magnitude of a steroid-induced LH surge or the percentage of GnRH neurons activated during the surge. Estradiol is known to influence expression of the long form of prolactin receptors (PRL-R) and components of prolactin's signaling pathway. To test the hypothesis that estrogen increases PRL-R expression and sensitivity to prolactin, we next demonstrated that estradiol greatly augments prolactin-induced STAT5 activation. Lastly, we measured PRL-R and suppressor of cytokine signaling (SOCS-1 and -3 and CIS, which reflect the level of prolactin signaling) mRNAs in response to sulpiride and estradiol. Sulpiride induced only SOCS-1 in the medial preoptic area, where GnRH neurons are regulated, but in the arcuate nucleus and choroid plexus, PRL-R, SOCS-3, and CIS mRNA levels were also induced. Estradiol enhanced these effects on SOCS-3 and CIS. Interestingly, estradiol also induced PRL-R, SOCS-3, and CIS mRNA levels independently. These data show that GnRH pulse frequency is inhibited by chronic hyperprolactinemia in a steroid-dependent manner. They also provide evidence for estradiol-dependent and brain region-specific regulation of PRL-R expression and signaling responses by prolactin.", "entity": "Estradiol", "aliases": "17 beta Estradiol Oestradiol beta-Estradiol beta-Oestradiol Aerodiol Estrace Estraderm TTS alpha 17beta Anhydrous Hemihydrate (17 alpha)-Isomer Monohydrate Orion Brand (+-)-Isomer (-)-Isomer (16 alpha,17 beta)-Isomer (17-alpha)-Isomer (8 beta)-(+-)-Isomer (9 beta,17 Monosodium Salt Sodium Estradiol-17 Estradiol-17beta Novartis Pharmaceuticals of Ovocyclin Vivelle", "definition": "The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.\n    ", "id": "MESH:D004958"}
{"mention": "cholesteryl ester", "mention_text": "Estrogen prevents cholesteryl ester accumulation in macrophages induced by the HIV protease inhibitor ritonavir.", "entity": "Cholesterol Esters", "aliases": "Cholesterol Esters Cholesteryl", "definition": "Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis.\n    ", "id": "MESH:D002788"}
{"mention": "ritonavir", "mention_text": "Estrogen prevents cholesteryl ester accumulation in macrophages induced by the HIV protease inhibitor ritonavir.", "entity": "Ritonavir", "aliases": "538 ABT ABT-538 ABT538 Norvir Ritonavir", "definition": "An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. It also inhibits CYTOCHROME P-450 CYP3A.\n    ", "id": "MESH:D019438"}
{"mention": "ritonavir", "mention_text": "Individuals with HIV can now live long lives with drug therapy that often includes protease inhibitors such as ritonavir. Many patients, however, develop negative long-term side effects such as premature atherosclerosis. We have previously demonstrated that ritonavir treatment increases atherosclerotic lesion formation in male mice to a greater extent than in female mice. Furthermore, peripheral blood monocytes isolated from ritonavir-treated females had less cholesteryl ester accumulation. In the present study, we have investigated the molecular mechanisms by which female hormones influence cholesterol metabolism in macrophages in response to the HIV protease inhibitor ritonavir. We have utilized the human monocyte cell line, THP-1 as a model to address this question. Briefly, cells were differentiated for 72 h with 100 nM PMA to obtain a macrophage-like phenotype in the presence or absence of 1 nM 17beta-estradiol (E2), 100 nM progesterone or vehicle (0.01% ethanol). Cells were then treated with 30 ng/ml ritonavir or vehicle in the presence of aggregated LDL for 24 h. Cell extracts were harvested, and lipid or total RNA was isolated. E2 decreased the accumulation of cholesteryl esters in macrophages following ritonavir treatment. Ritonavir increased the expression of the scavenger receptor, CD36 mRNA, responsible for the uptake of LDL. Additionally, ritonavir treatment selectively increased the relative levels of PPARgamma mRNA, a transcription factor responsible for the regulation of CD36 mRNA expression. Treatment with E2, however, failed to prevent these increases at the mRNA level. E2 did, however, significantly suppress CD36 protein levels as measured by fluorescent immunocytochemistry. This data suggests that E2 modifies the expression of CD36 at the level of protein expression in monocyte-derived macrophages resulting in reduced cholesteryl ester accumulation following ritonavir treatment.", "entity": "Ritonavir", "aliases": "538 ABT ABT-538 ABT538 Norvir Ritonavir", "definition": "An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. It also inhibits CYTOCHROME P-450 CYP3A.\n    ", "id": "MESH:D019438"}
{"mention": "premature atherosclerosis", "mention_text": "Individuals with HIV can now live long lives with drug therapy that often includes protease inhibitors such as ritonavir. Many patients, however, develop negative long-term side effects such as premature atherosclerosis. We have previously demonstrated that ritonavir treatment increases atherosclerotic lesion formation in male mice to a greater extent than in female mice. Furthermore, peripheral blood monocytes isolated from ritonavir-treated females had less cholesteryl ester accumulation. In the present study, we have investigated the molecular mechanisms by which female hormones influence cholesterol metabolism in macrophages in response to the HIV protease inhibitor ritonavir. We have utilized the human monocyte cell line, THP-1 as a model to address this question. Briefly, cells were differentiated for 72 h with 100 nM PMA to obtain a macrophage-like phenotype in the presence or absence of 1 nM 17beta-estradiol (E2), 100 nM progesterone or vehicle (0.01% ethanol). Cells were then treated with 30 ng/ml ritonavir or vehicle in the presence of aggregated LDL for 24 h. Cell extracts were harvested, and lipid or total RNA was isolated. E2 decreased the accumulation of cholesteryl esters in macrophages following ritonavir treatment. Ritonavir increased the expression of the scavenger receptor, CD36 mRNA, responsible for the uptake of LDL. Additionally, ritonavir treatment selectively increased the relative levels of PPARgamma mRNA, a transcription factor responsible for the regulation of CD36 mRNA expression. Treatment with E2, however, failed to prevent these increases at the mRNA level. E2 did, however, significantly suppress CD36 protein levels as measured by fluorescent immunocytochemistry. This data suggests that E2 modifies the expression of CD36 at the level of protein expression in monocyte-derived macrophages resulting in reduced cholesteryl ester accumulation following ritonavir treatment.", "entity": "Atherosclerosis", "aliases": "Atherogenesis Atheroscleroses Atherosclerosis", "definition": "A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA.\n    ", "id": "MESH:D050197"}
{"mention": "atherosclerotic lesion", "mention_text": "Individuals with HIV can now live long lives with drug therapy that often includes protease inhibitors such as ritonavir. Many patients, however, develop negative long-term side effects such as premature atherosclerosis. We have previously demonstrated that ritonavir treatment increases atherosclerotic lesion formation in male mice to a greater extent than in female mice. Furthermore, peripheral blood monocytes isolated from ritonavir-treated females had less cholesteryl ester accumulation. In the present study, we have investigated the molecular mechanisms by which female hormones influence cholesterol metabolism in macrophages in response to the HIV protease inhibitor ritonavir. We have utilized the human monocyte cell line, THP-1 as a model to address this question. Briefly, cells were differentiated for 72 h with 100 nM PMA to obtain a macrophage-like phenotype in the presence or absence of 1 nM 17beta-estradiol (E2), 100 nM progesterone or vehicle (0.01% ethanol). Cells were then treated with 30 ng/ml ritonavir or vehicle in the presence of aggregated LDL for 24 h. Cell extracts were harvested, and lipid or total RNA was isolated. E2 decreased the accumulation of cholesteryl esters in macrophages following ritonavir treatment. Ritonavir increased the expression of the scavenger receptor, CD36 mRNA, responsible for the uptake of LDL. Additionally, ritonavir treatment selectively increased the relative levels of PPARgamma mRNA, a transcription factor responsible for the regulation of CD36 mRNA expression. Treatment with E2, however, failed to prevent these increases at the mRNA level. E2 did, however, significantly suppress CD36 protein levels as measured by fluorescent immunocytochemistry. This data suggests that E2 modifies the expression of CD36 at the level of protein expression in monocyte-derived macrophages resulting in reduced cholesteryl ester accumulation following ritonavir treatment.", "entity": "Atherosclerosis", "aliases": "Atherogenesis Atheroscleroses Atherosclerosis", "definition": "A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA.\n    ", "id": "MESH:D050197"}
{"mention": "cholesteryl ester", "mention_text": "Individuals with HIV can now live long lives with drug therapy that often includes protease inhibitors such as ritonavir. Many patients, however, develop negative long-term side effects such as premature atherosclerosis. We have previously demonstrated that ritonavir treatment increases atherosclerotic lesion formation in male mice to a greater extent than in female mice. Furthermore, peripheral blood monocytes isolated from ritonavir-treated females had less cholesteryl ester accumulation. In the present study, we have investigated the molecular mechanisms by which female hormones influence cholesterol metabolism in macrophages in response to the HIV protease inhibitor ritonavir. We have utilized the human monocyte cell line, THP-1 as a model to address this question. Briefly, cells were differentiated for 72 h with 100 nM PMA to obtain a macrophage-like phenotype in the presence or absence of 1 nM 17beta-estradiol (E2), 100 nM progesterone or vehicle (0.01% ethanol). Cells were then treated with 30 ng/ml ritonavir or vehicle in the presence of aggregated LDL for 24 h. Cell extracts were harvested, and lipid or total RNA was isolated. E2 decreased the accumulation of cholesteryl esters in macrophages following ritonavir treatment. Ritonavir increased the expression of the scavenger receptor, CD36 mRNA, responsible for the uptake of LDL. Additionally, ritonavir treatment selectively increased the relative levels of PPARgamma mRNA, a transcription factor responsible for the regulation of CD36 mRNA expression. Treatment with E2, however, failed to prevent these increases at the mRNA level. E2 did, however, significantly suppress CD36 protein levels as measured by fluorescent immunocytochemistry. This data suggests that E2 modifies the expression of CD36 at the level of protein expression in monocyte-derived macrophages resulting in reduced cholesteryl ester accumulation following ritonavir treatment.", "entity": "Cholesterol Esters", "aliases": "Cholesterol Esters Cholesteryl", "definition": "Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis.\n    ", "id": "MESH:D002788"}
{"mention": "cholesterol", "mention_text": "Individuals with HIV can now live long lives with drug therapy that often includes protease inhibitors such as ritonavir. Many patients, however, develop negative long-term side effects such as premature atherosclerosis. We have previously demonstrated that ritonavir treatment increases atherosclerotic lesion formation in male mice to a greater extent than in female mice. Furthermore, peripheral blood monocytes isolated from ritonavir-treated females had less cholesteryl ester accumulation. In the present study, we have investigated the molecular mechanisms by which female hormones influence cholesterol metabolism in macrophages in response to the HIV protease inhibitor ritonavir. We have utilized the human monocyte cell line, THP-1 as a model to address this question. Briefly, cells were differentiated for 72 h with 100 nM PMA to obtain a macrophage-like phenotype in the presence or absence of 1 nM 17beta-estradiol (E2), 100 nM progesterone or vehicle (0.01% ethanol). Cells were then treated with 30 ng/ml ritonavir or vehicle in the presence of aggregated LDL for 24 h. Cell extracts were harvested, and lipid or total RNA was isolated. E2 decreased the accumulation of cholesteryl esters in macrophages following ritonavir treatment. Ritonavir increased the expression of the scavenger receptor, CD36 mRNA, responsible for the uptake of LDL. Additionally, ritonavir treatment selectively increased the relative levels of PPARgamma mRNA, a transcription factor responsible for the regulation of CD36 mRNA expression. Treatment with E2, however, failed to prevent these increases at the mRNA level. E2 did, however, significantly suppress CD36 protein levels as measured by fluorescent immunocytochemistry. This data suggests that E2 modifies the expression of CD36 at the level of protein expression in monocyte-derived macrophages resulting in reduced cholesteryl ester accumulation following ritonavir treatment.", "entity": "Cholesterol", "aliases": "Cholesterol Epicholesterol", "definition": "The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.\n    ", "id": "MESH:D002784"}
{"mention": "17beta-estradiol", "mention_text": "Individuals with HIV can now live long lives with drug therapy that often includes protease inhibitors such as ritonavir. Many patients, however, develop negative long-term side effects such as premature atherosclerosis. We have previously demonstrated that ritonavir treatment increases atherosclerotic lesion formation in male mice to a greater extent than in female mice. Furthermore, peripheral blood monocytes isolated from ritonavir-treated females had less cholesteryl ester accumulation. In the present study, we have investigated the molecular mechanisms by which female hormones influence cholesterol metabolism in macrophages in response to the HIV protease inhibitor ritonavir. We have utilized the human monocyte cell line, THP-1 as a model to address this question. Briefly, cells were differentiated for 72 h with 100 nM PMA to obtain a macrophage-like phenotype in the presence or absence of 1 nM 17beta-estradiol (E2), 100 nM progesterone or vehicle (0.01% ethanol). Cells were then treated with 30 ng/ml ritonavir or vehicle in the presence of aggregated LDL for 24 h. Cell extracts were harvested, and lipid or total RNA was isolated. E2 decreased the accumulation of cholesteryl esters in macrophages following ritonavir treatment. Ritonavir increased the expression of the scavenger receptor, CD36 mRNA, responsible for the uptake of LDL. Additionally, ritonavir treatment selectively increased the relative levels of PPARgamma mRNA, a transcription factor responsible for the regulation of CD36 mRNA expression. Treatment with E2, however, failed to prevent these increases at the mRNA level. E2 did, however, significantly suppress CD36 protein levels as measured by fluorescent immunocytochemistry. This data suggests that E2 modifies the expression of CD36 at the level of protein expression in monocyte-derived macrophages resulting in reduced cholesteryl ester accumulation following ritonavir treatment.", "entity": "Estradiol", "aliases": "17 beta Estradiol Oestradiol beta-Estradiol beta-Oestradiol Aerodiol Estrace Estraderm TTS alpha 17beta Anhydrous Hemihydrate (17 alpha)-Isomer Monohydrate Orion Brand (+-)-Isomer (-)-Isomer (16 alpha,17 beta)-Isomer (17-alpha)-Isomer (8 beta)-(+-)-Isomer (9 beta,17 Monosodium Salt Sodium Estradiol-17 Estradiol-17beta Novartis Pharmaceuticals of Ovocyclin Vivelle", "definition": "The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.\n    ", "id": "MESH:D004958"}
{"mention": "E2", "mention_text": "Individuals with HIV can now live long lives with drug therapy that often includes protease inhibitors such as ritonavir. Many patients, however, develop negative long-term side effects such as premature atherosclerosis. We have previously demonstrated that ritonavir treatment increases atherosclerotic lesion formation in male mice to a greater extent than in female mice. Furthermore, peripheral blood monocytes isolated from ritonavir-treated females had less cholesteryl ester accumulation. In the present study, we have investigated the molecular mechanisms by which female hormones influence cholesterol metabolism in macrophages in response to the HIV protease inhibitor ritonavir. We have utilized the human monocyte cell line, THP-1 as a model to address this question. Briefly, cells were differentiated for 72 h with 100 nM PMA to obtain a macrophage-like phenotype in the presence or absence of 1 nM 17beta-estradiol (E2), 100 nM progesterone or vehicle (0.01% ethanol). Cells were then treated with 30 ng/ml ritonavir or vehicle in the presence of aggregated LDL for 24 h. Cell extracts were harvested, and lipid or total RNA was isolated. E2 decreased the accumulation of cholesteryl esters in macrophages following ritonavir treatment. Ritonavir increased the expression of the scavenger receptor, CD36 mRNA, responsible for the uptake of LDL. Additionally, ritonavir treatment selectively increased the relative levels of PPARgamma mRNA, a transcription factor responsible for the regulation of CD36 mRNA expression. Treatment with E2, however, failed to prevent these increases at the mRNA level. E2 did, however, significantly suppress CD36 protein levels as measured by fluorescent immunocytochemistry. This data suggests that E2 modifies the expression of CD36 at the level of protein expression in monocyte-derived macrophages resulting in reduced cholesteryl ester accumulation following ritonavir treatment.", "entity": "Estradiol", "aliases": "17 beta Estradiol Oestradiol beta-Estradiol beta-Oestradiol Aerodiol Estrace Estraderm TTS alpha 17beta Anhydrous Hemihydrate (17 alpha)-Isomer Monohydrate Orion Brand (+-)-Isomer (-)-Isomer (16 alpha,17 beta)-Isomer (17-alpha)-Isomer (8 beta)-(+-)-Isomer (9 beta,17 Monosodium Salt Sodium Estradiol-17 Estradiol-17beta Novartis Pharmaceuticals of Ovocyclin Vivelle", "definition": "The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.\n    ", "id": "MESH:D004958"}
{"mention": "progesterone", "mention_text": "Individuals with HIV can now live long lives with drug therapy that often includes protease inhibitors such as ritonavir. Many patients, however, develop negative long-term side effects such as premature atherosclerosis. We have previously demonstrated that ritonavir treatment increases atherosclerotic lesion formation in male mice to a greater extent than in female mice. Furthermore, peripheral blood monocytes isolated from ritonavir-treated females had less cholesteryl ester accumulation. In the present study, we have investigated the molecular mechanisms by which female hormones influence cholesterol metabolism in macrophages in response to the HIV protease inhibitor ritonavir. We have utilized the human monocyte cell line, THP-1 as a model to address this question. Briefly, cells were differentiated for 72 h with 100 nM PMA to obtain a macrophage-like phenotype in the presence or absence of 1 nM 17beta-estradiol (E2), 100 nM progesterone or vehicle (0.01% ethanol). Cells were then treated with 30 ng/ml ritonavir or vehicle in the presence of aggregated LDL for 24 h. Cell extracts were harvested, and lipid or total RNA was isolated. E2 decreased the accumulation of cholesteryl esters in macrophages following ritonavir treatment. Ritonavir increased the expression of the scavenger receptor, CD36 mRNA, responsible for the uptake of LDL. Additionally, ritonavir treatment selectively increased the relative levels of PPARgamma mRNA, a transcription factor responsible for the regulation of CD36 mRNA expression. Treatment with E2, however, failed to prevent these increases at the mRNA level. E2 did, however, significantly suppress CD36 protein levels as measured by fluorescent immunocytochemistry. This data suggests that E2 modifies the expression of CD36 at the level of protein expression in monocyte-derived macrophages resulting in reduced cholesteryl ester accumulation following ritonavir treatment.", "entity": "Progesterone", "aliases": "Pregnenedione Progesterone (13 alpha,17 alpha)-(+-)-Isomer (17 alpha)-Isomer (9 beta,10", "definition": "The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION; PREGNANCY maintenance, and the development of mammary tissue for MILK production. Progesterone, converted from PREGNENOLONE, also serves as an intermediate in the biosynthesis of GONADAL STEROID HORMONES and adrenal CORTICOSTEROIDS.\n    ", "id": "MESH:D011374"}
{"mention": "ethanol", "mention_text": "Individuals with HIV can now live long lives with drug therapy that often includes protease inhibitors such as ritonavir. Many patients, however, develop negative long-term side effects such as premature atherosclerosis. We have previously demonstrated that ritonavir treatment increases atherosclerotic lesion formation in male mice to a greater extent than in female mice. Furthermore, peripheral blood monocytes isolated from ritonavir-treated females had less cholesteryl ester accumulation. In the present study, we have investigated the molecular mechanisms by which female hormones influence cholesterol metabolism in macrophages in response to the HIV protease inhibitor ritonavir. We have utilized the human monocyte cell line, THP-1 as a model to address this question. Briefly, cells were differentiated for 72 h with 100 nM PMA to obtain a macrophage-like phenotype in the presence or absence of 1 nM 17beta-estradiol (E2), 100 nM progesterone or vehicle (0.01% ethanol). Cells were then treated with 30 ng/ml ritonavir or vehicle in the presence of aggregated LDL for 24 h. Cell extracts were harvested, and lipid or total RNA was isolated. E2 decreased the accumulation of cholesteryl esters in macrophages following ritonavir treatment. Ritonavir increased the expression of the scavenger receptor, CD36 mRNA, responsible for the uptake of LDL. Additionally, ritonavir treatment selectively increased the relative levels of PPARgamma mRNA, a transcription factor responsible for the regulation of CD36 mRNA expression. Treatment with E2, however, failed to prevent these increases at the mRNA level. E2 did, however, significantly suppress CD36 protein levels as measured by fluorescent immunocytochemistry. This data suggests that E2 modifies the expression of CD36 at the level of protein expression in monocyte-derived macrophages resulting in reduced cholesteryl ester accumulation following ritonavir treatment.", "entity": "Ethanol", "aliases": "Absolute Alcohol Ethyl Grain Ethanol", "definition": "A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.\n    ", "id": "MESH:D000431"}
{"mention": "cholesteryl esters", "mention_text": "Individuals with HIV can now live long lives with drug therapy that often includes protease inhibitors such as ritonavir. Many patients, however, develop negative long-term side effects such as premature atherosclerosis. We have previously demonstrated that ritonavir treatment increases atherosclerotic lesion formation in male mice to a greater extent than in female mice. Furthermore, peripheral blood monocytes isolated from ritonavir-treated females had less cholesteryl ester accumulation. In the present study, we have investigated the molecular mechanisms by which female hormones influence cholesterol metabolism in macrophages in response to the HIV protease inhibitor ritonavir. We have utilized the human monocyte cell line, THP-1 as a model to address this question. Briefly, cells were differentiated for 72 h with 100 nM PMA to obtain a macrophage-like phenotype in the presence or absence of 1 nM 17beta-estradiol (E2), 100 nM progesterone or vehicle (0.01% ethanol). Cells were then treated with 30 ng/ml ritonavir or vehicle in the presence of aggregated LDL for 24 h. Cell extracts were harvested, and lipid or total RNA was isolated. E2 decreased the accumulation of cholesteryl esters in macrophages following ritonavir treatment. Ritonavir increased the expression of the scavenger receptor, CD36 mRNA, responsible for the uptake of LDL. Additionally, ritonavir treatment selectively increased the relative levels of PPARgamma mRNA, a transcription factor responsible for the regulation of CD36 mRNA expression. Treatment with E2, however, failed to prevent these increases at the mRNA level. E2 did, however, significantly suppress CD36 protein levels as measured by fluorescent immunocytochemistry. This data suggests that E2 modifies the expression of CD36 at the level of protein expression in monocyte-derived macrophages resulting in reduced cholesteryl ester accumulation following ritonavir treatment.", "entity": "Cholesterol Esters", "aliases": "Cholesterol Esters Cholesteryl", "definition": "Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis.\n    ", "id": "MESH:D002788"}
{"mention": "Ritonavir", "mention_text": "Individuals with HIV can now live long lives with drug therapy that often includes protease inhibitors such as ritonavir. Many patients, however, develop negative long-term side effects such as premature atherosclerosis. We have previously demonstrated that ritonavir treatment increases atherosclerotic lesion formation in male mice to a greater extent than in female mice. Furthermore, peripheral blood monocytes isolated from ritonavir-treated females had less cholesteryl ester accumulation. In the present study, we have investigated the molecular mechanisms by which female hormones influence cholesterol metabolism in macrophages in response to the HIV protease inhibitor ritonavir. We have utilized the human monocyte cell line, THP-1 as a model to address this question. Briefly, cells were differentiated for 72 h with 100 nM PMA to obtain a macrophage-like phenotype in the presence or absence of 1 nM 17beta-estradiol (E2), 100 nM progesterone or vehicle (0.01% ethanol). Cells were then treated with 30 ng/ml ritonavir or vehicle in the presence of aggregated LDL for 24 h. Cell extracts were harvested, and lipid or total RNA was isolated. E2 decreased the accumulation of cholesteryl esters in macrophages following ritonavir treatment. Ritonavir increased the expression of the scavenger receptor, CD36 mRNA, responsible for the uptake of LDL. Additionally, ritonavir treatment selectively increased the relative levels of PPARgamma mRNA, a transcription factor responsible for the regulation of CD36 mRNA expression. Treatment with E2, however, failed to prevent these increases at the mRNA level. E2 did, however, significantly suppress CD36 protein levels as measured by fluorescent immunocytochemistry. This data suggests that E2 modifies the expression of CD36 at the level of protein expression in monocyte-derived macrophages resulting in reduced cholesteryl ester accumulation following ritonavir treatment.", "entity": "Ritonavir", "aliases": "538 ABT ABT-538 ABT538 Norvir Ritonavir", "definition": "An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. It also inhibits CYTOCHROME P-450 CYP3A.\n    ", "id": "MESH:D019438"}
{"mention": "seizure", "mention_text": "Upregulation of brain expression of P-glycoprotein in MRP2-deficient TR(-) rats resembles seizure-induced up-regulation of this drug efflux transporter in normal rats.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "phenytoin", "mention_text": "PURPOSE: The multidrug resistance protein 2 (MRP2) is a drug efflux transporter that is expressed predominantly at the apical domain of hepatocytes but seems also to be expressed at the apical membrane of brain capillary endothelial cells that form the blood-brain barrier (BBB). MRP2 is absent in the transport-deficient (TR(-)) Wistar rat mutant, so that this rat strain was very helpful in defining substrates of MRP2 by comparing tissue concentrations or functional activities of compounds in MRP2-deficient rats with those in transport-competent Wistar rats. By using this strategy to study the involvement of MRP2 in brain access of antiepileptic drugs (AEDs), we recently reported that phenytoin is a substrate for MRP2 in the BBB. However, one drawback of such studies in genetically deficient rats is the fact that compensatory changes with upregulation of other transporters can occur. This prompted us to study the brain expression of P-glycoprotein (Pgp), a major drug efflux transporter in many tissues, including the BBB, in TR(-) rats compared with nonmutant (wild-type) Wistar rats. METHODS: The expression of MRP2 and Pgp in brain and liver sections of TR(-) rats and normal Wistar rats was determined with immunohistochemistry, by using a novel, highly selective monoclonal MRP2 antibody and the monoclonal Pgp antibody C219, respectively. RESULTS: Immunofluorescence staining with the MRP2 antibody was found to label a high number of microvessels throughout the brain in normal Wistar rats, whereas such labeling was absent in TR(-) rats. TR(-) rats exhibited a significant up-regulation of Pgp in brain capillary endothelial cells compared with wild-type controls. No such obvious upregulation of Pgp was observed in liver sections. A comparable overexpression of Pgp in the BBB was obtained after pilocarpine-induced seizures in wild-type Wistar rats. Experiments with systemic administration of the Pgp substrate phenobarbital and the selective Pgp inhibitor tariquidar in TR(-) rats substantiated that Pgp is functional and compensates for the lack of MRP2 in the BBB. CONCLUSIONS: The data on TR(-) rats indicate that Pgp plays an important role in the compensation of MRP2 deficiency in the BBB. Because such a compensatory mechanism most likely occurs to reduce injury to the brain from cytotoxic compounds, the present data substantiate the concept that MRP2 performs a protective role in the BBB. Furthermore, our data suggest that TR(-) rats are an interesting tool to study consequences of overexpression of Pgp in the BBB on access of drugs in the brain, without the need of inducing seizures or other Pgp-enhancing events for this purpose.", "entity": "Phenytoin", "aliases": "5,5-Diphenylhydantoin Antisacer Difenin Dihydan Dilantin Diphenylhydantoin Diphenylhydantoinate Sodium Epamin Epanutin Fenitoin Hydantol Park Davis brand of Phenytoin Pfizer Brand Phizer", "definition": "An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs.\n    ", "id": "MESH:D010672"}
{"mention": "pilocarpine", "mention_text": "PURPOSE: The multidrug resistance protein 2 (MRP2) is a drug efflux transporter that is expressed predominantly at the apical domain of hepatocytes but seems also to be expressed at the apical membrane of brain capillary endothelial cells that form the blood-brain barrier (BBB). MRP2 is absent in the transport-deficient (TR(-)) Wistar rat mutant, so that this rat strain was very helpful in defining substrates of MRP2 by comparing tissue concentrations or functional activities of compounds in MRP2-deficient rats with those in transport-competent Wistar rats. By using this strategy to study the involvement of MRP2 in brain access of antiepileptic drugs (AEDs), we recently reported that phenytoin is a substrate for MRP2 in the BBB. However, one drawback of such studies in genetically deficient rats is the fact that compensatory changes with upregulation of other transporters can occur. This prompted us to study the brain expression of P-glycoprotein (Pgp), a major drug efflux transporter in many tissues, including the BBB, in TR(-) rats compared with nonmutant (wild-type) Wistar rats. METHODS: The expression of MRP2 and Pgp in brain and liver sections of TR(-) rats and normal Wistar rats was determined with immunohistochemistry, by using a novel, highly selective monoclonal MRP2 antibody and the monoclonal Pgp antibody C219, respectively. RESULTS: Immunofluorescence staining with the MRP2 antibody was found to label a high number of microvessels throughout the brain in normal Wistar rats, whereas such labeling was absent in TR(-) rats. TR(-) rats exhibited a significant up-regulation of Pgp in brain capillary endothelial cells compared with wild-type controls. No such obvious upregulation of Pgp was observed in liver sections. A comparable overexpression of Pgp in the BBB was obtained after pilocarpine-induced seizures in wild-type Wistar rats. Experiments with systemic administration of the Pgp substrate phenobarbital and the selective Pgp inhibitor tariquidar in TR(-) rats substantiated that Pgp is functional and compensates for the lack of MRP2 in the BBB. CONCLUSIONS: The data on TR(-) rats indicate that Pgp plays an important role in the compensation of MRP2 deficiency in the BBB. Because such a compensatory mechanism most likely occurs to reduce injury to the brain from cytotoxic compounds, the present data substantiate the concept that MRP2 performs a protective role in the BBB. Furthermore, our data suggest that TR(-) rats are an interesting tool to study consequences of overexpression of Pgp in the BBB on access of drugs in the brain, without the need of inducing seizures or other Pgp-enhancing events for this purpose.", "entity": "Pilocarpine", "aliases": "Hydrochloride Pilocarpine Isopilocarpine Isoptocarpine Nitrate Ocusert Mononitrate (3S-cis)-Isomer Monohydrochloride Salagen", "definition": "A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma.\n    ", "id": "MESH:D010862"}
{"mention": "seizures", "mention_text": "PURPOSE: The multidrug resistance protein 2 (MRP2) is a drug efflux transporter that is expressed predominantly at the apical domain of hepatocytes but seems also to be expressed at the apical membrane of brain capillary endothelial cells that form the blood-brain barrier (BBB). MRP2 is absent in the transport-deficient (TR(-)) Wistar rat mutant, so that this rat strain was very helpful in defining substrates of MRP2 by comparing tissue concentrations or functional activities of compounds in MRP2-deficient rats with those in transport-competent Wistar rats. By using this strategy to study the involvement of MRP2 in brain access of antiepileptic drugs (AEDs), we recently reported that phenytoin is a substrate for MRP2 in the BBB. However, one drawback of such studies in genetically deficient rats is the fact that compensatory changes with upregulation of other transporters can occur. This prompted us to study the brain expression of P-glycoprotein (Pgp), a major drug efflux transporter in many tissues, including the BBB, in TR(-) rats compared with nonmutant (wild-type) Wistar rats. METHODS: The expression of MRP2 and Pgp in brain and liver sections of TR(-) rats and normal Wistar rats was determined with immunohistochemistry, by using a novel, highly selective monoclonal MRP2 antibody and the monoclonal Pgp antibody C219, respectively. RESULTS: Immunofluorescence staining with the MRP2 antibody was found to label a high number of microvessels throughout the brain in normal Wistar rats, whereas such labeling was absent in TR(-) rats. TR(-) rats exhibited a significant up-regulation of Pgp in brain capillary endothelial cells compared with wild-type controls. No such obvious upregulation of Pgp was observed in liver sections. A comparable overexpression of Pgp in the BBB was obtained after pilocarpine-induced seizures in wild-type Wistar rats. Experiments with systemic administration of the Pgp substrate phenobarbital and the selective Pgp inhibitor tariquidar in TR(-) rats substantiated that Pgp is functional and compensates for the lack of MRP2 in the BBB. CONCLUSIONS: The data on TR(-) rats indicate that Pgp plays an important role in the compensation of MRP2 deficiency in the BBB. Because such a compensatory mechanism most likely occurs to reduce injury to the brain from cytotoxic compounds, the present data substantiate the concept that MRP2 performs a protective role in the BBB. Furthermore, our data suggest that TR(-) rats are an interesting tool to study consequences of overexpression of Pgp in the BBB on access of drugs in the brain, without the need of inducing seizures or other Pgp-enhancing events for this purpose.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "phenobarbital", "mention_text": "PURPOSE: The multidrug resistance protein 2 (MRP2) is a drug efflux transporter that is expressed predominantly at the apical domain of hepatocytes but seems also to be expressed at the apical membrane of brain capillary endothelial cells that form the blood-brain barrier (BBB). MRP2 is absent in the transport-deficient (TR(-)) Wistar rat mutant, so that this rat strain was very helpful in defining substrates of MRP2 by comparing tissue concentrations or functional activities of compounds in MRP2-deficient rats with those in transport-competent Wistar rats. By using this strategy to study the involvement of MRP2 in brain access of antiepileptic drugs (AEDs), we recently reported that phenytoin is a substrate for MRP2 in the BBB. However, one drawback of such studies in genetically deficient rats is the fact that compensatory changes with upregulation of other transporters can occur. This prompted us to study the brain expression of P-glycoprotein (Pgp), a major drug efflux transporter in many tissues, including the BBB, in TR(-) rats compared with nonmutant (wild-type) Wistar rats. METHODS: The expression of MRP2 and Pgp in brain and liver sections of TR(-) rats and normal Wistar rats was determined with immunohistochemistry, by using a novel, highly selective monoclonal MRP2 antibody and the monoclonal Pgp antibody C219, respectively. RESULTS: Immunofluorescence staining with the MRP2 antibody was found to label a high number of microvessels throughout the brain in normal Wistar rats, whereas such labeling was absent in TR(-) rats. TR(-) rats exhibited a significant up-regulation of Pgp in brain capillary endothelial cells compared with wild-type controls. No such obvious upregulation of Pgp was observed in liver sections. A comparable overexpression of Pgp in the BBB was obtained after pilocarpine-induced seizures in wild-type Wistar rats. Experiments with systemic administration of the Pgp substrate phenobarbital and the selective Pgp inhibitor tariquidar in TR(-) rats substantiated that Pgp is functional and compensates for the lack of MRP2 in the BBB. CONCLUSIONS: The data on TR(-) rats indicate that Pgp plays an important role in the compensation of MRP2 deficiency in the BBB. Because such a compensatory mechanism most likely occurs to reduce injury to the brain from cytotoxic compounds, the present data substantiate the concept that MRP2 performs a protective role in the BBB. Furthermore, our data suggest that TR(-) rats are an interesting tool to study consequences of overexpression of Pgp in the BBB on access of drugs in the brain, without the need of inducing seizures or other Pgp-enhancing events for this purpose.", "entity": "Phenobarbital", "aliases": "Acid Phenylethylbarbituric Gardenal Hysteps Luminal Monosodium Salt Phenobarbital Phenemal Sodium Phenobarbitone Phenylbarbital", "definition": "A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.\n    ", "id": "MESH:D010634"}
{"mention": "tariquidar", "mention_text": "PURPOSE: The multidrug resistance protein 2 (MRP2) is a drug efflux transporter that is expressed predominantly at the apical domain of hepatocytes but seems also to be expressed at the apical membrane of brain capillary endothelial cells that form the blood-brain barrier (BBB). MRP2 is absent in the transport-deficient (TR(-)) Wistar rat mutant, so that this rat strain was very helpful in defining substrates of MRP2 by comparing tissue concentrations or functional activities of compounds in MRP2-deficient rats with those in transport-competent Wistar rats. By using this strategy to study the involvement of MRP2 in brain access of antiepileptic drugs (AEDs), we recently reported that phenytoin is a substrate for MRP2 in the BBB. However, one drawback of such studies in genetically deficient rats is the fact that compensatory changes with upregulation of other transporters can occur. This prompted us to study the brain expression of P-glycoprotein (Pgp), a major drug efflux transporter in many tissues, including the BBB, in TR(-) rats compared with nonmutant (wild-type) Wistar rats. METHODS: The expression of MRP2 and Pgp in brain and liver sections of TR(-) rats and normal Wistar rats was determined with immunohistochemistry, by using a novel, highly selective monoclonal MRP2 antibody and the monoclonal Pgp antibody C219, respectively. RESULTS: Immunofluorescence staining with the MRP2 antibody was found to label a high number of microvessels throughout the brain in normal Wistar rats, whereas such labeling was absent in TR(-) rats. TR(-) rats exhibited a significant up-regulation of Pgp in brain capillary endothelial cells compared with wild-type controls. No such obvious upregulation of Pgp was observed in liver sections. A comparable overexpression of Pgp in the BBB was obtained after pilocarpine-induced seizures in wild-type Wistar rats. Experiments with systemic administration of the Pgp substrate phenobarbital and the selective Pgp inhibitor tariquidar in TR(-) rats substantiated that Pgp is functional and compensates for the lack of MRP2 in the BBB. CONCLUSIONS: The data on TR(-) rats indicate that Pgp plays an important role in the compensation of MRP2 deficiency in the BBB. Because such a compensatory mechanism most likely occurs to reduce injury to the brain from cytotoxic compounds, the present data substantiate the concept that MRP2 performs a protective role in the BBB. Furthermore, our data suggest that TR(-) rats are an interesting tool to study consequences of overexpression of Pgp in the BBB on access of drugs in the brain, without the need of inducing seizures or other Pgp-enhancing events for this purpose.", "entity": "tariquidar", "aliases": "XR 9576 XR9576 tariquidar tariquidarth", "definition": "", "id": "MESH:C402343"}
{"mention": "injury to the brain", "mention_text": "PURPOSE: The multidrug resistance protein 2 (MRP2) is a drug efflux transporter that is expressed predominantly at the apical domain of hepatocytes but seems also to be expressed at the apical membrane of brain capillary endothelial cells that form the blood-brain barrier (BBB). MRP2 is absent in the transport-deficient (TR(-)) Wistar rat mutant, so that this rat strain was very helpful in defining substrates of MRP2 by comparing tissue concentrations or functional activities of compounds in MRP2-deficient rats with those in transport-competent Wistar rats. By using this strategy to study the involvement of MRP2 in brain access of antiepileptic drugs (AEDs), we recently reported that phenytoin is a substrate for MRP2 in the BBB. However, one drawback of such studies in genetically deficient rats is the fact that compensatory changes with upregulation of other transporters can occur. This prompted us to study the brain expression of P-glycoprotein (Pgp), a major drug efflux transporter in many tissues, including the BBB, in TR(-) rats compared with nonmutant (wild-type) Wistar rats. METHODS: The expression of MRP2 and Pgp in brain and liver sections of TR(-) rats and normal Wistar rats was determined with immunohistochemistry, by using a novel, highly selective monoclonal MRP2 antibody and the monoclonal Pgp antibody C219, respectively. RESULTS: Immunofluorescence staining with the MRP2 antibody was found to label a high number of microvessels throughout the brain in normal Wistar rats, whereas such labeling was absent in TR(-) rats. TR(-) rats exhibited a significant up-regulation of Pgp in brain capillary endothelial cells compared with wild-type controls. No such obvious upregulation of Pgp was observed in liver sections. A comparable overexpression of Pgp in the BBB was obtained after pilocarpine-induced seizures in wild-type Wistar rats. Experiments with systemic administration of the Pgp substrate phenobarbital and the selective Pgp inhibitor tariquidar in TR(-) rats substantiated that Pgp is functional and compensates for the lack of MRP2 in the BBB. CONCLUSIONS: The data on TR(-) rats indicate that Pgp plays an important role in the compensation of MRP2 deficiency in the BBB. Because such a compensatory mechanism most likely occurs to reduce injury to the brain from cytotoxic compounds, the present data substantiate the concept that MRP2 performs a protective role in the BBB. Furthermore, our data suggest that TR(-) rats are an interesting tool to study consequences of overexpression of Pgp in the BBB on access of drugs in the brain, without the need of inducing seizures or other Pgp-enhancing events for this purpose.", "entity": "Brain Diseases", "aliases": "Brain Disease Diseases Disorder Disorders CNS Intracranial Central Nervous System Encephalon", "definition": "Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.\n    ", "id": "MESH:D001927"}
{"mention": "seizure", "mention_text": "Use of chromosome substitution strains to identify seizure susceptibility loci in mice.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "Seizure", "mention_text": "Seizure susceptibility varies among inbred mouse strains. Chromosome substitution strains (CSS), in which a single chromosome from one inbred strain (donor) has been transferred onto a second strain (host) by repeated backcrossing, may be used to identify quantitative trait loci (QTLs) that contribute to seizure susceptibility. QTLs for susceptibility to pilocarpine-induced seizures, a model of temporal lobe epilepsy, have not been reported, and CSS have not previously been used to localize seizure susceptibility genes. We report QTLs identified using a B6 (host) x A/J (donor) CSS panel to localize genes involved in susceptibility to pilocarpine-induced seizures. Three hundred fifty-five adult male CSS mice, 58 B6, and 39 A/J were tested for susceptibility to pilocarpine-induced seizures. Highest stage reached and latency to each stage were recorded for all mice. B6 mice were resistant to seizures and slower to reach stages compared to A/J mice. The CSS for Chromosomes 10 and 18 progressed to the most severe stages, diverging dramatically from the B6 phenotype. Latencies to stages were also significantly shorter for CSS10 and CSS18 mice. CSS mapping suggests seizure susceptibility loci on mouse Chromosomes 10 and 18. This approach provides a framework for identifying potentially novel homologous candidate genes for human temporal lobe epilepsy.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "seizure", "mention_text": "Seizure susceptibility varies among inbred mouse strains. Chromosome substitution strains (CSS), in which a single chromosome from one inbred strain (donor) has been transferred onto a second strain (host) by repeated backcrossing, may be used to identify quantitative trait loci (QTLs) that contribute to seizure susceptibility. QTLs for susceptibility to pilocarpine-induced seizures, a model of temporal lobe epilepsy, have not been reported, and CSS have not previously been used to localize seizure susceptibility genes. We report QTLs identified using a B6 (host) x A/J (donor) CSS panel to localize genes involved in susceptibility to pilocarpine-induced seizures. Three hundred fifty-five adult male CSS mice, 58 B6, and 39 A/J were tested for susceptibility to pilocarpine-induced seizures. Highest stage reached and latency to each stage were recorded for all mice. B6 mice were resistant to seizures and slower to reach stages compared to A/J mice. The CSS for Chromosomes 10 and 18 progressed to the most severe stages, diverging dramatically from the B6 phenotype. Latencies to stages were also significantly shorter for CSS10 and CSS18 mice. CSS mapping suggests seizure susceptibility loci on mouse Chromosomes 10 and 18. This approach provides a framework for identifying potentially novel homologous candidate genes for human temporal lobe epilepsy.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "pilocarpine", "mention_text": "Seizure susceptibility varies among inbred mouse strains. Chromosome substitution strains (CSS), in which a single chromosome from one inbred strain (donor) has been transferred onto a second strain (host) by repeated backcrossing, may be used to identify quantitative trait loci (QTLs) that contribute to seizure susceptibility. QTLs for susceptibility to pilocarpine-induced seizures, a model of temporal lobe epilepsy, have not been reported, and CSS have not previously been used to localize seizure susceptibility genes. We report QTLs identified using a B6 (host) x A/J (donor) CSS panel to localize genes involved in susceptibility to pilocarpine-induced seizures. Three hundred fifty-five adult male CSS mice, 58 B6, and 39 A/J were tested for susceptibility to pilocarpine-induced seizures. Highest stage reached and latency to each stage were recorded for all mice. B6 mice were resistant to seizures and slower to reach stages compared to A/J mice. The CSS for Chromosomes 10 and 18 progressed to the most severe stages, diverging dramatically from the B6 phenotype. Latencies to stages were also significantly shorter for CSS10 and CSS18 mice. CSS mapping suggests seizure susceptibility loci on mouse Chromosomes 10 and 18. This approach provides a framework for identifying potentially novel homologous candidate genes for human temporal lobe epilepsy.", "entity": "Pilocarpine", "aliases": "Hydrochloride Pilocarpine Isopilocarpine Isoptocarpine Nitrate Ocusert Mononitrate (3S-cis)-Isomer Monohydrochloride Salagen", "definition": "A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma.\n    ", "id": "MESH:D010862"}
{"mention": "seizures", "mention_text": "Seizure susceptibility varies among inbred mouse strains. Chromosome substitution strains (CSS), in which a single chromosome from one inbred strain (donor) has been transferred onto a second strain (host) by repeated backcrossing, may be used to identify quantitative trait loci (QTLs) that contribute to seizure susceptibility. QTLs for susceptibility to pilocarpine-induced seizures, a model of temporal lobe epilepsy, have not been reported, and CSS have not previously been used to localize seizure susceptibility genes. We report QTLs identified using a B6 (host) x A/J (donor) CSS panel to localize genes involved in susceptibility to pilocarpine-induced seizures. Three hundred fifty-five adult male CSS mice, 58 B6, and 39 A/J were tested for susceptibility to pilocarpine-induced seizures. Highest stage reached and latency to each stage were recorded for all mice. B6 mice were resistant to seizures and slower to reach stages compared to A/J mice. The CSS for Chromosomes 10 and 18 progressed to the most severe stages, diverging dramatically from the B6 phenotype. Latencies to stages were also significantly shorter for CSS10 and CSS18 mice. CSS mapping suggests seizure susceptibility loci on mouse Chromosomes 10 and 18. This approach provides a framework for identifying potentially novel homologous candidate genes for human temporal lobe epilepsy.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "temporal lobe epilepsy", "mention_text": "Seizure susceptibility varies among inbred mouse strains. Chromosome substitution strains (CSS), in which a single chromosome from one inbred strain (donor) has been transferred onto a second strain (host) by repeated backcrossing, may be used to identify quantitative trait loci (QTLs) that contribute to seizure susceptibility. QTLs for susceptibility to pilocarpine-induced seizures, a model of temporal lobe epilepsy, have not been reported, and CSS have not previously been used to localize seizure susceptibility genes. We report QTLs identified using a B6 (host) x A/J (donor) CSS panel to localize genes involved in susceptibility to pilocarpine-induced seizures. Three hundred fifty-five adult male CSS mice, 58 B6, and 39 A/J were tested for susceptibility to pilocarpine-induced seizures. Highest stage reached and latency to each stage were recorded for all mice. B6 mice were resistant to seizures and slower to reach stages compared to A/J mice. The CSS for Chromosomes 10 and 18 progressed to the most severe stages, diverging dramatically from the B6 phenotype. Latencies to stages were also significantly shorter for CSS10 and CSS18 mice. CSS mapping suggests seizure susceptibility loci on mouse Chromosomes 10 and 18. This approach provides a framework for identifying potentially novel homologous candidate genes for human temporal lobe epilepsy.", "entity": "Epilepsy, Temporal Lobe", "aliases": "Benign Psychomotor Epilepsy Childhood Epilepsies Lateral Temporal Lobe Uncinate", "definition": "A localization-related (focal) form of epilepsy characterized by recurrent seizures that arise from foci within the temporal lobe, most commonly from its mesial aspect. A wide variety of psychic phenomena may be associated, including illusions, hallucinations, dyscognitive states, and affective experiences. The majority of complex partial seizures (see EPILEPSY, COMPLEX PARTIAL) originate from the temporal lobes. Temporal lobe seizures may be classified by etiology as cryptogenic, familial, or symptomatic (i.e., related to an identified disease process or lesion). (From Adams et al., Principles of Neurology, 6th ed, p321)\n    ", "id": "MESH:D004833"}
{"mention": "epilepsy", "mention_text": "Investigation of mitochondrial involvement in the experimental model of epilepsy induced by pilocarpine.", "entity": "Epilepsy", "aliases": "Aura Auras Awakening Epilepsy Cryptogenic Epilepsies Epileptic Seizure Seizures Disorder Disorders Single", "definition": "A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313)\n    ", "id": "MESH:D004827"}
{"mention": "pilocarpine", "mention_text": "Investigation of mitochondrial involvement in the experimental model of epilepsy induced by pilocarpine.", "entity": "Pilocarpine", "aliases": "Hydrochloride Pilocarpine Isopilocarpine Isoptocarpine Nitrate Ocusert Mononitrate (3S-cis)-Isomer Monohydrochloride Salagen", "definition": "A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma.\n    ", "id": "MESH:D010862"}
{"mention": "Mitochondrial abnormalities", "mention_text": "Mitochondrial abnormalities have been associated with several aspects of epileptogenesis, such as energy generation, control of cell death, neurotransmitter synthesis, and free radical (FR) production. Increased production of FRs may cause mtDNA damage leading to decreased activities of oxidative phosphorylation complexes containing mtDNA-encoded subunits. In this study, we investigated whether increased generation of FR during status epilepticus would be sufficient to provoke abnormalities in mtDNA and in the expression and activity of cytochrome c oxidase (CCO), complex IV of the respiratory chain, in the chronic phase of the pilocarpine model of temporal lobe epilepsy. DNA analysis revealed low amounts of a 4.8 kb mtDNA deletion but with no differences in frequency or quantity in the control and experimental groups. We did not find abnormalities in the expression and distribution of an mtDNA-encoded subunit of CCO (CCO-I) or a relative decrease in CCO-I when compared with nuclear-encoded subunits (CCO-IV and SDH-fp). No abnormality in CCO activity was observed through histochemistry. Although evidences of mitochondrial abnormalities were found in previously published studies, our results do not suggest that the FRs, generated during the acute phase, determined important abnormalities in mtDNA, in expression of CCO-I, and in CCO activity.", "entity": "Mitochondrial Diseases", "aliases": "Deficiencies Oxidative Phosphorylation Respiratory Chain Deficiency Disease Mitochondrial Disorder Disorders Electron Transport Diseases", "definition": "Diseases caused by abnormal function of the MITOCHONDRIA. They may be caused by mutations, acquired or inherited, in mitochondrial DNA or in nuclear genes that code for mitochondrial components. They may also be the result of acquired mitochondria dysfunction due to adverse effects of drugs, infections, or other environmental causes.\n    ", "id": "MESH:D028361"}
{"mention": "death", "mention_text": "Mitochondrial abnormalities have been associated with several aspects of epileptogenesis, such as energy generation, control of cell death, neurotransmitter synthesis, and free radical (FR) production. Increased production of FRs may cause mtDNA damage leading to decreased activities of oxidative phosphorylation complexes containing mtDNA-encoded subunits. In this study, we investigated whether increased generation of FR during status epilepticus would be sufficient to provoke abnormalities in mtDNA and in the expression and activity of cytochrome c oxidase (CCO), complex IV of the respiratory chain, in the chronic phase of the pilocarpine model of temporal lobe epilepsy. DNA analysis revealed low amounts of a 4.8 kb mtDNA deletion but with no differences in frequency or quantity in the control and experimental groups. We did not find abnormalities in the expression and distribution of an mtDNA-encoded subunit of CCO (CCO-I) or a relative decrease in CCO-I when compared with nuclear-encoded subunits (CCO-IV and SDH-fp). No abnormality in CCO activity was observed through histochemistry. Although evidences of mitochondrial abnormalities were found in previously published studies, our results do not suggest that the FRs, generated during the acute phase, determined important abnormalities in mtDNA, in expression of CCO-I, and in CCO activity.", "entity": "Death", "aliases": "Cardiac Death Determination of Near-Death Experience", "definition": "Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.\n    ", "id": "MESH:D003643"}
{"mention": "status epilepticus", "mention_text": "Mitochondrial abnormalities have been associated with several aspects of epileptogenesis, such as energy generation, control of cell death, neurotransmitter synthesis, and free radical (FR) production. Increased production of FRs may cause mtDNA damage leading to decreased activities of oxidative phosphorylation complexes containing mtDNA-encoded subunits. In this study, we investigated whether increased generation of FR during status epilepticus would be sufficient to provoke abnormalities in mtDNA and in the expression and activity of cytochrome c oxidase (CCO), complex IV of the respiratory chain, in the chronic phase of the pilocarpine model of temporal lobe epilepsy. DNA analysis revealed low amounts of a 4.8 kb mtDNA deletion but with no differences in frequency or quantity in the control and experimental groups. We did not find abnormalities in the expression and distribution of an mtDNA-encoded subunit of CCO (CCO-I) or a relative decrease in CCO-I when compared with nuclear-encoded subunits (CCO-IV and SDH-fp). No abnormality in CCO activity was observed through histochemistry. Although evidences of mitochondrial abnormalities were found in previously published studies, our results do not suggest that the FRs, generated during the acute phase, determined important abnormalities in mtDNA, in expression of CCO-I, and in CCO activity.", "entity": "Status Epilepticus", "aliases": "Absence Status Complex Partial Epilepticus Electrographic Generalized Convulsive Grand Mal Non Non-Convulsive Petit Simple Subclinical", "definition": "A prolonged seizure or seizures repeated frequently enough to prevent recovery between episodes occurring over a period of 20-30 minutes. The most common subtype is generalized tonic-clonic status epilepticus, a potentially fatal condition associated with neuronal injury and respiratory and metabolic dysfunction. Nonconvulsive forms include petit mal status and complex partial status, which may manifest as behavioral disturbances. Simple partial status epilepticus consists of persistent motor, sensory, or autonomic seizures that do not impair cognition (see also EPILEPSIA PARTIALIS CONTINUA). Subclinical status epilepticus generally refers to seizures occurring in an unresponsive or comatose individual in the absence of overt signs of seizure activity. (From N Engl J Med 1998 Apr 2;338(14):970-6; Neurologia 1997 Dec;12 Suppl 6:25-30)\n    ", "id": "MESH:D013226"}
{"mention": "pilocarpine", "mention_text": "Mitochondrial abnormalities have been associated with several aspects of epileptogenesis, such as energy generation, control of cell death, neurotransmitter synthesis, and free radical (FR) production. Increased production of FRs may cause mtDNA damage leading to decreased activities of oxidative phosphorylation complexes containing mtDNA-encoded subunits. In this study, we investigated whether increased generation of FR during status epilepticus would be sufficient to provoke abnormalities in mtDNA and in the expression and activity of cytochrome c oxidase (CCO), complex IV of the respiratory chain, in the chronic phase of the pilocarpine model of temporal lobe epilepsy. DNA analysis revealed low amounts of a 4.8 kb mtDNA deletion but with no differences in frequency or quantity in the control and experimental groups. We did not find abnormalities in the expression and distribution of an mtDNA-encoded subunit of CCO (CCO-I) or a relative decrease in CCO-I when compared with nuclear-encoded subunits (CCO-IV and SDH-fp). No abnormality in CCO activity was observed through histochemistry. Although evidences of mitochondrial abnormalities were found in previously published studies, our results do not suggest that the FRs, generated during the acute phase, determined important abnormalities in mtDNA, in expression of CCO-I, and in CCO activity.", "entity": "Pilocarpine", "aliases": "Hydrochloride Pilocarpine Isopilocarpine Isoptocarpine Nitrate Ocusert Mononitrate (3S-cis)-Isomer Monohydrochloride Salagen", "definition": "A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma.\n    ", "id": "MESH:D010862"}
{"mention": "temporal lobe epilepsy", "mention_text": "Mitochondrial abnormalities have been associated with several aspects of epileptogenesis, such as energy generation, control of cell death, neurotransmitter synthesis, and free radical (FR) production. Increased production of FRs may cause mtDNA damage leading to decreased activities of oxidative phosphorylation complexes containing mtDNA-encoded subunits. In this study, we investigated whether increased generation of FR during status epilepticus would be sufficient to provoke abnormalities in mtDNA and in the expression and activity of cytochrome c oxidase (CCO), complex IV of the respiratory chain, in the chronic phase of the pilocarpine model of temporal lobe epilepsy. DNA analysis revealed low amounts of a 4.8 kb mtDNA deletion but with no differences in frequency or quantity in the control and experimental groups. We did not find abnormalities in the expression and distribution of an mtDNA-encoded subunit of CCO (CCO-I) or a relative decrease in CCO-I when compared with nuclear-encoded subunits (CCO-IV and SDH-fp). No abnormality in CCO activity was observed through histochemistry. Although evidences of mitochondrial abnormalities were found in previously published studies, our results do not suggest that the FRs, generated during the acute phase, determined important abnormalities in mtDNA, in expression of CCO-I, and in CCO activity.", "entity": "Epilepsy, Temporal Lobe", "aliases": "Benign Psychomotor Epilepsy Childhood Epilepsies Lateral Temporal Lobe Uncinate", "definition": "A localization-related (focal) form of epilepsy characterized by recurrent seizures that arise from foci within the temporal lobe, most commonly from its mesial aspect. A wide variety of psychic phenomena may be associated, including illusions, hallucinations, dyscognitive states, and affective experiences. The majority of complex partial seizures (see EPILEPSY, COMPLEX PARTIAL) originate from the temporal lobes. Temporal lobe seizures may be classified by etiology as cryptogenic, familial, or symptomatic (i.e., related to an identified disease process or lesion). (From Adams et al., Principles of Neurology, 6th ed, p321)\n    ", "id": "MESH:D004833"}
{"mention": "mitochondrial abnormalities", "mention_text": "Mitochondrial abnormalities have been associated with several aspects of epileptogenesis, such as energy generation, control of cell death, neurotransmitter synthesis, and free radical (FR) production. Increased production of FRs may cause mtDNA damage leading to decreased activities of oxidative phosphorylation complexes containing mtDNA-encoded subunits. In this study, we investigated whether increased generation of FR during status epilepticus would be sufficient to provoke abnormalities in mtDNA and in the expression and activity of cytochrome c oxidase (CCO), complex IV of the respiratory chain, in the chronic phase of the pilocarpine model of temporal lobe epilepsy. DNA analysis revealed low amounts of a 4.8 kb mtDNA deletion but with no differences in frequency or quantity in the control and experimental groups. We did not find abnormalities in the expression and distribution of an mtDNA-encoded subunit of CCO (CCO-I) or a relative decrease in CCO-I when compared with nuclear-encoded subunits (CCO-IV and SDH-fp). No abnormality in CCO activity was observed through histochemistry. Although evidences of mitochondrial abnormalities were found in previously published studies, our results do not suggest that the FRs, generated during the acute phase, determined important abnormalities in mtDNA, in expression of CCO-I, and in CCO activity.", "entity": "Mitochondrial Diseases", "aliases": "Deficiencies Oxidative Phosphorylation Respiratory Chain Deficiency Disease Mitochondrial Disorder Disorders Electron Transport Diseases", "definition": "Diseases caused by abnormal function of the MITOCHONDRIA. They may be caused by mutations, acquired or inherited, in mitochondrial DNA or in nuclear genes that code for mitochondrial components. They may also be the result of acquired mitochondria dysfunction due to adverse effects of drugs, infections, or other environmental causes.\n    ", "id": "MESH:D028361"}
{"mention": "thrombotic microangiopathy", "mention_text": "Causes of acute thrombotic microangiopathy in patients receiving kidney transplantation.", "entity": "Thrombotic Microangiopathies", "aliases": "Microangiopathies Thrombotic Microangiopathy", "definition": "Diseases that result in THROMBOSIS in MICROVASCULATURE. The two most prominent diseases are PURPURA, THROMBOTIC THROMBOCYTOPENIC; and HEMOLYTIC-UREMIC SYNDROME. Multiple etiological factors include VASCULAR ENDOTHELIAL CELL damage due to SHIGA TOXIN; FACTOR H deficiency; and aberrant VON WILLEBRAND FACTOR formation.\n    ", "id": "MESH:D057049"}
{"mention": "Thrombotic microangiopathy", "mention_text": "OBJECTIVES: Thrombotic microangiopathy is a well-known problem in patients following renal transplantation. In postrenal transplantation, thrombotic microangiopathy is often a reflection of hemolytic uremic syndrome. We aimed to determine the causes of thrombotic microangiopathy in a population of renal transplantation recipients and discuss the literature. MATERIALS AND METHODS: We investigated the causes of thrombotic microangiopathy during a 1-year period, from June 2003 to June 2004, at the King Fahad National Guard Hospital in Riyadh, Saudi Arabia, by reviewing the slides of all transplant biopsies (n=25) performed during this interval. Pre- and posttransplant crossmatching was done when possible. RESULTS: Five cases of thrombotic microangiopathy were found. Three of these cases were from the 25 transplantations performed at King Fahad National Guard Hospital, while the other 2 transplantations had been performed abroad and were referred to us for follow-up. Three cases were related to cyclosporine, and 1 case was secondary to both cyclosporine and tacrolimus. The fifth case had features of thrombotic microangiopathy related to an antiphospholipid syndrome in a patient with systemic lupus erythematosus. CONCLUSIONS: In the literature, the most-frequent cause of hemolytic uremic syndrome in patients following renal transplantation is recurrence of the hemolytic uremic syndrome. Other causes include drug-related (cyclosporine, tacrolimus) toxicity, procoagulant status, and antibody-mediated rejection. We found that the most-frequent cause of thrombotic microangiopathy was drug related, secondary mainly to cyclosporine. In the current study, the frequency of thrombotic microangiopathy was similar to the percentage reported in the literature (20%).", "entity": "Thrombotic Microangiopathies", "aliases": "Microangiopathies Thrombotic Microangiopathy", "definition": "Diseases that result in THROMBOSIS in MICROVASCULATURE. The two most prominent diseases are PURPURA, THROMBOTIC THROMBOCYTOPENIC; and HEMOLYTIC-UREMIC SYNDROME. Multiple etiological factors include VASCULAR ENDOTHELIAL CELL damage due to SHIGA TOXIN; FACTOR H deficiency; and aberrant VON WILLEBRAND FACTOR formation.\n    ", "id": "MESH:D057049"}
{"mention": "thrombotic microangiopathy", "mention_text": "OBJECTIVES: Thrombotic microangiopathy is a well-known problem in patients following renal transplantation. In postrenal transplantation, thrombotic microangiopathy is often a reflection of hemolytic uremic syndrome. We aimed to determine the causes of thrombotic microangiopathy in a population of renal transplantation recipients and discuss the literature. MATERIALS AND METHODS: We investigated the causes of thrombotic microangiopathy during a 1-year period, from June 2003 to June 2004, at the King Fahad National Guard Hospital in Riyadh, Saudi Arabia, by reviewing the slides of all transplant biopsies (n=25) performed during this interval. Pre- and posttransplant crossmatching was done when possible. RESULTS: Five cases of thrombotic microangiopathy were found. Three of these cases were from the 25 transplantations performed at King Fahad National Guard Hospital, while the other 2 transplantations had been performed abroad and were referred to us for follow-up. Three cases were related to cyclosporine, and 1 case was secondary to both cyclosporine and tacrolimus. The fifth case had features of thrombotic microangiopathy related to an antiphospholipid syndrome in a patient with systemic lupus erythematosus. CONCLUSIONS: In the literature, the most-frequent cause of hemolytic uremic syndrome in patients following renal transplantation is recurrence of the hemolytic uremic syndrome. Other causes include drug-related (cyclosporine, tacrolimus) toxicity, procoagulant status, and antibody-mediated rejection. We found that the most-frequent cause of thrombotic microangiopathy was drug related, secondary mainly to cyclosporine. In the current study, the frequency of thrombotic microangiopathy was similar to the percentage reported in the literature (20%).", "entity": "Thrombotic Microangiopathies", "aliases": "Microangiopathies Thrombotic Microangiopathy", "definition": "Diseases that result in THROMBOSIS in MICROVASCULATURE. The two most prominent diseases are PURPURA, THROMBOTIC THROMBOCYTOPENIC; and HEMOLYTIC-UREMIC SYNDROME. Multiple etiological factors include VASCULAR ENDOTHELIAL CELL damage due to SHIGA TOXIN; FACTOR H deficiency; and aberrant VON WILLEBRAND FACTOR formation.\n    ", "id": "MESH:D057049"}
{"mention": "hemolytic uremic syndrome", "mention_text": "OBJECTIVES: Thrombotic microangiopathy is a well-known problem in patients following renal transplantation. In postrenal transplantation, thrombotic microangiopathy is often a reflection of hemolytic uremic syndrome. We aimed to determine the causes of thrombotic microangiopathy in a population of renal transplantation recipients and discuss the literature. MATERIALS AND METHODS: We investigated the causes of thrombotic microangiopathy during a 1-year period, from June 2003 to June 2004, at the King Fahad National Guard Hospital in Riyadh, Saudi Arabia, by reviewing the slides of all transplant biopsies (n=25) performed during this interval. Pre- and posttransplant crossmatching was done when possible. RESULTS: Five cases of thrombotic microangiopathy were found. Three of these cases were from the 25 transplantations performed at King Fahad National Guard Hospital, while the other 2 transplantations had been performed abroad and were referred to us for follow-up. Three cases were related to cyclosporine, and 1 case was secondary to both cyclosporine and tacrolimus. The fifth case had features of thrombotic microangiopathy related to an antiphospholipid syndrome in a patient with systemic lupus erythematosus. CONCLUSIONS: In the literature, the most-frequent cause of hemolytic uremic syndrome in patients following renal transplantation is recurrence of the hemolytic uremic syndrome. Other causes include drug-related (cyclosporine, tacrolimus) toxicity, procoagulant status, and antibody-mediated rejection. We found that the most-frequent cause of thrombotic microangiopathy was drug related, secondary mainly to cyclosporine. In the current study, the frequency of thrombotic microangiopathy was similar to the percentage reported in the literature (20%).", "entity": "Hemolytic-Uremic Syndrome", "aliases": "Gasser Syndrome Gasser's Gassers Hemolytic Uremic Hemolytic-Uremic", "definition": "A syndrome that is associated with microvascular diseases of the KIDNEY, such as RENAL CORTICAL NECROSIS. It is characterized by hemolytic anemia (ANEMIA, HEMOLYTIC); THROMBOCYTOPENIA; and ACUTE RENAL FAILURE.\n    ", "id": "MESH:D006463"}
{"mention": "cyclosporine", "mention_text": "OBJECTIVES: Thrombotic microangiopathy is a well-known problem in patients following renal transplantation. In postrenal transplantation, thrombotic microangiopathy is often a reflection of hemolytic uremic syndrome. We aimed to determine the causes of thrombotic microangiopathy in a population of renal transplantation recipients and discuss the literature. MATERIALS AND METHODS: We investigated the causes of thrombotic microangiopathy during a 1-year period, from June 2003 to June 2004, at the King Fahad National Guard Hospital in Riyadh, Saudi Arabia, by reviewing the slides of all transplant biopsies (n=25) performed during this interval. Pre- and posttransplant crossmatching was done when possible. RESULTS: Five cases of thrombotic microangiopathy were found. Three of these cases were from the 25 transplantations performed at King Fahad National Guard Hospital, while the other 2 transplantations had been performed abroad and were referred to us for follow-up. Three cases were related to cyclosporine, and 1 case was secondary to both cyclosporine and tacrolimus. The fifth case had features of thrombotic microangiopathy related to an antiphospholipid syndrome in a patient with systemic lupus erythematosus. CONCLUSIONS: In the literature, the most-frequent cause of hemolytic uremic syndrome in patients following renal transplantation is recurrence of the hemolytic uremic syndrome. Other causes include drug-related (cyclosporine, tacrolimus) toxicity, procoagulant status, and antibody-mediated rejection. We found that the most-frequent cause of thrombotic microangiopathy was drug related, secondary mainly to cyclosporine. In the current study, the frequency of thrombotic microangiopathy was similar to the percentage reported in the literature (20%).", "entity": "Cyclosporine", "aliases": "Ciclosporin CsA Neoral CsA-Neoral CsANeoral CyA NOF CyA-NOF Cyclosporin A Cyclosporine OL 27 400 27-400 27400 Sandimmun Sandimmune", "definition": "A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).\n    ", "id": "MESH:D016572"}
{"mention": "tacrolimus", "mention_text": "OBJECTIVES: Thrombotic microangiopathy is a well-known problem in patients following renal transplantation. In postrenal transplantation, thrombotic microangiopathy is often a reflection of hemolytic uremic syndrome. We aimed to determine the causes of thrombotic microangiopathy in a population of renal transplantation recipients and discuss the literature. MATERIALS AND METHODS: We investigated the causes of thrombotic microangiopathy during a 1-year period, from June 2003 to June 2004, at the King Fahad National Guard Hospital in Riyadh, Saudi Arabia, by reviewing the slides of all transplant biopsies (n=25) performed during this interval. Pre- and posttransplant crossmatching was done when possible. RESULTS: Five cases of thrombotic microangiopathy were found. Three of these cases were from the 25 transplantations performed at King Fahad National Guard Hospital, while the other 2 transplantations had been performed abroad and were referred to us for follow-up. Three cases were related to cyclosporine, and 1 case was secondary to both cyclosporine and tacrolimus. The fifth case had features of thrombotic microangiopathy related to an antiphospholipid syndrome in a patient with systemic lupus erythematosus. CONCLUSIONS: In the literature, the most-frequent cause of hemolytic uremic syndrome in patients following renal transplantation is recurrence of the hemolytic uremic syndrome. Other causes include drug-related (cyclosporine, tacrolimus) toxicity, procoagulant status, and antibody-mediated rejection. We found that the most-frequent cause of thrombotic microangiopathy was drug related, secondary mainly to cyclosporine. In the current study, the frequency of thrombotic microangiopathy was similar to the percentage reported in the literature (20%).", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "antiphospholipid syndrome", "mention_text": "OBJECTIVES: Thrombotic microangiopathy is a well-known problem in patients following renal transplantation. In postrenal transplantation, thrombotic microangiopathy is often a reflection of hemolytic uremic syndrome. We aimed to determine the causes of thrombotic microangiopathy in a population of renal transplantation recipients and discuss the literature. MATERIALS AND METHODS: We investigated the causes of thrombotic microangiopathy during a 1-year period, from June 2003 to June 2004, at the King Fahad National Guard Hospital in Riyadh, Saudi Arabia, by reviewing the slides of all transplant biopsies (n=25) performed during this interval. Pre- and posttransplant crossmatching was done when possible. RESULTS: Five cases of thrombotic microangiopathy were found. Three of these cases were from the 25 transplantations performed at King Fahad National Guard Hospital, while the other 2 transplantations had been performed abroad and were referred to us for follow-up. Three cases were related to cyclosporine, and 1 case was secondary to both cyclosporine and tacrolimus. The fifth case had features of thrombotic microangiopathy related to an antiphospholipid syndrome in a patient with systemic lupus erythematosus. CONCLUSIONS: In the literature, the most-frequent cause of hemolytic uremic syndrome in patients following renal transplantation is recurrence of the hemolytic uremic syndrome. Other causes include drug-related (cyclosporine, tacrolimus) toxicity, procoagulant status, and antibody-mediated rejection. We found that the most-frequent cause of thrombotic microangiopathy was drug related, secondary mainly to cyclosporine. In the current study, the frequency of thrombotic microangiopathy was similar to the percentage reported in the literature (20%).", "entity": "Antiphospholipid Syndrome", "aliases": "Anti Phospholipid Antibody Syndrome Anti-Phospholipid Antiphospholipid Syndromes Hughes", "definition": "The presence of antibodies directed against phospholipids (ANTIBODIES, ANTIPHOSPHOLIPID). The condition is associated with a variety of diseases, notably systemic lupus erythematosus and other connective tissue diseases, thrombopenia, and arterial or venous thromboses. In pregnancy it can cause abortion. Of the phospholipids, the cardiolipins show markedly elevated levels of anticardiolipin antibodies (ANTIBODIES, ANTICARDIOLIPIN). Present also are high levels of lupus anticoagulant (LUPUS COAGULATION INHIBITOR).\n    ", "id": "MESH:D016736"}
{"mention": "systemic lupus erythematosus", "mention_text": "OBJECTIVES: Thrombotic microangiopathy is a well-known problem in patients following renal transplantation. In postrenal transplantation, thrombotic microangiopathy is often a reflection of hemolytic uremic syndrome. We aimed to determine the causes of thrombotic microangiopathy in a population of renal transplantation recipients and discuss the literature. MATERIALS AND METHODS: We investigated the causes of thrombotic microangiopathy during a 1-year period, from June 2003 to June 2004, at the King Fahad National Guard Hospital in Riyadh, Saudi Arabia, by reviewing the slides of all transplant biopsies (n=25) performed during this interval. Pre- and posttransplant crossmatching was done when possible. RESULTS: Five cases of thrombotic microangiopathy were found. Three of these cases were from the 25 transplantations performed at King Fahad National Guard Hospital, while the other 2 transplantations had been performed abroad and were referred to us for follow-up. Three cases were related to cyclosporine, and 1 case was secondary to both cyclosporine and tacrolimus. The fifth case had features of thrombotic microangiopathy related to an antiphospholipid syndrome in a patient with systemic lupus erythematosus. CONCLUSIONS: In the literature, the most-frequent cause of hemolytic uremic syndrome in patients following renal transplantation is recurrence of the hemolytic uremic syndrome. Other causes include drug-related (cyclosporine, tacrolimus) toxicity, procoagulant status, and antibody-mediated rejection. We found that the most-frequent cause of thrombotic microangiopathy was drug related, secondary mainly to cyclosporine. In the current study, the frequency of thrombotic microangiopathy was similar to the percentage reported in the literature (20%).", "entity": "Lupus Erythematosus, Systemic", "aliases": "Disease Libman-Sacks Libman Sacks Lupus Erythematosus Disseminatus Systemic", "definition": "A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.\n    ", "id": "MESH:D008180"}
{"mention": "toxicity", "mention_text": "OBJECTIVES: Thrombotic microangiopathy is a well-known problem in patients following renal transplantation. In postrenal transplantation, thrombotic microangiopathy is often a reflection of hemolytic uremic syndrome. We aimed to determine the causes of thrombotic microangiopathy in a population of renal transplantation recipients and discuss the literature. MATERIALS AND METHODS: We investigated the causes of thrombotic microangiopathy during a 1-year period, from June 2003 to June 2004, at the King Fahad National Guard Hospital in Riyadh, Saudi Arabia, by reviewing the slides of all transplant biopsies (n=25) performed during this interval. Pre- and posttransplant crossmatching was done when possible. RESULTS: Five cases of thrombotic microangiopathy were found. Three of these cases were from the 25 transplantations performed at King Fahad National Guard Hospital, while the other 2 transplantations had been performed abroad and were referred to us for follow-up. Three cases were related to cyclosporine, and 1 case was secondary to both cyclosporine and tacrolimus. The fifth case had features of thrombotic microangiopathy related to an antiphospholipid syndrome in a patient with systemic lupus erythematosus. CONCLUSIONS: In the literature, the most-frequent cause of hemolytic uremic syndrome in patients following renal transplantation is recurrence of the hemolytic uremic syndrome. Other causes include drug-related (cyclosporine, tacrolimus) toxicity, procoagulant status, and antibody-mediated rejection. We found that the most-frequent cause of thrombotic microangiopathy was drug related, secondary mainly to cyclosporine. In the current study, the frequency of thrombotic microangiopathy was similar to the percentage reported in the literature (20%).", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "left ventricular systolic and diastolic dysfunction", "mention_text": "Severe reversible left ventricular systolic and diastolic dysfunction due to accidental iatrogenic epinephrine overdose.", "entity": "Ventricular Dysfunction, Left", "aliases": "Dysfunction Left Ventricular Dysfunctions", "definition": "A condition in which the LEFT VENTRICLE of the heart was functionally impaired. This condition usually leads to HEART FAILURE; MYOCARDIAL INFARCTION; and other cardiovascular complications. Diagnosis is made by measuring the diminished ejection fraction and a depressed level of motility of the left ventricular wall.\n    ", "id": "MESH:D018487"}
{"mention": "epinephrine", "mention_text": "Severe reversible left ventricular systolic and diastolic dysfunction due to accidental iatrogenic epinephrine overdose.", "entity": "Epinephrine", "aliases": "4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-benzenediol Acetate Epinephrine Adrenaline Acid Tartrate Bitartrate Hydrochloride Allergan Brand of Epifrin Hydrogen Epitrate Lyophrin Medihaler-Epi", "definition": "The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.\n    ", "id": "MESH:D004837"}
{"mention": "overdose", "mention_text": "Severe reversible left ventricular systolic and diastolic dysfunction due to accidental iatrogenic epinephrine overdose.", "entity": "Drug Overdose", "aliases": "Drug Overdose Overdoses", "definition": "Accidental or deliberate use of a medication or street drug in excess of normal dosage.\n    ", "id": "MESH:D062787"}
{"mention": "Catecholamine", "mention_text": "Catecholamine-induced cardiomyopathy due to chronic excess of endogenous catecholamines has been recognized for decades as a clinical phenomenon. In contrast, reports of myocardial dysfunction due to acute iatrogenic overdose are rare. A 35-year-old woman whose cervix uteri was inadvertently injected with 8 mg of epinephrine developed myocardial stunning that was characterized by severe hemodynamic compromise, profound, albeit transient, left ventricular systolic and diastolic dysfunction, and only modestly elevated biochemical markers of myocardial necrosis. Our case illustrates the serious consequences of medical errors that can be avoided through improved medication labeling and staff supervision.", "entity": "Catecholamines", "aliases": "Catecholamines Sympathins", "definition": "A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine.\n    ", "id": "MESH:D002395"}
{"mention": "cardiomyopathy", "mention_text": "Catecholamine-induced cardiomyopathy due to chronic excess of endogenous catecholamines has been recognized for decades as a clinical phenomenon. In contrast, reports of myocardial dysfunction due to acute iatrogenic overdose are rare. A 35-year-old woman whose cervix uteri was inadvertently injected with 8 mg of epinephrine developed myocardial stunning that was characterized by severe hemodynamic compromise, profound, albeit transient, left ventricular systolic and diastolic dysfunction, and only modestly elevated biochemical markers of myocardial necrosis. Our case illustrates the serious consequences of medical errors that can be avoided through improved medication labeling and staff supervision.", "entity": "Cardiomyopathies", "aliases": "Cardiomyopathies Primary Secondary Cardiomyopathy Disease Myocardial Diseases Myocardiopathies Myocardiopathy", "definition": "A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).\n    ", "id": "MESH:D009202"}
{"mention": "catecholamines", "mention_text": "Catecholamine-induced cardiomyopathy due to chronic excess of endogenous catecholamines has been recognized for decades as a clinical phenomenon. In contrast, reports of myocardial dysfunction due to acute iatrogenic overdose are rare. A 35-year-old woman whose cervix uteri was inadvertently injected with 8 mg of epinephrine developed myocardial stunning that was characterized by severe hemodynamic compromise, profound, albeit transient, left ventricular systolic and diastolic dysfunction, and only modestly elevated biochemical markers of myocardial necrosis. Our case illustrates the serious consequences of medical errors that can be avoided through improved medication labeling and staff supervision.", "entity": "Catecholamines", "aliases": "Catecholamines Sympathins", "definition": "A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine.\n    ", "id": "MESH:D002395"}
{"mention": "myocardial dysfunction", "mention_text": "Catecholamine-induced cardiomyopathy due to chronic excess of endogenous catecholamines has been recognized for decades as a clinical phenomenon. In contrast, reports of myocardial dysfunction due to acute iatrogenic overdose are rare. A 35-year-old woman whose cervix uteri was inadvertently injected with 8 mg of epinephrine developed myocardial stunning that was characterized by severe hemodynamic compromise, profound, albeit transient, left ventricular systolic and diastolic dysfunction, and only modestly elevated biochemical markers of myocardial necrosis. Our case illustrates the serious consequences of medical errors that can be avoided through improved medication labeling and staff supervision.", "entity": "Cardiomyopathies", "aliases": "Cardiomyopathies Primary Secondary Cardiomyopathy Disease Myocardial Diseases Myocardiopathies Myocardiopathy", "definition": "A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).\n    ", "id": "MESH:D009202"}
{"mention": "overdose", "mention_text": "Catecholamine-induced cardiomyopathy due to chronic excess of endogenous catecholamines has been recognized for decades as a clinical phenomenon. In contrast, reports of myocardial dysfunction due to acute iatrogenic overdose are rare. A 35-year-old woman whose cervix uteri was inadvertently injected with 8 mg of epinephrine developed myocardial stunning that was characterized by severe hemodynamic compromise, profound, albeit transient, left ventricular systolic and diastolic dysfunction, and only modestly elevated biochemical markers of myocardial necrosis. Our case illustrates the serious consequences of medical errors that can be avoided through improved medication labeling and staff supervision.", "entity": "Drug Overdose", "aliases": "Drug Overdose Overdoses", "definition": "Accidental or deliberate use of a medication or street drug in excess of normal dosage.\n    ", "id": "MESH:D062787"}
{"mention": "epinephrine", "mention_text": "Catecholamine-induced cardiomyopathy due to chronic excess of endogenous catecholamines has been recognized for decades as a clinical phenomenon. In contrast, reports of myocardial dysfunction due to acute iatrogenic overdose are rare. A 35-year-old woman whose cervix uteri was inadvertently injected with 8 mg of epinephrine developed myocardial stunning that was characterized by severe hemodynamic compromise, profound, albeit transient, left ventricular systolic and diastolic dysfunction, and only modestly elevated biochemical markers of myocardial necrosis. Our case illustrates the serious consequences of medical errors that can be avoided through improved medication labeling and staff supervision.", "entity": "Epinephrine", "aliases": "4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-benzenediol Acetate Epinephrine Adrenaline Acid Tartrate Bitartrate Hydrochloride Allergan Brand of Epifrin Hydrogen Epitrate Lyophrin Medihaler-Epi", "definition": "The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.\n    ", "id": "MESH:D004837"}
{"mention": "myocardial stunning", "mention_text": "Catecholamine-induced cardiomyopathy due to chronic excess of endogenous catecholamines has been recognized for decades as a clinical phenomenon. In contrast, reports of myocardial dysfunction due to acute iatrogenic overdose are rare. A 35-year-old woman whose cervix uteri was inadvertently injected with 8 mg of epinephrine developed myocardial stunning that was characterized by severe hemodynamic compromise, profound, albeit transient, left ventricular systolic and diastolic dysfunction, and only modestly elevated biochemical markers of myocardial necrosis. Our case illustrates the serious consequences of medical errors that can be avoided through improved medication labeling and staff supervision.", "entity": "Myocardial Stunning", "aliases": "Hibernation Myocardial Stunning Myocardium Stunned", "definition": "Prolonged dysfunction of the myocardium after a brief episode of severe ischemia, with gradual return of contractile activity. It occurs frequently, both in the experimental laboratory and in clinical medicine. Since stunned myocardium occurs adjacent to necrotic tissue after prolonged coronary occlusion, many myocardial infarcts may be a mixture of necrotic and stunned tissue. (Braunwald, Heart Disease, 1992, p1176)\n    ", "id": "MESH:D017682"}
{"mention": "left ventricular systolic and diastolic dysfunction", "mention_text": "Catecholamine-induced cardiomyopathy due to chronic excess of endogenous catecholamines has been recognized for decades as a clinical phenomenon. In contrast, reports of myocardial dysfunction due to acute iatrogenic overdose are rare. A 35-year-old woman whose cervix uteri was inadvertently injected with 8 mg of epinephrine developed myocardial stunning that was characterized by severe hemodynamic compromise, profound, albeit transient, left ventricular systolic and diastolic dysfunction, and only modestly elevated biochemical markers of myocardial necrosis. Our case illustrates the serious consequences of medical errors that can be avoided through improved medication labeling and staff supervision.", "entity": "Ventricular Dysfunction, Left", "aliases": "Dysfunction Left Ventricular Dysfunctions", "definition": "A condition in which the LEFT VENTRICLE of the heart was functionally impaired. This condition usually leads to HEART FAILURE; MYOCARDIAL INFARCTION; and other cardiovascular complications. Diagnosis is made by measuring the diminished ejection fraction and a depressed level of motility of the left ventricular wall.\n    ", "id": "MESH:D018487"}
{"mention": "myocardial necrosis", "mention_text": "Catecholamine-induced cardiomyopathy due to chronic excess of endogenous catecholamines has been recognized for decades as a clinical phenomenon. In contrast, reports of myocardial dysfunction due to acute iatrogenic overdose are rare. A 35-year-old woman whose cervix uteri was inadvertently injected with 8 mg of epinephrine developed myocardial stunning that was characterized by severe hemodynamic compromise, profound, albeit transient, left ventricular systolic and diastolic dysfunction, and only modestly elevated biochemical markers of myocardial necrosis. Our case illustrates the serious consequences of medical errors that can be avoided through improved medication labeling and staff supervision.", "entity": "Cardiomyopathies", "aliases": "Cardiomyopathies Primary Secondary Cardiomyopathy Disease Myocardial Diseases Myocardiopathies Myocardiopathy", "definition": "A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).\n    ", "id": "MESH:D009202"}
{"mention": "Urinary bladder cancer", "mention_text": "Urinary bladder cancer in Wegener's granulomatosis: risks and relation to cyclophosphamide.", "entity": "Urinary Bladder Neoplasms", "aliases": "Bladder Cancer Cancers Neoplasm Neoplasms Tumor Tumors of the Urinary Malignant", "definition": "Tumors or cancer of the URINARY BLADDER.\n    ", "id": "MESH:D001749"}
{"mention": "Wegener's granulomatosis", "mention_text": "Urinary bladder cancer in Wegener's granulomatosis: risks and relation to cyclophosphamide.", "entity": "Granulomatosis with Polyangiitis", "aliases": "Granulomatosis with Polyangiitides Polyangiitis Wegener Wegener's", "definition": "A multisystemic disease of a complex genetic background. It is characterized by inflammation of the blood vessels (VASCULITIS) leading to damage in any number of organs. The common features include granulomatous inflammation of the RESPIRATORY TRACT and KIDNEYS. Most patients have measurable autoantibodies (ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES) against MYELOBLASTIN.\n    ", "id": "MESH:D014890"}
{"mention": "cyclophosphamide", "mention_text": "Urinary bladder cancer in Wegener's granulomatosis: risks and relation to cyclophosphamide.", "entity": "Cyclophosphamide", "aliases": "Anhydrous Cyclophosphamide B 518 B-518 B518 Monohydrate (R)-Isomer (S)-Isomer Cyclophosphane Cytophosphan Cytophosphane Cytoxan Endoxan NSC 26271 NSC-26271 NSC26271 Neosar Procytox Sendoxan", "definition": "Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.\n    ", "id": "MESH:D003520"}
{"mention": "bladder cancer", "mention_text": "OBJECTIVE: To assess and characterise the risk of bladder cancer, and its relation to cyclophosphamide, in patients with Wegener's granulomatosis. METHODS: In the population based, nationwide Swedish Inpatient Register a cohort of 1065 patients with Wegener's granulomatosis, 1969-95, was identified. Through linkage with the Swedish Cancer Register, all subjects in this cohort diagnosed with bladder cancer were identified. Nested within the cohort, a matched case-control study was performed to estimate the association between cyclophosphamide and bladder cancer using odds ratios (ORs) as relative risk. In the cohort the cumulative risk of bladder cancer after Wegener's granulomatosis, and the relative prevalence of a history of bladder cancer at the time of diagnosis of Wegener's granulomatosis, were also estimated. RESULTS: The median cumulative doses of cyclophosphamide among cases (n = 11) and controls (n = 25) were 113 g and 25 g, respectively. The risk of bladder cancer doubled for every 10 g increment in cyclophosphamide (OR = 2.0, 95% confidence interval (CI) 0.8 to 4.9). Treatment duration longer than 1 year was associated with an eightfold increased risk (OR = 7.7, 95% CI 0.9 to 69). The absolute risk for bladder cancer in the cohort reached 10% 16 years after diagnosis of Wegener's granulomatosis, and a history of bladder cancer was (non-significantly) twice as common as expected at the time of diagnosis of Wegener's granulomatosis. CONCLUSION: The results indicate a dose-response relationship between cyclophosphamide and the risk of bladder cancer, high cumulative risks in the entire cohort, and also the possibility of risk factors operating even before Wegener's granulomatosis.", "entity": "Urinary Bladder Neoplasms", "aliases": "Bladder Cancer Cancers Neoplasm Neoplasms Tumor Tumors of the Urinary Malignant", "definition": "Tumors or cancer of the URINARY BLADDER.\n    ", "id": "MESH:D001749"}
{"mention": "cyclophosphamide", "mention_text": "OBJECTIVE: To assess and characterise the risk of bladder cancer, and its relation to cyclophosphamide, in patients with Wegener's granulomatosis. METHODS: In the population based, nationwide Swedish Inpatient Register a cohort of 1065 patients with Wegener's granulomatosis, 1969-95, was identified. Through linkage with the Swedish Cancer Register, all subjects in this cohort diagnosed with bladder cancer were identified. Nested within the cohort, a matched case-control study was performed to estimate the association between cyclophosphamide and bladder cancer using odds ratios (ORs) as relative risk. In the cohort the cumulative risk of bladder cancer after Wegener's granulomatosis, and the relative prevalence of a history of bladder cancer at the time of diagnosis of Wegener's granulomatosis, were also estimated. RESULTS: The median cumulative doses of cyclophosphamide among cases (n = 11) and controls (n = 25) were 113 g and 25 g, respectively. The risk of bladder cancer doubled for every 10 g increment in cyclophosphamide (OR = 2.0, 95% confidence interval (CI) 0.8 to 4.9). Treatment duration longer than 1 year was associated with an eightfold increased risk (OR = 7.7, 95% CI 0.9 to 69). The absolute risk for bladder cancer in the cohort reached 10% 16 years after diagnosis of Wegener's granulomatosis, and a history of bladder cancer was (non-significantly) twice as common as expected at the time of diagnosis of Wegener's granulomatosis. CONCLUSION: The results indicate a dose-response relationship between cyclophosphamide and the risk of bladder cancer, high cumulative risks in the entire cohort, and also the possibility of risk factors operating even before Wegener's granulomatosis.", "entity": "Cyclophosphamide", "aliases": "Anhydrous Cyclophosphamide B 518 B-518 B518 Monohydrate (R)-Isomer (S)-Isomer Cyclophosphane Cytophosphan Cytophosphane Cytoxan Endoxan NSC 26271 NSC-26271 NSC26271 Neosar Procytox Sendoxan", "definition": "Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.\n    ", "id": "MESH:D003520"}
{"mention": "Wegener's granulomatosis", "mention_text": "OBJECTIVE: To assess and characterise the risk of bladder cancer, and its relation to cyclophosphamide, in patients with Wegener's granulomatosis. METHODS: In the population based, nationwide Swedish Inpatient Register a cohort of 1065 patients with Wegener's granulomatosis, 1969-95, was identified. Through linkage with the Swedish Cancer Register, all subjects in this cohort diagnosed with bladder cancer were identified. Nested within the cohort, a matched case-control study was performed to estimate the association between cyclophosphamide and bladder cancer using odds ratios (ORs) as relative risk. In the cohort the cumulative risk of bladder cancer after Wegener's granulomatosis, and the relative prevalence of a history of bladder cancer at the time of diagnosis of Wegener's granulomatosis, were also estimated. RESULTS: The median cumulative doses of cyclophosphamide among cases (n = 11) and controls (n = 25) were 113 g and 25 g, respectively. The risk of bladder cancer doubled for every 10 g increment in cyclophosphamide (OR = 2.0, 95% confidence interval (CI) 0.8 to 4.9). Treatment duration longer than 1 year was associated with an eightfold increased risk (OR = 7.7, 95% CI 0.9 to 69). The absolute risk for bladder cancer in the cohort reached 10% 16 years after diagnosis of Wegener's granulomatosis, and a history of bladder cancer was (non-significantly) twice as common as expected at the time of diagnosis of Wegener's granulomatosis. CONCLUSION: The results indicate a dose-response relationship between cyclophosphamide and the risk of bladder cancer, high cumulative risks in the entire cohort, and also the possibility of risk factors operating even before Wegener's granulomatosis.", "entity": "Granulomatosis with Polyangiitis", "aliases": "Granulomatosis with Polyangiitides Polyangiitis Wegener Wegener's", "definition": "A multisystemic disease of a complex genetic background. It is characterized by inflammation of the blood vessels (VASCULITIS) leading to damage in any number of organs. The common features include granulomatous inflammation of the RESPIRATORY TRACT and KIDNEYS. Most patients have measurable autoantibodies (ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES) against MYELOBLASTIN.\n    ", "id": "MESH:D014890"}
{"mention": "Cancer", "mention_text": "OBJECTIVE: To assess and characterise the risk of bladder cancer, and its relation to cyclophosphamide, in patients with Wegener's granulomatosis. METHODS: In the population based, nationwide Swedish Inpatient Register a cohort of 1065 patients with Wegener's granulomatosis, 1969-95, was identified. Through linkage with the Swedish Cancer Register, all subjects in this cohort diagnosed with bladder cancer were identified. Nested within the cohort, a matched case-control study was performed to estimate the association between cyclophosphamide and bladder cancer using odds ratios (ORs) as relative risk. In the cohort the cumulative risk of bladder cancer after Wegener's granulomatosis, and the relative prevalence of a history of bladder cancer at the time of diagnosis of Wegener's granulomatosis, were also estimated. RESULTS: The median cumulative doses of cyclophosphamide among cases (n = 11) and controls (n = 25) were 113 g and 25 g, respectively. The risk of bladder cancer doubled for every 10 g increment in cyclophosphamide (OR = 2.0, 95% confidence interval (CI) 0.8 to 4.9). Treatment duration longer than 1 year was associated with an eightfold increased risk (OR = 7.7, 95% CI 0.9 to 69). The absolute risk for bladder cancer in the cohort reached 10% 16 years after diagnosis of Wegener's granulomatosis, and a history of bladder cancer was (non-significantly) twice as common as expected at the time of diagnosis of Wegener's granulomatosis. CONCLUSION: The results indicate a dose-response relationship between cyclophosphamide and the risk of bladder cancer, high cumulative risks in the entire cohort, and also the possibility of risk factors operating even before Wegener's granulomatosis.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "L-arginine", "mention_text": "L-arginine transport in humans with cortisol-induced hypertension.", "entity": "Arginine", "aliases": "Arginine Hydrochloride L Isomer L-Isomer DL Acetate Monohydrate DL-Arginine L-Arginine", "definition": "An essential amino acid that is physiologically active in the L-form.\n    ", "id": "MESH:D001120"}
{"mention": "cortisol", "mention_text": "L-arginine transport in humans with cortisol-induced hypertension.", "entity": "Hydrocortisone", "aliases": "11 Epicortisol 11-Epicortisol Cortifair Cortisol Cortril Hydrocortisone (11 alpha)-Isomer (9 beta,10 alpha,11", "definition": "The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.\n    ", "id": "MESH:D006854"}
{"mention": "hypertension", "mention_text": "L-arginine transport in humans with cortisol-induced hypertension.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "L-arginine", "mention_text": "A deficient L-arginine-nitric oxide system is implicated in cortisol-induced hypertension. We investigate whether abnormalities in L-arginine uptake contribute to this deficiency. Eight healthy men were recruited. Hydrocortisone acetate (50 mg) was given orally every 6 hours for 24 hours after a 5-day fixed-salt diet (150 mmol/d). Crossover studies were performed 2 weeks apart. Thirty milliliters of blood was obtained for isolation of peripheral blood mononuclear cells after each treatment period. L-arginine uptake was assessed in mononuclear cells incubated with L-arginine (1 to 300 micromol/L), incorporating 100 nmol/L [3H]-l-arginine for a period of 5 minutes at 37 degrees C. Forearm [3H]-L-arginine extraction was calculated after infusion of [3H]-L-arginine into the brachial artery at a rate of 100 nCi/min for 80 minutes. Deep forearm venous samples were collected for determination of L-arginine extraction. Plasma cortisol concentrations were significantly raised during the active phase (323+/-43 to 1082+/-245 mmol/L, P<0.05). Systolic blood pressure was elevated by an average of 7 mm Hg. Neither L-arginine transport into mononuclear cells (placebo vs active, 26.3+/-3.6 vs 29.0+/-2.1 pmol/10 000 cells per 5 minutes, respectively, at an l-arginine concentration of 300 micromol/L) nor L-arginine extraction in the forearm (at 80 minutes, placebo vs active, 1 868 904+/-434 962 vs 2 013 910+/-770 619 disintegrations per minute) was affected by cortisol treatment; ie, that L-arginine uptake is not affected by short-term cortisol treatment. We conclude that cortisol-induced increases in blood pressure are not associated with abnormalities in the l-arginine transport system.", "entity": "Arginine", "aliases": "Arginine Hydrochloride L Isomer L-Isomer DL Acetate Monohydrate DL-Arginine L-Arginine", "definition": "An essential amino acid that is physiologically active in the L-form.\n    ", "id": "MESH:D001120"}
{"mention": "nitric oxide", "mention_text": "A deficient L-arginine-nitric oxide system is implicated in cortisol-induced hypertension. We investigate whether abnormalities in L-arginine uptake contribute to this deficiency. Eight healthy men were recruited. Hydrocortisone acetate (50 mg) was given orally every 6 hours for 24 hours after a 5-day fixed-salt diet (150 mmol/d). Crossover studies were performed 2 weeks apart. Thirty milliliters of blood was obtained for isolation of peripheral blood mononuclear cells after each treatment period. L-arginine uptake was assessed in mononuclear cells incubated with L-arginine (1 to 300 micromol/L), incorporating 100 nmol/L [3H]-l-arginine for a period of 5 minutes at 37 degrees C. Forearm [3H]-L-arginine extraction was calculated after infusion of [3H]-L-arginine into the brachial artery at a rate of 100 nCi/min for 80 minutes. Deep forearm venous samples were collected for determination of L-arginine extraction. Plasma cortisol concentrations were significantly raised during the active phase (323+/-43 to 1082+/-245 mmol/L, P<0.05). Systolic blood pressure was elevated by an average of 7 mm Hg. Neither L-arginine transport into mononuclear cells (placebo vs active, 26.3+/-3.6 vs 29.0+/-2.1 pmol/10 000 cells per 5 minutes, respectively, at an l-arginine concentration of 300 micromol/L) nor L-arginine extraction in the forearm (at 80 minutes, placebo vs active, 1 868 904+/-434 962 vs 2 013 910+/-770 619 disintegrations per minute) was affected by cortisol treatment; ie, that L-arginine uptake is not affected by short-term cortisol treatment. We conclude that cortisol-induced increases in blood pressure are not associated with abnormalities in the l-arginine transport system.", "entity": "Nitric Oxide", "aliases": "Endogenous Nitrate Vasodilator Endothelium-Derived Nitric Oxide Mononitrogen Monoxide Nitrogen Endothelium Derived", "definition": "A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.\n    ", "id": "MESH:D009569"}
{"mention": "cortisol", "mention_text": "A deficient L-arginine-nitric oxide system is implicated in cortisol-induced hypertension. We investigate whether abnormalities in L-arginine uptake contribute to this deficiency. Eight healthy men were recruited. Hydrocortisone acetate (50 mg) was given orally every 6 hours for 24 hours after a 5-day fixed-salt diet (150 mmol/d). Crossover studies were performed 2 weeks apart. Thirty milliliters of blood was obtained for isolation of peripheral blood mononuclear cells after each treatment period. L-arginine uptake was assessed in mononuclear cells incubated with L-arginine (1 to 300 micromol/L), incorporating 100 nmol/L [3H]-l-arginine for a period of 5 minutes at 37 degrees C. Forearm [3H]-L-arginine extraction was calculated after infusion of [3H]-L-arginine into the brachial artery at a rate of 100 nCi/min for 80 minutes. Deep forearm venous samples were collected for determination of L-arginine extraction. Plasma cortisol concentrations were significantly raised during the active phase (323+/-43 to 1082+/-245 mmol/L, P<0.05). Systolic blood pressure was elevated by an average of 7 mm Hg. Neither L-arginine transport into mononuclear cells (placebo vs active, 26.3+/-3.6 vs 29.0+/-2.1 pmol/10 000 cells per 5 minutes, respectively, at an l-arginine concentration of 300 micromol/L) nor L-arginine extraction in the forearm (at 80 minutes, placebo vs active, 1 868 904+/-434 962 vs 2 013 910+/-770 619 disintegrations per minute) was affected by cortisol treatment; ie, that L-arginine uptake is not affected by short-term cortisol treatment. We conclude that cortisol-induced increases in blood pressure are not associated with abnormalities in the l-arginine transport system.", "entity": "Hydrocortisone", "aliases": "11 Epicortisol 11-Epicortisol Cortifair Cortisol Cortril Hydrocortisone (11 alpha)-Isomer (9 beta,10 alpha,11", "definition": "The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.\n    ", "id": "MESH:D006854"}
{"mention": "hypertension", "mention_text": "A deficient L-arginine-nitric oxide system is implicated in cortisol-induced hypertension. We investigate whether abnormalities in L-arginine uptake contribute to this deficiency. Eight healthy men were recruited. Hydrocortisone acetate (50 mg) was given orally every 6 hours for 24 hours after a 5-day fixed-salt diet (150 mmol/d). Crossover studies were performed 2 weeks apart. Thirty milliliters of blood was obtained for isolation of peripheral blood mononuclear cells after each treatment period. L-arginine uptake was assessed in mononuclear cells incubated with L-arginine (1 to 300 micromol/L), incorporating 100 nmol/L [3H]-l-arginine for a period of 5 minutes at 37 degrees C. Forearm [3H]-L-arginine extraction was calculated after infusion of [3H]-L-arginine into the brachial artery at a rate of 100 nCi/min for 80 minutes. Deep forearm venous samples were collected for determination of L-arginine extraction. Plasma cortisol concentrations were significantly raised during the active phase (323+/-43 to 1082+/-245 mmol/L, P<0.05). Systolic blood pressure was elevated by an average of 7 mm Hg. Neither L-arginine transport into mononuclear cells (placebo vs active, 26.3+/-3.6 vs 29.0+/-2.1 pmol/10 000 cells per 5 minutes, respectively, at an l-arginine concentration of 300 micromol/L) nor L-arginine extraction in the forearm (at 80 minutes, placebo vs active, 1 868 904+/-434 962 vs 2 013 910+/-770 619 disintegrations per minute) was affected by cortisol treatment; ie, that L-arginine uptake is not affected by short-term cortisol treatment. We conclude that cortisol-induced increases in blood pressure are not associated with abnormalities in the l-arginine transport system.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "Hydrocortisone acetate", "mention_text": "A deficient L-arginine-nitric oxide system is implicated in cortisol-induced hypertension. We investigate whether abnormalities in L-arginine uptake contribute to this deficiency. Eight healthy men were recruited. Hydrocortisone acetate (50 mg) was given orally every 6 hours for 24 hours after a 5-day fixed-salt diet (150 mmol/d). Crossover studies were performed 2 weeks apart. Thirty milliliters of blood was obtained for isolation of peripheral blood mononuclear cells after each treatment period. L-arginine uptake was assessed in mononuclear cells incubated with L-arginine (1 to 300 micromol/L), incorporating 100 nmol/L [3H]-l-arginine for a period of 5 minutes at 37 degrees C. Forearm [3H]-L-arginine extraction was calculated after infusion of [3H]-L-arginine into the brachial artery at a rate of 100 nCi/min for 80 minutes. Deep forearm venous samples were collected for determination of L-arginine extraction. Plasma cortisol concentrations were significantly raised during the active phase (323+/-43 to 1082+/-245 mmol/L, P<0.05). Systolic blood pressure was elevated by an average of 7 mm Hg. Neither L-arginine transport into mononuclear cells (placebo vs active, 26.3+/-3.6 vs 29.0+/-2.1 pmol/10 000 cells per 5 minutes, respectively, at an l-arginine concentration of 300 micromol/L) nor L-arginine extraction in the forearm (at 80 minutes, placebo vs active, 1 868 904+/-434 962 vs 2 013 910+/-770 619 disintegrations per minute) was affected by cortisol treatment; ie, that L-arginine uptake is not affected by short-term cortisol treatment. We conclude that cortisol-induced increases in blood pressure are not associated with abnormalities in the l-arginine transport system.", "entity": "hydrocortisone acetate", "aliases": "Colifoam Cortifoam Epifoam cortisol 21-acetate hydrocortisone acetate (11alpha)-isomer (11beta)-isomer (11beta,17alpha)-isomer monoammonium salt sodium", "definition": "", "id": "MESH:C021650"}
{"mention": "[3H]-l-arginine", "mention_text": "A deficient L-arginine-nitric oxide system is implicated in cortisol-induced hypertension. We investigate whether abnormalities in L-arginine uptake contribute to this deficiency. Eight healthy men were recruited. Hydrocortisone acetate (50 mg) was given orally every 6 hours for 24 hours after a 5-day fixed-salt diet (150 mmol/d). Crossover studies were performed 2 weeks apart. Thirty milliliters of blood was obtained for isolation of peripheral blood mononuclear cells after each treatment period. L-arginine uptake was assessed in mononuclear cells incubated with L-arginine (1 to 300 micromol/L), incorporating 100 nmol/L [3H]-l-arginine for a period of 5 minutes at 37 degrees C. Forearm [3H]-L-arginine extraction was calculated after infusion of [3H]-L-arginine into the brachial artery at a rate of 100 nCi/min for 80 minutes. Deep forearm venous samples were collected for determination of L-arginine extraction. Plasma cortisol concentrations were significantly raised during the active phase (323+/-43 to 1082+/-245 mmol/L, P<0.05). Systolic blood pressure was elevated by an average of 7 mm Hg. Neither L-arginine transport into mononuclear cells (placebo vs active, 26.3+/-3.6 vs 29.0+/-2.1 pmol/10 000 cells per 5 minutes, respectively, at an l-arginine concentration of 300 micromol/L) nor L-arginine extraction in the forearm (at 80 minutes, placebo vs active, 1 868 904+/-434 962 vs 2 013 910+/-770 619 disintegrations per minute) was affected by cortisol treatment; ie, that L-arginine uptake is not affected by short-term cortisol treatment. We conclude that cortisol-induced increases in blood pressure are not associated with abnormalities in the l-arginine transport system.", "entity": "Arginine", "aliases": "Arginine Hydrochloride L Isomer L-Isomer DL Acetate Monohydrate DL-Arginine L-Arginine", "definition": "An essential amino acid that is physiologically active in the L-form.\n    ", "id": "MESH:D001120"}
{"mention": "[3H]-L-arginine", "mention_text": "A deficient L-arginine-nitric oxide system is implicated in cortisol-induced hypertension. We investigate whether abnormalities in L-arginine uptake contribute to this deficiency. Eight healthy men were recruited. Hydrocortisone acetate (50 mg) was given orally every 6 hours for 24 hours after a 5-day fixed-salt diet (150 mmol/d). Crossover studies were performed 2 weeks apart. Thirty milliliters of blood was obtained for isolation of peripheral blood mononuclear cells after each treatment period. L-arginine uptake was assessed in mononuclear cells incubated with L-arginine (1 to 300 micromol/L), incorporating 100 nmol/L [3H]-l-arginine for a period of 5 minutes at 37 degrees C. Forearm [3H]-L-arginine extraction was calculated after infusion of [3H]-L-arginine into the brachial artery at a rate of 100 nCi/min for 80 minutes. Deep forearm venous samples were collected for determination of L-arginine extraction. Plasma cortisol concentrations were significantly raised during the active phase (323+/-43 to 1082+/-245 mmol/L, P<0.05). Systolic blood pressure was elevated by an average of 7 mm Hg. Neither L-arginine transport into mononuclear cells (placebo vs active, 26.3+/-3.6 vs 29.0+/-2.1 pmol/10 000 cells per 5 minutes, respectively, at an l-arginine concentration of 300 micromol/L) nor L-arginine extraction in the forearm (at 80 minutes, placebo vs active, 1 868 904+/-434 962 vs 2 013 910+/-770 619 disintegrations per minute) was affected by cortisol treatment; ie, that L-arginine uptake is not affected by short-term cortisol treatment. We conclude that cortisol-induced increases in blood pressure are not associated with abnormalities in the l-arginine transport system.", "entity": "Arginine", "aliases": "Arginine Hydrochloride L Isomer L-Isomer DL Acetate Monohydrate DL-Arginine L-Arginine", "definition": "An essential amino acid that is physiologically active in the L-form.\n    ", "id": "MESH:D001120"}
{"mention": "l-arginine", "mention_text": "A deficient L-arginine-nitric oxide system is implicated in cortisol-induced hypertension. We investigate whether abnormalities in L-arginine uptake contribute to this deficiency. Eight healthy men were recruited. Hydrocortisone acetate (50 mg) was given orally every 6 hours for 24 hours after a 5-day fixed-salt diet (150 mmol/d). Crossover studies were performed 2 weeks apart. Thirty milliliters of blood was obtained for isolation of peripheral blood mononuclear cells after each treatment period. L-arginine uptake was assessed in mononuclear cells incubated with L-arginine (1 to 300 micromol/L), incorporating 100 nmol/L [3H]-l-arginine for a period of 5 minutes at 37 degrees C. Forearm [3H]-L-arginine extraction was calculated after infusion of [3H]-L-arginine into the brachial artery at a rate of 100 nCi/min for 80 minutes. Deep forearm venous samples were collected for determination of L-arginine extraction. Plasma cortisol concentrations were significantly raised during the active phase (323+/-43 to 1082+/-245 mmol/L, P<0.05). Systolic blood pressure was elevated by an average of 7 mm Hg. Neither L-arginine transport into mononuclear cells (placebo vs active, 26.3+/-3.6 vs 29.0+/-2.1 pmol/10 000 cells per 5 minutes, respectively, at an l-arginine concentration of 300 micromol/L) nor L-arginine extraction in the forearm (at 80 minutes, placebo vs active, 1 868 904+/-434 962 vs 2 013 910+/-770 619 disintegrations per minute) was affected by cortisol treatment; ie, that L-arginine uptake is not affected by short-term cortisol treatment. We conclude that cortisol-induced increases in blood pressure are not associated with abnormalities in the l-arginine transport system.", "entity": "Arginine", "aliases": "Arginine Hydrochloride L Isomer L-Isomer DL Acetate Monohydrate DL-Arginine L-Arginine", "definition": "An essential amino acid that is physiologically active in the L-form.\n    ", "id": "MESH:D001120"}
{"mention": "increases in blood pressure", "mention_text": "A deficient L-arginine-nitric oxide system is implicated in cortisol-induced hypertension. We investigate whether abnormalities in L-arginine uptake contribute to this deficiency. Eight healthy men were recruited. Hydrocortisone acetate (50 mg) was given orally every 6 hours for 24 hours after a 5-day fixed-salt diet (150 mmol/d). Crossover studies were performed 2 weeks apart. Thirty milliliters of blood was obtained for isolation of peripheral blood mononuclear cells after each treatment period. L-arginine uptake was assessed in mononuclear cells incubated with L-arginine (1 to 300 micromol/L), incorporating 100 nmol/L [3H]-l-arginine for a period of 5 minutes at 37 degrees C. Forearm [3H]-L-arginine extraction was calculated after infusion of [3H]-L-arginine into the brachial artery at a rate of 100 nCi/min for 80 minutes. Deep forearm venous samples were collected for determination of L-arginine extraction. Plasma cortisol concentrations were significantly raised during the active phase (323+/-43 to 1082+/-245 mmol/L, P<0.05). Systolic blood pressure was elevated by an average of 7 mm Hg. Neither L-arginine transport into mononuclear cells (placebo vs active, 26.3+/-3.6 vs 29.0+/-2.1 pmol/10 000 cells per 5 minutes, respectively, at an l-arginine concentration of 300 micromol/L) nor L-arginine extraction in the forearm (at 80 minutes, placebo vs active, 1 868 904+/-434 962 vs 2 013 910+/-770 619 disintegrations per minute) was affected by cortisol treatment; ie, that L-arginine uptake is not affected by short-term cortisol treatment. We conclude that cortisol-induced increases in blood pressure are not associated with abnormalities in the l-arginine transport system.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "tacrolimus", "mention_text": "MR imaging with quantitative diffusion mapping of tacrolimus-induced neurotoxicity in organ transplant patients.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "neurotoxicity", "mention_text": "MR imaging with quantitative diffusion mapping of tacrolimus-induced neurotoxicity in organ transplant patients.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "tacrolimus", "mention_text": "Our objective was to investigate brain MR imaging findings and the utility of diffusion-weighted (DW) imaging in organ transplant patients who developed neurologic symptoms during tacrolimus therapy. Brain MR studies, including DW imaging, were prospectively performed in 14 organ transplant patients receiving tacrolimus who developed neurologic complications. In each patient who had abnormalities on the initial MR study, a follow-up MR study was performed 1 month later. Apparent diffusion coefficient (ADC) values on the initial MR study were correlated with reversibility of the lesions. Of the 14 patients, 5 (35.7%) had white matter abnormalities, 1 (7.1%) had putaminal hemorrhage, and 8 (57.1%) had normal findings on initial MR images. Among the 5 patients with white matter abnormalities, 4 patients (80.0%) showed higher than normal ADC values on initial MR images, and all showed complete resolution on follow-up images. The remaining 1 patient (20.0%) showed lower than normal ADC value and showed incomplete resolution with cortical laminar necrosis. Diffusion-weighted imaging may be useful in predicting the outcomes of the lesions of tacrolimus-induced neurotoxicity.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "neurologic complications", "mention_text": "Our objective was to investigate brain MR imaging findings and the utility of diffusion-weighted (DW) imaging in organ transplant patients who developed neurologic symptoms during tacrolimus therapy. Brain MR studies, including DW imaging, were prospectively performed in 14 organ transplant patients receiving tacrolimus who developed neurologic complications. In each patient who had abnormalities on the initial MR study, a follow-up MR study was performed 1 month later. Apparent diffusion coefficient (ADC) values on the initial MR study were correlated with reversibility of the lesions. Of the 14 patients, 5 (35.7%) had white matter abnormalities, 1 (7.1%) had putaminal hemorrhage, and 8 (57.1%) had normal findings on initial MR images. Among the 5 patients with white matter abnormalities, 4 patients (80.0%) showed higher than normal ADC values on initial MR images, and all showed complete resolution on follow-up images. The remaining 1 patient (20.0%) showed lower than normal ADC value and showed incomplete resolution with cortical laminar necrosis. Diffusion-weighted imaging may be useful in predicting the outcomes of the lesions of tacrolimus-induced neurotoxicity.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "white matter abnormalities", "mention_text": "Our objective was to investigate brain MR imaging findings and the utility of diffusion-weighted (DW) imaging in organ transplant patients who developed neurologic symptoms during tacrolimus therapy. Brain MR studies, including DW imaging, were prospectively performed in 14 organ transplant patients receiving tacrolimus who developed neurologic complications. In each patient who had abnormalities on the initial MR study, a follow-up MR study was performed 1 month later. Apparent diffusion coefficient (ADC) values on the initial MR study were correlated with reversibility of the lesions. Of the 14 patients, 5 (35.7%) had white matter abnormalities, 1 (7.1%) had putaminal hemorrhage, and 8 (57.1%) had normal findings on initial MR images. Among the 5 patients with white matter abnormalities, 4 patients (80.0%) showed higher than normal ADC values on initial MR images, and all showed complete resolution on follow-up images. The remaining 1 patient (20.0%) showed lower than normal ADC value and showed incomplete resolution with cortical laminar necrosis. Diffusion-weighted imaging may be useful in predicting the outcomes of the lesions of tacrolimus-induced neurotoxicity.", "entity": "Leukoencephalopathies", "aliases": "CACH Syndrome Syndromes CACH/VWM Centralis Diffusa Myelinosis Diffusas Childhood Ataxia with Central Nervous System Hypomyelination Hypomyelinization Diffuse Cree Leukoencephalopathies Leukoencephalopathy Disease White Matter Diseases Vanishing Leukodystrophy", "definition": "Any of various diseases affecting the white matter of the central nervous system.\n    ", "id": "MESH:D056784"}
{"mention": "putaminal hemorrhage", "mention_text": "Our objective was to investigate brain MR imaging findings and the utility of diffusion-weighted (DW) imaging in organ transplant patients who developed neurologic symptoms during tacrolimus therapy. Brain MR studies, including DW imaging, were prospectively performed in 14 organ transplant patients receiving tacrolimus who developed neurologic complications. In each patient who had abnormalities on the initial MR study, a follow-up MR study was performed 1 month later. Apparent diffusion coefficient (ADC) values on the initial MR study were correlated with reversibility of the lesions. Of the 14 patients, 5 (35.7%) had white matter abnormalities, 1 (7.1%) had putaminal hemorrhage, and 8 (57.1%) had normal findings on initial MR images. Among the 5 patients with white matter abnormalities, 4 patients (80.0%) showed higher than normal ADC values on initial MR images, and all showed complete resolution on follow-up images. The remaining 1 patient (20.0%) showed lower than normal ADC value and showed incomplete resolution with cortical laminar necrosis. Diffusion-weighted imaging may be useful in predicting the outcomes of the lesions of tacrolimus-induced neurotoxicity.", "entity": "Putaminal Hemorrhage", "aliases": "Brain Hemorrhage Putaminal Hemorrhages Putamen Hematoma", "definition": "Intracranial bleeding into the PUTAMEN, a BASAL GANGLIA nucleus. This is associated with HYPERTENSION and lipohyalinosis of small blood vessels in the putamen. Clinical manifestations vary with the size of hemorrhage, but include HEMIPARESIS; HEADACHE; and alterations of consciousness.\n    ", "id": "MESH:D020146"}
{"mention": "cortical laminar necrosis", "mention_text": "Our objective was to investigate brain MR imaging findings and the utility of diffusion-weighted (DW) imaging in organ transplant patients who developed neurologic symptoms during tacrolimus therapy. Brain MR studies, including DW imaging, were prospectively performed in 14 organ transplant patients receiving tacrolimus who developed neurologic complications. In each patient who had abnormalities on the initial MR study, a follow-up MR study was performed 1 month later. Apparent diffusion coefficient (ADC) values on the initial MR study were correlated with reversibility of the lesions. Of the 14 patients, 5 (35.7%) had white matter abnormalities, 1 (7.1%) had putaminal hemorrhage, and 8 (57.1%) had normal findings on initial MR images. Among the 5 patients with white matter abnormalities, 4 patients (80.0%) showed higher than normal ADC values on initial MR images, and all showed complete resolution on follow-up images. The remaining 1 patient (20.0%) showed lower than normal ADC value and showed incomplete resolution with cortical laminar necrosis. Diffusion-weighted imaging may be useful in predicting the outcomes of the lesions of tacrolimus-induced neurotoxicity.", "entity": "Brain Diseases", "aliases": "Brain Disease Diseases Disorder Disorders CNS Intracranial Central Nervous System Encephalon", "definition": "Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.\n    ", "id": "MESH:D001927"}
{"mention": "neurotoxicity", "mention_text": "Our objective was to investigate brain MR imaging findings and the utility of diffusion-weighted (DW) imaging in organ transplant patients who developed neurologic symptoms during tacrolimus therapy. Brain MR studies, including DW imaging, were prospectively performed in 14 organ transplant patients receiving tacrolimus who developed neurologic complications. In each patient who had abnormalities on the initial MR study, a follow-up MR study was performed 1 month later. Apparent diffusion coefficient (ADC) values on the initial MR study were correlated with reversibility of the lesions. Of the 14 patients, 5 (35.7%) had white matter abnormalities, 1 (7.1%) had putaminal hemorrhage, and 8 (57.1%) had normal findings on initial MR images. Among the 5 patients with white matter abnormalities, 4 patients (80.0%) showed higher than normal ADC values on initial MR images, and all showed complete resolution on follow-up images. The remaining 1 patient (20.0%) showed lower than normal ADC value and showed incomplete resolution with cortical laminar necrosis. Diffusion-weighted imaging may be useful in predicting the outcomes of the lesions of tacrolimus-induced neurotoxicity.", "entity": "Neurotoxicity Syndromes", "aliases": "Encephalitides Toxic Encephalitis Encephalopathies Encephalopathy Nervous System Poisoning Poisonings Neurotoxic Disorder Disorders Neurotoxicity Syndrome Syndromes Neurotoxin Disease Diseases", "definition": "Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.\n    ", "id": "MESH:D020258"}
{"mention": "Octreotide", "mention_text": "Octreotide-induced hypoxemia and pulmonary hypertension in premature neonates.", "entity": "Octreotide", "aliases": "Compound 201 995 201-995 201995 Octreotide Acetate Salt SAN SM SMS Sandostatin Sandostatine Sandoz", "definition": "A potent, long-acting synthetic SOMATOSTATIN octapeptide analog that inhibits secretion of GROWTH HORMONE and is used to treat hormone-secreting tumors; DIABETES MELLITUS; HYPOTENSION, ORTHOSTATIC; HYPERINSULINISM; hypergastrinemia; and small bowel fistula.\n    ", "id": "MESH:D015282"}
{"mention": "hypoxemia", "mention_text": "Octreotide-induced hypoxemia and pulmonary hypertension in premature neonates.", "entity": "Anoxia", "aliases": "Anoxemia Anoxemias Anoxia Anoxias Deficiencies Oxygen Deficiency Hypoxemia Hypoxemias Hypoxia Hypoxias", "definition": "Relatively complete absence of oxygen in one or more tissues.\n    ", "id": "MESH:D000860"}
{"mention": "pulmonary hypertension", "mention_text": "Octreotide-induced hypoxemia and pulmonary hypertension in premature neonates.", "entity": "Hypertension, Pulmonary", "aliases": "Hypertension Pulmonary", "definition": "Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES.\n    ", "id": "MESH:D006976"}
{"mention": "fistula", "mention_text": "The authors report 2 cases of premature neonates who had enterocutaneous fistula complicating necrotizing enterocolitis. Pulmonary hypertension developed after administration of a somatostatin analogue, octreotide, to enhance resolution of the fistula. The authors discuss the mechanism of the occurrence of this complication and recommend caution of its use in high-risk premature neonates.", "entity": "Fistula", "aliases": "Fistula Fistulas", "definition": "Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body.\n    ", "id": "MESH:D005402"}
{"mention": "necrotizing enterocolitis", "mention_text": "The authors report 2 cases of premature neonates who had enterocutaneous fistula complicating necrotizing enterocolitis. Pulmonary hypertension developed after administration of a somatostatin analogue, octreotide, to enhance resolution of the fistula. The authors discuss the mechanism of the occurrence of this complication and recommend caution of its use in high-risk premature neonates.", "entity": "Enterocolitis, Necrotizing", "aliases": "Enterocolitis Necrotizing", "definition": "ENTEROCOLITIS with extensive ulceration (ULCER) and NECROSIS. It is observed primarily in LOW BIRTH WEIGHT INFANT.\n    ", "id": "MESH:D020345"}
{"mention": "Pulmonary hypertension", "mention_text": "The authors report 2 cases of premature neonates who had enterocutaneous fistula complicating necrotizing enterocolitis. Pulmonary hypertension developed after administration of a somatostatin analogue, octreotide, to enhance resolution of the fistula. The authors discuss the mechanism of the occurrence of this complication and recommend caution of its use in high-risk premature neonates.", "entity": "Hypertension, Pulmonary", "aliases": "Hypertension Pulmonary", "definition": "Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES.\n    ", "id": "MESH:D006976"}
{"mention": "octreotide", "mention_text": "The authors report 2 cases of premature neonates who had enterocutaneous fistula complicating necrotizing enterocolitis. Pulmonary hypertension developed after administration of a somatostatin analogue, octreotide, to enhance resolution of the fistula. The authors discuss the mechanism of the occurrence of this complication and recommend caution of its use in high-risk premature neonates.", "entity": "Octreotide", "aliases": "Compound 201 995 201-995 201995 Octreotide Acetate Salt SAN SM SMS Sandostatin Sandostatine Sandoz", "definition": "A potent, long-acting synthetic SOMATOSTATIN octapeptide analog that inhibits secretion of GROWTH HORMONE and is used to treat hormone-secreting tumors; DIABETES MELLITUS; HYPOTENSION, ORTHOSTATIC; HYPERINSULINISM; hypergastrinemia; and small bowel fistula.\n    ", "id": "MESH:D015282"}
{"mention": "exencephaly", "mention_text": "Sequential observations of exencephaly and subsequent morphological changes by mouse exo utero development system: analysis of the mechanism of transformation from exencephaly to anencephaly.", "entity": "Neural Tube Defects", "aliases": "Acrania Acranias Craniorachischises Craniorachischisis Cyst Neurenteric Neuroenteric Cysts Defect Neural Tube Defects Developmental Diastematomyelia Diastematomyelias Dysraphism Occult Spinal Dysraphisms Exencephalies Exencephaly Iniencephalies Iniencephaly Myelodysplasia Cord Myelodysplasias Sequence Tethered Syndrome Syndromes", "definition": "Congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy generally occurring between days 18-29 of gestation. Ectodermal and mesodermal malformations (mainly involving the skull and vertebrae) may occur as a result of defects of neural tube closure. (From Joynt, Clinical Neurology, 1992, Ch55, pp31-41)\n    ", "id": "MESH:D009436"}
{"mention": "anencephaly", "mention_text": "Sequential observations of exencephaly and subsequent morphological changes by mouse exo utero development system: analysis of the mechanism of transformation from exencephaly to anencephaly.", "entity": "Anencephaly", "aliases": "Absence of Brain Congenital Anencephalia Anencephalias Anencephalies Partial Anencephalus Anencephaly Hemicranial Incomplete Aprosencephalies Aprosencephaly", "definition": "A malformation of the nervous system caused by failure of the anterior neuropore to close. Infants are born with intact spinal cords, cerebellums, and brainstems, but lack formation of neural structures above this level. The skull is only partially formed but the eyes are usually normal. This condition may be associated with folate deficiency. Affected infants are only capable of primitive (brain stem) reflexes and usually do not survive for more than two weeks. (From Menkes, Textbook of Child Neurology, 5th ed, p247)\n    ", "id": "MESH:D000757"}
{"mention": "Anencephaly", "mention_text": "Anencephaly has been suggested to develop from exencephaly; however, there is little direct experimental evidence to support this, and the mechanism of transformation remains unclear. We examined this theory using the exo utero development system that allows direct and sequential observations of mid- to late-gestation mouse embryos. We observed the exencephaly induced by 5-azacytidine at embryonic day 13.5 (E13.5), let the embryos develop exo utero until E18.5, and re-observed the same embryos at E18.5. We confirmed several cases of transformation from exencephaly to anencephaly. However, in many cases, the exencephalic brain tissue was preserved with more or less reduction during this period. To analyze the transformation patterns, we classified the exencephaly by size and shape of the exencephalic tissue into several types at E13.5 and E18.5. It was found that the transformation of exencephalic tissue was not simply size-dependent, and all cases of anencephaly at E18.5 resulted from embryos with a large amount of exencephalic tissue at E13.5. Microscopic observation showed the configuration of exencephaly at E13.5, frequent hemorrhaging and detachment of the neural plate from surface ectoderm in the exencephalic head at E15.5, and multiple modes of reduction in the exencephalic tissue at E18.5. From observations of the vasculature, altered distribution patterns of vessels were identified in the exencephalic head. These findings suggest that overgrowth of the exencephalic neural tissue causes the altered distribution patterns of vessels, subsequent peripheral circulatory failure and/or hemorrhaging in various parts of the exencephalic head, leading to the multiple modes of tissue reduction during transformation from exencephaly to anencephaly.", "entity": "Anencephaly", "aliases": "Absence of Brain Congenital Anencephalia Anencephalias Anencephalies Partial Anencephalus Anencephaly Hemicranial Incomplete Aprosencephalies Aprosencephaly", "definition": "A malformation of the nervous system caused by failure of the anterior neuropore to close. Infants are born with intact spinal cords, cerebellums, and brainstems, but lack formation of neural structures above this level. The skull is only partially formed but the eyes are usually normal. This condition may be associated with folate deficiency. Affected infants are only capable of primitive (brain stem) reflexes and usually do not survive for more than two weeks. (From Menkes, Textbook of Child Neurology, 5th ed, p247)\n    ", "id": "MESH:D000757"}
{"mention": "exencephaly", "mention_text": "Anencephaly has been suggested to develop from exencephaly; however, there is little direct experimental evidence to support this, and the mechanism of transformation remains unclear. We examined this theory using the exo utero development system that allows direct and sequential observations of mid- to late-gestation mouse embryos. We observed the exencephaly induced by 5-azacytidine at embryonic day 13.5 (E13.5), let the embryos develop exo utero until E18.5, and re-observed the same embryos at E18.5. We confirmed several cases of transformation from exencephaly to anencephaly. However, in many cases, the exencephalic brain tissue was preserved with more or less reduction during this period. To analyze the transformation patterns, we classified the exencephaly by size and shape of the exencephalic tissue into several types at E13.5 and E18.5. It was found that the transformation of exencephalic tissue was not simply size-dependent, and all cases of anencephaly at E18.5 resulted from embryos with a large amount of exencephalic tissue at E13.5. Microscopic observation showed the configuration of exencephaly at E13.5, frequent hemorrhaging and detachment of the neural plate from surface ectoderm in the exencephalic head at E15.5, and multiple modes of reduction in the exencephalic tissue at E18.5. From observations of the vasculature, altered distribution patterns of vessels were identified in the exencephalic head. These findings suggest that overgrowth of the exencephalic neural tissue causes the altered distribution patterns of vessels, subsequent peripheral circulatory failure and/or hemorrhaging in various parts of the exencephalic head, leading to the multiple modes of tissue reduction during transformation from exencephaly to anencephaly.", "entity": "Neural Tube Defects", "aliases": "Acrania Acranias Craniorachischises Craniorachischisis Cyst Neurenteric Neuroenteric Cysts Defect Neural Tube Defects Developmental Diastematomyelia Diastematomyelias Dysraphism Occult Spinal Dysraphisms Exencephalies Exencephaly Iniencephalies Iniencephaly Myelodysplasia Cord Myelodysplasias Sequence Tethered Syndrome Syndromes", "definition": "Congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy generally occurring between days 18-29 of gestation. Ectodermal and mesodermal malformations (mainly involving the skull and vertebrae) may occur as a result of defects of neural tube closure. (From Joynt, Clinical Neurology, 1992, Ch55, pp31-41)\n    ", "id": "MESH:D009436"}
{"mention": "5-azacytidine", "mention_text": "Anencephaly has been suggested to develop from exencephaly; however, there is little direct experimental evidence to support this, and the mechanism of transformation remains unclear. We examined this theory using the exo utero development system that allows direct and sequential observations of mid- to late-gestation mouse embryos. We observed the exencephaly induced by 5-azacytidine at embryonic day 13.5 (E13.5), let the embryos develop exo utero until E18.5, and re-observed the same embryos at E18.5. We confirmed several cases of transformation from exencephaly to anencephaly. However, in many cases, the exencephalic brain tissue was preserved with more or less reduction during this period. To analyze the transformation patterns, we classified the exencephaly by size and shape of the exencephalic tissue into several types at E13.5 and E18.5. It was found that the transformation of exencephalic tissue was not simply size-dependent, and all cases of anencephaly at E18.5 resulted from embryos with a large amount of exencephalic tissue at E13.5. Microscopic observation showed the configuration of exencephaly at E13.5, frequent hemorrhaging and detachment of the neural plate from surface ectoderm in the exencephalic head at E15.5, and multiple modes of reduction in the exencephalic tissue at E18.5. From observations of the vasculature, altered distribution patterns of vessels were identified in the exencephalic head. These findings suggest that overgrowth of the exencephalic neural tissue causes the altered distribution patterns of vessels, subsequent peripheral circulatory failure and/or hemorrhaging in various parts of the exencephalic head, leading to the multiple modes of tissue reduction during transformation from exencephaly to anencephaly.", "entity": "Azacitidine", "aliases": "5 Azacytidine 5-Azacytidine Azacitidine NSC 102816 NSC-102816 NSC102816 Pharmion Brand of Vidaza", "definition": "A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.\n    ", "id": "MESH:D001374"}
{"mention": "anencephaly", "mention_text": "Anencephaly has been suggested to develop from exencephaly; however, there is little direct experimental evidence to support this, and the mechanism of transformation remains unclear. We examined this theory using the exo utero development system that allows direct and sequential observations of mid- to late-gestation mouse embryos. We observed the exencephaly induced by 5-azacytidine at embryonic day 13.5 (E13.5), let the embryos develop exo utero until E18.5, and re-observed the same embryos at E18.5. We confirmed several cases of transformation from exencephaly to anencephaly. However, in many cases, the exencephalic brain tissue was preserved with more or less reduction during this period. To analyze the transformation patterns, we classified the exencephaly by size and shape of the exencephalic tissue into several types at E13.5 and E18.5. It was found that the transformation of exencephalic tissue was not simply size-dependent, and all cases of anencephaly at E18.5 resulted from embryos with a large amount of exencephalic tissue at E13.5. Microscopic observation showed the configuration of exencephaly at E13.5, frequent hemorrhaging and detachment of the neural plate from surface ectoderm in the exencephalic head at E15.5, and multiple modes of reduction in the exencephalic tissue at E18.5. From observations of the vasculature, altered distribution patterns of vessels were identified in the exencephalic head. These findings suggest that overgrowth of the exencephalic neural tissue causes the altered distribution patterns of vessels, subsequent peripheral circulatory failure and/or hemorrhaging in various parts of the exencephalic head, leading to the multiple modes of tissue reduction during transformation from exencephaly to anencephaly.", "entity": "Anencephaly", "aliases": "Absence of Brain Congenital Anencephalia Anencephalias Anencephalies Partial Anencephalus Anencephaly Hemicranial Incomplete Aprosencephalies Aprosencephaly", "definition": "A malformation of the nervous system caused by failure of the anterior neuropore to close. Infants are born with intact spinal cords, cerebellums, and brainstems, but lack formation of neural structures above this level. The skull is only partially formed but the eyes are usually normal. This condition may be associated with folate deficiency. Affected infants are only capable of primitive (brain stem) reflexes and usually do not survive for more than two weeks. (From Menkes, Textbook of Child Neurology, 5th ed, p247)\n    ", "id": "MESH:D000757"}
{"mention": "exencephalic", "mention_text": "Anencephaly has been suggested to develop from exencephaly; however, there is little direct experimental evidence to support this, and the mechanism of transformation remains unclear. We examined this theory using the exo utero development system that allows direct and sequential observations of mid- to late-gestation mouse embryos. We observed the exencephaly induced by 5-azacytidine at embryonic day 13.5 (E13.5), let the embryos develop exo utero until E18.5, and re-observed the same embryos at E18.5. We confirmed several cases of transformation from exencephaly to anencephaly. However, in many cases, the exencephalic brain tissue was preserved with more or less reduction during this period. To analyze the transformation patterns, we classified the exencephaly by size and shape of the exencephalic tissue into several types at E13.5 and E18.5. It was found that the transformation of exencephalic tissue was not simply size-dependent, and all cases of anencephaly at E18.5 resulted from embryos with a large amount of exencephalic tissue at E13.5. Microscopic observation showed the configuration of exencephaly at E13.5, frequent hemorrhaging and detachment of the neural plate from surface ectoderm in the exencephalic head at E15.5, and multiple modes of reduction in the exencephalic tissue at E18.5. From observations of the vasculature, altered distribution patterns of vessels were identified in the exencephalic head. These findings suggest that overgrowth of the exencephalic neural tissue causes the altered distribution patterns of vessels, subsequent peripheral circulatory failure and/or hemorrhaging in various parts of the exencephalic head, leading to the multiple modes of tissue reduction during transformation from exencephaly to anencephaly.", "entity": "Neural Tube Defects", "aliases": "Acrania Acranias Craniorachischises Craniorachischisis Cyst Neurenteric Neuroenteric Cysts Defect Neural Tube Defects Developmental Diastematomyelia Diastematomyelias Dysraphism Occult Spinal Dysraphisms Exencephalies Exencephaly Iniencephalies Iniencephaly Myelodysplasia Cord Myelodysplasias Sequence Tethered Syndrome Syndromes", "definition": "Congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy generally occurring between days 18-29 of gestation. Ectodermal and mesodermal malformations (mainly involving the skull and vertebrae) may occur as a result of defects of neural tube closure. (From Joynt, Clinical Neurology, 1992, Ch55, pp31-41)\n    ", "id": "MESH:D009436"}
{"mention": "hemorrhaging", "mention_text": "Anencephaly has been suggested to develop from exencephaly; however, there is little direct experimental evidence to support this, and the mechanism of transformation remains unclear. We examined this theory using the exo utero development system that allows direct and sequential observations of mid- to late-gestation mouse embryos. We observed the exencephaly induced by 5-azacytidine at embryonic day 13.5 (E13.5), let the embryos develop exo utero until E18.5, and re-observed the same embryos at E18.5. We confirmed several cases of transformation from exencephaly to anencephaly. However, in many cases, the exencephalic brain tissue was preserved with more or less reduction during this period. To analyze the transformation patterns, we classified the exencephaly by size and shape of the exencephalic tissue into several types at E13.5 and E18.5. It was found that the transformation of exencephalic tissue was not simply size-dependent, and all cases of anencephaly at E18.5 resulted from embryos with a large amount of exencephalic tissue at E13.5. Microscopic observation showed the configuration of exencephaly at E13.5, frequent hemorrhaging and detachment of the neural plate from surface ectoderm in the exencephalic head at E15.5, and multiple modes of reduction in the exencephalic tissue at E18.5. From observations of the vasculature, altered distribution patterns of vessels were identified in the exencephalic head. These findings suggest that overgrowth of the exencephalic neural tissue causes the altered distribution patterns of vessels, subsequent peripheral circulatory failure and/or hemorrhaging in various parts of the exencephalic head, leading to the multiple modes of tissue reduction during transformation from exencephaly to anencephaly.", "entity": "Hemorrhage", "aliases": "Bleeding Hemorrhage Hemorrhages", "definition": "Bleeding or escape of blood from a vessel.\n    ", "id": "MESH:D006470"}
{"mention": "circulatory failure", "mention_text": "Anencephaly has been suggested to develop from exencephaly; however, there is little direct experimental evidence to support this, and the mechanism of transformation remains unclear. We examined this theory using the exo utero development system that allows direct and sequential observations of mid- to late-gestation mouse embryos. We observed the exencephaly induced by 5-azacytidine at embryonic day 13.5 (E13.5), let the embryos develop exo utero until E18.5, and re-observed the same embryos at E18.5. We confirmed several cases of transformation from exencephaly to anencephaly. However, in many cases, the exencephalic brain tissue was preserved with more or less reduction during this period. To analyze the transformation patterns, we classified the exencephaly by size and shape of the exencephalic tissue into several types at E13.5 and E18.5. It was found that the transformation of exencephalic tissue was not simply size-dependent, and all cases of anencephaly at E18.5 resulted from embryos with a large amount of exencephalic tissue at E13.5. Microscopic observation showed the configuration of exencephaly at E13.5, frequent hemorrhaging and detachment of the neural plate from surface ectoderm in the exencephalic head at E15.5, and multiple modes of reduction in the exencephalic tissue at E18.5. From observations of the vasculature, altered distribution patterns of vessels were identified in the exencephalic head. These findings suggest that overgrowth of the exencephalic neural tissue causes the altered distribution patterns of vessels, subsequent peripheral circulatory failure and/or hemorrhaging in various parts of the exencephalic head, leading to the multiple modes of tissue reduction during transformation from exencephaly to anencephaly.", "entity": "Shock", "aliases": "Circulatory Collapse Failure Hypovolemic Shock", "definition": "A pathological condition manifested by failure to perfuse or oxygenate vital organs.\n    ", "id": "MESH:D012769"}
{"mention": "cocaine", "mention_text": "Acute cocaine-induced seizures: differential sensitivity of six inbred mouse strains.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "seizures", "mention_text": "Acute cocaine-induced seizures: differential sensitivity of six inbred mouse strains.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "seizures", "mention_text": "Mature male and female mice from six inbred stains were tested for susceptibility to behavioral seizures induced by a single injection of cocaine. Cocaine was injected ip over a range of doses (50-100 mg/kg) and behavior was monitored for 20 minutes. Seizure end points included latency to forelimb or hindlimb clonus, latency to clonic running seizure and latency to jumping bouncing seizure. A range of strain specific sensitivities was documented with A/J and SJL mice being most sensitive and C57BL/6J most resistant. DBA/2J, BALB/cByJ and NZW/LacJ strains exhibited intermediate sensitivity. EEG recordings were made in SJL, A/J and C57BL/6J mice revealing a close correspondence between electrical activity and behavior. Additionally, levels of cocaine determined in hippocampus and cortex were not different between sensitive and resistant strains. Additional studies of these murine strains may be useful for investigating genetic influences on cocaine-induced seizures.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "cocaine", "mention_text": "Mature male and female mice from six inbred stains were tested for susceptibility to behavioral seizures induced by a single injection of cocaine. Cocaine was injected ip over a range of doses (50-100 mg/kg) and behavior was monitored for 20 minutes. Seizure end points included latency to forelimb or hindlimb clonus, latency to clonic running seizure and latency to jumping bouncing seizure. A range of strain specific sensitivities was documented with A/J and SJL mice being most sensitive and C57BL/6J most resistant. DBA/2J, BALB/cByJ and NZW/LacJ strains exhibited intermediate sensitivity. EEG recordings were made in SJL, A/J and C57BL/6J mice revealing a close correspondence between electrical activity and behavior. Additionally, levels of cocaine determined in hippocampus and cortex were not different between sensitive and resistant strains. Additional studies of these murine strains may be useful for investigating genetic influences on cocaine-induced seizures.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "Cocaine", "mention_text": "Mature male and female mice from six inbred stains were tested for susceptibility to behavioral seizures induced by a single injection of cocaine. Cocaine was injected ip over a range of doses (50-100 mg/kg) and behavior was monitored for 20 minutes. Seizure end points included latency to forelimb or hindlimb clonus, latency to clonic running seizure and latency to jumping bouncing seizure. A range of strain specific sensitivities was documented with A/J and SJL mice being most sensitive and C57BL/6J most resistant. DBA/2J, BALB/cByJ and NZW/LacJ strains exhibited intermediate sensitivity. EEG recordings were made in SJL, A/J and C57BL/6J mice revealing a close correspondence between electrical activity and behavior. Additionally, levels of cocaine determined in hippocampus and cortex were not different between sensitive and resistant strains. Additional studies of these murine strains may be useful for investigating genetic influences on cocaine-induced seizures.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "Seizure", "mention_text": "Mature male and female mice from six inbred stains were tested for susceptibility to behavioral seizures induced by a single injection of cocaine. Cocaine was injected ip over a range of doses (50-100 mg/kg) and behavior was monitored for 20 minutes. Seizure end points included latency to forelimb or hindlimb clonus, latency to clonic running seizure and latency to jumping bouncing seizure. A range of strain specific sensitivities was documented with A/J and SJL mice being most sensitive and C57BL/6J most resistant. DBA/2J, BALB/cByJ and NZW/LacJ strains exhibited intermediate sensitivity. EEG recordings were made in SJL, A/J and C57BL/6J mice revealing a close correspondence between electrical activity and behavior. Additionally, levels of cocaine determined in hippocampus and cortex were not different between sensitive and resistant strains. Additional studies of these murine strains may be useful for investigating genetic influences on cocaine-induced seizures.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "seizure", "mention_text": "Mature male and female mice from six inbred stains were tested for susceptibility to behavioral seizures induced by a single injection of cocaine. Cocaine was injected ip over a range of doses (50-100 mg/kg) and behavior was monitored for 20 minutes. Seizure end points included latency to forelimb or hindlimb clonus, latency to clonic running seizure and latency to jumping bouncing seizure. A range of strain specific sensitivities was documented with A/J and SJL mice being most sensitive and C57BL/6J most resistant. DBA/2J, BALB/cByJ and NZW/LacJ strains exhibited intermediate sensitivity. EEG recordings were made in SJL, A/J and C57BL/6J mice revealing a close correspondence between electrical activity and behavior. Additionally, levels of cocaine determined in hippocampus and cortex were not different between sensitive and resistant strains. Additional studies of these murine strains may be useful for investigating genetic influences on cocaine-induced seizures.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "Microangiopathic hemolytic anemia", "mention_text": "Microangiopathic hemolytic anemia complicating FK506 (tacrolimus) therapy.", "entity": "Anemia, Hemolytic", "aliases": "Acquired Hemolytic Anemia Microangiopathic", "definition": "A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES).\n    ", "id": "MESH:D000743"}
{"mention": "FK506", "mention_text": "Microangiopathic hemolytic anemia complicating FK506 (tacrolimus) therapy.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "tacrolimus", "mention_text": "Microangiopathic hemolytic anemia complicating FK506 (tacrolimus) therapy.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "microangiopathic hemolytic anemia", "mention_text": "We describe 3 episodes of microangiopathic hemolytic anemia (MAHA) in 2 solid organ recipients under FK506 (tacrolimus) therapy. In both cases, discontinuation of FK506 and treatment with plasma exchange, fresh frozen plasma replacement, corticosteroids, aspirin, and dipyridamole led to resolution of MAHA. In one patient, reintroduction of FK506 led to rapid recurrence of MAHA. FK506-associated MAHA is probably rare but physicians must be aware of this severe complication. In our experience and according to the literature, FK506 does not seem to cross-react with cyclosporin A (CyA), an immuno-suppressive drug already known to induce MAHA.", "entity": "Anemia, Hemolytic", "aliases": "Acquired Hemolytic Anemia Microangiopathic", "definition": "A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES).\n    ", "id": "MESH:D000743"}
{"mention": "MAHA", "mention_text": "We describe 3 episodes of microangiopathic hemolytic anemia (MAHA) in 2 solid organ recipients under FK506 (tacrolimus) therapy. In both cases, discontinuation of FK506 and treatment with plasma exchange, fresh frozen plasma replacement, corticosteroids, aspirin, and dipyridamole led to resolution of MAHA. In one patient, reintroduction of FK506 led to rapid recurrence of MAHA. FK506-associated MAHA is probably rare but physicians must be aware of this severe complication. In our experience and according to the literature, FK506 does not seem to cross-react with cyclosporin A (CyA), an immuno-suppressive drug already known to induce MAHA.", "entity": "Anemia, Hemolytic", "aliases": "Acquired Hemolytic Anemia Microangiopathic", "definition": "A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES).\n    ", "id": "MESH:D000743"}
{"mention": "FK506", "mention_text": "We describe 3 episodes of microangiopathic hemolytic anemia (MAHA) in 2 solid organ recipients under FK506 (tacrolimus) therapy. In both cases, discontinuation of FK506 and treatment with plasma exchange, fresh frozen plasma replacement, corticosteroids, aspirin, and dipyridamole led to resolution of MAHA. In one patient, reintroduction of FK506 led to rapid recurrence of MAHA. FK506-associated MAHA is probably rare but physicians must be aware of this severe complication. In our experience and according to the literature, FK506 does not seem to cross-react with cyclosporin A (CyA), an immuno-suppressive drug already known to induce MAHA.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "tacrolimus", "mention_text": "We describe 3 episodes of microangiopathic hemolytic anemia (MAHA) in 2 solid organ recipients under FK506 (tacrolimus) therapy. In both cases, discontinuation of FK506 and treatment with plasma exchange, fresh frozen plasma replacement, corticosteroids, aspirin, and dipyridamole led to resolution of MAHA. In one patient, reintroduction of FK506 led to rapid recurrence of MAHA. FK506-associated MAHA is probably rare but physicians must be aware of this severe complication. In our experience and according to the literature, FK506 does not seem to cross-react with cyclosporin A (CyA), an immuno-suppressive drug already known to induce MAHA.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "corticosteroids", "mention_text": "We describe 3 episodes of microangiopathic hemolytic anemia (MAHA) in 2 solid organ recipients under FK506 (tacrolimus) therapy. In both cases, discontinuation of FK506 and treatment with plasma exchange, fresh frozen plasma replacement, corticosteroids, aspirin, and dipyridamole led to resolution of MAHA. In one patient, reintroduction of FK506 led to rapid recurrence of MAHA. FK506-associated MAHA is probably rare but physicians must be aware of this severe complication. In our experience and according to the literature, FK506 does not seem to cross-react with cyclosporin A (CyA), an immuno-suppressive drug already known to induce MAHA.", "entity": "Adrenal Cortex Hormones", "aliases": "Adrenal Cortex Hormones Corticoids Corticosteroids", "definition": "", "id": "MESH:D000305"}
{"mention": "aspirin", "mention_text": "We describe 3 episodes of microangiopathic hemolytic anemia (MAHA) in 2 solid organ recipients under FK506 (tacrolimus) therapy. In both cases, discontinuation of FK506 and treatment with plasma exchange, fresh frozen plasma replacement, corticosteroids, aspirin, and dipyridamole led to resolution of MAHA. In one patient, reintroduction of FK506 led to rapid recurrence of MAHA. FK506-associated MAHA is probably rare but physicians must be aware of this severe complication. In our experience and according to the literature, FK506 does not seem to cross-react with cyclosporin A (CyA), an immuno-suppressive drug already known to induce MAHA.", "entity": "Aspirin", "aliases": "2-(Acetyloxy)benzoic Acid Acetylsalicylic Acetysal Acylpyrin Aloxiprimum Aspirin Colfarit Dispril Easprin Ecotrin Endosprin Magnecyl Micristin Polopirin Polopiryna Solprin Solupsan Zorprin", "definition": "The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)\n    ", "id": "MESH:D001241"}
{"mention": "dipyridamole", "mention_text": "We describe 3 episodes of microangiopathic hemolytic anemia (MAHA) in 2 solid organ recipients under FK506 (tacrolimus) therapy. In both cases, discontinuation of FK506 and treatment with plasma exchange, fresh frozen plasma replacement, corticosteroids, aspirin, and dipyridamole led to resolution of MAHA. In one patient, reintroduction of FK506 led to rapid recurrence of MAHA. FK506-associated MAHA is probably rare but physicians must be aware of this severe complication. In our experience and according to the literature, FK506 does not seem to cross-react with cyclosporin A (CyA), an immuno-suppressive drug already known to induce MAHA.", "entity": "Dipyridamole", "aliases": "Antistenocardin Apo-Dipyridamole Apotex Brand of Dipyridamole Ashbourne Belmac Berlin Chemie Berlin-Chemie Boehringer Ingelheim Cerebrovase Cléridium Curantil Curantyl Dipyramidole IPRAD Kurantil Miosen Novo-Dipiradol Novopharm Persantin Persantine", "definition": "A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752)\n    ", "id": "MESH:D004176"}
{"mention": "cyclosporin A", "mention_text": "We describe 3 episodes of microangiopathic hemolytic anemia (MAHA) in 2 solid organ recipients under FK506 (tacrolimus) therapy. In both cases, discontinuation of FK506 and treatment with plasma exchange, fresh frozen plasma replacement, corticosteroids, aspirin, and dipyridamole led to resolution of MAHA. In one patient, reintroduction of FK506 led to rapid recurrence of MAHA. FK506-associated MAHA is probably rare but physicians must be aware of this severe complication. In our experience and according to the literature, FK506 does not seem to cross-react with cyclosporin A (CyA), an immuno-suppressive drug already known to induce MAHA.", "entity": "Cyclosporine", "aliases": "Ciclosporin CsA Neoral CsA-Neoral CsANeoral CyA NOF CyA-NOF Cyclosporin A Cyclosporine OL 27 400 27-400 27400 Sandimmun Sandimmune", "definition": "A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).\n    ", "id": "MESH:D016572"}
{"mention": "CyA", "mention_text": "We describe 3 episodes of microangiopathic hemolytic anemia (MAHA) in 2 solid organ recipients under FK506 (tacrolimus) therapy. In both cases, discontinuation of FK506 and treatment with plasma exchange, fresh frozen plasma replacement, corticosteroids, aspirin, and dipyridamole led to resolution of MAHA. In one patient, reintroduction of FK506 led to rapid recurrence of MAHA. FK506-associated MAHA is probably rare but physicians must be aware of this severe complication. In our experience and according to the literature, FK506 does not seem to cross-react with cyclosporin A (CyA), an immuno-suppressive drug already known to induce MAHA.", "entity": "Cyclosporine", "aliases": "Ciclosporin CsA Neoral CsA-Neoral CsANeoral CyA NOF CyA-NOF Cyclosporin A Cyclosporine OL 27 400 27-400 27400 Sandimmun Sandimmune", "definition": "A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).\n    ", "id": "MESH:D016572"}
{"mention": "ventricular tachycardia", "mention_text": "Variant ventricular tachycardia in desipramine toxicity.", "entity": "Tachycardia, Ventricular", "aliases": "Tachycardia Ventricular Tachycardias", "definition": "An abnormally rapid ventricular rhythm usually in excess of 150 beats per minute. It is generated within the ventricle below the BUNDLE OF HIS, either as autonomic impulse formation or reentrant impulse conduction. Depending on the etiology, onset of ventricular tachycardia can be paroxysmal (sudden) or nonparoxysmal, its wide QRS complexes can be uniform or polymorphic, and the ventricular beating may be independent of the atrial beating (AV dissociation).\n    ", "id": "MESH:D017180"}
{"mention": "desipramine", "mention_text": "Variant ventricular tachycardia in desipramine toxicity.", "entity": "Desipramine", "aliases": "Apo-Desipramine Apotex Brand of Desipramine Hydrochloride Aventis Behring Demethylimipramine Desmethylimipramine Norpramin Novartis Novo-Desipramine Novopharm Nu Pharm Nu-Desipramine Nu-Pharm PMS-Desipramine Pertofran Pertofrane Pertrofran Petylyl Pharmascience Ratiopharm Rhône Poulenc Rorer Rhône-Poulenc Temmler ratio-Desipramine", "definition": "A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholinergic activity, through its affinity to muscarinic receptors.\n    ", "id": "MESH:D003891"}
{"mention": "toxicity", "mention_text": "Variant ventricular tachycardia in desipramine toxicity.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "ventricular tachycardia", "mention_text": "We report a case of variant ventricular tachycardia induced by desipramine toxicity. Unusual features of the arrhythmia are repetitive group beating, progressive shortening of the R-R interval, progressive widening of the QRS complex with eventual failure of intraventricular conduction, and changes in direction of the QRS axis. Recognition of variant ventricular tachycardia is important because therapy differs from that of classic ventricular tachycardia.", "entity": "Tachycardia, Ventricular", "aliases": "Tachycardia Ventricular Tachycardias", "definition": "An abnormally rapid ventricular rhythm usually in excess of 150 beats per minute. It is generated within the ventricle below the BUNDLE OF HIS, either as autonomic impulse formation or reentrant impulse conduction. Depending on the etiology, onset of ventricular tachycardia can be paroxysmal (sudden) or nonparoxysmal, its wide QRS complexes can be uniform or polymorphic, and the ventricular beating may be independent of the atrial beating (AV dissociation).\n    ", "id": "MESH:D017180"}
{"mention": "desipramine", "mention_text": "We report a case of variant ventricular tachycardia induced by desipramine toxicity. Unusual features of the arrhythmia are repetitive group beating, progressive shortening of the R-R interval, progressive widening of the QRS complex with eventual failure of intraventricular conduction, and changes in direction of the QRS axis. Recognition of variant ventricular tachycardia is important because therapy differs from that of classic ventricular tachycardia.", "entity": "Desipramine", "aliases": "Apo-Desipramine Apotex Brand of Desipramine Hydrochloride Aventis Behring Demethylimipramine Desmethylimipramine Norpramin Novartis Novo-Desipramine Novopharm Nu Pharm Nu-Desipramine Nu-Pharm PMS-Desipramine Pertofran Pertofrane Pertrofran Petylyl Pharmascience Ratiopharm Rhône Poulenc Rorer Rhône-Poulenc Temmler ratio-Desipramine", "definition": "A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholinergic activity, through its affinity to muscarinic receptors.\n    ", "id": "MESH:D003891"}
{"mention": "toxicity", "mention_text": "We report a case of variant ventricular tachycardia induced by desipramine toxicity. Unusual features of the arrhythmia are repetitive group beating, progressive shortening of the R-R interval, progressive widening of the QRS complex with eventual failure of intraventricular conduction, and changes in direction of the QRS axis. Recognition of variant ventricular tachycardia is important because therapy differs from that of classic ventricular tachycardia.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "arrhythmia", "mention_text": "We report a case of variant ventricular tachycardia induced by desipramine toxicity. Unusual features of the arrhythmia are repetitive group beating, progressive shortening of the R-R interval, progressive widening of the QRS complex with eventual failure of intraventricular conduction, and changes in direction of the QRS axis. Recognition of variant ventricular tachycardia is important because therapy differs from that of classic ventricular tachycardia.", "entity": "Arrhythmias, Cardiac", "aliases": "Arrhythmia Cardiac Arrhythmias Arrythmia Dysrhythmia", "definition": "Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.\n    ", "id": "MESH:D001145"}
{"mention": "Desipramine", "mention_text": "Desipramine-induced delirium at \"subtherapeutic\" concentrations: a case report.", "entity": "Desipramine", "aliases": "Apo-Desipramine Apotex Brand of Desipramine Hydrochloride Aventis Behring Demethylimipramine Desmethylimipramine Norpramin Novartis Novo-Desipramine Novopharm Nu Pharm Nu-Desipramine Nu-Pharm PMS-Desipramine Pertofran Pertofrane Pertrofran Petylyl Pharmascience Ratiopharm Rhône Poulenc Rorer Rhône-Poulenc Temmler ratio-Desipramine", "definition": "A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholinergic activity, through its affinity to muscarinic receptors.\n    ", "id": "MESH:D003891"}
{"mention": "delirium", "mention_text": "Desipramine-induced delirium at \"subtherapeutic\" concentrations: a case report.", "entity": "Delirium", "aliases": "Delirium of Mixed Origin Subacute Deliriums", "definition": "A disorder characterized by CONFUSION; inattentiveness; disorientation; ILLUSIONS; HALLUCINATIONS; agitation; and in some instances autonomic nervous system overactivity. It may result from toxic/metabolic conditions or structural brain lesions. (From Adams et al., Principles of Neurology, 6th ed, pp411-2)\n    ", "id": "MESH:D003693"}
{"mention": "Desipramine", "mention_text": "An elderly patient treated with low dose Desipramine developed a delirium while her plasma level was in the \"subtherapeutic\" range. Delirium, which may be induced by tricyclic drug therapy in the elderly, can be caused by tricyclics with low anticholinergic potency. Therapeutic ranges for antidepressants that have been derived from general adult population studies may not be appropriate for the elderly. Further studies of specifically elderly patients are now required to establish safer and more appropriate guidelines for drug therapy.", "entity": "Desipramine", "aliases": "Apo-Desipramine Apotex Brand of Desipramine Hydrochloride Aventis Behring Demethylimipramine Desmethylimipramine Norpramin Novartis Novo-Desipramine Novopharm Nu Pharm Nu-Desipramine Nu-Pharm PMS-Desipramine Pertofran Pertofrane Pertrofran Petylyl Pharmascience Ratiopharm Rhône Poulenc Rorer Rhône-Poulenc Temmler ratio-Desipramine", "definition": "A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholinergic activity, through its affinity to muscarinic receptors.\n    ", "id": "MESH:D003891"}
{"mention": "delirium", "mention_text": "An elderly patient treated with low dose Desipramine developed a delirium while her plasma level was in the \"subtherapeutic\" range. Delirium, which may be induced by tricyclic drug therapy in the elderly, can be caused by tricyclics with low anticholinergic potency. Therapeutic ranges for antidepressants that have been derived from general adult population studies may not be appropriate for the elderly. Further studies of specifically elderly patients are now required to establish safer and more appropriate guidelines for drug therapy.", "entity": "Delirium", "aliases": "Delirium of Mixed Origin Subacute Deliriums", "definition": "A disorder characterized by CONFUSION; inattentiveness; disorientation; ILLUSIONS; HALLUCINATIONS; agitation; and in some instances autonomic nervous system overactivity. It may result from toxic/metabolic conditions or structural brain lesions. (From Adams et al., Principles of Neurology, 6th ed, pp411-2)\n    ", "id": "MESH:D003693"}
{"mention": "Delirium", "mention_text": "An elderly patient treated with low dose Desipramine developed a delirium while her plasma level was in the \"subtherapeutic\" range. Delirium, which may be induced by tricyclic drug therapy in the elderly, can be caused by tricyclics with low anticholinergic potency. Therapeutic ranges for antidepressants that have been derived from general adult population studies may not be appropriate for the elderly. Further studies of specifically elderly patients are now required to establish safer and more appropriate guidelines for drug therapy.", "entity": "Delirium", "aliases": "Delirium of Mixed Origin Subacute Deliriums", "definition": "A disorder characterized by CONFUSION; inattentiveness; disorientation; ILLUSIONS; HALLUCINATIONS; agitation; and in some instances autonomic nervous system overactivity. It may result from toxic/metabolic conditions or structural brain lesions. (From Adams et al., Principles of Neurology, 6th ed, pp411-2)\n    ", "id": "MESH:D003693"}
{"mention": "antidepressants", "mention_text": "An elderly patient treated with low dose Desipramine developed a delirium while her plasma level was in the \"subtherapeutic\" range. Delirium, which may be induced by tricyclic drug therapy in the elderly, can be caused by tricyclics with low anticholinergic potency. Therapeutic ranges for antidepressants that have been derived from general adult population studies may not be appropriate for the elderly. Further studies of specifically elderly patients are now required to establish safer and more appropriate guidelines for drug therapy.", "entity": "Antidepressive Agents", "aliases": "Agents Antidepressive Antidepressant Drugs Antidepressants Thymoanaleptics Thymoleptics", "definition": "Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.\n    ", "id": "MESH:D000928"}
{"mention": "amantadine", "mention_text": "Mouse strain-dependent effect of amantadine on motility and brain biogenic amines.", "entity": "Amantadine", "aliases": "1 Aminoadamantane 1-Aminoadamantane AL Amantadin AZU AbZ Brand of Amantadine Hydrochloride Adamantylamine Adekin Aliud Sulfate Alliance Aman Amanta HCI Amanta-HCI-AZU Amanta-Sulfate-AZU AmantaHCIAZU AmantaSulfateAZU Stada neuraxpharm ratiopharm Amantadin-neuraxpharm Amantadin-ratiopharm Amantadina Juventus Llorente Amantadinneuraxpharm Amantadinratiopharm Amixx Azupharma Cerebramed Ciba Geigy Ciba-Geigy Desitin Du Pont Endantadine Endo Gen Gen-Amantadine GenAmantadine Genpharm Hexal Hormosan Inf", "definition": "An antiviral that is used in the prophylactic or symptomatic treatment of influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake.\n    ", "id": "MESH:D000547"}
{"mention": "amines", "mention_text": "Mouse strain-dependent effect of amantadine on motility and brain biogenic amines.", "entity": "Amines", "aliases": "Amines", "definition": "A group of compounds derived from ammonia by substituting organic radicals for the hydrogens. (From Grant & Hackh's Chemical Dictionary, 5th ed)\n    ", "id": "MESH:D000588"}
{"mention": "amantadine hydrochloride", "mention_text": "The effect of amantadine hydrochloride, injected i.p. in 6 increments of 100 mg/kg each over 30 hr, on mouse motility and whole brain content of selected biogenic amines and major metabolites was studied in 4 strains of mice. These were the albino Sprague-Dawley ICR and BALB/C, the black C57BL/6 and the brown CDF-I mouse strains. Amantadine treatment produced a biphasic effect on mouse motility. The initial dose of amantadine depressed locomotor activity in all mouse strains studied with the BALB/C mice being the most sensitive. Subsequent amantadine treatments produced enhancement of motility from corresponding control in all mouse strains with the BALB/C mice being the least sensitive. The locomotor activity was decreased from corresponding controls in all strains studied, except for the ICR mice, during an overnight drug-free period following the fourth amantadine treatment. Readministration of amantadine, after a drug-free overnight period, increased motility from respective saline control in all strains with exception of the BALB/C mice where suppression of motility occurred. Treatment with amantadine did not alter whole brain dopamine levels but decreased the amounts of 3,4-dihydroxyphenylacetic acid in the BALB/C mice compared to saline control. Conversely, brain normetanephrine concentration was increased from saline control by amantadine in the BALB/C mice. The results suggest a strain-dependent effect of amantadine on motility and indicate a differential response to the acute and multiple dose regimens used. The BALB/C mouse was the most sensitive strain and could serve as the strain of choice for evaluating the side effects of amantadine. The biochemical results of brain biogenic amines of BALB/C mouse strain suggest a probable decrease of catecholamine turnover rate and/or metabolism by monoamine oxidase and a resulting increase in O-methylation of norepinephrine which may account for a behavioral depression caused by amantadine in the BALB/C mice.", "entity": "Amantadine", "aliases": "1 Aminoadamantane 1-Aminoadamantane AL Amantadin AZU AbZ Brand of Amantadine Hydrochloride Adamantylamine Adekin Aliud Sulfate Alliance Aman Amanta HCI Amanta-HCI-AZU Amanta-Sulfate-AZU AmantaHCIAZU AmantaSulfateAZU Stada neuraxpharm ratiopharm Amantadin-neuraxpharm Amantadin-ratiopharm Amantadina Juventus Llorente Amantadinneuraxpharm Amantadinratiopharm Amixx Azupharma Cerebramed Ciba Geigy Ciba-Geigy Desitin Du Pont Endantadine Endo Gen Gen-Amantadine GenAmantadine Genpharm Hexal Hormosan Inf", "definition": "An antiviral that is used in the prophylactic or symptomatic treatment of influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake.\n    ", "id": "MESH:D000547"}
{"mention": "amines", "mention_text": "The effect of amantadine hydrochloride, injected i.p. in 6 increments of 100 mg/kg each over 30 hr, on mouse motility and whole brain content of selected biogenic amines and major metabolites was studied in 4 strains of mice. These were the albino Sprague-Dawley ICR and BALB/C, the black C57BL/6 and the brown CDF-I mouse strains. Amantadine treatment produced a biphasic effect on mouse motility. The initial dose of amantadine depressed locomotor activity in all mouse strains studied with the BALB/C mice being the most sensitive. Subsequent amantadine treatments produced enhancement of motility from corresponding control in all mouse strains with the BALB/C mice being the least sensitive. The locomotor activity was decreased from corresponding controls in all strains studied, except for the ICR mice, during an overnight drug-free period following the fourth amantadine treatment. Readministration of amantadine, after a drug-free overnight period, increased motility from respective saline control in all strains with exception of the BALB/C mice where suppression of motility occurred. Treatment with amantadine did not alter whole brain dopamine levels but decreased the amounts of 3,4-dihydroxyphenylacetic acid in the BALB/C mice compared to saline control. Conversely, brain normetanephrine concentration was increased from saline control by amantadine in the BALB/C mice. The results suggest a strain-dependent effect of amantadine on motility and indicate a differential response to the acute and multiple dose regimens used. The BALB/C mouse was the most sensitive strain and could serve as the strain of choice for evaluating the side effects of amantadine. The biochemical results of brain biogenic amines of BALB/C mouse strain suggest a probable decrease of catecholamine turnover rate and/or metabolism by monoamine oxidase and a resulting increase in O-methylation of norepinephrine which may account for a behavioral depression caused by amantadine in the BALB/C mice.", "entity": "Amines", "aliases": "Amines", "definition": "A group of compounds derived from ammonia by substituting organic radicals for the hydrogens. (From Grant & Hackh's Chemical Dictionary, 5th ed)\n    ", "id": "MESH:D000588"}
{"mention": "Amantadine", "mention_text": "The effect of amantadine hydrochloride, injected i.p. in 6 increments of 100 mg/kg each over 30 hr, on mouse motility and whole brain content of selected biogenic amines and major metabolites was studied in 4 strains of mice. These were the albino Sprague-Dawley ICR and BALB/C, the black C57BL/6 and the brown CDF-I mouse strains. Amantadine treatment produced a biphasic effect on mouse motility. The initial dose of amantadine depressed locomotor activity in all mouse strains studied with the BALB/C mice being the most sensitive. Subsequent amantadine treatments produced enhancement of motility from corresponding control in all mouse strains with the BALB/C mice being the least sensitive. The locomotor activity was decreased from corresponding controls in all strains studied, except for the ICR mice, during an overnight drug-free period following the fourth amantadine treatment. Readministration of amantadine, after a drug-free overnight period, increased motility from respective saline control in all strains with exception of the BALB/C mice where suppression of motility occurred. Treatment with amantadine did not alter whole brain dopamine levels but decreased the amounts of 3,4-dihydroxyphenylacetic acid in the BALB/C mice compared to saline control. Conversely, brain normetanephrine concentration was increased from saline control by amantadine in the BALB/C mice. The results suggest a strain-dependent effect of amantadine on motility and indicate a differential response to the acute and multiple dose regimens used. The BALB/C mouse was the most sensitive strain and could serve as the strain of choice for evaluating the side effects of amantadine. The biochemical results of brain biogenic amines of BALB/C mouse strain suggest a probable decrease of catecholamine turnover rate and/or metabolism by monoamine oxidase and a resulting increase in O-methylation of norepinephrine which may account for a behavioral depression caused by amantadine in the BALB/C mice.", "entity": "Amantadine", "aliases": "1 Aminoadamantane 1-Aminoadamantane AL Amantadin AZU AbZ Brand of Amantadine Hydrochloride Adamantylamine Adekin Aliud Sulfate Alliance Aman Amanta HCI Amanta-HCI-AZU Amanta-Sulfate-AZU AmantaHCIAZU AmantaSulfateAZU Stada neuraxpharm ratiopharm Amantadin-neuraxpharm Amantadin-ratiopharm Amantadina Juventus Llorente Amantadinneuraxpharm Amantadinratiopharm Amixx Azupharma Cerebramed Ciba Geigy Ciba-Geigy Desitin Du Pont Endantadine Endo Gen Gen-Amantadine GenAmantadine Genpharm Hexal Hormosan Inf", "definition": "An antiviral that is used in the prophylactic or symptomatic treatment of influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake.\n    ", "id": "MESH:D000547"}
{"mention": "amantadine", "mention_text": "The effect of amantadine hydrochloride, injected i.p. in 6 increments of 100 mg/kg each over 30 hr, on mouse motility and whole brain content of selected biogenic amines and major metabolites was studied in 4 strains of mice. These were the albino Sprague-Dawley ICR and BALB/C, the black C57BL/6 and the brown CDF-I mouse strains. Amantadine treatment produced a biphasic effect on mouse motility. The initial dose of amantadine depressed locomotor activity in all mouse strains studied with the BALB/C mice being the most sensitive. Subsequent amantadine treatments produced enhancement of motility from corresponding control in all mouse strains with the BALB/C mice being the least sensitive. The locomotor activity was decreased from corresponding controls in all strains studied, except for the ICR mice, during an overnight drug-free period following the fourth amantadine treatment. Readministration of amantadine, after a drug-free overnight period, increased motility from respective saline control in all strains with exception of the BALB/C mice where suppression of motility occurred. Treatment with amantadine did not alter whole brain dopamine levels but decreased the amounts of 3,4-dihydroxyphenylacetic acid in the BALB/C mice compared to saline control. Conversely, brain normetanephrine concentration was increased from saline control by amantadine in the BALB/C mice. The results suggest a strain-dependent effect of amantadine on motility and indicate a differential response to the acute and multiple dose regimens used. The BALB/C mouse was the most sensitive strain and could serve as the strain of choice for evaluating the side effects of amantadine. The biochemical results of brain biogenic amines of BALB/C mouse strain suggest a probable decrease of catecholamine turnover rate and/or metabolism by monoamine oxidase and a resulting increase in O-methylation of norepinephrine which may account for a behavioral depression caused by amantadine in the BALB/C mice.", "entity": "Amantadine", "aliases": "1 Aminoadamantane 1-Aminoadamantane AL Amantadin AZU AbZ Brand of Amantadine Hydrochloride Adamantylamine Adekin Aliud Sulfate Alliance Aman Amanta HCI Amanta-HCI-AZU Amanta-Sulfate-AZU AmantaHCIAZU AmantaSulfateAZU Stada neuraxpharm ratiopharm Amantadin-neuraxpharm Amantadin-ratiopharm Amantadina Juventus Llorente Amantadinneuraxpharm Amantadinratiopharm Amixx Azupharma Cerebramed Ciba Geigy Ciba-Geigy Desitin Du Pont Endantadine Endo Gen Gen-Amantadine GenAmantadine Genpharm Hexal Hormosan Inf", "definition": "An antiviral that is used in the prophylactic or symptomatic treatment of influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake.\n    ", "id": "MESH:D000547"}
{"mention": "depressed", "mention_text": "The effect of amantadine hydrochloride, injected i.p. in 6 increments of 100 mg/kg each over 30 hr, on mouse motility and whole brain content of selected biogenic amines and major metabolites was studied in 4 strains of mice. These were the albino Sprague-Dawley ICR and BALB/C, the black C57BL/6 and the brown CDF-I mouse strains. Amantadine treatment produced a biphasic effect on mouse motility. The initial dose of amantadine depressed locomotor activity in all mouse strains studied with the BALB/C mice being the most sensitive. Subsequent amantadine treatments produced enhancement of motility from corresponding control in all mouse strains with the BALB/C mice being the least sensitive. The locomotor activity was decreased from corresponding controls in all strains studied, except for the ICR mice, during an overnight drug-free period following the fourth amantadine treatment. Readministration of amantadine, after a drug-free overnight period, increased motility from respective saline control in all strains with exception of the BALB/C mice where suppression of motility occurred. Treatment with amantadine did not alter whole brain dopamine levels but decreased the amounts of 3,4-dihydroxyphenylacetic acid in the BALB/C mice compared to saline control. Conversely, brain normetanephrine concentration was increased from saline control by amantadine in the BALB/C mice. The results suggest a strain-dependent effect of amantadine on motility and indicate a differential response to the acute and multiple dose regimens used. The BALB/C mouse was the most sensitive strain and could serve as the strain of choice for evaluating the side effects of amantadine. The biochemical results of brain biogenic amines of BALB/C mouse strain suggest a probable decrease of catecholamine turnover rate and/or metabolism by monoamine oxidase and a resulting increase in O-methylation of norepinephrine which may account for a behavioral depression caused by amantadine in the BALB/C mice.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "suppression of motility", "mention_text": "The effect of amantadine hydrochloride, injected i.p. in 6 increments of 100 mg/kg each over 30 hr, on mouse motility and whole brain content of selected biogenic amines and major metabolites was studied in 4 strains of mice. These were the albino Sprague-Dawley ICR and BALB/C, the black C57BL/6 and the brown CDF-I mouse strains. Amantadine treatment produced a biphasic effect on mouse motility. The initial dose of amantadine depressed locomotor activity in all mouse strains studied with the BALB/C mice being the most sensitive. Subsequent amantadine treatments produced enhancement of motility from corresponding control in all mouse strains with the BALB/C mice being the least sensitive. The locomotor activity was decreased from corresponding controls in all strains studied, except for the ICR mice, during an overnight drug-free period following the fourth amantadine treatment. Readministration of amantadine, after a drug-free overnight period, increased motility from respective saline control in all strains with exception of the BALB/C mice where suppression of motility occurred. Treatment with amantadine did not alter whole brain dopamine levels but decreased the amounts of 3,4-dihydroxyphenylacetic acid in the BALB/C mice compared to saline control. Conversely, brain normetanephrine concentration was increased from saline control by amantadine in the BALB/C mice. The results suggest a strain-dependent effect of amantadine on motility and indicate a differential response to the acute and multiple dose regimens used. The BALB/C mouse was the most sensitive strain and could serve as the strain of choice for evaluating the side effects of amantadine. The biochemical results of brain biogenic amines of BALB/C mouse strain suggest a probable decrease of catecholamine turnover rate and/or metabolism by monoamine oxidase and a resulting increase in O-methylation of norepinephrine which may account for a behavioral depression caused by amantadine in the BALB/C mice.", "entity": "Psychomotor Disorders", "aliases": "Developmental Psychomotor Disorder Disorders Impairment Impairments", "definition": "Abnormalities of motor function that are associated with organic and non-organic cognitive disorders.\n    ", "id": "MESH:D011596"}
{"mention": "dopamine", "mention_text": "The effect of amantadine hydrochloride, injected i.p. in 6 increments of 100 mg/kg each over 30 hr, on mouse motility and whole brain content of selected biogenic amines and major metabolites was studied in 4 strains of mice. These were the albino Sprague-Dawley ICR and BALB/C, the black C57BL/6 and the brown CDF-I mouse strains. Amantadine treatment produced a biphasic effect on mouse motility. The initial dose of amantadine depressed locomotor activity in all mouse strains studied with the BALB/C mice being the most sensitive. Subsequent amantadine treatments produced enhancement of motility from corresponding control in all mouse strains with the BALB/C mice being the least sensitive. The locomotor activity was decreased from corresponding controls in all strains studied, except for the ICR mice, during an overnight drug-free period following the fourth amantadine treatment. Readministration of amantadine, after a drug-free overnight period, increased motility from respective saline control in all strains with exception of the BALB/C mice where suppression of motility occurred. Treatment with amantadine did not alter whole brain dopamine levels but decreased the amounts of 3,4-dihydroxyphenylacetic acid in the BALB/C mice compared to saline control. Conversely, brain normetanephrine concentration was increased from saline control by amantadine in the BALB/C mice. The results suggest a strain-dependent effect of amantadine on motility and indicate a differential response to the acute and multiple dose regimens used. The BALB/C mouse was the most sensitive strain and could serve as the strain of choice for evaluating the side effects of amantadine. The biochemical results of brain biogenic amines of BALB/C mouse strain suggest a probable decrease of catecholamine turnover rate and/or metabolism by monoamine oxidase and a resulting increase in O-methylation of norepinephrine which may account for a behavioral depression caused by amantadine in the BALB/C mice.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "3,4-dihydroxyphenylacetic acid", "mention_text": "The effect of amantadine hydrochloride, injected i.p. in 6 increments of 100 mg/kg each over 30 hr, on mouse motility and whole brain content of selected biogenic amines and major metabolites was studied in 4 strains of mice. These were the albino Sprague-Dawley ICR and BALB/C, the black C57BL/6 and the brown CDF-I mouse strains. Amantadine treatment produced a biphasic effect on mouse motility. The initial dose of amantadine depressed locomotor activity in all mouse strains studied with the BALB/C mice being the most sensitive. Subsequent amantadine treatments produced enhancement of motility from corresponding control in all mouse strains with the BALB/C mice being the least sensitive. The locomotor activity was decreased from corresponding controls in all strains studied, except for the ICR mice, during an overnight drug-free period following the fourth amantadine treatment. Readministration of amantadine, after a drug-free overnight period, increased motility from respective saline control in all strains with exception of the BALB/C mice where suppression of motility occurred. Treatment with amantadine did not alter whole brain dopamine levels but decreased the amounts of 3,4-dihydroxyphenylacetic acid in the BALB/C mice compared to saline control. Conversely, brain normetanephrine concentration was increased from saline control by amantadine in the BALB/C mice. The results suggest a strain-dependent effect of amantadine on motility and indicate a differential response to the acute and multiple dose regimens used. The BALB/C mouse was the most sensitive strain and could serve as the strain of choice for evaluating the side effects of amantadine. The biochemical results of brain biogenic amines of BALB/C mouse strain suggest a probable decrease of catecholamine turnover rate and/or metabolism by monoamine oxidase and a resulting increase in O-methylation of norepinephrine which may account for a behavioral depression caused by amantadine in the BALB/C mice.", "entity": "3,4-Dihydroxyphenylacetic Acid", "aliases": "3,4 Dihydroxyphenylacetic Acid 3,4-Dihydroxyphenylacetic Monosodium Salt DOPAC Homoprotocatechuic", "definition": "A deaminated metabolite of LEVODOPA.\n    ", "id": "MESH:D015102"}
{"mention": "normetanephrine", "mention_text": "The effect of amantadine hydrochloride, injected i.p. in 6 increments of 100 mg/kg each over 30 hr, on mouse motility and whole brain content of selected biogenic amines and major metabolites was studied in 4 strains of mice. These were the albino Sprague-Dawley ICR and BALB/C, the black C57BL/6 and the brown CDF-I mouse strains. Amantadine treatment produced a biphasic effect on mouse motility. The initial dose of amantadine depressed locomotor activity in all mouse strains studied with the BALB/C mice being the most sensitive. Subsequent amantadine treatments produced enhancement of motility from corresponding control in all mouse strains with the BALB/C mice being the least sensitive. The locomotor activity was decreased from corresponding controls in all strains studied, except for the ICR mice, during an overnight drug-free period following the fourth amantadine treatment. Readministration of amantadine, after a drug-free overnight period, increased motility from respective saline control in all strains with exception of the BALB/C mice where suppression of motility occurred. Treatment with amantadine did not alter whole brain dopamine levels but decreased the amounts of 3,4-dihydroxyphenylacetic acid in the BALB/C mice compared to saline control. Conversely, brain normetanephrine concentration was increased from saline control by amantadine in the BALB/C mice. The results suggest a strain-dependent effect of amantadine on motility and indicate a differential response to the acute and multiple dose regimens used. The BALB/C mouse was the most sensitive strain and could serve as the strain of choice for evaluating the side effects of amantadine. The biochemical results of brain biogenic amines of BALB/C mouse strain suggest a probable decrease of catecholamine turnover rate and/or metabolism by monoamine oxidase and a resulting increase in O-methylation of norepinephrine which may account for a behavioral depression caused by amantadine in the BALB/C mice.", "entity": "Normetanephrine", "aliases": "3 Methoxynoradrenaline 3-Methoxynoradrenaline Normetadrenaline Normetanephrine", "definition": "A methylated metabolite of norepinephrine that is excreted in the urine and found in certain tissues. It is a marker for tumors.\n    ", "id": "MESH:D009647"}
{"mention": "catecholamine", "mention_text": "The effect of amantadine hydrochloride, injected i.p. in 6 increments of 100 mg/kg each over 30 hr, on mouse motility and whole brain content of selected biogenic amines and major metabolites was studied in 4 strains of mice. These were the albino Sprague-Dawley ICR and BALB/C, the black C57BL/6 and the brown CDF-I mouse strains. Amantadine treatment produced a biphasic effect on mouse motility. The initial dose of amantadine depressed locomotor activity in all mouse strains studied with the BALB/C mice being the most sensitive. Subsequent amantadine treatments produced enhancement of motility from corresponding control in all mouse strains with the BALB/C mice being the least sensitive. The locomotor activity was decreased from corresponding controls in all strains studied, except for the ICR mice, during an overnight drug-free period following the fourth amantadine treatment. Readministration of amantadine, after a drug-free overnight period, increased motility from respective saline control in all strains with exception of the BALB/C mice where suppression of motility occurred. Treatment with amantadine did not alter whole brain dopamine levels but decreased the amounts of 3,4-dihydroxyphenylacetic acid in the BALB/C mice compared to saline control. Conversely, brain normetanephrine concentration was increased from saline control by amantadine in the BALB/C mice. The results suggest a strain-dependent effect of amantadine on motility and indicate a differential response to the acute and multiple dose regimens used. The BALB/C mouse was the most sensitive strain and could serve as the strain of choice for evaluating the side effects of amantadine. The biochemical results of brain biogenic amines of BALB/C mouse strain suggest a probable decrease of catecholamine turnover rate and/or metabolism by monoamine oxidase and a resulting increase in O-methylation of norepinephrine which may account for a behavioral depression caused by amantadine in the BALB/C mice.", "entity": "Catecholamines", "aliases": "Catecholamines Sympathins", "definition": "A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine.\n    ", "id": "MESH:D002395"}
{"mention": "norepinephrine", "mention_text": "The effect of amantadine hydrochloride, injected i.p. in 6 increments of 100 mg/kg each over 30 hr, on mouse motility and whole brain content of selected biogenic amines and major metabolites was studied in 4 strains of mice. These were the albino Sprague-Dawley ICR and BALB/C, the black C57BL/6 and the brown CDF-I mouse strains. Amantadine treatment produced a biphasic effect on mouse motility. The initial dose of amantadine depressed locomotor activity in all mouse strains studied with the BALB/C mice being the most sensitive. Subsequent amantadine treatments produced enhancement of motility from corresponding control in all mouse strains with the BALB/C mice being the least sensitive. The locomotor activity was decreased from corresponding controls in all strains studied, except for the ICR mice, during an overnight drug-free period following the fourth amantadine treatment. Readministration of amantadine, after a drug-free overnight period, increased motility from respective saline control in all strains with exception of the BALB/C mice where suppression of motility occurred. Treatment with amantadine did not alter whole brain dopamine levels but decreased the amounts of 3,4-dihydroxyphenylacetic acid in the BALB/C mice compared to saline control. Conversely, brain normetanephrine concentration was increased from saline control by amantadine in the BALB/C mice. The results suggest a strain-dependent effect of amantadine on motility and indicate a differential response to the acute and multiple dose regimens used. The BALB/C mouse was the most sensitive strain and could serve as the strain of choice for evaluating the side effects of amantadine. The biochemical results of brain biogenic amines of BALB/C mouse strain suggest a probable decrease of catecholamine turnover rate and/or metabolism by monoamine oxidase and a resulting increase in O-methylation of norepinephrine which may account for a behavioral depression caused by amantadine in the BALB/C mice.", "entity": "Norepinephrine", "aliases": "Abbott Brand of Levophed Bitartrate Arterenol Aventis Norepinephrine Hydrochloride Noradrenaline Levarterenol Levonor Levonorepinephrine Noradrénaline tartrate renaudin Norepinephrin d-Tartrate (1:1) (+)-Isomer (+,-)-Isomer l-Tartrate Monohydrate (1:2) Renaudin", "definition": "Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.\n    ", "id": "MESH:D009638"}
{"mention": "behavioral depression", "mention_text": "The effect of amantadine hydrochloride, injected i.p. in 6 increments of 100 mg/kg each over 30 hr, on mouse motility and whole brain content of selected biogenic amines and major metabolites was studied in 4 strains of mice. These were the albino Sprague-Dawley ICR and BALB/C, the black C57BL/6 and the brown CDF-I mouse strains. Amantadine treatment produced a biphasic effect on mouse motility. The initial dose of amantadine depressed locomotor activity in all mouse strains studied with the BALB/C mice being the most sensitive. Subsequent amantadine treatments produced enhancement of motility from corresponding control in all mouse strains with the BALB/C mice being the least sensitive. The locomotor activity was decreased from corresponding controls in all strains studied, except for the ICR mice, during an overnight drug-free period following the fourth amantadine treatment. Readministration of amantadine, after a drug-free overnight period, increased motility from respective saline control in all strains with exception of the BALB/C mice where suppression of motility occurred. Treatment with amantadine did not alter whole brain dopamine levels but decreased the amounts of 3,4-dihydroxyphenylacetic acid in the BALB/C mice compared to saline control. Conversely, brain normetanephrine concentration was increased from saline control by amantadine in the BALB/C mice. The results suggest a strain-dependent effect of amantadine on motility and indicate a differential response to the acute and multiple dose regimens used. The BALB/C mouse was the most sensitive strain and could serve as the strain of choice for evaluating the side effects of amantadine. The biochemical results of brain biogenic amines of BALB/C mouse strain suggest a probable decrease of catecholamine turnover rate and/or metabolism by monoamine oxidase and a resulting increase in O-methylation of norepinephrine which may account for a behavioral depression caused by amantadine in the BALB/C mice.", "entity": "Psychomotor Disorders", "aliases": "Developmental Psychomotor Disorder Disorders Impairment Impairments", "definition": "Abnormalities of motor function that are associated with organic and non-organic cognitive disorders.\n    ", "id": "MESH:D011596"}
{"mention": "phenobarbital", "mention_text": "No enhancement by phenobarbital of the hepatocarcinogenicity of a choline-devoid diet in the rat.", "entity": "Phenobarbital", "aliases": "Acid Phenylethylbarbituric Gardenal Hysteps Luminal Monosodium Salt Phenobarbital Phenemal Sodium Phenobarbitone Phenylbarbital", "definition": "A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.\n    ", "id": "MESH:D010634"}
{"mention": "choline", "mention_text": "No enhancement by phenobarbital of the hepatocarcinogenicity of a choline-devoid diet in the rat.", "entity": "Choline", "aliases": "2-Hydroxy-N,N,N-trimethylethanaminium Bitartrate Choline Bursine Chloride Citrate Hydroxide O Sulfate O-Sulfate Fagine Vidine", "definition": "A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism.\n    ", "id": "MESH:D002794"}
{"mention": "phenobarbital", "mention_text": "An experiment was performed to test whether inclusion of phenobarbital in a choline-devoid diet would increase the hepatocarcinogenicity of the diet. Groups of 5-week old male Fischer-344 rats were fed for 7-25 months semipurified choline-devoid or choline-supplemented diets, containing or not 0.06% phenobarbital. No hepatic preneoplastic nodules or hepatocellular carcinomas developed in rats fed the plain choline-supplemented diet, while one preneoplastic nodule and one hepatocellular carcinoma developed in two rats fed the same diet containing phenobarbital. The incidence of preneoplastic nodules and of hepatocellular carcinomas was 10% and 37%, respectively, in rats fed the plain choline-devoid diet, and 17% and 30%, in rats fed the phenobarbital-containing choline-devoid diet. The results evinced no enhancement of the hepatocarcinogenicity of the choline-devoid diet by phenobarbital. Sporadic neoplastic lesions were observed in organs other than the liver of some of the animals, irrespective of the diet fed.", "entity": "Phenobarbital", "aliases": "Acid Phenylethylbarbituric Gardenal Hysteps Luminal Monosodium Salt Phenobarbital Phenemal Sodium Phenobarbitone Phenylbarbital", "definition": "A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.\n    ", "id": "MESH:D010634"}
{"mention": "choline", "mention_text": "An experiment was performed to test whether inclusion of phenobarbital in a choline-devoid diet would increase the hepatocarcinogenicity of the diet. Groups of 5-week old male Fischer-344 rats were fed for 7-25 months semipurified choline-devoid or choline-supplemented diets, containing or not 0.06% phenobarbital. No hepatic preneoplastic nodules or hepatocellular carcinomas developed in rats fed the plain choline-supplemented diet, while one preneoplastic nodule and one hepatocellular carcinoma developed in two rats fed the same diet containing phenobarbital. The incidence of preneoplastic nodules and of hepatocellular carcinomas was 10% and 37%, respectively, in rats fed the plain choline-devoid diet, and 17% and 30%, in rats fed the phenobarbital-containing choline-devoid diet. The results evinced no enhancement of the hepatocarcinogenicity of the choline-devoid diet by phenobarbital. Sporadic neoplastic lesions were observed in organs other than the liver of some of the animals, irrespective of the diet fed.", "entity": "Choline", "aliases": "2-Hydroxy-N,N,N-trimethylethanaminium Bitartrate Choline Bursine Chloride Citrate Hydroxide O Sulfate O-Sulfate Fagine Vidine", "definition": "A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism.\n    ", "id": "MESH:D002794"}
{"mention": "hepatocellular carcinomas", "mention_text": "An experiment was performed to test whether inclusion of phenobarbital in a choline-devoid diet would increase the hepatocarcinogenicity of the diet. Groups of 5-week old male Fischer-344 rats were fed for 7-25 months semipurified choline-devoid or choline-supplemented diets, containing or not 0.06% phenobarbital. No hepatic preneoplastic nodules or hepatocellular carcinomas developed in rats fed the plain choline-supplemented diet, while one preneoplastic nodule and one hepatocellular carcinoma developed in two rats fed the same diet containing phenobarbital. The incidence of preneoplastic nodules and of hepatocellular carcinomas was 10% and 37%, respectively, in rats fed the plain choline-devoid diet, and 17% and 30%, in rats fed the phenobarbital-containing choline-devoid diet. The results evinced no enhancement of the hepatocarcinogenicity of the choline-devoid diet by phenobarbital. Sporadic neoplastic lesions were observed in organs other than the liver of some of the animals, irrespective of the diet fed.", "entity": "Carcinoma, Hepatocellular", "aliases": "Adult Liver Cancer Cancers Carcinoma Hepatocellular Cell Carcinomas Hepatoma Hepatomas", "definition": "A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.\n    ", "id": "MESH:D006528"}
{"mention": "hepatocellular carcinoma", "mention_text": "An experiment was performed to test whether inclusion of phenobarbital in a choline-devoid diet would increase the hepatocarcinogenicity of the diet. Groups of 5-week old male Fischer-344 rats were fed for 7-25 months semipurified choline-devoid or choline-supplemented diets, containing or not 0.06% phenobarbital. No hepatic preneoplastic nodules or hepatocellular carcinomas developed in rats fed the plain choline-supplemented diet, while one preneoplastic nodule and one hepatocellular carcinoma developed in two rats fed the same diet containing phenobarbital. The incidence of preneoplastic nodules and of hepatocellular carcinomas was 10% and 37%, respectively, in rats fed the plain choline-devoid diet, and 17% and 30%, in rats fed the phenobarbital-containing choline-devoid diet. The results evinced no enhancement of the hepatocarcinogenicity of the choline-devoid diet by phenobarbital. Sporadic neoplastic lesions were observed in organs other than the liver of some of the animals, irrespective of the diet fed.", "entity": "Carcinoma, Hepatocellular", "aliases": "Adult Liver Cancer Cancers Carcinoma Hepatocellular Cell Carcinomas Hepatoma Hepatomas", "definition": "A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.\n    ", "id": "MESH:D006528"}
{"mention": "methylergonovine", "mention_text": "Effect of direct intracoronary administration of methylergonovine in patients with and without variant angina.", "entity": "Methylergonovine", "aliases": "Methergin Methergine Methylergobasin Methylergometrin Methylergometrine Maleate Methylergonovine Méthergin Novartis Brand of", "definition": "A homolog of ERGONOVINE containing one more CH2 group. (Merck Index, 11th ed)\n    ", "id": "MESH:D008755"}
{"mention": "variant angina", "mention_text": "Effect of direct intracoronary administration of methylergonovine in patients with and without variant angina.", "entity": "Angina Pectoris, Variant", "aliases": "Angina Pectoris Variant Prinzmetal Prinzmetal's Prinzmetals", "definition": "A clinical syndrome characterized by the development of CHEST PAIN at rest with concomitant transient ST segment elevation in the ELECTROCARDIOGRAM, but with preserved exercise capacity.\n    ", "id": "MESH:D000788"}
{"mention": "methylergonovine", "mention_text": "The effects of intracoronary administration of methylergonovine were studied in 21 patients with variant angina and 22 patients with atypical chest pain and in others without angina pectoris (control group). Methylergonovine was administered continuously at a rate of 10 micrograms/min up to 50 micrograms. In all patients with variant angina, coronary spasm was provoked at a mean dose of 28 +/- 13 micrograms (mean +/- SD). In the control group neither ischemic ST change nor localized spasm occurred. The basal tone of the right coronary artery was significantly lower than that of the left coronary artery. The percentage of vasoconstriction of the right coronary artery was significantly higher than that of the left coronary artery. These results suggest that spasm provocation tests, which use an intracoronary injection of a relatively low dose of methylergonovine, have a high sensitivity in variant angina and the vasoreactivity of the right coronary artery may be greater than that of the other coronary arteries.", "entity": "Methylergonovine", "aliases": "Methergin Methergine Methylergobasin Methylergometrin Methylergometrine Maleate Methylergonovine Méthergin Novartis Brand of", "definition": "A homolog of ERGONOVINE containing one more CH2 group. (Merck Index, 11th ed)\n    ", "id": "MESH:D008755"}
{"mention": "variant angina", "mention_text": "The effects of intracoronary administration of methylergonovine were studied in 21 patients with variant angina and 22 patients with atypical chest pain and in others without angina pectoris (control group). Methylergonovine was administered continuously at a rate of 10 micrograms/min up to 50 micrograms. In all patients with variant angina, coronary spasm was provoked at a mean dose of 28 +/- 13 micrograms (mean +/- SD). In the control group neither ischemic ST change nor localized spasm occurred. The basal tone of the right coronary artery was significantly lower than that of the left coronary artery. The percentage of vasoconstriction of the right coronary artery was significantly higher than that of the left coronary artery. These results suggest that spasm provocation tests, which use an intracoronary injection of a relatively low dose of methylergonovine, have a high sensitivity in variant angina and the vasoreactivity of the right coronary artery may be greater than that of the other coronary arteries.", "entity": "Angina Pectoris, Variant", "aliases": "Angina Pectoris Variant Prinzmetal Prinzmetal's Prinzmetals", "definition": "A clinical syndrome characterized by the development of CHEST PAIN at rest with concomitant transient ST segment elevation in the ELECTROCARDIOGRAM, but with preserved exercise capacity.\n    ", "id": "MESH:D000788"}
{"mention": "chest pain", "mention_text": "The effects of intracoronary administration of methylergonovine were studied in 21 patients with variant angina and 22 patients with atypical chest pain and in others without angina pectoris (control group). Methylergonovine was administered continuously at a rate of 10 micrograms/min up to 50 micrograms. In all patients with variant angina, coronary spasm was provoked at a mean dose of 28 +/- 13 micrograms (mean +/- SD). In the control group neither ischemic ST change nor localized spasm occurred. The basal tone of the right coronary artery was significantly lower than that of the left coronary artery. The percentage of vasoconstriction of the right coronary artery was significantly higher than that of the left coronary artery. These results suggest that spasm provocation tests, which use an intracoronary injection of a relatively low dose of methylergonovine, have a high sensitivity in variant angina and the vasoreactivity of the right coronary artery may be greater than that of the other coronary arteries.", "entity": "Chest Pain", "aliases": "Chest Pain Pains", "definition": "Pressure, burning, or numbness in the chest.\n    ", "id": "MESH:D002637"}
{"mention": "angina pectoris", "mention_text": "The effects of intracoronary administration of methylergonovine were studied in 21 patients with variant angina and 22 patients with atypical chest pain and in others without angina pectoris (control group). Methylergonovine was administered continuously at a rate of 10 micrograms/min up to 50 micrograms. In all patients with variant angina, coronary spasm was provoked at a mean dose of 28 +/- 13 micrograms (mean +/- SD). In the control group neither ischemic ST change nor localized spasm occurred. The basal tone of the right coronary artery was significantly lower than that of the left coronary artery. The percentage of vasoconstriction of the right coronary artery was significantly higher than that of the left coronary artery. These results suggest that spasm provocation tests, which use an intracoronary injection of a relatively low dose of methylergonovine, have a high sensitivity in variant angina and the vasoreactivity of the right coronary artery may be greater than that of the other coronary arteries.", "entity": "Angina Pectoris", "aliases": "Angina Pectoris Angor Stenocardia Stenocardias", "definition": "The symptom of paroxysmal pain consequent to MYOCARDIAL ISCHEMIA usually of distinctive character, location and radiation. It is thought to be provoked by a transient stressful situation during which the oxygen requirements of the MYOCARDIUM exceed that supplied by the CORONARY CIRCULATION.\n    ", "id": "MESH:D000787"}
{"mention": "Methylergonovine", "mention_text": "The effects of intracoronary administration of methylergonovine were studied in 21 patients with variant angina and 22 patients with atypical chest pain and in others without angina pectoris (control group). Methylergonovine was administered continuously at a rate of 10 micrograms/min up to 50 micrograms. In all patients with variant angina, coronary spasm was provoked at a mean dose of 28 +/- 13 micrograms (mean +/- SD). In the control group neither ischemic ST change nor localized spasm occurred. The basal tone of the right coronary artery was significantly lower than that of the left coronary artery. The percentage of vasoconstriction of the right coronary artery was significantly higher than that of the left coronary artery. These results suggest that spasm provocation tests, which use an intracoronary injection of a relatively low dose of methylergonovine, have a high sensitivity in variant angina and the vasoreactivity of the right coronary artery may be greater than that of the other coronary arteries.", "entity": "Methylergonovine", "aliases": "Methergin Methergine Methylergobasin Methylergometrin Methylergometrine Maleate Methylergonovine Méthergin Novartis Brand of", "definition": "A homolog of ERGONOVINE containing one more CH2 group. (Merck Index, 11th ed)\n    ", "id": "MESH:D008755"}
{"mention": "coronary spasm", "mention_text": "The effects of intracoronary administration of methylergonovine were studied in 21 patients with variant angina and 22 patients with atypical chest pain and in others without angina pectoris (control group). Methylergonovine was administered continuously at a rate of 10 micrograms/min up to 50 micrograms. In all patients with variant angina, coronary spasm was provoked at a mean dose of 28 +/- 13 micrograms (mean +/- SD). In the control group neither ischemic ST change nor localized spasm occurred. The basal tone of the right coronary artery was significantly lower than that of the left coronary artery. The percentage of vasoconstriction of the right coronary artery was significantly higher than that of the left coronary artery. These results suggest that spasm provocation tests, which use an intracoronary injection of a relatively low dose of methylergonovine, have a high sensitivity in variant angina and the vasoreactivity of the right coronary artery may be greater than that of the other coronary arteries.", "entity": "Coronary Vasospasm", "aliases": "Artery Vasospasm Coronary Vasospasms", "definition": "Spasm of the large- or medium-sized coronary arteries.\n    ", "id": "MESH:D003329"}
{"mention": "spasm", "mention_text": "The effects of intracoronary administration of methylergonovine were studied in 21 patients with variant angina and 22 patients with atypical chest pain and in others without angina pectoris (control group). Methylergonovine was administered continuously at a rate of 10 micrograms/min up to 50 micrograms. In all patients with variant angina, coronary spasm was provoked at a mean dose of 28 +/- 13 micrograms (mean +/- SD). In the control group neither ischemic ST change nor localized spasm occurred. The basal tone of the right coronary artery was significantly lower than that of the left coronary artery. The percentage of vasoconstriction of the right coronary artery was significantly higher than that of the left coronary artery. These results suggest that spasm provocation tests, which use an intracoronary injection of a relatively low dose of methylergonovine, have a high sensitivity in variant angina and the vasoreactivity of the right coronary artery may be greater than that of the other coronary arteries.", "entity": "Spasm", "aliases": "Ciliary Body Spasm Spasms Generalized Muscle Muscular", "definition": "An involuntary contraction of a muscle or group of muscles. Spasms may involve SKELETAL MUSCLE or SMOOTH MUSCLE.\n    ", "id": "MESH:D013035"}
{"mention": "Dobutamine", "mention_text": "Dobutamine stress echocardiography: a sensitive indicator of diminished myocardial function in asymptomatic doxorubicin-treated long-term survivors of childhood cancer.", "entity": "Dobutamine", "aliases": "Boehringer Ingelheim Brand of Dobutamine Hydrochloride Dobucor Dobuject Dobutamin Fresenius Hexal Solvay ratiopharm Dobutamin-ratiopharm Dobutamina Inibsa Rovi (+)-Isomer Hydrobromide Lactobionate Phosphate (1:1) Salt (-)-Isomer Tartrate (R-(R*,R*))-Isomer (S-(R*,R*))-Isomer Dobutrex Eli Lilly Irisfarma Juste Kendrick 81929 Oxiken Pisa Posiject", "definition": "A catecholamine derivative with specificity for BETA-1 ADRENERGIC RECEPTORS. It is commonly used as a cardiotonic agent after CARDIAC SURGERY and during DOBUTAMINE STRESS ECHOCARDIOGRAPHY.\n    ", "id": "MESH:D004280"}
{"mention": "doxorubicin", "mention_text": "Dobutamine stress echocardiography: a sensitive indicator of diminished myocardial function in asymptomatic doxorubicin-treated long-term survivors of childhood cancer.", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "cancer", "mention_text": "Dobutamine stress echocardiography: a sensitive indicator of diminished myocardial function in asymptomatic doxorubicin-treated long-term survivors of childhood cancer.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "Doxorubicin", "mention_text": "Doxorubicin is an effective anticancer chemotherapeutic agent known to cause acute and chronic cardiomyopathy. To develop a more sensitive echocardiographic screening test for cardiac damage due to doxorubicin, a cohort study was performed using dobutamine infusion to differentiate asymptomatic long-term survivors of childhood cancer treated with doxorubicin from healthy control subjects. Echocardiographic data from the experimental group of 21 patients (mean age 16 +/- 5 years) treated from 1.6 to 14.3 years (median 5.3) before this study with 27 to 532 mg/m2 of doxorubicin (mean 196) were compared with echocardiographic data from 12 normal age-matched control subjects. Graded dobutamine infusions of 0.5, 2.5, 5 and 10 micrograms/kg per min were administered. Echocardiographic Doppler studies were performed before infusion and after 15 min of infusion at each rate. Dobutamine infusion at 10 micrograms/kg per min was discontinued after six studies secondary to a 50% incidence rate of adverse symptoms. The most important findings were that compared with values in control subjects, end-systolic left ventricular posterior wall dimension and percent of left ventricular posterior wall thickening in doxorubicin-treated patients were decreased at baseline study and these findings were more clearly delineated with dobutamine stimulation. End-systolic left ventricular posterior wall dimension at baseline for the doxorubicin-treated group was 11 +/- 1.9 mm versus 13.1 +/- 1.5 mm for control subjects (p less than 0.01). End-systolic left ventricular posterior wall dimension at the 5-micrograms/kg per min dobutamine infusion for the doxorubicin-treated group was 14.1 +/- 2.4 mm versus 19.3 +/- 2.6 mm for control subjects (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "cardiomyopathy", "mention_text": "Doxorubicin is an effective anticancer chemotherapeutic agent known to cause acute and chronic cardiomyopathy. To develop a more sensitive echocardiographic screening test for cardiac damage due to doxorubicin, a cohort study was performed using dobutamine infusion to differentiate asymptomatic long-term survivors of childhood cancer treated with doxorubicin from healthy control subjects. Echocardiographic data from the experimental group of 21 patients (mean age 16 +/- 5 years) treated from 1.6 to 14.3 years (median 5.3) before this study with 27 to 532 mg/m2 of doxorubicin (mean 196) were compared with echocardiographic data from 12 normal age-matched control subjects. Graded dobutamine infusions of 0.5, 2.5, 5 and 10 micrograms/kg per min were administered. Echocardiographic Doppler studies were performed before infusion and after 15 min of infusion at each rate. Dobutamine infusion at 10 micrograms/kg per min was discontinued after six studies secondary to a 50% incidence rate of adverse symptoms. The most important findings were that compared with values in control subjects, end-systolic left ventricular posterior wall dimension and percent of left ventricular posterior wall thickening in doxorubicin-treated patients were decreased at baseline study and these findings were more clearly delineated with dobutamine stimulation. End-systolic left ventricular posterior wall dimension at baseline for the doxorubicin-treated group was 11 +/- 1.9 mm versus 13.1 +/- 1.5 mm for control subjects (p less than 0.01). End-systolic left ventricular posterior wall dimension at the 5-micrograms/kg per min dobutamine infusion for the doxorubicin-treated group was 14.1 +/- 2.4 mm versus 19.3 +/- 2.6 mm for control subjects (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Cardiomyopathies", "aliases": "Cardiomyopathies Primary Secondary Cardiomyopathy Disease Myocardial Diseases Myocardiopathies Myocardiopathy", "definition": "A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).\n    ", "id": "MESH:D009202"}
{"mention": "cardiac damage", "mention_text": "Doxorubicin is an effective anticancer chemotherapeutic agent known to cause acute and chronic cardiomyopathy. To develop a more sensitive echocardiographic screening test for cardiac damage due to doxorubicin, a cohort study was performed using dobutamine infusion to differentiate asymptomatic long-term survivors of childhood cancer treated with doxorubicin from healthy control subjects. Echocardiographic data from the experimental group of 21 patients (mean age 16 +/- 5 years) treated from 1.6 to 14.3 years (median 5.3) before this study with 27 to 532 mg/m2 of doxorubicin (mean 196) were compared with echocardiographic data from 12 normal age-matched control subjects. Graded dobutamine infusions of 0.5, 2.5, 5 and 10 micrograms/kg per min were administered. Echocardiographic Doppler studies were performed before infusion and after 15 min of infusion at each rate. Dobutamine infusion at 10 micrograms/kg per min was discontinued after six studies secondary to a 50% incidence rate of adverse symptoms. The most important findings were that compared with values in control subjects, end-systolic left ventricular posterior wall dimension and percent of left ventricular posterior wall thickening in doxorubicin-treated patients were decreased at baseline study and these findings were more clearly delineated with dobutamine stimulation. End-systolic left ventricular posterior wall dimension at baseline for the doxorubicin-treated group was 11 +/- 1.9 mm versus 13.1 +/- 1.5 mm for control subjects (p less than 0.01). End-systolic left ventricular posterior wall dimension at the 5-micrograms/kg per min dobutamine infusion for the doxorubicin-treated group was 14.1 +/- 2.4 mm versus 19.3 +/- 2.6 mm for control subjects (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Heart Diseases", "aliases": "Cardiac Disease Diseases Heart", "definition": "Pathological conditions involving the HEART including its structural and functional abnormalities.\n    ", "id": "MESH:D006331"}
{"mention": "doxorubicin", "mention_text": "Doxorubicin is an effective anticancer chemotherapeutic agent known to cause acute and chronic cardiomyopathy. To develop a more sensitive echocardiographic screening test for cardiac damage due to doxorubicin, a cohort study was performed using dobutamine infusion to differentiate asymptomatic long-term survivors of childhood cancer treated with doxorubicin from healthy control subjects. Echocardiographic data from the experimental group of 21 patients (mean age 16 +/- 5 years) treated from 1.6 to 14.3 years (median 5.3) before this study with 27 to 532 mg/m2 of doxorubicin (mean 196) were compared with echocardiographic data from 12 normal age-matched control subjects. Graded dobutamine infusions of 0.5, 2.5, 5 and 10 micrograms/kg per min were administered. Echocardiographic Doppler studies were performed before infusion and after 15 min of infusion at each rate. Dobutamine infusion at 10 micrograms/kg per min was discontinued after six studies secondary to a 50% incidence rate of adverse symptoms. The most important findings were that compared with values in control subjects, end-systolic left ventricular posterior wall dimension and percent of left ventricular posterior wall thickening in doxorubicin-treated patients were decreased at baseline study and these findings were more clearly delineated with dobutamine stimulation. End-systolic left ventricular posterior wall dimension at baseline for the doxorubicin-treated group was 11 +/- 1.9 mm versus 13.1 +/- 1.5 mm for control subjects (p less than 0.01). End-systolic left ventricular posterior wall dimension at the 5-micrograms/kg per min dobutamine infusion for the doxorubicin-treated group was 14.1 +/- 2.4 mm versus 19.3 +/- 2.6 mm for control subjects (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Doxorubicin", "aliases": "Adriablastin Adriablastine Adriamycin Adriblastin Adriblastina Adriblastine Adrimedac Baxter Brand of Doxorubicin Hydrochloride Bedford Bristol-Myers Squibb Columbia DOXO cell DOXO-cell Doxolem Hexal NC Doxorubicina Ferrer Farm Funk Tedec Doxorubicine Doxotec Elan Farmiblastina Kenfarma Lemery Myocet Neocorp Onkodox Onkoworks Pfizer Prasfarma Ribodoxo Rubex Meiji Urokit Doxo Doxo-cell pharm medac ribosepharm", "definition": "Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.\n    ", "id": "MESH:D004317"}
{"mention": "dobutamine", "mention_text": "Doxorubicin is an effective anticancer chemotherapeutic agent known to cause acute and chronic cardiomyopathy. To develop a more sensitive echocardiographic screening test for cardiac damage due to doxorubicin, a cohort study was performed using dobutamine infusion to differentiate asymptomatic long-term survivors of childhood cancer treated with doxorubicin from healthy control subjects. Echocardiographic data from the experimental group of 21 patients (mean age 16 +/- 5 years) treated from 1.6 to 14.3 years (median 5.3) before this study with 27 to 532 mg/m2 of doxorubicin (mean 196) were compared with echocardiographic data from 12 normal age-matched control subjects. Graded dobutamine infusions of 0.5, 2.5, 5 and 10 micrograms/kg per min were administered. Echocardiographic Doppler studies were performed before infusion and after 15 min of infusion at each rate. Dobutamine infusion at 10 micrograms/kg per min was discontinued after six studies secondary to a 50% incidence rate of adverse symptoms. The most important findings were that compared with values in control subjects, end-systolic left ventricular posterior wall dimension and percent of left ventricular posterior wall thickening in doxorubicin-treated patients were decreased at baseline study and these findings were more clearly delineated with dobutamine stimulation. End-systolic left ventricular posterior wall dimension at baseline for the doxorubicin-treated group was 11 +/- 1.9 mm versus 13.1 +/- 1.5 mm for control subjects (p less than 0.01). End-systolic left ventricular posterior wall dimension at the 5-micrograms/kg per min dobutamine infusion for the doxorubicin-treated group was 14.1 +/- 2.4 mm versus 19.3 +/- 2.6 mm for control subjects (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Dobutamine", "aliases": "Boehringer Ingelheim Brand of Dobutamine Hydrochloride Dobucor Dobuject Dobutamin Fresenius Hexal Solvay ratiopharm Dobutamin-ratiopharm Dobutamina Inibsa Rovi (+)-Isomer Hydrobromide Lactobionate Phosphate (1:1) Salt (-)-Isomer Tartrate (R-(R*,R*))-Isomer (S-(R*,R*))-Isomer Dobutrex Eli Lilly Irisfarma Juste Kendrick 81929 Oxiken Pisa Posiject", "definition": "A catecholamine derivative with specificity for BETA-1 ADRENERGIC RECEPTORS. It is commonly used as a cardiotonic agent after CARDIAC SURGERY and during DOBUTAMINE STRESS ECHOCARDIOGRAPHY.\n    ", "id": "MESH:D004280"}
{"mention": "cancer", "mention_text": "Doxorubicin is an effective anticancer chemotherapeutic agent known to cause acute and chronic cardiomyopathy. To develop a more sensitive echocardiographic screening test for cardiac damage due to doxorubicin, a cohort study was performed using dobutamine infusion to differentiate asymptomatic long-term survivors of childhood cancer treated with doxorubicin from healthy control subjects. Echocardiographic data from the experimental group of 21 patients (mean age 16 +/- 5 years) treated from 1.6 to 14.3 years (median 5.3) before this study with 27 to 532 mg/m2 of doxorubicin (mean 196) were compared with echocardiographic data from 12 normal age-matched control subjects. Graded dobutamine infusions of 0.5, 2.5, 5 and 10 micrograms/kg per min were administered. Echocardiographic Doppler studies were performed before infusion and after 15 min of infusion at each rate. Dobutamine infusion at 10 micrograms/kg per min was discontinued after six studies secondary to a 50% incidence rate of adverse symptoms. The most important findings were that compared with values in control subjects, end-systolic left ventricular posterior wall dimension and percent of left ventricular posterior wall thickening in doxorubicin-treated patients were decreased at baseline study and these findings were more clearly delineated with dobutamine stimulation. End-systolic left ventricular posterior wall dimension at baseline for the doxorubicin-treated group was 11 +/- 1.9 mm versus 13.1 +/- 1.5 mm for control subjects (p less than 0.01). End-systolic left ventricular posterior wall dimension at the 5-micrograms/kg per min dobutamine infusion for the doxorubicin-treated group was 14.1 +/- 2.4 mm versus 19.3 +/- 2.6 mm for control subjects (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "Dobutamine", "mention_text": "Doxorubicin is an effective anticancer chemotherapeutic agent known to cause acute and chronic cardiomyopathy. To develop a more sensitive echocardiographic screening test for cardiac damage due to doxorubicin, a cohort study was performed using dobutamine infusion to differentiate asymptomatic long-term survivors of childhood cancer treated with doxorubicin from healthy control subjects. Echocardiographic data from the experimental group of 21 patients (mean age 16 +/- 5 years) treated from 1.6 to 14.3 years (median 5.3) before this study with 27 to 532 mg/m2 of doxorubicin (mean 196) were compared with echocardiographic data from 12 normal age-matched control subjects. Graded dobutamine infusions of 0.5, 2.5, 5 and 10 micrograms/kg per min were administered. Echocardiographic Doppler studies were performed before infusion and after 15 min of infusion at each rate. Dobutamine infusion at 10 micrograms/kg per min was discontinued after six studies secondary to a 50% incidence rate of adverse symptoms. The most important findings were that compared with values in control subjects, end-systolic left ventricular posterior wall dimension and percent of left ventricular posterior wall thickening in doxorubicin-treated patients were decreased at baseline study and these findings were more clearly delineated with dobutamine stimulation. End-systolic left ventricular posterior wall dimension at baseline for the doxorubicin-treated group was 11 +/- 1.9 mm versus 13.1 +/- 1.5 mm for control subjects (p less than 0.01). End-systolic left ventricular posterior wall dimension at the 5-micrograms/kg per min dobutamine infusion for the doxorubicin-treated group was 14.1 +/- 2.4 mm versus 19.3 +/- 2.6 mm for control subjects (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Dobutamine", "aliases": "Boehringer Ingelheim Brand of Dobutamine Hydrochloride Dobucor Dobuject Dobutamin Fresenius Hexal Solvay ratiopharm Dobutamin-ratiopharm Dobutamina Inibsa Rovi (+)-Isomer Hydrobromide Lactobionate Phosphate (1:1) Salt (-)-Isomer Tartrate (R-(R*,R*))-Isomer (S-(R*,R*))-Isomer Dobutrex Eli Lilly Irisfarma Juste Kendrick 81929 Oxiken Pisa Posiject", "definition": "A catecholamine derivative with specificity for BETA-1 ADRENERGIC RECEPTORS. It is commonly used as a cardiotonic agent after CARDIAC SURGERY and during DOBUTAMINE STRESS ECHOCARDIOGRAPHY.\n    ", "id": "MESH:D004280"}
{"mention": "aminophylline", "mention_text": "Effects of aminophylline on the threshold for initiating ventricular fibrillation during respiratory failure.", "entity": "Aminophylline", "aliases": "Afonilum Aminodur Aminophyllin Aminophylline DF Barre Brand of Berlex Byk Cardophyllin Carine Clonmel Clonofilin Corophyllin Diaphyllin Drafilyn Durachemie Duraphyllin Elmuquimica Ethylenediamine Theophylline Eufilina Venosa Euphyllin Retard Euphylline Ferndale G & W Godafilin Hamilton Interstate Drug Exchange Jenapharm Key Knoll Major Merck Mini-Lix Mundipharma Mundiphyllin Napp Novophyllin OPW Phyllocontin Phyllotemp Purdue Frederick Roxanne Rugby Schein Searle SmithKline Beecham Somophyllin T", "definition": "A drug combination that contains THEOPHYLLINE and ethylenediamine. It is more soluble in water than theophylline but has similar pharmacologic actions. It's most common use is in bronchial asthma, but it has been investigated for several other applications.\n    ", "id": "MESH:D000628"}
{"mention": "ventricular fibrillation", "mention_text": "Effects of aminophylline on the threshold for initiating ventricular fibrillation during respiratory failure.", "entity": "Ventricular Fibrillation", "aliases": "Fibrillation Ventricular Fibrillations", "definition": "A potentially lethal cardiac arrhythmia that is characterized by uncoordinated extremely rapid firing of electrical impulses (400-600/min) in HEART VENTRICLES. Such asynchronous ventricular quivering or fibrillation prevents any effective cardiac output and results in unconsciousness (SYNCOPE). It is one of the major electrocardiographic patterns seen with CARDIAC ARREST.\n    ", "id": "MESH:D014693"}
{"mention": "respiratory failure", "mention_text": "Effects of aminophylline on the threshold for initiating ventricular fibrillation during respiratory failure.", "entity": "Respiratory Insufficiency", "aliases": "Depressions Ventilatory Respiratory Depression Failure Insufficiency", "definition": "Failure to adequately provide oxygen to cells of the body and to remove excess carbon dioxide from them. (Stedman, 25th ed)\n    ", "id": "MESH:D012131"}
{"mention": "Cardiac arrhythmias", "mention_text": "Cardiac arrhythmias have frequently been reported in association with respiratory failure. The possible additive role of pharmacologic agents in precipitating cardiac disturbances in patients with respiratory failure has only recently been emphasized. The effects of aminophylline on the ventricular fibrillation threshold during normal acid-base conditions and during respiratory failure were studied in anesthetized open chest dogs. The ventricular fibrillation threshold was measured by passing a gated train of 12 constant current pulses through the ventricular myocardium during the vulnerable period of the cardiac cycle. During the infusion of aminophylline, the ventricular fibrillation threshold was reduced by 30 to 40 percent of the control when pH and partial pressures of oxygen (PO2) and carbon dioxide (CO2) were kept within normal limits. When respiratory failure was produced by hypoventilation (pH 7.05 to 7.25; PC02 70 to 100 mm Hg: P02 20 to 40 mm Hg), infusion of aminophylline resulted in an even greater decrease in ventricular fibrillation threshold to 60 percent of the control level. These experiments suggest that although many factors may contribute to the increased incidence of ventricular arrhythmias in respiratory failure, pharmacologic agents, particularly aminophylline, may play a significant role.", "entity": "Arrhythmias, Cardiac", "aliases": "Arrhythmia Cardiac Arrhythmias Arrythmia Dysrhythmia", "definition": "Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.\n    ", "id": "MESH:D001145"}
{"mention": "respiratory failure", "mention_text": "Cardiac arrhythmias have frequently been reported in association with respiratory failure. The possible additive role of pharmacologic agents in precipitating cardiac disturbances in patients with respiratory failure has only recently been emphasized. The effects of aminophylline on the ventricular fibrillation threshold during normal acid-base conditions and during respiratory failure were studied in anesthetized open chest dogs. The ventricular fibrillation threshold was measured by passing a gated train of 12 constant current pulses through the ventricular myocardium during the vulnerable period of the cardiac cycle. During the infusion of aminophylline, the ventricular fibrillation threshold was reduced by 30 to 40 percent of the control when pH and partial pressures of oxygen (PO2) and carbon dioxide (CO2) were kept within normal limits. When respiratory failure was produced by hypoventilation (pH 7.05 to 7.25; PC02 70 to 100 mm Hg: P02 20 to 40 mm Hg), infusion of aminophylline resulted in an even greater decrease in ventricular fibrillation threshold to 60 percent of the control level. These experiments suggest that although many factors may contribute to the increased incidence of ventricular arrhythmias in respiratory failure, pharmacologic agents, particularly aminophylline, may play a significant role.", "entity": "Respiratory Insufficiency", "aliases": "Depressions Ventilatory Respiratory Depression Failure Insufficiency", "definition": "Failure to adequately provide oxygen to cells of the body and to remove excess carbon dioxide from them. (Stedman, 25th ed)\n    ", "id": "MESH:D012131"}
{"mention": "cardiac disturbances", "mention_text": "Cardiac arrhythmias have frequently been reported in association with respiratory failure. The possible additive role of pharmacologic agents in precipitating cardiac disturbances in patients with respiratory failure has only recently been emphasized. The effects of aminophylline on the ventricular fibrillation threshold during normal acid-base conditions and during respiratory failure were studied in anesthetized open chest dogs. The ventricular fibrillation threshold was measured by passing a gated train of 12 constant current pulses through the ventricular myocardium during the vulnerable period of the cardiac cycle. During the infusion of aminophylline, the ventricular fibrillation threshold was reduced by 30 to 40 percent of the control when pH and partial pressures of oxygen (PO2) and carbon dioxide (CO2) were kept within normal limits. When respiratory failure was produced by hypoventilation (pH 7.05 to 7.25; PC02 70 to 100 mm Hg: P02 20 to 40 mm Hg), infusion of aminophylline resulted in an even greater decrease in ventricular fibrillation threshold to 60 percent of the control level. These experiments suggest that although many factors may contribute to the increased incidence of ventricular arrhythmias in respiratory failure, pharmacologic agents, particularly aminophylline, may play a significant role.", "entity": "Heart Diseases", "aliases": "Cardiac Disease Diseases Heart", "definition": "Pathological conditions involving the HEART including its structural and functional abnormalities.\n    ", "id": "MESH:D006331"}
{"mention": "aminophylline", "mention_text": "Cardiac arrhythmias have frequently been reported in association with respiratory failure. The possible additive role of pharmacologic agents in precipitating cardiac disturbances in patients with respiratory failure has only recently been emphasized. The effects of aminophylline on the ventricular fibrillation threshold during normal acid-base conditions and during respiratory failure were studied in anesthetized open chest dogs. The ventricular fibrillation threshold was measured by passing a gated train of 12 constant current pulses through the ventricular myocardium during the vulnerable period of the cardiac cycle. During the infusion of aminophylline, the ventricular fibrillation threshold was reduced by 30 to 40 percent of the control when pH and partial pressures of oxygen (PO2) and carbon dioxide (CO2) were kept within normal limits. When respiratory failure was produced by hypoventilation (pH 7.05 to 7.25; PC02 70 to 100 mm Hg: P02 20 to 40 mm Hg), infusion of aminophylline resulted in an even greater decrease in ventricular fibrillation threshold to 60 percent of the control level. These experiments suggest that although many factors may contribute to the increased incidence of ventricular arrhythmias in respiratory failure, pharmacologic agents, particularly aminophylline, may play a significant role.", "entity": "Aminophylline", "aliases": "Afonilum Aminodur Aminophyllin Aminophylline DF Barre Brand of Berlex Byk Cardophyllin Carine Clonmel Clonofilin Corophyllin Diaphyllin Drafilyn Durachemie Duraphyllin Elmuquimica Ethylenediamine Theophylline Eufilina Venosa Euphyllin Retard Euphylline Ferndale G & W Godafilin Hamilton Interstate Drug Exchange Jenapharm Key Knoll Major Merck Mini-Lix Mundipharma Mundiphyllin Napp Novophyllin OPW Phyllocontin Phyllotemp Purdue Frederick Roxanne Rugby Schein Searle SmithKline Beecham Somophyllin T", "definition": "A drug combination that contains THEOPHYLLINE and ethylenediamine. It is more soluble in water than theophylline but has similar pharmacologic actions. It's most common use is in bronchial asthma, but it has been investigated for several other applications.\n    ", "id": "MESH:D000628"}
{"mention": "ventricular fibrillation", "mention_text": "Cardiac arrhythmias have frequently been reported in association with respiratory failure. The possible additive role of pharmacologic agents in precipitating cardiac disturbances in patients with respiratory failure has only recently been emphasized. The effects of aminophylline on the ventricular fibrillation threshold during normal acid-base conditions and during respiratory failure were studied in anesthetized open chest dogs. The ventricular fibrillation threshold was measured by passing a gated train of 12 constant current pulses through the ventricular myocardium during the vulnerable period of the cardiac cycle. During the infusion of aminophylline, the ventricular fibrillation threshold was reduced by 30 to 40 percent of the control when pH and partial pressures of oxygen (PO2) and carbon dioxide (CO2) were kept within normal limits. When respiratory failure was produced by hypoventilation (pH 7.05 to 7.25; PC02 70 to 100 mm Hg: P02 20 to 40 mm Hg), infusion of aminophylline resulted in an even greater decrease in ventricular fibrillation threshold to 60 percent of the control level. These experiments suggest that although many factors may contribute to the increased incidence of ventricular arrhythmias in respiratory failure, pharmacologic agents, particularly aminophylline, may play a significant role.", "entity": "Ventricular Fibrillation", "aliases": "Fibrillation Ventricular Fibrillations", "definition": "A potentially lethal cardiac arrhythmia that is characterized by uncoordinated extremely rapid firing of electrical impulses (400-600/min) in HEART VENTRICLES. Such asynchronous ventricular quivering or fibrillation prevents any effective cardiac output and results in unconsciousness (SYNCOPE). It is one of the major electrocardiographic patterns seen with CARDIAC ARREST.\n    ", "id": "MESH:D014693"}
{"mention": "oxygen", "mention_text": "Cardiac arrhythmias have frequently been reported in association with respiratory failure. The possible additive role of pharmacologic agents in precipitating cardiac disturbances in patients with respiratory failure has only recently been emphasized. The effects of aminophylline on the ventricular fibrillation threshold during normal acid-base conditions and during respiratory failure were studied in anesthetized open chest dogs. The ventricular fibrillation threshold was measured by passing a gated train of 12 constant current pulses through the ventricular myocardium during the vulnerable period of the cardiac cycle. During the infusion of aminophylline, the ventricular fibrillation threshold was reduced by 30 to 40 percent of the control when pH and partial pressures of oxygen (PO2) and carbon dioxide (CO2) were kept within normal limits. When respiratory failure was produced by hypoventilation (pH 7.05 to 7.25; PC02 70 to 100 mm Hg: P02 20 to 40 mm Hg), infusion of aminophylline resulted in an even greater decrease in ventricular fibrillation threshold to 60 percent of the control level. These experiments suggest that although many factors may contribute to the increased incidence of ventricular arrhythmias in respiratory failure, pharmacologic agents, particularly aminophylline, may play a significant role.", "entity": "Oxygen", "aliases": "Dioxygen Oxygen", "definition": "An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.\n    ", "id": "MESH:D010100"}
{"mention": "PO2", "mention_text": "Cardiac arrhythmias have frequently been reported in association with respiratory failure. The possible additive role of pharmacologic agents in precipitating cardiac disturbances in patients with respiratory failure has only recently been emphasized. The effects of aminophylline on the ventricular fibrillation threshold during normal acid-base conditions and during respiratory failure were studied in anesthetized open chest dogs. The ventricular fibrillation threshold was measured by passing a gated train of 12 constant current pulses through the ventricular myocardium during the vulnerable period of the cardiac cycle. During the infusion of aminophylline, the ventricular fibrillation threshold was reduced by 30 to 40 percent of the control when pH and partial pressures of oxygen (PO2) and carbon dioxide (CO2) were kept within normal limits. When respiratory failure was produced by hypoventilation (pH 7.05 to 7.25; PC02 70 to 100 mm Hg: P02 20 to 40 mm Hg), infusion of aminophylline resulted in an even greater decrease in ventricular fibrillation threshold to 60 percent of the control level. These experiments suggest that although many factors may contribute to the increased incidence of ventricular arrhythmias in respiratory failure, pharmacologic agents, particularly aminophylline, may play a significant role.", "entity": "PO-2", "aliases": "PO-2", "definition": "", "id": "MESH:C093415"}
{"mention": "carbon dioxide", "mention_text": "Cardiac arrhythmias have frequently been reported in association with respiratory failure. The possible additive role of pharmacologic agents in precipitating cardiac disturbances in patients with respiratory failure has only recently been emphasized. The effects of aminophylline on the ventricular fibrillation threshold during normal acid-base conditions and during respiratory failure were studied in anesthetized open chest dogs. The ventricular fibrillation threshold was measured by passing a gated train of 12 constant current pulses through the ventricular myocardium during the vulnerable period of the cardiac cycle. During the infusion of aminophylline, the ventricular fibrillation threshold was reduced by 30 to 40 percent of the control when pH and partial pressures of oxygen (PO2) and carbon dioxide (CO2) were kept within normal limits. When respiratory failure was produced by hypoventilation (pH 7.05 to 7.25; PC02 70 to 100 mm Hg: P02 20 to 40 mm Hg), infusion of aminophylline resulted in an even greater decrease in ventricular fibrillation threshold to 60 percent of the control level. These experiments suggest that although many factors may contribute to the increased incidence of ventricular arrhythmias in respiratory failure, pharmacologic agents, particularly aminophylline, may play a significant role.", "entity": "Carbon Dioxide", "aliases": "Anhydride Carbonic Carbon Dioxide", "definition": "A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals.\n    ", "id": "MESH:D002245"}
{"mention": "CO2", "mention_text": "Cardiac arrhythmias have frequently been reported in association with respiratory failure. The possible additive role of pharmacologic agents in precipitating cardiac disturbances in patients with respiratory failure has only recently been emphasized. The effects of aminophylline on the ventricular fibrillation threshold during normal acid-base conditions and during respiratory failure were studied in anesthetized open chest dogs. The ventricular fibrillation threshold was measured by passing a gated train of 12 constant current pulses through the ventricular myocardium during the vulnerable period of the cardiac cycle. During the infusion of aminophylline, the ventricular fibrillation threshold was reduced by 30 to 40 percent of the control when pH and partial pressures of oxygen (PO2) and carbon dioxide (CO2) were kept within normal limits. When respiratory failure was produced by hypoventilation (pH 7.05 to 7.25; PC02 70 to 100 mm Hg: P02 20 to 40 mm Hg), infusion of aminophylline resulted in an even greater decrease in ventricular fibrillation threshold to 60 percent of the control level. These experiments suggest that although many factors may contribute to the increased incidence of ventricular arrhythmias in respiratory failure, pharmacologic agents, particularly aminophylline, may play a significant role.", "entity": "Carbon Dioxide", "aliases": "Anhydride Carbonic Carbon Dioxide", "definition": "A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals.\n    ", "id": "MESH:D002245"}
{"mention": "hypoventilation", "mention_text": "Cardiac arrhythmias have frequently been reported in association with respiratory failure. The possible additive role of pharmacologic agents in precipitating cardiac disturbances in patients with respiratory failure has only recently been emphasized. The effects of aminophylline on the ventricular fibrillation threshold during normal acid-base conditions and during respiratory failure were studied in anesthetized open chest dogs. The ventricular fibrillation threshold was measured by passing a gated train of 12 constant current pulses through the ventricular myocardium during the vulnerable period of the cardiac cycle. During the infusion of aminophylline, the ventricular fibrillation threshold was reduced by 30 to 40 percent of the control when pH and partial pressures of oxygen (PO2) and carbon dioxide (CO2) were kept within normal limits. When respiratory failure was produced by hypoventilation (pH 7.05 to 7.25; PC02 70 to 100 mm Hg: P02 20 to 40 mm Hg), infusion of aminophylline resulted in an even greater decrease in ventricular fibrillation threshold to 60 percent of the control level. These experiments suggest that although many factors may contribute to the increased incidence of ventricular arrhythmias in respiratory failure, pharmacologic agents, particularly aminophylline, may play a significant role.", "entity": "Hypoventilation", "aliases": "Hypoventilation Hypoventilations", "definition": "A reduction in the amount of air entering the pulmonary alveoli.\n    ", "id": "MESH:D007040"}
{"mention": "ventricular arrhythmias", "mention_text": "Cardiac arrhythmias have frequently been reported in association with respiratory failure. The possible additive role of pharmacologic agents in precipitating cardiac disturbances in patients with respiratory failure has only recently been emphasized. The effects of aminophylline on the ventricular fibrillation threshold during normal acid-base conditions and during respiratory failure were studied in anesthetized open chest dogs. The ventricular fibrillation threshold was measured by passing a gated train of 12 constant current pulses through the ventricular myocardium during the vulnerable period of the cardiac cycle. During the infusion of aminophylline, the ventricular fibrillation threshold was reduced by 30 to 40 percent of the control when pH and partial pressures of oxygen (PO2) and carbon dioxide (CO2) were kept within normal limits. When respiratory failure was produced by hypoventilation (pH 7.05 to 7.25; PC02 70 to 100 mm Hg: P02 20 to 40 mm Hg), infusion of aminophylline resulted in an even greater decrease in ventricular fibrillation threshold to 60 percent of the control level. These experiments suggest that although many factors may contribute to the increased incidence of ventricular arrhythmias in respiratory failure, pharmacologic agents, particularly aminophylline, may play a significant role.", "entity": "Arrhythmias, Cardiac", "aliases": "Arrhythmia Cardiac Arrhythmias Arrythmia Dysrhythmia", "definition": "Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.\n    ", "id": "MESH:D001145"}
{"mention": "carbachol", "mention_text": "Case report: acute unintentional carbachol intoxication.", "entity": "Carbachol", "aliases": "Alcon Brand 1 of Carbachol 2 Allphar Bioniche Bipharma Isopto Carbacholine Carbamann Carbamoylcholine Carbamylcholine Carbastat Carbocholine Carboptic Chauvin Doryl Jestryl Mann Merck Miostat Novartis NutraMax Optopics", "definition": "A slowly hydrolyzed cholinergic agonist that acts at both muscarinic and nicotinic receptors.\n    ", "id": "MESH:D002217"}
{"mention": "carbachol", "mention_text": "INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.", "entity": "Carbachol", "aliases": "Alcon Brand 1 of Carbachol 2 Allphar Bioniche Bipharma Isopto Carbacholine Carbamann Carbamoylcholine Carbamylcholine Carbastat Carbocholine Carboptic Chauvin Doryl Jestryl Mann Merck Miostat Novartis NutraMax Optopics", "definition": "A slowly hydrolyzed cholinergic agonist that acts at both muscarinic and nicotinic receptors.\n    ", "id": "MESH:D002217"}
{"mention": "poisoning", "mention_text": "INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.", "entity": "Poisoning", "aliases": "Poisoning Poisonings", "definition": "A condition or physical state produced by the ingestion, injection, inhalation of or exposure to a deleterious agent.\n    ", "id": "MESH:D011041"}
{"mention": "Alzheimer's disease", "mention_text": "INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.", "entity": "Alzheimer Disease", "aliases": "Acute Confusional Senile Dementia Alzheimer (AD) Disease Early Onset Late Sclerosis Syndrome Type (ATD) Alzheimer's Focal Alzheimer-Type Presenile Primary Degenerative Familial (FAD)", "definition": "A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)\n    ", "id": "MESH:D000544"}
{"mention": "carbamylcholin", "mention_text": "INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.", "entity": "Carbachol", "aliases": "Alcon Brand 1 of Carbachol 2 Allphar Bioniche Bipharma Isopto Carbacholine Carbamann Carbamoylcholine Carbamylcholine Carbastat Carbocholine Carboptic Chauvin Doryl Jestryl Mann Merck Miostat Novartis NutraMax Optopics", "definition": "A slowly hydrolyzed cholinergic agonist that acts at both muscarinic and nicotinic receptors.\n    ", "id": "MESH:D002217"}
{"mention": "Carbachol", "mention_text": "INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.", "entity": "Carbachol", "aliases": "Alcon Brand 1 of Carbachol 2 Allphar Bioniche Bipharma Isopto Carbacholine Carbamann Carbamoylcholine Carbamylcholine Carbastat Carbocholine Carboptic Chauvin Doryl Jestryl Mann Merck Miostat Novartis NutraMax Optopics", "definition": "A slowly hydrolyzed cholinergic agonist that acts at both muscarinic and nicotinic receptors.\n    ", "id": "MESH:D002217"}
{"mention": "nausea", "mention_text": "INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.", "entity": "Nausea", "aliases": "Nausea", "definition": "An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.\n    ", "id": "MESH:D009325"}
{"mention": "hypotension", "mention_text": "INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "Bradycardia", "mention_text": "INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.", "entity": "Bradycardia", "aliases": "Bradyarrhythmia Bradyarrhythmias Bradycardia Bradycardias", "definition": "Cardiac arrhythmias that are characterized by excessively slow HEART RATE, usually below 50 beats per minute in human adults. They can be classified broadly into SINOATRIAL NODE dysfunction and ATRIOVENTRICULAR BLOCK.\n    ", "id": "MESH:D001919"}
{"mention": "asystole", "mention_text": "INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.", "entity": "Heart Arrest", "aliases": "Arrest Cardiac Cardiopulmonary Heart Asystole Asystoles", "definition": "Cessation of heart beat or MYOCARDIAL CONTRACTION. If it is treated within a few minutes, heart arrest can be reversed in most cases to normal cardiac rhythm and effective circulation.\n    ", "id": "MESH:D006323"}
{"mention": "adrenaline", "mention_text": "INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.", "entity": "Epinephrine", "aliases": "4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-benzenediol Acetate Epinephrine Adrenaline Acid Tartrate Bitartrate Hydrochloride Allergan Brand of Epifrin Hydrogen Epitrate Lyophrin Medihaler-Epi", "definition": "The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.\n    ", "id": "MESH:D004837"}
{"mention": "epinephrine", "mention_text": "INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.", "entity": "Epinephrine", "aliases": "4-(1-Hydroxy-2-(methylamino)ethyl)-1,2-benzenediol Acetate Epinephrine Adrenaline Acid Tartrate Bitartrate Hydrochloride Allergan Brand of Epifrin Hydrogen Epitrate Lyophrin Medihaler-Epi", "definition": "The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.\n    ", "id": "MESH:D004837"}
{"mention": "atropine", "mention_text": "INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.", "entity": "Atropine", "aliases": "Anhydrous Atropine Sulfate AtroPen Atropin Augenöl Chauvin Brand Winzer Atropinol of Survival Technology", "definition": "An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.\n    ", "id": "MESH:D001285"}
{"mention": "furosemide", "mention_text": "INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.", "entity": "Furosemide", "aliases": "Errolon Frusemid Frusemide Furanthril Furantral Furosemide Monohydrochloride Monosodium Salt Fursemide Fusid Lasix Salix (brand of furosemide)", "definition": "A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for EDEMA and chronic RENAL INSUFFICIENCY.\n    ", "id": "MESH:D005665"}
{"mention": "hyperhidrosis", "mention_text": "INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.", "entity": "Hyperhidrosis", "aliases": "Hyperhidrosis", "definition": "Excessive sweating. In the localized type, the most frequent sites are the palms, soles, axillae, inguinal folds, and the perineal area. Its chief cause is thought to be emotional. Generalized hyperhidrosis may be induced by a hot, humid environment, by fever, or by vigorous exercise.\n    ", "id": "MESH:D006945"}
{"mention": "hypersalivation", "mention_text": "INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.", "entity": "Sialorrhea", "aliases": "Drooling Hypersalivation Sialorrhea", "definition": "Increased salivary flow.\n    ", "id": "MESH:D012798"}
{"mention": "miosis", "mention_text": "INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.", "entity": "Miosis", "aliases": "Constricted Pupil Pupils Mioses Persistent Pupillary Miosis Small", "definition": "Pupillary constriction. This may result from congenital absence of the dilatator pupillary muscle, defective sympathetic innervation, or irritation of the CONJUNCTIVA or CORNEA.\n    ", "id": "MESH:D015877"}
{"mention": "atrio-ventricular dissociation", "mention_text": "INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.", "entity": "Heart Block", "aliases": "A V Dissociation A-V Dissociations Atrioventricular Auriculo Ventricular Auriculo-Ventricular Block Heart Blocks", "definition": "Impaired conduction of cardiac impulse that can occur anywhere along the conduction pathway, such as between the SINOATRIAL NODE and the right atrium (SA block) or between atria and ventricles (AV block). Heart blocks can be classified by the duration, frequency, or completeness of conduction block. Reversibility depends on the degree of structural or functional defects.\n    ", "id": "MESH:D006327"}
{"mention": "dopamine", "mention_text": "INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "dyspnoea", "mention_text": "INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.", "entity": "Dyspnea", "aliases": "Breath Shortness Shortnesses Breathlessness Breathlessnesses Dyspnea Dyspneas of", "definition": "Difficult or labored breathing.\n    ", "id": "MESH:D004417"}
{"mention": "bronchospasm", "mention_text": "INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.", "entity": "Bronchial Spasm", "aliases": "Bronchial Spasm Spasms Bronchospasm Bronchospasms", "definition": "Spasmodic contraction of the smooth muscle of the bronchi.\n    ", "id": "MESH:D001986"}
{"mention": "Respiratory insufficiency", "mention_text": "INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.", "entity": "Respiratory Insufficiency", "aliases": "Depressions Ventilatory Respiratory Depression Failure Insufficiency", "definition": "Failure to adequately provide oxygen to cells of the body and to remove excess carbon dioxide from them. (Stedman, 25th ed)\n    ", "id": "MESH:D012131"}
{"mention": "Proteus mirabilis infection", "mention_text": "INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.", "entity": "Proteus Infections", "aliases": "Infection Proteus Infections", "definition": "Infections with bacteria of the genus PROTEUS.\n    ", "id": "MESH:D011512"}
{"mention": "heart failure", "mention_text": "INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.", "entity": "Heart Failure", "aliases": "Cardiac Failure Congestive Heart Decompensation Left Sided Left-Sided Right Right-Sided Myocardial", "definition": "A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.\n    ", "id": "MESH:D006333"}
{"mention": "acute cardiovascular failure", "mention_text": "INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.", "entity": "Cardiovascular Diseases", "aliases": "Cardiovascular Disease Diseases", "definition": "Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.\n    ", "id": "MESH:D002318"}
{"mention": "rizatriptan", "mention_text": "Crossover comparison of efficacy and preference for rizatriptan 10 mg versus ergotamine/caffeine in migraine.", "entity": "rizatriptan", "aliases": "L 705,126 705126 L-705,126 L-705126 MK 0462 462 MK-0462 MK-462 Maxalt N,N-dimethyl-2-(5-(1,2,4-triazol-1-ylmethyl)-1H-indole-3-yl)ethylamine rizatriptan benzoate", "definition": "", "id": "MESH:C093622"}
{"mention": "ergotamine", "mention_text": "Crossover comparison of efficacy and preference for rizatriptan 10 mg versus ergotamine/caffeine in migraine.", "entity": "Ergotamine", "aliases": "Cornutamine Ergo Kranit Ergo-Kranit ErgoKranit Ergodryl Mono Ergomar Ergostat Ergotamine Tartrate (2:1) Ergotaminine Gynergen Krewel Brand of Lingraine Lotus Pfizer Sanofi Winthrop ergo sanol", "definition": "A vasoconstrictor found in ergot of Central Europe. It is a serotonin agonist that has been used as an oxytocic agent and in the treatment of MIGRAINE DISORDERS.\n    ", "id": "MESH:D004878"}
{"mention": "caffeine", "mention_text": "Crossover comparison of efficacy and preference for rizatriptan 10 mg versus ergotamine/caffeine in migraine.", "entity": "Caffeine", "aliases": "1,3,7-Trimethylxanthine Berlin-Chemie Brand of Caffeine Bristol-Myers Squibb Caffedrine Coffeinum N Purrum Dexitac Durvitan GlaxoSmithKline Merck dura No Doz Passauer Percoffedrinol Percutaféine Pierre Fabre Quick-Pep Republic Drug Seid Thompson 1 2 Vivarin", "definition": "A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling.\n    ", "id": "MESH:D002110"}
{"mention": "migraine", "mention_text": "Crossover comparison of efficacy and preference for rizatriptan 10 mg versus ergotamine/caffeine in migraine.", "entity": "Migraine Disorders", "aliases": "Abdominal Migraine Migraines Acute Confusional Cervical Syndrome Syndromes Disorder Disorders Headache Sick Headaches Hemicrania Variant Variants Status Migrainosus", "definition": "A class of disabling primary headache disorders, characterized by recurrent unilateral pulsatile headaches. The two major subtypes are common migraine (without aura) and classic migraine (with aura or neurological symptoms). (International Classification of Headache Disorders, 2nd ed. Cephalalgia 2004: suppl 1)\n    ", "id": "MESH:D008881"}
{"mention": "Rizatriptan", "mention_text": "Rizatriptan is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized double- blind crossover outpatient study assessed the preference for 1 rizatriptan 10 mg tablet to 2 ergotamine 1 mg/caffeine 100 mg tablets in 439 patients treating a single migraine attack with each therapy. Of patients expressing a preference (89.1%), more than twice as many preferred rizatriptan to ergotamine/caffeine (69.9 vs. 30.1%, p < or = 0.001). Faster relief of headache was the most important reason for preference, cited by 67.3% of patients preferring rizatriptan and 54.2% of patients who preferred ergotamine/caffeine. The co-primary endpoint of being pain free at 2 h was also in favor of rizatriptan. Forty-nine percent of patients were pain free 2 h after rizatriptan, compared with 24.3% treated with ergotamine/caffeine (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Headache relief at 2 h was 75.9% for rizatriptan and 47.3% for ergotamine/caffeine (p < or = 0.001), with rizatriptan being superior to ergotamine/caffeine within 30 min of dosing. Almost 36% of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication within 24 h, compared to 20% of patients on ergotamine/caffeine (p < or = 0.001). Rizatriptan was also superior to ergotamine/caffeine in the proportions of patients with no nausea, vomiting, phonophobia or photophobia and for patients with normal function 2 h after drug intake (p < or = 0.001). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (69.8%) than at 2 h after treatment with ergotamine/caffeine (38.6%, p < or = 0.001). Recurrence rates were 31.4% with rizatriptan and 15.3% with ergotamine/caffeine. Both active treatments were well tolerated. The most common adverse events (incidence > or = 5% in one group) after rizatriptan and ergotamine/caffeine, respectively, were dizziness (6.7 and 5.3%), nausea (4.2 and 8.5%) and somnolence (5.5 and 2.3%).", "entity": "rizatriptan", "aliases": "L 705,126 705126 L-705,126 L-705126 MK 0462 462 MK-0462 MK-462 Maxalt N,N-dimethyl-2-(5-(1,2,4-triazol-1-ylmethyl)-1H-indole-3-yl)ethylamine rizatriptan benzoate", "definition": "", "id": "MESH:C093622"}
{"mention": "5-HT", "mention_text": "Rizatriptan is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized double- blind crossover outpatient study assessed the preference for 1 rizatriptan 10 mg tablet to 2 ergotamine 1 mg/caffeine 100 mg tablets in 439 patients treating a single migraine attack with each therapy. Of patients expressing a preference (89.1%), more than twice as many preferred rizatriptan to ergotamine/caffeine (69.9 vs. 30.1%, p < or = 0.001). Faster relief of headache was the most important reason for preference, cited by 67.3% of patients preferring rizatriptan and 54.2% of patients who preferred ergotamine/caffeine. The co-primary endpoint of being pain free at 2 h was also in favor of rizatriptan. Forty-nine percent of patients were pain free 2 h after rizatriptan, compared with 24.3% treated with ergotamine/caffeine (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Headache relief at 2 h was 75.9% for rizatriptan and 47.3% for ergotamine/caffeine (p < or = 0.001), with rizatriptan being superior to ergotamine/caffeine within 30 min of dosing. Almost 36% of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication within 24 h, compared to 20% of patients on ergotamine/caffeine (p < or = 0.001). Rizatriptan was also superior to ergotamine/caffeine in the proportions of patients with no nausea, vomiting, phonophobia or photophobia and for patients with normal function 2 h after drug intake (p < or = 0.001). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (69.8%) than at 2 h after treatment with ergotamine/caffeine (38.6%, p < or = 0.001). Recurrence rates were 31.4% with rizatriptan and 15.3% with ergotamine/caffeine. Both active treatments were well tolerated. The most common adverse events (incidence > or = 5% in one group) after rizatriptan and ergotamine/caffeine, respectively, were dizziness (6.7 and 5.3%), nausea (4.2 and 8.5%) and somnolence (5.5 and 2.3%).", "entity": "Serotonin", "aliases": "3-(2-Aminoethyl)-1H-indol-5-ol 5 Hydroxytryptamine 5-HT 5-Hydroxytryptamine Enteramine Hippophaine Serotonin", "definition": "A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.\n    ", "id": "MESH:D012701"}
{"mention": "migraine", "mention_text": "Rizatriptan is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized double- blind crossover outpatient study assessed the preference for 1 rizatriptan 10 mg tablet to 2 ergotamine 1 mg/caffeine 100 mg tablets in 439 patients treating a single migraine attack with each therapy. Of patients expressing a preference (89.1%), more than twice as many preferred rizatriptan to ergotamine/caffeine (69.9 vs. 30.1%, p < or = 0.001). Faster relief of headache was the most important reason for preference, cited by 67.3% of patients preferring rizatriptan and 54.2% of patients who preferred ergotamine/caffeine. The co-primary endpoint of being pain free at 2 h was also in favor of rizatriptan. Forty-nine percent of patients were pain free 2 h after rizatriptan, compared with 24.3% treated with ergotamine/caffeine (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Headache relief at 2 h was 75.9% for rizatriptan and 47.3% for ergotamine/caffeine (p < or = 0.001), with rizatriptan being superior to ergotamine/caffeine within 30 min of dosing. Almost 36% of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication within 24 h, compared to 20% of patients on ergotamine/caffeine (p < or = 0.001). Rizatriptan was also superior to ergotamine/caffeine in the proportions of patients with no nausea, vomiting, phonophobia or photophobia and for patients with normal function 2 h after drug intake (p < or = 0.001). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (69.8%) than at 2 h after treatment with ergotamine/caffeine (38.6%, p < or = 0.001). Recurrence rates were 31.4% with rizatriptan and 15.3% with ergotamine/caffeine. Both active treatments were well tolerated. The most common adverse events (incidence > or = 5% in one group) after rizatriptan and ergotamine/caffeine, respectively, were dizziness (6.7 and 5.3%), nausea (4.2 and 8.5%) and somnolence (5.5 and 2.3%).", "entity": "Migraine Disorders", "aliases": "Abdominal Migraine Migraines Acute Confusional Cervical Syndrome Syndromes Disorder Disorders Headache Sick Headaches Hemicrania Variant Variants Status Migrainosus", "definition": "A class of disabling primary headache disorders, characterized by recurrent unilateral pulsatile headaches. The two major subtypes are common migraine (without aura) and classic migraine (with aura or neurological symptoms). (International Classification of Headache Disorders, 2nd ed. Cephalalgia 2004: suppl 1)\n    ", "id": "MESH:D008881"}
{"mention": "rizatriptan", "mention_text": "Rizatriptan is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized double- blind crossover outpatient study assessed the preference for 1 rizatriptan 10 mg tablet to 2 ergotamine 1 mg/caffeine 100 mg tablets in 439 patients treating a single migraine attack with each therapy. Of patients expressing a preference (89.1%), more than twice as many preferred rizatriptan to ergotamine/caffeine (69.9 vs. 30.1%, p < or = 0.001). Faster relief of headache was the most important reason for preference, cited by 67.3% of patients preferring rizatriptan and 54.2% of patients who preferred ergotamine/caffeine. The co-primary endpoint of being pain free at 2 h was also in favor of rizatriptan. Forty-nine percent of patients were pain free 2 h after rizatriptan, compared with 24.3% treated with ergotamine/caffeine (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Headache relief at 2 h was 75.9% for rizatriptan and 47.3% for ergotamine/caffeine (p < or = 0.001), with rizatriptan being superior to ergotamine/caffeine within 30 min of dosing. Almost 36% of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication within 24 h, compared to 20% of patients on ergotamine/caffeine (p < or = 0.001). Rizatriptan was also superior to ergotamine/caffeine in the proportions of patients with no nausea, vomiting, phonophobia or photophobia and for patients with normal function 2 h after drug intake (p < or = 0.001). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (69.8%) than at 2 h after treatment with ergotamine/caffeine (38.6%, p < or = 0.001). Recurrence rates were 31.4% with rizatriptan and 15.3% with ergotamine/caffeine. Both active treatments were well tolerated. The most common adverse events (incidence > or = 5% in one group) after rizatriptan and ergotamine/caffeine, respectively, were dizziness (6.7 and 5.3%), nausea (4.2 and 8.5%) and somnolence (5.5 and 2.3%).", "entity": "rizatriptan", "aliases": "L 705,126 705126 L-705,126 L-705126 MK 0462 462 MK-0462 MK-462 Maxalt N,N-dimethyl-2-(5-(1,2,4-triazol-1-ylmethyl)-1H-indole-3-yl)ethylamine rizatriptan benzoate", "definition": "", "id": "MESH:C093622"}
{"mention": "ergotamine", "mention_text": "Rizatriptan is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized double- blind crossover outpatient study assessed the preference for 1 rizatriptan 10 mg tablet to 2 ergotamine 1 mg/caffeine 100 mg tablets in 439 patients treating a single migraine attack with each therapy. Of patients expressing a preference (89.1%), more than twice as many preferred rizatriptan to ergotamine/caffeine (69.9 vs. 30.1%, p < or = 0.001). Faster relief of headache was the most important reason for preference, cited by 67.3% of patients preferring rizatriptan and 54.2% of patients who preferred ergotamine/caffeine. The co-primary endpoint of being pain free at 2 h was also in favor of rizatriptan. Forty-nine percent of patients were pain free 2 h after rizatriptan, compared with 24.3% treated with ergotamine/caffeine (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Headache relief at 2 h was 75.9% for rizatriptan and 47.3% for ergotamine/caffeine (p < or = 0.001), with rizatriptan being superior to ergotamine/caffeine within 30 min of dosing. Almost 36% of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication within 24 h, compared to 20% of patients on ergotamine/caffeine (p < or = 0.001). Rizatriptan was also superior to ergotamine/caffeine in the proportions of patients with no nausea, vomiting, phonophobia or photophobia and for patients with normal function 2 h after drug intake (p < or = 0.001). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (69.8%) than at 2 h after treatment with ergotamine/caffeine (38.6%, p < or = 0.001). Recurrence rates were 31.4% with rizatriptan and 15.3% with ergotamine/caffeine. Both active treatments were well tolerated. The most common adverse events (incidence > or = 5% in one group) after rizatriptan and ergotamine/caffeine, respectively, were dizziness (6.7 and 5.3%), nausea (4.2 and 8.5%) and somnolence (5.5 and 2.3%).", "entity": "Ergotamine", "aliases": "Cornutamine Ergo Kranit Ergo-Kranit ErgoKranit Ergodryl Mono Ergomar Ergostat Ergotamine Tartrate (2:1) Ergotaminine Gynergen Krewel Brand of Lingraine Lotus Pfizer Sanofi Winthrop ergo sanol", "definition": "A vasoconstrictor found in ergot of Central Europe. It is a serotonin agonist that has been used as an oxytocic agent and in the treatment of MIGRAINE DISORDERS.\n    ", "id": "MESH:D004878"}
{"mention": "caffeine", "mention_text": "Rizatriptan is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized double- blind crossover outpatient study assessed the preference for 1 rizatriptan 10 mg tablet to 2 ergotamine 1 mg/caffeine 100 mg tablets in 439 patients treating a single migraine attack with each therapy. Of patients expressing a preference (89.1%), more than twice as many preferred rizatriptan to ergotamine/caffeine (69.9 vs. 30.1%, p < or = 0.001). Faster relief of headache was the most important reason for preference, cited by 67.3% of patients preferring rizatriptan and 54.2% of patients who preferred ergotamine/caffeine. The co-primary endpoint of being pain free at 2 h was also in favor of rizatriptan. Forty-nine percent of patients were pain free 2 h after rizatriptan, compared with 24.3% treated with ergotamine/caffeine (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Headache relief at 2 h was 75.9% for rizatriptan and 47.3% for ergotamine/caffeine (p < or = 0.001), with rizatriptan being superior to ergotamine/caffeine within 30 min of dosing. Almost 36% of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication within 24 h, compared to 20% of patients on ergotamine/caffeine (p < or = 0.001). Rizatriptan was also superior to ergotamine/caffeine in the proportions of patients with no nausea, vomiting, phonophobia or photophobia and for patients with normal function 2 h after drug intake (p < or = 0.001). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (69.8%) than at 2 h after treatment with ergotamine/caffeine (38.6%, p < or = 0.001). Recurrence rates were 31.4% with rizatriptan and 15.3% with ergotamine/caffeine. Both active treatments were well tolerated. The most common adverse events (incidence > or = 5% in one group) after rizatriptan and ergotamine/caffeine, respectively, were dizziness (6.7 and 5.3%), nausea (4.2 and 8.5%) and somnolence (5.5 and 2.3%).", "entity": "Caffeine", "aliases": "1,3,7-Trimethylxanthine Berlin-Chemie Brand of Caffeine Bristol-Myers Squibb Caffedrine Coffeinum N Purrum Dexitac Durvitan GlaxoSmithKline Merck dura No Doz Passauer Percoffedrinol Percutaféine Pierre Fabre Quick-Pep Republic Drug Seid Thompson 1 2 Vivarin", "definition": "A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling.\n    ", "id": "MESH:D002110"}
{"mention": "headache", "mention_text": "Rizatriptan is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized double- blind crossover outpatient study assessed the preference for 1 rizatriptan 10 mg tablet to 2 ergotamine 1 mg/caffeine 100 mg tablets in 439 patients treating a single migraine attack with each therapy. Of patients expressing a preference (89.1%), more than twice as many preferred rizatriptan to ergotamine/caffeine (69.9 vs. 30.1%, p < or = 0.001). Faster relief of headache was the most important reason for preference, cited by 67.3% of patients preferring rizatriptan and 54.2% of patients who preferred ergotamine/caffeine. The co-primary endpoint of being pain free at 2 h was also in favor of rizatriptan. Forty-nine percent of patients were pain free 2 h after rizatriptan, compared with 24.3% treated with ergotamine/caffeine (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Headache relief at 2 h was 75.9% for rizatriptan and 47.3% for ergotamine/caffeine (p < or = 0.001), with rizatriptan being superior to ergotamine/caffeine within 30 min of dosing. Almost 36% of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication within 24 h, compared to 20% of patients on ergotamine/caffeine (p < or = 0.001). Rizatriptan was also superior to ergotamine/caffeine in the proportions of patients with no nausea, vomiting, phonophobia or photophobia and for patients with normal function 2 h after drug intake (p < or = 0.001). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (69.8%) than at 2 h after treatment with ergotamine/caffeine (38.6%, p < or = 0.001). Recurrence rates were 31.4% with rizatriptan and 15.3% with ergotamine/caffeine. Both active treatments were well tolerated. The most common adverse events (incidence > or = 5% in one group) after rizatriptan and ergotamine/caffeine, respectively, were dizziness (6.7 and 5.3%), nausea (4.2 and 8.5%) and somnolence (5.5 and 2.3%).", "entity": "Headache", "aliases": "Bilateral Headache Headaches Cephalalgia Cephalalgias Cephalgia Cephalgias Cephalodynia Cephalodynias Cranial Pain Pains Generalized Head Ocular Orthostatic Periorbital Retro-Ocular Sharp Throbbing Unilateral Vertex Hemicrania Retro", "definition": "The symptom of PAIN in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of HEADACHE DISORDERS.\n    ", "id": "MESH:D006261"}
{"mention": "pain", "mention_text": "Rizatriptan is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized double- blind crossover outpatient study assessed the preference for 1 rizatriptan 10 mg tablet to 2 ergotamine 1 mg/caffeine 100 mg tablets in 439 patients treating a single migraine attack with each therapy. Of patients expressing a preference (89.1%), more than twice as many preferred rizatriptan to ergotamine/caffeine (69.9 vs. 30.1%, p < or = 0.001). Faster relief of headache was the most important reason for preference, cited by 67.3% of patients preferring rizatriptan and 54.2% of patients who preferred ergotamine/caffeine. The co-primary endpoint of being pain free at 2 h was also in favor of rizatriptan. Forty-nine percent of patients were pain free 2 h after rizatriptan, compared with 24.3% treated with ergotamine/caffeine (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Headache relief at 2 h was 75.9% for rizatriptan and 47.3% for ergotamine/caffeine (p < or = 0.001), with rizatriptan being superior to ergotamine/caffeine within 30 min of dosing. Almost 36% of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication within 24 h, compared to 20% of patients on ergotamine/caffeine (p < or = 0.001). Rizatriptan was also superior to ergotamine/caffeine in the proportions of patients with no nausea, vomiting, phonophobia or photophobia and for patients with normal function 2 h after drug intake (p < or = 0.001). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (69.8%) than at 2 h after treatment with ergotamine/caffeine (38.6%, p < or = 0.001). Recurrence rates were 31.4% with rizatriptan and 15.3% with ergotamine/caffeine. Both active treatments were well tolerated. The most common adverse events (incidence > or = 5% in one group) after rizatriptan and ergotamine/caffeine, respectively, were dizziness (6.7 and 5.3%), nausea (4.2 and 8.5%) and somnolence (5.5 and 2.3%).", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "Headache", "mention_text": "Rizatriptan is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized double- blind crossover outpatient study assessed the preference for 1 rizatriptan 10 mg tablet to 2 ergotamine 1 mg/caffeine 100 mg tablets in 439 patients treating a single migraine attack with each therapy. Of patients expressing a preference (89.1%), more than twice as many preferred rizatriptan to ergotamine/caffeine (69.9 vs. 30.1%, p < or = 0.001). Faster relief of headache was the most important reason for preference, cited by 67.3% of patients preferring rizatriptan and 54.2% of patients who preferred ergotamine/caffeine. The co-primary endpoint of being pain free at 2 h was also in favor of rizatriptan. Forty-nine percent of patients were pain free 2 h after rizatriptan, compared with 24.3% treated with ergotamine/caffeine (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Headache relief at 2 h was 75.9% for rizatriptan and 47.3% for ergotamine/caffeine (p < or = 0.001), with rizatriptan being superior to ergotamine/caffeine within 30 min of dosing. Almost 36% of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication within 24 h, compared to 20% of patients on ergotamine/caffeine (p < or = 0.001). Rizatriptan was also superior to ergotamine/caffeine in the proportions of patients with no nausea, vomiting, phonophobia or photophobia and for patients with normal function 2 h after drug intake (p < or = 0.001). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (69.8%) than at 2 h after treatment with ergotamine/caffeine (38.6%, p < or = 0.001). Recurrence rates were 31.4% with rizatriptan and 15.3% with ergotamine/caffeine. Both active treatments were well tolerated. The most common adverse events (incidence > or = 5% in one group) after rizatriptan and ergotamine/caffeine, respectively, were dizziness (6.7 and 5.3%), nausea (4.2 and 8.5%) and somnolence (5.5 and 2.3%).", "entity": "Headache", "aliases": "Bilateral Headache Headaches Cephalalgia Cephalalgias Cephalgia Cephalgias Cephalodynia Cephalodynias Cranial Pain Pains Generalized Head Ocular Orthostatic Periorbital Retro-Ocular Sharp Throbbing Unilateral Vertex Hemicrania Retro", "definition": "The symptom of PAIN in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of HEADACHE DISORDERS.\n    ", "id": "MESH:D006261"}
{"mention": "nausea", "mention_text": "Rizatriptan is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized double- blind crossover outpatient study assessed the preference for 1 rizatriptan 10 mg tablet to 2 ergotamine 1 mg/caffeine 100 mg tablets in 439 patients treating a single migraine attack with each therapy. Of patients expressing a preference (89.1%), more than twice as many preferred rizatriptan to ergotamine/caffeine (69.9 vs. 30.1%, p < or = 0.001). Faster relief of headache was the most important reason for preference, cited by 67.3% of patients preferring rizatriptan and 54.2% of patients who preferred ergotamine/caffeine. The co-primary endpoint of being pain free at 2 h was also in favor of rizatriptan. Forty-nine percent of patients were pain free 2 h after rizatriptan, compared with 24.3% treated with ergotamine/caffeine (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Headache relief at 2 h was 75.9% for rizatriptan and 47.3% for ergotamine/caffeine (p < or = 0.001), with rizatriptan being superior to ergotamine/caffeine within 30 min of dosing. Almost 36% of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication within 24 h, compared to 20% of patients on ergotamine/caffeine (p < or = 0.001). Rizatriptan was also superior to ergotamine/caffeine in the proportions of patients with no nausea, vomiting, phonophobia or photophobia and for patients with normal function 2 h after drug intake (p < or = 0.001). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (69.8%) than at 2 h after treatment with ergotamine/caffeine (38.6%, p < or = 0.001). Recurrence rates were 31.4% with rizatriptan and 15.3% with ergotamine/caffeine. Both active treatments were well tolerated. The most common adverse events (incidence > or = 5% in one group) after rizatriptan and ergotamine/caffeine, respectively, were dizziness (6.7 and 5.3%), nausea (4.2 and 8.5%) and somnolence (5.5 and 2.3%).", "entity": "Nausea", "aliases": "Nausea", "definition": "An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.\n    ", "id": "MESH:D009325"}
{"mention": "vomiting", "mention_text": "Rizatriptan is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized double- blind crossover outpatient study assessed the preference for 1 rizatriptan 10 mg tablet to 2 ergotamine 1 mg/caffeine 100 mg tablets in 439 patients treating a single migraine attack with each therapy. Of patients expressing a preference (89.1%), more than twice as many preferred rizatriptan to ergotamine/caffeine (69.9 vs. 30.1%, p < or = 0.001). Faster relief of headache was the most important reason for preference, cited by 67.3% of patients preferring rizatriptan and 54.2% of patients who preferred ergotamine/caffeine. The co-primary endpoint of being pain free at 2 h was also in favor of rizatriptan. Forty-nine percent of patients were pain free 2 h after rizatriptan, compared with 24.3% treated with ergotamine/caffeine (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Headache relief at 2 h was 75.9% for rizatriptan and 47.3% for ergotamine/caffeine (p < or = 0.001), with rizatriptan being superior to ergotamine/caffeine within 30 min of dosing. Almost 36% of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication within 24 h, compared to 20% of patients on ergotamine/caffeine (p < or = 0.001). Rizatriptan was also superior to ergotamine/caffeine in the proportions of patients with no nausea, vomiting, phonophobia or photophobia and for patients with normal function 2 h after drug intake (p < or = 0.001). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (69.8%) than at 2 h after treatment with ergotamine/caffeine (38.6%, p < or = 0.001). Recurrence rates were 31.4% with rizatriptan and 15.3% with ergotamine/caffeine. Both active treatments were well tolerated. The most common adverse events (incidence > or = 5% in one group) after rizatriptan and ergotamine/caffeine, respectively, were dizziness (6.7 and 5.3%), nausea (4.2 and 8.5%) and somnolence (5.5 and 2.3%).", "entity": "Vomiting", "aliases": "Emesis Vomiting", "definition": "The forcible expulsion of the contents of the STOMACH through the MOUTH.\n    ", "id": "MESH:D014839"}
{"mention": "phonophobia", "mention_text": "Rizatriptan is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized double- blind crossover outpatient study assessed the preference for 1 rizatriptan 10 mg tablet to 2 ergotamine 1 mg/caffeine 100 mg tablets in 439 patients treating a single migraine attack with each therapy. Of patients expressing a preference (89.1%), more than twice as many preferred rizatriptan to ergotamine/caffeine (69.9 vs. 30.1%, p < or = 0.001). Faster relief of headache was the most important reason for preference, cited by 67.3% of patients preferring rizatriptan and 54.2% of patients who preferred ergotamine/caffeine. The co-primary endpoint of being pain free at 2 h was also in favor of rizatriptan. Forty-nine percent of patients were pain free 2 h after rizatriptan, compared with 24.3% treated with ergotamine/caffeine (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Headache relief at 2 h was 75.9% for rizatriptan and 47.3% for ergotamine/caffeine (p < or = 0.001), with rizatriptan being superior to ergotamine/caffeine within 30 min of dosing. Almost 36% of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication within 24 h, compared to 20% of patients on ergotamine/caffeine (p < or = 0.001). Rizatriptan was also superior to ergotamine/caffeine in the proportions of patients with no nausea, vomiting, phonophobia or photophobia and for patients with normal function 2 h after drug intake (p < or = 0.001). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (69.8%) than at 2 h after treatment with ergotamine/caffeine (38.6%, p < or = 0.001). Recurrence rates were 31.4% with rizatriptan and 15.3% with ergotamine/caffeine. Both active treatments were well tolerated. The most common adverse events (incidence > or = 5% in one group) after rizatriptan and ergotamine/caffeine, respectively, were dizziness (6.7 and 5.3%), nausea (4.2 and 8.5%) and somnolence (5.5 and 2.3%).", "entity": "Hyperacusis", "aliases": "Auditory Hyperesthesia Hyperesthesias Disturbance Loudness Perception Disturbances Hyperacuses Hyperacusia Hyperacusias Hyperacusis Recruitment Recruitments Phonophobia Phonophobias", "definition": "An abnormally disproportionate increase in the sensation of loudness in response to auditory stimuli of normal volume. COCHLEAR DISEASES; VESTIBULOCOCHLEAR NERVE DISEASES; FACIAL NERVE DISEASES; STAPES SURGERY; and other disorders may be associated with this condition.\n    ", "id": "MESH:D012001"}
{"mention": "photophobia", "mention_text": "Rizatriptan is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized double- blind crossover outpatient study assessed the preference for 1 rizatriptan 10 mg tablet to 2 ergotamine 1 mg/caffeine 100 mg tablets in 439 patients treating a single migraine attack with each therapy. Of patients expressing a preference (89.1%), more than twice as many preferred rizatriptan to ergotamine/caffeine (69.9 vs. 30.1%, p < or = 0.001). Faster relief of headache was the most important reason for preference, cited by 67.3% of patients preferring rizatriptan and 54.2% of patients who preferred ergotamine/caffeine. The co-primary endpoint of being pain free at 2 h was also in favor of rizatriptan. Forty-nine percent of patients were pain free 2 h after rizatriptan, compared with 24.3% treated with ergotamine/caffeine (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Headache relief at 2 h was 75.9% for rizatriptan and 47.3% for ergotamine/caffeine (p < or = 0.001), with rizatriptan being superior to ergotamine/caffeine within 30 min of dosing. Almost 36% of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication within 24 h, compared to 20% of patients on ergotamine/caffeine (p < or = 0.001). Rizatriptan was also superior to ergotamine/caffeine in the proportions of patients with no nausea, vomiting, phonophobia or photophobia and for patients with normal function 2 h after drug intake (p < or = 0.001). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (69.8%) than at 2 h after treatment with ergotamine/caffeine (38.6%, p < or = 0.001). Recurrence rates were 31.4% with rizatriptan and 15.3% with ergotamine/caffeine. Both active treatments were well tolerated. The most common adverse events (incidence > or = 5% in one group) after rizatriptan and ergotamine/caffeine, respectively, were dizziness (6.7 and 5.3%), nausea (4.2 and 8.5%) and somnolence (5.5 and 2.3%).", "entity": "Photophobia", "aliases": "Light Sensitivities Sensitivity Photophobia Photophobias", "definition": "Abnormal sensitivity to light. This may occur as a manifestation of EYE DISEASES; MIGRAINE; SUBARACHNOID HEMORRHAGE; MENINGITIS; and other disorders. Photophobia may also occur in association with DEPRESSION and other MENTAL DISORDERS.\n    ", "id": "MESH:D020795"}
{"mention": "dizziness", "mention_text": "Rizatriptan is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized double- blind crossover outpatient study assessed the preference for 1 rizatriptan 10 mg tablet to 2 ergotamine 1 mg/caffeine 100 mg tablets in 439 patients treating a single migraine attack with each therapy. Of patients expressing a preference (89.1%), more than twice as many preferred rizatriptan to ergotamine/caffeine (69.9 vs. 30.1%, p < or = 0.001). Faster relief of headache was the most important reason for preference, cited by 67.3% of patients preferring rizatriptan and 54.2% of patients who preferred ergotamine/caffeine. The co-primary endpoint of being pain free at 2 h was also in favor of rizatriptan. Forty-nine percent of patients were pain free 2 h after rizatriptan, compared with 24.3% treated with ergotamine/caffeine (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Headache relief at 2 h was 75.9% for rizatriptan and 47.3% for ergotamine/caffeine (p < or = 0.001), with rizatriptan being superior to ergotamine/caffeine within 30 min of dosing. Almost 36% of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication within 24 h, compared to 20% of patients on ergotamine/caffeine (p < or = 0.001). Rizatriptan was also superior to ergotamine/caffeine in the proportions of patients with no nausea, vomiting, phonophobia or photophobia and for patients with normal function 2 h after drug intake (p < or = 0.001). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (69.8%) than at 2 h after treatment with ergotamine/caffeine (38.6%, p < or = 0.001). Recurrence rates were 31.4% with rizatriptan and 15.3% with ergotamine/caffeine. Both active treatments were well tolerated. The most common adverse events (incidence > or = 5% in one group) after rizatriptan and ergotamine/caffeine, respectively, were dizziness (6.7 and 5.3%), nausea (4.2 and 8.5%) and somnolence (5.5 and 2.3%).", "entity": "Dizziness", "aliases": "Dizziness Dizzyness Light Headedness Light-Headedness Lightheadedness Orthostasis", "definition": "An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness.\n    ", "id": "MESH:D004244"}
{"mention": "somnolence", "mention_text": "Rizatriptan is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized double- blind crossover outpatient study assessed the preference for 1 rizatriptan 10 mg tablet to 2 ergotamine 1 mg/caffeine 100 mg tablets in 439 patients treating a single migraine attack with each therapy. Of patients expressing a preference (89.1%), more than twice as many preferred rizatriptan to ergotamine/caffeine (69.9 vs. 30.1%, p < or = 0.001). Faster relief of headache was the most important reason for preference, cited by 67.3% of patients preferring rizatriptan and 54.2% of patients who preferred ergotamine/caffeine. The co-primary endpoint of being pain free at 2 h was also in favor of rizatriptan. Forty-nine percent of patients were pain free 2 h after rizatriptan, compared with 24.3% treated with ergotamine/caffeine (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Headache relief at 2 h was 75.9% for rizatriptan and 47.3% for ergotamine/caffeine (p < or = 0.001), with rizatriptan being superior to ergotamine/caffeine within 30 min of dosing. Almost 36% of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication within 24 h, compared to 20% of patients on ergotamine/caffeine (p < or = 0.001). Rizatriptan was also superior to ergotamine/caffeine in the proportions of patients with no nausea, vomiting, phonophobia or photophobia and for patients with normal function 2 h after drug intake (p < or = 0.001). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (69.8%) than at 2 h after treatment with ergotamine/caffeine (38.6%, p < or = 0.001). Recurrence rates were 31.4% with rizatriptan and 15.3% with ergotamine/caffeine. Both active treatments were well tolerated. The most common adverse events (incidence > or = 5% in one group) after rizatriptan and ergotamine/caffeine, respectively, were dizziness (6.7 and 5.3%), nausea (4.2 and 8.5%) and somnolence (5.5 and 2.3%).", "entity": "Disorders of Excessive Somnolence", "aliases": "DOES (Disorders of Excessive Somnolence) DOESs Disorders Somnolence Disorder Hypersomnia Recurrent Hypersomnias Hypersomnolence Primary Secondary", "definition": "Disorders characterized by hypersomnolence during normal waking hours that may impair cognitive functioning. Subtypes include primary hypersomnia disorders (e.g., IDIOPATHIC HYPERSOMNOLENCE; NARCOLEPSY; and KLEINE-LEVIN SYNDROME) and secondary hypersomnia disorders where excessive somnolence can be attributed to a known cause (e.g., drug affect, MENTAL DISORDERS, and SLEEP APNEA SYNDROME). (From J Neurol Sci 1998 Jan 8;153(2):192-202; Thorpy, Principles and Practice of Sleep Medicine, 2nd ed, p320)\n    ", "id": "MESH:D006970"}
{"mention": "Thrombotic microangiopathy", "mention_text": "Thrombotic microangiopathy and renal failure associated with antineoplastic chemotherapy.", "entity": "Thrombotic Microangiopathies", "aliases": "Microangiopathies Thrombotic Microangiopathy", "definition": "Diseases that result in THROMBOSIS in MICROVASCULATURE. The two most prominent diseases are PURPURA, THROMBOTIC THROMBOCYTOPENIC; and HEMOLYTIC-UREMIC SYNDROME. Multiple etiological factors include VASCULAR ENDOTHELIAL CELL damage due to SHIGA TOXIN; FACTOR H deficiency; and aberrant VON WILLEBRAND FACTOR formation.\n    ", "id": "MESH:D057049"}
{"mention": "renal failure", "mention_text": "Thrombotic microangiopathy and renal failure associated with antineoplastic chemotherapy.", "entity": "Renal Insufficiency", "aliases": "Failure Kidney Renal Failures Insufficiency Insufficiencies", "definition": "Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.\n    ", "id": "MESH:D051437"}
{"mention": "carcinoma", "mention_text": "Five patients with carcinoma developed thrombotic microangiopathy (characterized by renal insufficiency, microangiopathic hemolytic anemia, and usually thrombocytopenia) after treatment with cisplatin, bleomycin, and a vinca alkaloid. One patient had thrombotic thrombocytopenic purpura, three the hemolytic-uremic syndrome, and one an apparent forme fruste of one of these disorders. Histologic examination of the renal tissue showed evidence of intravascular coagulation, primarily affecting the small arteries, arterioles, and glomeruli. Because each patient was tumor-free or had only a small tumor at the onset of this syndrome, the thrombotic microangiopathy may have been induced by chemotherapy. Diagnosis of this potentially fatal complication may be delayed or missed if renal tissue or the peripheral blood smear is not examined, because renal failure may be ascribed to cisplatin nephrotoxicity and the anemia and thrombocytopenia to drug-induced bone marrow suppression.", "entity": "Carcinoma", "aliases": "Anaplastic Carcinoma Carcinomas Spindle Cell Spindle-Cell Undifferentiated Carcinomatoses Carcinomatosis Epithelial Neoplasm Malignant Neoplasms Tumor Tumors Epithelioma Epitheliomas", "definition": "A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm but is often wrongly used as a synonym for \"cancer.\" (From Dorland, 27th ed)\n    ", "id": "MESH:D002277"}
{"mention": "thrombotic microangiopathy", "mention_text": "Five patients with carcinoma developed thrombotic microangiopathy (characterized by renal insufficiency, microangiopathic hemolytic anemia, and usually thrombocytopenia) after treatment with cisplatin, bleomycin, and a vinca alkaloid. One patient had thrombotic thrombocytopenic purpura, three the hemolytic-uremic syndrome, and one an apparent forme fruste of one of these disorders. Histologic examination of the renal tissue showed evidence of intravascular coagulation, primarily affecting the small arteries, arterioles, and glomeruli. Because each patient was tumor-free or had only a small tumor at the onset of this syndrome, the thrombotic microangiopathy may have been induced by chemotherapy. Diagnosis of this potentially fatal complication may be delayed or missed if renal tissue or the peripheral blood smear is not examined, because renal failure may be ascribed to cisplatin nephrotoxicity and the anemia and thrombocytopenia to drug-induced bone marrow suppression.", "entity": "Thrombotic Microangiopathies", "aliases": "Microangiopathies Thrombotic Microangiopathy", "definition": "Diseases that result in THROMBOSIS in MICROVASCULATURE. The two most prominent diseases are PURPURA, THROMBOTIC THROMBOCYTOPENIC; and HEMOLYTIC-UREMIC SYNDROME. Multiple etiological factors include VASCULAR ENDOTHELIAL CELL damage due to SHIGA TOXIN; FACTOR H deficiency; and aberrant VON WILLEBRAND FACTOR formation.\n    ", "id": "MESH:D057049"}
{"mention": "renal insufficiency", "mention_text": "Five patients with carcinoma developed thrombotic microangiopathy (characterized by renal insufficiency, microangiopathic hemolytic anemia, and usually thrombocytopenia) after treatment with cisplatin, bleomycin, and a vinca alkaloid. One patient had thrombotic thrombocytopenic purpura, three the hemolytic-uremic syndrome, and one an apparent forme fruste of one of these disorders. Histologic examination of the renal tissue showed evidence of intravascular coagulation, primarily affecting the small arteries, arterioles, and glomeruli. Because each patient was tumor-free or had only a small tumor at the onset of this syndrome, the thrombotic microangiopathy may have been induced by chemotherapy. Diagnosis of this potentially fatal complication may be delayed or missed if renal tissue or the peripheral blood smear is not examined, because renal failure may be ascribed to cisplatin nephrotoxicity and the anemia and thrombocytopenia to drug-induced bone marrow suppression.", "entity": "Renal Insufficiency", "aliases": "Failure Kidney Renal Failures Insufficiency Insufficiencies", "definition": "Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.\n    ", "id": "MESH:D051437"}
{"mention": "microangiopathic hemolytic anemia", "mention_text": "Five patients with carcinoma developed thrombotic microangiopathy (characterized by renal insufficiency, microangiopathic hemolytic anemia, and usually thrombocytopenia) after treatment with cisplatin, bleomycin, and a vinca alkaloid. One patient had thrombotic thrombocytopenic purpura, three the hemolytic-uremic syndrome, and one an apparent forme fruste of one of these disorders. Histologic examination of the renal tissue showed evidence of intravascular coagulation, primarily affecting the small arteries, arterioles, and glomeruli. Because each patient was tumor-free or had only a small tumor at the onset of this syndrome, the thrombotic microangiopathy may have been induced by chemotherapy. Diagnosis of this potentially fatal complication may be delayed or missed if renal tissue or the peripheral blood smear is not examined, because renal failure may be ascribed to cisplatin nephrotoxicity and the anemia and thrombocytopenia to drug-induced bone marrow suppression.", "entity": "Anemia, Hemolytic", "aliases": "Acquired Hemolytic Anemia Microangiopathic", "definition": "A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES).\n    ", "id": "MESH:D000743"}
{"mention": "thrombocytopenia", "mention_text": "Five patients with carcinoma developed thrombotic microangiopathy (characterized by renal insufficiency, microangiopathic hemolytic anemia, and usually thrombocytopenia) after treatment with cisplatin, bleomycin, and a vinca alkaloid. One patient had thrombotic thrombocytopenic purpura, three the hemolytic-uremic syndrome, and one an apparent forme fruste of one of these disorders. Histologic examination of the renal tissue showed evidence of intravascular coagulation, primarily affecting the small arteries, arterioles, and glomeruli. Because each patient was tumor-free or had only a small tumor at the onset of this syndrome, the thrombotic microangiopathy may have been induced by chemotherapy. Diagnosis of this potentially fatal complication may be delayed or missed if renal tissue or the peripheral blood smear is not examined, because renal failure may be ascribed to cisplatin nephrotoxicity and the anemia and thrombocytopenia to drug-induced bone marrow suppression.", "entity": "Thrombocytopenia", "aliases": "Thrombocytopenia Thrombocytopenias Thrombopenia Thrombopenias", "definition": "A subnormal level of BLOOD PLATELETS.\n    ", "id": "MESH:D013921"}
{"mention": "cisplatin", "mention_text": "Five patients with carcinoma developed thrombotic microangiopathy (characterized by renal insufficiency, microangiopathic hemolytic anemia, and usually thrombocytopenia) after treatment with cisplatin, bleomycin, and a vinca alkaloid. One patient had thrombotic thrombocytopenic purpura, three the hemolytic-uremic syndrome, and one an apparent forme fruste of one of these disorders. Histologic examination of the renal tissue showed evidence of intravascular coagulation, primarily affecting the small arteries, arterioles, and glomeruli. Because each patient was tumor-free or had only a small tumor at the onset of this syndrome, the thrombotic microangiopathy may have been induced by chemotherapy. Diagnosis of this potentially fatal complication may be delayed or missed if renal tissue or the peripheral blood smear is not examined, because renal failure may be ascribed to cisplatin nephrotoxicity and the anemia and thrombocytopenia to drug-induced bone marrow suppression.", "entity": "Cisplatin", "aliases": "Biocisplatinum Cisplatin Diamminodichloride Platinum Dichlorodiammineplatinum NSC-119875 Platidiam Platino Platinol cis Diamminedichloroplatinum cis-Diamminedichloroplatinum cis-Diamminedichloroplatinum(II) cis-Dichlorodiammineplatinum(II) cis-Platinum", "definition": "An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.\n    ", "id": "MESH:D002945"}
{"mention": "bleomycin", "mention_text": "Five patients with carcinoma developed thrombotic microangiopathy (characterized by renal insufficiency, microangiopathic hemolytic anemia, and usually thrombocytopenia) after treatment with cisplatin, bleomycin, and a vinca alkaloid. One patient had thrombotic thrombocytopenic purpura, three the hemolytic-uremic syndrome, and one an apparent forme fruste of one of these disorders. Histologic examination of the renal tissue showed evidence of intravascular coagulation, primarily affecting the small arteries, arterioles, and glomeruli. Because each patient was tumor-free or had only a small tumor at the onset of this syndrome, the thrombotic microangiopathy may have been induced by chemotherapy. Diagnosis of this potentially fatal complication may be delayed or missed if renal tissue or the peripheral blood smear is not examined, because renal failure may be ascribed to cisplatin nephrotoxicity and the anemia and thrombocytopenia to drug-induced bone marrow suppression.", "entity": "Bleomycin", "aliases": "Almirall Brand of Bleomycin Sulfate BLEO cell BLEO-cell BLEOcell Bellon Bléomycine Blanoxan Blenoxane Bleolem Bleomicina A(2) A2 B(2) B2 Bleomycins Bleomycinum Mack Bristol Myers Squibb Bristol-Myers Bull Lemery Lundbeck pharm", "definition": "A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors.\n    ", "id": "MESH:D001761"}
{"mention": "vinca alkaloid", "mention_text": "Five patients with carcinoma developed thrombotic microangiopathy (characterized by renal insufficiency, microangiopathic hemolytic anemia, and usually thrombocytopenia) after treatment with cisplatin, bleomycin, and a vinca alkaloid. One patient had thrombotic thrombocytopenic purpura, three the hemolytic-uremic syndrome, and one an apparent forme fruste of one of these disorders. Histologic examination of the renal tissue showed evidence of intravascular coagulation, primarily affecting the small arteries, arterioles, and glomeruli. Because each patient was tumor-free or had only a small tumor at the onset of this syndrome, the thrombotic microangiopathy may have been induced by chemotherapy. Diagnosis of this potentially fatal complication may be delayed or missed if renal tissue or the peripheral blood smear is not examined, because renal failure may be ascribed to cisplatin nephrotoxicity and the anemia and thrombocytopenia to drug-induced bone marrow suppression.", "entity": "Vinca Alkaloids", "aliases": "Alkaloids Vinca", "definition": "A group of indole-indoline dimers which are ALKALOIDS obtained from the VINCA genus of plants. They inhibit polymerization of TUBULIN into MICROTUBULES thus blocking spindle formation and arresting cells in METAPHASE. They are some of the most useful ANTINEOPLASTIC AGENTS.\n    ", "id": "MESH:D014748"}
{"mention": "thrombotic thrombocytopenic purpura", "mention_text": "Five patients with carcinoma developed thrombotic microangiopathy (characterized by renal insufficiency, microangiopathic hemolytic anemia, and usually thrombocytopenia) after treatment with cisplatin, bleomycin, and a vinca alkaloid. One patient had thrombotic thrombocytopenic purpura, three the hemolytic-uremic syndrome, and one an apparent forme fruste of one of these disorders. Histologic examination of the renal tissue showed evidence of intravascular coagulation, primarily affecting the small arteries, arterioles, and glomeruli. Because each patient was tumor-free or had only a small tumor at the onset of this syndrome, the thrombotic microangiopathy may have been induced by chemotherapy. Diagnosis of this potentially fatal complication may be delayed or missed if renal tissue or the peripheral blood smear is not examined, because renal failure may be ascribed to cisplatin nephrotoxicity and the anemia and thrombocytopenia to drug-induced bone marrow suppression.", "entity": "Purpura, Thrombotic Thrombocytopenic", "aliases": "Congenital Thrombotic Thrombocytopenic Purpura Disease Moschcowitz Moschkowitz Familial Microangiopathy Thrombocytopenia Microangiopathic Hemolytic Anemia Thrombopenic Schulman Upshaw Syndrome Schulman-Upshaw Upshaw-Schulman Factor Deficiency of", "definition": "An acquired, congenital, or familial disorder caused by PLATELET AGGREGATION with THROMBOSIS in terminal arterioles and capillaries. Clinical features include THROMBOCYTOPENIA; HEMOLYTIC ANEMIA; AZOTEMIA; FEVER; and thrombotic microangiopathy. The classical form also includes neurological symptoms and end-organ damage, such as RENAL FAILURE.\n    ", "id": "MESH:D011697"}
{"mention": "hemolytic-uremic syndrome", "mention_text": "Five patients with carcinoma developed thrombotic microangiopathy (characterized by renal insufficiency, microangiopathic hemolytic anemia, and usually thrombocytopenia) after treatment with cisplatin, bleomycin, and a vinca alkaloid. One patient had thrombotic thrombocytopenic purpura, three the hemolytic-uremic syndrome, and one an apparent forme fruste of one of these disorders. Histologic examination of the renal tissue showed evidence of intravascular coagulation, primarily affecting the small arteries, arterioles, and glomeruli. Because each patient was tumor-free or had only a small tumor at the onset of this syndrome, the thrombotic microangiopathy may have been induced by chemotherapy. Diagnosis of this potentially fatal complication may be delayed or missed if renal tissue or the peripheral blood smear is not examined, because renal failure may be ascribed to cisplatin nephrotoxicity and the anemia and thrombocytopenia to drug-induced bone marrow suppression.", "entity": "Hemolytic-Uremic Syndrome", "aliases": "Gasser Syndrome Gasser's Gassers Hemolytic Uremic Hemolytic-Uremic", "definition": "A syndrome that is associated with microvascular diseases of the KIDNEY, such as RENAL CORTICAL NECROSIS. It is characterized by hemolytic anemia (ANEMIA, HEMOLYTIC); THROMBOCYTOPENIA; and ACUTE RENAL FAILURE.\n    ", "id": "MESH:D006463"}
{"mention": "intravascular coagulation", "mention_text": "Five patients with carcinoma developed thrombotic microangiopathy (characterized by renal insufficiency, microangiopathic hemolytic anemia, and usually thrombocytopenia) after treatment with cisplatin, bleomycin, and a vinca alkaloid. One patient had thrombotic thrombocytopenic purpura, three the hemolytic-uremic syndrome, and one an apparent forme fruste of one of these disorders. Histologic examination of the renal tissue showed evidence of intravascular coagulation, primarily affecting the small arteries, arterioles, and glomeruli. Because each patient was tumor-free or had only a small tumor at the onset of this syndrome, the thrombotic microangiopathy may have been induced by chemotherapy. Diagnosis of this potentially fatal complication may be delayed or missed if renal tissue or the peripheral blood smear is not examined, because renal failure may be ascribed to cisplatin nephrotoxicity and the anemia and thrombocytopenia to drug-induced bone marrow suppression.", "entity": "Disseminated Intravascular Coagulation", "aliases": "Coagulation Disseminated Intravascular Coagulations Coagulopathies Consumption Coagulopathy", "definition": "A disorder characterized by procoagulant substances entering the general circulation causing a systemic thrombotic process. The activation of the clotting mechanism may arise from any of a number of disorders. A majority of the patients manifest skin lesions, sometimes leading to PURPURA FULMINANS.\n    ", "id": "MESH:D004211"}
{"mention": "tumor", "mention_text": "Five patients with carcinoma developed thrombotic microangiopathy (characterized by renal insufficiency, microangiopathic hemolytic anemia, and usually thrombocytopenia) after treatment with cisplatin, bleomycin, and a vinca alkaloid. One patient had thrombotic thrombocytopenic purpura, three the hemolytic-uremic syndrome, and one an apparent forme fruste of one of these disorders. Histologic examination of the renal tissue showed evidence of intravascular coagulation, primarily affecting the small arteries, arterioles, and glomeruli. Because each patient was tumor-free or had only a small tumor at the onset of this syndrome, the thrombotic microangiopathy may have been induced by chemotherapy. Diagnosis of this potentially fatal complication may be delayed or missed if renal tissue or the peripheral blood smear is not examined, because renal failure may be ascribed to cisplatin nephrotoxicity and the anemia and thrombocytopenia to drug-induced bone marrow suppression.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "renal failure", "mention_text": "Five patients with carcinoma developed thrombotic microangiopathy (characterized by renal insufficiency, microangiopathic hemolytic anemia, and usually thrombocytopenia) after treatment with cisplatin, bleomycin, and a vinca alkaloid. One patient had thrombotic thrombocytopenic purpura, three the hemolytic-uremic syndrome, and one an apparent forme fruste of one of these disorders. Histologic examination of the renal tissue showed evidence of intravascular coagulation, primarily affecting the small arteries, arterioles, and glomeruli. Because each patient was tumor-free or had only a small tumor at the onset of this syndrome, the thrombotic microangiopathy may have been induced by chemotherapy. Diagnosis of this potentially fatal complication may be delayed or missed if renal tissue or the peripheral blood smear is not examined, because renal failure may be ascribed to cisplatin nephrotoxicity and the anemia and thrombocytopenia to drug-induced bone marrow suppression.", "entity": "Renal Insufficiency", "aliases": "Failure Kidney Renal Failures Insufficiency Insufficiencies", "definition": "Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.\n    ", "id": "MESH:D051437"}
{"mention": "nephrotoxicity", "mention_text": "Five patients with carcinoma developed thrombotic microangiopathy (characterized by renal insufficiency, microangiopathic hemolytic anemia, and usually thrombocytopenia) after treatment with cisplatin, bleomycin, and a vinca alkaloid. One patient had thrombotic thrombocytopenic purpura, three the hemolytic-uremic syndrome, and one an apparent forme fruste of one of these disorders. Histologic examination of the renal tissue showed evidence of intravascular coagulation, primarily affecting the small arteries, arterioles, and glomeruli. Because each patient was tumor-free or had only a small tumor at the onset of this syndrome, the thrombotic microangiopathy may have been induced by chemotherapy. Diagnosis of this potentially fatal complication may be delayed or missed if renal tissue or the peripheral blood smear is not examined, because renal failure may be ascribed to cisplatin nephrotoxicity and the anemia and thrombocytopenia to drug-induced bone marrow suppression.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "anemia", "mention_text": "Five patients with carcinoma developed thrombotic microangiopathy (characterized by renal insufficiency, microangiopathic hemolytic anemia, and usually thrombocytopenia) after treatment with cisplatin, bleomycin, and a vinca alkaloid. One patient had thrombotic thrombocytopenic purpura, three the hemolytic-uremic syndrome, and one an apparent forme fruste of one of these disorders. Histologic examination of the renal tissue showed evidence of intravascular coagulation, primarily affecting the small arteries, arterioles, and glomeruli. Because each patient was tumor-free or had only a small tumor at the onset of this syndrome, the thrombotic microangiopathy may have been induced by chemotherapy. Diagnosis of this potentially fatal complication may be delayed or missed if renal tissue or the peripheral blood smear is not examined, because renal failure may be ascribed to cisplatin nephrotoxicity and the anemia and thrombocytopenia to drug-induced bone marrow suppression.", "entity": "Anemia", "aliases": "Anemia Anemias", "definition": "A reduction in the number of circulating ERYTHROCYTES or in the quantity of HEMOGLOBIN.\n    ", "id": "MESH:D000740"}
{"mention": "bone marrow suppression", "mention_text": "Five patients with carcinoma developed thrombotic microangiopathy (characterized by renal insufficiency, microangiopathic hemolytic anemia, and usually thrombocytopenia) after treatment with cisplatin, bleomycin, and a vinca alkaloid. One patient had thrombotic thrombocytopenic purpura, three the hemolytic-uremic syndrome, and one an apparent forme fruste of one of these disorders. Histologic examination of the renal tissue showed evidence of intravascular coagulation, primarily affecting the small arteries, arterioles, and glomeruli. Because each patient was tumor-free or had only a small tumor at the onset of this syndrome, the thrombotic microangiopathy may have been induced by chemotherapy. Diagnosis of this potentially fatal complication may be delayed or missed if renal tissue or the peripheral blood smear is not examined, because renal failure may be ascribed to cisplatin nephrotoxicity and the anemia and thrombocytopenia to drug-induced bone marrow suppression.", "entity": "Bone Marrow Diseases", "aliases": "Bone Marrow Disease Diseases", "definition": "", "id": "MESH:D001855"}
{"mention": "nelarabine", "mention_text": "Salvage therapy with nelarabine, etoposide, and cyclophosphamide in relapsed/refractory paediatric T-cell lymphoblastic leukaemia and lymphoma.", "entity": "nelarabine", "aliases": "2-amino-6-methoxypurine arabinoside 2-amino-9-beta-D-arabinofuranosyl-6-methoxy-9H-purine 506U78 Arranon GW506U78 GlaxoSmithKline brand of nelarabine compound", "definition": "", "id": "MESH:C104457"}
{"mention": "etoposide", "mention_text": "Salvage therapy with nelarabine, etoposide, and cyclophosphamide in relapsed/refractory paediatric T-cell lymphoblastic leukaemia and lymphoma.", "entity": "Etoposide", "aliases": "Baxter Brand of Etoposide Oncology Bristol Myers Squibb Bristol-Myers Celltop Demethyl Epipodophyllotoxin Ethylidine Glucoside Eposide Eposin Eto GRY Eto-GRY Etomedac Etopos Pierre Fabre Teva (5S)-Isomer (5a alpha)-Isomer alpha,9 alpha D Glucopyranosyl Isomer alpha-D-Glucopyranosyl Etoposido Ferrer Farma Exitop Gry Lastet Lemery Medac NSC 141540 NSC-141540 NSC141540 Novartis Onkoposid Onkoworks Pharmachemie Prasfarma Riboposid Sanfer Tedec Meiji Toposar VP 16 213 16-213 16213 VP-16 VP16 Vepesid ", "definition": "A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.\n    ", "id": "MESH:D005047"}
{"mention": "cyclophosphamide", "mention_text": "Salvage therapy with nelarabine, etoposide, and cyclophosphamide in relapsed/refractory paediatric T-cell lymphoblastic leukaemia and lymphoma.", "entity": "Cyclophosphamide", "aliases": "Anhydrous Cyclophosphamide B 518 B-518 B518 Monohydrate (R)-Isomer (S)-Isomer Cyclophosphane Cytophosphan Cytophosphane Cytoxan Endoxan NSC 26271 NSC-26271 NSC26271 Neosar Procytox Sendoxan", "definition": "Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.\n    ", "id": "MESH:D003520"}
{"mention": "T-cell lymphoblastic leukaemia", "mention_text": "Salvage therapy with nelarabine, etoposide, and cyclophosphamide in relapsed/refractory paediatric T-cell lymphoblastic leukaemia and lymphoma.", "entity": "Leukemia, T-Cell", "aliases": "Leukemia Lymphocytic T Cell T-Cell T-Lymphocytic Leukemias", "definition": "A malignant disease of the T-LYMPHOCYTES in the bone marrow, thymus, and/or blood.\n    ", "id": "MESH:D015458"}
{"mention": "nelarabine", "mention_text": "A combination of 5 d of nelarabine (AraG) with 5 d of etoposide (VP) and cyclophosphamide (CPM) and prophylactic intrathecal chemotherapy was used as salvage therapy in seven children with refractory or relapsed T-cell leukaemia or lymphoma. The most common side effects attributable to the AraG included Grade 2 and 3 sensory and motor neuropathy and musculoskeletal pain. Haematological toxicity was greater for the combination than AraG alone, although median time to neutrophil and platelet recovery was consistent with other salvage therapies. All patients had some response to the combined therapy and five of the seven went into complete remission after one or two courses of AraG/VP/CPM. Our experience supports the safety of giving AraG as salvage therapy in synchrony with etoposide and cyclophosphamide, although neurological toxicity must be closely monitored.", "entity": "nelarabine", "aliases": "2-amino-6-methoxypurine arabinoside 2-amino-9-beta-D-arabinofuranosyl-6-methoxy-9H-purine 506U78 Arranon GW506U78 GlaxoSmithKline brand of nelarabine compound", "definition": "", "id": "MESH:C104457"}
{"mention": "AraG", "mention_text": "A combination of 5 d of nelarabine (AraG) with 5 d of etoposide (VP) and cyclophosphamide (CPM) and prophylactic intrathecal chemotherapy was used as salvage therapy in seven children with refractory or relapsed T-cell leukaemia or lymphoma. The most common side effects attributable to the AraG included Grade 2 and 3 sensory and motor neuropathy and musculoskeletal pain. Haematological toxicity was greater for the combination than AraG alone, although median time to neutrophil and platelet recovery was consistent with other salvage therapies. All patients had some response to the combined therapy and five of the seven went into complete remission after one or two courses of AraG/VP/CPM. Our experience supports the safety of giving AraG as salvage therapy in synchrony with etoposide and cyclophosphamide, although neurological toxicity must be closely monitored.", "entity": "nelarabine", "aliases": "2-amino-6-methoxypurine arabinoside 2-amino-9-beta-D-arabinofuranosyl-6-methoxy-9H-purine 506U78 Arranon GW506U78 GlaxoSmithKline brand of nelarabine compound", "definition": "", "id": "MESH:C104457"}
{"mention": "etoposide", "mention_text": "A combination of 5 d of nelarabine (AraG) with 5 d of etoposide (VP) and cyclophosphamide (CPM) and prophylactic intrathecal chemotherapy was used as salvage therapy in seven children with refractory or relapsed T-cell leukaemia or lymphoma. The most common side effects attributable to the AraG included Grade 2 and 3 sensory and motor neuropathy and musculoskeletal pain. Haematological toxicity was greater for the combination than AraG alone, although median time to neutrophil and platelet recovery was consistent with other salvage therapies. All patients had some response to the combined therapy and five of the seven went into complete remission after one or two courses of AraG/VP/CPM. Our experience supports the safety of giving AraG as salvage therapy in synchrony with etoposide and cyclophosphamide, although neurological toxicity must be closely monitored.", "entity": "Etoposide", "aliases": "Baxter Brand of Etoposide Oncology Bristol Myers Squibb Bristol-Myers Celltop Demethyl Epipodophyllotoxin Ethylidine Glucoside Eposide Eposin Eto GRY Eto-GRY Etomedac Etopos Pierre Fabre Teva (5S)-Isomer (5a alpha)-Isomer alpha,9 alpha D Glucopyranosyl Isomer alpha-D-Glucopyranosyl Etoposido Ferrer Farma Exitop Gry Lastet Lemery Medac NSC 141540 NSC-141540 NSC141540 Novartis Onkoposid Onkoworks Pharmachemie Prasfarma Riboposid Sanfer Tedec Meiji Toposar VP 16 213 16-213 16213 VP-16 VP16 Vepesid ", "definition": "A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.\n    ", "id": "MESH:D005047"}
{"mention": "VP", "mention_text": "A combination of 5 d of nelarabine (AraG) with 5 d of etoposide (VP) and cyclophosphamide (CPM) and prophylactic intrathecal chemotherapy was used as salvage therapy in seven children with refractory or relapsed T-cell leukaemia or lymphoma. The most common side effects attributable to the AraG included Grade 2 and 3 sensory and motor neuropathy and musculoskeletal pain. Haematological toxicity was greater for the combination than AraG alone, although median time to neutrophil and platelet recovery was consistent with other salvage therapies. All patients had some response to the combined therapy and five of the seven went into complete remission after one or two courses of AraG/VP/CPM. Our experience supports the safety of giving AraG as salvage therapy in synchrony with etoposide and cyclophosphamide, although neurological toxicity must be closely monitored.", "entity": "Etoposide", "aliases": "Baxter Brand of Etoposide Oncology Bristol Myers Squibb Bristol-Myers Celltop Demethyl Epipodophyllotoxin Ethylidine Glucoside Eposide Eposin Eto GRY Eto-GRY Etomedac Etopos Pierre Fabre Teva (5S)-Isomer (5a alpha)-Isomer alpha,9 alpha D Glucopyranosyl Isomer alpha-D-Glucopyranosyl Etoposido Ferrer Farma Exitop Gry Lastet Lemery Medac NSC 141540 NSC-141540 NSC141540 Novartis Onkoposid Onkoworks Pharmachemie Prasfarma Riboposid Sanfer Tedec Meiji Toposar VP 16 213 16-213 16213 VP-16 VP16 Vepesid ", "definition": "A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.\n    ", "id": "MESH:D005047"}
{"mention": "cyclophosphamide", "mention_text": "A combination of 5 d of nelarabine (AraG) with 5 d of etoposide (VP) and cyclophosphamide (CPM) and prophylactic intrathecal chemotherapy was used as salvage therapy in seven children with refractory or relapsed T-cell leukaemia or lymphoma. The most common side effects attributable to the AraG included Grade 2 and 3 sensory and motor neuropathy and musculoskeletal pain. Haematological toxicity was greater for the combination than AraG alone, although median time to neutrophil and platelet recovery was consistent with other salvage therapies. All patients had some response to the combined therapy and five of the seven went into complete remission after one or two courses of AraG/VP/CPM. Our experience supports the safety of giving AraG as salvage therapy in synchrony with etoposide and cyclophosphamide, although neurological toxicity must be closely monitored.", "entity": "Cyclophosphamide", "aliases": "Anhydrous Cyclophosphamide B 518 B-518 B518 Monohydrate (R)-Isomer (S)-Isomer Cyclophosphane Cytophosphan Cytophosphane Cytoxan Endoxan NSC 26271 NSC-26271 NSC26271 Neosar Procytox Sendoxan", "definition": "Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.\n    ", "id": "MESH:D003520"}
{"mention": "CPM", "mention_text": "A combination of 5 d of nelarabine (AraG) with 5 d of etoposide (VP) and cyclophosphamide (CPM) and prophylactic intrathecal chemotherapy was used as salvage therapy in seven children with refractory or relapsed T-cell leukaemia or lymphoma. The most common side effects attributable to the AraG included Grade 2 and 3 sensory and motor neuropathy and musculoskeletal pain. Haematological toxicity was greater for the combination than AraG alone, although median time to neutrophil and platelet recovery was consistent with other salvage therapies. All patients had some response to the combined therapy and five of the seven went into complete remission after one or two courses of AraG/VP/CPM. Our experience supports the safety of giving AraG as salvage therapy in synchrony with etoposide and cyclophosphamide, although neurological toxicity must be closely monitored.", "entity": "Cyclophosphamide", "aliases": "Anhydrous Cyclophosphamide B 518 B-518 B518 Monohydrate (R)-Isomer (S)-Isomer Cyclophosphane Cytophosphan Cytophosphane Cytoxan Endoxan NSC 26271 NSC-26271 NSC26271 Neosar Procytox Sendoxan", "definition": "Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.\n    ", "id": "MESH:D003520"}
{"mention": "T-cell leukaemia", "mention_text": "A combination of 5 d of nelarabine (AraG) with 5 d of etoposide (VP) and cyclophosphamide (CPM) and prophylactic intrathecal chemotherapy was used as salvage therapy in seven children with refractory or relapsed T-cell leukaemia or lymphoma. The most common side effects attributable to the AraG included Grade 2 and 3 sensory and motor neuropathy and musculoskeletal pain. Haematological toxicity was greater for the combination than AraG alone, although median time to neutrophil and platelet recovery was consistent with other salvage therapies. All patients had some response to the combined therapy and five of the seven went into complete remission after one or two courses of AraG/VP/CPM. Our experience supports the safety of giving AraG as salvage therapy in synchrony with etoposide and cyclophosphamide, although neurological toxicity must be closely monitored.", "entity": "Leukemia, T-Cell", "aliases": "Leukemia Lymphocytic T Cell T-Cell T-Lymphocytic Leukemias", "definition": "A malignant disease of the T-LYMPHOCYTES in the bone marrow, thymus, and/or blood.\n    ", "id": "MESH:D015458"}
{"mention": "neuropathy", "mention_text": "A combination of 5 d of nelarabine (AraG) with 5 d of etoposide (VP) and cyclophosphamide (CPM) and prophylactic intrathecal chemotherapy was used as salvage therapy in seven children with refractory or relapsed T-cell leukaemia or lymphoma. The most common side effects attributable to the AraG included Grade 2 and 3 sensory and motor neuropathy and musculoskeletal pain. Haematological toxicity was greater for the combination than AraG alone, although median time to neutrophil and platelet recovery was consistent with other salvage therapies. All patients had some response to the combined therapy and five of the seven went into complete remission after one or two courses of AraG/VP/CPM. Our experience supports the safety of giving AraG as salvage therapy in synchrony with etoposide and cyclophosphamide, although neurological toxicity must be closely monitored.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "musculoskeletal pain", "mention_text": "A combination of 5 d of nelarabine (AraG) with 5 d of etoposide (VP) and cyclophosphamide (CPM) and prophylactic intrathecal chemotherapy was used as salvage therapy in seven children with refractory or relapsed T-cell leukaemia or lymphoma. The most common side effects attributable to the AraG included Grade 2 and 3 sensory and motor neuropathy and musculoskeletal pain. Haematological toxicity was greater for the combination than AraG alone, although median time to neutrophil and platelet recovery was consistent with other salvage therapies. All patients had some response to the combined therapy and five of the seven went into complete remission after one or two courses of AraG/VP/CPM. Our experience supports the safety of giving AraG as salvage therapy in synchrony with etoposide and cyclophosphamide, although neurological toxicity must be closely monitored.", "entity": "Musculoskeletal Pain", "aliases": "Musculoskeletal Pain Pains", "definition": "Discomfort stemming from muscles, LIGAMENTS, tendons, and bones.\n    ", "id": "MESH:D059352"}
{"mention": "Haematological toxicity", "mention_text": "A combination of 5 d of nelarabine (AraG) with 5 d of etoposide (VP) and cyclophosphamide (CPM) and prophylactic intrathecal chemotherapy was used as salvage therapy in seven children with refractory or relapsed T-cell leukaemia or lymphoma. The most common side effects attributable to the AraG included Grade 2 and 3 sensory and motor neuropathy and musculoskeletal pain. Haematological toxicity was greater for the combination than AraG alone, although median time to neutrophil and platelet recovery was consistent with other salvage therapies. All patients had some response to the combined therapy and five of the seven went into complete remission after one or two courses of AraG/VP/CPM. Our experience supports the safety of giving AraG as salvage therapy in synchrony with etoposide and cyclophosphamide, although neurological toxicity must be closely monitored.", "entity": "Hematologic Diseases", "aliases": "Blood Disease Diseases Hematologic Hematological", "definition": "Disorders of the blood and blood forming tissues.\n    ", "id": "MESH:D006402"}
{"mention": "neurological toxicity", "mention_text": "A combination of 5 d of nelarabine (AraG) with 5 d of etoposide (VP) and cyclophosphamide (CPM) and prophylactic intrathecal chemotherapy was used as salvage therapy in seven children with refractory or relapsed T-cell leukaemia or lymphoma. The most common side effects attributable to the AraG included Grade 2 and 3 sensory and motor neuropathy and musculoskeletal pain. Haematological toxicity was greater for the combination than AraG alone, although median time to neutrophil and platelet recovery was consistent with other salvage therapies. All patients had some response to the combined therapy and five of the seven went into complete remission after one or two courses of AraG/VP/CPM. Our experience supports the safety of giving AraG as salvage therapy in synchrony with etoposide and cyclophosphamide, although neurological toxicity must be closely monitored.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "sulphasalazine", "mention_text": "The 3-week sulphasalazine syndrome strikes again.", "entity": "Sulfasalazine", "aliases": "Alphapharm Brand of Sulfasalazine Ashbourne Asulfidine Azulfadine Azulfidine EN Colo Pleon Colo-Pleon FNA Henning Berlin Heyl Pfizer Pyralin Ratiopharm Salazopyrin Salazosulfapyridine Salicylazosulfapyridine Sanofi Synthelabo Sulfasalazin medac Sulfasalazin-Heyl Sulphasalazine Ucine Ulcol ratio ratio-Sulfasalazine", "definition": "A drug that is used in the management of inflammatory bowel diseases. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid (see MESALAMINE) released in the colon. (From Martindale, The Extra Pharmacopoeia, 30th ed, p907)\n    ", "id": "MESH:D012460"}
{"mention": "dermatitis", "mention_text": "A 34-year-old lady developed a constellation of dermatitis, fever, lymphadenopathy and hepatitis, beginning on the 17th day of a course of oral sulphasalazine for sero-negative rheumatoid arthritis. Cervical and inguinal lymph node biopsies showed the features of severe necrotising lymphadenitis, associated with erythrophagocytosis and prominent eosinophilic infiltrates, without viral inclusion bodies, suggestive of an adverse drug reaction.A week later, fulminant drug-induced hepatitis, associated with the presence of anti-nuclear autoantibodies (but not with other markers of autoimmunity), and accompanied by multi-organ failure and sepsis, supervened. She subsequently died some 5 weeks after the commencement of her drug therapy.Post-mortem examination showed evidence of massive hepatocellular necrosis, acute hypersensitivity myocarditis, focal acute tubulo-interstitial nephritis and extensive bone marrow necrosis, with no evidence of malignancy. It is thought that the clinico-pathological features and chronology of this case bore the hallmarks of the so-called \"3-week sulphasalazine syndrome\", a rare, but often fatal, immunoallergic reaction to sulphasalazine.", "entity": "Dermatitis", "aliases": "Dermatitides Dermatitis", "definition": "Any inflammation of the skin.\n    ", "id": "MESH:D003872"}
{"mention": "fever", "mention_text": "A 34-year-old lady developed a constellation of dermatitis, fever, lymphadenopathy and hepatitis, beginning on the 17th day of a course of oral sulphasalazine for sero-negative rheumatoid arthritis. Cervical and inguinal lymph node biopsies showed the features of severe necrotising lymphadenitis, associated with erythrophagocytosis and prominent eosinophilic infiltrates, without viral inclusion bodies, suggestive of an adverse drug reaction.A week later, fulminant drug-induced hepatitis, associated with the presence of anti-nuclear autoantibodies (but not with other markers of autoimmunity), and accompanied by multi-organ failure and sepsis, supervened. She subsequently died some 5 weeks after the commencement of her drug therapy.Post-mortem examination showed evidence of massive hepatocellular necrosis, acute hypersensitivity myocarditis, focal acute tubulo-interstitial nephritis and extensive bone marrow necrosis, with no evidence of malignancy. It is thought that the clinico-pathological features and chronology of this case bore the hallmarks of the so-called \"3-week sulphasalazine syndrome\", a rare, but often fatal, immunoallergic reaction to sulphasalazine.", "entity": "Fever", "aliases": "Fever Fevers Hyperthermia Hyperthermias Pyrexia Pyrexias", "definition": "An abnormal elevation of body temperature, usually as a result of a pathologic process.\n    ", "id": "MESH:D005334"}
{"mention": "lymphadenopathy", "mention_text": "A 34-year-old lady developed a constellation of dermatitis, fever, lymphadenopathy and hepatitis, beginning on the 17th day of a course of oral sulphasalazine for sero-negative rheumatoid arthritis. Cervical and inguinal lymph node biopsies showed the features of severe necrotising lymphadenitis, associated with erythrophagocytosis and prominent eosinophilic infiltrates, without viral inclusion bodies, suggestive of an adverse drug reaction.A week later, fulminant drug-induced hepatitis, associated with the presence of anti-nuclear autoantibodies (but not with other markers of autoimmunity), and accompanied by multi-organ failure and sepsis, supervened. She subsequently died some 5 weeks after the commencement of her drug therapy.Post-mortem examination showed evidence of massive hepatocellular necrosis, acute hypersensitivity myocarditis, focal acute tubulo-interstitial nephritis and extensive bone marrow necrosis, with no evidence of malignancy. It is thought that the clinico-pathological features and chronology of this case bore the hallmarks of the so-called \"3-week sulphasalazine syndrome\", a rare, but often fatal, immunoallergic reaction to sulphasalazine.", "entity": "Lymphatic Diseases", "aliases": "Disease Lymphatic Diseases Lymphadenopathy Lymphatism Status Lymphaticus", "definition": "Diseases of LYMPH; LYMPH NODES; or LYMPHATIC VESSELS.\n    ", "id": "MESH:D008206"}
{"mention": "hepatitis", "mention_text": "A 34-year-old lady developed a constellation of dermatitis, fever, lymphadenopathy and hepatitis, beginning on the 17th day of a course of oral sulphasalazine for sero-negative rheumatoid arthritis. Cervical and inguinal lymph node biopsies showed the features of severe necrotising lymphadenitis, associated with erythrophagocytosis and prominent eosinophilic infiltrates, without viral inclusion bodies, suggestive of an adverse drug reaction.A week later, fulminant drug-induced hepatitis, associated with the presence of anti-nuclear autoantibodies (but not with other markers of autoimmunity), and accompanied by multi-organ failure and sepsis, supervened. She subsequently died some 5 weeks after the commencement of her drug therapy.Post-mortem examination showed evidence of massive hepatocellular necrosis, acute hypersensitivity myocarditis, focal acute tubulo-interstitial nephritis and extensive bone marrow necrosis, with no evidence of malignancy. It is thought that the clinico-pathological features and chronology of this case bore the hallmarks of the so-called \"3-week sulphasalazine syndrome\", a rare, but often fatal, immunoallergic reaction to sulphasalazine.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "sulphasalazine", "mention_text": "A 34-year-old lady developed a constellation of dermatitis, fever, lymphadenopathy and hepatitis, beginning on the 17th day of a course of oral sulphasalazine for sero-negative rheumatoid arthritis. Cervical and inguinal lymph node biopsies showed the features of severe necrotising lymphadenitis, associated with erythrophagocytosis and prominent eosinophilic infiltrates, without viral inclusion bodies, suggestive of an adverse drug reaction.A week later, fulminant drug-induced hepatitis, associated with the presence of anti-nuclear autoantibodies (but not with other markers of autoimmunity), and accompanied by multi-organ failure and sepsis, supervened. She subsequently died some 5 weeks after the commencement of her drug therapy.Post-mortem examination showed evidence of massive hepatocellular necrosis, acute hypersensitivity myocarditis, focal acute tubulo-interstitial nephritis and extensive bone marrow necrosis, with no evidence of malignancy. It is thought that the clinico-pathological features and chronology of this case bore the hallmarks of the so-called \"3-week sulphasalazine syndrome\", a rare, but often fatal, immunoallergic reaction to sulphasalazine.", "entity": "Sulfasalazine", "aliases": "Alphapharm Brand of Sulfasalazine Ashbourne Asulfidine Azulfadine Azulfidine EN Colo Pleon Colo-Pleon FNA Henning Berlin Heyl Pfizer Pyralin Ratiopharm Salazopyrin Salazosulfapyridine Salicylazosulfapyridine Sanofi Synthelabo Sulfasalazin medac Sulfasalazin-Heyl Sulphasalazine Ucine Ulcol ratio ratio-Sulfasalazine", "definition": "A drug that is used in the management of inflammatory bowel diseases. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid (see MESALAMINE) released in the colon. (From Martindale, The Extra Pharmacopoeia, 30th ed, p907)\n    ", "id": "MESH:D012460"}
{"mention": "rheumatoid arthritis", "mention_text": "A 34-year-old lady developed a constellation of dermatitis, fever, lymphadenopathy and hepatitis, beginning on the 17th day of a course of oral sulphasalazine for sero-negative rheumatoid arthritis. Cervical and inguinal lymph node biopsies showed the features of severe necrotising lymphadenitis, associated with erythrophagocytosis and prominent eosinophilic infiltrates, without viral inclusion bodies, suggestive of an adverse drug reaction.A week later, fulminant drug-induced hepatitis, associated with the presence of anti-nuclear autoantibodies (but not with other markers of autoimmunity), and accompanied by multi-organ failure and sepsis, supervened. She subsequently died some 5 weeks after the commencement of her drug therapy.Post-mortem examination showed evidence of massive hepatocellular necrosis, acute hypersensitivity myocarditis, focal acute tubulo-interstitial nephritis and extensive bone marrow necrosis, with no evidence of malignancy. It is thought that the clinico-pathological features and chronology of this case bore the hallmarks of the so-called \"3-week sulphasalazine syndrome\", a rare, but often fatal, immunoallergic reaction to sulphasalazine.", "entity": "Arthritis, Rheumatoid", "aliases": "Arthritis Rheumatoid", "definition": "A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.\n    ", "id": "MESH:D001172"}
{"mention": "lymphadenitis", "mention_text": "A 34-year-old lady developed a constellation of dermatitis, fever, lymphadenopathy and hepatitis, beginning on the 17th day of a course of oral sulphasalazine for sero-negative rheumatoid arthritis. Cervical and inguinal lymph node biopsies showed the features of severe necrotising lymphadenitis, associated with erythrophagocytosis and prominent eosinophilic infiltrates, without viral inclusion bodies, suggestive of an adverse drug reaction.A week later, fulminant drug-induced hepatitis, associated with the presence of anti-nuclear autoantibodies (but not with other markers of autoimmunity), and accompanied by multi-organ failure and sepsis, supervened. She subsequently died some 5 weeks after the commencement of her drug therapy.Post-mortem examination showed evidence of massive hepatocellular necrosis, acute hypersensitivity myocarditis, focal acute tubulo-interstitial nephritis and extensive bone marrow necrosis, with no evidence of malignancy. It is thought that the clinico-pathological features and chronology of this case bore the hallmarks of the so-called \"3-week sulphasalazine syndrome\", a rare, but often fatal, immunoallergic reaction to sulphasalazine.", "entity": "Lymphadenitis", "aliases": "Adenitides Adenitis Lymphadenitides Lymphadenitis", "definition": "Inflammation of the lymph nodes.\n    ", "id": "MESH:D008199"}
{"mention": "adverse drug reaction", "mention_text": "A 34-year-old lady developed a constellation of dermatitis, fever, lymphadenopathy and hepatitis, beginning on the 17th day of a course of oral sulphasalazine for sero-negative rheumatoid arthritis. Cervical and inguinal lymph node biopsies showed the features of severe necrotising lymphadenitis, associated with erythrophagocytosis and prominent eosinophilic infiltrates, without viral inclusion bodies, suggestive of an adverse drug reaction.A week later, fulminant drug-induced hepatitis, associated with the presence of anti-nuclear autoantibodies (but not with other markers of autoimmunity), and accompanied by multi-organ failure and sepsis, supervened. She subsequently died some 5 weeks after the commencement of her drug therapy.Post-mortem examination showed evidence of massive hepatocellular necrosis, acute hypersensitivity myocarditis, focal acute tubulo-interstitial nephritis and extensive bone marrow necrosis, with no evidence of malignancy. It is thought that the clinico-pathological features and chronology of this case bore the hallmarks of the so-called \"3-week sulphasalazine syndrome\", a rare, but often fatal, immunoallergic reaction to sulphasalazine.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "drug-induced hepatitis", "mention_text": "A 34-year-old lady developed a constellation of dermatitis, fever, lymphadenopathy and hepatitis, beginning on the 17th day of a course of oral sulphasalazine for sero-negative rheumatoid arthritis. Cervical and inguinal lymph node biopsies showed the features of severe necrotising lymphadenitis, associated with erythrophagocytosis and prominent eosinophilic infiltrates, without viral inclusion bodies, suggestive of an adverse drug reaction.A week later, fulminant drug-induced hepatitis, associated with the presence of anti-nuclear autoantibodies (but not with other markers of autoimmunity), and accompanied by multi-organ failure and sepsis, supervened. She subsequently died some 5 weeks after the commencement of her drug therapy.Post-mortem examination showed evidence of massive hepatocellular necrosis, acute hypersensitivity myocarditis, focal acute tubulo-interstitial nephritis and extensive bone marrow necrosis, with no evidence of malignancy. It is thought that the clinico-pathological features and chronology of this case bore the hallmarks of the so-called \"3-week sulphasalazine syndrome\", a rare, but often fatal, immunoallergic reaction to sulphasalazine.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "autoimmunity", "mention_text": "A 34-year-old lady developed a constellation of dermatitis, fever, lymphadenopathy and hepatitis, beginning on the 17th day of a course of oral sulphasalazine for sero-negative rheumatoid arthritis. Cervical and inguinal lymph node biopsies showed the features of severe necrotising lymphadenitis, associated with erythrophagocytosis and prominent eosinophilic infiltrates, without viral inclusion bodies, suggestive of an adverse drug reaction.A week later, fulminant drug-induced hepatitis, associated with the presence of anti-nuclear autoantibodies (but not with other markers of autoimmunity), and accompanied by multi-organ failure and sepsis, supervened. She subsequently died some 5 weeks after the commencement of her drug therapy.Post-mortem examination showed evidence of massive hepatocellular necrosis, acute hypersensitivity myocarditis, focal acute tubulo-interstitial nephritis and extensive bone marrow necrosis, with no evidence of malignancy. It is thought that the clinico-pathological features and chronology of this case bore the hallmarks of the so-called \"3-week sulphasalazine syndrome\", a rare, but often fatal, immunoallergic reaction to sulphasalazine.", "entity": "Autoimmune Diseases", "aliases": "Autoimmune Disease Diseases", "definition": "Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.\n    ", "id": "MESH:D001327"}
{"mention": "multi-organ failure", "mention_text": "A 34-year-old lady developed a constellation of dermatitis, fever, lymphadenopathy and hepatitis, beginning on the 17th day of a course of oral sulphasalazine for sero-negative rheumatoid arthritis. Cervical and inguinal lymph node biopsies showed the features of severe necrotising lymphadenitis, associated with erythrophagocytosis and prominent eosinophilic infiltrates, without viral inclusion bodies, suggestive of an adverse drug reaction.A week later, fulminant drug-induced hepatitis, associated with the presence of anti-nuclear autoantibodies (but not with other markers of autoimmunity), and accompanied by multi-organ failure and sepsis, supervened. She subsequently died some 5 weeks after the commencement of her drug therapy.Post-mortem examination showed evidence of massive hepatocellular necrosis, acute hypersensitivity myocarditis, focal acute tubulo-interstitial nephritis and extensive bone marrow necrosis, with no evidence of malignancy. It is thought that the clinico-pathological features and chronology of this case bore the hallmarks of the so-called \"3-week sulphasalazine syndrome\", a rare, but often fatal, immunoallergic reaction to sulphasalazine.", "entity": "Multiple Organ Failure", "aliases": "Failure Multiple Organ MODS Dysfunction Syndrome Failures", "definition": "A progressive condition usually characterized by combined failure of several organs such as the lungs, liver, kidney, along with some clotting mechanisms, usually postinjury or postoperative.\n    ", "id": "MESH:D009102"}
{"mention": "sepsis", "mention_text": "A 34-year-old lady developed a constellation of dermatitis, fever, lymphadenopathy and hepatitis, beginning on the 17th day of a course of oral sulphasalazine for sero-negative rheumatoid arthritis. Cervical and inguinal lymph node biopsies showed the features of severe necrotising lymphadenitis, associated with erythrophagocytosis and prominent eosinophilic infiltrates, without viral inclusion bodies, suggestive of an adverse drug reaction.A week later, fulminant drug-induced hepatitis, associated with the presence of anti-nuclear autoantibodies (but not with other markers of autoimmunity), and accompanied by multi-organ failure and sepsis, supervened. She subsequently died some 5 weeks after the commencement of her drug therapy.Post-mortem examination showed evidence of massive hepatocellular necrosis, acute hypersensitivity myocarditis, focal acute tubulo-interstitial nephritis and extensive bone marrow necrosis, with no evidence of malignancy. It is thought that the clinico-pathological features and chronology of this case bore the hallmarks of the so-called \"3-week sulphasalazine syndrome\", a rare, but often fatal, immunoallergic reaction to sulphasalazine.", "entity": "Sepsis", "aliases": "Blood Poisoning Poisonings Pyaemia Pyaemias Pyemia Pyemias Pyohemia Pyohemias Sepsis Severe Septicemia Septicemias", "definition": "Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by HYPOTENSION despite adequate fluid infusion, it is called SEPTIC SHOCK.\n    ", "id": "MESH:D018805"}
{"mention": "massive hepatocellular necrosis", "mention_text": "A 34-year-old lady developed a constellation of dermatitis, fever, lymphadenopathy and hepatitis, beginning on the 17th day of a course of oral sulphasalazine for sero-negative rheumatoid arthritis. Cervical and inguinal lymph node biopsies showed the features of severe necrotising lymphadenitis, associated with erythrophagocytosis and prominent eosinophilic infiltrates, without viral inclusion bodies, suggestive of an adverse drug reaction.A week later, fulminant drug-induced hepatitis, associated with the presence of anti-nuclear autoantibodies (but not with other markers of autoimmunity), and accompanied by multi-organ failure and sepsis, supervened. She subsequently died some 5 weeks after the commencement of her drug therapy.Post-mortem examination showed evidence of massive hepatocellular necrosis, acute hypersensitivity myocarditis, focal acute tubulo-interstitial nephritis and extensive bone marrow necrosis, with no evidence of malignancy. It is thought that the clinico-pathological features and chronology of this case bore the hallmarks of the so-called \"3-week sulphasalazine syndrome\", a rare, but often fatal, immunoallergic reaction to sulphasalazine.", "entity": "Massive Hepatic Necrosis", "aliases": "Acute Yellow Atrophies Atrophy of Liver Hepatic Necrosis Massive", "definition": "Extensive and rapid death of parenchymal cells in the LIVER, often due to exposure to toxic materials. It is characterized by a soft, flabby, yellow-brown wrinkled, and shrunken liver. It was called \"acute yellow atrophy\".\n    ", "id": "MESH:D047508"}
{"mention": "myocarditis", "mention_text": "A 34-year-old lady developed a constellation of dermatitis, fever, lymphadenopathy and hepatitis, beginning on the 17th day of a course of oral sulphasalazine for sero-negative rheumatoid arthritis. Cervical and inguinal lymph node biopsies showed the features of severe necrotising lymphadenitis, associated with erythrophagocytosis and prominent eosinophilic infiltrates, without viral inclusion bodies, suggestive of an adverse drug reaction.A week later, fulminant drug-induced hepatitis, associated with the presence of anti-nuclear autoantibodies (but not with other markers of autoimmunity), and accompanied by multi-organ failure and sepsis, supervened. She subsequently died some 5 weeks after the commencement of her drug therapy.Post-mortem examination showed evidence of massive hepatocellular necrosis, acute hypersensitivity myocarditis, focal acute tubulo-interstitial nephritis and extensive bone marrow necrosis, with no evidence of malignancy. It is thought that the clinico-pathological features and chronology of this case bore the hallmarks of the so-called \"3-week sulphasalazine syndrome\", a rare, but often fatal, immunoallergic reaction to sulphasalazine.", "entity": "Myocarditis", "aliases": "Carditis Myocarditides Myocarditis", "definition": "Inflammatory processes of the muscular walls of the heart (MYOCARDIUM) which result in injury to the cardiac muscle cells (MYOCYTES, CARDIAC). Manifestations range from subclinical to sudden death (DEATH, SUDDEN). Myocarditis in association with cardiac dysfunction is classified as inflammatory CARDIOMYOPATHY usually caused by INFECTION, autoimmune diseases, or responses to toxic substances. Myocarditis is also a common cause of DILATED CARDIOMYOPATHY and other cardiomyopathies.\n    ", "id": "MESH:D009205"}
{"mention": "nephritis", "mention_text": "A 34-year-old lady developed a constellation of dermatitis, fever, lymphadenopathy and hepatitis, beginning on the 17th day of a course of oral sulphasalazine for sero-negative rheumatoid arthritis. Cervical and inguinal lymph node biopsies showed the features of severe necrotising lymphadenitis, associated with erythrophagocytosis and prominent eosinophilic infiltrates, without viral inclusion bodies, suggestive of an adverse drug reaction.A week later, fulminant drug-induced hepatitis, associated with the presence of anti-nuclear autoantibodies (but not with other markers of autoimmunity), and accompanied by multi-organ failure and sepsis, supervened. She subsequently died some 5 weeks after the commencement of her drug therapy.Post-mortem examination showed evidence of massive hepatocellular necrosis, acute hypersensitivity myocarditis, focal acute tubulo-interstitial nephritis and extensive bone marrow necrosis, with no evidence of malignancy. It is thought that the clinico-pathological features and chronology of this case bore the hallmarks of the so-called \"3-week sulphasalazine syndrome\", a rare, but often fatal, immunoallergic reaction to sulphasalazine.", "entity": "Nephritis", "aliases": "Nephritides Nephritis", "definition": "Inflammation of any part of the KIDNEY.\n    ", "id": "MESH:D009393"}
{"mention": "bone marrow necrosis", "mention_text": "A 34-year-old lady developed a constellation of dermatitis, fever, lymphadenopathy and hepatitis, beginning on the 17th day of a course of oral sulphasalazine for sero-negative rheumatoid arthritis. Cervical and inguinal lymph node biopsies showed the features of severe necrotising lymphadenitis, associated with erythrophagocytosis and prominent eosinophilic infiltrates, without viral inclusion bodies, suggestive of an adverse drug reaction.A week later, fulminant drug-induced hepatitis, associated with the presence of anti-nuclear autoantibodies (but not with other markers of autoimmunity), and accompanied by multi-organ failure and sepsis, supervened. She subsequently died some 5 weeks after the commencement of her drug therapy.Post-mortem examination showed evidence of massive hepatocellular necrosis, acute hypersensitivity myocarditis, focal acute tubulo-interstitial nephritis and extensive bone marrow necrosis, with no evidence of malignancy. It is thought that the clinico-pathological features and chronology of this case bore the hallmarks of the so-called \"3-week sulphasalazine syndrome\", a rare, but often fatal, immunoallergic reaction to sulphasalazine.", "entity": "Bone Marrow Diseases", "aliases": "Bone Marrow Disease Diseases", "definition": "", "id": "MESH:D001855"}
{"mention": "malignancy", "mention_text": "A 34-year-old lady developed a constellation of dermatitis, fever, lymphadenopathy and hepatitis, beginning on the 17th day of a course of oral sulphasalazine for sero-negative rheumatoid arthritis. Cervical and inguinal lymph node biopsies showed the features of severe necrotising lymphadenitis, associated with erythrophagocytosis and prominent eosinophilic infiltrates, without viral inclusion bodies, suggestive of an adverse drug reaction.A week later, fulminant drug-induced hepatitis, associated with the presence of anti-nuclear autoantibodies (but not with other markers of autoimmunity), and accompanied by multi-organ failure and sepsis, supervened. She subsequently died some 5 weeks after the commencement of her drug therapy.Post-mortem examination showed evidence of massive hepatocellular necrosis, acute hypersensitivity myocarditis, focal acute tubulo-interstitial nephritis and extensive bone marrow necrosis, with no evidence of malignancy. It is thought that the clinico-pathological features and chronology of this case bore the hallmarks of the so-called \"3-week sulphasalazine syndrome\", a rare, but often fatal, immunoallergic reaction to sulphasalazine.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "Bupropion", "mention_text": "Bupropion (Zyban) toxicity.", "entity": "Bupropion", "aliases": "(+-)-1-(3-Chlorophenyl)-2-((1,1-dimethylethyl)amino)-1-propanone Amfebutamone Bupropion Hydrochloride (+-)-Isomer Esteve Brand of Glaxo Wellcome 1 2 3 GlaxoSmithKline Quomen Wellbutrin Zyban (Anti-Smoking) Zyntabac", "definition": "A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment.\n    ", "id": "MESH:D016642"}
{"mention": "Zyban", "mention_text": "Bupropion (Zyban) toxicity.", "entity": "Bupropion", "aliases": "(+-)-1-(3-Chlorophenyl)-2-((1,1-dimethylethyl)amino)-1-propanone Amfebutamone Bupropion Hydrochloride (+-)-Isomer Esteve Brand of Glaxo Wellcome 1 2 3 GlaxoSmithKline Quomen Wellbutrin Zyban (Anti-Smoking) Zyntabac", "definition": "A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment.\n    ", "id": "MESH:D016642"}
{"mention": "toxicity", "mention_text": "Bupropion (Zyban) toxicity.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "Bupropion", "mention_text": "Bupropion is a monocyclic antidepressant structurally related to amphetamine. Zyban, a sustained-release formulation of bupropion hydrochloride, was recently released in Ireland, as a smoking cessation aid. In the initial 6 months since it's introduction, 12 overdose cases have been reported to The National Poisons Information Centre. 8 patients developed symptoms of toxicity. Common features included tachycardia, drowsiness, hallucinations and convulsions. Two patients developed severe cardiac arrhythmias, including one patient who was resuscitated following a cardiac arrest. All patients recovered without sequelae. We report a case of a 31 year old female who required admission to the Intensive Care Unit for ventilation and full supportive therapy, following ingestion of 13.5g bupropion. Recurrent seizures were treated with diazepam and broad complex tachycardia was successfully treated with adenosine. Zyban caused significant neurological and cardiovascular toxicity in overdose. The potential toxic effects should be considered when prescribing it as a smoking cessation aid.", "entity": "Bupropion", "aliases": "(+-)-1-(3-Chlorophenyl)-2-((1,1-dimethylethyl)amino)-1-propanone Amfebutamone Bupropion Hydrochloride (+-)-Isomer Esteve Brand of Glaxo Wellcome 1 2 3 GlaxoSmithKline Quomen Wellbutrin Zyban (Anti-Smoking) Zyntabac", "definition": "A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment.\n    ", "id": "MESH:D016642"}
{"mention": "antidepressant", "mention_text": "Bupropion is a monocyclic antidepressant structurally related to amphetamine. Zyban, a sustained-release formulation of bupropion hydrochloride, was recently released in Ireland, as a smoking cessation aid. In the initial 6 months since it's introduction, 12 overdose cases have been reported to The National Poisons Information Centre. 8 patients developed symptoms of toxicity. Common features included tachycardia, drowsiness, hallucinations and convulsions. Two patients developed severe cardiac arrhythmias, including one patient who was resuscitated following a cardiac arrest. All patients recovered without sequelae. We report a case of a 31 year old female who required admission to the Intensive Care Unit for ventilation and full supportive therapy, following ingestion of 13.5g bupropion. Recurrent seizures were treated with diazepam and broad complex tachycardia was successfully treated with adenosine. Zyban caused significant neurological and cardiovascular toxicity in overdose. The potential toxic effects should be considered when prescribing it as a smoking cessation aid.", "entity": "Antidepressive Agents", "aliases": "Agents Antidepressive Antidepressant Drugs Antidepressants Thymoanaleptics Thymoleptics", "definition": "Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.\n    ", "id": "MESH:D000928"}
{"mention": "amphetamine", "mention_text": "Bupropion is a monocyclic antidepressant structurally related to amphetamine. Zyban, a sustained-release formulation of bupropion hydrochloride, was recently released in Ireland, as a smoking cessation aid. In the initial 6 months since it's introduction, 12 overdose cases have been reported to The National Poisons Information Centre. 8 patients developed symptoms of toxicity. Common features included tachycardia, drowsiness, hallucinations and convulsions. Two patients developed severe cardiac arrhythmias, including one patient who was resuscitated following a cardiac arrest. All patients recovered without sequelae. We report a case of a 31 year old female who required admission to the Intensive Care Unit for ventilation and full supportive therapy, following ingestion of 13.5g bupropion. Recurrent seizures were treated with diazepam and broad complex tachycardia was successfully treated with adenosine. Zyban caused significant neurological and cardiovascular toxicity in overdose. The potential toxic effects should be considered when prescribing it as a smoking cessation aid.", "entity": "Amphetamine", "aliases": "Amfetamine Amphetamine Sulfate (2:1) Centramina Desoxynorephedrin Fenamine Levoamphetamine Miquel Brand of Mydrial Phenamine Phenopromin Thyramine l l-Amphetamine levo levo-Amphetamine", "definition": "A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE.\n    ", "id": "MESH:D000661"}
{"mention": "Zyban", "mention_text": "Bupropion is a monocyclic antidepressant structurally related to amphetamine. Zyban, a sustained-release formulation of bupropion hydrochloride, was recently released in Ireland, as a smoking cessation aid. In the initial 6 months since it's introduction, 12 overdose cases have been reported to The National Poisons Information Centre. 8 patients developed symptoms of toxicity. Common features included tachycardia, drowsiness, hallucinations and convulsions. Two patients developed severe cardiac arrhythmias, including one patient who was resuscitated following a cardiac arrest. All patients recovered without sequelae. We report a case of a 31 year old female who required admission to the Intensive Care Unit for ventilation and full supportive therapy, following ingestion of 13.5g bupropion. Recurrent seizures were treated with diazepam and broad complex tachycardia was successfully treated with adenosine. Zyban caused significant neurological and cardiovascular toxicity in overdose. The potential toxic effects should be considered when prescribing it as a smoking cessation aid.", "entity": "Bupropion", "aliases": "(+-)-1-(3-Chlorophenyl)-2-((1,1-dimethylethyl)amino)-1-propanone Amfebutamone Bupropion Hydrochloride (+-)-Isomer Esteve Brand of Glaxo Wellcome 1 2 3 GlaxoSmithKline Quomen Wellbutrin Zyban (Anti-Smoking) Zyntabac", "definition": "A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment.\n    ", "id": "MESH:D016642"}
{"mention": "bupropion hydrochloride", "mention_text": "Bupropion is a monocyclic antidepressant structurally related to amphetamine. Zyban, a sustained-release formulation of bupropion hydrochloride, was recently released in Ireland, as a smoking cessation aid. In the initial 6 months since it's introduction, 12 overdose cases have been reported to The National Poisons Information Centre. 8 patients developed symptoms of toxicity. Common features included tachycardia, drowsiness, hallucinations and convulsions. Two patients developed severe cardiac arrhythmias, including one patient who was resuscitated following a cardiac arrest. All patients recovered without sequelae. We report a case of a 31 year old female who required admission to the Intensive Care Unit for ventilation and full supportive therapy, following ingestion of 13.5g bupropion. Recurrent seizures were treated with diazepam and broad complex tachycardia was successfully treated with adenosine. Zyban caused significant neurological and cardiovascular toxicity in overdose. The potential toxic effects should be considered when prescribing it as a smoking cessation aid.", "entity": "Bupropion", "aliases": "(+-)-1-(3-Chlorophenyl)-2-((1,1-dimethylethyl)amino)-1-propanone Amfebutamone Bupropion Hydrochloride (+-)-Isomer Esteve Brand of Glaxo Wellcome 1 2 3 GlaxoSmithKline Quomen Wellbutrin Zyban (Anti-Smoking) Zyntabac", "definition": "A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment.\n    ", "id": "MESH:D016642"}
{"mention": "overdose", "mention_text": "Bupropion is a monocyclic antidepressant structurally related to amphetamine. Zyban, a sustained-release formulation of bupropion hydrochloride, was recently released in Ireland, as a smoking cessation aid. In the initial 6 months since it's introduction, 12 overdose cases have been reported to The National Poisons Information Centre. 8 patients developed symptoms of toxicity. Common features included tachycardia, drowsiness, hallucinations and convulsions. Two patients developed severe cardiac arrhythmias, including one patient who was resuscitated following a cardiac arrest. All patients recovered without sequelae. We report a case of a 31 year old female who required admission to the Intensive Care Unit for ventilation and full supportive therapy, following ingestion of 13.5g bupropion. Recurrent seizures were treated with diazepam and broad complex tachycardia was successfully treated with adenosine. Zyban caused significant neurological and cardiovascular toxicity in overdose. The potential toxic effects should be considered when prescribing it as a smoking cessation aid.", "entity": "Drug Overdose", "aliases": "Drug Overdose Overdoses", "definition": "Accidental or deliberate use of a medication or street drug in excess of normal dosage.\n    ", "id": "MESH:D062787"}
{"mention": "toxicity", "mention_text": "Bupropion is a monocyclic antidepressant structurally related to amphetamine. Zyban, a sustained-release formulation of bupropion hydrochloride, was recently released in Ireland, as a smoking cessation aid. In the initial 6 months since it's introduction, 12 overdose cases have been reported to The National Poisons Information Centre. 8 patients developed symptoms of toxicity. Common features included tachycardia, drowsiness, hallucinations and convulsions. Two patients developed severe cardiac arrhythmias, including one patient who was resuscitated following a cardiac arrest. All patients recovered without sequelae. We report a case of a 31 year old female who required admission to the Intensive Care Unit for ventilation and full supportive therapy, following ingestion of 13.5g bupropion. Recurrent seizures were treated with diazepam and broad complex tachycardia was successfully treated with adenosine. Zyban caused significant neurological and cardiovascular toxicity in overdose. The potential toxic effects should be considered when prescribing it as a smoking cessation aid.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "tachycardia", "mention_text": "Bupropion is a monocyclic antidepressant structurally related to amphetamine. Zyban, a sustained-release formulation of bupropion hydrochloride, was recently released in Ireland, as a smoking cessation aid. In the initial 6 months since it's introduction, 12 overdose cases have been reported to The National Poisons Information Centre. 8 patients developed symptoms of toxicity. Common features included tachycardia, drowsiness, hallucinations and convulsions. Two patients developed severe cardiac arrhythmias, including one patient who was resuscitated following a cardiac arrest. All patients recovered without sequelae. We report a case of a 31 year old female who required admission to the Intensive Care Unit for ventilation and full supportive therapy, following ingestion of 13.5g bupropion. Recurrent seizures were treated with diazepam and broad complex tachycardia was successfully treated with adenosine. Zyban caused significant neurological and cardiovascular toxicity in overdose. The potential toxic effects should be considered when prescribing it as a smoking cessation aid.", "entity": "Tachycardia", "aliases": "Tachyarrhythmia Tachyarrhythmias Tachycardia Tachycardias", "definition": "Abnormally rapid heartbeat, usually with a HEART RATE above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia.\n    ", "id": "MESH:D013610"}
{"mention": "hallucinations", "mention_text": "Bupropion is a monocyclic antidepressant structurally related to amphetamine. Zyban, a sustained-release formulation of bupropion hydrochloride, was recently released in Ireland, as a smoking cessation aid. In the initial 6 months since it's introduction, 12 overdose cases have been reported to The National Poisons Information Centre. 8 patients developed symptoms of toxicity. Common features included tachycardia, drowsiness, hallucinations and convulsions. Two patients developed severe cardiac arrhythmias, including one patient who was resuscitated following a cardiac arrest. All patients recovered without sequelae. We report a case of a 31 year old female who required admission to the Intensive Care Unit for ventilation and full supportive therapy, following ingestion of 13.5g bupropion. Recurrent seizures were treated with diazepam and broad complex tachycardia was successfully treated with adenosine. Zyban caused significant neurological and cardiovascular toxicity in overdose. The potential toxic effects should be considered when prescribing it as a smoking cessation aid.", "entity": "Hallucinations", "aliases": "Auditory Hallucination Verbal Hallucinations Body Sensation Dissociative Elementary Gustatory of Hypnagogic Hypnapompic Kinesthetic Mood Congruent Incongruent Olfactory Organic Reflex Sensory Somatic Tactile Visual Formed People Internal Unformed", "definition": "Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with MENTAL DISORDERS.\n    ", "id": "MESH:D006212"}
{"mention": "convulsions", "mention_text": "Bupropion is a monocyclic antidepressant structurally related to amphetamine. Zyban, a sustained-release formulation of bupropion hydrochloride, was recently released in Ireland, as a smoking cessation aid. In the initial 6 months since it's introduction, 12 overdose cases have been reported to The National Poisons Information Centre. 8 patients developed symptoms of toxicity. Common features included tachycardia, drowsiness, hallucinations and convulsions. Two patients developed severe cardiac arrhythmias, including one patient who was resuscitated following a cardiac arrest. All patients recovered without sequelae. We report a case of a 31 year old female who required admission to the Intensive Care Unit for ventilation and full supportive therapy, following ingestion of 13.5g bupropion. Recurrent seizures were treated with diazepam and broad complex tachycardia was successfully treated with adenosine. Zyban caused significant neurological and cardiovascular toxicity in overdose. The potential toxic effects should be considered when prescribing it as a smoking cessation aid.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "cardiac arrhythmias", "mention_text": "Bupropion is a monocyclic antidepressant structurally related to amphetamine. Zyban, a sustained-release formulation of bupropion hydrochloride, was recently released in Ireland, as a smoking cessation aid. In the initial 6 months since it's introduction, 12 overdose cases have been reported to The National Poisons Information Centre. 8 patients developed symptoms of toxicity. Common features included tachycardia, drowsiness, hallucinations and convulsions. Two patients developed severe cardiac arrhythmias, including one patient who was resuscitated following a cardiac arrest. All patients recovered without sequelae. We report a case of a 31 year old female who required admission to the Intensive Care Unit for ventilation and full supportive therapy, following ingestion of 13.5g bupropion. Recurrent seizures were treated with diazepam and broad complex tachycardia was successfully treated with adenosine. Zyban caused significant neurological and cardiovascular toxicity in overdose. The potential toxic effects should be considered when prescribing it as a smoking cessation aid.", "entity": "Arrhythmias, Cardiac", "aliases": "Arrhythmia Cardiac Arrhythmias Arrythmia Dysrhythmia", "definition": "Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.\n    ", "id": "MESH:D001145"}
{"mention": "cardiac arrest", "mention_text": "Bupropion is a monocyclic antidepressant structurally related to amphetamine. Zyban, a sustained-release formulation of bupropion hydrochloride, was recently released in Ireland, as a smoking cessation aid. In the initial 6 months since it's introduction, 12 overdose cases have been reported to The National Poisons Information Centre. 8 patients developed symptoms of toxicity. Common features included tachycardia, drowsiness, hallucinations and convulsions. Two patients developed severe cardiac arrhythmias, including one patient who was resuscitated following a cardiac arrest. All patients recovered without sequelae. We report a case of a 31 year old female who required admission to the Intensive Care Unit for ventilation and full supportive therapy, following ingestion of 13.5g bupropion. Recurrent seizures were treated with diazepam and broad complex tachycardia was successfully treated with adenosine. Zyban caused significant neurological and cardiovascular toxicity in overdose. The potential toxic effects should be considered when prescribing it as a smoking cessation aid.", "entity": "Heart Arrest", "aliases": "Arrest Cardiac Cardiopulmonary Heart Asystole Asystoles", "definition": "Cessation of heart beat or MYOCARDIAL CONTRACTION. If it is treated within a few minutes, heart arrest can be reversed in most cases to normal cardiac rhythm and effective circulation.\n    ", "id": "MESH:D006323"}
{"mention": "bupropion", "mention_text": "Bupropion is a monocyclic antidepressant structurally related to amphetamine. Zyban, a sustained-release formulation of bupropion hydrochloride, was recently released in Ireland, as a smoking cessation aid. In the initial 6 months since it's introduction, 12 overdose cases have been reported to The National Poisons Information Centre. 8 patients developed symptoms of toxicity. Common features included tachycardia, drowsiness, hallucinations and convulsions. Two patients developed severe cardiac arrhythmias, including one patient who was resuscitated following a cardiac arrest. All patients recovered without sequelae. We report a case of a 31 year old female who required admission to the Intensive Care Unit for ventilation and full supportive therapy, following ingestion of 13.5g bupropion. Recurrent seizures were treated with diazepam and broad complex tachycardia was successfully treated with adenosine. Zyban caused significant neurological and cardiovascular toxicity in overdose. The potential toxic effects should be considered when prescribing it as a smoking cessation aid.", "entity": "Bupropion", "aliases": "(+-)-1-(3-Chlorophenyl)-2-((1,1-dimethylethyl)amino)-1-propanone Amfebutamone Bupropion Hydrochloride (+-)-Isomer Esteve Brand of Glaxo Wellcome 1 2 3 GlaxoSmithKline Quomen Wellbutrin Zyban (Anti-Smoking) Zyntabac", "definition": "A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment.\n    ", "id": "MESH:D016642"}
{"mention": "seizures", "mention_text": "Bupropion is a monocyclic antidepressant structurally related to amphetamine. Zyban, a sustained-release formulation of bupropion hydrochloride, was recently released in Ireland, as a smoking cessation aid. In the initial 6 months since it's introduction, 12 overdose cases have been reported to The National Poisons Information Centre. 8 patients developed symptoms of toxicity. Common features included tachycardia, drowsiness, hallucinations and convulsions. Two patients developed severe cardiac arrhythmias, including one patient who was resuscitated following a cardiac arrest. All patients recovered without sequelae. We report a case of a 31 year old female who required admission to the Intensive Care Unit for ventilation and full supportive therapy, following ingestion of 13.5g bupropion. Recurrent seizures were treated with diazepam and broad complex tachycardia was successfully treated with adenosine. Zyban caused significant neurological and cardiovascular toxicity in overdose. The potential toxic effects should be considered when prescribing it as a smoking cessation aid.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "diazepam", "mention_text": "Bupropion is a monocyclic antidepressant structurally related to amphetamine. Zyban, a sustained-release formulation of bupropion hydrochloride, was recently released in Ireland, as a smoking cessation aid. In the initial 6 months since it's introduction, 12 overdose cases have been reported to The National Poisons Information Centre. 8 patients developed symptoms of toxicity. Common features included tachycardia, drowsiness, hallucinations and convulsions. Two patients developed severe cardiac arrhythmias, including one patient who was resuscitated following a cardiac arrest. All patients recovered without sequelae. We report a case of a 31 year old female who required admission to the Intensive Care Unit for ventilation and full supportive therapy, following ingestion of 13.5g bupropion. Recurrent seizures were treated with diazepam and broad complex tachycardia was successfully treated with adenosine. Zyban caused significant neurological and cardiovascular toxicity in overdose. The potential toxic effects should be considered when prescribing it as a smoking cessation aid.", "entity": "Diazepam", "aliases": "7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one Apaurin Diazemuls Diazepam Faustan Relanium Seduxen Sibazon Stesolid Valium", "definition": "A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity.\n    ", "id": "MESH:D003975"}
{"mention": "adenosine", "mention_text": "Bupropion is a monocyclic antidepressant structurally related to amphetamine. Zyban, a sustained-release formulation of bupropion hydrochloride, was recently released in Ireland, as a smoking cessation aid. In the initial 6 months since it's introduction, 12 overdose cases have been reported to The National Poisons Information Centre. 8 patients developed symptoms of toxicity. Common features included tachycardia, drowsiness, hallucinations and convulsions. Two patients developed severe cardiac arrhythmias, including one patient who was resuscitated following a cardiac arrest. All patients recovered without sequelae. We report a case of a 31 year old female who required admission to the Intensive Care Unit for ventilation and full supportive therapy, following ingestion of 13.5g bupropion. Recurrent seizures were treated with diazepam and broad complex tachycardia was successfully treated with adenosine. Zyban caused significant neurological and cardiovascular toxicity in overdose. The potential toxic effects should be considered when prescribing it as a smoking cessation aid.", "entity": "Adenosine", "aliases": "Adenocard Adenoscan Adenosine", "definition": "A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.\n    ", "id": "MESH:D000241"}
{"mention": "cardiovascular toxicity", "mention_text": "Bupropion is a monocyclic antidepressant structurally related to amphetamine. Zyban, a sustained-release formulation of bupropion hydrochloride, was recently released in Ireland, as a smoking cessation aid. In the initial 6 months since it's introduction, 12 overdose cases have been reported to The National Poisons Information Centre. 8 patients developed symptoms of toxicity. Common features included tachycardia, drowsiness, hallucinations and convulsions. Two patients developed severe cardiac arrhythmias, including one patient who was resuscitated following a cardiac arrest. All patients recovered without sequelae. We report a case of a 31 year old female who required admission to the Intensive Care Unit for ventilation and full supportive therapy, following ingestion of 13.5g bupropion. Recurrent seizures were treated with diazepam and broad complex tachycardia was successfully treated with adenosine. Zyban caused significant neurological and cardiovascular toxicity in overdose. The potential toxic effects should be considered when prescribing it as a smoking cessation aid.", "entity": "Cardiovascular Diseases", "aliases": "Cardiovascular Disease Diseases", "definition": "Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.\n    ", "id": "MESH:D002318"}
{"mention": "indocyanine green", "mention_text": "Survey of complications of indocyanine green angiography in Japan.", "entity": "Indocyanine Green", "aliases": "Cardio Green Cardio-Green Cardiogreen Indocyanine Ujoveridin Vofaverdin Vophaverdin Wofaverdin", "definition": "A tricarbocyanine dye that is used diagnostically in liver function tests and to determine blood volume and cardiac output.\n    ", "id": "MESH:D007208"}
{"mention": "indocyanine green", "mention_text": "PURPOSE: We evaluated the safety of indocyanine green for use in fundus angiography. METHODS: We sent a questionnaire concerning complications of indocyanine green to 32 institutions in Japan, which were selected on the basis of the client list from the Topcon Company, which manufactures the indocyanine green fundus camera. RESULTS: Ophthalmologists at 15 institutions responded, reporting a total of 3,774 indocyanine green angiograms performed on 2,820 patients between June 1984 and September 1992. Before angiography, intradermal or intravenous indocyanine green testing, or both was performed at 13 of 15 institutions. For three patients, the decision was made not to proceed with angiography after positive preangiographic testing. The dosage of indocyanine green used for angiography varied from 25 to 75 mg, depending upon the institution. There were 13 cases of adverse reactions (0.34%), ten of which were mild reactions such as nausea, exanthema, urtication, itchiness, and urgency to defecate, and did not require treatment. Also recorded were one case of pain of the vein, which required treatment, and two cases of hypotension. The two hypotensive patients required treatment for shock. CONCLUSIONS: A comparison of frequency of adverse reactions to indocyanine green with the previously reported frequency of such reactions to fluorescein sodium indicated that indocyanine green is a safe as fluorescein for use in angiography.", "entity": "Indocyanine Green", "aliases": "Cardio Green Cardio-Green Cardiogreen Indocyanine Ujoveridin Vofaverdin Vophaverdin Wofaverdin", "definition": "A tricarbocyanine dye that is used diagnostically in liver function tests and to determine blood volume and cardiac output.\n    ", "id": "MESH:D007208"}
{"mention": "nausea", "mention_text": "PURPOSE: We evaluated the safety of indocyanine green for use in fundus angiography. METHODS: We sent a questionnaire concerning complications of indocyanine green to 32 institutions in Japan, which were selected on the basis of the client list from the Topcon Company, which manufactures the indocyanine green fundus camera. RESULTS: Ophthalmologists at 15 institutions responded, reporting a total of 3,774 indocyanine green angiograms performed on 2,820 patients between June 1984 and September 1992. Before angiography, intradermal or intravenous indocyanine green testing, or both was performed at 13 of 15 institutions. For three patients, the decision was made not to proceed with angiography after positive preangiographic testing. The dosage of indocyanine green used for angiography varied from 25 to 75 mg, depending upon the institution. There were 13 cases of adverse reactions (0.34%), ten of which were mild reactions such as nausea, exanthema, urtication, itchiness, and urgency to defecate, and did not require treatment. Also recorded were one case of pain of the vein, which required treatment, and two cases of hypotension. The two hypotensive patients required treatment for shock. CONCLUSIONS: A comparison of frequency of adverse reactions to indocyanine green with the previously reported frequency of such reactions to fluorescein sodium indicated that indocyanine green is a safe as fluorescein for use in angiography.", "entity": "Nausea", "aliases": "Nausea", "definition": "An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.\n    ", "id": "MESH:D009325"}
{"mention": "exanthema", "mention_text": "PURPOSE: We evaluated the safety of indocyanine green for use in fundus angiography. METHODS: We sent a questionnaire concerning complications of indocyanine green to 32 institutions in Japan, which were selected on the basis of the client list from the Topcon Company, which manufactures the indocyanine green fundus camera. RESULTS: Ophthalmologists at 15 institutions responded, reporting a total of 3,774 indocyanine green angiograms performed on 2,820 patients between June 1984 and September 1992. Before angiography, intradermal or intravenous indocyanine green testing, or both was performed at 13 of 15 institutions. For three patients, the decision was made not to proceed with angiography after positive preangiographic testing. The dosage of indocyanine green used for angiography varied from 25 to 75 mg, depending upon the institution. There were 13 cases of adverse reactions (0.34%), ten of which were mild reactions such as nausea, exanthema, urtication, itchiness, and urgency to defecate, and did not require treatment. Also recorded were one case of pain of the vein, which required treatment, and two cases of hypotension. The two hypotensive patients required treatment for shock. CONCLUSIONS: A comparison of frequency of adverse reactions to indocyanine green with the previously reported frequency of such reactions to fluorescein sodium indicated that indocyanine green is a safe as fluorescein for use in angiography.", "entity": "Exanthema", "aliases": "Exanthem Exanthema Rash Skin", "definition": "Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke's disease), fifth (ERYTHEMA INFECTIOSUM), and sixth (EXANTHEMA SUBITUM) numeric designations survive as occasional synonyms in current terminology.\n    ", "id": "MESH:D005076"}
{"mention": "urtication", "mention_text": "PURPOSE: We evaluated the safety of indocyanine green for use in fundus angiography. METHODS: We sent a questionnaire concerning complications of indocyanine green to 32 institutions in Japan, which were selected on the basis of the client list from the Topcon Company, which manufactures the indocyanine green fundus camera. RESULTS: Ophthalmologists at 15 institutions responded, reporting a total of 3,774 indocyanine green angiograms performed on 2,820 patients between June 1984 and September 1992. Before angiography, intradermal or intravenous indocyanine green testing, or both was performed at 13 of 15 institutions. For three patients, the decision was made not to proceed with angiography after positive preangiographic testing. The dosage of indocyanine green used for angiography varied from 25 to 75 mg, depending upon the institution. There were 13 cases of adverse reactions (0.34%), ten of which were mild reactions such as nausea, exanthema, urtication, itchiness, and urgency to defecate, and did not require treatment. Also recorded were one case of pain of the vein, which required treatment, and two cases of hypotension. The two hypotensive patients required treatment for shock. CONCLUSIONS: A comparison of frequency of adverse reactions to indocyanine green with the previously reported frequency of such reactions to fluorescein sodium indicated that indocyanine green is a safe as fluorescein for use in angiography.", "entity": "Urticaria", "aliases": "Hives Urticaria Urticarias", "definition": "A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress.\n    ", "id": "MESH:D014581"}
{"mention": "itchiness", "mention_text": "PURPOSE: We evaluated the safety of indocyanine green for use in fundus angiography. METHODS: We sent a questionnaire concerning complications of indocyanine green to 32 institutions in Japan, which were selected on the basis of the client list from the Topcon Company, which manufactures the indocyanine green fundus camera. RESULTS: Ophthalmologists at 15 institutions responded, reporting a total of 3,774 indocyanine green angiograms performed on 2,820 patients between June 1984 and September 1992. Before angiography, intradermal or intravenous indocyanine green testing, or both was performed at 13 of 15 institutions. For three patients, the decision was made not to proceed with angiography after positive preangiographic testing. The dosage of indocyanine green used for angiography varied from 25 to 75 mg, depending upon the institution. There were 13 cases of adverse reactions (0.34%), ten of which were mild reactions such as nausea, exanthema, urtication, itchiness, and urgency to defecate, and did not require treatment. Also recorded were one case of pain of the vein, which required treatment, and two cases of hypotension. The two hypotensive patients required treatment for shock. CONCLUSIONS: A comparison of frequency of adverse reactions to indocyanine green with the previously reported frequency of such reactions to fluorescein sodium indicated that indocyanine green is a safe as fluorescein for use in angiography.", "entity": "Pruritus", "aliases": "Itching Pruritis Pruritus", "definition": "An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief.\n    ", "id": "MESH:D011537"}
{"mention": "pain", "mention_text": "PURPOSE: We evaluated the safety of indocyanine green for use in fundus angiography. METHODS: We sent a questionnaire concerning complications of indocyanine green to 32 institutions in Japan, which were selected on the basis of the client list from the Topcon Company, which manufactures the indocyanine green fundus camera. RESULTS: Ophthalmologists at 15 institutions responded, reporting a total of 3,774 indocyanine green angiograms performed on 2,820 patients between June 1984 and September 1992. Before angiography, intradermal or intravenous indocyanine green testing, or both was performed at 13 of 15 institutions. For three patients, the decision was made not to proceed with angiography after positive preangiographic testing. The dosage of indocyanine green used for angiography varied from 25 to 75 mg, depending upon the institution. There were 13 cases of adverse reactions (0.34%), ten of which were mild reactions such as nausea, exanthema, urtication, itchiness, and urgency to defecate, and did not require treatment. Also recorded were one case of pain of the vein, which required treatment, and two cases of hypotension. The two hypotensive patients required treatment for shock. CONCLUSIONS: A comparison of frequency of adverse reactions to indocyanine green with the previously reported frequency of such reactions to fluorescein sodium indicated that indocyanine green is a safe as fluorescein for use in angiography.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "hypotension", "mention_text": "PURPOSE: We evaluated the safety of indocyanine green for use in fundus angiography. METHODS: We sent a questionnaire concerning complications of indocyanine green to 32 institutions in Japan, which were selected on the basis of the client list from the Topcon Company, which manufactures the indocyanine green fundus camera. RESULTS: Ophthalmologists at 15 institutions responded, reporting a total of 3,774 indocyanine green angiograms performed on 2,820 patients between June 1984 and September 1992. Before angiography, intradermal or intravenous indocyanine green testing, or both was performed at 13 of 15 institutions. For three patients, the decision was made not to proceed with angiography after positive preangiographic testing. The dosage of indocyanine green used for angiography varied from 25 to 75 mg, depending upon the institution. There were 13 cases of adverse reactions (0.34%), ten of which were mild reactions such as nausea, exanthema, urtication, itchiness, and urgency to defecate, and did not require treatment. Also recorded were one case of pain of the vein, which required treatment, and two cases of hypotension. The two hypotensive patients required treatment for shock. CONCLUSIONS: A comparison of frequency of adverse reactions to indocyanine green with the previously reported frequency of such reactions to fluorescein sodium indicated that indocyanine green is a safe as fluorescein for use in angiography.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "hypotensive", "mention_text": "PURPOSE: We evaluated the safety of indocyanine green for use in fundus angiography. METHODS: We sent a questionnaire concerning complications of indocyanine green to 32 institutions in Japan, which were selected on the basis of the client list from the Topcon Company, which manufactures the indocyanine green fundus camera. RESULTS: Ophthalmologists at 15 institutions responded, reporting a total of 3,774 indocyanine green angiograms performed on 2,820 patients between June 1984 and September 1992. Before angiography, intradermal or intravenous indocyanine green testing, or both was performed at 13 of 15 institutions. For three patients, the decision was made not to proceed with angiography after positive preangiographic testing. The dosage of indocyanine green used for angiography varied from 25 to 75 mg, depending upon the institution. There were 13 cases of adverse reactions (0.34%), ten of which were mild reactions such as nausea, exanthema, urtication, itchiness, and urgency to defecate, and did not require treatment. Also recorded were one case of pain of the vein, which required treatment, and two cases of hypotension. The two hypotensive patients required treatment for shock. CONCLUSIONS: A comparison of frequency of adverse reactions to indocyanine green with the previously reported frequency of such reactions to fluorescein sodium indicated that indocyanine green is a safe as fluorescein for use in angiography.", "entity": "Hypotension", "aliases": "Blood Pressure Low Hypotension Vascular", "definition": "Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.\n    ", "id": "MESH:D007022"}
{"mention": "shock", "mention_text": "PURPOSE: We evaluated the safety of indocyanine green for use in fundus angiography. METHODS: We sent a questionnaire concerning complications of indocyanine green to 32 institutions in Japan, which were selected on the basis of the client list from the Topcon Company, which manufactures the indocyanine green fundus camera. RESULTS: Ophthalmologists at 15 institutions responded, reporting a total of 3,774 indocyanine green angiograms performed on 2,820 patients between June 1984 and September 1992. Before angiography, intradermal or intravenous indocyanine green testing, or both was performed at 13 of 15 institutions. For three patients, the decision was made not to proceed with angiography after positive preangiographic testing. The dosage of indocyanine green used for angiography varied from 25 to 75 mg, depending upon the institution. There were 13 cases of adverse reactions (0.34%), ten of which were mild reactions such as nausea, exanthema, urtication, itchiness, and urgency to defecate, and did not require treatment. Also recorded were one case of pain of the vein, which required treatment, and two cases of hypotension. The two hypotensive patients required treatment for shock. CONCLUSIONS: A comparison of frequency of adverse reactions to indocyanine green with the previously reported frequency of such reactions to fluorescein sodium indicated that indocyanine green is a safe as fluorescein for use in angiography.", "entity": "Shock", "aliases": "Circulatory Collapse Failure Hypovolemic Shock", "definition": "A pathological condition manifested by failure to perfuse or oxygenate vital organs.\n    ", "id": "MESH:D012769"}
{"mention": "fluorescein sodium", "mention_text": "PURPOSE: We evaluated the safety of indocyanine green for use in fundus angiography. METHODS: We sent a questionnaire concerning complications of indocyanine green to 32 institutions in Japan, which were selected on the basis of the client list from the Topcon Company, which manufactures the indocyanine green fundus camera. RESULTS: Ophthalmologists at 15 institutions responded, reporting a total of 3,774 indocyanine green angiograms performed on 2,820 patients between June 1984 and September 1992. Before angiography, intradermal or intravenous indocyanine green testing, or both was performed at 13 of 15 institutions. For three patients, the decision was made not to proceed with angiography after positive preangiographic testing. The dosage of indocyanine green used for angiography varied from 25 to 75 mg, depending upon the institution. There were 13 cases of adverse reactions (0.34%), ten of which were mild reactions such as nausea, exanthema, urtication, itchiness, and urgency to defecate, and did not require treatment. Also recorded were one case of pain of the vein, which required treatment, and two cases of hypotension. The two hypotensive patients required treatment for shock. CONCLUSIONS: A comparison of frequency of adverse reactions to indocyanine green with the previously reported frequency of such reactions to fluorescein sodium indicated that indocyanine green is a safe as fluorescein for use in angiography.", "entity": "Fluorescein", "aliases": "Alcon Brand of Fluorescein Sodium Allergan C.I. 45350 Cahill May Roberts Chauvin Colircusi Fluoresceina D & C Yellow No. 7 8 and D&C Diba Diofluor Dioptic Dipotassium Salt Disodium Fluor I Strip A.T. Fluor-I-Strip Monosodium Minims Fluoresceine Fluorescite Fluorescéine sodique Faure Fluorets Ful Glo Ful-Glo Funduscein Stains Novartis Optifluor Smith Nephew Sola Barnes Hind Sola-Barnes-Hind Uranine Wyeth", "definition": "A phthalic indicator dye that appears yellow-green in normal tear film and bright green in a more alkaline medium such as the aqueous humor, used as a diagnostic aid in corneal injuries and corneal trauma.\n    ", "id": "MESH:D019793"}
{"mention": "fluorescein", "mention_text": "PURPOSE: We evaluated the safety of indocyanine green for use in fundus angiography. METHODS: We sent a questionnaire concerning complications of indocyanine green to 32 institutions in Japan, which were selected on the basis of the client list from the Topcon Company, which manufactures the indocyanine green fundus camera. RESULTS: Ophthalmologists at 15 institutions responded, reporting a total of 3,774 indocyanine green angiograms performed on 2,820 patients between June 1984 and September 1992. Before angiography, intradermal or intravenous indocyanine green testing, or both was performed at 13 of 15 institutions. For three patients, the decision was made not to proceed with angiography after positive preangiographic testing. The dosage of indocyanine green used for angiography varied from 25 to 75 mg, depending upon the institution. There were 13 cases of adverse reactions (0.34%), ten of which were mild reactions such as nausea, exanthema, urtication, itchiness, and urgency to defecate, and did not require treatment. Also recorded were one case of pain of the vein, which required treatment, and two cases of hypotension. The two hypotensive patients required treatment for shock. CONCLUSIONS: A comparison of frequency of adverse reactions to indocyanine green with the previously reported frequency of such reactions to fluorescein sodium indicated that indocyanine green is a safe as fluorescein for use in angiography.", "entity": "Fluorescein", "aliases": "Alcon Brand of Fluorescein Sodium Allergan C.I. 45350 Cahill May Roberts Chauvin Colircusi Fluoresceina D & C Yellow No. 7 8 and D&C Diba Diofluor Dioptic Dipotassium Salt Disodium Fluor I Strip A.T. Fluor-I-Strip Monosodium Minims Fluoresceine Fluorescite Fluorescéine sodique Faure Fluorets Ful Glo Ful-Glo Funduscein Stains Novartis Optifluor Smith Nephew Sola Barnes Hind Sola-Barnes-Hind Uranine Wyeth", "definition": "A phthalic indicator dye that appears yellow-green in normal tear film and bright green in a more alkaline medium such as the aqueous humor, used as a diagnostic aid in corneal injuries and corneal trauma.\n    ", "id": "MESH:D019793"}
{"mention": "Bradykinin", "mention_text": "Bradykinin receptors antagonists and nitric oxide synthase inhibitors in vincristine and streptozotocin induced hyperalgesia in chemotherapy and diabetic neuropathy rat model.", "entity": "Bradykinin", "aliases": "Arg Pro Pro Gly Phe Ser Pro Phe Arg Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg Bradykinin Acetate (9-D-Arg)-Isomer Diacetate Hydrochloride Triacetate (1-D-Arg)-Isomer (2-D-Pro)-Isomer (2-D-Pro-3-D-Pro-7-D-Pro)-Isomer (2-D-Pro-7-D-Pro)-Isomer (3-D-Pro)-Isomer (3-D-Pro-7-D-Pro)-Isomer (5-D-Phe)-Isomer (5-D-Phe-8-D-Phe)-Isomer (6-D-Ser)-Isomer (7-D-Pro)-Isomer (8-D-Phe)-Isomer", "definition": "A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.\n    ", "id": "MESH:D001920"}
{"mention": "nitric oxide", "mention_text": "Bradykinin receptors antagonists and nitric oxide synthase inhibitors in vincristine and streptozotocin induced hyperalgesia in chemotherapy and diabetic neuropathy rat model.", "entity": "Nitric Oxide", "aliases": "Endogenous Nitrate Vasodilator Endothelium-Derived Nitric Oxide Mononitrogen Monoxide Nitrogen Endothelium Derived", "definition": "A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.\n    ", "id": "MESH:D009569"}
{"mention": "vincristine", "mention_text": "Bradykinin receptors antagonists and nitric oxide synthase inhibitors in vincristine and streptozotocin induced hyperalgesia in chemotherapy and diabetic neuropathy rat model.", "entity": "Vincristine", "aliases": "Bristol-Myers Squibb Brand of Vincristine Sulfate Citomid Columbia EG Labo Farmistin Irisfarma Lemery Leurocristine Lilly Oncovin Oncovine Onkocristin Onkoworks PFS Vincasar Pfizer Teva Vincristin Bristol Liquid medac Vincrisul Vintec cell pharm cellcristin", "definition": "Antitumor alkaloid isolated from Vinca Rosea. (Merck, 11th ed.)\n    ", "id": "MESH:D014750"}
{"mention": "streptozotocin", "mention_text": "Bradykinin receptors antagonists and nitric oxide synthase inhibitors in vincristine and streptozotocin induced hyperalgesia in chemotherapy and diabetic neuropathy rat model.", "entity": "Streptozocin", "aliases": "2-Deoxy-2-((methylnitrosoamino)carbonyl)amino-D-glucose Streptozocin Teva Brand Streptozotocin Streptozotocine of Zanosar", "definition": "An antibiotic that is produced by Stretomyces achromogenes. It is used as an antineoplastic agent and to induce diabetes in experimental animals.\n    ", "id": "MESH:D013311"}
{"mention": "hyperalgesia", "mention_text": "Bradykinin receptors antagonists and nitric oxide synthase inhibitors in vincristine and streptozotocin induced hyperalgesia in chemotherapy and diabetic neuropathy rat model.", "entity": "Hyperalgesia", "aliases": "Allodynia Mechanical Tactile Thermal Allodynias Hyperalgesia Primary Secondary Hyperalgesias Hyperalgesic Sensations", "definition": "An increased sensation of pain or discomfort produced by mimimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve.\n    ", "id": "MESH:D006930"}
{"mention": "diabetic neuropathy", "mention_text": "Bradykinin receptors antagonists and nitric oxide synthase inhibitors in vincristine and streptozotocin induced hyperalgesia in chemotherapy and diabetic neuropathy rat model.", "entity": "Diabetic Neuropathies", "aliases": "Amyotrophies Diabetic Amyotrophy Asymmetric Proximal Motor Neuropathy Polyneuropathies Polyneuropathy Autonomic Neuropathies Mononeuropathies Mononeuropathy Simplex Simplices Neuralgia Neuralgias Painful Symmetric", "definition": "Peripheral, autonomic, and cranial nerve disorders that are associated with DIABETES MELLITUS. These conditions usually result from diabetic microvascular injury involving small blood vessels that supply nerves (VASA NERVORUM). Relatively common conditions which may be associated with diabetic neuropathy include third nerve palsy (see OCULOMOTOR NERVE DISEASES); MONONEUROPATHY; mononeuropathy multiplex; diabetic amyotrophy; a painful POLYNEUROPATHY; autonomic neuropathy; and thoracoabdominal neuropathy. (From Adams et al., Principles of Neurology, 6th ed, p1325)\n    ", "id": "MESH:D003929"}
{"mention": "NO", "mention_text": "PURPOSE: The influence of an irreversible inhibitor of constitutive NO synthase (L-NOArg; 1.0 mg/kg ip), a relatively selective inhibitor of inducible NO synthase (L-NIL; 1.0 mg/kg ip) and a relatively specific inhibitor of neuronal NO synthase (7-NI; 0.1 mg/kg ip), on antihyperalgesic action of selective antagonists of B2 and B1 receptors: D-Arg-[Hyp3,Thi5,D-Tic7,Oic8] bradykinin (HOE 140; 70 nmol/kg ip) or des Arg10 HOE 140 (70 nmol/kg ip) respectively, in model of diabetic (streptozotocin-induced) and toxic (vincristine-induced) neuropathy was investigated. METHODS: The changes in pain thresholds were determined using mechanical stimuli--the modification of the classic paw withdrawal test described by Randall-Selitto. RESULTS: The results of this paper confirm that inhibition of bradykinin receptors and inducible NO synthase but not neuronal NO synthase activity reduces diabetic hyperalgesia. Pretreatment with L-NOArg and L-NIL but not 7-NI, significantly increases antihyperalgesic activity both HOE 140 and des Arg10 HOE 140. It was also shown that both products of inducible NO synthase and neuronal NO synthase activation as well as bradykinin are involved in hyperalgesia produced by vincristine. Moreover, L-NOArg and 7-NI but not L-NIL intensify antihyperalgesic activity of HOE 140 or des-Arg10HOE 140 in toxic neuropathy. CONCLUSIONS: Results of these studies suggest that B1 and B2 receptors are engaged in transmission of nociceptive stimuli in both diabetic and toxic neuropathy. In streptozotocin-induced hyperalgesia, inducible NO synthase participates in pronociceptive activity of bradykinin, whereas in vincristine-induced hyperalgesia bradykinin seemed to activate neuronal NO synthase pathway. Therefore, concomitant administration of small doses of bradykinin receptor antagonists and NO synthase inhibitors can be effective in alleviation of neuropathic pain, even in hospital care.", "entity": "Nitric Oxide", "aliases": "Endogenous Nitrate Vasodilator Endothelium-Derived Nitric Oxide Mononitrogen Monoxide Nitrogen Endothelium Derived", "definition": "A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.\n    ", "id": "MESH:D009569"}
{"mention": "bradykinin", "mention_text": "PURPOSE: The influence of an irreversible inhibitor of constitutive NO synthase (L-NOArg; 1.0 mg/kg ip), a relatively selective inhibitor of inducible NO synthase (L-NIL; 1.0 mg/kg ip) and a relatively specific inhibitor of neuronal NO synthase (7-NI; 0.1 mg/kg ip), on antihyperalgesic action of selective antagonists of B2 and B1 receptors: D-Arg-[Hyp3,Thi5,D-Tic7,Oic8] bradykinin (HOE 140; 70 nmol/kg ip) or des Arg10 HOE 140 (70 nmol/kg ip) respectively, in model of diabetic (streptozotocin-induced) and toxic (vincristine-induced) neuropathy was investigated. METHODS: The changes in pain thresholds were determined using mechanical stimuli--the modification of the classic paw withdrawal test described by Randall-Selitto. RESULTS: The results of this paper confirm that inhibition of bradykinin receptors and inducible NO synthase but not neuronal NO synthase activity reduces diabetic hyperalgesia. Pretreatment with L-NOArg and L-NIL but not 7-NI, significantly increases antihyperalgesic activity both HOE 140 and des Arg10 HOE 140. It was also shown that both products of inducible NO synthase and neuronal NO synthase activation as well as bradykinin are involved in hyperalgesia produced by vincristine. Moreover, L-NOArg and 7-NI but not L-NIL intensify antihyperalgesic activity of HOE 140 or des-Arg10HOE 140 in toxic neuropathy. CONCLUSIONS: Results of these studies suggest that B1 and B2 receptors are engaged in transmission of nociceptive stimuli in both diabetic and toxic neuropathy. In streptozotocin-induced hyperalgesia, inducible NO synthase participates in pronociceptive activity of bradykinin, whereas in vincristine-induced hyperalgesia bradykinin seemed to activate neuronal NO synthase pathway. Therefore, concomitant administration of small doses of bradykinin receptor antagonists and NO synthase inhibitors can be effective in alleviation of neuropathic pain, even in hospital care.", "entity": "Bradykinin", "aliases": "Arg Pro Pro Gly Phe Ser Pro Phe Arg Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg Bradykinin Acetate (9-D-Arg)-Isomer Diacetate Hydrochloride Triacetate (1-D-Arg)-Isomer (2-D-Pro)-Isomer (2-D-Pro-3-D-Pro-7-D-Pro)-Isomer (2-D-Pro-7-D-Pro)-Isomer (3-D-Pro)-Isomer (3-D-Pro-7-D-Pro)-Isomer (5-D-Phe)-Isomer (5-D-Phe-8-D-Phe)-Isomer (6-D-Ser)-Isomer (7-D-Pro)-Isomer (8-D-Phe)-Isomer", "definition": "A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.\n    ", "id": "MESH:D001920"}
{"mention": "HOE 140", "mention_text": "PURPOSE: The influence of an irreversible inhibitor of constitutive NO synthase (L-NOArg; 1.0 mg/kg ip), a relatively selective inhibitor of inducible NO synthase (L-NIL; 1.0 mg/kg ip) and a relatively specific inhibitor of neuronal NO synthase (7-NI; 0.1 mg/kg ip), on antihyperalgesic action of selective antagonists of B2 and B1 receptors: D-Arg-[Hyp3,Thi5,D-Tic7,Oic8] bradykinin (HOE 140; 70 nmol/kg ip) or des Arg10 HOE 140 (70 nmol/kg ip) respectively, in model of diabetic (streptozotocin-induced) and toxic (vincristine-induced) neuropathy was investigated. METHODS: The changes in pain thresholds were determined using mechanical stimuli--the modification of the classic paw withdrawal test described by Randall-Selitto. RESULTS: The results of this paper confirm that inhibition of bradykinin receptors and inducible NO synthase but not neuronal NO synthase activity reduces diabetic hyperalgesia. Pretreatment with L-NOArg and L-NIL but not 7-NI, significantly increases antihyperalgesic activity both HOE 140 and des Arg10 HOE 140. It was also shown that both products of inducible NO synthase and neuronal NO synthase activation as well as bradykinin are involved in hyperalgesia produced by vincristine. Moreover, L-NOArg and 7-NI but not L-NIL intensify antihyperalgesic activity of HOE 140 or des-Arg10HOE 140 in toxic neuropathy. CONCLUSIONS: Results of these studies suggest that B1 and B2 receptors are engaged in transmission of nociceptive stimuli in both diabetic and toxic neuropathy. In streptozotocin-induced hyperalgesia, inducible NO synthase participates in pronociceptive activity of bradykinin, whereas in vincristine-induced hyperalgesia bradykinin seemed to activate neuronal NO synthase pathway. Therefore, concomitant administration of small doses of bradykinin receptor antagonists and NO synthase inhibitors can be effective in alleviation of neuropathic pain, even in hospital care.", "entity": "icatibant", "aliases": "D-Arg(Hyp(3)-Thi(5)-D-Tic(7)-Oic(8))BK HOE 140 HOE-140 HOE140 Hoechst Hoechst-140 JE 049 JE-049 WIN 65365 WIN-65365 icatibant acetate", "definition": "", "id": "MESH:C065679"}
{"mention": "des Arg10 HOE 140", "mention_text": "PURPOSE: The influence of an irreversible inhibitor of constitutive NO synthase (L-NOArg; 1.0 mg/kg ip), a relatively selective inhibitor of inducible NO synthase (L-NIL; 1.0 mg/kg ip) and a relatively specific inhibitor of neuronal NO synthase (7-NI; 0.1 mg/kg ip), on antihyperalgesic action of selective antagonists of B2 and B1 receptors: D-Arg-[Hyp3,Thi5,D-Tic7,Oic8] bradykinin (HOE 140; 70 nmol/kg ip) or des Arg10 HOE 140 (70 nmol/kg ip) respectively, in model of diabetic (streptozotocin-induced) and toxic (vincristine-induced) neuropathy was investigated. METHODS: The changes in pain thresholds were determined using mechanical stimuli--the modification of the classic paw withdrawal test described by Randall-Selitto. RESULTS: The results of this paper confirm that inhibition of bradykinin receptors and inducible NO synthase but not neuronal NO synthase activity reduces diabetic hyperalgesia. Pretreatment with L-NOArg and L-NIL but not 7-NI, significantly increases antihyperalgesic activity both HOE 140 and des Arg10 HOE 140. It was also shown that both products of inducible NO synthase and neuronal NO synthase activation as well as bradykinin are involved in hyperalgesia produced by vincristine. Moreover, L-NOArg and 7-NI but not L-NIL intensify antihyperalgesic activity of HOE 140 or des-Arg10HOE 140 in toxic neuropathy. CONCLUSIONS: Results of these studies suggest that B1 and B2 receptors are engaged in transmission of nociceptive stimuli in both diabetic and toxic neuropathy. In streptozotocin-induced hyperalgesia, inducible NO synthase participates in pronociceptive activity of bradykinin, whereas in vincristine-induced hyperalgesia bradykinin seemed to activate neuronal NO synthase pathway. Therefore, concomitant administration of small doses of bradykinin receptor antagonists and NO synthase inhibitors can be effective in alleviation of neuropathic pain, even in hospital care.", "entity": "HOE 140, desArg(10)-", "aliases": "10-desArg-HOE 140 Arg-(3-Hyp-5-Thi-7-Tic-9-Oic)-9-desArg-bradykinin D-Arg(Hyp(3)-Thi(5)-D-Tic(7)-Oic(8)-desArg(10))BK DArg(Hyp(3)-Thi(5)-DTic(7)-Oic(8))desArg(9)-BK HOE desArg(10)- desarginyl(10)- bradykinin Arg-(Hyp(3)-Thi(5)-Tic(7)-Oic(8))-desArg(9)- arginyl-(hydroxypropyl(3)-3-thienylalanyl(5)-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl(7)-octahydro-1H-indole-2-carbonyl(8))-desarginyl(9)- des-Arg(10)-HOE140", "definition": "", "id": "MESH:C078665"}
{"mention": "toxic (vincristine-induced) neuropathy", "mention_text": "PURPOSE: The influence of an irreversible inhibitor of constitutive NO synthase (L-NOArg; 1.0 mg/kg ip), a relatively selective inhibitor of inducible NO synthase (L-NIL; 1.0 mg/kg ip) and a relatively specific inhibitor of neuronal NO synthase (7-NI; 0.1 mg/kg ip), on antihyperalgesic action of selective antagonists of B2 and B1 receptors: D-Arg-[Hyp3,Thi5,D-Tic7,Oic8] bradykinin (HOE 140; 70 nmol/kg ip) or des Arg10 HOE 140 (70 nmol/kg ip) respectively, in model of diabetic (streptozotocin-induced) and toxic (vincristine-induced) neuropathy was investigated. METHODS: The changes in pain thresholds were determined using mechanical stimuli--the modification of the classic paw withdrawal test described by Randall-Selitto. RESULTS: The results of this paper confirm that inhibition of bradykinin receptors and inducible NO synthase but not neuronal NO synthase activity reduces diabetic hyperalgesia. Pretreatment with L-NOArg and L-NIL but not 7-NI, significantly increases antihyperalgesic activity both HOE 140 and des Arg10 HOE 140. It was also shown that both products of inducible NO synthase and neuronal NO synthase activation as well as bradykinin are involved in hyperalgesia produced by vincristine. Moreover, L-NOArg and 7-NI but not L-NIL intensify antihyperalgesic activity of HOE 140 or des-Arg10HOE 140 in toxic neuropathy. CONCLUSIONS: Results of these studies suggest that B1 and B2 receptors are engaged in transmission of nociceptive stimuli in both diabetic and toxic neuropathy. In streptozotocin-induced hyperalgesia, inducible NO synthase participates in pronociceptive activity of bradykinin, whereas in vincristine-induced hyperalgesia bradykinin seemed to activate neuronal NO synthase pathway. Therefore, concomitant administration of small doses of bradykinin receptor antagonists and NO synthase inhibitors can be effective in alleviation of neuropathic pain, even in hospital care.", "entity": "Peripheral Nervous System Diseases", "aliases": "Nerve Disease Peripheral Diseases Neuropathy PNS (Peripheral Nervous System) System Disorders Neuropathies", "definition": "Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.\n    ", "id": "MESH:D010523"}
{"mention": "pain", "mention_text": "PURPOSE: The influence of an irreversible inhibitor of constitutive NO synthase (L-NOArg; 1.0 mg/kg ip), a relatively selective inhibitor of inducible NO synthase (L-NIL; 1.0 mg/kg ip) and a relatively specific inhibitor of neuronal NO synthase (7-NI; 0.1 mg/kg ip), on antihyperalgesic action of selective antagonists of B2 and B1 receptors: D-Arg-[Hyp3,Thi5,D-Tic7,Oic8] bradykinin (HOE 140; 70 nmol/kg ip) or des Arg10 HOE 140 (70 nmol/kg ip) respectively, in model of diabetic (streptozotocin-induced) and toxic (vincristine-induced) neuropathy was investigated. METHODS: The changes in pain thresholds were determined using mechanical stimuli--the modification of the classic paw withdrawal test described by Randall-Selitto. RESULTS: The results of this paper confirm that inhibition of bradykinin receptors and inducible NO synthase but not neuronal NO synthase activity reduces diabetic hyperalgesia. Pretreatment with L-NOArg and L-NIL but not 7-NI, significantly increases antihyperalgesic activity both HOE 140 and des Arg10 HOE 140. It was also shown that both products of inducible NO synthase and neuronal NO synthase activation as well as bradykinin are involved in hyperalgesia produced by vincristine. Moreover, L-NOArg and 7-NI but not L-NIL intensify antihyperalgesic activity of HOE 140 or des-Arg10HOE 140 in toxic neuropathy. CONCLUSIONS: Results of these studies suggest that B1 and B2 receptors are engaged in transmission of nociceptive stimuli in both diabetic and toxic neuropathy. In streptozotocin-induced hyperalgesia, inducible NO synthase participates in pronociceptive activity of bradykinin, whereas in vincristine-induced hyperalgesia bradykinin seemed to activate neuronal NO synthase pathway. Therefore, concomitant administration of small doses of bradykinin receptor antagonists and NO synthase inhibitors can be effective in alleviation of neuropathic pain, even in hospital care.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "diabetic hyperalgesia", "mention_text": "PURPOSE: The influence of an irreversible inhibitor of constitutive NO synthase (L-NOArg; 1.0 mg/kg ip), a relatively selective inhibitor of inducible NO synthase (L-NIL; 1.0 mg/kg ip) and a relatively specific inhibitor of neuronal NO synthase (7-NI; 0.1 mg/kg ip), on antihyperalgesic action of selective antagonists of B2 and B1 receptors: D-Arg-[Hyp3,Thi5,D-Tic7,Oic8] bradykinin (HOE 140; 70 nmol/kg ip) or des Arg10 HOE 140 (70 nmol/kg ip) respectively, in model of diabetic (streptozotocin-induced) and toxic (vincristine-induced) neuropathy was investigated. METHODS: The changes in pain thresholds were determined using mechanical stimuli--the modification of the classic paw withdrawal test described by Randall-Selitto. RESULTS: The results of this paper confirm that inhibition of bradykinin receptors and inducible NO synthase but not neuronal NO synthase activity reduces diabetic hyperalgesia. Pretreatment with L-NOArg and L-NIL but not 7-NI, significantly increases antihyperalgesic activity both HOE 140 and des Arg10 HOE 140. It was also shown that both products of inducible NO synthase and neuronal NO synthase activation as well as bradykinin are involved in hyperalgesia produced by vincristine. Moreover, L-NOArg and 7-NI but not L-NIL intensify antihyperalgesic activity of HOE 140 or des-Arg10HOE 140 in toxic neuropathy. CONCLUSIONS: Results of these studies suggest that B1 and B2 receptors are engaged in transmission of nociceptive stimuli in both diabetic and toxic neuropathy. In streptozotocin-induced hyperalgesia, inducible NO synthase participates in pronociceptive activity of bradykinin, whereas in vincristine-induced hyperalgesia bradykinin seemed to activate neuronal NO synthase pathway. Therefore, concomitant administration of small doses of bradykinin receptor antagonists and NO synthase inhibitors can be effective in alleviation of neuropathic pain, even in hospital care.", "entity": "Hyperalgesia", "aliases": "Allodynia Mechanical Tactile Thermal Allodynias Hyperalgesia Primary Secondary Hyperalgesias Hyperalgesic Sensations", "definition": "An increased sensation of pain or discomfort produced by mimimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve.\n    ", "id": "MESH:D006930"}
{"mention": "hyperalgesia", "mention_text": "PURPOSE: The influence of an irreversible inhibitor of constitutive NO synthase (L-NOArg; 1.0 mg/kg ip), a relatively selective inhibitor of inducible NO synthase (L-NIL; 1.0 mg/kg ip) and a relatively specific inhibitor of neuronal NO synthase (7-NI; 0.1 mg/kg ip), on antihyperalgesic action of selective antagonists of B2 and B1 receptors: D-Arg-[Hyp3,Thi5,D-Tic7,Oic8] bradykinin (HOE 140; 70 nmol/kg ip) or des Arg10 HOE 140 (70 nmol/kg ip) respectively, in model of diabetic (streptozotocin-induced) and toxic (vincristine-induced) neuropathy was investigated. METHODS: The changes in pain thresholds were determined using mechanical stimuli--the modification of the classic paw withdrawal test described by Randall-Selitto. RESULTS: The results of this paper confirm that inhibition of bradykinin receptors and inducible NO synthase but not neuronal NO synthase activity reduces diabetic hyperalgesia. Pretreatment with L-NOArg and L-NIL but not 7-NI, significantly increases antihyperalgesic activity both HOE 140 and des Arg10 HOE 140. It was also shown that both products of inducible NO synthase and neuronal NO synthase activation as well as bradykinin are involved in hyperalgesia produced by vincristine. Moreover, L-NOArg and 7-NI but not L-NIL intensify antihyperalgesic activity of HOE 140 or des-Arg10HOE 140 in toxic neuropathy. CONCLUSIONS: Results of these studies suggest that B1 and B2 receptors are engaged in transmission of nociceptive stimuli in both diabetic and toxic neuropathy. In streptozotocin-induced hyperalgesia, inducible NO synthase participates in pronociceptive activity of bradykinin, whereas in vincristine-induced hyperalgesia bradykinin seemed to activate neuronal NO synthase pathway. Therefore, concomitant administration of small doses of bradykinin receptor antagonists and NO synthase inhibitors can be effective in alleviation of neuropathic pain, even in hospital care.", "entity": "Hyperalgesia", "aliases": "Allodynia Mechanical Tactile Thermal Allodynias Hyperalgesia Primary Secondary Hyperalgesias Hyperalgesic Sensations", "definition": "An increased sensation of pain or discomfort produced by mimimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve.\n    ", "id": "MESH:D006930"}
{"mention": "vincristine", "mention_text": "PURPOSE: The influence of an irreversible inhibitor of constitutive NO synthase (L-NOArg; 1.0 mg/kg ip), a relatively selective inhibitor of inducible NO synthase (L-NIL; 1.0 mg/kg ip) and a relatively specific inhibitor of neuronal NO synthase (7-NI; 0.1 mg/kg ip), on antihyperalgesic action of selective antagonists of B2 and B1 receptors: D-Arg-[Hyp3,Thi5,D-Tic7,Oic8] bradykinin (HOE 140; 70 nmol/kg ip) or des Arg10 HOE 140 (70 nmol/kg ip) respectively, in model of diabetic (streptozotocin-induced) and toxic (vincristine-induced) neuropathy was investigated. METHODS: The changes in pain thresholds were determined using mechanical stimuli--the modification of the classic paw withdrawal test described by Randall-Selitto. RESULTS: The results of this paper confirm that inhibition of bradykinin receptors and inducible NO synthase but not neuronal NO synthase activity reduces diabetic hyperalgesia. Pretreatment with L-NOArg and L-NIL but not 7-NI, significantly increases antihyperalgesic activity both HOE 140 and des Arg10 HOE 140. It was also shown that both products of inducible NO synthase and neuronal NO synthase activation as well as bradykinin are involved in hyperalgesia produced by vincristine. Moreover, L-NOArg and 7-NI but not L-NIL intensify antihyperalgesic activity of HOE 140 or des-Arg10HOE 140 in toxic neuropathy. CONCLUSIONS: Results of these studies suggest that B1 and B2 receptors are engaged in transmission of nociceptive stimuli in both diabetic and toxic neuropathy. In streptozotocin-induced hyperalgesia, inducible NO synthase participates in pronociceptive activity of bradykinin, whereas in vincristine-induced hyperalgesia bradykinin seemed to activate neuronal NO synthase pathway. Therefore, concomitant administration of small doses of bradykinin receptor antagonists and NO synthase inhibitors can be effective in alleviation of neuropathic pain, even in hospital care.", "entity": "Vincristine", "aliases": "Bristol-Myers Squibb Brand of Vincristine Sulfate Citomid Columbia EG Labo Farmistin Irisfarma Lemery Leurocristine Lilly Oncovin Oncovine Onkocristin Onkoworks PFS Vincasar Pfizer Teva Vincristin Bristol Liquid medac Vincrisul Vintec cell pharm cellcristin", "definition": "Antitumor alkaloid isolated from Vinca Rosea. (Merck, 11th ed.)\n    ", "id": "MESH:D014750"}
{"mention": "des-Arg10HOE 140", "mention_text": "PURPOSE: The influence of an irreversible inhibitor of constitutive NO synthase (L-NOArg; 1.0 mg/kg ip), a relatively selective inhibitor of inducible NO synthase (L-NIL; 1.0 mg/kg ip) and a relatively specific inhibitor of neuronal NO synthase (7-NI; 0.1 mg/kg ip), on antihyperalgesic action of selective antagonists of B2 and B1 receptors: D-Arg-[Hyp3,Thi5,D-Tic7,Oic8] bradykinin (HOE 140; 70 nmol/kg ip) or des Arg10 HOE 140 (70 nmol/kg ip) respectively, in model of diabetic (streptozotocin-induced) and toxic (vincristine-induced) neuropathy was investigated. METHODS: The changes in pain thresholds were determined using mechanical stimuli--the modification of the classic paw withdrawal test described by Randall-Selitto. RESULTS: The results of this paper confirm that inhibition of bradykinin receptors and inducible NO synthase but not neuronal NO synthase activity reduces diabetic hyperalgesia. Pretreatment with L-NOArg and L-NIL but not 7-NI, significantly increases antihyperalgesic activity both HOE 140 and des Arg10 HOE 140. It was also shown that both products of inducible NO synthase and neuronal NO synthase activation as well as bradykinin are involved in hyperalgesia produced by vincristine. Moreover, L-NOArg and 7-NI but not L-NIL intensify antihyperalgesic activity of HOE 140 or des-Arg10HOE 140 in toxic neuropathy. CONCLUSIONS: Results of these studies suggest that B1 and B2 receptors are engaged in transmission of nociceptive stimuli in both diabetic and toxic neuropathy. In streptozotocin-induced hyperalgesia, inducible NO synthase participates in pronociceptive activity of bradykinin, whereas in vincristine-induced hyperalgesia bradykinin seemed to activate neuronal NO synthase pathway. Therefore, concomitant administration of small doses of bradykinin receptor antagonists and NO synthase inhibitors can be effective in alleviation of neuropathic pain, even in hospital care.", "entity": "HOE 140, desArg(10)-", "aliases": "10-desArg-HOE 140 Arg-(3-Hyp-5-Thi-7-Tic-9-Oic)-9-desArg-bradykinin D-Arg(Hyp(3)-Thi(5)-D-Tic(7)-Oic(8)-desArg(10))BK DArg(Hyp(3)-Thi(5)-DTic(7)-Oic(8))desArg(9)-BK HOE desArg(10)- desarginyl(10)- bradykinin Arg-(Hyp(3)-Thi(5)-Tic(7)-Oic(8))-desArg(9)- arginyl-(hydroxypropyl(3)-3-thienylalanyl(5)-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl(7)-octahydro-1H-indole-2-carbonyl(8))-desarginyl(9)- des-Arg(10)-HOE140", "definition": "", "id": "MESH:C078665"}
{"mention": "toxic neuropathy", "mention_text": "PURPOSE: The influence of an irreversible inhibitor of constitutive NO synthase (L-NOArg; 1.0 mg/kg ip), a relatively selective inhibitor of inducible NO synthase (L-NIL; 1.0 mg/kg ip) and a relatively specific inhibitor of neuronal NO synthase (7-NI; 0.1 mg/kg ip), on antihyperalgesic action of selective antagonists of B2 and B1 receptors: D-Arg-[Hyp3,Thi5,D-Tic7,Oic8] bradykinin (HOE 140; 70 nmol/kg ip) or des Arg10 HOE 140 (70 nmol/kg ip) respectively, in model of diabetic (streptozotocin-induced) and toxic (vincristine-induced) neuropathy was investigated. METHODS: The changes in pain thresholds were determined using mechanical stimuli--the modification of the classic paw withdrawal test described by Randall-Selitto. RESULTS: The results of this paper confirm that inhibition of bradykinin receptors and inducible NO synthase but not neuronal NO synthase activity reduces diabetic hyperalgesia. Pretreatment with L-NOArg and L-NIL but not 7-NI, significantly increases antihyperalgesic activity both HOE 140 and des Arg10 HOE 140. It was also shown that both products of inducible NO synthase and neuronal NO synthase activation as well as bradykinin are involved in hyperalgesia produced by vincristine. Moreover, L-NOArg and 7-NI but not L-NIL intensify antihyperalgesic activity of HOE 140 or des-Arg10HOE 140 in toxic neuropathy. CONCLUSIONS: Results of these studies suggest that B1 and B2 receptors are engaged in transmission of nociceptive stimuli in both diabetic and toxic neuropathy. In streptozotocin-induced hyperalgesia, inducible NO synthase participates in pronociceptive activity of bradykinin, whereas in vincristine-induced hyperalgesia bradykinin seemed to activate neuronal NO synthase pathway. Therefore, concomitant administration of small doses of bradykinin receptor antagonists and NO synthase inhibitors can be effective in alleviation of neuropathic pain, even in hospital care.", "entity": "Peripheral Nervous System Diseases", "aliases": "Nerve Disease Peripheral Diseases Neuropathy PNS (Peripheral Nervous System) System Disorders Neuropathies", "definition": "Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.\n    ", "id": "MESH:D010523"}
{"mention": "streptozotocin", "mention_text": "PURPOSE: The influence of an irreversible inhibitor of constitutive NO synthase (L-NOArg; 1.0 mg/kg ip), a relatively selective inhibitor of inducible NO synthase (L-NIL; 1.0 mg/kg ip) and a relatively specific inhibitor of neuronal NO synthase (7-NI; 0.1 mg/kg ip), on antihyperalgesic action of selective antagonists of B2 and B1 receptors: D-Arg-[Hyp3,Thi5,D-Tic7,Oic8] bradykinin (HOE 140; 70 nmol/kg ip) or des Arg10 HOE 140 (70 nmol/kg ip) respectively, in model of diabetic (streptozotocin-induced) and toxic (vincristine-induced) neuropathy was investigated. METHODS: The changes in pain thresholds were determined using mechanical stimuli--the modification of the classic paw withdrawal test described by Randall-Selitto. RESULTS: The results of this paper confirm that inhibition of bradykinin receptors and inducible NO synthase but not neuronal NO synthase activity reduces diabetic hyperalgesia. Pretreatment with L-NOArg and L-NIL but not 7-NI, significantly increases antihyperalgesic activity both HOE 140 and des Arg10 HOE 140. It was also shown that both products of inducible NO synthase and neuronal NO synthase activation as well as bradykinin are involved in hyperalgesia produced by vincristine. Moreover, L-NOArg and 7-NI but not L-NIL intensify antihyperalgesic activity of HOE 140 or des-Arg10HOE 140 in toxic neuropathy. CONCLUSIONS: Results of these studies suggest that B1 and B2 receptors are engaged in transmission of nociceptive stimuli in both diabetic and toxic neuropathy. In streptozotocin-induced hyperalgesia, inducible NO synthase participates in pronociceptive activity of bradykinin, whereas in vincristine-induced hyperalgesia bradykinin seemed to activate neuronal NO synthase pathway. Therefore, concomitant administration of small doses of bradykinin receptor antagonists and NO synthase inhibitors can be effective in alleviation of neuropathic pain, even in hospital care.", "entity": "Streptozocin", "aliases": "2-Deoxy-2-((methylnitrosoamino)carbonyl)amino-D-glucose Streptozocin Teva Brand Streptozotocin Streptozotocine of Zanosar", "definition": "An antibiotic that is produced by Stretomyces achromogenes. It is used as an antineoplastic agent and to induce diabetes in experimental animals.\n    ", "id": "MESH:D013311"}
{"mention": "neuropathic pain", "mention_text": "PURPOSE: The influence of an irreversible inhibitor of constitutive NO synthase (L-NOArg; 1.0 mg/kg ip), a relatively selective inhibitor of inducible NO synthase (L-NIL; 1.0 mg/kg ip) and a relatively specific inhibitor of neuronal NO synthase (7-NI; 0.1 mg/kg ip), on antihyperalgesic action of selective antagonists of B2 and B1 receptors: D-Arg-[Hyp3,Thi5,D-Tic7,Oic8] bradykinin (HOE 140; 70 nmol/kg ip) or des Arg10 HOE 140 (70 nmol/kg ip) respectively, in model of diabetic (streptozotocin-induced) and toxic (vincristine-induced) neuropathy was investigated. METHODS: The changes in pain thresholds were determined using mechanical stimuli--the modification of the classic paw withdrawal test described by Randall-Selitto. RESULTS: The results of this paper confirm that inhibition of bradykinin receptors and inducible NO synthase but not neuronal NO synthase activity reduces diabetic hyperalgesia. Pretreatment with L-NOArg and L-NIL but not 7-NI, significantly increases antihyperalgesic activity both HOE 140 and des Arg10 HOE 140. It was also shown that both products of inducible NO synthase and neuronal NO synthase activation as well as bradykinin are involved in hyperalgesia produced by vincristine. Moreover, L-NOArg and 7-NI but not L-NIL intensify antihyperalgesic activity of HOE 140 or des-Arg10HOE 140 in toxic neuropathy. CONCLUSIONS: Results of these studies suggest that B1 and B2 receptors are engaged in transmission of nociceptive stimuli in both diabetic and toxic neuropathy. In streptozotocin-induced hyperalgesia, inducible NO synthase participates in pronociceptive activity of bradykinin, whereas in vincristine-induced hyperalgesia bradykinin seemed to activate neuronal NO synthase pathway. Therefore, concomitant administration of small doses of bradykinin receptor antagonists and NO synthase inhibitors can be effective in alleviation of neuropathic pain, even in hospital care.", "entity": "Neuralgia", "aliases": "Atypical Neuralgia Neuralgias Iliohypogastric Nerve Ilioinguinal Pain Paroxysmal Pains Perineal Stump Supraorbital Vidian Neurodynia Neurodynias Neuropathic", "definition": "Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve.\n    ", "id": "MESH:D009437"}
{"mention": "Cardiac toxicity", "mention_text": "Cardiac toxicity observed in association with high-dose cyclophosphamide-based chemotherapy for metastatic breast cancer.", "entity": "Cardiotoxicity", "aliases": "Cardiac Toxicities Toxicity Cardiotoxicities Cardiotoxicity", "definition": "Damage to the heart or its function secondary to exposure to toxic substances such as drugs used in CHEMOTHERAPY; IMMUNOTHERAPY; or RADIATION.\n    ", "id": "MESH:D066126"}
{"mention": "cyclophosphamide", "mention_text": "Cardiac toxicity observed in association with high-dose cyclophosphamide-based chemotherapy for metastatic breast cancer.", "entity": "Cyclophosphamide", "aliases": "Anhydrous Cyclophosphamide B 518 B-518 B518 Monohydrate (R)-Isomer (S)-Isomer Cyclophosphane Cytophosphan Cytophosphane Cytoxan Endoxan NSC 26271 NSC-26271 NSC26271 Neosar Procytox Sendoxan", "definition": "Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.\n    ", "id": "MESH:D003520"}
{"mention": "breast cancer", "mention_text": "Cardiac toxicity observed in association with high-dose cyclophosphamide-based chemotherapy for metastatic breast cancer.", "entity": "Breast Neoplasms", "aliases": "Breast Cancer Carcinoma Neoplasm Neoplasms Tumor Tumors of the Human Mammary Carcinomas Malignant", "definition": "Tumors or cancer of the human BREAST.\n    ", "id": "MESH:D001943"}
{"mention": "Cyclophosphamide", "mention_text": "INTRODUCTION: Cyclophosphamide is an alkylating agent given frequently as a component of many conditioning regimens. In high doses, its nonhematological dose-limiting toxicity is cardiomyopathy. STUDY DESIGN: We combined paclitaxel, melphalan and high-dose cyclophosphamide, thiotepa, and carboplatin in a triple sequential high-dose regimen for patients with metastatic breast cancer. Analysis was performed on 61 women with chemotherapy-responsive metastatic breast cancer receiving 96-h infusional cyclophosphamide as part of a triple sequential high-dose regimen to assess association between presence of peritransplant congestive heart failure (CHF) and the following pretreatment characteristics: presence of electrocardiogram (EKG) abnormalities, age, hypertension, prior cardiac history, smoking, diabetes mellitus, prior use of anthracyclines, and left-sided chest irradiation. RESULTS: Six of 61 women (10%) developed clinically reversible grade 3 CHF following infusional cyclophosphamide with a median percent decline in ejection fraction of 31%. Incidence of transient cyclophosphamide-related cardiac toxicity (10%) is comparable to previous recorded literature. Older age was significantly correlated with the CHF development; with median ages for the entire group and for patients developing CHF of 45 and 59, respectively. No association was found with other pretreatment characteristics. CONCLUSIONS: As a result of these findings, oncologists should carefully monitor fluid balance in older patients. Routine EKG monitoring during infusional cyclophosphamide did not predict CHF development.", "entity": "Cyclophosphamide", "aliases": "Anhydrous Cyclophosphamide B 518 B-518 B518 Monohydrate (R)-Isomer (S)-Isomer Cyclophosphane Cytophosphan Cytophosphane Cytoxan Endoxan NSC 26271 NSC-26271 NSC26271 Neosar Procytox Sendoxan", "definition": "Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.\n    ", "id": "MESH:D003520"}
{"mention": "toxicity", "mention_text": "INTRODUCTION: Cyclophosphamide is an alkylating agent given frequently as a component of many conditioning regimens. In high doses, its nonhematological dose-limiting toxicity is cardiomyopathy. STUDY DESIGN: We combined paclitaxel, melphalan and high-dose cyclophosphamide, thiotepa, and carboplatin in a triple sequential high-dose regimen for patients with metastatic breast cancer. Analysis was performed on 61 women with chemotherapy-responsive metastatic breast cancer receiving 96-h infusional cyclophosphamide as part of a triple sequential high-dose regimen to assess association between presence of peritransplant congestive heart failure (CHF) and the following pretreatment characteristics: presence of electrocardiogram (EKG) abnormalities, age, hypertension, prior cardiac history, smoking, diabetes mellitus, prior use of anthracyclines, and left-sided chest irradiation. RESULTS: Six of 61 women (10%) developed clinically reversible grade 3 CHF following infusional cyclophosphamide with a median percent decline in ejection fraction of 31%. Incidence of transient cyclophosphamide-related cardiac toxicity (10%) is comparable to previous recorded literature. Older age was significantly correlated with the CHF development; with median ages for the entire group and for patients developing CHF of 45 and 59, respectively. No association was found with other pretreatment characteristics. CONCLUSIONS: As a result of these findings, oncologists should carefully monitor fluid balance in older patients. Routine EKG monitoring during infusional cyclophosphamide did not predict CHF development.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "cardiomyopathy", "mention_text": "INTRODUCTION: Cyclophosphamide is an alkylating agent given frequently as a component of many conditioning regimens. In high doses, its nonhematological dose-limiting toxicity is cardiomyopathy. STUDY DESIGN: We combined paclitaxel, melphalan and high-dose cyclophosphamide, thiotepa, and carboplatin in a triple sequential high-dose regimen for patients with metastatic breast cancer. Analysis was performed on 61 women with chemotherapy-responsive metastatic breast cancer receiving 96-h infusional cyclophosphamide as part of a triple sequential high-dose regimen to assess association between presence of peritransplant congestive heart failure (CHF) and the following pretreatment characteristics: presence of electrocardiogram (EKG) abnormalities, age, hypertension, prior cardiac history, smoking, diabetes mellitus, prior use of anthracyclines, and left-sided chest irradiation. RESULTS: Six of 61 women (10%) developed clinically reversible grade 3 CHF following infusional cyclophosphamide with a median percent decline in ejection fraction of 31%. Incidence of transient cyclophosphamide-related cardiac toxicity (10%) is comparable to previous recorded literature. Older age was significantly correlated with the CHF development; with median ages for the entire group and for patients developing CHF of 45 and 59, respectively. No association was found with other pretreatment characteristics. CONCLUSIONS: As a result of these findings, oncologists should carefully monitor fluid balance in older patients. Routine EKG monitoring during infusional cyclophosphamide did not predict CHF development.", "entity": "Cardiomyopathies", "aliases": "Cardiomyopathies Primary Secondary Cardiomyopathy Disease Myocardial Diseases Myocardiopathies Myocardiopathy", "definition": "A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).\n    ", "id": "MESH:D009202"}
{"mention": "paclitaxel", "mention_text": "INTRODUCTION: Cyclophosphamide is an alkylating agent given frequently as a component of many conditioning regimens. In high doses, its nonhematological dose-limiting toxicity is cardiomyopathy. STUDY DESIGN: We combined paclitaxel, melphalan and high-dose cyclophosphamide, thiotepa, and carboplatin in a triple sequential high-dose regimen for patients with metastatic breast cancer. Analysis was performed on 61 women with chemotherapy-responsive metastatic breast cancer receiving 96-h infusional cyclophosphamide as part of a triple sequential high-dose regimen to assess association between presence of peritransplant congestive heart failure (CHF) and the following pretreatment characteristics: presence of electrocardiogram (EKG) abnormalities, age, hypertension, prior cardiac history, smoking, diabetes mellitus, prior use of anthracyclines, and left-sided chest irradiation. RESULTS: Six of 61 women (10%) developed clinically reversible grade 3 CHF following infusional cyclophosphamide with a median percent decline in ejection fraction of 31%. Incidence of transient cyclophosphamide-related cardiac toxicity (10%) is comparable to previous recorded literature. Older age was significantly correlated with the CHF development; with median ages for the entire group and for patients developing CHF of 45 and 59, respectively. No association was found with other pretreatment characteristics. CONCLUSIONS: As a result of these findings, oncologists should carefully monitor fluid balance in older patients. Routine EKG monitoring during infusional cyclophosphamide did not predict CHF development.", "entity": "Paclitaxel", "aliases": "7 epi Taxol 7-epi-Taxol Anzatax Bris Bristol-Myers Brand of Paclitaxel Squibb Bull Ivax Lemery NSC 125973 NSC-125973 NSC125973 Onxol (4 alpha)-Isomer Paxene Praxel A", "definition": "A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.\n    ", "id": "MESH:D017239"}
{"mention": "melphalan", "mention_text": "INTRODUCTION: Cyclophosphamide is an alkylating agent given frequently as a component of many conditioning regimens. In high doses, its nonhematological dose-limiting toxicity is cardiomyopathy. STUDY DESIGN: We combined paclitaxel, melphalan and high-dose cyclophosphamide, thiotepa, and carboplatin in a triple sequential high-dose regimen for patients with metastatic breast cancer. Analysis was performed on 61 women with chemotherapy-responsive metastatic breast cancer receiving 96-h infusional cyclophosphamide as part of a triple sequential high-dose regimen to assess association between presence of peritransplant congestive heart failure (CHF) and the following pretreatment characteristics: presence of electrocardiogram (EKG) abnormalities, age, hypertension, prior cardiac history, smoking, diabetes mellitus, prior use of anthracyclines, and left-sided chest irradiation. RESULTS: Six of 61 women (10%) developed clinically reversible grade 3 CHF following infusional cyclophosphamide with a median percent decline in ejection fraction of 31%. Incidence of transient cyclophosphamide-related cardiac toxicity (10%) is comparable to previous recorded literature. Older age was significantly correlated with the CHF development; with median ages for the entire group and for patients developing CHF of 45 and 59, respectively. No association was found with other pretreatment characteristics. CONCLUSIONS: As a result of these findings, oncologists should carefully monitor fluid balance in older patients. Routine EKG monitoring during infusional cyclophosphamide did not predict CHF development.", "entity": "Melphalan", "aliases": "4-(Bis(2-chloroethyl)amino)phenylalanine Alkeran L-PAM Medphalan Melphalan Merphalan Mustard Phenylalanine Sarcolysine Sarkolysin", "definition": "An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - MELPHALAN, the racemic mixture - MERPHALAN, and the dextro isomer - MEDPHALAN; toxic to bone marrow, but little vesicant action; potential carcinogen.\n    ", "id": "MESH:D008558"}
{"mention": "cyclophosphamide", "mention_text": "INTRODUCTION: Cyclophosphamide is an alkylating agent given frequently as a component of many conditioning regimens. In high doses, its nonhematological dose-limiting toxicity is cardiomyopathy. STUDY DESIGN: We combined paclitaxel, melphalan and high-dose cyclophosphamide, thiotepa, and carboplatin in a triple sequential high-dose regimen for patients with metastatic breast cancer. Analysis was performed on 61 women with chemotherapy-responsive metastatic breast cancer receiving 96-h infusional cyclophosphamide as part of a triple sequential high-dose regimen to assess association between presence of peritransplant congestive heart failure (CHF) and the following pretreatment characteristics: presence of electrocardiogram (EKG) abnormalities, age, hypertension, prior cardiac history, smoking, diabetes mellitus, prior use of anthracyclines, and left-sided chest irradiation. RESULTS: Six of 61 women (10%) developed clinically reversible grade 3 CHF following infusional cyclophosphamide with a median percent decline in ejection fraction of 31%. Incidence of transient cyclophosphamide-related cardiac toxicity (10%) is comparable to previous recorded literature. Older age was significantly correlated with the CHF development; with median ages for the entire group and for patients developing CHF of 45 and 59, respectively. No association was found with other pretreatment characteristics. CONCLUSIONS: As a result of these findings, oncologists should carefully monitor fluid balance in older patients. Routine EKG monitoring during infusional cyclophosphamide did not predict CHF development.", "entity": "Cyclophosphamide", "aliases": "Anhydrous Cyclophosphamide B 518 B-518 B518 Monohydrate (R)-Isomer (S)-Isomer Cyclophosphane Cytophosphan Cytophosphane Cytoxan Endoxan NSC 26271 NSC-26271 NSC26271 Neosar Procytox Sendoxan", "definition": "Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.\n    ", "id": "MESH:D003520"}
{"mention": "thiotepa", "mention_text": "INTRODUCTION: Cyclophosphamide is an alkylating agent given frequently as a component of many conditioning regimens. In high doses, its nonhematological dose-limiting toxicity is cardiomyopathy. STUDY DESIGN: We combined paclitaxel, melphalan and high-dose cyclophosphamide, thiotepa, and carboplatin in a triple sequential high-dose regimen for patients with metastatic breast cancer. Analysis was performed on 61 women with chemotherapy-responsive metastatic breast cancer receiving 96-h infusional cyclophosphamide as part of a triple sequential high-dose regimen to assess association between presence of peritransplant congestive heart failure (CHF) and the following pretreatment characteristics: presence of electrocardiogram (EKG) abnormalities, age, hypertension, prior cardiac history, smoking, diabetes mellitus, prior use of anthracyclines, and left-sided chest irradiation. RESULTS: Six of 61 women (10%) developed clinically reversible grade 3 CHF following infusional cyclophosphamide with a median percent decline in ejection fraction of 31%. Incidence of transient cyclophosphamide-related cardiac toxicity (10%) is comparable to previous recorded literature. Older age was significantly correlated with the CHF development; with median ages for the entire group and for patients developing CHF of 45 and 59, respectively. No association was found with other pretreatment characteristics. CONCLUSIONS: As a result of these findings, oncologists should carefully monitor fluid balance in older patients. Routine EKG monitoring during infusional cyclophosphamide did not predict CHF development.", "entity": "Thiotepa", "aliases": "AI3 24916 AI3-24916 AI324916 Girostan NSC 6396 NSC-6396 NSC6396 Tespa Tespamin Thio Tepa Thio-Tepa Thiophosphamide Thiotepa Triethylenethiophosphoramide Tris(1-aziridinyl)phosphine Sulfide", "definition": "A very toxic alkylating antineoplastic agent also used as an insect sterilant. It causes skin, gastrointestinal, CNS, and bone marrow damage. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), thiotepa may reasonably be anticipated to be a carcinogen (Merck Index, 11th ed).\n    ", "id": "MESH:D013852"}
{"mention": "carboplatin", "mention_text": "INTRODUCTION: Cyclophosphamide is an alkylating agent given frequently as a component of many conditioning regimens. In high doses, its nonhematological dose-limiting toxicity is cardiomyopathy. STUDY DESIGN: We combined paclitaxel, melphalan and high-dose cyclophosphamide, thiotepa, and carboplatin in a triple sequential high-dose regimen for patients with metastatic breast cancer. Analysis was performed on 61 women with chemotherapy-responsive metastatic breast cancer receiving 96-h infusional cyclophosphamide as part of a triple sequential high-dose regimen to assess association between presence of peritransplant congestive heart failure (CHF) and the following pretreatment characteristics: presence of electrocardiogram (EKG) abnormalities, age, hypertension, prior cardiac history, smoking, diabetes mellitus, prior use of anthracyclines, and left-sided chest irradiation. RESULTS: Six of 61 women (10%) developed clinically reversible grade 3 CHF following infusional cyclophosphamide with a median percent decline in ejection fraction of 31%. Incidence of transient cyclophosphamide-related cardiac toxicity (10%) is comparable to previous recorded literature. Older age was significantly correlated with the CHF development; with median ages for the entire group and for patients developing CHF of 45 and 59, respectively. No association was found with other pretreatment characteristics. CONCLUSIONS: As a result of these findings, oncologists should carefully monitor fluid balance in older patients. Routine EKG monitoring during infusional cyclophosphamide did not predict CHF development.", "entity": "Carboplatin", "aliases": "Almirall Brand of Carboplatin Blastocarb Bristol-Myers Squibb CBDCA Carboplat Carbosin Carbotec Chiesi Columbia Ercar JM 8 JM-8 JM8 Lemery NSC 241240 NSC-241240 NSC241240 Nealorin Neocarbo Neocorp Paraplatin Paraplatine Pharmachemie Platinwas Prasfarma Ribocarbo cis-Diammine(cyclobutanedicarboxylato)platinum II ribosepharm", "definition": "An organoplatinum compound that possesses antineoplastic activity.\n    ", "id": "MESH:D016190"}
{"mention": "breast cancer", "mention_text": "INTRODUCTION: Cyclophosphamide is an alkylating agent given frequently as a component of many conditioning regimens. In high doses, its nonhematological dose-limiting toxicity is cardiomyopathy. STUDY DESIGN: We combined paclitaxel, melphalan and high-dose cyclophosphamide, thiotepa, and carboplatin in a triple sequential high-dose regimen for patients with metastatic breast cancer. Analysis was performed on 61 women with chemotherapy-responsive metastatic breast cancer receiving 96-h infusional cyclophosphamide as part of a triple sequential high-dose regimen to assess association between presence of peritransplant congestive heart failure (CHF) and the following pretreatment characteristics: presence of electrocardiogram (EKG) abnormalities, age, hypertension, prior cardiac history, smoking, diabetes mellitus, prior use of anthracyclines, and left-sided chest irradiation. RESULTS: Six of 61 women (10%) developed clinically reversible grade 3 CHF following infusional cyclophosphamide with a median percent decline in ejection fraction of 31%. Incidence of transient cyclophosphamide-related cardiac toxicity (10%) is comparable to previous recorded literature. Older age was significantly correlated with the CHF development; with median ages for the entire group and for patients developing CHF of 45 and 59, respectively. No association was found with other pretreatment characteristics. CONCLUSIONS: As a result of these findings, oncologists should carefully monitor fluid balance in older patients. Routine EKG monitoring during infusional cyclophosphamide did not predict CHF development.", "entity": "Breast Neoplasms", "aliases": "Breast Cancer Carcinoma Neoplasm Neoplasms Tumor Tumors of the Human Mammary Carcinomas Malignant", "definition": "Tumors or cancer of the human BREAST.\n    ", "id": "MESH:D001943"}
{"mention": "congestive heart failure", "mention_text": "INTRODUCTION: Cyclophosphamide is an alkylating agent given frequently as a component of many conditioning regimens. In high doses, its nonhematological dose-limiting toxicity is cardiomyopathy. STUDY DESIGN: We combined paclitaxel, melphalan and high-dose cyclophosphamide, thiotepa, and carboplatin in a triple sequential high-dose regimen for patients with metastatic breast cancer. Analysis was performed on 61 women with chemotherapy-responsive metastatic breast cancer receiving 96-h infusional cyclophosphamide as part of a triple sequential high-dose regimen to assess association between presence of peritransplant congestive heart failure (CHF) and the following pretreatment characteristics: presence of electrocardiogram (EKG) abnormalities, age, hypertension, prior cardiac history, smoking, diabetes mellitus, prior use of anthracyclines, and left-sided chest irradiation. RESULTS: Six of 61 women (10%) developed clinically reversible grade 3 CHF following infusional cyclophosphamide with a median percent decline in ejection fraction of 31%. Incidence of transient cyclophosphamide-related cardiac toxicity (10%) is comparable to previous recorded literature. Older age was significantly correlated with the CHF development; with median ages for the entire group and for patients developing CHF of 45 and 59, respectively. No association was found with other pretreatment characteristics. CONCLUSIONS: As a result of these findings, oncologists should carefully monitor fluid balance in older patients. Routine EKG monitoring during infusional cyclophosphamide did not predict CHF development.", "entity": "Heart Failure", "aliases": "Cardiac Failure Congestive Heart Decompensation Left Sided Left-Sided Right Right-Sided Myocardial", "definition": "A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.\n    ", "id": "MESH:D006333"}
{"mention": "CHF", "mention_text": "INTRODUCTION: Cyclophosphamide is an alkylating agent given frequently as a component of many conditioning regimens. In high doses, its nonhematological dose-limiting toxicity is cardiomyopathy. STUDY DESIGN: We combined paclitaxel, melphalan and high-dose cyclophosphamide, thiotepa, and carboplatin in a triple sequential high-dose regimen for patients with metastatic breast cancer. Analysis was performed on 61 women with chemotherapy-responsive metastatic breast cancer receiving 96-h infusional cyclophosphamide as part of a triple sequential high-dose regimen to assess association between presence of peritransplant congestive heart failure (CHF) and the following pretreatment characteristics: presence of electrocardiogram (EKG) abnormalities, age, hypertension, prior cardiac history, smoking, diabetes mellitus, prior use of anthracyclines, and left-sided chest irradiation. RESULTS: Six of 61 women (10%) developed clinically reversible grade 3 CHF following infusional cyclophosphamide with a median percent decline in ejection fraction of 31%. Incidence of transient cyclophosphamide-related cardiac toxicity (10%) is comparable to previous recorded literature. Older age was significantly correlated with the CHF development; with median ages for the entire group and for patients developing CHF of 45 and 59, respectively. No association was found with other pretreatment characteristics. CONCLUSIONS: As a result of these findings, oncologists should carefully monitor fluid balance in older patients. Routine EKG monitoring during infusional cyclophosphamide did not predict CHF development.", "entity": "Heart Failure", "aliases": "Cardiac Failure Congestive Heart Decompensation Left Sided Left-Sided Right Right-Sided Myocardial", "definition": "A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.\n    ", "id": "MESH:D006333"}
{"mention": "hypertension", "mention_text": "INTRODUCTION: Cyclophosphamide is an alkylating agent given frequently as a component of many conditioning regimens. In high doses, its nonhematological dose-limiting toxicity is cardiomyopathy. STUDY DESIGN: We combined paclitaxel, melphalan and high-dose cyclophosphamide, thiotepa, and carboplatin in a triple sequential high-dose regimen for patients with metastatic breast cancer. Analysis was performed on 61 women with chemotherapy-responsive metastatic breast cancer receiving 96-h infusional cyclophosphamide as part of a triple sequential high-dose regimen to assess association between presence of peritransplant congestive heart failure (CHF) and the following pretreatment characteristics: presence of electrocardiogram (EKG) abnormalities, age, hypertension, prior cardiac history, smoking, diabetes mellitus, prior use of anthracyclines, and left-sided chest irradiation. RESULTS: Six of 61 women (10%) developed clinically reversible grade 3 CHF following infusional cyclophosphamide with a median percent decline in ejection fraction of 31%. Incidence of transient cyclophosphamide-related cardiac toxicity (10%) is comparable to previous recorded literature. Older age was significantly correlated with the CHF development; with median ages for the entire group and for patients developing CHF of 45 and 59, respectively. No association was found with other pretreatment characteristics. CONCLUSIONS: As a result of these findings, oncologists should carefully monitor fluid balance in older patients. Routine EKG monitoring during infusional cyclophosphamide did not predict CHF development.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "diabetes mellitus", "mention_text": "INTRODUCTION: Cyclophosphamide is an alkylating agent given frequently as a component of many conditioning regimens. In high doses, its nonhematological dose-limiting toxicity is cardiomyopathy. STUDY DESIGN: We combined paclitaxel, melphalan and high-dose cyclophosphamide, thiotepa, and carboplatin in a triple sequential high-dose regimen for patients with metastatic breast cancer. Analysis was performed on 61 women with chemotherapy-responsive metastatic breast cancer receiving 96-h infusional cyclophosphamide as part of a triple sequential high-dose regimen to assess association between presence of peritransplant congestive heart failure (CHF) and the following pretreatment characteristics: presence of electrocardiogram (EKG) abnormalities, age, hypertension, prior cardiac history, smoking, diabetes mellitus, prior use of anthracyclines, and left-sided chest irradiation. RESULTS: Six of 61 women (10%) developed clinically reversible grade 3 CHF following infusional cyclophosphamide with a median percent decline in ejection fraction of 31%. Incidence of transient cyclophosphamide-related cardiac toxicity (10%) is comparable to previous recorded literature. Older age was significantly correlated with the CHF development; with median ages for the entire group and for patients developing CHF of 45 and 59, respectively. No association was found with other pretreatment characteristics. CONCLUSIONS: As a result of these findings, oncologists should carefully monitor fluid balance in older patients. Routine EKG monitoring during infusional cyclophosphamide did not predict CHF development.", "entity": "Diabetes Mellitus", "aliases": "Diabetes Mellitus", "definition": "A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.\n    ", "id": "MESH:D003920"}
{"mention": "anthracyclines", "mention_text": "INTRODUCTION: Cyclophosphamide is an alkylating agent given frequently as a component of many conditioning regimens. In high doses, its nonhematological dose-limiting toxicity is cardiomyopathy. STUDY DESIGN: We combined paclitaxel, melphalan and high-dose cyclophosphamide, thiotepa, and carboplatin in a triple sequential high-dose regimen for patients with metastatic breast cancer. Analysis was performed on 61 women with chemotherapy-responsive metastatic breast cancer receiving 96-h infusional cyclophosphamide as part of a triple sequential high-dose regimen to assess association between presence of peritransplant congestive heart failure (CHF) and the following pretreatment characteristics: presence of electrocardiogram (EKG) abnormalities, age, hypertension, prior cardiac history, smoking, diabetes mellitus, prior use of anthracyclines, and left-sided chest irradiation. RESULTS: Six of 61 women (10%) developed clinically reversible grade 3 CHF following infusional cyclophosphamide with a median percent decline in ejection fraction of 31%. Incidence of transient cyclophosphamide-related cardiac toxicity (10%) is comparable to previous recorded literature. Older age was significantly correlated with the CHF development; with median ages for the entire group and for patients developing CHF of 45 and 59, respectively. No association was found with other pretreatment characteristics. CONCLUSIONS: As a result of these findings, oncologists should carefully monitor fluid balance in older patients. Routine EKG monitoring during infusional cyclophosphamide did not predict CHF development.", "entity": "Anthracyclines", "aliases": "Anthracyclines", "definition": "Organic compounds that have a tetrahydronaphthacenedione ring structure attached by a glycosidic linkage to the amino sugar daunosamine.\n    ", "id": "MESH:D018943"}
{"mention": "cardiac toxicity", "mention_text": "INTRODUCTION: Cyclophosphamide is an alkylating agent given frequently as a component of many conditioning regimens. In high doses, its nonhematological dose-limiting toxicity is cardiomyopathy. STUDY DESIGN: We combined paclitaxel, melphalan and high-dose cyclophosphamide, thiotepa, and carboplatin in a triple sequential high-dose regimen for patients with metastatic breast cancer. Analysis was performed on 61 women with chemotherapy-responsive metastatic breast cancer receiving 96-h infusional cyclophosphamide as part of a triple sequential high-dose regimen to assess association between presence of peritransplant congestive heart failure (CHF) and the following pretreatment characteristics: presence of electrocardiogram (EKG) abnormalities, age, hypertension, prior cardiac history, smoking, diabetes mellitus, prior use of anthracyclines, and left-sided chest irradiation. RESULTS: Six of 61 women (10%) developed clinically reversible grade 3 CHF following infusional cyclophosphamide with a median percent decline in ejection fraction of 31%. Incidence of transient cyclophosphamide-related cardiac toxicity (10%) is comparable to previous recorded literature. Older age was significantly correlated with the CHF development; with median ages for the entire group and for patients developing CHF of 45 and 59, respectively. No association was found with other pretreatment characteristics. CONCLUSIONS: As a result of these findings, oncologists should carefully monitor fluid balance in older patients. Routine EKG monitoring during infusional cyclophosphamide did not predict CHF development.", "entity": "Cardiotoxicity", "aliases": "Cardiac Toxicities Toxicity Cardiotoxicities Cardiotoxicity", "definition": "Damage to the heart or its function secondary to exposure to toxic substances such as drugs used in CHEMOTHERAPY; IMMUNOTHERAPY; or RADIATION.\n    ", "id": "MESH:D066126"}
{"mention": "carbamazepine", "mention_text": "Inappropriate use of carbamazepine and vigabatrin in typical absence seizures.", "entity": "Carbamazepine", "aliases": "Amizepine Carbamazepine Acetate Anhydrous Dihydrate Hydrochloride L-Tartrate (4:1) Phosphate Sulfate (2:1) Carbazepin Epitol Finlepsin Neurotol Tegretol", "definition": "An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of PHENYTOIN; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar.\n    ", "id": "MESH:D002220"}
{"mention": "vigabatrin", "mention_text": "Inappropriate use of carbamazepine and vigabatrin in typical absence seizures.", "entity": "Vigabatrin", "aliases": "Acid gamma-Vinyl-gamma-Aminobutyric Aventis Brand of Vigabatrin Hoechst Sabril Sabrilex Yamanouchi gamma Vinyl GABA Aminobutyric gamma-Vinyl-GABA", "definition": "An analogue of GAMMA-AMINOBUTYRIC ACID. It is an irreversible inhibitor of 4-AMINOBUTYRATE TRANSAMINASE, the enzyme responsible for the catabolism of GAMMA-AMINOBUTYRIC ACID. (From Martindale The Extra Pharmacopoeia, 31st ed)\n    ", "id": "MESH:D020888"}
{"mention": "absence seizures", "mention_text": "Inappropriate use of carbamazepine and vigabatrin in typical absence seizures.", "entity": "Epilepsy, Absence", "aliases": "Absence Epilepsies Childhood Juvenile Epilepsy Seizure Disorder Disorders Atonic Seizures Akinetic Petit Mal Convulsion Absences Atypical Minor Pykno Pykno-Epilepsies Pykno-Epilepsy Pyknolepsies Pyknolepsy", "definition": "A childhood seizure disorder characterized by rhythmic electrical brain discharges of generalized onset. Clinical features include a sudden cessation of ongoing activity usually without loss of postural tone. Rhythmic blinking of the eyelids or lip smacking frequently accompanies the SEIZURES. The usual duration is 5-10 seconds, and multiple episodes may occur daily. Juvenile absence epilepsy is characterized by the juvenile onset of absence seizures and an increased incidence of myoclonus and tonic-clonic seizures. (Menkes, Textbook of Child Neurology, 5th ed, p736)\n    ", "id": "MESH:D004832"}
{"mention": "Carbamazepine", "mention_text": "Carbamazepine and vigabatrin are contraindicated in typical absence seizures. Of 18 consecutive referrals of children with resistant typical absences only, eight were erroneously treated with carbamazepine either as monotherapy or as an add-on. Vigabatrin was also used in the treatment of two children. Frequency of absences increased in four children treated with carbamazepine and two of these developed myoclonic jerks, which resolved on withdrawal of carbamazepine. Absences were aggravated in both cases where vigabatrin was added on to concurrent treatment. Optimal control of the absences was achieved with sodium valproate, lamotrigine, or ethosuximide alone or in combination.", "entity": "Carbamazepine", "aliases": "Amizepine Carbamazepine Acetate Anhydrous Dihydrate Hydrochloride L-Tartrate (4:1) Phosphate Sulfate (2:1) Carbazepin Epitol Finlepsin Neurotol Tegretol", "definition": "An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of PHENYTOIN; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar.\n    ", "id": "MESH:D002220"}
{"mention": "vigabatrin", "mention_text": "Carbamazepine and vigabatrin are contraindicated in typical absence seizures. Of 18 consecutive referrals of children with resistant typical absences only, eight were erroneously treated with carbamazepine either as monotherapy or as an add-on. Vigabatrin was also used in the treatment of two children. Frequency of absences increased in four children treated with carbamazepine and two of these developed myoclonic jerks, which resolved on withdrawal of carbamazepine. Absences were aggravated in both cases where vigabatrin was added on to concurrent treatment. Optimal control of the absences was achieved with sodium valproate, lamotrigine, or ethosuximide alone or in combination.", "entity": "Vigabatrin", "aliases": "Acid gamma-Vinyl-gamma-Aminobutyric Aventis Brand of Vigabatrin Hoechst Sabril Sabrilex Yamanouchi gamma Vinyl GABA Aminobutyric gamma-Vinyl-GABA", "definition": "An analogue of GAMMA-AMINOBUTYRIC ACID. It is an irreversible inhibitor of 4-AMINOBUTYRATE TRANSAMINASE, the enzyme responsible for the catabolism of GAMMA-AMINOBUTYRIC ACID. (From Martindale The Extra Pharmacopoeia, 31st ed)\n    ", "id": "MESH:D020888"}
{"mention": "absence seizures", "mention_text": "Carbamazepine and vigabatrin are contraindicated in typical absence seizures. Of 18 consecutive referrals of children with resistant typical absences only, eight were erroneously treated with carbamazepine either as monotherapy or as an add-on. Vigabatrin was also used in the treatment of two children. Frequency of absences increased in four children treated with carbamazepine and two of these developed myoclonic jerks, which resolved on withdrawal of carbamazepine. Absences were aggravated in both cases where vigabatrin was added on to concurrent treatment. Optimal control of the absences was achieved with sodium valproate, lamotrigine, or ethosuximide alone or in combination.", "entity": "Epilepsy, Absence", "aliases": "Absence Epilepsies Childhood Juvenile Epilepsy Seizure Disorder Disorders Atonic Seizures Akinetic Petit Mal Convulsion Absences Atypical Minor Pykno Pykno-Epilepsies Pykno-Epilepsy Pyknolepsies Pyknolepsy", "definition": "A childhood seizure disorder characterized by rhythmic electrical brain discharges of generalized onset. Clinical features include a sudden cessation of ongoing activity usually without loss of postural tone. Rhythmic blinking of the eyelids or lip smacking frequently accompanies the SEIZURES. The usual duration is 5-10 seconds, and multiple episodes may occur daily. Juvenile absence epilepsy is characterized by the juvenile onset of absence seizures and an increased incidence of myoclonus and tonic-clonic seizures. (Menkes, Textbook of Child Neurology, 5th ed, p736)\n    ", "id": "MESH:D004832"}
{"mention": "carbamazepine", "mention_text": "Carbamazepine and vigabatrin are contraindicated in typical absence seizures. Of 18 consecutive referrals of children with resistant typical absences only, eight were erroneously treated with carbamazepine either as monotherapy or as an add-on. Vigabatrin was also used in the treatment of two children. Frequency of absences increased in four children treated with carbamazepine and two of these developed myoclonic jerks, which resolved on withdrawal of carbamazepine. Absences were aggravated in both cases where vigabatrin was added on to concurrent treatment. Optimal control of the absences was achieved with sodium valproate, lamotrigine, or ethosuximide alone or in combination.", "entity": "Carbamazepine", "aliases": "Amizepine Carbamazepine Acetate Anhydrous Dihydrate Hydrochloride L-Tartrate (4:1) Phosphate Sulfate (2:1) Carbazepin Epitol Finlepsin Neurotol Tegretol", "definition": "An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of PHENYTOIN; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar.\n    ", "id": "MESH:D002220"}
{"mention": "Vigabatrin", "mention_text": "Carbamazepine and vigabatrin are contraindicated in typical absence seizures. Of 18 consecutive referrals of children with resistant typical absences only, eight were erroneously treated with carbamazepine either as monotherapy or as an add-on. Vigabatrin was also used in the treatment of two children. Frequency of absences increased in four children treated with carbamazepine and two of these developed myoclonic jerks, which resolved on withdrawal of carbamazepine. Absences were aggravated in both cases where vigabatrin was added on to concurrent treatment. Optimal control of the absences was achieved with sodium valproate, lamotrigine, or ethosuximide alone or in combination.", "entity": "Vigabatrin", "aliases": "Acid gamma-Vinyl-gamma-Aminobutyric Aventis Brand of Vigabatrin Hoechst Sabril Sabrilex Yamanouchi gamma Vinyl GABA Aminobutyric gamma-Vinyl-GABA", "definition": "An analogue of GAMMA-AMINOBUTYRIC ACID. It is an irreversible inhibitor of 4-AMINOBUTYRATE TRANSAMINASE, the enzyme responsible for the catabolism of GAMMA-AMINOBUTYRIC ACID. (From Martindale The Extra Pharmacopoeia, 31st ed)\n    ", "id": "MESH:D020888"}
{"mention": "myoclonic jerks", "mention_text": "Carbamazepine and vigabatrin are contraindicated in typical absence seizures. Of 18 consecutive referrals of children with resistant typical absences only, eight were erroneously treated with carbamazepine either as monotherapy or as an add-on. Vigabatrin was also used in the treatment of two children. Frequency of absences increased in four children treated with carbamazepine and two of these developed myoclonic jerks, which resolved on withdrawal of carbamazepine. Absences were aggravated in both cases where vigabatrin was added on to concurrent treatment. Optimal control of the absences was achieved with sodium valproate, lamotrigine, or ethosuximide alone or in combination.", "entity": "Myoclonus", "aliases": "Action Myoclonus Extremity Lower Upper Eyelid Intention Jerk Myoclonic Jerking Jerks Simplex Nocturnal Oculopalatal Palatal Segmental Sleep Polymyoclonus", "definition": "Involuntary shock-like contractions, irregular in rhythm and amplitude, followed by relaxation, of a muscle or a group of muscles. This condition may be a feature of some CENTRAL NERVOUS SYSTEM DISEASES; (e.g., EPILEPSY, MYOCLONIC). Nocturnal myoclonus is the principal feature of the NOCTURNAL MYOCLONUS SYNDROME. (From Adams et al., Principles of Neurology, 6th ed, pp102-3).\n    ", "id": "MESH:D009207"}
{"mention": "sodium valproate", "mention_text": "Carbamazepine and vigabatrin are contraindicated in typical absence seizures. Of 18 consecutive referrals of children with resistant typical absences only, eight were erroneously treated with carbamazepine either as monotherapy or as an add-on. Vigabatrin was also used in the treatment of two children. Frequency of absences increased in four children treated with carbamazepine and two of these developed myoclonic jerks, which resolved on withdrawal of carbamazepine. Absences were aggravated in both cases where vigabatrin was added on to concurrent treatment. Optimal control of the absences was achieved with sodium valproate, lamotrigine, or ethosuximide alone or in combination.", "entity": "Valproic Acid", "aliases": "2 Propylpentanoic Acid 2-Propylpentanoic Acetate Dipropyl Propylisopropylacetic Valproic Calcium Valproate Convulsofin Depakene Depakine Depakote Divalproex Sodium Ergenyl Magnesium Semisodium Salt (2:1) Vupral", "definition": "A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of voltage dependent sodium channels.\n    ", "id": "MESH:D014635"}
{"mention": "lamotrigine", "mention_text": "Carbamazepine and vigabatrin are contraindicated in typical absence seizures. Of 18 consecutive referrals of children with resistant typical absences only, eight were erroneously treated with carbamazepine either as monotherapy or as an add-on. Vigabatrin was also used in the treatment of two children. Frequency of absences increased in four children treated with carbamazepine and two of these developed myoclonic jerks, which resolved on withdrawal of carbamazepine. Absences were aggravated in both cases where vigabatrin was added on to concurrent treatment. Optimal control of the absences was achieved with sodium valproate, lamotrigine, or ethosuximide alone or in combination.", "entity": "lamotrigine", "aliases": "3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine 3,5-diamino-6-(2,3-dichlorophenyl)-as-triazine BW-430C Crisomet Labileno Lamictal Lamiktal lamotrigine", "definition": "", "id": "MESH:C047781"}
{"mention": "ethosuximide", "mention_text": "Carbamazepine and vigabatrin are contraindicated in typical absence seizures. Of 18 consecutive referrals of children with resistant typical absences only, eight were erroneously treated with carbamazepine either as monotherapy or as an add-on. Vigabatrin was also used in the treatment of two children. Frequency of absences increased in four children treated with carbamazepine and two of these developed myoclonic jerks, which resolved on withdrawal of carbamazepine. Absences were aggravated in both cases where vigabatrin was added on to concurrent treatment. Optimal control of the absences was achieved with sodium valproate, lamotrigine, or ethosuximide alone or in combination.", "entity": "Ethosuximide", "aliases": "Desitin Brand of Ethosuximide Emeside Ethosuccimid Ethylmethylsuccimide Ethymal Etosuximida Faes Fortbenton Jenapharm Katwijk LAB Parke Davis Petnidan Pfizer Pyknolepsinum Suksilep Suxilep United Drug Warner Lambert Warner-Lambert Wernigerode Zarontin", "definition": "An anticonvulsant especially useful in the treatment of absence seizures unaccompanied by other types of seizures.\n    ", "id": "MESH:D005013"}
{"mention": "Hemolytic anemia", "mention_text": "Hemolytic anemia associated with the use of omeprazole.", "entity": "Anemia, Hemolytic", "aliases": "Acquired Hemolytic Anemia Microangiopathic", "definition": "A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES).\n    ", "id": "MESH:D000743"}
{"mention": "omeprazole", "mention_text": "Hemolytic anemia associated with the use of omeprazole.", "entity": "Omeprazole", "aliases": "H 168 68 168-68 16868 Magnesium Omeprazole Sodium Prilosec", "definition": "A 4-methoxy-3,5-dimethylpyridyl, 5-methoxybenzimidazole derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits an H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS.\n    ", "id": "MESH:D009853"}
{"mention": "Omeprazole", "mention_text": "Omeprazole is the first drug designed to block the final step in the acid secretory process within the parietal cell. It has been shown to be extremely effective in the treatment of peptic ulcer disease, reflux esophagitis, and the Zollinger-Ellison syndrome. Although clinical experience with omeprazole is still limited, many controlled studies have established the short-term safety of this drug. We report the first case of a serious short-term adverse reaction with the use of omeprazole: hemolytic anemia. The patient developed weakness, lethargy, and shortness of breath 2 days after starting therapy with omeprazole. Two weeks after the initiation of therapy, her hematocrit had decreased from 44.1% to 20.4%, and she had a positive direct Coombs antiglobulin test and an elevated indirect bilirubin. After she discontinued the omeprazole, her hemoglobin and hematocrit gradually returned to normal. The mechanism by which omeprazole caused the patient's hemolytic anemia is uncertain, but physicians should be alerted to this possible adverse effect.", "entity": "Omeprazole", "aliases": "H 168 68 168-68 16868 Magnesium Omeprazole Sodium Prilosec", "definition": "A 4-methoxy-3,5-dimethylpyridyl, 5-methoxybenzimidazole derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits an H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS.\n    ", "id": "MESH:D009853"}
{"mention": "peptic ulcer disease", "mention_text": "Omeprazole is the first drug designed to block the final step in the acid secretory process within the parietal cell. It has been shown to be extremely effective in the treatment of peptic ulcer disease, reflux esophagitis, and the Zollinger-Ellison syndrome. Although clinical experience with omeprazole is still limited, many controlled studies have established the short-term safety of this drug. We report the first case of a serious short-term adverse reaction with the use of omeprazole: hemolytic anemia. The patient developed weakness, lethargy, and shortness of breath 2 days after starting therapy with omeprazole. Two weeks after the initiation of therapy, her hematocrit had decreased from 44.1% to 20.4%, and she had a positive direct Coombs antiglobulin test and an elevated indirect bilirubin. After she discontinued the omeprazole, her hemoglobin and hematocrit gradually returned to normal. The mechanism by which omeprazole caused the patient's hemolytic anemia is uncertain, but physicians should be alerted to this possible adverse effect.", "entity": "Peptic Ulcer", "aliases": "Gastroduodenal Ulcer Ulcers Marginal Peptic", "definition": "Ulcer that occurs in the regions of the GASTROINTESTINAL TRACT which come into contact with GASTRIC JUICE containing PEPSIN and GASTRIC ACID. It occurs when there are defects in the MUCOSA barrier. The common forms of peptic ulcers are associated with HELICOBACTER PYLORI and the consumption of nonsteroidal anti-inflammatory drugs (NSAIDS).\n    ", "id": "MESH:D010437"}
{"mention": "reflux esophagitis", "mention_text": "Omeprazole is the first drug designed to block the final step in the acid secretory process within the parietal cell. It has been shown to be extremely effective in the treatment of peptic ulcer disease, reflux esophagitis, and the Zollinger-Ellison syndrome. Although clinical experience with omeprazole is still limited, many controlled studies have established the short-term safety of this drug. We report the first case of a serious short-term adverse reaction with the use of omeprazole: hemolytic anemia. The patient developed weakness, lethargy, and shortness of breath 2 days after starting therapy with omeprazole. Two weeks after the initiation of therapy, her hematocrit had decreased from 44.1% to 20.4%, and she had a positive direct Coombs antiglobulin test and an elevated indirect bilirubin. After she discontinued the omeprazole, her hemoglobin and hematocrit gradually returned to normal. The mechanism by which omeprazole caused the patient's hemolytic anemia is uncertain, but physicians should be alerted to this possible adverse effect.", "entity": "Gastroesophageal Reflux", "aliases": "Acid Reflux Gastric Esophageal GERD Disease Gastro oesophageal Gastro-Esophageal Gastro-oesophageal Gastroesophageal", "definition": "Retrograde flow of gastric juice (GASTRIC ACID) and/or duodenal contents (BILE ACIDS; PANCREATIC JUICE) into the distal ESOPHAGUS, commonly due to incompetence of the LOWER ESOPHAGEAL SPHINCTER.\n    ", "id": "MESH:D005764"}
{"mention": "Zollinger-Ellison syndrome", "mention_text": "Omeprazole is the first drug designed to block the final step in the acid secretory process within the parietal cell. It has been shown to be extremely effective in the treatment of peptic ulcer disease, reflux esophagitis, and the Zollinger-Ellison syndrome. Although clinical experience with omeprazole is still limited, many controlled studies have established the short-term safety of this drug. We report the first case of a serious short-term adverse reaction with the use of omeprazole: hemolytic anemia. The patient developed weakness, lethargy, and shortness of breath 2 days after starting therapy with omeprazole. Two weeks after the initiation of therapy, her hematocrit had decreased from 44.1% to 20.4%, and she had a positive direct Coombs antiglobulin test and an elevated indirect bilirubin. After she discontinued the omeprazole, her hemoglobin and hematocrit gradually returned to normal. The mechanism by which omeprazole caused the patient's hemolytic anemia is uncertain, but physicians should be alerted to this possible adverse effect.", "entity": "Zollinger-Ellison Syndrome", "aliases": "Syndrome Zollinger-Ellison Zollinger Ellison", "definition": "A syndrome that is characterized by the triad of severe PEPTIC ULCER, hypersecretion of GASTRIC ACID, and GASTRIN-producing tumors of the PANCREAS or other tissue (GASTRINOMA). This syndrome may be sporadic or be associated with MULTIPLE ENDOCRINE NEOPLASIA TYPE 1.\n    ", "id": "MESH:D015043"}
{"mention": "omeprazole", "mention_text": "Omeprazole is the first drug designed to block the final step in the acid secretory process within the parietal cell. It has been shown to be extremely effective in the treatment of peptic ulcer disease, reflux esophagitis, and the Zollinger-Ellison syndrome. Although clinical experience with omeprazole is still limited, many controlled studies have established the short-term safety of this drug. We report the first case of a serious short-term adverse reaction with the use of omeprazole: hemolytic anemia. The patient developed weakness, lethargy, and shortness of breath 2 days after starting therapy with omeprazole. Two weeks after the initiation of therapy, her hematocrit had decreased from 44.1% to 20.4%, and she had a positive direct Coombs antiglobulin test and an elevated indirect bilirubin. After she discontinued the omeprazole, her hemoglobin and hematocrit gradually returned to normal. The mechanism by which omeprazole caused the patient's hemolytic anemia is uncertain, but physicians should be alerted to this possible adverse effect.", "entity": "Omeprazole", "aliases": "H 168 68 168-68 16868 Magnesium Omeprazole Sodium Prilosec", "definition": "A 4-methoxy-3,5-dimethylpyridyl, 5-methoxybenzimidazole derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits an H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS.\n    ", "id": "MESH:D009853"}
{"mention": "hemolytic anemia", "mention_text": "Omeprazole is the first drug designed to block the final step in the acid secretory process within the parietal cell. It has been shown to be extremely effective in the treatment of peptic ulcer disease, reflux esophagitis, and the Zollinger-Ellison syndrome. Although clinical experience with omeprazole is still limited, many controlled studies have established the short-term safety of this drug. We report the first case of a serious short-term adverse reaction with the use of omeprazole: hemolytic anemia. The patient developed weakness, lethargy, and shortness of breath 2 days after starting therapy with omeprazole. Two weeks after the initiation of therapy, her hematocrit had decreased from 44.1% to 20.4%, and she had a positive direct Coombs antiglobulin test and an elevated indirect bilirubin. After she discontinued the omeprazole, her hemoglobin and hematocrit gradually returned to normal. The mechanism by which omeprazole caused the patient's hemolytic anemia is uncertain, but physicians should be alerted to this possible adverse effect.", "entity": "Anemia, Hemolytic", "aliases": "Acquired Hemolytic Anemia Microangiopathic", "definition": "A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES).\n    ", "id": "MESH:D000743"}
{"mention": "lethargy", "mention_text": "Omeprazole is the first drug designed to block the final step in the acid secretory process within the parietal cell. It has been shown to be extremely effective in the treatment of peptic ulcer disease, reflux esophagitis, and the Zollinger-Ellison syndrome. Although clinical experience with omeprazole is still limited, many controlled studies have established the short-term safety of this drug. We report the first case of a serious short-term adverse reaction with the use of omeprazole: hemolytic anemia. The patient developed weakness, lethargy, and shortness of breath 2 days after starting therapy with omeprazole. Two weeks after the initiation of therapy, her hematocrit had decreased from 44.1% to 20.4%, and she had a positive direct Coombs antiglobulin test and an elevated indirect bilirubin. After she discontinued the omeprazole, her hemoglobin and hematocrit gradually returned to normal. The mechanism by which omeprazole caused the patient's hemolytic anemia is uncertain, but physicians should be alerted to this possible adverse effect.", "entity": "Lethargy", "aliases": "Lethargy", "definition": "A general state of sluggishness, listless, or uninterested, with being tired, and having difficulty concentrating and doing simple tasks. It may be related to DEPRESSION or DRUG ADDICTION.\n    ", "id": "MESH:D053609"}
{"mention": "shortness of breath", "mention_text": "Omeprazole is the first drug designed to block the final step in the acid secretory process within the parietal cell. It has been shown to be extremely effective in the treatment of peptic ulcer disease, reflux esophagitis, and the Zollinger-Ellison syndrome. Although clinical experience with omeprazole is still limited, many controlled studies have established the short-term safety of this drug. We report the first case of a serious short-term adverse reaction with the use of omeprazole: hemolytic anemia. The patient developed weakness, lethargy, and shortness of breath 2 days after starting therapy with omeprazole. Two weeks after the initiation of therapy, her hematocrit had decreased from 44.1% to 20.4%, and she had a positive direct Coombs antiglobulin test and an elevated indirect bilirubin. After she discontinued the omeprazole, her hemoglobin and hematocrit gradually returned to normal. The mechanism by which omeprazole caused the patient's hemolytic anemia is uncertain, but physicians should be alerted to this possible adverse effect.", "entity": "Dyspnea", "aliases": "Breath Shortness Shortnesses Breathlessness Breathlessnesses Dyspnea Dyspneas of", "definition": "Difficult or labored breathing.\n    ", "id": "MESH:D004417"}
{"mention": "bilirubin", "mention_text": "Omeprazole is the first drug designed to block the final step in the acid secretory process within the parietal cell. It has been shown to be extremely effective in the treatment of peptic ulcer disease, reflux esophagitis, and the Zollinger-Ellison syndrome. Although clinical experience with omeprazole is still limited, many controlled studies have established the short-term safety of this drug. We report the first case of a serious short-term adverse reaction with the use of omeprazole: hemolytic anemia. The patient developed weakness, lethargy, and shortness of breath 2 days after starting therapy with omeprazole. Two weeks after the initiation of therapy, her hematocrit had decreased from 44.1% to 20.4%, and she had a positive direct Coombs antiglobulin test and an elevated indirect bilirubin. After she discontinued the omeprazole, her hemoglobin and hematocrit gradually returned to normal. The mechanism by which omeprazole caused the patient's hemolytic anemia is uncertain, but physicians should be alerted to this possible adverse effect.", "entity": "Bilirubin", "aliases": "Bilirubin IX alpha (15E)-Isomer (4E)-Isomer (4E,15E)-Isomer Calcium Salt Disodium Monosodium Bilirubinate Hematoidin delta delta-Bilirubin", "definition": "A bile pigment that is a degradation product of HEME.\n    ", "id": "MESH:D001663"}
{"mention": "toxicity", "mention_text": "The use and toxicity of didanosine (ddI) in HIV antibody-positive individuals intolerant to zidovudine (AZT)", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "didanosine", "mention_text": "The use and toxicity of didanosine (ddI) in HIV antibody-positive individuals intolerant to zidovudine (AZT)", "entity": "Didanosine", "aliases": "2',3' Dideoxyinosine 2',3'-Dideoxyinosine Bristol Myers Brand of Didanosine Squibb Bristol-Myers NSC 612049 NSC-612049 NSC612049 Videx ddI (Antiviral)", "definition": "A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite.\n    ", "id": "MESH:D016049"}
{"mention": "ddI", "mention_text": "The use and toxicity of didanosine (ddI) in HIV antibody-positive individuals intolerant to zidovudine (AZT)", "entity": "Didanosine", "aliases": "2',3' Dideoxyinosine 2',3'-Dideoxyinosine Bristol Myers Brand of Didanosine Squibb Bristol-Myers NSC 612049 NSC-612049 NSC612049 Videx ddI (Antiviral)", "definition": "A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite.\n    ", "id": "MESH:D016049"}
{"mention": "HIV antibody-positive", "mention_text": "The use and toxicity of didanosine (ddI) in HIV antibody-positive individuals intolerant to zidovudine (AZT)", "entity": "HIV Infections", "aliases": "HIV Infection Infections HTLV III LAV HTLV-III HTLV-III-LAV T Lymphotropic Virus Type Human T-Lymphotropic", "definition": "Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).\n    ", "id": "MESH:D015658"}
{"mention": "zidovudine", "mention_text": "The use and toxicity of didanosine (ddI) in HIV antibody-positive individuals intolerant to zidovudine (AZT)", "entity": "Zidovudine", "aliases": "3' Azido 2',3' Dideoxythymidine deoxythymidine 3'-Azido-2',3'-Dideoxythymidine 3'-Azido-3'-deoxythymidine AZT (Antiviral) Antiviral Azidothymidine BW A509U BWA 509U BWA-509U BWA509U Retrovir Zidovudine", "definition": "A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.\n    ", "id": "MESH:D015215"}
{"mention": "AZT", "mention_text": "The use and toxicity of didanosine (ddI) in HIV antibody-positive individuals intolerant to zidovudine (AZT)", "entity": "Zidovudine", "aliases": "3' Azido 2',3' Dideoxythymidine deoxythymidine 3'-Azido-2',3'-Dideoxythymidine 3'-Azido-3'-deoxythymidine AZT (Antiviral) Antiviral Azidothymidine BW A509U BWA 509U BWA-509U BWA509U Retrovir Zidovudine", "definition": "A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.\n    ", "id": "MESH:D015215"}
{"mention": "zidovudine", "mention_text": "One hundred and fifty-one patients intolerant to zidovudine (AZT) received didanosine (ddI) to a maximum dose of 12.5 mg/kg/day. Patient response was assessed using changes in CD4+ lymphocyte subset count, HIV p24 antigen, weight, and quality of life. Seventy patients developed major opportunistic infections whilst on therapy; this was the first AIDS diagnosis in 17. Only minor changes in CD4+ lymphocyte subset count were observed in AIDS patients, although a more significant rise occurred in those with earlier stages of disease. Of those positive for p24 antigen at the commencement of the study 67% showed a positive response, and this was most likely in those with CD4+ lymphocyte subset counts above 100 mm3. A positive weight response was seen in 16% of patients. Most patients showed improvement in individual parameters and global score of quality of life. Adverse reactions possibly attributable to didanosine were common. The most common side-effect was diarrhoea, which resulted in cessation of therapy in 19 individuals. Peripheral neuropathy occurred in 12 patients and pancreatitis in six. Thirteen patients developed a raised serum amylase without abdominal pain. Seven patients developed glucose tolerance curves characteristic of diabetes but these were mild, did not require treatment and returned to normal on ceasing didanosine.", "entity": "Zidovudine", "aliases": "3' Azido 2',3' Dideoxythymidine deoxythymidine 3'-Azido-2',3'-Dideoxythymidine 3'-Azido-3'-deoxythymidine AZT (Antiviral) Antiviral Azidothymidine BW A509U BWA 509U BWA-509U BWA509U Retrovir Zidovudine", "definition": "A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.\n    ", "id": "MESH:D015215"}
{"mention": "AZT", "mention_text": "One hundred and fifty-one patients intolerant to zidovudine (AZT) received didanosine (ddI) to a maximum dose of 12.5 mg/kg/day. Patient response was assessed using changes in CD4+ lymphocyte subset count, HIV p24 antigen, weight, and quality of life. Seventy patients developed major opportunistic infections whilst on therapy; this was the first AIDS diagnosis in 17. Only minor changes in CD4+ lymphocyte subset count were observed in AIDS patients, although a more significant rise occurred in those with earlier stages of disease. Of those positive for p24 antigen at the commencement of the study 67% showed a positive response, and this was most likely in those with CD4+ lymphocyte subset counts above 100 mm3. A positive weight response was seen in 16% of patients. Most patients showed improvement in individual parameters and global score of quality of life. Adverse reactions possibly attributable to didanosine were common. The most common side-effect was diarrhoea, which resulted in cessation of therapy in 19 individuals. Peripheral neuropathy occurred in 12 patients and pancreatitis in six. Thirteen patients developed a raised serum amylase without abdominal pain. Seven patients developed glucose tolerance curves characteristic of diabetes but these were mild, did not require treatment and returned to normal on ceasing didanosine.", "entity": "Zidovudine", "aliases": "3' Azido 2',3' Dideoxythymidine deoxythymidine 3'-Azido-2',3'-Dideoxythymidine 3'-Azido-3'-deoxythymidine AZT (Antiviral) Antiviral Azidothymidine BW A509U BWA 509U BWA-509U BWA509U Retrovir Zidovudine", "definition": "A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.\n    ", "id": "MESH:D015215"}
{"mention": "didanosine", "mention_text": "One hundred and fifty-one patients intolerant to zidovudine (AZT) received didanosine (ddI) to a maximum dose of 12.5 mg/kg/day. Patient response was assessed using changes in CD4+ lymphocyte subset count, HIV p24 antigen, weight, and quality of life. Seventy patients developed major opportunistic infections whilst on therapy; this was the first AIDS diagnosis in 17. Only minor changes in CD4+ lymphocyte subset count were observed in AIDS patients, although a more significant rise occurred in those with earlier stages of disease. Of those positive for p24 antigen at the commencement of the study 67% showed a positive response, and this was most likely in those with CD4+ lymphocyte subset counts above 100 mm3. A positive weight response was seen in 16% of patients. Most patients showed improvement in individual parameters and global score of quality of life. Adverse reactions possibly attributable to didanosine were common. The most common side-effect was diarrhoea, which resulted in cessation of therapy in 19 individuals. Peripheral neuropathy occurred in 12 patients and pancreatitis in six. Thirteen patients developed a raised serum amylase without abdominal pain. Seven patients developed glucose tolerance curves characteristic of diabetes but these were mild, did not require treatment and returned to normal on ceasing didanosine.", "entity": "Didanosine", "aliases": "2',3' Dideoxyinosine 2',3'-Dideoxyinosine Bristol Myers Brand of Didanosine Squibb Bristol-Myers NSC 612049 NSC-612049 NSC612049 Videx ddI (Antiviral)", "definition": "A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite.\n    ", "id": "MESH:D016049"}
{"mention": "ddI", "mention_text": "One hundred and fifty-one patients intolerant to zidovudine (AZT) received didanosine (ddI) to a maximum dose of 12.5 mg/kg/day. Patient response was assessed using changes in CD4+ lymphocyte subset count, HIV p24 antigen, weight, and quality of life. Seventy patients developed major opportunistic infections whilst on therapy; this was the first AIDS diagnosis in 17. Only minor changes in CD4+ lymphocyte subset count were observed in AIDS patients, although a more significant rise occurred in those with earlier stages of disease. Of those positive for p24 antigen at the commencement of the study 67% showed a positive response, and this was most likely in those with CD4+ lymphocyte subset counts above 100 mm3. A positive weight response was seen in 16% of patients. Most patients showed improvement in individual parameters and global score of quality of life. Adverse reactions possibly attributable to didanosine were common. The most common side-effect was diarrhoea, which resulted in cessation of therapy in 19 individuals. Peripheral neuropathy occurred in 12 patients and pancreatitis in six. Thirteen patients developed a raised serum amylase without abdominal pain. Seven patients developed glucose tolerance curves characteristic of diabetes but these were mild, did not require treatment and returned to normal on ceasing didanosine.", "entity": "Didanosine", "aliases": "2',3' Dideoxyinosine 2',3'-Dideoxyinosine Bristol Myers Brand of Didanosine Squibb Bristol-Myers NSC 612049 NSC-612049 NSC612049 Videx ddI (Antiviral)", "definition": "A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite.\n    ", "id": "MESH:D016049"}
{"mention": "opportunistic infections", "mention_text": "One hundred and fifty-one patients intolerant to zidovudine (AZT) received didanosine (ddI) to a maximum dose of 12.5 mg/kg/day. Patient response was assessed using changes in CD4+ lymphocyte subset count, HIV p24 antigen, weight, and quality of life. Seventy patients developed major opportunistic infections whilst on therapy; this was the first AIDS diagnosis in 17. Only minor changes in CD4+ lymphocyte subset count were observed in AIDS patients, although a more significant rise occurred in those with earlier stages of disease. Of those positive for p24 antigen at the commencement of the study 67% showed a positive response, and this was most likely in those with CD4+ lymphocyte subset counts above 100 mm3. A positive weight response was seen in 16% of patients. Most patients showed improvement in individual parameters and global score of quality of life. Adverse reactions possibly attributable to didanosine were common. The most common side-effect was diarrhoea, which resulted in cessation of therapy in 19 individuals. Peripheral neuropathy occurred in 12 patients and pancreatitis in six. Thirteen patients developed a raised serum amylase without abdominal pain. Seven patients developed glucose tolerance curves characteristic of diabetes but these were mild, did not require treatment and returned to normal on ceasing didanosine.", "entity": "Opportunistic Infections", "aliases": "Infection Opportunistic Infections", "definition": "An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression.\n    ", "id": "MESH:D009894"}
{"mention": "AIDS", "mention_text": "One hundred and fifty-one patients intolerant to zidovudine (AZT) received didanosine (ddI) to a maximum dose of 12.5 mg/kg/day. Patient response was assessed using changes in CD4+ lymphocyte subset count, HIV p24 antigen, weight, and quality of life. Seventy patients developed major opportunistic infections whilst on therapy; this was the first AIDS diagnosis in 17. Only minor changes in CD4+ lymphocyte subset count were observed in AIDS patients, although a more significant rise occurred in those with earlier stages of disease. Of those positive for p24 antigen at the commencement of the study 67% showed a positive response, and this was most likely in those with CD4+ lymphocyte subset counts above 100 mm3. A positive weight response was seen in 16% of patients. Most patients showed improvement in individual parameters and global score of quality of life. Adverse reactions possibly attributable to didanosine were common. The most common side-effect was diarrhoea, which resulted in cessation of therapy in 19 individuals. Peripheral neuropathy occurred in 12 patients and pancreatitis in six. Thirteen patients developed a raised serum amylase without abdominal pain. Seven patients developed glucose tolerance curves characteristic of diabetes but these were mild, did not require treatment and returned to normal on ceasing didanosine.", "entity": "Acquired Immunodeficiency Syndrome", "aliases": "AIDS Acquired Immune Deficiency Syndrome Immuno Immuno-Deficiency Syndromes Immunodeficiency Immunologic", "definition": "An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive T-lymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993.\n    ", "id": "MESH:D000163"}
{"mention": "diarrhoea", "mention_text": "One hundred and fifty-one patients intolerant to zidovudine (AZT) received didanosine (ddI) to a maximum dose of 12.5 mg/kg/day. Patient response was assessed using changes in CD4+ lymphocyte subset count, HIV p24 antigen, weight, and quality of life. Seventy patients developed major opportunistic infections whilst on therapy; this was the first AIDS diagnosis in 17. Only minor changes in CD4+ lymphocyte subset count were observed in AIDS patients, although a more significant rise occurred in those with earlier stages of disease. Of those positive for p24 antigen at the commencement of the study 67% showed a positive response, and this was most likely in those with CD4+ lymphocyte subset counts above 100 mm3. A positive weight response was seen in 16% of patients. Most patients showed improvement in individual parameters and global score of quality of life. Adverse reactions possibly attributable to didanosine were common. The most common side-effect was diarrhoea, which resulted in cessation of therapy in 19 individuals. Peripheral neuropathy occurred in 12 patients and pancreatitis in six. Thirteen patients developed a raised serum amylase without abdominal pain. Seven patients developed glucose tolerance curves characteristic of diabetes but these were mild, did not require treatment and returned to normal on ceasing didanosine.", "entity": "Diarrhea", "aliases": "Diarrhea Diarrheas", "definition": "An increased liquidity or decreased consistency of FECES, such as running stool. Fecal consistency is related to the ratio of water-holding capacity of insoluble solids to total water, rather than the amount of water present. Diarrhea is not hyperdefecation or increased fecal weight.\n    ", "id": "MESH:D003967"}
{"mention": "Peripheral neuropathy", "mention_text": "One hundred and fifty-one patients intolerant to zidovudine (AZT) received didanosine (ddI) to a maximum dose of 12.5 mg/kg/day. Patient response was assessed using changes in CD4+ lymphocyte subset count, HIV p24 antigen, weight, and quality of life. Seventy patients developed major opportunistic infections whilst on therapy; this was the first AIDS diagnosis in 17. Only minor changes in CD4+ lymphocyte subset count were observed in AIDS patients, although a more significant rise occurred in those with earlier stages of disease. Of those positive for p24 antigen at the commencement of the study 67% showed a positive response, and this was most likely in those with CD4+ lymphocyte subset counts above 100 mm3. A positive weight response was seen in 16% of patients. Most patients showed improvement in individual parameters and global score of quality of life. Adverse reactions possibly attributable to didanosine were common. The most common side-effect was diarrhoea, which resulted in cessation of therapy in 19 individuals. Peripheral neuropathy occurred in 12 patients and pancreatitis in six. Thirteen patients developed a raised serum amylase without abdominal pain. Seven patients developed glucose tolerance curves characteristic of diabetes but these were mild, did not require treatment and returned to normal on ceasing didanosine.", "entity": "Peripheral Nervous System Diseases", "aliases": "Nerve Disease Peripheral Diseases Neuropathy PNS (Peripheral Nervous System) System Disorders Neuropathies", "definition": "Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.\n    ", "id": "MESH:D010523"}
{"mention": "pancreatitis", "mention_text": "One hundred and fifty-one patients intolerant to zidovudine (AZT) received didanosine (ddI) to a maximum dose of 12.5 mg/kg/day. Patient response was assessed using changes in CD4+ lymphocyte subset count, HIV p24 antigen, weight, and quality of life. Seventy patients developed major opportunistic infections whilst on therapy; this was the first AIDS diagnosis in 17. Only minor changes in CD4+ lymphocyte subset count were observed in AIDS patients, although a more significant rise occurred in those with earlier stages of disease. Of those positive for p24 antigen at the commencement of the study 67% showed a positive response, and this was most likely in those with CD4+ lymphocyte subset counts above 100 mm3. A positive weight response was seen in 16% of patients. Most patients showed improvement in individual parameters and global score of quality of life. Adverse reactions possibly attributable to didanosine were common. The most common side-effect was diarrhoea, which resulted in cessation of therapy in 19 individuals. Peripheral neuropathy occurred in 12 patients and pancreatitis in six. Thirteen patients developed a raised serum amylase without abdominal pain. Seven patients developed glucose tolerance curves characteristic of diabetes but these were mild, did not require treatment and returned to normal on ceasing didanosine.", "entity": "Pancreatitis", "aliases": "Pancreatitides Pancreatitis", "definition": "INFLAMMATION of the PANCREAS. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of CHRONIC PANCREATITIS (International Symposium on Acute Pancreatitis, Atlanta, 1992). The two most common forms of acute pancreatitis are ALCOHOLIC PANCREATITIS and gallstone pancreatitis.\n    ", "id": "MESH:D010195"}
{"mention": "abdominal pain", "mention_text": "One hundred and fifty-one patients intolerant to zidovudine (AZT) received didanosine (ddI) to a maximum dose of 12.5 mg/kg/day. Patient response was assessed using changes in CD4+ lymphocyte subset count, HIV p24 antigen, weight, and quality of life. Seventy patients developed major opportunistic infections whilst on therapy; this was the first AIDS diagnosis in 17. Only minor changes in CD4+ lymphocyte subset count were observed in AIDS patients, although a more significant rise occurred in those with earlier stages of disease. Of those positive for p24 antigen at the commencement of the study 67% showed a positive response, and this was most likely in those with CD4+ lymphocyte subset counts above 100 mm3. A positive weight response was seen in 16% of patients. Most patients showed improvement in individual parameters and global score of quality of life. Adverse reactions possibly attributable to didanosine were common. The most common side-effect was diarrhoea, which resulted in cessation of therapy in 19 individuals. Peripheral neuropathy occurred in 12 patients and pancreatitis in six. Thirteen patients developed a raised serum amylase without abdominal pain. Seven patients developed glucose tolerance curves characteristic of diabetes but these were mild, did not require treatment and returned to normal on ceasing didanosine.", "entity": "Abdominal Pain", "aliases": "Abdominal Pain Pains", "definition": "Sensation of discomfort, distress, or agony in the abdominal region; generally associated with functional disorders, tissue injuries, or diseases.\n    ", "id": "MESH:D015746"}
{"mention": "glucose tolerance curves", "mention_text": "One hundred and fifty-one patients intolerant to zidovudine (AZT) received didanosine (ddI) to a maximum dose of 12.5 mg/kg/day. Patient response was assessed using changes in CD4+ lymphocyte subset count, HIV p24 antigen, weight, and quality of life. Seventy patients developed major opportunistic infections whilst on therapy; this was the first AIDS diagnosis in 17. Only minor changes in CD4+ lymphocyte subset count were observed in AIDS patients, although a more significant rise occurred in those with earlier stages of disease. Of those positive for p24 antigen at the commencement of the study 67% showed a positive response, and this was most likely in those with CD4+ lymphocyte subset counts above 100 mm3. A positive weight response was seen in 16% of patients. Most patients showed improvement in individual parameters and global score of quality of life. Adverse reactions possibly attributable to didanosine were common. The most common side-effect was diarrhoea, which resulted in cessation of therapy in 19 individuals. Peripheral neuropathy occurred in 12 patients and pancreatitis in six. Thirteen patients developed a raised serum amylase without abdominal pain. Seven patients developed glucose tolerance curves characteristic of diabetes but these were mild, did not require treatment and returned to normal on ceasing didanosine.", "entity": "Glucose Intolerance", "aliases": "Glucose Intolerance Intolerances", "definition": "A pathological state in which BLOOD GLUCOSE level is less than approximately 140 mg/100 ml of PLASMA at fasting, and above approximately 200 mg/100 ml plasma at 30-, 60-, or 90-minute during a GLUCOSE TOLERANCE TEST. This condition is seen frequently in DIABETES MELLITUS, but also occurs with other diseases and MALNUTRITION.\n    ", "id": "MESH:D018149"}
{"mention": "diabetes", "mention_text": "One hundred and fifty-one patients intolerant to zidovudine (AZT) received didanosine (ddI) to a maximum dose of 12.5 mg/kg/day. Patient response was assessed using changes in CD4+ lymphocyte subset count, HIV p24 antigen, weight, and quality of life. Seventy patients developed major opportunistic infections whilst on therapy; this was the first AIDS diagnosis in 17. Only minor changes in CD4+ lymphocyte subset count were observed in AIDS patients, although a more significant rise occurred in those with earlier stages of disease. Of those positive for p24 antigen at the commencement of the study 67% showed a positive response, and this was most likely in those with CD4+ lymphocyte subset counts above 100 mm3. A positive weight response was seen in 16% of patients. Most patients showed improvement in individual parameters and global score of quality of life. Adverse reactions possibly attributable to didanosine were common. The most common side-effect was diarrhoea, which resulted in cessation of therapy in 19 individuals. Peripheral neuropathy occurred in 12 patients and pancreatitis in six. Thirteen patients developed a raised serum amylase without abdominal pain. Seven patients developed glucose tolerance curves characteristic of diabetes but these were mild, did not require treatment and returned to normal on ceasing didanosine.", "entity": "Diabetes Mellitus", "aliases": "Diabetes Mellitus", "definition": "A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.\n    ", "id": "MESH:D003920"}
{"mention": "ribavirin", "mention_text": "Can angiogenesis be a target of treatment for ribavirin associated hemolytic anemia?", "entity": "Ribavirin", "aliases": "Dermatech Brand of Ribavirin Essex Grossman ICN 1229 ICN-1229 ICN1229 Merck Pfizer Rebetol Ribamide Ribamidil Ribamidyl Ribasphere Ribovirin Three Rivers Pharmaceuticals Tribavirin Vilona Viramide Virazide Virazole", "definition": "A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses.\n    ", "id": "MESH:D012254"}
{"mention": "hemolytic anemia", "mention_text": "Can angiogenesis be a target of treatment for ribavirin associated hemolytic anemia?", "entity": "Anemia, Hemolytic", "aliases": "Acquired Hemolytic Anemia Microangiopathic", "definition": "A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES).\n    ", "id": "MESH:D000743"}
{"mention": "ribavirin", "mention_text": "BACKGROUND/AIMS: Recently ribavirin has been found to inhibit angiogenesis and a number of angiogenesis inhibitors such as sunitinib and sorafenib have been found to cause acute hemolysis. We aimed to investigate whether there is a relation between hemoglobin, haptoglobin and angiogenesis soluble markers which are modifiable and can help in developing strategies against anemia. METHODS: Fourteen patients chronically infected with hepatitis C virus were treated by pegylated interferon alpha 2a and ribavirin. Serum hemoglobin, haptoglobin and angiogenesis markers of vascular endothelial growth factor and angiopoetin-2 were investigated before and after therapy. RESULTS: We observed a significant decrease in haptoglobin levels at the end of the treatment period. Hemoglobin levels also decreased but insignificantly by treatment. In contrast with the literature, serum levels of angiogenesis factors did not change significantly by pegylated interferon and ribavirin therapy. We found no correlation of angiogenesis soluble markers with either hemoglobin or haptoglobin. CONCLUSION: This is the first study in the literature investigating a link between angiogenesis soluble markers and ribavirin induced anemia in patients with hepatitis C and we could not find any relation. Future research with larger number of patients is needed to find out modifiable factors that will improve the safety of ribavirin therapy.", "entity": "Ribavirin", "aliases": "Dermatech Brand of Ribavirin Essex Grossman ICN 1229 ICN-1229 ICN1229 Merck Pfizer Rebetol Ribamide Ribamidil Ribamidyl Ribasphere Ribovirin Three Rivers Pharmaceuticals Tribavirin Vilona Viramide Virazide Virazole", "definition": "A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses.\n    ", "id": "MESH:D012254"}
{"mention": "sunitinib", "mention_text": "BACKGROUND/AIMS: Recently ribavirin has been found to inhibit angiogenesis and a number of angiogenesis inhibitors such as sunitinib and sorafenib have been found to cause acute hemolysis. We aimed to investigate whether there is a relation between hemoglobin, haptoglobin and angiogenesis soluble markers which are modifiable and can help in developing strategies against anemia. METHODS: Fourteen patients chronically infected with hepatitis C virus were treated by pegylated interferon alpha 2a and ribavirin. Serum hemoglobin, haptoglobin and angiogenesis markers of vascular endothelial growth factor and angiopoetin-2 were investigated before and after therapy. RESULTS: We observed a significant decrease in haptoglobin levels at the end of the treatment period. Hemoglobin levels also decreased but insignificantly by treatment. In contrast with the literature, serum levels of angiogenesis factors did not change significantly by pegylated interferon and ribavirin therapy. We found no correlation of angiogenesis soluble markers with either hemoglobin or haptoglobin. CONCLUSION: This is the first study in the literature investigating a link between angiogenesis soluble markers and ribavirin induced anemia in patients with hepatitis C and we could not find any relation. Future research with larger number of patients is needed to find out modifiable factors that will improve the safety of ribavirin therapy.", "entity": "sunitinib", "aliases": "5-(5-fluoro-2-oxo-1,2-dihydroindolylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide SU 011248 11248 SU-011248 SU-11248 SU011248 SU11248 Sutent sunitinib malate", "definition": "", "id": "MESH:C473478"}
{"mention": "sorafenib", "mention_text": "BACKGROUND/AIMS: Recently ribavirin has been found to inhibit angiogenesis and a number of angiogenesis inhibitors such as sunitinib and sorafenib have been found to cause acute hemolysis. We aimed to investigate whether there is a relation between hemoglobin, haptoglobin and angiogenesis soluble markers which are modifiable and can help in developing strategies against anemia. METHODS: Fourteen patients chronically infected with hepatitis C virus were treated by pegylated interferon alpha 2a and ribavirin. Serum hemoglobin, haptoglobin and angiogenesis markers of vascular endothelial growth factor and angiopoetin-2 were investigated before and after therapy. RESULTS: We observed a significant decrease in haptoglobin levels at the end of the treatment period. Hemoglobin levels also decreased but insignificantly by treatment. In contrast with the literature, serum levels of angiogenesis factors did not change significantly by pegylated interferon and ribavirin therapy. We found no correlation of angiogenesis soluble markers with either hemoglobin or haptoglobin. CONCLUSION: This is the first study in the literature investigating a link between angiogenesis soluble markers and ribavirin induced anemia in patients with hepatitis C and we could not find any relation. Future research with larger number of patients is needed to find out modifiable factors that will improve the safety of ribavirin therapy.", "entity": "sorafenib", "aliases": "4-(4-(3-(4-chloro-3-trifluoromethylphenyl)ureido)phenoxy)pyridine-2-carboxyllic acid methyamide-4-methylbenzenesulfonate BAY 43-9006 545-9085 BAY-545-9085 Nexavar sorafenib N-oxide tosylate", "definition": "", "id": "MESH:C471405"}
{"mention": "hemolysis", "mention_text": "BACKGROUND/AIMS: Recently ribavirin has been found to inhibit angiogenesis and a number of angiogenesis inhibitors such as sunitinib and sorafenib have been found to cause acute hemolysis. We aimed to investigate whether there is a relation between hemoglobin, haptoglobin and angiogenesis soluble markers which are modifiable and can help in developing strategies against anemia. METHODS: Fourteen patients chronically infected with hepatitis C virus were treated by pegylated interferon alpha 2a and ribavirin. Serum hemoglobin, haptoglobin and angiogenesis markers of vascular endothelial growth factor and angiopoetin-2 were investigated before and after therapy. RESULTS: We observed a significant decrease in haptoglobin levels at the end of the treatment period. Hemoglobin levels also decreased but insignificantly by treatment. In contrast with the literature, serum levels of angiogenesis factors did not change significantly by pegylated interferon and ribavirin therapy. We found no correlation of angiogenesis soluble markers with either hemoglobin or haptoglobin. CONCLUSION: This is the first study in the literature investigating a link between angiogenesis soluble markers and ribavirin induced anemia in patients with hepatitis C and we could not find any relation. Future research with larger number of patients is needed to find out modifiable factors that will improve the safety of ribavirin therapy.", "entity": "Hemolysis", "aliases": "Hemolysis", "definition": "The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.\n    ", "id": "MESH:D006461"}
{"mention": "anemia", "mention_text": "BACKGROUND/AIMS: Recently ribavirin has been found to inhibit angiogenesis and a number of angiogenesis inhibitors such as sunitinib and sorafenib have been found to cause acute hemolysis. We aimed to investigate whether there is a relation between hemoglobin, haptoglobin and angiogenesis soluble markers which are modifiable and can help in developing strategies against anemia. METHODS: Fourteen patients chronically infected with hepatitis C virus were treated by pegylated interferon alpha 2a and ribavirin. Serum hemoglobin, haptoglobin and angiogenesis markers of vascular endothelial growth factor and angiopoetin-2 were investigated before and after therapy. RESULTS: We observed a significant decrease in haptoglobin levels at the end of the treatment period. Hemoglobin levels also decreased but insignificantly by treatment. In contrast with the literature, serum levels of angiogenesis factors did not change significantly by pegylated interferon and ribavirin therapy. We found no correlation of angiogenesis soluble markers with either hemoglobin or haptoglobin. CONCLUSION: This is the first study in the literature investigating a link between angiogenesis soluble markers and ribavirin induced anemia in patients with hepatitis C and we could not find any relation. Future research with larger number of patients is needed to find out modifiable factors that will improve the safety of ribavirin therapy.", "entity": "Anemia", "aliases": "Anemia Anemias", "definition": "A reduction in the number of circulating ERYTHROCYTES or in the quantity of HEMOGLOBIN.\n    ", "id": "MESH:D000740"}
{"mention": "chronically infected with hepatitis C virus", "mention_text": "BACKGROUND/AIMS: Recently ribavirin has been found to inhibit angiogenesis and a number of angiogenesis inhibitors such as sunitinib and sorafenib have been found to cause acute hemolysis. We aimed to investigate whether there is a relation between hemoglobin, haptoglobin and angiogenesis soluble markers which are modifiable and can help in developing strategies against anemia. METHODS: Fourteen patients chronically infected with hepatitis C virus were treated by pegylated interferon alpha 2a and ribavirin. Serum hemoglobin, haptoglobin and angiogenesis markers of vascular endothelial growth factor and angiopoetin-2 were investigated before and after therapy. RESULTS: We observed a significant decrease in haptoglobin levels at the end of the treatment period. Hemoglobin levels also decreased but insignificantly by treatment. In contrast with the literature, serum levels of angiogenesis factors did not change significantly by pegylated interferon and ribavirin therapy. We found no correlation of angiogenesis soluble markers with either hemoglobin or haptoglobin. CONCLUSION: This is the first study in the literature investigating a link between angiogenesis soluble markers and ribavirin induced anemia in patients with hepatitis C and we could not find any relation. Future research with larger number of patients is needed to find out modifiable factors that will improve the safety of ribavirin therapy.", "entity": "Hepatitis C, Chronic", "aliases": "Chronic Hepatitis C", "definition": "INFLAMMATION of the LIVER in humans that is caused by HEPATITIS C VIRUS lasting six months or more. Chronic hepatitis C can lead to LIVER CIRRHOSIS.\n    ", "id": "MESH:D019698"}
{"mention": "pegylated interferon alpha 2a", "mention_text": "BACKGROUND/AIMS: Recently ribavirin has been found to inhibit angiogenesis and a number of angiogenesis inhibitors such as sunitinib and sorafenib have been found to cause acute hemolysis. We aimed to investigate whether there is a relation between hemoglobin, haptoglobin and angiogenesis soluble markers which are modifiable and can help in developing strategies against anemia. METHODS: Fourteen patients chronically infected with hepatitis C virus were treated by pegylated interferon alpha 2a and ribavirin. Serum hemoglobin, haptoglobin and angiogenesis markers of vascular endothelial growth factor and angiopoetin-2 were investigated before and after therapy. RESULTS: We observed a significant decrease in haptoglobin levels at the end of the treatment period. Hemoglobin levels also decreased but insignificantly by treatment. In contrast with the literature, serum levels of angiogenesis factors did not change significantly by pegylated interferon and ribavirin therapy. We found no correlation of angiogenesis soluble markers with either hemoglobin or haptoglobin. CONCLUSION: This is the first study in the literature investigating a link between angiogenesis soluble markers and ribavirin induced anemia in patients with hepatitis C and we could not find any relation. Future research with larger number of patients is needed to find out modifiable factors that will improve the safety of ribavirin therapy.", "entity": "peginterferon alfa-2a", "aliases": "PEG-IFN alfa-2A alpha-2A PEG-interferon Pegasys peginterferon alfa-2a pegylated interferon polyethylene glycol-interferon", "definition": "", "id": "MESH:C100416"}
{"mention": "pegylated interferon", "mention_text": "BACKGROUND/AIMS: Recently ribavirin has been found to inhibit angiogenesis and a number of angiogenesis inhibitors such as sunitinib and sorafenib have been found to cause acute hemolysis. We aimed to investigate whether there is a relation between hemoglobin, haptoglobin and angiogenesis soluble markers which are modifiable and can help in developing strategies against anemia. METHODS: Fourteen patients chronically infected with hepatitis C virus were treated by pegylated interferon alpha 2a and ribavirin. Serum hemoglobin, haptoglobin and angiogenesis markers of vascular endothelial growth factor and angiopoetin-2 were investigated before and after therapy. RESULTS: We observed a significant decrease in haptoglobin levels at the end of the treatment period. Hemoglobin levels also decreased but insignificantly by treatment. In contrast with the literature, serum levels of angiogenesis factors did not change significantly by pegylated interferon and ribavirin therapy. We found no correlation of angiogenesis soluble markers with either hemoglobin or haptoglobin. CONCLUSION: This is the first study in the literature investigating a link between angiogenesis soluble markers and ribavirin induced anemia in patients with hepatitis C and we could not find any relation. Future research with larger number of patients is needed to find out modifiable factors that will improve the safety of ribavirin therapy.", "entity": "peginterferon alfa-2b", "aliases": "PEG INF alfa-2b alpha-2b PEG-IFNalpha-2b PEG-Intron Pegintron ViraferonPeg peg-proline-INFalpha-2b peg-proline-interferon peginterferon pegylated interferon polyethylene glycol-interferon", "definition": "", "id": "MESH:C417083"}
{"mention": "hepatitis C", "mention_text": "BACKGROUND/AIMS: Recently ribavirin has been found to inhibit angiogenesis and a number of angiogenesis inhibitors such as sunitinib and sorafenib have been found to cause acute hemolysis. We aimed to investigate whether there is a relation between hemoglobin, haptoglobin and angiogenesis soluble markers which are modifiable and can help in developing strategies against anemia. METHODS: Fourteen patients chronically infected with hepatitis C virus were treated by pegylated interferon alpha 2a and ribavirin. Serum hemoglobin, haptoglobin and angiogenesis markers of vascular endothelial growth factor and angiopoetin-2 were investigated before and after therapy. RESULTS: We observed a significant decrease in haptoglobin levels at the end of the treatment period. Hemoglobin levels also decreased but insignificantly by treatment. In contrast with the literature, serum levels of angiogenesis factors did not change significantly by pegylated interferon and ribavirin therapy. We found no correlation of angiogenesis soluble markers with either hemoglobin or haptoglobin. CONCLUSION: This is the first study in the literature investigating a link between angiogenesis soluble markers and ribavirin induced anemia in patients with hepatitis C and we could not find any relation. Future research with larger number of patients is needed to find out modifiable factors that will improve the safety of ribavirin therapy.", "entity": "Hepatitis C, Chronic", "aliases": "Chronic Hepatitis C", "definition": "INFLAMMATION of the LIVER in humans that is caused by HEPATITIS C VIRUS lasting six months or more. Chronic hepatitis C can lead to LIVER CIRRHOSIS.\n    ", "id": "MESH:D019698"}
{"mention": "Cocaine", "mention_text": "Cocaine causes memory and learning impairments in rats: involvement of nuclear factor kappa B and oxidative stress, and prevention by topiramate.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "learning impairments", "mention_text": "Cocaine causes memory and learning impairments in rats: involvement of nuclear factor kappa B and oxidative stress, and prevention by topiramate.", "entity": "Learning Disorders", "aliases": "Academic Disorder Developmental Disorders Adult Learning of Scholastic Skills Disabilities Disability Disturbance Disturbances Development", "definition": "Conditions characterized by a significant discrepancy between an individual's perceived level of intellect and their ability to acquire new language and other cognitive skills. These disorders may result from organic or psychological conditions. Relatively common subtypes include DYSLEXIA, dyscalculia, and dysgraphia.\n    ", "id": "MESH:D007859"}
{"mention": "topiramate", "mention_text": "Cocaine causes memory and learning impairments in rats: involvement of nuclear factor kappa B and oxidative stress, and prevention by topiramate.", "entity": "topiramate", "aliases": "2,3-4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate Epitomax McN 4853 McN-4853 Topamax USL255 topiramate", "definition": "", "id": "MESH:C052342"}
{"mention": "cocaine", "mention_text": "Different mechanisms have been suggested for cocaine toxicity including an increase in oxidative stress but the association between oxidative status in the brain and cocaine induced-behaviour is poorly understood. Nuclear factor kappa B (NFkappaB) is a sensor of oxidative stress and participates in memory formation that could be involved in drug toxicity and addiction mechanisms. Therefore NFkappaB activity, oxidative stress, neuronal nitric oxide synthase (nNOS) activity, spatial learning and memory as well as the effect of topiramate, a previously proposed therapy for cocaine addiction, were evaluated in an experimental model of cocaine administration in rats. NFkappaB activity was decreased in the frontal cortex of cocaine treated rats, as well as GSH concentration and glutathione peroxidase activity in the hippocampus, whereas nNOS activity in the hippocampus was increased. Memory retrieval of experiences acquired prior to cocaine administration was impaired and negatively correlated with NFkappaB activity in the frontal cortex. In contrast, learning of new tasks was enhanced and correlated with the increase of nNOS activity and the decrease of glutathione peroxidase. These results provide evidence for a possible mechanistic role of oxidative and nitrosative stress and NFkappaB in the alterations induced by cocaine. Topiramate prevented all the alterations observed, showing novel neuroprotective properties.", "entity": "Cocaine", "aliases": "Cocaine HCl Hydrochloride", "definition": "An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.\n    ", "id": "MESH:D003042"}
{"mention": "toxicity", "mention_text": "Different mechanisms have been suggested for cocaine toxicity including an increase in oxidative stress but the association between oxidative status in the brain and cocaine induced-behaviour is poorly understood. Nuclear factor kappa B (NFkappaB) is a sensor of oxidative stress and participates in memory formation that could be involved in drug toxicity and addiction mechanisms. Therefore NFkappaB activity, oxidative stress, neuronal nitric oxide synthase (nNOS) activity, spatial learning and memory as well as the effect of topiramate, a previously proposed therapy for cocaine addiction, were evaluated in an experimental model of cocaine administration in rats. NFkappaB activity was decreased in the frontal cortex of cocaine treated rats, as well as GSH concentration and glutathione peroxidase activity in the hippocampus, whereas nNOS activity in the hippocampus was increased. Memory retrieval of experiences acquired prior to cocaine administration was impaired and negatively correlated with NFkappaB activity in the frontal cortex. In contrast, learning of new tasks was enhanced and correlated with the increase of nNOS activity and the decrease of glutathione peroxidase. These results provide evidence for a possible mechanistic role of oxidative and nitrosative stress and NFkappaB in the alterations induced by cocaine. Topiramate prevented all the alterations observed, showing novel neuroprotective properties.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "nitric oxide", "mention_text": "Different mechanisms have been suggested for cocaine toxicity including an increase in oxidative stress but the association between oxidative status in the brain and cocaine induced-behaviour is poorly understood. Nuclear factor kappa B (NFkappaB) is a sensor of oxidative stress and participates in memory formation that could be involved in drug toxicity and addiction mechanisms. Therefore NFkappaB activity, oxidative stress, neuronal nitric oxide synthase (nNOS) activity, spatial learning and memory as well as the effect of topiramate, a previously proposed therapy for cocaine addiction, were evaluated in an experimental model of cocaine administration in rats. NFkappaB activity was decreased in the frontal cortex of cocaine treated rats, as well as GSH concentration and glutathione peroxidase activity in the hippocampus, whereas nNOS activity in the hippocampus was increased. Memory retrieval of experiences acquired prior to cocaine administration was impaired and negatively correlated with NFkappaB activity in the frontal cortex. In contrast, learning of new tasks was enhanced and correlated with the increase of nNOS activity and the decrease of glutathione peroxidase. These results provide evidence for a possible mechanistic role of oxidative and nitrosative stress and NFkappaB in the alterations induced by cocaine. Topiramate prevented all the alterations observed, showing novel neuroprotective properties.", "entity": "Nitric Oxide", "aliases": "Endogenous Nitrate Vasodilator Endothelium-Derived Nitric Oxide Mononitrogen Monoxide Nitrogen Endothelium Derived", "definition": "A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.\n    ", "id": "MESH:D009569"}
{"mention": "topiramate", "mention_text": "Different mechanisms have been suggested for cocaine toxicity including an increase in oxidative stress but the association between oxidative status in the brain and cocaine induced-behaviour is poorly understood. Nuclear factor kappa B (NFkappaB) is a sensor of oxidative stress and participates in memory formation that could be involved in drug toxicity and addiction mechanisms. Therefore NFkappaB activity, oxidative stress, neuronal nitric oxide synthase (nNOS) activity, spatial learning and memory as well as the effect of topiramate, a previously proposed therapy for cocaine addiction, were evaluated in an experimental model of cocaine administration in rats. NFkappaB activity was decreased in the frontal cortex of cocaine treated rats, as well as GSH concentration and glutathione peroxidase activity in the hippocampus, whereas nNOS activity in the hippocampus was increased. Memory retrieval of experiences acquired prior to cocaine administration was impaired and negatively correlated with NFkappaB activity in the frontal cortex. In contrast, learning of new tasks was enhanced and correlated with the increase of nNOS activity and the decrease of glutathione peroxidase. These results provide evidence for a possible mechanistic role of oxidative and nitrosative stress and NFkappaB in the alterations induced by cocaine. Topiramate prevented all the alterations observed, showing novel neuroprotective properties.", "entity": "topiramate", "aliases": "2,3-4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate Epitomax McN 4853 McN-4853 Topamax USL255 topiramate", "definition": "", "id": "MESH:C052342"}
{"mention": "cocaine addiction", "mention_text": "Different mechanisms have been suggested for cocaine toxicity including an increase in oxidative stress but the association between oxidative status in the brain and cocaine induced-behaviour is poorly understood. Nuclear factor kappa B (NFkappaB) is a sensor of oxidative stress and participates in memory formation that could be involved in drug toxicity and addiction mechanisms. Therefore NFkappaB activity, oxidative stress, neuronal nitric oxide synthase (nNOS) activity, spatial learning and memory as well as the effect of topiramate, a previously proposed therapy for cocaine addiction, were evaluated in an experimental model of cocaine administration in rats. NFkappaB activity was decreased in the frontal cortex of cocaine treated rats, as well as GSH concentration and glutathione peroxidase activity in the hippocampus, whereas nNOS activity in the hippocampus was increased. Memory retrieval of experiences acquired prior to cocaine administration was impaired and negatively correlated with NFkappaB activity in the frontal cortex. In contrast, learning of new tasks was enhanced and correlated with the increase of nNOS activity and the decrease of glutathione peroxidase. These results provide evidence for a possible mechanistic role of oxidative and nitrosative stress and NFkappaB in the alterations induced by cocaine. Topiramate prevented all the alterations observed, showing novel neuroprotective properties.", "entity": "Cocaine-Related Disorders", "aliases": "Abuse Cocaine Addiction Dependence Related Disorders Cocaine-Related Disorder Dependences", "definition": "Disorders related or resulting from use of cocaine.\n    ", "id": "MESH:D019970"}
{"mention": "GSH", "mention_text": "Different mechanisms have been suggested for cocaine toxicity including an increase in oxidative stress but the association between oxidative status in the brain and cocaine induced-behaviour is poorly understood. Nuclear factor kappa B (NFkappaB) is a sensor of oxidative stress and participates in memory formation that could be involved in drug toxicity and addiction mechanisms. Therefore NFkappaB activity, oxidative stress, neuronal nitric oxide synthase (nNOS) activity, spatial learning and memory as well as the effect of topiramate, a previously proposed therapy for cocaine addiction, were evaluated in an experimental model of cocaine administration in rats. NFkappaB activity was decreased in the frontal cortex of cocaine treated rats, as well as GSH concentration and glutathione peroxidase activity in the hippocampus, whereas nNOS activity in the hippocampus was increased. Memory retrieval of experiences acquired prior to cocaine administration was impaired and negatively correlated with NFkappaB activity in the frontal cortex. In contrast, learning of new tasks was enhanced and correlated with the increase of nNOS activity and the decrease of glutathione peroxidase. These results provide evidence for a possible mechanistic role of oxidative and nitrosative stress and NFkappaB in the alterations induced by cocaine. Topiramate prevented all the alterations observed, showing novel neuroprotective properties.", "entity": "Glutathione", "aliases": "Glutathione Reduced gamma L Glu L Cys Gly Glutamyl Cysteinylglycine gamma-L-Glu-L-Cys-Gly gamma-L-Glutamyl-L-Cysteinylglycine", "definition": "A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.\n    ", "id": "MESH:D005978"}
{"mention": "glutathione", "mention_text": "Different mechanisms have been suggested for cocaine toxicity including an increase in oxidative stress but the association between oxidative status in the brain and cocaine induced-behaviour is poorly understood. Nuclear factor kappa B (NFkappaB) is a sensor of oxidative stress and participates in memory formation that could be involved in drug toxicity and addiction mechanisms. Therefore NFkappaB activity, oxidative stress, neuronal nitric oxide synthase (nNOS) activity, spatial learning and memory as well as the effect of topiramate, a previously proposed therapy for cocaine addiction, were evaluated in an experimental model of cocaine administration in rats. NFkappaB activity was decreased in the frontal cortex of cocaine treated rats, as well as GSH concentration and glutathione peroxidase activity in the hippocampus, whereas nNOS activity in the hippocampus was increased. Memory retrieval of experiences acquired prior to cocaine administration was impaired and negatively correlated with NFkappaB activity in the frontal cortex. In contrast, learning of new tasks was enhanced and correlated with the increase of nNOS activity and the decrease of glutathione peroxidase. These results provide evidence for a possible mechanistic role of oxidative and nitrosative stress and NFkappaB in the alterations induced by cocaine. Topiramate prevented all the alterations observed, showing novel neuroprotective properties.", "entity": "Glutathione", "aliases": "Glutathione Reduced gamma L Glu L Cys Gly Glutamyl Cysteinylglycine gamma-L-Glu-L-Cys-Gly gamma-L-Glutamyl-L-Cysteinylglycine", "definition": "A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.\n    ", "id": "MESH:D005978"}
{"mention": "Topiramate", "mention_text": "Different mechanisms have been suggested for cocaine toxicity including an increase in oxidative stress but the association between oxidative status in the brain and cocaine induced-behaviour is poorly understood. Nuclear factor kappa B (NFkappaB) is a sensor of oxidative stress and participates in memory formation that could be involved in drug toxicity and addiction mechanisms. Therefore NFkappaB activity, oxidative stress, neuronal nitric oxide synthase (nNOS) activity, spatial learning and memory as well as the effect of topiramate, a previously proposed therapy for cocaine addiction, were evaluated in an experimental model of cocaine administration in rats. NFkappaB activity was decreased in the frontal cortex of cocaine treated rats, as well as GSH concentration and glutathione peroxidase activity in the hippocampus, whereas nNOS activity in the hippocampus was increased. Memory retrieval of experiences acquired prior to cocaine administration was impaired and negatively correlated with NFkappaB activity in the frontal cortex. In contrast, learning of new tasks was enhanced and correlated with the increase of nNOS activity and the decrease of glutathione peroxidase. These results provide evidence for a possible mechanistic role of oxidative and nitrosative stress and NFkappaB in the alterations induced by cocaine. Topiramate prevented all the alterations observed, showing novel neuroprotective properties.", "entity": "topiramate", "aliases": "2,3-4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate Epitomax McN 4853 McN-4853 Topamax USL255 topiramate", "definition": "", "id": "MESH:C052342"}
{"mention": "PG-9", "mention_text": "Antinociceptive and antiamnesic properties of the presynaptic cholinergic amplifier PG-9.", "entity": "N-methyltropan-3-yl 2-(4-bromophenyl)propionate", "aliases": "N-methyltropan-3-yl 2-(4-bromophenyl)propionate (+)-stereoisomer (+-)-stereoisomer NMT-3-BPP PG 9 cpd PG-9", "definition": "", "id": "MESH:C087567"}
{"mention": "3 alpha-tropyl 2-(p-bromophenyl)propionate", "mention_text": "The antinociceptive effect of 3 alpha-tropyl 2-(p-bromophenyl)propionate [(+/-)-PG-9] (10-40 mg kg-1 s.c.; 30-60 mg kg-1 p.o.; 10-30 mg kg-1 i.v.; 10-30 micrograms/mouse i.c.v.) was examined in mice, rats and guinea pigs by use of the hot-plate, abdominal-constriction, tail-flick and paw-pressure tests. (+/-)-PG-9 antinociception peaked 15 min after injection and then slowly diminished. The antinociception produced by (+/-)-PG-9 was prevented by the unselective muscarinic antagonist atropine, the M1-selective antagonists pirenzepine and dicyclomine and the acetylcholine depletor hemicholinium-3, but not by the opioid antagonist naloxone, the gamma-aminobutyric acidB antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid, the H3 agonist R-(alpha)-methylhistamine, the D2 antagonist quinpirole, the 5-hydroxytryptamine4 antagonist 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester hydrochloride, the 5-hydroxytryptamin1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide and the polyamines depletor reserpine. Based on these data, it can be postulated that (+/-)-PG-9 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. (+/-)-PG-9 (10-40 mg kg-1 i.p.) was able to prevent amnesia induced by scopolamine (1 mg kg-1 i.p.) and dicyclomine (2 mg kg-1 i.p.) in the mouse passive-avoidance test. Affinity profiles of (+/-)-PG-9 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M1, guinea pig atrium for M2, guinea pig ileum for M3 and immature guinea pig uterus for putative M4), have shown an M4/M1 selectivity ratio of 10.2 that might be responsible for the antinociception and the anti-amnesic effect induced by (+/-)-PG-9 through an increase in acetylcholine extracellular levels. In the antinociceptive and antiamnesic dose range, (+/-)-PG-9 did not impair mouse performance evaluated by the rota-rod test and Animex apparatus.", "entity": "N-methyltropan-3-yl 2-(4-bromophenyl)propionate", "aliases": "N-methyltropan-3-yl 2-(4-bromophenyl)propionate (+)-stereoisomer (+-)-stereoisomer NMT-3-BPP PG 9 cpd PG-9", "definition": "", "id": "MESH:C087567"}
{"mention": "PG-9", "mention_text": "The antinociceptive effect of 3 alpha-tropyl 2-(p-bromophenyl)propionate [(+/-)-PG-9] (10-40 mg kg-1 s.c.; 30-60 mg kg-1 p.o.; 10-30 mg kg-1 i.v.; 10-30 micrograms/mouse i.c.v.) was examined in mice, rats and guinea pigs by use of the hot-plate, abdominal-constriction, tail-flick and paw-pressure tests. (+/-)-PG-9 antinociception peaked 15 min after injection and then slowly diminished. The antinociception produced by (+/-)-PG-9 was prevented by the unselective muscarinic antagonist atropine, the M1-selective antagonists pirenzepine and dicyclomine and the acetylcholine depletor hemicholinium-3, but not by the opioid antagonist naloxone, the gamma-aminobutyric acidB antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid, the H3 agonist R-(alpha)-methylhistamine, the D2 antagonist quinpirole, the 5-hydroxytryptamine4 antagonist 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester hydrochloride, the 5-hydroxytryptamin1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide and the polyamines depletor reserpine. Based on these data, it can be postulated that (+/-)-PG-9 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. (+/-)-PG-9 (10-40 mg kg-1 i.p.) was able to prevent amnesia induced by scopolamine (1 mg kg-1 i.p.) and dicyclomine (2 mg kg-1 i.p.) in the mouse passive-avoidance test. Affinity profiles of (+/-)-PG-9 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M1, guinea pig atrium for M2, guinea pig ileum for M3 and immature guinea pig uterus for putative M4), have shown an M4/M1 selectivity ratio of 10.2 that might be responsible for the antinociception and the anti-amnesic effect induced by (+/-)-PG-9 through an increase in acetylcholine extracellular levels. In the antinociceptive and antiamnesic dose range, (+/-)-PG-9 did not impair mouse performance evaluated by the rota-rod test and Animex apparatus.", "entity": "N-methyltropan-3-yl 2-(4-bromophenyl)propionate", "aliases": "N-methyltropan-3-yl 2-(4-bromophenyl)propionate (+)-stereoisomer (+-)-stereoisomer NMT-3-BPP PG 9 cpd PG-9", "definition": "", "id": "MESH:C087567"}
{"mention": "atropine", "mention_text": "The antinociceptive effect of 3 alpha-tropyl 2-(p-bromophenyl)propionate [(+/-)-PG-9] (10-40 mg kg-1 s.c.; 30-60 mg kg-1 p.o.; 10-30 mg kg-1 i.v.; 10-30 micrograms/mouse i.c.v.) was examined in mice, rats and guinea pigs by use of the hot-plate, abdominal-constriction, tail-flick and paw-pressure tests. (+/-)-PG-9 antinociception peaked 15 min after injection and then slowly diminished. The antinociception produced by (+/-)-PG-9 was prevented by the unselective muscarinic antagonist atropine, the M1-selective antagonists pirenzepine and dicyclomine and the acetylcholine depletor hemicholinium-3, but not by the opioid antagonist naloxone, the gamma-aminobutyric acidB antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid, the H3 agonist R-(alpha)-methylhistamine, the D2 antagonist quinpirole, the 5-hydroxytryptamine4 antagonist 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester hydrochloride, the 5-hydroxytryptamin1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide and the polyamines depletor reserpine. Based on these data, it can be postulated that (+/-)-PG-9 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. (+/-)-PG-9 (10-40 mg kg-1 i.p.) was able to prevent amnesia induced by scopolamine (1 mg kg-1 i.p.) and dicyclomine (2 mg kg-1 i.p.) in the mouse passive-avoidance test. Affinity profiles of (+/-)-PG-9 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M1, guinea pig atrium for M2, guinea pig ileum for M3 and immature guinea pig uterus for putative M4), have shown an M4/M1 selectivity ratio of 10.2 that might be responsible for the antinociception and the anti-amnesic effect induced by (+/-)-PG-9 through an increase in acetylcholine extracellular levels. In the antinociceptive and antiamnesic dose range, (+/-)-PG-9 did not impair mouse performance evaluated by the rota-rod test and Animex apparatus.", "entity": "Atropine", "aliases": "Anhydrous Atropine Sulfate AtroPen Atropin Augenöl Chauvin Brand Winzer Atropinol of Survival Technology", "definition": "An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.\n    ", "id": "MESH:D001285"}
{"mention": "pirenzepine", "mention_text": "The antinociceptive effect of 3 alpha-tropyl 2-(p-bromophenyl)propionate [(+/-)-PG-9] (10-40 mg kg-1 s.c.; 30-60 mg kg-1 p.o.; 10-30 mg kg-1 i.v.; 10-30 micrograms/mouse i.c.v.) was examined in mice, rats and guinea pigs by use of the hot-plate, abdominal-constriction, tail-flick and paw-pressure tests. (+/-)-PG-9 antinociception peaked 15 min after injection and then slowly diminished. The antinociception produced by (+/-)-PG-9 was prevented by the unselective muscarinic antagonist atropine, the M1-selective antagonists pirenzepine and dicyclomine and the acetylcholine depletor hemicholinium-3, but not by the opioid antagonist naloxone, the gamma-aminobutyric acidB antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid, the H3 agonist R-(alpha)-methylhistamine, the D2 antagonist quinpirole, the 5-hydroxytryptamine4 antagonist 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester hydrochloride, the 5-hydroxytryptamin1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide and the polyamines depletor reserpine. Based on these data, it can be postulated that (+/-)-PG-9 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. (+/-)-PG-9 (10-40 mg kg-1 i.p.) was able to prevent amnesia induced by scopolamine (1 mg kg-1 i.p.) and dicyclomine (2 mg kg-1 i.p.) in the mouse passive-avoidance test. Affinity profiles of (+/-)-PG-9 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M1, guinea pig atrium for M2, guinea pig ileum for M3 and immature guinea pig uterus for putative M4), have shown an M4/M1 selectivity ratio of 10.2 that might be responsible for the antinociception and the anti-amnesic effect induced by (+/-)-PG-9 through an increase in acetylcholine extracellular levels. In the antinociceptive and antiamnesic dose range, (+/-)-PG-9 did not impair mouse performance evaluated by the rota-rod test and Animex apparatus.", "entity": "Pirenzepine", "aliases": "Azupharma Brand of Pirenzepine Dihydrochloride Boehringer Ingelheim Dolorgiet Gastrotsepin Gastrozepin L-S 519 LS LS-519 LS519 Piren basan Piren-basan Pirenzepin ratiopharm Pirenzepin-ratiopharm Pyrenzepine Sagitta Ulcoprotect Ulgescum ct-Arzneimittel pirenzepin von ct", "definition": "An antimuscarinic agent that inhibits gastric secretion at lower doses than are required to affect gastrointestinal motility, salivary, central nervous system, cardiovascular, ocular, and urinary function. It promotes the healing of duodenal ulcers and due to its cytoprotective action is beneficial in the prevention of duodenal ulcer recurrence. It also potentiates the effect of other antiulcer agents such as CIMETIDINE and RANITIDINE. It is generally well tolerated by patients.\n    ", "id": "MESH:D010890"}
{"mention": "dicyclomine", "mention_text": "The antinociceptive effect of 3 alpha-tropyl 2-(p-bromophenyl)propionate [(+/-)-PG-9] (10-40 mg kg-1 s.c.; 30-60 mg kg-1 p.o.; 10-30 mg kg-1 i.v.; 10-30 micrograms/mouse i.c.v.) was examined in mice, rats and guinea pigs by use of the hot-plate, abdominal-constriction, tail-flick and paw-pressure tests. (+/-)-PG-9 antinociception peaked 15 min after injection and then slowly diminished. The antinociception produced by (+/-)-PG-9 was prevented by the unselective muscarinic antagonist atropine, the M1-selective antagonists pirenzepine and dicyclomine and the acetylcholine depletor hemicholinium-3, but not by the opioid antagonist naloxone, the gamma-aminobutyric acidB antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid, the H3 agonist R-(alpha)-methylhistamine, the D2 antagonist quinpirole, the 5-hydroxytryptamine4 antagonist 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester hydrochloride, the 5-hydroxytryptamin1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide and the polyamines depletor reserpine. Based on these data, it can be postulated that (+/-)-PG-9 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. (+/-)-PG-9 (10-40 mg kg-1 i.p.) was able to prevent amnesia induced by scopolamine (1 mg kg-1 i.p.) and dicyclomine (2 mg kg-1 i.p.) in the mouse passive-avoidance test. Affinity profiles of (+/-)-PG-9 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M1, guinea pig atrium for M2, guinea pig ileum for M3 and immature guinea pig uterus for putative M4), have shown an M4/M1 selectivity ratio of 10.2 that might be responsible for the antinociception and the anti-amnesic effect induced by (+/-)-PG-9 through an increase in acetylcholine extracellular levels. In the antinociceptive and antiamnesic dose range, (+/-)-PG-9 did not impair mouse performance evaluated by the rota-rod test and Animex apparatus.", "entity": "Dicyclomine", "aliases": "Atlantis Brand of Dicyclomine Hydrochloride Aventis Behring Bentyl Bentylol Di Cyclonex Spaz Di-Cyclonex Di-Spaz Dibent Diclomin Dicycloverin Florizel Hauck Hoechst Lomine Merbentyl OR Tyl OR-Tyl Ortega Pasadena Riva Sigma Spascol Vangard Vortech", "definition": "A muscarinic antagonist used as an antispasmodic and in urinary incontinence. It has little effect on glandular secretion or the cardiovascular system. It does have some local anesthetic properties and is used in gastrointestinal, biliary, and urinary tract spasms.\n    ", "id": "MESH:D004025"}
{"mention": "acetylcholine", "mention_text": "The antinociceptive effect of 3 alpha-tropyl 2-(p-bromophenyl)propionate [(+/-)-PG-9] (10-40 mg kg-1 s.c.; 30-60 mg kg-1 p.o.; 10-30 mg kg-1 i.v.; 10-30 micrograms/mouse i.c.v.) was examined in mice, rats and guinea pigs by use of the hot-plate, abdominal-constriction, tail-flick and paw-pressure tests. (+/-)-PG-9 antinociception peaked 15 min after injection and then slowly diminished. The antinociception produced by (+/-)-PG-9 was prevented by the unselective muscarinic antagonist atropine, the M1-selective antagonists pirenzepine and dicyclomine and the acetylcholine depletor hemicholinium-3, but not by the opioid antagonist naloxone, the gamma-aminobutyric acidB antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid, the H3 agonist R-(alpha)-methylhistamine, the D2 antagonist quinpirole, the 5-hydroxytryptamine4 antagonist 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester hydrochloride, the 5-hydroxytryptamin1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide and the polyamines depletor reserpine. Based on these data, it can be postulated that (+/-)-PG-9 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. (+/-)-PG-9 (10-40 mg kg-1 i.p.) was able to prevent amnesia induced by scopolamine (1 mg kg-1 i.p.) and dicyclomine (2 mg kg-1 i.p.) in the mouse passive-avoidance test. Affinity profiles of (+/-)-PG-9 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M1, guinea pig atrium for M2, guinea pig ileum for M3 and immature guinea pig uterus for putative M4), have shown an M4/M1 selectivity ratio of 10.2 that might be responsible for the antinociception and the anti-amnesic effect induced by (+/-)-PG-9 through an increase in acetylcholine extracellular levels. In the antinociceptive and antiamnesic dose range, (+/-)-PG-9 did not impair mouse performance evaluated by the rota-rod test and Animex apparatus.", "entity": "Acetylcholine", "aliases": "2-(Acetyloxy)-N,N,N-trimethylethanaminium Acetilcolina Cusi Acetylcholine Bromide Chloride Fluoride Hydroxide Iodide L Tartrate L-Tartrate Perchlorate Picrate (1:1) Sulfate Alcon Brand of Bournonville Bromoacetylcholine Chloroacetylcholine Ciba Vision Iolab Miochol", "definition": "A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.\n    ", "id": "MESH:D000109"}
{"mention": "hemicholinium-3", "mention_text": "The antinociceptive effect of 3 alpha-tropyl 2-(p-bromophenyl)propionate [(+/-)-PG-9] (10-40 mg kg-1 s.c.; 30-60 mg kg-1 p.o.; 10-30 mg kg-1 i.v.; 10-30 micrograms/mouse i.c.v.) was examined in mice, rats and guinea pigs by use of the hot-plate, abdominal-constriction, tail-flick and paw-pressure tests. (+/-)-PG-9 antinociception peaked 15 min after injection and then slowly diminished. The antinociception produced by (+/-)-PG-9 was prevented by the unselective muscarinic antagonist atropine, the M1-selective antagonists pirenzepine and dicyclomine and the acetylcholine depletor hemicholinium-3, but not by the opioid antagonist naloxone, the gamma-aminobutyric acidB antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid, the H3 agonist R-(alpha)-methylhistamine, the D2 antagonist quinpirole, the 5-hydroxytryptamine4 antagonist 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester hydrochloride, the 5-hydroxytryptamin1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide and the polyamines depletor reserpine. Based on these data, it can be postulated that (+/-)-PG-9 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. (+/-)-PG-9 (10-40 mg kg-1 i.p.) was able to prevent amnesia induced by scopolamine (1 mg kg-1 i.p.) and dicyclomine (2 mg kg-1 i.p.) in the mouse passive-avoidance test. Affinity profiles of (+/-)-PG-9 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M1, guinea pig atrium for M2, guinea pig ileum for M3 and immature guinea pig uterus for putative M4), have shown an M4/M1 selectivity ratio of 10.2 that might be responsible for the antinociception and the anti-amnesic effect induced by (+/-)-PG-9 through an increase in acetylcholine extracellular levels. In the antinociceptive and antiamnesic dose range, (+/-)-PG-9 did not impair mouse performance evaluated by the rota-rod test and Animex apparatus.", "entity": "Hemicholinium 3", "aliases": "Hemicholinium 3", "definition": "A potent inhibitor of the high affinity uptake system for CHOLINE. It has less effect on the low affinity uptake system. Since choline is one of the components of ACETYLCHOLINE, treatment with hemicholinium can deplete acetylcholine from cholinergic terminals. Hemicholinium 3 is commonly used as a research tool in animal and in vitro experiments.\n    ", "id": "MESH:D006426"}
{"mention": "naloxone", "mention_text": "The antinociceptive effect of 3 alpha-tropyl 2-(p-bromophenyl)propionate [(+/-)-PG-9] (10-40 mg kg-1 s.c.; 30-60 mg kg-1 p.o.; 10-30 mg kg-1 i.v.; 10-30 micrograms/mouse i.c.v.) was examined in mice, rats and guinea pigs by use of the hot-plate, abdominal-constriction, tail-flick and paw-pressure tests. (+/-)-PG-9 antinociception peaked 15 min after injection and then slowly diminished. The antinociception produced by (+/-)-PG-9 was prevented by the unselective muscarinic antagonist atropine, the M1-selective antagonists pirenzepine and dicyclomine and the acetylcholine depletor hemicholinium-3, but not by the opioid antagonist naloxone, the gamma-aminobutyric acidB antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid, the H3 agonist R-(alpha)-methylhistamine, the D2 antagonist quinpirole, the 5-hydroxytryptamine4 antagonist 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester hydrochloride, the 5-hydroxytryptamin1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide and the polyamines depletor reserpine. Based on these data, it can be postulated that (+/-)-PG-9 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. (+/-)-PG-9 (10-40 mg kg-1 i.p.) was able to prevent amnesia induced by scopolamine (1 mg kg-1 i.p.) and dicyclomine (2 mg kg-1 i.p.) in the mouse passive-avoidance test. Affinity profiles of (+/-)-PG-9 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M1, guinea pig atrium for M2, guinea pig ileum for M3 and immature guinea pig uterus for putative M4), have shown an M4/M1 selectivity ratio of 10.2 that might be responsible for the antinociception and the anti-amnesic effect induced by (+/-)-PG-9 through an increase in acetylcholine extracellular levels. In the antinociceptive and antiamnesic dose range, (+/-)-PG-9 did not impair mouse performance evaluated by the rota-rod test and Animex apparatus.", "entity": "Naloxone", "aliases": "Abello Brand of Naloxone Hydrochloride Boots Bristol Myers Squibb Bristol-Myers Curamed Naloxon Dihydride Endo Hydrobromide Lamepro MRZ 2593 Br 2593-Br 2593Br MRZ-2593 MRZ2593 Nalone ratiopharm Naloxon-ratiopharm (5 beta,9 alpha,13 alpha,14 alpha)-Isomer Naloxonratiopharm Narcan Narcanti SERB United Drug", "definition": "A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.\n    ", "id": "MESH:D009270"}
{"mention": "gamma-aminobutyric acidB", "mention_text": "The antinociceptive effect of 3 alpha-tropyl 2-(p-bromophenyl)propionate [(+/-)-PG-9] (10-40 mg kg-1 s.c.; 30-60 mg kg-1 p.o.; 10-30 mg kg-1 i.v.; 10-30 micrograms/mouse i.c.v.) was examined in mice, rats and guinea pigs by use of the hot-plate, abdominal-constriction, tail-flick and paw-pressure tests. (+/-)-PG-9 antinociception peaked 15 min after injection and then slowly diminished. The antinociception produced by (+/-)-PG-9 was prevented by the unselective muscarinic antagonist atropine, the M1-selective antagonists pirenzepine and dicyclomine and the acetylcholine depletor hemicholinium-3, but not by the opioid antagonist naloxone, the gamma-aminobutyric acidB antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid, the H3 agonist R-(alpha)-methylhistamine, the D2 antagonist quinpirole, the 5-hydroxytryptamine4 antagonist 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester hydrochloride, the 5-hydroxytryptamin1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide and the polyamines depletor reserpine. Based on these data, it can be postulated that (+/-)-PG-9 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. (+/-)-PG-9 (10-40 mg kg-1 i.p.) was able to prevent amnesia induced by scopolamine (1 mg kg-1 i.p.) and dicyclomine (2 mg kg-1 i.p.) in the mouse passive-avoidance test. Affinity profiles of (+/-)-PG-9 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M1, guinea pig atrium for M2, guinea pig ileum for M3 and immature guinea pig uterus for putative M4), have shown an M4/M1 selectivity ratio of 10.2 that might be responsible for the antinociception and the anti-amnesic effect induced by (+/-)-PG-9 through an increase in acetylcholine extracellular levels. In the antinociceptive and antiamnesic dose range, (+/-)-PG-9 did not impair mouse performance evaluated by the rota-rod test and Animex apparatus.", "entity": "gamma-Aminobutyric Acid", "aliases": "4 Aminobutanoic Acid Aminobutyric 4-Aminobutanoic 4-Aminobutyric Hydrochloride gamma-Aminobutyric Aminalon Aminalone GABA Lithium Gammalon gamma Monolithium Salt Monosodium Calcium (2:1) Zinc", "definition": "The most common inhibitory neurotransmitter in the central nervous system.\n    ", "id": "MESH:D005680"}
{"mention": "3-aminopropyl-diethoxy-methyl-phosphinic acid", "mention_text": "The antinociceptive effect of 3 alpha-tropyl 2-(p-bromophenyl)propionate [(+/-)-PG-9] (10-40 mg kg-1 s.c.; 30-60 mg kg-1 p.o.; 10-30 mg kg-1 i.v.; 10-30 micrograms/mouse i.c.v.) was examined in mice, rats and guinea pigs by use of the hot-plate, abdominal-constriction, tail-flick and paw-pressure tests. (+/-)-PG-9 antinociception peaked 15 min after injection and then slowly diminished. The antinociception produced by (+/-)-PG-9 was prevented by the unselective muscarinic antagonist atropine, the M1-selective antagonists pirenzepine and dicyclomine and the acetylcholine depletor hemicholinium-3, but not by the opioid antagonist naloxone, the gamma-aminobutyric acidB antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid, the H3 agonist R-(alpha)-methylhistamine, the D2 antagonist quinpirole, the 5-hydroxytryptamine4 antagonist 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester hydrochloride, the 5-hydroxytryptamin1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide and the polyamines depletor reserpine. Based on these data, it can be postulated that (+/-)-PG-9 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. (+/-)-PG-9 (10-40 mg kg-1 i.p.) was able to prevent amnesia induced by scopolamine (1 mg kg-1 i.p.) and dicyclomine (2 mg kg-1 i.p.) in the mouse passive-avoidance test. Affinity profiles of (+/-)-PG-9 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M1, guinea pig atrium for M2, guinea pig ileum for M3 and immature guinea pig uterus for putative M4), have shown an M4/M1 selectivity ratio of 10.2 that might be responsible for the antinociception and the anti-amnesic effect induced by (+/-)-PG-9 through an increase in acetylcholine extracellular levels. In the antinociceptive and antiamnesic dose range, (+/-)-PG-9 did not impair mouse performance evaluated by the rota-rod test and Animex apparatus.", "entity": "CGP 35348", "aliases": "CGP 35348 CGP-35348 P-(3-aminopropyl)-P-diethoxymethylphosphinic acid", "definition": "", "id": "MESH:C066430"}
{"mention": "R-(alpha)-methylhistamine", "mention_text": "The antinociceptive effect of 3 alpha-tropyl 2-(p-bromophenyl)propionate [(+/-)-PG-9] (10-40 mg kg-1 s.c.; 30-60 mg kg-1 p.o.; 10-30 mg kg-1 i.v.; 10-30 micrograms/mouse i.c.v.) was examined in mice, rats and guinea pigs by use of the hot-plate, abdominal-constriction, tail-flick and paw-pressure tests. (+/-)-PG-9 antinociception peaked 15 min after injection and then slowly diminished. The antinociception produced by (+/-)-PG-9 was prevented by the unselective muscarinic antagonist atropine, the M1-selective antagonists pirenzepine and dicyclomine and the acetylcholine depletor hemicholinium-3, but not by the opioid antagonist naloxone, the gamma-aminobutyric acidB antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid, the H3 agonist R-(alpha)-methylhistamine, the D2 antagonist quinpirole, the 5-hydroxytryptamine4 antagonist 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester hydrochloride, the 5-hydroxytryptamin1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide and the polyamines depletor reserpine. Based on these data, it can be postulated that (+/-)-PG-9 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. (+/-)-PG-9 (10-40 mg kg-1 i.p.) was able to prevent amnesia induced by scopolamine (1 mg kg-1 i.p.) and dicyclomine (2 mg kg-1 i.p.) in the mouse passive-avoidance test. Affinity profiles of (+/-)-PG-9 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M1, guinea pig atrium for M2, guinea pig ileum for M3 and immature guinea pig uterus for putative M4), have shown an M4/M1 selectivity ratio of 10.2 that might be responsible for the antinociception and the anti-amnesic effect induced by (+/-)-PG-9 through an increase in acetylcholine extracellular levels. In the antinociceptive and antiamnesic dose range, (+/-)-PG-9 did not impair mouse performance evaluated by the rota-rod test and Animex apparatus.", "entity": "alpha-methylhistamine", "aliases": "alpha-methylhistamine dihydrochloride (R)-isomer (S)-isomer", "definition": "", "id": "MESH:C069357"}
{"mention": "quinpirole", "mention_text": "The antinociceptive effect of 3 alpha-tropyl 2-(p-bromophenyl)propionate [(+/-)-PG-9] (10-40 mg kg-1 s.c.; 30-60 mg kg-1 p.o.; 10-30 mg kg-1 i.v.; 10-30 micrograms/mouse i.c.v.) was examined in mice, rats and guinea pigs by use of the hot-plate, abdominal-constriction, tail-flick and paw-pressure tests. (+/-)-PG-9 antinociception peaked 15 min after injection and then slowly diminished. The antinociception produced by (+/-)-PG-9 was prevented by the unselective muscarinic antagonist atropine, the M1-selective antagonists pirenzepine and dicyclomine and the acetylcholine depletor hemicholinium-3, but not by the opioid antagonist naloxone, the gamma-aminobutyric acidB antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid, the H3 agonist R-(alpha)-methylhistamine, the D2 antagonist quinpirole, the 5-hydroxytryptamine4 antagonist 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester hydrochloride, the 5-hydroxytryptamin1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide and the polyamines depletor reserpine. Based on these data, it can be postulated that (+/-)-PG-9 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. (+/-)-PG-9 (10-40 mg kg-1 i.p.) was able to prevent amnesia induced by scopolamine (1 mg kg-1 i.p.) and dicyclomine (2 mg kg-1 i.p.) in the mouse passive-avoidance test. Affinity profiles of (+/-)-PG-9 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M1, guinea pig atrium for M2, guinea pig ileum for M3 and immature guinea pig uterus for putative M4), have shown an M4/M1 selectivity ratio of 10.2 that might be responsible for the antinociception and the anti-amnesic effect induced by (+/-)-PG-9 through an increase in acetylcholine extracellular levels. In the antinociceptive and antiamnesic dose range, (+/-)-PG-9 did not impair mouse performance evaluated by the rota-rod test and Animex apparatus.", "entity": "Quinpirole", "aliases": "Quinpirole Hydrochloride Monohydrochloride", "definition": "A dopamine D2/D3 receptor agonist.\n    ", "id": "MESH:D019257"}
{"mention": "5-hydroxytryptamine4", "mention_text": "The antinociceptive effect of 3 alpha-tropyl 2-(p-bromophenyl)propionate [(+/-)-PG-9] (10-40 mg kg-1 s.c.; 30-60 mg kg-1 p.o.; 10-30 mg kg-1 i.v.; 10-30 micrograms/mouse i.c.v.) was examined in mice, rats and guinea pigs by use of the hot-plate, abdominal-constriction, tail-flick and paw-pressure tests. (+/-)-PG-9 antinociception peaked 15 min after injection and then slowly diminished. The antinociception produced by (+/-)-PG-9 was prevented by the unselective muscarinic antagonist atropine, the M1-selective antagonists pirenzepine and dicyclomine and the acetylcholine depletor hemicholinium-3, but not by the opioid antagonist naloxone, the gamma-aminobutyric acidB antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid, the H3 agonist R-(alpha)-methylhistamine, the D2 antagonist quinpirole, the 5-hydroxytryptamine4 antagonist 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester hydrochloride, the 5-hydroxytryptamin1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide and the polyamines depletor reserpine. Based on these data, it can be postulated that (+/-)-PG-9 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. (+/-)-PG-9 (10-40 mg kg-1 i.p.) was able to prevent amnesia induced by scopolamine (1 mg kg-1 i.p.) and dicyclomine (2 mg kg-1 i.p.) in the mouse passive-avoidance test. Affinity profiles of (+/-)-PG-9 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M1, guinea pig atrium for M2, guinea pig ileum for M3 and immature guinea pig uterus for putative M4), have shown an M4/M1 selectivity ratio of 10.2 that might be responsible for the antinociception and the anti-amnesic effect induced by (+/-)-PG-9 through an increase in acetylcholine extracellular levels. In the antinociceptive and antiamnesic dose range, (+/-)-PG-9 did not impair mouse performance evaluated by the rota-rod test and Animex apparatus.", "entity": "Serotonin", "aliases": "3-(2-Aminoethyl)-1H-indol-5-ol 5 Hydroxytryptamine 5-HT 5-Hydroxytryptamine Enteramine Hippophaine Serotonin", "definition": "A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.\n    ", "id": "MESH:D012701"}
{"mention": "2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester", "mention_text": "The antinociceptive effect of 3 alpha-tropyl 2-(p-bromophenyl)propionate [(+/-)-PG-9] (10-40 mg kg-1 s.c.; 30-60 mg kg-1 p.o.; 10-30 mg kg-1 i.v.; 10-30 micrograms/mouse i.c.v.) was examined in mice, rats and guinea pigs by use of the hot-plate, abdominal-constriction, tail-flick and paw-pressure tests. (+/-)-PG-9 antinociception peaked 15 min after injection and then slowly diminished. The antinociception produced by (+/-)-PG-9 was prevented by the unselective muscarinic antagonist atropine, the M1-selective antagonists pirenzepine and dicyclomine and the acetylcholine depletor hemicholinium-3, but not by the opioid antagonist naloxone, the gamma-aminobutyric acidB antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid, the H3 agonist R-(alpha)-methylhistamine, the D2 antagonist quinpirole, the 5-hydroxytryptamine4 antagonist 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester hydrochloride, the 5-hydroxytryptamin1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide and the polyamines depletor reserpine. Based on these data, it can be postulated that (+/-)-PG-9 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. (+/-)-PG-9 (10-40 mg kg-1 i.p.) was able to prevent amnesia induced by scopolamine (1 mg kg-1 i.p.) and dicyclomine (2 mg kg-1 i.p.) in the mouse passive-avoidance test. Affinity profiles of (+/-)-PG-9 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M1, guinea pig atrium for M2, guinea pig ileum for M3 and immature guinea pig uterus for putative M4), have shown an M4/M1 selectivity ratio of 10.2 that might be responsible for the antinociception and the anti-amnesic effect induced by (+/-)-PG-9 through an increase in acetylcholine extracellular levels. In the antinociceptive and antiamnesic dose range, (+/-)-PG-9 did not impair mouse performance evaluated by the rota-rod test and Animex apparatus.", "entity": "2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester", "aliases": "2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester SDZ 205,557 205-557 205557 SDZ-205-557 SDZ-205557", "definition": "", "id": "MESH:C072790"}
{"mention": "5-hydroxytryptamin1A", "mention_text": "The antinociceptive effect of 3 alpha-tropyl 2-(p-bromophenyl)propionate [(+/-)-PG-9] (10-40 mg kg-1 s.c.; 30-60 mg kg-1 p.o.; 10-30 mg kg-1 i.v.; 10-30 micrograms/mouse i.c.v.) was examined in mice, rats and guinea pigs by use of the hot-plate, abdominal-constriction, tail-flick and paw-pressure tests. (+/-)-PG-9 antinociception peaked 15 min after injection and then slowly diminished. The antinociception produced by (+/-)-PG-9 was prevented by the unselective muscarinic antagonist atropine, the M1-selective antagonists pirenzepine and dicyclomine and the acetylcholine depletor hemicholinium-3, but not by the opioid antagonist naloxone, the gamma-aminobutyric acidB antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid, the H3 agonist R-(alpha)-methylhistamine, the D2 antagonist quinpirole, the 5-hydroxytryptamine4 antagonist 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester hydrochloride, the 5-hydroxytryptamin1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide and the polyamines depletor reserpine. Based on these data, it can be postulated that (+/-)-PG-9 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. (+/-)-PG-9 (10-40 mg kg-1 i.p.) was able to prevent amnesia induced by scopolamine (1 mg kg-1 i.p.) and dicyclomine (2 mg kg-1 i.p.) in the mouse passive-avoidance test. Affinity profiles of (+/-)-PG-9 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M1, guinea pig atrium for M2, guinea pig ileum for M3 and immature guinea pig uterus for putative M4), have shown an M4/M1 selectivity ratio of 10.2 that might be responsible for the antinociception and the anti-amnesic effect induced by (+/-)-PG-9 through an increase in acetylcholine extracellular levels. In the antinociceptive and antiamnesic dose range, (+/-)-PG-9 did not impair mouse performance evaluated by the rota-rod test and Animex apparatus.", "entity": "Serotonin", "aliases": "3-(2-Aminoethyl)-1H-indol-5-ol 5 Hydroxytryptamine 5-HT 5-Hydroxytryptamine Enteramine Hippophaine Serotonin", "definition": "A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.\n    ", "id": "MESH:D012701"}
{"mention": "1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine", "mention_text": "The antinociceptive effect of 3 alpha-tropyl 2-(p-bromophenyl)propionate [(+/-)-PG-9] (10-40 mg kg-1 s.c.; 30-60 mg kg-1 p.o.; 10-30 mg kg-1 i.v.; 10-30 micrograms/mouse i.c.v.) was examined in mice, rats and guinea pigs by use of the hot-plate, abdominal-constriction, tail-flick and paw-pressure tests. (+/-)-PG-9 antinociception peaked 15 min after injection and then slowly diminished. The antinociception produced by (+/-)-PG-9 was prevented by the unselective muscarinic antagonist atropine, the M1-selective antagonists pirenzepine and dicyclomine and the acetylcholine depletor hemicholinium-3, but not by the opioid antagonist naloxone, the gamma-aminobutyric acidB antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid, the H3 agonist R-(alpha)-methylhistamine, the D2 antagonist quinpirole, the 5-hydroxytryptamine4 antagonist 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester hydrochloride, the 5-hydroxytryptamin1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide and the polyamines depletor reserpine. Based on these data, it can be postulated that (+/-)-PG-9 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. (+/-)-PG-9 (10-40 mg kg-1 i.p.) was able to prevent amnesia induced by scopolamine (1 mg kg-1 i.p.) and dicyclomine (2 mg kg-1 i.p.) in the mouse passive-avoidance test. Affinity profiles of (+/-)-PG-9 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M1, guinea pig atrium for M2, guinea pig ileum for M3 and immature guinea pig uterus for putative M4), have shown an M4/M1 selectivity ratio of 10.2 that might be responsible for the antinociception and the anti-amnesic effect induced by (+/-)-PG-9 through an increase in acetylcholine extracellular levels. In the antinociceptive and antiamnesic dose range, (+/-)-PG-9 did not impair mouse performance evaluated by the rota-rod test and Animex apparatus.", "entity": "1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine", "aliases": "1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine NAN 190 NAN-190", "definition": "", "id": "MESH:C058895"}
{"mention": "reserpine", "mention_text": "The antinociceptive effect of 3 alpha-tropyl 2-(p-bromophenyl)propionate [(+/-)-PG-9] (10-40 mg kg-1 s.c.; 30-60 mg kg-1 p.o.; 10-30 mg kg-1 i.v.; 10-30 micrograms/mouse i.c.v.) was examined in mice, rats and guinea pigs by use of the hot-plate, abdominal-constriction, tail-flick and paw-pressure tests. (+/-)-PG-9 antinociception peaked 15 min after injection and then slowly diminished. The antinociception produced by (+/-)-PG-9 was prevented by the unselective muscarinic antagonist atropine, the M1-selective antagonists pirenzepine and dicyclomine and the acetylcholine depletor hemicholinium-3, but not by the opioid antagonist naloxone, the gamma-aminobutyric acidB antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid, the H3 agonist R-(alpha)-methylhistamine, the D2 antagonist quinpirole, the 5-hydroxytryptamine4 antagonist 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester hydrochloride, the 5-hydroxytryptamin1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide and the polyamines depletor reserpine. Based on these data, it can be postulated that (+/-)-PG-9 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. (+/-)-PG-9 (10-40 mg kg-1 i.p.) was able to prevent amnesia induced by scopolamine (1 mg kg-1 i.p.) and dicyclomine (2 mg kg-1 i.p.) in the mouse passive-avoidance test. Affinity profiles of (+/-)-PG-9 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M1, guinea pig atrium for M2, guinea pig ileum for M3 and immature guinea pig uterus for putative M4), have shown an M4/M1 selectivity ratio of 10.2 that might be responsible for the antinociception and the anti-amnesic effect induced by (+/-)-PG-9 through an increase in acetylcholine extracellular levels. In the antinociceptive and antiamnesic dose range, (+/-)-PG-9 did not impair mouse performance evaluated by the rota-rod test and Animex apparatus.", "entity": "Reserpine", "aliases": "Raunervil Raupasil Rausedil Rausedyl Reserpine Serpasil Serpivite V Serp V-Serp Vangarde Brand of Vitarine", "definition": "An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use.\n    ", "id": "MESH:D012110"}
{"mention": "amnesia", "mention_text": "The antinociceptive effect of 3 alpha-tropyl 2-(p-bromophenyl)propionate [(+/-)-PG-9] (10-40 mg kg-1 s.c.; 30-60 mg kg-1 p.o.; 10-30 mg kg-1 i.v.; 10-30 micrograms/mouse i.c.v.) was examined in mice, rats and guinea pigs by use of the hot-plate, abdominal-constriction, tail-flick and paw-pressure tests. (+/-)-PG-9 antinociception peaked 15 min after injection and then slowly diminished. The antinociception produced by (+/-)-PG-9 was prevented by the unselective muscarinic antagonist atropine, the M1-selective antagonists pirenzepine and dicyclomine and the acetylcholine depletor hemicholinium-3, but not by the opioid antagonist naloxone, the gamma-aminobutyric acidB antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid, the H3 agonist R-(alpha)-methylhistamine, the D2 antagonist quinpirole, the 5-hydroxytryptamine4 antagonist 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester hydrochloride, the 5-hydroxytryptamin1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide and the polyamines depletor reserpine. Based on these data, it can be postulated that (+/-)-PG-9 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. (+/-)-PG-9 (10-40 mg kg-1 i.p.) was able to prevent amnesia induced by scopolamine (1 mg kg-1 i.p.) and dicyclomine (2 mg kg-1 i.p.) in the mouse passive-avoidance test. Affinity profiles of (+/-)-PG-9 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M1, guinea pig atrium for M2, guinea pig ileum for M3 and immature guinea pig uterus for putative M4), have shown an M4/M1 selectivity ratio of 10.2 that might be responsible for the antinociception and the anti-amnesic effect induced by (+/-)-PG-9 through an increase in acetylcholine extracellular levels. In the antinociceptive and antiamnesic dose range, (+/-)-PG-9 did not impair mouse performance evaluated by the rota-rod test and Animex apparatus.", "entity": "Amnesia", "aliases": "Amnesia Memory Loss Dissociative Global Hysterical Tactile Temporary Amnesia-Memory Losses Amnesias Amnestic State States", "definition": "Pathologic partial or complete loss of the ability to recall past experiences (AMNESIA, RETROGRADE) or to form new memories (AMNESIA, ANTEROGRADE). This condition may be of organic or psychologic origin. Organic forms of amnesia are usually associated with dysfunction of the DIENCEPHALON or HIPPOCAMPUS. (From Adams et al., Principles of Neurology, 6th ed, pp426-7)\n    ", "id": "MESH:D000647"}
{"mention": "scopolamine", "mention_text": "The antinociceptive effect of 3 alpha-tropyl 2-(p-bromophenyl)propionate [(+/-)-PG-9] (10-40 mg kg-1 s.c.; 30-60 mg kg-1 p.o.; 10-30 mg kg-1 i.v.; 10-30 micrograms/mouse i.c.v.) was examined in mice, rats and guinea pigs by use of the hot-plate, abdominal-constriction, tail-flick and paw-pressure tests. (+/-)-PG-9 antinociception peaked 15 min after injection and then slowly diminished. The antinociception produced by (+/-)-PG-9 was prevented by the unselective muscarinic antagonist atropine, the M1-selective antagonists pirenzepine and dicyclomine and the acetylcholine depletor hemicholinium-3, but not by the opioid antagonist naloxone, the gamma-aminobutyric acidB antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid, the H3 agonist R-(alpha)-methylhistamine, the D2 antagonist quinpirole, the 5-hydroxytryptamine4 antagonist 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester hydrochloride, the 5-hydroxytryptamin1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide and the polyamines depletor reserpine. Based on these data, it can be postulated that (+/-)-PG-9 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. (+/-)-PG-9 (10-40 mg kg-1 i.p.) was able to prevent amnesia induced by scopolamine (1 mg kg-1 i.p.) and dicyclomine (2 mg kg-1 i.p.) in the mouse passive-avoidance test. Affinity profiles of (+/-)-PG-9 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M1, guinea pig atrium for M2, guinea pig ileum for M3 and immature guinea pig uterus for putative M4), have shown an M4/M1 selectivity ratio of 10.2 that might be responsible for the antinociception and the anti-amnesic effect induced by (+/-)-PG-9 through an increase in acetylcholine extracellular levels. In the antinociceptive and antiamnesic dose range, (+/-)-PG-9 did not impair mouse performance evaluated by the rota-rod test and Animex apparatus.", "entity": "Scopolamine Hydrobromide", "aliases": "Alcon Brand of Scopolamine Hydrobromide Boro Scopol Boro-Scopol BoroScopol Bull Cooper Hamilton Hope Hyoscine Inibisa Isopto Kwells Novartis Consumer Health Renaudin Roche Scoburen Scopace Scopoderm TTS Transderm Scop V Transderm-V Travacalm HO Vorigeno Winzer Borate", "definition": "An alkaloid from SOLANACEAE, especially DATURA and SCOPOLIA. Scopolamine and its quaternary derivatives act as antimuscarinics like ATROPINE, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in URINARY INCONTINENCE, in MOTION SICKNESS, as an antispasmodic, and as a mydriatic and cycloplegic.\n    ", "id": "MESH:D012601"}
{"mention": "amnesic", "mention_text": "The antinociceptive effect of 3 alpha-tropyl 2-(p-bromophenyl)propionate [(+/-)-PG-9] (10-40 mg kg-1 s.c.; 30-60 mg kg-1 p.o.; 10-30 mg kg-1 i.v.; 10-30 micrograms/mouse i.c.v.) was examined in mice, rats and guinea pigs by use of the hot-plate, abdominal-constriction, tail-flick and paw-pressure tests. (+/-)-PG-9 antinociception peaked 15 min after injection and then slowly diminished. The antinociception produced by (+/-)-PG-9 was prevented by the unselective muscarinic antagonist atropine, the M1-selective antagonists pirenzepine and dicyclomine and the acetylcholine depletor hemicholinium-3, but not by the opioid antagonist naloxone, the gamma-aminobutyric acidB antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid, the H3 agonist R-(alpha)-methylhistamine, the D2 antagonist quinpirole, the 5-hydroxytryptamine4 antagonist 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester hydrochloride, the 5-hydroxytryptamin1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide and the polyamines depletor reserpine. Based on these data, it can be postulated that (+/-)-PG-9 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. (+/-)-PG-9 (10-40 mg kg-1 i.p.) was able to prevent amnesia induced by scopolamine (1 mg kg-1 i.p.) and dicyclomine (2 mg kg-1 i.p.) in the mouse passive-avoidance test. Affinity profiles of (+/-)-PG-9 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M1, guinea pig atrium for M2, guinea pig ileum for M3 and immature guinea pig uterus for putative M4), have shown an M4/M1 selectivity ratio of 10.2 that might be responsible for the antinociception and the anti-amnesic effect induced by (+/-)-PG-9 through an increase in acetylcholine extracellular levels. In the antinociceptive and antiamnesic dose range, (+/-)-PG-9 did not impair mouse performance evaluated by the rota-rod test and Animex apparatus.", "entity": "Amnesia", "aliases": "Amnesia Memory Loss Dissociative Global Hysterical Tactile Temporary Amnesia-Memory Losses Amnesias Amnestic State States", "definition": "Pathologic partial or complete loss of the ability to recall past experiences (AMNESIA, RETROGRADE) or to form new memories (AMNESIA, ANTEROGRADE). This condition may be of organic or psychologic origin. Organic forms of amnesia are usually associated with dysfunction of the DIENCEPHALON or HIPPOCAMPUS. (From Adams et al., Principles of Neurology, 6th ed, pp426-7)\n    ", "id": "MESH:D000647"}
{"mention": "oxygen", "mention_text": "Hyperbaric oxygen therapy for control of intractable cyclophosphamide-induced hemorrhagic cystitis.", "entity": "Oxygen", "aliases": "Dioxygen Oxygen", "definition": "An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.\n    ", "id": "MESH:D010100"}
{"mention": "cyclophosphamide", "mention_text": "Hyperbaric oxygen therapy for control of intractable cyclophosphamide-induced hemorrhagic cystitis.", "entity": "Cyclophosphamide", "aliases": "Anhydrous Cyclophosphamide B 518 B-518 B518 Monohydrate (R)-Isomer (S)-Isomer Cyclophosphane Cytophosphan Cytophosphane Cytoxan Endoxan NSC 26271 NSC-26271 NSC26271 Neosar Procytox Sendoxan", "definition": "Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.\n    ", "id": "MESH:D003520"}
{"mention": "hemorrhagic", "mention_text": "Hyperbaric oxygen therapy for control of intractable cyclophosphamide-induced hemorrhagic cystitis.", "entity": "Hemorrhage", "aliases": "Bleeding Hemorrhage Hemorrhages", "definition": "Bleeding or escape of blood from a vessel.\n    ", "id": "MESH:D006470"}
{"mention": "cystitis", "mention_text": "Hyperbaric oxygen therapy for control of intractable cyclophosphamide-induced hemorrhagic cystitis.", "entity": "Cystitis", "aliases": "Cystitides Cystitis", "definition": "Inflammation of the URINARY BLADDER, either from bacterial or non-bacterial causes. Cystitis is usually associated with painful urination (dysuria), increased frequency, urgency, and suprapubic pain.\n    ", "id": "MESH:D003556"}
{"mention": "hemorrhagic", "mention_text": "We report a case of intractable hemorrhagic cystitis due to cyclophosphamide therapy for Wegener's granulomatosis. Conservative treatment, including bladder irrigation with physiological saline and instillation of prostaglandin F2 alpha, failed to totally control hemorrhage. We then used hyperbaric oxygen at an absolute pressure of 2 atm, 5 days a week for 8 consecutive weeks. The bleeding ceased completely by the end of treatment and the patient remained free of hematuria thereafter. No side effect was noted during the course of therapy. In future, this form of therapy can offer a safe alternative in the treatment of cyclophosphamide-induced hemorrhagic cystitis.", "entity": "Hemorrhage", "aliases": "Bleeding Hemorrhage Hemorrhages", "definition": "Bleeding or escape of blood from a vessel.\n    ", "id": "MESH:D006470"}
{"mention": "cystitis", "mention_text": "We report a case of intractable hemorrhagic cystitis due to cyclophosphamide therapy for Wegener's granulomatosis. Conservative treatment, including bladder irrigation with physiological saline and instillation of prostaglandin F2 alpha, failed to totally control hemorrhage. We then used hyperbaric oxygen at an absolute pressure of 2 atm, 5 days a week for 8 consecutive weeks. The bleeding ceased completely by the end of treatment and the patient remained free of hematuria thereafter. No side effect was noted during the course of therapy. In future, this form of therapy can offer a safe alternative in the treatment of cyclophosphamide-induced hemorrhagic cystitis.", "entity": "Cystitis", "aliases": "Cystitides Cystitis", "definition": "Inflammation of the URINARY BLADDER, either from bacterial or non-bacterial causes. Cystitis is usually associated with painful urination (dysuria), increased frequency, urgency, and suprapubic pain.\n    ", "id": "MESH:D003556"}
{"mention": "cyclophosphamide", "mention_text": "We report a case of intractable hemorrhagic cystitis due to cyclophosphamide therapy for Wegener's granulomatosis. Conservative treatment, including bladder irrigation with physiological saline and instillation of prostaglandin F2 alpha, failed to totally control hemorrhage. We then used hyperbaric oxygen at an absolute pressure of 2 atm, 5 days a week for 8 consecutive weeks. The bleeding ceased completely by the end of treatment and the patient remained free of hematuria thereafter. No side effect was noted during the course of therapy. In future, this form of therapy can offer a safe alternative in the treatment of cyclophosphamide-induced hemorrhagic cystitis.", "entity": "Cyclophosphamide", "aliases": "Anhydrous Cyclophosphamide B 518 B-518 B518 Monohydrate (R)-Isomer (S)-Isomer Cyclophosphane Cytophosphan Cytophosphane Cytoxan Endoxan NSC 26271 NSC-26271 NSC26271 Neosar Procytox Sendoxan", "definition": "Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.\n    ", "id": "MESH:D003520"}
{"mention": "Wegener's granulomatosis", "mention_text": "We report a case of intractable hemorrhagic cystitis due to cyclophosphamide therapy for Wegener's granulomatosis. Conservative treatment, including bladder irrigation with physiological saline and instillation of prostaglandin F2 alpha, failed to totally control hemorrhage. We then used hyperbaric oxygen at an absolute pressure of 2 atm, 5 days a week for 8 consecutive weeks. The bleeding ceased completely by the end of treatment and the patient remained free of hematuria thereafter. No side effect was noted during the course of therapy. In future, this form of therapy can offer a safe alternative in the treatment of cyclophosphamide-induced hemorrhagic cystitis.", "entity": "Granulomatosis with Polyangiitis", "aliases": "Granulomatosis with Polyangiitides Polyangiitis Wegener Wegener's", "definition": "A multisystemic disease of a complex genetic background. It is characterized by inflammation of the blood vessels (VASCULITIS) leading to damage in any number of organs. The common features include granulomatous inflammation of the RESPIRATORY TRACT and KIDNEYS. Most patients have measurable autoantibodies (ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES) against MYELOBLASTIN.\n    ", "id": "MESH:D014890"}
{"mention": "prostaglandin F2 alpha", "mention_text": "We report a case of intractable hemorrhagic cystitis due to cyclophosphamide therapy for Wegener's granulomatosis. Conservative treatment, including bladder irrigation with physiological saline and instillation of prostaglandin F2 alpha, failed to totally control hemorrhage. We then used hyperbaric oxygen at an absolute pressure of 2 atm, 5 days a week for 8 consecutive weeks. The bleeding ceased completely by the end of treatment and the patient remained free of hematuria thereafter. No side effect was noted during the course of therapy. In future, this form of therapy can offer a safe alternative in the treatment of cyclophosphamide-induced hemorrhagic cystitis.", "entity": "Dinoprost", "aliases": "9alpha,11beta PGF2 9alpha,11beta-PGF2 Dinoprost Enzaprost F Estrofan F2 alpha Prostaglandin F2alpha PGF2alpha", "definition": "A naturally occurring prostaglandin that has oxytocic, luteolytic, and abortifacient activities. Due to its vasocontractile properties, the compound has a variety of other biological actions.\n    ", "id": "MESH:D015237"}
{"mention": "hemorrhage", "mention_text": "We report a case of intractable hemorrhagic cystitis due to cyclophosphamide therapy for Wegener's granulomatosis. Conservative treatment, including bladder irrigation with physiological saline and instillation of prostaglandin F2 alpha, failed to totally control hemorrhage. We then used hyperbaric oxygen at an absolute pressure of 2 atm, 5 days a week for 8 consecutive weeks. The bleeding ceased completely by the end of treatment and the patient remained free of hematuria thereafter. No side effect was noted during the course of therapy. In future, this form of therapy can offer a safe alternative in the treatment of cyclophosphamide-induced hemorrhagic cystitis.", "entity": "Hemorrhage", "aliases": "Bleeding Hemorrhage Hemorrhages", "definition": "Bleeding or escape of blood from a vessel.\n    ", "id": "MESH:D006470"}
{"mention": "oxygen", "mention_text": "We report a case of intractable hemorrhagic cystitis due to cyclophosphamide therapy for Wegener's granulomatosis. Conservative treatment, including bladder irrigation with physiological saline and instillation of prostaglandin F2 alpha, failed to totally control hemorrhage. We then used hyperbaric oxygen at an absolute pressure of 2 atm, 5 days a week for 8 consecutive weeks. The bleeding ceased completely by the end of treatment and the patient remained free of hematuria thereafter. No side effect was noted during the course of therapy. In future, this form of therapy can offer a safe alternative in the treatment of cyclophosphamide-induced hemorrhagic cystitis.", "entity": "Oxygen", "aliases": "Dioxygen Oxygen", "definition": "An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.\n    ", "id": "MESH:D010100"}
{"mention": "bleeding", "mention_text": "We report a case of intractable hemorrhagic cystitis due to cyclophosphamide therapy for Wegener's granulomatosis. Conservative treatment, including bladder irrigation with physiological saline and instillation of prostaglandin F2 alpha, failed to totally control hemorrhage. We then used hyperbaric oxygen at an absolute pressure of 2 atm, 5 days a week for 8 consecutive weeks. The bleeding ceased completely by the end of treatment and the patient remained free of hematuria thereafter. No side effect was noted during the course of therapy. In future, this form of therapy can offer a safe alternative in the treatment of cyclophosphamide-induced hemorrhagic cystitis.", "entity": "Hemorrhage", "aliases": "Bleeding Hemorrhage Hemorrhages", "definition": "Bleeding or escape of blood from a vessel.\n    ", "id": "MESH:D006470"}
{"mention": "hematuria", "mention_text": "We report a case of intractable hemorrhagic cystitis due to cyclophosphamide therapy for Wegener's granulomatosis. Conservative treatment, including bladder irrigation with physiological saline and instillation of prostaglandin F2 alpha, failed to totally control hemorrhage. We then used hyperbaric oxygen at an absolute pressure of 2 atm, 5 days a week for 8 consecutive weeks. The bleeding ceased completely by the end of treatment and the patient remained free of hematuria thereafter. No side effect was noted during the course of therapy. In future, this form of therapy can offer a safe alternative in the treatment of cyclophosphamide-induced hemorrhagic cystitis.", "entity": "Hematuria", "aliases": "Hematuria Hematurias", "definition": "Presence of blood in the urine.\n    ", "id": "MESH:D006417"}
{"mention": "p-choloroaniline", "mention_text": "Further studies on the effects of certain irrigating fluids on the rat bladder for 18 hours are reported. The results have shown that the degradation product p-choloroaniline is not a significant factor in chlorhexidine-digluconate associated erosive cystitis. A high percentage of kanamycin-colistin and povidone-iodine irrigations were associated with erosive cystitis and suggested a possible complication with human usage. Picloxydine irrigations appeared to have a lower incidence of erosive cystitis but further studies would have to be performed before it could be recommended for use in urological procedures.", "entity": "4-chloroaniline", "aliases": "4-chloroaniline hydrochloride trifluoroboron salt (1:1) p-chloroaniline p-chlorophenylamine para-chloroaniline", "definition": "", "id": "MESH:C004658"}
{"mention": "chlorhexidine-digluconate", "mention_text": "Further studies on the effects of certain irrigating fluids on the rat bladder for 18 hours are reported. The results have shown that the degradation product p-choloroaniline is not a significant factor in chlorhexidine-digluconate associated erosive cystitis. A high percentage of kanamycin-colistin and povidone-iodine irrigations were associated with erosive cystitis and suggested a possible complication with human usage. Picloxydine irrigations appeared to have a lower incidence of erosive cystitis but further studies would have to be performed before it could be recommended for use in urological procedures.", "entity": "chlorhexidine gluconate", "aliases": "1,1'-HBCB Chlorhexamed Corsodyl ICI Curasept ADS 220 Dyna-Hex Eludril Gibitan Hexidine Hibiclens Hibident Hibiscrub Hibisol Hibitane Peridex Perio Chip avagard chlorhexidine bigluconate digluconate gluconate", "definition": "", "id": "MESH:C010882"}
{"mention": "cystitis", "mention_text": "Further studies on the effects of certain irrigating fluids on the rat bladder for 18 hours are reported. The results have shown that the degradation product p-choloroaniline is not a significant factor in chlorhexidine-digluconate associated erosive cystitis. A high percentage of kanamycin-colistin and povidone-iodine irrigations were associated with erosive cystitis and suggested a possible complication with human usage. Picloxydine irrigations appeared to have a lower incidence of erosive cystitis but further studies would have to be performed before it could be recommended for use in urological procedures.", "entity": "Cystitis", "aliases": "Cystitides Cystitis", "definition": "Inflammation of the URINARY BLADDER, either from bacterial or non-bacterial causes. Cystitis is usually associated with painful urination (dysuria), increased frequency, urgency, and suprapubic pain.\n    ", "id": "MESH:D003556"}
{"mention": "kanamycin", "mention_text": "Further studies on the effects of certain irrigating fluids on the rat bladder for 18 hours are reported. The results have shown that the degradation product p-choloroaniline is not a significant factor in chlorhexidine-digluconate associated erosive cystitis. A high percentage of kanamycin-colistin and povidone-iodine irrigations were associated with erosive cystitis and suggested a possible complication with human usage. Picloxydine irrigations appeared to have a lower incidence of erosive cystitis but further studies would have to be performed before it could be recommended for use in urological procedures.", "entity": "Kanamycin", "aliases": "Kanamycin A Sulfate Kantrex", "definition": "Antibiotic complex produced by Streptomyces kanamyceticus from Japanese soil. Comprises 3 components: kanamycin A, the major component, and kanamycins B and C, the minor components.\n    ", "id": "MESH:D007612"}
{"mention": "colistin", "mention_text": "Further studies on the effects of certain irrigating fluids on the rat bladder for 18 hours are reported. The results have shown that the degradation product p-choloroaniline is not a significant factor in chlorhexidine-digluconate associated erosive cystitis. A high percentage of kanamycin-colistin and povidone-iodine irrigations were associated with erosive cystitis and suggested a possible complication with human usage. Picloxydine irrigations appeared to have a lower incidence of erosive cystitis but further studies would have to be performed before it could be recommended for use in urological procedures.", "entity": "Colistin", "aliases": "Colimycin Colisticin Colistin Sulfate Coly-Mycin Polymyxin E Totazina", "definition": "Cyclic polypeptide antibiotic from Bacillus colistinus. It is composed of Polymyxins E1 and E2 (or Colistins A, B, and C) which act as detergents on cell membranes. Colistin is less toxic than Polymyxin B, but otherwise similar; the methanesulfonate is used orally.\n    ", "id": "MESH:D003091"}
{"mention": "povidone-iodine", "mention_text": "Further studies on the effects of certain irrigating fluids on the rat bladder for 18 hours are reported. The results have shown that the degradation product p-choloroaniline is not a significant factor in chlorhexidine-digluconate associated erosive cystitis. A high percentage of kanamycin-colistin and povidone-iodine irrigations were associated with erosive cystitis and suggested a possible complication with human usage. Picloxydine irrigations appeared to have a lower incidence of erosive cystitis but further studies would have to be performed before it could be recommended for use in urological procedures.", "entity": "Povidone-Iodine", "aliases": "Alphadine Alphadines Betadine Betadines Betaisodona Betaisodonas Disadine Disadines Huntington Laboratories Brand of Povidone Iodine Povidone-Iodine Isodine Isodines PVP PVP-I PVP-Iodine PVP-Iodines Pharmadine Pharmadines Polyvinylpyrrolidone Iodines Povidone-Iodines Providine Providines", "definition": "An iodinated polyvinyl polymer used as topical antiseptic in surgery and for skin and mucous membrane infections, also as aerosol. The iodine may be radiolabeled for research purposes.\n    ", "id": "MESH:D011206"}
{"mention": "Picloxydine", "mention_text": "Further studies on the effects of certain irrigating fluids on the rat bladder for 18 hours are reported. The results have shown that the degradation product p-choloroaniline is not a significant factor in chlorhexidine-digluconate associated erosive cystitis. A high percentage of kanamycin-colistin and povidone-iodine irrigations were associated with erosive cystitis and suggested a possible complication with human usage. Picloxydine irrigations appeared to have a lower incidence of erosive cystitis but further studies would have to be performed before it could be recommended for use in urological procedures.", "entity": "picloxydine", "aliases": "1,1-(p-chlorophenylguanidinoformimidonyl)bis piperazine Vitabact picloxidine picloxydine dihydrochloride", "definition": "", "id": "MESH:C005253"}
{"mention": "bromperidol", "mention_text": "A total of sixty patients were trated with bromperidol first in open conditions (20 patients), then on a double blind basis (40 patients) with haloperidol as the reference substance. The open study lasted for four weeks; the drug was administrated in the form of 1 mg tablets. The daily dose (initial dose: 1 mg; mean dose at the end of the trial: 4.47 mg) was always administered in one single dose. Nineteen patients finished the trial, and in 18 cases the therapeutic result was considered very good to good. These results were confirmed by statistical analysis. Nine patients exhibited mild to moderate extrapyramidal concomitant symptoms; no other side effects were observed. The results of detailed laboratory tests and evaluations of various quantitative and qualitative tolerability parameters were not indicative of toxic effects. In the double blind study with haloperidol, both substances were found to be highly effective in the treatment of psychotic syndromes belonging predominantly to the schizophrenia group. Certain clues, including the onset of action, seem to be indicative of the superiority of bromperidol. No differences were observed with respect to side effects and general tolerability.", "entity": "bromperidol", "aliases": "C-C 2489/21 Impromen R 11,333 Tesoprel bromoperidol bromperidol hydrochloride 82Br-labeled", "definition": "", "id": "MESH:C006820"}
{"mention": "haloperidol", "mention_text": "A total of sixty patients were trated with bromperidol first in open conditions (20 patients), then on a double blind basis (40 patients) with haloperidol as the reference substance. The open study lasted for four weeks; the drug was administrated in the form of 1 mg tablets. The daily dose (initial dose: 1 mg; mean dose at the end of the trial: 4.47 mg) was always administered in one single dose. Nineteen patients finished the trial, and in 18 cases the therapeutic result was considered very good to good. These results were confirmed by statistical analysis. Nine patients exhibited mild to moderate extrapyramidal concomitant symptoms; no other side effects were observed. The results of detailed laboratory tests and evaluations of various quantitative and qualitative tolerability parameters were not indicative of toxic effects. In the double blind study with haloperidol, both substances were found to be highly effective in the treatment of psychotic syndromes belonging predominantly to the schizophrenia group. Certain clues, including the onset of action, seem to be indicative of the superiority of bromperidol. No differences were observed with respect to side effects and general tolerability.", "entity": "Haloperidol", "aliases": "Haldol Haloperidol", "definition": "A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)\n    ", "id": "MESH:D006220"}
{"mention": "extrapyramidal concomitant symptoms", "mention_text": "A total of sixty patients were trated with bromperidol first in open conditions (20 patients), then on a double blind basis (40 patients) with haloperidol as the reference substance. The open study lasted for four weeks; the drug was administrated in the form of 1 mg tablets. The daily dose (initial dose: 1 mg; mean dose at the end of the trial: 4.47 mg) was always administered in one single dose. Nineteen patients finished the trial, and in 18 cases the therapeutic result was considered very good to good. These results were confirmed by statistical analysis. Nine patients exhibited mild to moderate extrapyramidal concomitant symptoms; no other side effects were observed. The results of detailed laboratory tests and evaluations of various quantitative and qualitative tolerability parameters were not indicative of toxic effects. In the double blind study with haloperidol, both substances were found to be highly effective in the treatment of psychotic syndromes belonging predominantly to the schizophrenia group. Certain clues, including the onset of action, seem to be indicative of the superiority of bromperidol. No differences were observed with respect to side effects and general tolerability.", "entity": "Basal Ganglia Diseases", "aliases": "Basal Ganglia Disease Diseases Disorder Disorders Extrapyramidal Lenticulostriate", "definition": "Diseases of the BASAL GANGLIA including the PUTAMEN; GLOBUS PALLIDUS; claustrum; AMYGDALA; and CAUDATE NUCLEUS. DYSKINESIAS (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include CEREBROVASCULAR DISORDERS; NEURODEGENERATIVE DISEASES; and CRANIOCEREBRAL TRAUMA.\n    ", "id": "MESH:D001480"}
{"mention": "psychotic syndromes belonging predominantly to the schizophrenia group", "mention_text": "A total of sixty patients were trated with bromperidol first in open conditions (20 patients), then on a double blind basis (40 patients) with haloperidol as the reference substance. The open study lasted for four weeks; the drug was administrated in the form of 1 mg tablets. The daily dose (initial dose: 1 mg; mean dose at the end of the trial: 4.47 mg) was always administered in one single dose. Nineteen patients finished the trial, and in 18 cases the therapeutic result was considered very good to good. These results were confirmed by statistical analysis. Nine patients exhibited mild to moderate extrapyramidal concomitant symptoms; no other side effects were observed. The results of detailed laboratory tests and evaluations of various quantitative and qualitative tolerability parameters were not indicative of toxic effects. In the double blind study with haloperidol, both substances were found to be highly effective in the treatment of psychotic syndromes belonging predominantly to the schizophrenia group. Certain clues, including the onset of action, seem to be indicative of the superiority of bromperidol. No differences were observed with respect to side effects and general tolerability.", "entity": "Schizophrenia and Disorders with Psychotic Features", "aliases": "Schizophrenia and Disorders with Psychotic Features", "definition": "Marked disorders of thought (delusions, hallucinations, or other thought disorder accompanied by disordered affect or behavior), and deterioration from a previous level of functioning.\n    ", "id": "MESH:D019967"}
{"mention": "Curcumin", "mention_text": "Curcumin ameliorates cognitive dysfunction and oxidative damage in phenobarbitone and carbamazepine administered rats.", "entity": "Curcumin", "aliases": "Curcumin Diferuloylmethane Turmeric Yellow", "definition": "A yellow-orange dye obtained from tumeric, the powdered root of CURCUMA longa. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes.\n    ", "id": "MESH:D003474"}
{"mention": "cognitive dysfunction", "mention_text": "Curcumin ameliorates cognitive dysfunction and oxidative damage in phenobarbitone and carbamazepine administered rats.", "entity": "Cognition Disorders", "aliases": "Cognition Disorders Disorder Overinclusion", "definition": "Disturbances in the mental process related to thinking, reasoning, and judgment.\n    ", "id": "MESH:D003072"}
{"mention": "phenobarbitone", "mention_text": "Curcumin ameliorates cognitive dysfunction and oxidative damage in phenobarbitone and carbamazepine administered rats.", "entity": "Phenobarbital", "aliases": "Acid Phenylethylbarbituric Gardenal Hysteps Luminal Monosodium Salt Phenobarbital Phenemal Sodium Phenobarbitone Phenylbarbital", "definition": "A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.\n    ", "id": "MESH:D010634"}
{"mention": "carbamazepine", "mention_text": "Curcumin ameliorates cognitive dysfunction and oxidative damage in phenobarbitone and carbamazepine administered rats.", "entity": "Carbamazepine", "aliases": "Amizepine Carbamazepine Acetate Anhydrous Dihydrate Hydrochloride L-Tartrate (4:1) Phosphate Sulfate (2:1) Carbazepin Epitol Finlepsin Neurotol Tegretol", "definition": "An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of PHENYTOIN; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar.\n    ", "id": "MESH:D002220"}
{"mention": "phenobarbitone", "mention_text": "The antiepileptic drugs, phenobarbitone and carbamazepine are well known to cause cognitive impairment on chronic use. The increase in free radical generation has been implicated as one of the important mechanisms of cognitive impairment by antiepileptic drugs. Curcumin has shown antioxidant, anti-inflammatory and neuro-protective properties. Therefore, the present study was carried out to investigate the effect of chronic curcumin administration on phenobarbitone- and carbamazepine-induced cognitive impairment and oxidative stress in rats. Pharmacokinetic interactions of curcumin with phenobarbitone and carbamazepine were also studied. Vehicle/drugs were administered daily for 21days to male Wistar rats. Passive avoidance paradigm and elevated plus maze test were used to assess cognitive function. At the end of study period, serum phenobarbitone and carbamazepine, whole brain malondialdehyde and reduced glutathione levels were estimated. The administration of phenobarbitone and carbamazepine for 21days caused a significant impairment of learning and memory as well as an increased oxidative stress. Concomitant curcumin administration prevented the cognitive impairment and decreased the increased oxidative stress induced by these antiepileptic drugs. Curcumin co-administration did not cause any significant alteration in the serum concentrations of both phenobarbitone as well as carbamazepine. These results show that curcumin has beneficial effect in mitigating the deterioration of cognitive functions and oxidative damage in rats treated with phenobarbitone and carbamazepine without significantly altering their serum concentrations. The findings suggest that curcumin can be considered as a potential safe and effective adjuvant to phenobarbitone and carbamazepine therapy in preventing cognitive impairment associated with these drugs.", "entity": "Phenobarbital", "aliases": "Acid Phenylethylbarbituric Gardenal Hysteps Luminal Monosodium Salt Phenobarbital Phenemal Sodium Phenobarbitone Phenylbarbital", "definition": "A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.\n    ", "id": "MESH:D010634"}
{"mention": "carbamazepine", "mention_text": "The antiepileptic drugs, phenobarbitone and carbamazepine are well known to cause cognitive impairment on chronic use. The increase in free radical generation has been implicated as one of the important mechanisms of cognitive impairment by antiepileptic drugs. Curcumin has shown antioxidant, anti-inflammatory and neuro-protective properties. Therefore, the present study was carried out to investigate the effect of chronic curcumin administration on phenobarbitone- and carbamazepine-induced cognitive impairment and oxidative stress in rats. Pharmacokinetic interactions of curcumin with phenobarbitone and carbamazepine were also studied. Vehicle/drugs were administered daily for 21days to male Wistar rats. Passive avoidance paradigm and elevated plus maze test were used to assess cognitive function. At the end of study period, serum phenobarbitone and carbamazepine, whole brain malondialdehyde and reduced glutathione levels were estimated. The administration of phenobarbitone and carbamazepine for 21days caused a significant impairment of learning and memory as well as an increased oxidative stress. Concomitant curcumin administration prevented the cognitive impairment and decreased the increased oxidative stress induced by these antiepileptic drugs. Curcumin co-administration did not cause any significant alteration in the serum concentrations of both phenobarbitone as well as carbamazepine. These results show that curcumin has beneficial effect in mitigating the deterioration of cognitive functions and oxidative damage in rats treated with phenobarbitone and carbamazepine without significantly altering their serum concentrations. The findings suggest that curcumin can be considered as a potential safe and effective adjuvant to phenobarbitone and carbamazepine therapy in preventing cognitive impairment associated with these drugs.", "entity": "Carbamazepine", "aliases": "Amizepine Carbamazepine Acetate Anhydrous Dihydrate Hydrochloride L-Tartrate (4:1) Phosphate Sulfate (2:1) Carbazepin Epitol Finlepsin Neurotol Tegretol", "definition": "An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of PHENYTOIN; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar.\n    ", "id": "MESH:D002220"}
{"mention": "cognitive impairment", "mention_text": "The antiepileptic drugs, phenobarbitone and carbamazepine are well known to cause cognitive impairment on chronic use. The increase in free radical generation has been implicated as one of the important mechanisms of cognitive impairment by antiepileptic drugs. Curcumin has shown antioxidant, anti-inflammatory and neuro-protective properties. Therefore, the present study was carried out to investigate the effect of chronic curcumin administration on phenobarbitone- and carbamazepine-induced cognitive impairment and oxidative stress in rats. Pharmacokinetic interactions of curcumin with phenobarbitone and carbamazepine were also studied. Vehicle/drugs were administered daily for 21days to male Wistar rats. Passive avoidance paradigm and elevated plus maze test were used to assess cognitive function. At the end of study period, serum phenobarbitone and carbamazepine, whole brain malondialdehyde and reduced glutathione levels were estimated. The administration of phenobarbitone and carbamazepine for 21days caused a significant impairment of learning and memory as well as an increased oxidative stress. Concomitant curcumin administration prevented the cognitive impairment and decreased the increased oxidative stress induced by these antiepileptic drugs. Curcumin co-administration did not cause any significant alteration in the serum concentrations of both phenobarbitone as well as carbamazepine. These results show that curcumin has beneficial effect in mitigating the deterioration of cognitive functions and oxidative damage in rats treated with phenobarbitone and carbamazepine without significantly altering their serum concentrations. The findings suggest that curcumin can be considered as a potential safe and effective adjuvant to phenobarbitone and carbamazepine therapy in preventing cognitive impairment associated with these drugs.", "entity": "Cognition Disorders", "aliases": "Cognition Disorders Disorder Overinclusion", "definition": "Disturbances in the mental process related to thinking, reasoning, and judgment.\n    ", "id": "MESH:D003072"}
{"mention": "Curcumin", "mention_text": "The antiepileptic drugs, phenobarbitone and carbamazepine are well known to cause cognitive impairment on chronic use. The increase in free radical generation has been implicated as one of the important mechanisms of cognitive impairment by antiepileptic drugs. Curcumin has shown antioxidant, anti-inflammatory and neuro-protective properties. Therefore, the present study was carried out to investigate the effect of chronic curcumin administration on phenobarbitone- and carbamazepine-induced cognitive impairment and oxidative stress in rats. Pharmacokinetic interactions of curcumin with phenobarbitone and carbamazepine were also studied. Vehicle/drugs were administered daily for 21days to male Wistar rats. Passive avoidance paradigm and elevated plus maze test were used to assess cognitive function. At the end of study period, serum phenobarbitone and carbamazepine, whole brain malondialdehyde and reduced glutathione levels were estimated. The administration of phenobarbitone and carbamazepine for 21days caused a significant impairment of learning and memory as well as an increased oxidative stress. Concomitant curcumin administration prevented the cognitive impairment and decreased the increased oxidative stress induced by these antiepileptic drugs. Curcumin co-administration did not cause any significant alteration in the serum concentrations of both phenobarbitone as well as carbamazepine. These results show that curcumin has beneficial effect in mitigating the deterioration of cognitive functions and oxidative damage in rats treated with phenobarbitone and carbamazepine without significantly altering their serum concentrations. The findings suggest that curcumin can be considered as a potential safe and effective adjuvant to phenobarbitone and carbamazepine therapy in preventing cognitive impairment associated with these drugs.", "entity": "Curcumin", "aliases": "Curcumin Diferuloylmethane Turmeric Yellow", "definition": "A yellow-orange dye obtained from tumeric, the powdered root of CURCUMA longa. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes.\n    ", "id": "MESH:D003474"}
{"mention": "curcumin", "mention_text": "The antiepileptic drugs, phenobarbitone and carbamazepine are well known to cause cognitive impairment on chronic use. The increase in free radical generation has been implicated as one of the important mechanisms of cognitive impairment by antiepileptic drugs. Curcumin has shown antioxidant, anti-inflammatory and neuro-protective properties. Therefore, the present study was carried out to investigate the effect of chronic curcumin administration on phenobarbitone- and carbamazepine-induced cognitive impairment and oxidative stress in rats. Pharmacokinetic interactions of curcumin with phenobarbitone and carbamazepine were also studied. Vehicle/drugs were administered daily for 21days to male Wistar rats. Passive avoidance paradigm and elevated plus maze test were used to assess cognitive function. At the end of study period, serum phenobarbitone and carbamazepine, whole brain malondialdehyde and reduced glutathione levels were estimated. The administration of phenobarbitone and carbamazepine for 21days caused a significant impairment of learning and memory as well as an increased oxidative stress. Concomitant curcumin administration prevented the cognitive impairment and decreased the increased oxidative stress induced by these antiepileptic drugs. Curcumin co-administration did not cause any significant alteration in the serum concentrations of both phenobarbitone as well as carbamazepine. These results show that curcumin has beneficial effect in mitigating the deterioration of cognitive functions and oxidative damage in rats treated with phenobarbitone and carbamazepine without significantly altering their serum concentrations. The findings suggest that curcumin can be considered as a potential safe and effective adjuvant to phenobarbitone and carbamazepine therapy in preventing cognitive impairment associated with these drugs.", "entity": "Curcumin", "aliases": "Curcumin Diferuloylmethane Turmeric Yellow", "definition": "A yellow-orange dye obtained from tumeric, the powdered root of CURCUMA longa. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes.\n    ", "id": "MESH:D003474"}
{"mention": "malondialdehyde", "mention_text": "The antiepileptic drugs, phenobarbitone and carbamazepine are well known to cause cognitive impairment on chronic use. The increase in free radical generation has been implicated as one of the important mechanisms of cognitive impairment by antiepileptic drugs. Curcumin has shown antioxidant, anti-inflammatory and neuro-protective properties. Therefore, the present study was carried out to investigate the effect of chronic curcumin administration on phenobarbitone- and carbamazepine-induced cognitive impairment and oxidative stress in rats. Pharmacokinetic interactions of curcumin with phenobarbitone and carbamazepine were also studied. Vehicle/drugs were administered daily for 21days to male Wistar rats. Passive avoidance paradigm and elevated plus maze test were used to assess cognitive function. At the end of study period, serum phenobarbitone and carbamazepine, whole brain malondialdehyde and reduced glutathione levels were estimated. The administration of phenobarbitone and carbamazepine for 21days caused a significant impairment of learning and memory as well as an increased oxidative stress. Concomitant curcumin administration prevented the cognitive impairment and decreased the increased oxidative stress induced by these antiepileptic drugs. Curcumin co-administration did not cause any significant alteration in the serum concentrations of both phenobarbitone as well as carbamazepine. These results show that curcumin has beneficial effect in mitigating the deterioration of cognitive functions and oxidative damage in rats treated with phenobarbitone and carbamazepine without significantly altering their serum concentrations. The findings suggest that curcumin can be considered as a potential safe and effective adjuvant to phenobarbitone and carbamazepine therapy in preventing cognitive impairment associated with these drugs.", "entity": "Malondialdehyde", "aliases": "Malonaldehyde Malondialdehyde Sodium Malonylaldehyde Malonyldialdehyde Propanedial", "definition": "The dialdehyde of malonic acid.\n    ", "id": "MESH:D008315"}
{"mention": "glutathione", "mention_text": "The antiepileptic drugs, phenobarbitone and carbamazepine are well known to cause cognitive impairment on chronic use. The increase in free radical generation has been implicated as one of the important mechanisms of cognitive impairment by antiepileptic drugs. Curcumin has shown antioxidant, anti-inflammatory and neuro-protective properties. Therefore, the present study was carried out to investigate the effect of chronic curcumin administration on phenobarbitone- and carbamazepine-induced cognitive impairment and oxidative stress in rats. Pharmacokinetic interactions of curcumin with phenobarbitone and carbamazepine were also studied. Vehicle/drugs were administered daily for 21days to male Wistar rats. Passive avoidance paradigm and elevated plus maze test were used to assess cognitive function. At the end of study period, serum phenobarbitone and carbamazepine, whole brain malondialdehyde and reduced glutathione levels were estimated. The administration of phenobarbitone and carbamazepine for 21days caused a significant impairment of learning and memory as well as an increased oxidative stress. Concomitant curcumin administration prevented the cognitive impairment and decreased the increased oxidative stress induced by these antiepileptic drugs. Curcumin co-administration did not cause any significant alteration in the serum concentrations of both phenobarbitone as well as carbamazepine. These results show that curcumin has beneficial effect in mitigating the deterioration of cognitive functions and oxidative damage in rats treated with phenobarbitone and carbamazepine without significantly altering their serum concentrations. The findings suggest that curcumin can be considered as a potential safe and effective adjuvant to phenobarbitone and carbamazepine therapy in preventing cognitive impairment associated with these drugs.", "entity": "Glutathione", "aliases": "Glutathione Reduced gamma L Glu L Cys Gly Glutamyl Cysteinylglycine gamma-L-Glu-L-Cys-Gly gamma-L-Glutamyl-L-Cysteinylglycine", "definition": "A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.\n    ", "id": "MESH:D005978"}
{"mention": "impairment of learning and memory", "mention_text": "The antiepileptic drugs, phenobarbitone and carbamazepine are well known to cause cognitive impairment on chronic use. The increase in free radical generation has been implicated as one of the important mechanisms of cognitive impairment by antiepileptic drugs. Curcumin has shown antioxidant, anti-inflammatory and neuro-protective properties. Therefore, the present study was carried out to investigate the effect of chronic curcumin administration on phenobarbitone- and carbamazepine-induced cognitive impairment and oxidative stress in rats. Pharmacokinetic interactions of curcumin with phenobarbitone and carbamazepine were also studied. Vehicle/drugs were administered daily for 21days to male Wistar rats. Passive avoidance paradigm and elevated plus maze test were used to assess cognitive function. At the end of study period, serum phenobarbitone and carbamazepine, whole brain malondialdehyde and reduced glutathione levels were estimated. The administration of phenobarbitone and carbamazepine for 21days caused a significant impairment of learning and memory as well as an increased oxidative stress. Concomitant curcumin administration prevented the cognitive impairment and decreased the increased oxidative stress induced by these antiepileptic drugs. Curcumin co-administration did not cause any significant alteration in the serum concentrations of both phenobarbitone as well as carbamazepine. These results show that curcumin has beneficial effect in mitigating the deterioration of cognitive functions and oxidative damage in rats treated with phenobarbitone and carbamazepine without significantly altering their serum concentrations. The findings suggest that curcumin can be considered as a potential safe and effective adjuvant to phenobarbitone and carbamazepine therapy in preventing cognitive impairment associated with these drugs.", "entity": "Cognition Disorders", "aliases": "Cognition Disorders Disorder Overinclusion", "definition": "Disturbances in the mental process related to thinking, reasoning, and judgment.\n    ", "id": "MESH:D003072"}
{"mention": "deterioration of cognitive functions", "mention_text": "The antiepileptic drugs, phenobarbitone and carbamazepine are well known to cause cognitive impairment on chronic use. The increase in free radical generation has been implicated as one of the important mechanisms of cognitive impairment by antiepileptic drugs. Curcumin has shown antioxidant, anti-inflammatory and neuro-protective properties. Therefore, the present study was carried out to investigate the effect of chronic curcumin administration on phenobarbitone- and carbamazepine-induced cognitive impairment and oxidative stress in rats. Pharmacokinetic interactions of curcumin with phenobarbitone and carbamazepine were also studied. Vehicle/drugs were administered daily for 21days to male Wistar rats. Passive avoidance paradigm and elevated plus maze test were used to assess cognitive function. At the end of study period, serum phenobarbitone and carbamazepine, whole brain malondialdehyde and reduced glutathione levels were estimated. The administration of phenobarbitone and carbamazepine for 21days caused a significant impairment of learning and memory as well as an increased oxidative stress. Concomitant curcumin administration prevented the cognitive impairment and decreased the increased oxidative stress induced by these antiepileptic drugs. Curcumin co-administration did not cause any significant alteration in the serum concentrations of both phenobarbitone as well as carbamazepine. These results show that curcumin has beneficial effect in mitigating the deterioration of cognitive functions and oxidative damage in rats treated with phenobarbitone and carbamazepine without significantly altering their serum concentrations. The findings suggest that curcumin can be considered as a potential safe and effective adjuvant to phenobarbitone and carbamazepine therapy in preventing cognitive impairment associated with these drugs.", "entity": "Cognition Disorders", "aliases": "Cognition Disorders Disorder Overinclusion", "definition": "Disturbances in the mental process related to thinking, reasoning, and judgment.\n    ", "id": "MESH:D003072"}
{"mention": "Pyrrolidine dithiocarbamate", "mention_text": "Pyrrolidine dithiocarbamate protects the piriform cortex in the pilocarpine status epilepticus model.", "entity": "pyrrolidine dithiocarbamic acid", "aliases": "Pyrrolidinedithiocarbamate ammonium pyrrolidine dithiocarbamate tetramethylene dithiocarbamic acid salt sodium", "definition": "", "id": "MESH:C020972"}
{"mention": "pilocarpine", "mention_text": "Pyrrolidine dithiocarbamate protects the piriform cortex in the pilocarpine status epilepticus model.", "entity": "Pilocarpine", "aliases": "Hydrochloride Pilocarpine Isopilocarpine Isoptocarpine Nitrate Ocusert Mononitrate (3S-cis)-Isomer Monohydrochloride Salagen", "definition": "A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma.\n    ", "id": "MESH:D010862"}
{"mention": "status epilepticus", "mention_text": "Pyrrolidine dithiocarbamate protects the piriform cortex in the pilocarpine status epilepticus model.", "entity": "Status Epilepticus", "aliases": "Absence Status Complex Partial Epilepticus Electrographic Generalized Convulsive Grand Mal Non Non-Convulsive Petit Simple Subclinical", "definition": "A prolonged seizure or seizures repeated frequently enough to prevent recovery between episodes occurring over a period of 20-30 minutes. The most common subtype is generalized tonic-clonic status epilepticus, a potentially fatal condition associated with neuronal injury and respiratory and metabolic dysfunction. Nonconvulsive forms include petit mal status and complex partial status, which may manifest as behavioral disturbances. Simple partial status epilepticus consists of persistent motor, sensory, or autonomic seizures that do not impair cognition (see also EPILEPSIA PARTIALIS CONTINUA). Subclinical status epilepticus generally refers to seizures occurring in an unresponsive or comatose individual in the absence of overt signs of seizure activity. (From N Engl J Med 1998 Apr 2;338(14):970-6; Neurologia 1997 Dec;12 Suppl 6:25-30)\n    ", "id": "MESH:D013226"}
{"mention": "Pyrrolidine dithiocarbamate", "mention_text": "Pyrrolidine dithiocarbamate (PDTC) has a dual mechanism of action as an antioxidant and an inhibitor of the transcription factor kappa-beta. Both, production of reactive oxygen species as well as activation of NF-kappaB have been implicated in severe neuronal damage in different sub-regions of the hippocampus as well as in the surrounding cortices. The effect of PDTC on status epilepticus-associated cell loss in the hippocampus and piriform cortex was evaluated in the rat fractionated pilocarpine model. Treatment with 150 mg/kg PDTC before and following status epilepticus significantly increased the mortality rate to 100%. Administration of 50 mg/kg PDTC (low-dose) did not exert major effects on the development of a status epilepticus or the mortality rate. In vehicle-treated rats, status epilepticus caused pronounced neuronal damage in the piriform cortex comprising both pyramidal cells and interneurons. Low-dose PDTC treatment almost completely protected from lesions in the piriform cortex. A significant decrease in neuronal density of the hippocampal hilar formation was identified in vehicle- and PDTC-treated rats following status epilepticus. In conclusion, the NF-kappaB inhibitor and antioxidant PDTC protected the piriform cortex, whereas it did not affect hilar neuronal loss. These data might indicate that the generation of reactive oxygen species and activation of NF-kappaB plays a more central role in seizure-associated neuronal damage in the temporal cortex as compared to the hippocampal hilus. However, future investigations are necessary to exactly analyze the biochemical mechanisms by which PDTC exerted its beneficial effects in the piriform cortex.", "entity": "pyrrolidine dithiocarbamic acid", "aliases": "Pyrrolidinedithiocarbamate ammonium pyrrolidine dithiocarbamate tetramethylene dithiocarbamic acid salt sodium", "definition": "", "id": "MESH:C020972"}
{"mention": "PDTC", "mention_text": "Pyrrolidine dithiocarbamate (PDTC) has a dual mechanism of action as an antioxidant and an inhibitor of the transcription factor kappa-beta. Both, production of reactive oxygen species as well as activation of NF-kappaB have been implicated in severe neuronal damage in different sub-regions of the hippocampus as well as in the surrounding cortices. The effect of PDTC on status epilepticus-associated cell loss in the hippocampus and piriform cortex was evaluated in the rat fractionated pilocarpine model. Treatment with 150 mg/kg PDTC before and following status epilepticus significantly increased the mortality rate to 100%. Administration of 50 mg/kg PDTC (low-dose) did not exert major effects on the development of a status epilepticus or the mortality rate. In vehicle-treated rats, status epilepticus caused pronounced neuronal damage in the piriform cortex comprising both pyramidal cells and interneurons. Low-dose PDTC treatment almost completely protected from lesions in the piriform cortex. A significant decrease in neuronal density of the hippocampal hilar formation was identified in vehicle- and PDTC-treated rats following status epilepticus. In conclusion, the NF-kappaB inhibitor and antioxidant PDTC protected the piriform cortex, whereas it did not affect hilar neuronal loss. These data might indicate that the generation of reactive oxygen species and activation of NF-kappaB plays a more central role in seizure-associated neuronal damage in the temporal cortex as compared to the hippocampal hilus. However, future investigations are necessary to exactly analyze the biochemical mechanisms by which PDTC exerted its beneficial effects in the piriform cortex.", "entity": "pyrrolidine dithiocarbamic acid", "aliases": "Pyrrolidinedithiocarbamate ammonium pyrrolidine dithiocarbamate tetramethylene dithiocarbamic acid salt sodium", "definition": "", "id": "MESH:C020972"}
{"mention": "oxygen", "mention_text": "Pyrrolidine dithiocarbamate (PDTC) has a dual mechanism of action as an antioxidant and an inhibitor of the transcription factor kappa-beta. Both, production of reactive oxygen species as well as activation of NF-kappaB have been implicated in severe neuronal damage in different sub-regions of the hippocampus as well as in the surrounding cortices. The effect of PDTC on status epilepticus-associated cell loss in the hippocampus and piriform cortex was evaluated in the rat fractionated pilocarpine model. Treatment with 150 mg/kg PDTC before and following status epilepticus significantly increased the mortality rate to 100%. Administration of 50 mg/kg PDTC (low-dose) did not exert major effects on the development of a status epilepticus or the mortality rate. In vehicle-treated rats, status epilepticus caused pronounced neuronal damage in the piriform cortex comprising both pyramidal cells and interneurons. Low-dose PDTC treatment almost completely protected from lesions in the piriform cortex. A significant decrease in neuronal density of the hippocampal hilar formation was identified in vehicle- and PDTC-treated rats following status epilepticus. In conclusion, the NF-kappaB inhibitor and antioxidant PDTC protected the piriform cortex, whereas it did not affect hilar neuronal loss. These data might indicate that the generation of reactive oxygen species and activation of NF-kappaB plays a more central role in seizure-associated neuronal damage in the temporal cortex as compared to the hippocampal hilus. However, future investigations are necessary to exactly analyze the biochemical mechanisms by which PDTC exerted its beneficial effects in the piriform cortex.", "entity": "Oxygen", "aliases": "Dioxygen Oxygen", "definition": "An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.\n    ", "id": "MESH:D010100"}
{"mention": "neuronal damage", "mention_text": "Pyrrolidine dithiocarbamate (PDTC) has a dual mechanism of action as an antioxidant and an inhibitor of the transcription factor kappa-beta. Both, production of reactive oxygen species as well as activation of NF-kappaB have been implicated in severe neuronal damage in different sub-regions of the hippocampus as well as in the surrounding cortices. The effect of PDTC on status epilepticus-associated cell loss in the hippocampus and piriform cortex was evaluated in the rat fractionated pilocarpine model. Treatment with 150 mg/kg PDTC before and following status epilepticus significantly increased the mortality rate to 100%. Administration of 50 mg/kg PDTC (low-dose) did not exert major effects on the development of a status epilepticus or the mortality rate. In vehicle-treated rats, status epilepticus caused pronounced neuronal damage in the piriform cortex comprising both pyramidal cells and interneurons. Low-dose PDTC treatment almost completely protected from lesions in the piriform cortex. A significant decrease in neuronal density of the hippocampal hilar formation was identified in vehicle- and PDTC-treated rats following status epilepticus. In conclusion, the NF-kappaB inhibitor and antioxidant PDTC protected the piriform cortex, whereas it did not affect hilar neuronal loss. These data might indicate that the generation of reactive oxygen species and activation of NF-kappaB plays a more central role in seizure-associated neuronal damage in the temporal cortex as compared to the hippocampal hilus. However, future investigations are necessary to exactly analyze the biochemical mechanisms by which PDTC exerted its beneficial effects in the piriform cortex.", "entity": "Nerve Degeneration", "aliases": "Degeneration Nerve Neuron Degenerations", "definition": "Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.\n    ", "id": "MESH:D009410"}
{"mention": "status epilepticus", "mention_text": "Pyrrolidine dithiocarbamate (PDTC) has a dual mechanism of action as an antioxidant and an inhibitor of the transcription factor kappa-beta. Both, production of reactive oxygen species as well as activation of NF-kappaB have been implicated in severe neuronal damage in different sub-regions of the hippocampus as well as in the surrounding cortices. The effect of PDTC on status epilepticus-associated cell loss in the hippocampus and piriform cortex was evaluated in the rat fractionated pilocarpine model. Treatment with 150 mg/kg PDTC before and following status epilepticus significantly increased the mortality rate to 100%. Administration of 50 mg/kg PDTC (low-dose) did not exert major effects on the development of a status epilepticus or the mortality rate. In vehicle-treated rats, status epilepticus caused pronounced neuronal damage in the piriform cortex comprising both pyramidal cells and interneurons. Low-dose PDTC treatment almost completely protected from lesions in the piriform cortex. A significant decrease in neuronal density of the hippocampal hilar formation was identified in vehicle- and PDTC-treated rats following status epilepticus. In conclusion, the NF-kappaB inhibitor and antioxidant PDTC protected the piriform cortex, whereas it did not affect hilar neuronal loss. These data might indicate that the generation of reactive oxygen species and activation of NF-kappaB plays a more central role in seizure-associated neuronal damage in the temporal cortex as compared to the hippocampal hilus. However, future investigations are necessary to exactly analyze the biochemical mechanisms by which PDTC exerted its beneficial effects in the piriform cortex.", "entity": "Status Epilepticus", "aliases": "Absence Status Complex Partial Epilepticus Electrographic Generalized Convulsive Grand Mal Non Non-Convulsive Petit Simple Subclinical", "definition": "A prolonged seizure or seizures repeated frequently enough to prevent recovery between episodes occurring over a period of 20-30 minutes. The most common subtype is generalized tonic-clonic status epilepticus, a potentially fatal condition associated with neuronal injury and respiratory and metabolic dysfunction. Nonconvulsive forms include petit mal status and complex partial status, which may manifest as behavioral disturbances. Simple partial status epilepticus consists of persistent motor, sensory, or autonomic seizures that do not impair cognition (see also EPILEPSIA PARTIALIS CONTINUA). Subclinical status epilepticus generally refers to seizures occurring in an unresponsive or comatose individual in the absence of overt signs of seizure activity. (From N Engl J Med 1998 Apr 2;338(14):970-6; Neurologia 1997 Dec;12 Suppl 6:25-30)\n    ", "id": "MESH:D013226"}
{"mention": "pilocarpine", "mention_text": "Pyrrolidine dithiocarbamate (PDTC) has a dual mechanism of action as an antioxidant and an inhibitor of the transcription factor kappa-beta. Both, production of reactive oxygen species as well as activation of NF-kappaB have been implicated in severe neuronal damage in different sub-regions of the hippocampus as well as in the surrounding cortices. The effect of PDTC on status epilepticus-associated cell loss in the hippocampus and piriform cortex was evaluated in the rat fractionated pilocarpine model. Treatment with 150 mg/kg PDTC before and following status epilepticus significantly increased the mortality rate to 100%. Administration of 50 mg/kg PDTC (low-dose) did not exert major effects on the development of a status epilepticus or the mortality rate. In vehicle-treated rats, status epilepticus caused pronounced neuronal damage in the piriform cortex comprising both pyramidal cells and interneurons. Low-dose PDTC treatment almost completely protected from lesions in the piriform cortex. A significant decrease in neuronal density of the hippocampal hilar formation was identified in vehicle- and PDTC-treated rats following status epilepticus. In conclusion, the NF-kappaB inhibitor and antioxidant PDTC protected the piriform cortex, whereas it did not affect hilar neuronal loss. These data might indicate that the generation of reactive oxygen species and activation of NF-kappaB plays a more central role in seizure-associated neuronal damage in the temporal cortex as compared to the hippocampal hilus. However, future investigations are necessary to exactly analyze the biochemical mechanisms by which PDTC exerted its beneficial effects in the piriform cortex.", "entity": "Pilocarpine", "aliases": "Hydrochloride Pilocarpine Isopilocarpine Isoptocarpine Nitrate Ocusert Mononitrate (3S-cis)-Isomer Monohydrochloride Salagen", "definition": "A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Pilocarpine is used as a miotic and in the treatment of glaucoma.\n    ", "id": "MESH:D010862"}
{"mention": "neuronal loss", "mention_text": "Pyrrolidine dithiocarbamate (PDTC) has a dual mechanism of action as an antioxidant and an inhibitor of the transcription factor kappa-beta. Both, production of reactive oxygen species as well as activation of NF-kappaB have been implicated in severe neuronal damage in different sub-regions of the hippocampus as well as in the surrounding cortices. The effect of PDTC on status epilepticus-associated cell loss in the hippocampus and piriform cortex was evaluated in the rat fractionated pilocarpine model. Treatment with 150 mg/kg PDTC before and following status epilepticus significantly increased the mortality rate to 100%. Administration of 50 mg/kg PDTC (low-dose) did not exert major effects on the development of a status epilepticus or the mortality rate. In vehicle-treated rats, status epilepticus caused pronounced neuronal damage in the piriform cortex comprising both pyramidal cells and interneurons. Low-dose PDTC treatment almost completely protected from lesions in the piriform cortex. A significant decrease in neuronal density of the hippocampal hilar formation was identified in vehicle- and PDTC-treated rats following status epilepticus. In conclusion, the NF-kappaB inhibitor and antioxidant PDTC protected the piriform cortex, whereas it did not affect hilar neuronal loss. These data might indicate that the generation of reactive oxygen species and activation of NF-kappaB plays a more central role in seizure-associated neuronal damage in the temporal cortex as compared to the hippocampal hilus. However, future investigations are necessary to exactly analyze the biochemical mechanisms by which PDTC exerted its beneficial effects in the piriform cortex.", "entity": "Nerve Degeneration", "aliases": "Degeneration Nerve Neuron Degenerations", "definition": "Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.\n    ", "id": "MESH:D009410"}
{"mention": "seizure", "mention_text": "Pyrrolidine dithiocarbamate (PDTC) has a dual mechanism of action as an antioxidant and an inhibitor of the transcription factor kappa-beta. Both, production of reactive oxygen species as well as activation of NF-kappaB have been implicated in severe neuronal damage in different sub-regions of the hippocampus as well as in the surrounding cortices. The effect of PDTC on status epilepticus-associated cell loss in the hippocampus and piriform cortex was evaluated in the rat fractionated pilocarpine model. Treatment with 150 mg/kg PDTC before and following status epilepticus significantly increased the mortality rate to 100%. Administration of 50 mg/kg PDTC (low-dose) did not exert major effects on the development of a status epilepticus or the mortality rate. In vehicle-treated rats, status epilepticus caused pronounced neuronal damage in the piriform cortex comprising both pyramidal cells and interneurons. Low-dose PDTC treatment almost completely protected from lesions in the piriform cortex. A significant decrease in neuronal density of the hippocampal hilar formation was identified in vehicle- and PDTC-treated rats following status epilepticus. In conclusion, the NF-kappaB inhibitor and antioxidant PDTC protected the piriform cortex, whereas it did not affect hilar neuronal loss. These data might indicate that the generation of reactive oxygen species and activation of NF-kappaB plays a more central role in seizure-associated neuronal damage in the temporal cortex as compared to the hippocampal hilus. However, future investigations are necessary to exactly analyze the biochemical mechanisms by which PDTC exerted its beneficial effects in the piriform cortex.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "nicotine", "mention_text": "Safety profile of a nicotine lozenge compared with that of nicotine gum in adult smokers with underlying medical conditions: a 12-week, randomized, open-label study.", "entity": "Nicotine", "aliases": "Bitartrate Nicotine Tartrate", "definition": "Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.\n    ", "id": "MESH:D009538"}
{"mention": "Nicotine", "mention_text": "BACKGROUND: Nicotine polacrilex lozenges deliver 25% to 27% more nicotine compared with equivalent doses of nicotine polacrilex gum. The increased nicotine exposure from the lozenge has raised questions about the relative safety of the lozenge and gum. OBJECTIVE: The objective of this study was to compare the safety profiles of the 4-mg nicotine lozenge and 4-mg nicotine gum in smokers with selected label-restricted diseases. METHODS: This was a multicenter, randomized, open-label study in adult smokers with heart disease, hypertension not controlled by medication, and/or diabetes mellitus. Patients were randomized in a 1:1 ratio to receive the 4-mg nicotine lozenge or 4-mg nicotine gum. Safety assessments were made at baseline and at 2, 4, 6, and 12 weeks after the start of product use. RESULTS: Nine hundred one patients were randomized to treatment, 447 who received the lozenge and 454 who received the gum (safety population). The majority were women (52.7%). Patients' mean age was 53.9 years, their mean weight was 193.9 pounds, and they smoked a mean of 25.2 cigarettes per day at baseline. Five hundred fifty-three patients, 264 taking the lozenge and 289 taking the gum, used the study product for > or =4 days per week during the first 2 weeks (evaluable population). The nicotine lozenge and nicotine gum were equally well tolerated, despite increased nicotine exposure from the lozenge. The incidence of adverse events in the 2 groups was similar during the first 2 weeks of product use (evaluation population: 55.3% lozenge, 54.7% gum), as well as during the entire study (safety population: 63.8% and 58.6%, respectively). Stratification of patients by sex, age, extent of concurrent smoking, extent of product use, and severity of adverse events revealed no clinically significant differences between the lozenge and gum. The most common adverse events were nausea (17.2% and 16.1%; 95% CI, -3.7 to 6.0), hiccups (10.7% and 6.6%; 95% CI, 0.5 to 7.8), and headache (8.7% and 9.9%; 95% Cl, -5.0 to 2.6). Serious adverse events were reported in 11 and 13 patients in the respective groups. Fewer than 6% of patients in either group were considered by the investigator to have a worsening of their overall disease condition during the study. The majority of patients (>60%) experienced no change in their disease status from baseline. CONCLUSION: The 4-mg nicotine lozenge and 4-mg nicotine gum had comparable safety profiles in these patients with label-restricted medical conditions.", "entity": "Nicotine", "aliases": "Bitartrate Nicotine Tartrate", "definition": "Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.\n    ", "id": "MESH:D009538"}
{"mention": "nicotine", "mention_text": "BACKGROUND: Nicotine polacrilex lozenges deliver 25% to 27% more nicotine compared with equivalent doses of nicotine polacrilex gum. The increased nicotine exposure from the lozenge has raised questions about the relative safety of the lozenge and gum. OBJECTIVE: The objective of this study was to compare the safety profiles of the 4-mg nicotine lozenge and 4-mg nicotine gum in smokers with selected label-restricted diseases. METHODS: This was a multicenter, randomized, open-label study in adult smokers with heart disease, hypertension not controlled by medication, and/or diabetes mellitus. Patients were randomized in a 1:1 ratio to receive the 4-mg nicotine lozenge or 4-mg nicotine gum. Safety assessments were made at baseline and at 2, 4, 6, and 12 weeks after the start of product use. RESULTS: Nine hundred one patients were randomized to treatment, 447 who received the lozenge and 454 who received the gum (safety population). The majority were women (52.7%). Patients' mean age was 53.9 years, their mean weight was 193.9 pounds, and they smoked a mean of 25.2 cigarettes per day at baseline. Five hundred fifty-three patients, 264 taking the lozenge and 289 taking the gum, used the study product for > or =4 days per week during the first 2 weeks (evaluable population). The nicotine lozenge and nicotine gum were equally well tolerated, despite increased nicotine exposure from the lozenge. The incidence of adverse events in the 2 groups was similar during the first 2 weeks of product use (evaluation population: 55.3% lozenge, 54.7% gum), as well as during the entire study (safety population: 63.8% and 58.6%, respectively). Stratification of patients by sex, age, extent of concurrent smoking, extent of product use, and severity of adverse events revealed no clinically significant differences between the lozenge and gum. The most common adverse events were nausea (17.2% and 16.1%; 95% CI, -3.7 to 6.0), hiccups (10.7% and 6.6%; 95% CI, 0.5 to 7.8), and headache (8.7% and 9.9%; 95% Cl, -5.0 to 2.6). Serious adverse events were reported in 11 and 13 patients in the respective groups. Fewer than 6% of patients in either group were considered by the investigator to have a worsening of their overall disease condition during the study. The majority of patients (>60%) experienced no change in their disease status from baseline. CONCLUSION: The 4-mg nicotine lozenge and 4-mg nicotine gum had comparable safety profiles in these patients with label-restricted medical conditions.", "entity": "Nicotine", "aliases": "Bitartrate Nicotine Tartrate", "definition": "Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.\n    ", "id": "MESH:D009538"}
{"mention": "heart disease", "mention_text": "BACKGROUND: Nicotine polacrilex lozenges deliver 25% to 27% more nicotine compared with equivalent doses of nicotine polacrilex gum. The increased nicotine exposure from the lozenge has raised questions about the relative safety of the lozenge and gum. OBJECTIVE: The objective of this study was to compare the safety profiles of the 4-mg nicotine lozenge and 4-mg nicotine gum in smokers with selected label-restricted diseases. METHODS: This was a multicenter, randomized, open-label study in adult smokers with heart disease, hypertension not controlled by medication, and/or diabetes mellitus. Patients were randomized in a 1:1 ratio to receive the 4-mg nicotine lozenge or 4-mg nicotine gum. Safety assessments were made at baseline and at 2, 4, 6, and 12 weeks after the start of product use. RESULTS: Nine hundred one patients were randomized to treatment, 447 who received the lozenge and 454 who received the gum (safety population). The majority were women (52.7%). Patients' mean age was 53.9 years, their mean weight was 193.9 pounds, and they smoked a mean of 25.2 cigarettes per day at baseline. Five hundred fifty-three patients, 264 taking the lozenge and 289 taking the gum, used the study product for > or =4 days per week during the first 2 weeks (evaluable population). The nicotine lozenge and nicotine gum were equally well tolerated, despite increased nicotine exposure from the lozenge. The incidence of adverse events in the 2 groups was similar during the first 2 weeks of product use (evaluation population: 55.3% lozenge, 54.7% gum), as well as during the entire study (safety population: 63.8% and 58.6%, respectively). Stratification of patients by sex, age, extent of concurrent smoking, extent of product use, and severity of adverse events revealed no clinically significant differences between the lozenge and gum. The most common adverse events were nausea (17.2% and 16.1%; 95% CI, -3.7 to 6.0), hiccups (10.7% and 6.6%; 95% CI, 0.5 to 7.8), and headache (8.7% and 9.9%; 95% Cl, -5.0 to 2.6). Serious adverse events were reported in 11 and 13 patients in the respective groups. Fewer than 6% of patients in either group were considered by the investigator to have a worsening of their overall disease condition during the study. The majority of patients (>60%) experienced no change in their disease status from baseline. CONCLUSION: The 4-mg nicotine lozenge and 4-mg nicotine gum had comparable safety profiles in these patients with label-restricted medical conditions.", "entity": "Heart Diseases", "aliases": "Cardiac Disease Diseases Heart", "definition": "Pathological conditions involving the HEART including its structural and functional abnormalities.\n    ", "id": "MESH:D006331"}
{"mention": "hypertension", "mention_text": "BACKGROUND: Nicotine polacrilex lozenges deliver 25% to 27% more nicotine compared with equivalent doses of nicotine polacrilex gum. The increased nicotine exposure from the lozenge has raised questions about the relative safety of the lozenge and gum. OBJECTIVE: The objective of this study was to compare the safety profiles of the 4-mg nicotine lozenge and 4-mg nicotine gum in smokers with selected label-restricted diseases. METHODS: This was a multicenter, randomized, open-label study in adult smokers with heart disease, hypertension not controlled by medication, and/or diabetes mellitus. Patients were randomized in a 1:1 ratio to receive the 4-mg nicotine lozenge or 4-mg nicotine gum. Safety assessments were made at baseline and at 2, 4, 6, and 12 weeks after the start of product use. RESULTS: Nine hundred one patients were randomized to treatment, 447 who received the lozenge and 454 who received the gum (safety population). The majority were women (52.7%). Patients' mean age was 53.9 years, their mean weight was 193.9 pounds, and they smoked a mean of 25.2 cigarettes per day at baseline. Five hundred fifty-three patients, 264 taking the lozenge and 289 taking the gum, used the study product for > or =4 days per week during the first 2 weeks (evaluable population). The nicotine lozenge and nicotine gum were equally well tolerated, despite increased nicotine exposure from the lozenge. The incidence of adverse events in the 2 groups was similar during the first 2 weeks of product use (evaluation population: 55.3% lozenge, 54.7% gum), as well as during the entire study (safety population: 63.8% and 58.6%, respectively). Stratification of patients by sex, age, extent of concurrent smoking, extent of product use, and severity of adverse events revealed no clinically significant differences between the lozenge and gum. The most common adverse events were nausea (17.2% and 16.1%; 95% CI, -3.7 to 6.0), hiccups (10.7% and 6.6%; 95% CI, 0.5 to 7.8), and headache (8.7% and 9.9%; 95% Cl, -5.0 to 2.6). Serious adverse events were reported in 11 and 13 patients in the respective groups. Fewer than 6% of patients in either group were considered by the investigator to have a worsening of their overall disease condition during the study. The majority of patients (>60%) experienced no change in their disease status from baseline. CONCLUSION: The 4-mg nicotine lozenge and 4-mg nicotine gum had comparable safety profiles in these patients with label-restricted medical conditions.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "diabetes mellitus", "mention_text": "BACKGROUND: Nicotine polacrilex lozenges deliver 25% to 27% more nicotine compared with equivalent doses of nicotine polacrilex gum. The increased nicotine exposure from the lozenge has raised questions about the relative safety of the lozenge and gum. OBJECTIVE: The objective of this study was to compare the safety profiles of the 4-mg nicotine lozenge and 4-mg nicotine gum in smokers with selected label-restricted diseases. METHODS: This was a multicenter, randomized, open-label study in adult smokers with heart disease, hypertension not controlled by medication, and/or diabetes mellitus. Patients were randomized in a 1:1 ratio to receive the 4-mg nicotine lozenge or 4-mg nicotine gum. Safety assessments were made at baseline and at 2, 4, 6, and 12 weeks after the start of product use. RESULTS: Nine hundred one patients were randomized to treatment, 447 who received the lozenge and 454 who received the gum (safety population). The majority were women (52.7%). Patients' mean age was 53.9 years, their mean weight was 193.9 pounds, and they smoked a mean of 25.2 cigarettes per day at baseline. Five hundred fifty-three patients, 264 taking the lozenge and 289 taking the gum, used the study product for > or =4 days per week during the first 2 weeks (evaluable population). The nicotine lozenge and nicotine gum were equally well tolerated, despite increased nicotine exposure from the lozenge. The incidence of adverse events in the 2 groups was similar during the first 2 weeks of product use (evaluation population: 55.3% lozenge, 54.7% gum), as well as during the entire study (safety population: 63.8% and 58.6%, respectively). Stratification of patients by sex, age, extent of concurrent smoking, extent of product use, and severity of adverse events revealed no clinically significant differences between the lozenge and gum. The most common adverse events were nausea (17.2% and 16.1%; 95% CI, -3.7 to 6.0), hiccups (10.7% and 6.6%; 95% CI, 0.5 to 7.8), and headache (8.7% and 9.9%; 95% Cl, -5.0 to 2.6). Serious adverse events were reported in 11 and 13 patients in the respective groups. Fewer than 6% of patients in either group were considered by the investigator to have a worsening of their overall disease condition during the study. The majority of patients (>60%) experienced no change in their disease status from baseline. CONCLUSION: The 4-mg nicotine lozenge and 4-mg nicotine gum had comparable safety profiles in these patients with label-restricted medical conditions.", "entity": "Diabetes Mellitus", "aliases": "Diabetes Mellitus", "definition": "A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.\n    ", "id": "MESH:D003920"}
{"mention": "nausea", "mention_text": "BACKGROUND: Nicotine polacrilex lozenges deliver 25% to 27% more nicotine compared with equivalent doses of nicotine polacrilex gum. The increased nicotine exposure from the lozenge has raised questions about the relative safety of the lozenge and gum. OBJECTIVE: The objective of this study was to compare the safety profiles of the 4-mg nicotine lozenge and 4-mg nicotine gum in smokers with selected label-restricted diseases. METHODS: This was a multicenter, randomized, open-label study in adult smokers with heart disease, hypertension not controlled by medication, and/or diabetes mellitus. Patients were randomized in a 1:1 ratio to receive the 4-mg nicotine lozenge or 4-mg nicotine gum. Safety assessments were made at baseline and at 2, 4, 6, and 12 weeks after the start of product use. RESULTS: Nine hundred one patients were randomized to treatment, 447 who received the lozenge and 454 who received the gum (safety population). The majority were women (52.7%). Patients' mean age was 53.9 years, their mean weight was 193.9 pounds, and they smoked a mean of 25.2 cigarettes per day at baseline. Five hundred fifty-three patients, 264 taking the lozenge and 289 taking the gum, used the study product for > or =4 days per week during the first 2 weeks (evaluable population). The nicotine lozenge and nicotine gum were equally well tolerated, despite increased nicotine exposure from the lozenge. The incidence of adverse events in the 2 groups was similar during the first 2 weeks of product use (evaluation population: 55.3% lozenge, 54.7% gum), as well as during the entire study (safety population: 63.8% and 58.6%, respectively). Stratification of patients by sex, age, extent of concurrent smoking, extent of product use, and severity of adverse events revealed no clinically significant differences between the lozenge and gum. The most common adverse events were nausea (17.2% and 16.1%; 95% CI, -3.7 to 6.0), hiccups (10.7% and 6.6%; 95% CI, 0.5 to 7.8), and headache (8.7% and 9.9%; 95% Cl, -5.0 to 2.6). Serious adverse events were reported in 11 and 13 patients in the respective groups. Fewer than 6% of patients in either group were considered by the investigator to have a worsening of their overall disease condition during the study. The majority of patients (>60%) experienced no change in their disease status from baseline. CONCLUSION: The 4-mg nicotine lozenge and 4-mg nicotine gum had comparable safety profiles in these patients with label-restricted medical conditions.", "entity": "Nausea", "aliases": "Nausea", "definition": "An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.\n    ", "id": "MESH:D009325"}
{"mention": "hiccups", "mention_text": "BACKGROUND: Nicotine polacrilex lozenges deliver 25% to 27% more nicotine compared with equivalent doses of nicotine polacrilex gum. The increased nicotine exposure from the lozenge has raised questions about the relative safety of the lozenge and gum. OBJECTIVE: The objective of this study was to compare the safety profiles of the 4-mg nicotine lozenge and 4-mg nicotine gum in smokers with selected label-restricted diseases. METHODS: This was a multicenter, randomized, open-label study in adult smokers with heart disease, hypertension not controlled by medication, and/or diabetes mellitus. Patients were randomized in a 1:1 ratio to receive the 4-mg nicotine lozenge or 4-mg nicotine gum. Safety assessments were made at baseline and at 2, 4, 6, and 12 weeks after the start of product use. RESULTS: Nine hundred one patients were randomized to treatment, 447 who received the lozenge and 454 who received the gum (safety population). The majority were women (52.7%). Patients' mean age was 53.9 years, their mean weight was 193.9 pounds, and they smoked a mean of 25.2 cigarettes per day at baseline. Five hundred fifty-three patients, 264 taking the lozenge and 289 taking the gum, used the study product for > or =4 days per week during the first 2 weeks (evaluable population). The nicotine lozenge and nicotine gum were equally well tolerated, despite increased nicotine exposure from the lozenge. The incidence of adverse events in the 2 groups was similar during the first 2 weeks of product use (evaluation population: 55.3% lozenge, 54.7% gum), as well as during the entire study (safety population: 63.8% and 58.6%, respectively). Stratification of patients by sex, age, extent of concurrent smoking, extent of product use, and severity of adverse events revealed no clinically significant differences between the lozenge and gum. The most common adverse events were nausea (17.2% and 16.1%; 95% CI, -3.7 to 6.0), hiccups (10.7% and 6.6%; 95% CI, 0.5 to 7.8), and headache (8.7% and 9.9%; 95% Cl, -5.0 to 2.6). Serious adverse events were reported in 11 and 13 patients in the respective groups. Fewer than 6% of patients in either group were considered by the investigator to have a worsening of their overall disease condition during the study. The majority of patients (>60%) experienced no change in their disease status from baseline. CONCLUSION: The 4-mg nicotine lozenge and 4-mg nicotine gum had comparable safety profiles in these patients with label-restricted medical conditions.", "entity": "Hiccup", "aliases": "Hiccough Hiccoughs Hiccup Hiccups", "definition": "A spasm of the diaphragm that causes a sudden inhalation followed by rapid closure of the glottis which produces a sound.\n    ", "id": "MESH:D006606"}
{"mention": "headache", "mention_text": "BACKGROUND: Nicotine polacrilex lozenges deliver 25% to 27% more nicotine compared with equivalent doses of nicotine polacrilex gum. The increased nicotine exposure from the lozenge has raised questions about the relative safety of the lozenge and gum. OBJECTIVE: The objective of this study was to compare the safety profiles of the 4-mg nicotine lozenge and 4-mg nicotine gum in smokers with selected label-restricted diseases. METHODS: This was a multicenter, randomized, open-label study in adult smokers with heart disease, hypertension not controlled by medication, and/or diabetes mellitus. Patients were randomized in a 1:1 ratio to receive the 4-mg nicotine lozenge or 4-mg nicotine gum. Safety assessments were made at baseline and at 2, 4, 6, and 12 weeks after the start of product use. RESULTS: Nine hundred one patients were randomized to treatment, 447 who received the lozenge and 454 who received the gum (safety population). The majority were women (52.7%). Patients' mean age was 53.9 years, their mean weight was 193.9 pounds, and they smoked a mean of 25.2 cigarettes per day at baseline. Five hundred fifty-three patients, 264 taking the lozenge and 289 taking the gum, used the study product for > or =4 days per week during the first 2 weeks (evaluable population). The nicotine lozenge and nicotine gum were equally well tolerated, despite increased nicotine exposure from the lozenge. The incidence of adverse events in the 2 groups was similar during the first 2 weeks of product use (evaluation population: 55.3% lozenge, 54.7% gum), as well as during the entire study (safety population: 63.8% and 58.6%, respectively). Stratification of patients by sex, age, extent of concurrent smoking, extent of product use, and severity of adverse events revealed no clinically significant differences between the lozenge and gum. The most common adverse events were nausea (17.2% and 16.1%; 95% CI, -3.7 to 6.0), hiccups (10.7% and 6.6%; 95% CI, 0.5 to 7.8), and headache (8.7% and 9.9%; 95% Cl, -5.0 to 2.6). Serious adverse events were reported in 11 and 13 patients in the respective groups. Fewer than 6% of patients in either group were considered by the investigator to have a worsening of their overall disease condition during the study. The majority of patients (>60%) experienced no change in their disease status from baseline. CONCLUSION: The 4-mg nicotine lozenge and 4-mg nicotine gum had comparable safety profiles in these patients with label-restricted medical conditions.", "entity": "Headache", "aliases": "Bilateral Headache Headaches Cephalalgia Cephalalgias Cephalgia Cephalgias Cephalodynia Cephalodynias Cranial Pain Pains Generalized Head Ocular Orthostatic Periorbital Retro-Ocular Sharp Throbbing Unilateral Vertex Hemicrania Retro", "definition": "The symptom of PAIN in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of HEADACHE DISORDERS.\n    ", "id": "MESH:D006261"}
{"mention": "levodopa", "mention_text": "Development of levodopa-induced dyskinesias in parkinsonian monkeys may depend upon rate of symptom onset and/or duration of symptoms.", "entity": "Levodopa", "aliases": "3 Hydroxy L tyrosine 3-Hydroxy-L-tyrosine Dopaflex Dopar 3,4 Dihydroxyphenylalanine Dopa L-3,4-Dihydroxyphenylalanine L-Dopa Larodopa Levodopa Levopa Medphano Brand of Roberts Roche", "definition": "The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.\n    ", "id": "MESH:D007980"}
{"mention": "dyskinesias", "mention_text": "Development of levodopa-induced dyskinesias in parkinsonian monkeys may depend upon rate of symptom onset and/or duration of symptoms.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "parkinsonian", "mention_text": "Development of levodopa-induced dyskinesias in parkinsonian monkeys may depend upon rate of symptom onset and/or duration of symptoms.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "Levodopa", "mention_text": "Levodopa-induced dyskinesias (LIDs) present a major problem for the long-term management of Parkinson's disease (PD) patients. Due to the interdependence of risk factors in clinical populations, it is difficult to independently examine factors that may influence the development of LIDs. Using macaque monkeys with different types of MPTP-induced parkinsonism, the current study evaluated the degree to which rate of symptom progression, symptom severity, and response to and duration of levodopa therapy may be involved in the development of LIDs. Monkeys with acute (short-term) MPTP exposure, rapid symptom onset and short symptom duration prior to initiation of levodopa therapy developed dyskinesia between 11 and 24 days of daily levodopa administration. In contrast, monkeys with long-term MPTP exposure, slow symptom progression and/or long symptom duration prior to initiation of levodopa therapy were more resistant to developing LIDs (e.g., dyskinesia developed no sooner than 146 days of chronic levodopa administration). All animals were similarly symptomatic at the start of levodopa treatment and had similar therapeutic responses to the drug. These data suggest distinct differences in the propensity to develop LIDs in monkeys with different rates of symptom progression or symptom durations prior to levodopa and demonstrate the value of these models for further studying the pathophysiology of LIDs.", "entity": "Levodopa", "aliases": "3 Hydroxy L tyrosine 3-Hydroxy-L-tyrosine Dopaflex Dopar 3,4 Dihydroxyphenylalanine Dopa L-3,4-Dihydroxyphenylalanine L-Dopa Larodopa Levodopa Levopa Medphano Brand of Roberts Roche", "definition": "The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.\n    ", "id": "MESH:D007980"}
{"mention": "dyskinesias", "mention_text": "Levodopa-induced dyskinesias (LIDs) present a major problem for the long-term management of Parkinson's disease (PD) patients. Due to the interdependence of risk factors in clinical populations, it is difficult to independently examine factors that may influence the development of LIDs. Using macaque monkeys with different types of MPTP-induced parkinsonism, the current study evaluated the degree to which rate of symptom progression, symptom severity, and response to and duration of levodopa therapy may be involved in the development of LIDs. Monkeys with acute (short-term) MPTP exposure, rapid symptom onset and short symptom duration prior to initiation of levodopa therapy developed dyskinesia between 11 and 24 days of daily levodopa administration. In contrast, monkeys with long-term MPTP exposure, slow symptom progression and/or long symptom duration prior to initiation of levodopa therapy were more resistant to developing LIDs (e.g., dyskinesia developed no sooner than 146 days of chronic levodopa administration). All animals were similarly symptomatic at the start of levodopa treatment and had similar therapeutic responses to the drug. These data suggest distinct differences in the propensity to develop LIDs in monkeys with different rates of symptom progression or symptom durations prior to levodopa and demonstrate the value of these models for further studying the pathophysiology of LIDs.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "LIDs", "mention_text": "Levodopa-induced dyskinesias (LIDs) present a major problem for the long-term management of Parkinson's disease (PD) patients. Due to the interdependence of risk factors in clinical populations, it is difficult to independently examine factors that may influence the development of LIDs. Using macaque monkeys with different types of MPTP-induced parkinsonism, the current study evaluated the degree to which rate of symptom progression, symptom severity, and response to and duration of levodopa therapy may be involved in the development of LIDs. Monkeys with acute (short-term) MPTP exposure, rapid symptom onset and short symptom duration prior to initiation of levodopa therapy developed dyskinesia between 11 and 24 days of daily levodopa administration. In contrast, monkeys with long-term MPTP exposure, slow symptom progression and/or long symptom duration prior to initiation of levodopa therapy were more resistant to developing LIDs (e.g., dyskinesia developed no sooner than 146 days of chronic levodopa administration). All animals were similarly symptomatic at the start of levodopa treatment and had similar therapeutic responses to the drug. These data suggest distinct differences in the propensity to develop LIDs in monkeys with different rates of symptom progression or symptom durations prior to levodopa and demonstrate the value of these models for further studying the pathophysiology of LIDs.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "Parkinson's disease", "mention_text": "Levodopa-induced dyskinesias (LIDs) present a major problem for the long-term management of Parkinson's disease (PD) patients. Due to the interdependence of risk factors in clinical populations, it is difficult to independently examine factors that may influence the development of LIDs. Using macaque monkeys with different types of MPTP-induced parkinsonism, the current study evaluated the degree to which rate of symptom progression, symptom severity, and response to and duration of levodopa therapy may be involved in the development of LIDs. Monkeys with acute (short-term) MPTP exposure, rapid symptom onset and short symptom duration prior to initiation of levodopa therapy developed dyskinesia between 11 and 24 days of daily levodopa administration. In contrast, monkeys with long-term MPTP exposure, slow symptom progression and/or long symptom duration prior to initiation of levodopa therapy were more resistant to developing LIDs (e.g., dyskinesia developed no sooner than 146 days of chronic levodopa administration). All animals were similarly symptomatic at the start of levodopa treatment and had similar therapeutic responses to the drug. These data suggest distinct differences in the propensity to develop LIDs in monkeys with different rates of symptom progression or symptom durations prior to levodopa and demonstrate the value of these models for further studying the pathophysiology of LIDs.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "PD", "mention_text": "Levodopa-induced dyskinesias (LIDs) present a major problem for the long-term management of Parkinson's disease (PD) patients. Due to the interdependence of risk factors in clinical populations, it is difficult to independently examine factors that may influence the development of LIDs. Using macaque monkeys with different types of MPTP-induced parkinsonism, the current study evaluated the degree to which rate of symptom progression, symptom severity, and response to and duration of levodopa therapy may be involved in the development of LIDs. Monkeys with acute (short-term) MPTP exposure, rapid symptom onset and short symptom duration prior to initiation of levodopa therapy developed dyskinesia between 11 and 24 days of daily levodopa administration. In contrast, monkeys with long-term MPTP exposure, slow symptom progression and/or long symptom duration prior to initiation of levodopa therapy were more resistant to developing LIDs (e.g., dyskinesia developed no sooner than 146 days of chronic levodopa administration). All animals were similarly symptomatic at the start of levodopa treatment and had similar therapeutic responses to the drug. These data suggest distinct differences in the propensity to develop LIDs in monkeys with different rates of symptom progression or symptom durations prior to levodopa and demonstrate the value of these models for further studying the pathophysiology of LIDs.", "entity": "Parkinson Disease", "aliases": "Idiopathic Parkinson Disease Parkinson's Lewy Body Paralysis Agitans Parkinsonism Primary", "definition": "A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)\n    ", "id": "MESH:D010300"}
{"mention": "MPTP", "mention_text": "Levodopa-induced dyskinesias (LIDs) present a major problem for the long-term management of Parkinson's disease (PD) patients. Due to the interdependence of risk factors in clinical populations, it is difficult to independently examine factors that may influence the development of LIDs. Using macaque monkeys with different types of MPTP-induced parkinsonism, the current study evaluated the degree to which rate of symptom progression, symptom severity, and response to and duration of levodopa therapy may be involved in the development of LIDs. Monkeys with acute (short-term) MPTP exposure, rapid symptom onset and short symptom duration prior to initiation of levodopa therapy developed dyskinesia between 11 and 24 days of daily levodopa administration. In contrast, monkeys with long-term MPTP exposure, slow symptom progression and/or long symptom duration prior to initiation of levodopa therapy were more resistant to developing LIDs (e.g., dyskinesia developed no sooner than 146 days of chronic levodopa administration). All animals were similarly symptomatic at the start of levodopa treatment and had similar therapeutic responses to the drug. These data suggest distinct differences in the propensity to develop LIDs in monkeys with different rates of symptom progression or symptom durations prior to levodopa and demonstrate the value of these models for further studying the pathophysiology of LIDs.", "entity": "1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine", "aliases": "1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine MPTP N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine", "definition": "A dopaminergic neurotoxic compound which produces irreversible clinical, chemical, and pathological alterations that mimic those found in Parkinson disease.\n    ", "id": "MESH:D015632"}
{"mention": "parkinsonism", "mention_text": "Levodopa-induced dyskinesias (LIDs) present a major problem for the long-term management of Parkinson's disease (PD) patients. Due to the interdependence of risk factors in clinical populations, it is difficult to independently examine factors that may influence the development of LIDs. Using macaque monkeys with different types of MPTP-induced parkinsonism, the current study evaluated the degree to which rate of symptom progression, symptom severity, and response to and duration of levodopa therapy may be involved in the development of LIDs. Monkeys with acute (short-term) MPTP exposure, rapid symptom onset and short symptom duration prior to initiation of levodopa therapy developed dyskinesia between 11 and 24 days of daily levodopa administration. In contrast, monkeys with long-term MPTP exposure, slow symptom progression and/or long symptom duration prior to initiation of levodopa therapy were more resistant to developing LIDs (e.g., dyskinesia developed no sooner than 146 days of chronic levodopa administration). All animals were similarly symptomatic at the start of levodopa treatment and had similar therapeutic responses to the drug. These data suggest distinct differences in the propensity to develop LIDs in monkeys with different rates of symptom progression or symptom durations prior to levodopa and demonstrate the value of these models for further studying the pathophysiology of LIDs.", "entity": "Parkinson Disease, Secondary", "aliases": "Atherosclerotic Parkinsonism Parkinson Disease Secondary Vascular Symptomatic", "definition": "Conditions which feature clinical manifestations resembling primary Parkinson disease that are caused by a known or suspected condition. Examples include parkinsonism caused by vascular injury, drugs, trauma, toxin exposure, neoplasms, infections and degenerative or hereditary conditions. Clinical features may include bradykinesia, rigidity, parkinsonian gait, and masked facies. In general, tremor is less prominent in secondary parkinsonism than in the primary form. (From Joynt, Clinical Neurology, 1998, Ch38, pp39-42)\n    ", "id": "MESH:D010302"}
{"mention": "levodopa", "mention_text": "Levodopa-induced dyskinesias (LIDs) present a major problem for the long-term management of Parkinson's disease (PD) patients. Due to the interdependence of risk factors in clinical populations, it is difficult to independently examine factors that may influence the development of LIDs. Using macaque monkeys with different types of MPTP-induced parkinsonism, the current study evaluated the degree to which rate of symptom progression, symptom severity, and response to and duration of levodopa therapy may be involved in the development of LIDs. Monkeys with acute (short-term) MPTP exposure, rapid symptom onset and short symptom duration prior to initiation of levodopa therapy developed dyskinesia between 11 and 24 days of daily levodopa administration. In contrast, monkeys with long-term MPTP exposure, slow symptom progression and/or long symptom duration prior to initiation of levodopa therapy were more resistant to developing LIDs (e.g., dyskinesia developed no sooner than 146 days of chronic levodopa administration). All animals were similarly symptomatic at the start of levodopa treatment and had similar therapeutic responses to the drug. These data suggest distinct differences in the propensity to develop LIDs in monkeys with different rates of symptom progression or symptom durations prior to levodopa and demonstrate the value of these models for further studying the pathophysiology of LIDs.", "entity": "Levodopa", "aliases": "3 Hydroxy L tyrosine 3-Hydroxy-L-tyrosine Dopaflex Dopar 3,4 Dihydroxyphenylalanine Dopa L-3,4-Dihydroxyphenylalanine L-Dopa Larodopa Levodopa Levopa Medphano Brand of Roberts Roche", "definition": "The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.\n    ", "id": "MESH:D007980"}
{"mention": "dyskinesia", "mention_text": "Levodopa-induced dyskinesias (LIDs) present a major problem for the long-term management of Parkinson's disease (PD) patients. Due to the interdependence of risk factors in clinical populations, it is difficult to independently examine factors that may influence the development of LIDs. Using macaque monkeys with different types of MPTP-induced parkinsonism, the current study evaluated the degree to which rate of symptom progression, symptom severity, and response to and duration of levodopa therapy may be involved in the development of LIDs. Monkeys with acute (short-term) MPTP exposure, rapid symptom onset and short symptom duration prior to initiation of levodopa therapy developed dyskinesia between 11 and 24 days of daily levodopa administration. In contrast, monkeys with long-term MPTP exposure, slow symptom progression and/or long symptom duration prior to initiation of levodopa therapy were more resistant to developing LIDs (e.g., dyskinesia developed no sooner than 146 days of chronic levodopa administration). All animals were similarly symptomatic at the start of levodopa treatment and had similar therapeutic responses to the drug. These data suggest distinct differences in the propensity to develop LIDs in monkeys with different rates of symptom progression or symptom durations prior to levodopa and demonstrate the value of these models for further studying the pathophysiology of LIDs.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "Propylthiouracil", "mention_text": "Propylthiouracil-induced perinuclear-staining antineutrophil cytoplasmic autoantibody-positive vasculitis in conjunction with pericarditis.", "entity": "Propylthiouracil", "aliases": "6 Propyl 2 Thiouracil 6-Propyl-2-Thiouracil Propylthiouracil", "definition": "A thiourea antithyroid agent. Propythiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of throxine to tri-iodothyronine. It is used in the treatment of hyperthyroidism. (From Martindale, The Extra Pharmacopeoia, 30th ed, p534)\n    ", "id": "MESH:D011441"}
{"mention": "vasculitis", "mention_text": "Propylthiouracil-induced perinuclear-staining antineutrophil cytoplasmic autoantibody-positive vasculitis in conjunction with pericarditis.", "entity": "Vasculitis", "aliases": "Angiitides Angiitis Vasculitides Vasculitis", "definition": "Inflammation of any one of the blood vessels, including the ARTERIES; VEINS; and rest of the vasculature system in the body.\n    ", "id": "MESH:D014657"}
{"mention": "pericarditis", "mention_text": "Propylthiouracil-induced perinuclear-staining antineutrophil cytoplasmic autoantibody-positive vasculitis in conjunction with pericarditis.", "entity": "Pericarditis", "aliases": "Pericarditis Pleuropericarditis", "definition": "Inflammation of the PERICARDIUM from various origins, such as infection, neoplasm, autoimmune process, injuries, or drug-induced. Pericarditis usually leads to PERICARDIAL EFFUSION, or CONSTRICTIVE PERICARDITIS.\n    ", "id": "MESH:D010493"}
{"mention": "propylthiouracil", "mention_text": "OBJECTIVE: To describe a case of propylthiouracil-induced vasculitis manifesting with pericarditis. METHODS: We present the first case report of a woman with hyperthyroidism treated with propylthiouracil in whom a syndrome of pericarditis, fever, and glomerulonephritis developed. Serologic testing and immunologic studies were done, and a pericardial biopsy was performed. RESULTS: A 25-year-old woman with Graves' disease had a febrile illness and evidence of pericarditis, which was confirmed by biopsy. Serologic evaluation revealed the presence of perinuclear-staining antineutrophil cytoplasmic autoantibodies (pANCA) against myeloperoxidase (MPO). Propylthiouracil therapy was withdrawn, and she was treated with a 1-month course of prednisone, which alleviated her symptoms. A literature review revealed no prior reports of pericarditis in anti-MPO pANCA-positive vasculitis associated with propylthio- uracil therapy. CONCLUSION: Pericarditis may be the initial manifestation of drug-induced vasculitis attributable to propylthio- uracil therapy.", "entity": "Propylthiouracil", "aliases": "6 Propyl 2 Thiouracil 6-Propyl-2-Thiouracil Propylthiouracil", "definition": "A thiourea antithyroid agent. Propythiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of throxine to tri-iodothyronine. It is used in the treatment of hyperthyroidism. (From Martindale, The Extra Pharmacopeoia, 30th ed, p534)\n    ", "id": "MESH:D011441"}
{"mention": "vasculitis", "mention_text": "OBJECTIVE: To describe a case of propylthiouracil-induced vasculitis manifesting with pericarditis. METHODS: We present the first case report of a woman with hyperthyroidism treated with propylthiouracil in whom a syndrome of pericarditis, fever, and glomerulonephritis developed. Serologic testing and immunologic studies were done, and a pericardial biopsy was performed. RESULTS: A 25-year-old woman with Graves' disease had a febrile illness and evidence of pericarditis, which was confirmed by biopsy. Serologic evaluation revealed the presence of perinuclear-staining antineutrophil cytoplasmic autoantibodies (pANCA) against myeloperoxidase (MPO). Propylthiouracil therapy was withdrawn, and she was treated with a 1-month course of prednisone, which alleviated her symptoms. A literature review revealed no prior reports of pericarditis in anti-MPO pANCA-positive vasculitis associated with propylthio- uracil therapy. CONCLUSION: Pericarditis may be the initial manifestation of drug-induced vasculitis attributable to propylthio- uracil therapy.", "entity": "Vasculitis", "aliases": "Angiitides Angiitis Vasculitides Vasculitis", "definition": "Inflammation of any one of the blood vessels, including the ARTERIES; VEINS; and rest of the vasculature system in the body.\n    ", "id": "MESH:D014657"}
{"mention": "pericarditis", "mention_text": "OBJECTIVE: To describe a case of propylthiouracil-induced vasculitis manifesting with pericarditis. METHODS: We present the first case report of a woman with hyperthyroidism treated with propylthiouracil in whom a syndrome of pericarditis, fever, and glomerulonephritis developed. Serologic testing and immunologic studies were done, and a pericardial biopsy was performed. RESULTS: A 25-year-old woman with Graves' disease had a febrile illness and evidence of pericarditis, which was confirmed by biopsy. Serologic evaluation revealed the presence of perinuclear-staining antineutrophil cytoplasmic autoantibodies (pANCA) against myeloperoxidase (MPO). Propylthiouracil therapy was withdrawn, and she was treated with a 1-month course of prednisone, which alleviated her symptoms. A literature review revealed no prior reports of pericarditis in anti-MPO pANCA-positive vasculitis associated with propylthio- uracil therapy. CONCLUSION: Pericarditis may be the initial manifestation of drug-induced vasculitis attributable to propylthio- uracil therapy.", "entity": "Pericarditis", "aliases": "Pericarditis Pleuropericarditis", "definition": "Inflammation of the PERICARDIUM from various origins, such as infection, neoplasm, autoimmune process, injuries, or drug-induced. Pericarditis usually leads to PERICARDIAL EFFUSION, or CONSTRICTIVE PERICARDITIS.\n    ", "id": "MESH:D010493"}
{"mention": "hyperthyroidism", "mention_text": "OBJECTIVE: To describe a case of propylthiouracil-induced vasculitis manifesting with pericarditis. METHODS: We present the first case report of a woman with hyperthyroidism treated with propylthiouracil in whom a syndrome of pericarditis, fever, and glomerulonephritis developed. Serologic testing and immunologic studies were done, and a pericardial biopsy was performed. RESULTS: A 25-year-old woman with Graves' disease had a febrile illness and evidence of pericarditis, which was confirmed by biopsy. Serologic evaluation revealed the presence of perinuclear-staining antineutrophil cytoplasmic autoantibodies (pANCA) against myeloperoxidase (MPO). Propylthiouracil therapy was withdrawn, and she was treated with a 1-month course of prednisone, which alleviated her symptoms. A literature review revealed no prior reports of pericarditis in anti-MPO pANCA-positive vasculitis associated with propylthio- uracil therapy. CONCLUSION: Pericarditis may be the initial manifestation of drug-induced vasculitis attributable to propylthio- uracil therapy.", "entity": "Hyperthyroidism", "aliases": "Hyperthyroidism Primary Hyperthyroidisms", "definition": "Hypersecretion of THYROID HORMONES from the THYROID GLAND. Elevated levels of thyroid hormones increase BASAL METABOLIC RATE.\n    ", "id": "MESH:D006980"}
{"mention": "fever", "mention_text": "OBJECTIVE: To describe a case of propylthiouracil-induced vasculitis manifesting with pericarditis. METHODS: We present the first case report of a woman with hyperthyroidism treated with propylthiouracil in whom a syndrome of pericarditis, fever, and glomerulonephritis developed. Serologic testing and immunologic studies were done, and a pericardial biopsy was performed. RESULTS: A 25-year-old woman with Graves' disease had a febrile illness and evidence of pericarditis, which was confirmed by biopsy. Serologic evaluation revealed the presence of perinuclear-staining antineutrophil cytoplasmic autoantibodies (pANCA) against myeloperoxidase (MPO). Propylthiouracil therapy was withdrawn, and she was treated with a 1-month course of prednisone, which alleviated her symptoms. A literature review revealed no prior reports of pericarditis in anti-MPO pANCA-positive vasculitis associated with propylthio- uracil therapy. CONCLUSION: Pericarditis may be the initial manifestation of drug-induced vasculitis attributable to propylthio- uracil therapy.", "entity": "Fever", "aliases": "Fever Fevers Hyperthermia Hyperthermias Pyrexia Pyrexias", "definition": "An abnormal elevation of body temperature, usually as a result of a pathologic process.\n    ", "id": "MESH:D005334"}
{"mention": "glomerulonephritis", "mention_text": "OBJECTIVE: To describe a case of propylthiouracil-induced vasculitis manifesting with pericarditis. METHODS: We present the first case report of a woman with hyperthyroidism treated with propylthiouracil in whom a syndrome of pericarditis, fever, and glomerulonephritis developed. Serologic testing and immunologic studies were done, and a pericardial biopsy was performed. RESULTS: A 25-year-old woman with Graves' disease had a febrile illness and evidence of pericarditis, which was confirmed by biopsy. Serologic evaluation revealed the presence of perinuclear-staining antineutrophil cytoplasmic autoantibodies (pANCA) against myeloperoxidase (MPO). Propylthiouracil therapy was withdrawn, and she was treated with a 1-month course of prednisone, which alleviated her symptoms. A literature review revealed no prior reports of pericarditis in anti-MPO pANCA-positive vasculitis associated with propylthio- uracil therapy. CONCLUSION: Pericarditis may be the initial manifestation of drug-induced vasculitis attributable to propylthio- uracil therapy.", "entity": "Glomerulonephritis", "aliases": "Bright Disease Glomerulonephritides Glomerulonephritis", "definition": "Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.\n    ", "id": "MESH:D005921"}
{"mention": "Graves' disease", "mention_text": "OBJECTIVE: To describe a case of propylthiouracil-induced vasculitis manifesting with pericarditis. METHODS: We present the first case report of a woman with hyperthyroidism treated with propylthiouracil in whom a syndrome of pericarditis, fever, and glomerulonephritis developed. Serologic testing and immunologic studies were done, and a pericardial biopsy was performed. RESULTS: A 25-year-old woman with Graves' disease had a febrile illness and evidence of pericarditis, which was confirmed by biopsy. Serologic evaluation revealed the presence of perinuclear-staining antineutrophil cytoplasmic autoantibodies (pANCA) against myeloperoxidase (MPO). Propylthiouracil therapy was withdrawn, and she was treated with a 1-month course of prednisone, which alleviated her symptoms. A literature review revealed no prior reports of pericarditis in anti-MPO pANCA-positive vasculitis associated with propylthio- uracil therapy. CONCLUSION: Pericarditis may be the initial manifestation of drug-induced vasculitis attributable to propylthio- uracil therapy.", "entity": "Graves Disease", "aliases": "Basedow Disease Basedow's Basedows Graves Graves' Exophthalmic Goiter Goiters Hyperthyroidism Autoimmune", "definition": "A common form of hyperthyroidism with a diffuse hyperplastic GOITER. It is an autoimmune disorder that produces antibodies against the THYROID STIMULATING HORMONE RECEPTOR. These autoantibodies activate the TSH receptor, thereby stimulating the THYROID GLAND and hypersecretion of THYROID HORMONES. These autoantibodies can also affect the eyes (GRAVES OPHTHALMOPATHY) and the skin (Graves dermopathy).\n    ", "id": "MESH:D006111"}
{"mention": "febrile illness", "mention_text": "OBJECTIVE: To describe a case of propylthiouracil-induced vasculitis manifesting with pericarditis. METHODS: We present the first case report of a woman with hyperthyroidism treated with propylthiouracil in whom a syndrome of pericarditis, fever, and glomerulonephritis developed. Serologic testing and immunologic studies were done, and a pericardial biopsy was performed. RESULTS: A 25-year-old woman with Graves' disease had a febrile illness and evidence of pericarditis, which was confirmed by biopsy. Serologic evaluation revealed the presence of perinuclear-staining antineutrophil cytoplasmic autoantibodies (pANCA) against myeloperoxidase (MPO). Propylthiouracil therapy was withdrawn, and she was treated with a 1-month course of prednisone, which alleviated her symptoms. A literature review revealed no prior reports of pericarditis in anti-MPO pANCA-positive vasculitis associated with propylthio- uracil therapy. CONCLUSION: Pericarditis may be the initial manifestation of drug-induced vasculitis attributable to propylthio- uracil therapy.", "entity": "Fever", "aliases": "Fever Fevers Hyperthermia Hyperthermias Pyrexia Pyrexias", "definition": "An abnormal elevation of body temperature, usually as a result of a pathologic process.\n    ", "id": "MESH:D005334"}
{"mention": "Propylthiouracil", "mention_text": "OBJECTIVE: To describe a case of propylthiouracil-induced vasculitis manifesting with pericarditis. METHODS: We present the first case report of a woman with hyperthyroidism treated with propylthiouracil in whom a syndrome of pericarditis, fever, and glomerulonephritis developed. Serologic testing and immunologic studies were done, and a pericardial biopsy was performed. RESULTS: A 25-year-old woman with Graves' disease had a febrile illness and evidence of pericarditis, which was confirmed by biopsy. Serologic evaluation revealed the presence of perinuclear-staining antineutrophil cytoplasmic autoantibodies (pANCA) against myeloperoxidase (MPO). Propylthiouracil therapy was withdrawn, and she was treated with a 1-month course of prednisone, which alleviated her symptoms. A literature review revealed no prior reports of pericarditis in anti-MPO pANCA-positive vasculitis associated with propylthio- uracil therapy. CONCLUSION: Pericarditis may be the initial manifestation of drug-induced vasculitis attributable to propylthio- uracil therapy.", "entity": "Propylthiouracil", "aliases": "6 Propyl 2 Thiouracil 6-Propyl-2-Thiouracil Propylthiouracil", "definition": "A thiourea antithyroid agent. Propythiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of throxine to tri-iodothyronine. It is used in the treatment of hyperthyroidism. (From Martindale, The Extra Pharmacopeoia, 30th ed, p534)\n    ", "id": "MESH:D011441"}
{"mention": "prednisone", "mention_text": "OBJECTIVE: To describe a case of propylthiouracil-induced vasculitis manifesting with pericarditis. METHODS: We present the first case report of a woman with hyperthyroidism treated with propylthiouracil in whom a syndrome of pericarditis, fever, and glomerulonephritis developed. Serologic testing and immunologic studies were done, and a pericardial biopsy was performed. RESULTS: A 25-year-old woman with Graves' disease had a febrile illness and evidence of pericarditis, which was confirmed by biopsy. Serologic evaluation revealed the presence of perinuclear-staining antineutrophil cytoplasmic autoantibodies (pANCA) against myeloperoxidase (MPO). Propylthiouracil therapy was withdrawn, and she was treated with a 1-month course of prednisone, which alleviated her symptoms. A literature review revealed no prior reports of pericarditis in anti-MPO pANCA-positive vasculitis associated with propylthio- uracil therapy. CONCLUSION: Pericarditis may be the initial manifestation of drug-induced vasculitis attributable to propylthio- uracil therapy.", "entity": "Prednisone", "aliases": "Apo-Prednisone Apotex Brand of Prednisone Aventis Cortan Cortancyl Cutason Dacortin Decortin Decortisyl Dehydrocortisone Deltasone Diba Encorton Encortone Enkortolon Fawns & McAllan Ferring GALENpharma Halsey Drug Hexal Hoechst ICN Kortancyl Lichtenstein Liquid Pred Merck Merz Meticorten Orasone Panafcort Panasol Pharmacia Predni Tablinen Prednidib Predniment Prednison Galen acsis Pronisone Rectodelt Schering-Plough Seatrace Solvay Sone Sterapred Trommsdorff Ultracorten Winpred acis delta-Cortis", "definition": "A synthetic anti-inflammatory glucocorticoid derived from CORTISONE. It is biologically inert and converted to PREDNISOLONE in the liver.\n    ", "id": "MESH:D011241"}
{"mention": "propylthio- uracil", "mention_text": "OBJECTIVE: To describe a case of propylthiouracil-induced vasculitis manifesting with pericarditis. METHODS: We present the first case report of a woman with hyperthyroidism treated with propylthiouracil in whom a syndrome of pericarditis, fever, and glomerulonephritis developed. Serologic testing and immunologic studies were done, and a pericardial biopsy was performed. RESULTS: A 25-year-old woman with Graves' disease had a febrile illness and evidence of pericarditis, which was confirmed by biopsy. Serologic evaluation revealed the presence of perinuclear-staining antineutrophil cytoplasmic autoantibodies (pANCA) against myeloperoxidase (MPO). Propylthiouracil therapy was withdrawn, and she was treated with a 1-month course of prednisone, which alleviated her symptoms. A literature review revealed no prior reports of pericarditis in anti-MPO pANCA-positive vasculitis associated with propylthio- uracil therapy. CONCLUSION: Pericarditis may be the initial manifestation of drug-induced vasculitis attributable to propylthio- uracil therapy.", "entity": "Propylthiouracil", "aliases": "6 Propyl 2 Thiouracil 6-Propyl-2-Thiouracil Propylthiouracil", "definition": "A thiourea antithyroid agent. Propythiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of throxine to tri-iodothyronine. It is used in the treatment of hyperthyroidism. (From Martindale, The Extra Pharmacopeoia, 30th ed, p534)\n    ", "id": "MESH:D011441"}
{"mention": "Pericarditis", "mention_text": "OBJECTIVE: To describe a case of propylthiouracil-induced vasculitis manifesting with pericarditis. METHODS: We present the first case report of a woman with hyperthyroidism treated with propylthiouracil in whom a syndrome of pericarditis, fever, and glomerulonephritis developed. Serologic testing and immunologic studies were done, and a pericardial biopsy was performed. RESULTS: A 25-year-old woman with Graves' disease had a febrile illness and evidence of pericarditis, which was confirmed by biopsy. Serologic evaluation revealed the presence of perinuclear-staining antineutrophil cytoplasmic autoantibodies (pANCA) against myeloperoxidase (MPO). Propylthiouracil therapy was withdrawn, and she was treated with a 1-month course of prednisone, which alleviated her symptoms. A literature review revealed no prior reports of pericarditis in anti-MPO pANCA-positive vasculitis associated with propylthio- uracil therapy. CONCLUSION: Pericarditis may be the initial manifestation of drug-induced vasculitis attributable to propylthio- uracil therapy.", "entity": "Pericarditis", "aliases": "Pericarditis Pleuropericarditis", "definition": "Inflammation of the PERICARDIUM from various origins, such as infection, neoplasm, autoimmune process, injuries, or drug-induced. Pericarditis usually leads to PERICARDIAL EFFUSION, or CONSTRICTIVE PERICARDITIS.\n    ", "id": "MESH:D010493"}
{"mention": "beta-carboline", "mention_text": "Two mouse lines selected for differential sensitivities to beta-carboline-induced seizures are also differentially sensitive to various pharmacological effects of other GABA(A) receptor ligands.", "entity": "beta-carboline-3-carboxylic acid methyl ester", "aliases": "3-carbomethoxy-beta-carboline beta-CCM beta-carboline-3-carboxylic acid methyl ester beta-carboline-3-carboxylate", "definition": "", "id": "MESH:C036150"}
{"mention": "seizures", "mention_text": "Two mouse lines selected for differential sensitivities to beta-carboline-induced seizures are also differentially sensitive to various pharmacological effects of other GABA(A) receptor ligands.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "GABA", "mention_text": "Two mouse lines selected for differential sensitivities to beta-carboline-induced seizures are also differentially sensitive to various pharmacological effects of other GABA(A) receptor ligands.", "entity": "gamma-Aminobutyric Acid", "aliases": "4 Aminobutanoic Acid Aminobutyric 4-Aminobutanoic 4-Aminobutyric Hydrochloride gamma-Aminobutyric Aminalon Aminalone GABA Lithium Gammalon gamma Monolithium Salt Monosodium Calcium (2:1) Zinc", "definition": "The most common inhibitory neurotransmitter in the central nervous system.\n    ", "id": "MESH:D005680"}
{"mention": "seizures", "mention_text": "Two mouse lines were selectively bred according to their sensitivity (BS line) or resistance (BR line) to seizures induced by a single i.p. injection of methyl beta-carboline-3-carboxylate (beta-CCM), an inverse agonist of the GABA(A) receptor benzodiazepine site. Our aim was to characterize both lines' sensitivities to various physiological effects of other ligands of the GABA(A) receptor. We measured diazepam-induced anxiolysis with the elevated plus-maze test, diazepam-induced sedation by recording the vigilance states, and picrotoxin- and pentylenetetrazol-induced seizures after i.p. injections. Results presented here show that the differential sensitivities of BS and BR lines to beta-CCM can be extended to diazepam, picrotoxin, and pentylenetetrazol, suggesting a genetic selection of a general sensitivity and resistance to several ligands of the GABA(A) receptor.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "methyl beta-carboline-3-carboxylate", "mention_text": "Two mouse lines were selectively bred according to their sensitivity (BS line) or resistance (BR line) to seizures induced by a single i.p. injection of methyl beta-carboline-3-carboxylate (beta-CCM), an inverse agonist of the GABA(A) receptor benzodiazepine site. Our aim was to characterize both lines' sensitivities to various physiological effects of other ligands of the GABA(A) receptor. We measured diazepam-induced anxiolysis with the elevated plus-maze test, diazepam-induced sedation by recording the vigilance states, and picrotoxin- and pentylenetetrazol-induced seizures after i.p. injections. Results presented here show that the differential sensitivities of BS and BR lines to beta-CCM can be extended to diazepam, picrotoxin, and pentylenetetrazol, suggesting a genetic selection of a general sensitivity and resistance to several ligands of the GABA(A) receptor.", "entity": "beta-carboline-3-carboxylic acid methyl ester", "aliases": "3-carbomethoxy-beta-carboline beta-CCM beta-carboline-3-carboxylic acid methyl ester beta-carboline-3-carboxylate", "definition": "", "id": "MESH:C036150"}
{"mention": "beta-CCM", "mention_text": "Two mouse lines were selectively bred according to their sensitivity (BS line) or resistance (BR line) to seizures induced by a single i.p. injection of methyl beta-carboline-3-carboxylate (beta-CCM), an inverse agonist of the GABA(A) receptor benzodiazepine site. Our aim was to characterize both lines' sensitivities to various physiological effects of other ligands of the GABA(A) receptor. We measured diazepam-induced anxiolysis with the elevated plus-maze test, diazepam-induced sedation by recording the vigilance states, and picrotoxin- and pentylenetetrazol-induced seizures after i.p. injections. Results presented here show that the differential sensitivities of BS and BR lines to beta-CCM can be extended to diazepam, picrotoxin, and pentylenetetrazol, suggesting a genetic selection of a general sensitivity and resistance to several ligands of the GABA(A) receptor.", "entity": "beta-carboline-3-carboxylic acid methyl ester", "aliases": "3-carbomethoxy-beta-carboline beta-CCM beta-carboline-3-carboxylic acid methyl ester beta-carboline-3-carboxylate", "definition": "", "id": "MESH:C036150"}
{"mention": "GABA", "mention_text": "Two mouse lines were selectively bred according to their sensitivity (BS line) or resistance (BR line) to seizures induced by a single i.p. injection of methyl beta-carboline-3-carboxylate (beta-CCM), an inverse agonist of the GABA(A) receptor benzodiazepine site. Our aim was to characterize both lines' sensitivities to various physiological effects of other ligands of the GABA(A) receptor. We measured diazepam-induced anxiolysis with the elevated plus-maze test, diazepam-induced sedation by recording the vigilance states, and picrotoxin- and pentylenetetrazol-induced seizures after i.p. injections. Results presented here show that the differential sensitivities of BS and BR lines to beta-CCM can be extended to diazepam, picrotoxin, and pentylenetetrazol, suggesting a genetic selection of a general sensitivity and resistance to several ligands of the GABA(A) receptor.", "entity": "gamma-Aminobutyric Acid", "aliases": "4 Aminobutanoic Acid Aminobutyric 4-Aminobutanoic 4-Aminobutyric Hydrochloride gamma-Aminobutyric Aminalon Aminalone GABA Lithium Gammalon gamma Monolithium Salt Monosodium Calcium (2:1) Zinc", "definition": "The most common inhibitory neurotransmitter in the central nervous system.\n    ", "id": "MESH:D005680"}
{"mention": "benzodiazepine", "mention_text": "Two mouse lines were selectively bred according to their sensitivity (BS line) or resistance (BR line) to seizures induced by a single i.p. injection of methyl beta-carboline-3-carboxylate (beta-CCM), an inverse agonist of the GABA(A) receptor benzodiazepine site. Our aim was to characterize both lines' sensitivities to various physiological effects of other ligands of the GABA(A) receptor. We measured diazepam-induced anxiolysis with the elevated plus-maze test, diazepam-induced sedation by recording the vigilance states, and picrotoxin- and pentylenetetrazol-induced seizures after i.p. injections. Results presented here show that the differential sensitivities of BS and BR lines to beta-CCM can be extended to diazepam, picrotoxin, and pentylenetetrazol, suggesting a genetic selection of a general sensitivity and resistance to several ligands of the GABA(A) receptor.", "entity": "Benzodiazepines", "aliases": "Benzodiazepine Compounds Benzodiazepines", "definition": "A group of two-ring heterocyclic compounds consisting of a benzene ring fused to a diazepine ring.\n    ", "id": "MESH:D001569"}
{"mention": "diazepam", "mention_text": "Two mouse lines were selectively bred according to their sensitivity (BS line) or resistance (BR line) to seizures induced by a single i.p. injection of methyl beta-carboline-3-carboxylate (beta-CCM), an inverse agonist of the GABA(A) receptor benzodiazepine site. Our aim was to characterize both lines' sensitivities to various physiological effects of other ligands of the GABA(A) receptor. We measured diazepam-induced anxiolysis with the elevated plus-maze test, diazepam-induced sedation by recording the vigilance states, and picrotoxin- and pentylenetetrazol-induced seizures after i.p. injections. Results presented here show that the differential sensitivities of BS and BR lines to beta-CCM can be extended to diazepam, picrotoxin, and pentylenetetrazol, suggesting a genetic selection of a general sensitivity and resistance to several ligands of the GABA(A) receptor.", "entity": "Diazepam", "aliases": "7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one Apaurin Diazemuls Diazepam Faustan Relanium Seduxen Sibazon Stesolid Valium", "definition": "A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity.\n    ", "id": "MESH:D003975"}
{"mention": "picrotoxin", "mention_text": "Two mouse lines were selectively bred according to their sensitivity (BS line) or resistance (BR line) to seizures induced by a single i.p. injection of methyl beta-carboline-3-carboxylate (beta-CCM), an inverse agonist of the GABA(A) receptor benzodiazepine site. Our aim was to characterize both lines' sensitivities to various physiological effects of other ligands of the GABA(A) receptor. We measured diazepam-induced anxiolysis with the elevated plus-maze test, diazepam-induced sedation by recording the vigilance states, and picrotoxin- and pentylenetetrazol-induced seizures after i.p. injections. Results presented here show that the differential sensitivities of BS and BR lines to beta-CCM can be extended to diazepam, picrotoxin, and pentylenetetrazol, suggesting a genetic selection of a general sensitivity and resistance to several ligands of the GABA(A) receptor.", "entity": "Picrotoxin", "aliases": "Picrotoxin", "definition": "A noncompetitive antagonist at GABA-A receptors and thus a convulsant. Picrotoxin blocks the GAMMA-AMINOBUTYRIC ACID-activated chloride ionophore. Although it is most often used as a research tool, it has been used as a CNS stimulant and an antidote in poisoning by CNS depressants, especially the barbiturates.\n    ", "id": "MESH:D010852"}
{"mention": "pentylenetetrazol", "mention_text": "Two mouse lines were selectively bred according to their sensitivity (BS line) or resistance (BR line) to seizures induced by a single i.p. injection of methyl beta-carboline-3-carboxylate (beta-CCM), an inverse agonist of the GABA(A) receptor benzodiazepine site. Our aim was to characterize both lines' sensitivities to various physiological effects of other ligands of the GABA(A) receptor. We measured diazepam-induced anxiolysis with the elevated plus-maze test, diazepam-induced sedation by recording the vigilance states, and picrotoxin- and pentylenetetrazol-induced seizures after i.p. injections. Results presented here show that the differential sensitivities of BS and BR lines to beta-CCM can be extended to diazepam, picrotoxin, and pentylenetetrazol, suggesting a genetic selection of a general sensitivity and resistance to several ligands of the GABA(A) receptor.", "entity": "Pentylenetetrazole", "aliases": "Cardiazol Corasol Corazol Corazole Korazol Korazole Leptazole Metrazol Metrazole Pentamethylenetetrazole Pentazol Pentetrazole Pentylenetetrazol Pentylenetetrazole", "definition": "A pharmaceutical agent that displays activity as a central nervous system and respiratory stimulant. It is considered a non-competitive GAMMA-AMINOBUTYRIC ACID antagonist. Pentylenetetrazole has been used experimentally to study seizure phenomenon and to identify pharmaceuticals that may control seizure susceptibility.\n    ", "id": "MESH:D010433"}
{"mention": "ketamine", "mention_text": "Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: a randomized, controlled, double-blind, crossover, double-dose study.", "entity": "Ketamine", "aliases": "2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone CI 581 CI-581 CI581 Calipsol Calypsol Kalipsol Ketalar Ketamine Hydrochloride Ketanest Ketaset", "definition": "A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors.\n    ", "id": "MESH:D007649"}
{"mention": "cancer", "mention_text": "Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: a randomized, controlled, double-blind, crossover, double-dose study.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "morphine", "mention_text": "Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: a randomized, controlled, double-blind, crossover, double-dose study.", "entity": "Morphine", "aliases": "Chloride Morphine Contin MS Duramorph Morphia Sulfate (2:1) Anhydrous Pentahydrate Oramorph SR SDZ 202 250 202-250 202250 SDZ202 SDZ202-250 SDZ202250", "definition": "The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.\n    ", "id": "MESH:D009020"}
{"mention": "Pain", "mention_text": "Pain not responsive to morphine is often problematic. Animal and clinical studies have suggested that N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of ketamine (0.25 mg/kg or 0.50 mg/kg) was given to 10 cancer patients whose pain was unrelieved by morphine in a randomized, double-blind, crossover, double-dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomiting, drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not at all, slight, a lot, awful); Mini-Mental State Examination (MMSE) (0-30); and arterial pressure were recorded before administration of drugs (T0) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minutes (T180). Ketamine, but not saline solution, significantly reduced the pain intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, and an unpleasant sensation (\"empty head\") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg/kg. A significant difference in MMSE was observed at T30 in patients who received 0.50 mg/kg of ketamine. Ketamine can improve morphine analgesia in difficult pain syndromes, such as neuropathic pain. However, the occurrence of central adverse effects should be taken into account, especially when using higher doses. This observation should be tested in studies of prolonged ketamine administration.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "morphine", "mention_text": "Pain not responsive to morphine is often problematic. Animal and clinical studies have suggested that N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of ketamine (0.25 mg/kg or 0.50 mg/kg) was given to 10 cancer patients whose pain was unrelieved by morphine in a randomized, double-blind, crossover, double-dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomiting, drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not at all, slight, a lot, awful); Mini-Mental State Examination (MMSE) (0-30); and arterial pressure were recorded before administration of drugs (T0) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minutes (T180). Ketamine, but not saline solution, significantly reduced the pain intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, and an unpleasant sensation (\"empty head\") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg/kg. A significant difference in MMSE was observed at T30 in patients who received 0.50 mg/kg of ketamine. Ketamine can improve morphine analgesia in difficult pain syndromes, such as neuropathic pain. However, the occurrence of central adverse effects should be taken into account, especially when using higher doses. This observation should be tested in studies of prolonged ketamine administration.", "entity": "Morphine", "aliases": "Chloride Morphine Contin MS Duramorph Morphia Sulfate (2:1) Anhydrous Pentahydrate Oramorph SR SDZ 202 250 202-250 202250 SDZ202 SDZ202-250 SDZ202250", "definition": "The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.\n    ", "id": "MESH:D009020"}
{"mention": "N-methyl-D-aspartate", "mention_text": "Pain not responsive to morphine is often problematic. Animal and clinical studies have suggested that N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of ketamine (0.25 mg/kg or 0.50 mg/kg) was given to 10 cancer patients whose pain was unrelieved by morphine in a randomized, double-blind, crossover, double-dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomiting, drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not at all, slight, a lot, awful); Mini-Mental State Examination (MMSE) (0-30); and arterial pressure were recorded before administration of drugs (T0) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minutes (T180). Ketamine, but not saline solution, significantly reduced the pain intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, and an unpleasant sensation (\"empty head\") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg/kg. A significant difference in MMSE was observed at T30 in patients who received 0.50 mg/kg of ketamine. Ketamine can improve morphine analgesia in difficult pain syndromes, such as neuropathic pain. However, the occurrence of central adverse effects should be taken into account, especially when using higher doses. This observation should be tested in studies of prolonged ketamine administration.", "entity": "N-Methylaspartate", "aliases": "Acid N-Methyl-D-aspartic N Methyl D aspartate aspartic Methylaspartate N-Methyl-D-aspartate N-Methylaspartate NMDA", "definition": "An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).\n    ", "id": "MESH:D016202"}
{"mention": "NMDA", "mention_text": "Pain not responsive to morphine is often problematic. Animal and clinical studies have suggested that N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of ketamine (0.25 mg/kg or 0.50 mg/kg) was given to 10 cancer patients whose pain was unrelieved by morphine in a randomized, double-blind, crossover, double-dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomiting, drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not at all, slight, a lot, awful); Mini-Mental State Examination (MMSE) (0-30); and arterial pressure were recorded before administration of drugs (T0) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minutes (T180). Ketamine, but not saline solution, significantly reduced the pain intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, and an unpleasant sensation (\"empty head\") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg/kg. A significant difference in MMSE was observed at T30 in patients who received 0.50 mg/kg of ketamine. Ketamine can improve morphine analgesia in difficult pain syndromes, such as neuropathic pain. However, the occurrence of central adverse effects should be taken into account, especially when using higher doses. This observation should be tested in studies of prolonged ketamine administration.", "entity": "N-Methylaspartate", "aliases": "Acid N-Methyl-D-aspartic N Methyl D aspartate aspartic Methylaspartate N-Methyl-D-aspartate N-Methylaspartate NMDA", "definition": "An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).\n    ", "id": "MESH:D016202"}
{"mention": "ketamine", "mention_text": "Pain not responsive to morphine is often problematic. Animal and clinical studies have suggested that N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of ketamine (0.25 mg/kg or 0.50 mg/kg) was given to 10 cancer patients whose pain was unrelieved by morphine in a randomized, double-blind, crossover, double-dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomiting, drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not at all, slight, a lot, awful); Mini-Mental State Examination (MMSE) (0-30); and arterial pressure were recorded before administration of drugs (T0) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minutes (T180). Ketamine, but not saline solution, significantly reduced the pain intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, and an unpleasant sensation (\"empty head\") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg/kg. A significant difference in MMSE was observed at T30 in patients who received 0.50 mg/kg of ketamine. Ketamine can improve morphine analgesia in difficult pain syndromes, such as neuropathic pain. However, the occurrence of central adverse effects should be taken into account, especially when using higher doses. This observation should be tested in studies of prolonged ketamine administration.", "entity": "Ketamine", "aliases": "2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone CI 581 CI-581 CI581 Calipsol Calypsol Kalipsol Ketalar Ketamine Hydrochloride Ketanest Ketaset", "definition": "A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors.\n    ", "id": "MESH:D007649"}
{"mention": "pain", "mention_text": "Pain not responsive to morphine is often problematic. Animal and clinical studies have suggested that N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of ketamine (0.25 mg/kg or 0.50 mg/kg) was given to 10 cancer patients whose pain was unrelieved by morphine in a randomized, double-blind, crossover, double-dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomiting, drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not at all, slight, a lot, awful); Mini-Mental State Examination (MMSE) (0-30); and arterial pressure were recorded before administration of drugs (T0) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minutes (T180). Ketamine, but not saline solution, significantly reduced the pain intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, and an unpleasant sensation (\"empty head\") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg/kg. A significant difference in MMSE was observed at T30 in patients who received 0.50 mg/kg of ketamine. Ketamine can improve morphine analgesia in difficult pain syndromes, such as neuropathic pain. However, the occurrence of central adverse effects should be taken into account, especially when using higher doses. This observation should be tested in studies of prolonged ketamine administration.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "neuropathic pain", "mention_text": "Pain not responsive to morphine is often problematic. Animal and clinical studies have suggested that N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of ketamine (0.25 mg/kg or 0.50 mg/kg) was given to 10 cancer patients whose pain was unrelieved by morphine in a randomized, double-blind, crossover, double-dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomiting, drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not at all, slight, a lot, awful); Mini-Mental State Examination (MMSE) (0-30); and arterial pressure were recorded before administration of drugs (T0) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minutes (T180). Ketamine, but not saline solution, significantly reduced the pain intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, and an unpleasant sensation (\"empty head\") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg/kg. A significant difference in MMSE was observed at T30 in patients who received 0.50 mg/kg of ketamine. Ketamine can improve morphine analgesia in difficult pain syndromes, such as neuropathic pain. However, the occurrence of central adverse effects should be taken into account, especially when using higher doses. This observation should be tested in studies of prolonged ketamine administration.", "entity": "Neuralgia", "aliases": "Atypical Neuralgia Neuralgias Iliohypogastric Nerve Ilioinguinal Pain Paroxysmal Pains Perineal Stump Supraorbital Vidian Neurodynia Neurodynias Neuropathic", "definition": "Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve.\n    ", "id": "MESH:D009437"}
{"mention": "cancer", "mention_text": "Pain not responsive to morphine is often problematic. Animal and clinical studies have suggested that N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of ketamine (0.25 mg/kg or 0.50 mg/kg) was given to 10 cancer patients whose pain was unrelieved by morphine in a randomized, double-blind, crossover, double-dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomiting, drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not at all, slight, a lot, awful); Mini-Mental State Examination (MMSE) (0-30); and arterial pressure were recorded before administration of drugs (T0) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minutes (T180). Ketamine, but not saline solution, significantly reduced the pain intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, and an unpleasant sensation (\"empty head\") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg/kg. A significant difference in MMSE was observed at T30 in patients who received 0.50 mg/kg of ketamine. Ketamine can improve morphine analgesia in difficult pain syndromes, such as neuropathic pain. However, the occurrence of central adverse effects should be taken into account, especially when using higher doses. This observation should be tested in studies of prolonged ketamine administration.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "nausea", "mention_text": "Pain not responsive to morphine is often problematic. Animal and clinical studies have suggested that N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of ketamine (0.25 mg/kg or 0.50 mg/kg) was given to 10 cancer patients whose pain was unrelieved by morphine in a randomized, double-blind, crossover, double-dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomiting, drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not at all, slight, a lot, awful); Mini-Mental State Examination (MMSE) (0-30); and arterial pressure were recorded before administration of drugs (T0) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minutes (T180). Ketamine, but not saline solution, significantly reduced the pain intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, and an unpleasant sensation (\"empty head\") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg/kg. A significant difference in MMSE was observed at T30 in patients who received 0.50 mg/kg of ketamine. Ketamine can improve morphine analgesia in difficult pain syndromes, such as neuropathic pain. However, the occurrence of central adverse effects should be taken into account, especially when using higher doses. This observation should be tested in studies of prolonged ketamine administration.", "entity": "Nausea", "aliases": "Nausea", "definition": "An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.\n    ", "id": "MESH:D009325"}
{"mention": "vomiting", "mention_text": "Pain not responsive to morphine is often problematic. Animal and clinical studies have suggested that N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of ketamine (0.25 mg/kg or 0.50 mg/kg) was given to 10 cancer patients whose pain was unrelieved by morphine in a randomized, double-blind, crossover, double-dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomiting, drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not at all, slight, a lot, awful); Mini-Mental State Examination (MMSE) (0-30); and arterial pressure were recorded before administration of drugs (T0) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minutes (T180). Ketamine, but not saline solution, significantly reduced the pain intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, and an unpleasant sensation (\"empty head\") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg/kg. A significant difference in MMSE was observed at T30 in patients who received 0.50 mg/kg of ketamine. Ketamine can improve morphine analgesia in difficult pain syndromes, such as neuropathic pain. However, the occurrence of central adverse effects should be taken into account, especially when using higher doses. This observation should be tested in studies of prolonged ketamine administration.", "entity": "Vomiting", "aliases": "Emesis Vomiting", "definition": "The forcible expulsion of the contents of the STOMACH through the MOUTH.\n    ", "id": "MESH:D014839"}
{"mention": "confusion", "mention_text": "Pain not responsive to morphine is often problematic. Animal and clinical studies have suggested that N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of ketamine (0.25 mg/kg or 0.50 mg/kg) was given to 10 cancer patients whose pain was unrelieved by morphine in a randomized, double-blind, crossover, double-dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomiting, drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not at all, slight, a lot, awful); Mini-Mental State Examination (MMSE) (0-30); and arterial pressure were recorded before administration of drugs (T0) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minutes (T180). Ketamine, but not saline solution, significantly reduced the pain intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, and an unpleasant sensation (\"empty head\") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg/kg. A significant difference in MMSE was observed at T30 in patients who received 0.50 mg/kg of ketamine. Ketamine can improve morphine analgesia in difficult pain syndromes, such as neuropathic pain. However, the occurrence of central adverse effects should be taken into account, especially when using higher doses. This observation should be tested in studies of prolonged ketamine administration.", "entity": "Confusion", "aliases": "Bewilderment Confusion Post Ictal Post-Ictal Reactive Confusional State States Disorientation", "definition": "A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation.\n    ", "id": "MESH:D003221"}
{"mention": "dry mouth", "mention_text": "Pain not responsive to morphine is often problematic. Animal and clinical studies have suggested that N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of ketamine (0.25 mg/kg or 0.50 mg/kg) was given to 10 cancer patients whose pain was unrelieved by morphine in a randomized, double-blind, crossover, double-dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomiting, drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not at all, slight, a lot, awful); Mini-Mental State Examination (MMSE) (0-30); and arterial pressure were recorded before administration of drugs (T0) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minutes (T180). Ketamine, but not saline solution, significantly reduced the pain intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, and an unpleasant sensation (\"empty head\") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg/kg. A significant difference in MMSE was observed at T30 in patients who received 0.50 mg/kg of ketamine. Ketamine can improve morphine analgesia in difficult pain syndromes, such as neuropathic pain. However, the occurrence of central adverse effects should be taken into account, especially when using higher doses. This observation should be tested in studies of prolonged ketamine administration.", "entity": "Xerostomia", "aliases": "Asialia Asialias Dryness Mouth Hyposalivation Hyposalivations Xerostomia Xerostomias", "definition": "Decreased salivary flow.\n    ", "id": "MESH:D014987"}
{"mention": "Ketamine", "mention_text": "Pain not responsive to morphine is often problematic. Animal and clinical studies have suggested that N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of ketamine (0.25 mg/kg or 0.50 mg/kg) was given to 10 cancer patients whose pain was unrelieved by morphine in a randomized, double-blind, crossover, double-dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomiting, drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not at all, slight, a lot, awful); Mini-Mental State Examination (MMSE) (0-30); and arterial pressure were recorded before administration of drugs (T0) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minutes (T180). Ketamine, but not saline solution, significantly reduced the pain intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, and an unpleasant sensation (\"empty head\") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg/kg. A significant difference in MMSE was observed at T30 in patients who received 0.50 mg/kg of ketamine. Ketamine can improve morphine analgesia in difficult pain syndromes, such as neuropathic pain. However, the occurrence of central adverse effects should be taken into account, especially when using higher doses. This observation should be tested in studies of prolonged ketamine administration.", "entity": "Ketamine", "aliases": "2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone CI 581 CI-581 CI581 Calipsol Calypsol Kalipsol Ketalar Ketamine Hydrochloride Ketanest Ketaset", "definition": "A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors.\n    ", "id": "MESH:D007649"}
{"mention": "Hallucinations", "mention_text": "Pain not responsive to morphine is often problematic. Animal and clinical studies have suggested that N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of ketamine (0.25 mg/kg or 0.50 mg/kg) was given to 10 cancer patients whose pain was unrelieved by morphine in a randomized, double-blind, crossover, double-dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomiting, drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not at all, slight, a lot, awful); Mini-Mental State Examination (MMSE) (0-30); and arterial pressure were recorded before administration of drugs (T0) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minutes (T180). Ketamine, but not saline solution, significantly reduced the pain intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, and an unpleasant sensation (\"empty head\") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg/kg. A significant difference in MMSE was observed at T30 in patients who received 0.50 mg/kg of ketamine. Ketamine can improve morphine analgesia in difficult pain syndromes, such as neuropathic pain. However, the occurrence of central adverse effects should be taken into account, especially when using higher doses. This observation should be tested in studies of prolonged ketamine administration.", "entity": "Hallucinations", "aliases": "Auditory Hallucination Verbal Hallucinations Body Sensation Dissociative Elementary Gustatory of Hypnagogic Hypnapompic Kinesthetic Mood Congruent Incongruent Olfactory Organic Reflex Sensory Somatic Tactile Visual Formed People Internal Unformed", "definition": "Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with MENTAL DISORDERS.\n    ", "id": "MESH:D006212"}
{"mention": "diazepam", "mention_text": "Pain not responsive to morphine is often problematic. Animal and clinical studies have suggested that N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of ketamine (0.25 mg/kg or 0.50 mg/kg) was given to 10 cancer patients whose pain was unrelieved by morphine in a randomized, double-blind, crossover, double-dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomiting, drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not at all, slight, a lot, awful); Mini-Mental State Examination (MMSE) (0-30); and arterial pressure were recorded before administration of drugs (T0) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minutes (T180). Ketamine, but not saline solution, significantly reduced the pain intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, and an unpleasant sensation (\"empty head\") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg/kg. A significant difference in MMSE was observed at T30 in patients who received 0.50 mg/kg of ketamine. Ketamine can improve morphine analgesia in difficult pain syndromes, such as neuropathic pain. However, the occurrence of central adverse effects should be taken into account, especially when using higher doses. This observation should be tested in studies of prolonged ketamine administration.", "entity": "Diazepam", "aliases": "7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one Apaurin Diazemuls Diazepam Faustan Relanium Seduxen Sibazon Stesolid Valium", "definition": "A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity.\n    ", "id": "MESH:D003975"}
{"mention": "erectile dysfunction", "mention_text": "Endocrine screening in 1,022 men with erectile dysfunction: clinical significance and cost-effective strategy.", "entity": "Erectile Dysfunction", "aliases": "Dysfunction Erectile Impotence Male Sexual", "definition": "The inability in the male to have a PENILE ERECTION due to psychological or organ dysfunction.\n    ", "id": "MESH:D007172"}
{"mention": "testosterone", "mention_text": "PURPOSE: We reviewed the results of serum testosterone and prolactin determination in 1,022 patients referred because of erectile dysfunction and compared the data with history, results of physical examination, other etiological investigations and effects of endocrine therapy to refine the rules of cost-effective endocrine screening and to pinpoint actual responsibility for hormonal abnormalities. MATERIALS AND METHODS: Testosterone and prolactin were determined by radioimmunoassay. Every patient was screened for testosterone and 451 were screened for prolactin on the basis of low sexual desire, gynecomastia or testosterone less than 4 ng./ml. Determination was repeated in case of abnormal first results. Prolactin results were compared with those of a previous personal cohort of 1,340 patients with erectile dysfunction and systematic prolactin determination. Main clinical criteria tested regarding efficiency in hormone determination were low sexual desire, small testes and gynecomastia. Endocrine therapy consisted of testosterone heptylate or human chorionic gonadotropin for hypogonadism and bromocriptine for hyperprolactinemia. RESULTS: Testosterone was less than 3 ng./ml. in 107 patients but normal in 40% at repeat determination. The prevalence of repeatedly low testosterone increased with age (4% before age 50 years and 9% 50 years or older). Two pituitary tumors were discovered after testosterone determination. Most of the other low testosterone levels seemed to result from nonorganic hypothalamic dysfunction because of normal serum luteinizing hormone and prolactin and to have only a small role in erectile dysfunction (definite improvement in only 16 of 44 [36%] after androgen therapy, normal morning or nocturnal erections in 30% and definite vasculogenic contributions in 42%). Determining testosterone only in cases of low sexual desire or abnormal physical examination would have missed 40% of the cases with low testosterone, including 37% of those subsequently improved by androgen therapy. Prolactin exceeded 20 ng./ml. in 5 men and was normal in 2 at repeat determination. Only 1 prolactinoma was discovered. These data are lower than those we found during the last 2 decades (overall prolactin greater than 20 ng./ml. in 1.86% of 1,821 patients, prolactinomas in 7, 0.38%). Bromocriptine was definitely effective in cases with prolactin greater than 35 ng./ml. (8 of 12 compared to only 9 of 22 cases with prolactin between 20 and 35 ng./ml.). Testosterone was low in less than 50% of cases with prolactin greater than 35 ng./ml. CONCLUSIONS: Low prevalences and effects of low testosterone and high prolactin in erectile dysfunction cannot justify their routine determination. However, cost-effective screening strategies recommended so far missed 40 to 50% of cases improved with endocrine therapy and the pituitary tumors. We now advocate that before age 50 years testosterone be determined only in cases of low sexual desire and abnormal physical examination but that it be measured in all men older than 50 years. Prolactin should be determined only in cases of low sexual desire, gynecomastia and/or testosterone less than 4 ng./ml.", "entity": "Testosterone", "aliases": "17 beta Hydroxy 4 Androsten 3 one 8 alpha 17-beta-Hydroxy-4-Androsten-3-one 17-beta-Hydroxy-8 alpha-4-Androsten-3-one Isotestosterone 8-Isotestosterone AndroGel Androderm Andropatch Androtop AstraZeneca Brand of Testosterone Auxilium Pharmaceuticals Inc. Bartor CEPA Dr. Kade Faulding Ferring GlaxoSmithKline Hauck Histerone Ortho Paladin Pasadena Schering SmithKline Beecham Solvay Sterotate Sustanon Testim Testoderm Testolin Testopel Sulfate Ulmer Unimed Watson", "definition": "A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.\n    ", "id": "MESH:D013739"}
{"mention": "erectile dysfunction", "mention_text": "PURPOSE: We reviewed the results of serum testosterone and prolactin determination in 1,022 patients referred because of erectile dysfunction and compared the data with history, results of physical examination, other etiological investigations and effects of endocrine therapy to refine the rules of cost-effective endocrine screening and to pinpoint actual responsibility for hormonal abnormalities. MATERIALS AND METHODS: Testosterone and prolactin were determined by radioimmunoassay. Every patient was screened for testosterone and 451 were screened for prolactin on the basis of low sexual desire, gynecomastia or testosterone less than 4 ng./ml. Determination was repeated in case of abnormal first results. Prolactin results were compared with those of a previous personal cohort of 1,340 patients with erectile dysfunction and systematic prolactin determination. Main clinical criteria tested regarding efficiency in hormone determination were low sexual desire, small testes and gynecomastia. Endocrine therapy consisted of testosterone heptylate or human chorionic gonadotropin for hypogonadism and bromocriptine for hyperprolactinemia. RESULTS: Testosterone was less than 3 ng./ml. in 107 patients but normal in 40% at repeat determination. The prevalence of repeatedly low testosterone increased with age (4% before age 50 years and 9% 50 years or older). Two pituitary tumors were discovered after testosterone determination. Most of the other low testosterone levels seemed to result from nonorganic hypothalamic dysfunction because of normal serum luteinizing hormone and prolactin and to have only a small role in erectile dysfunction (definite improvement in only 16 of 44 [36%] after androgen therapy, normal morning or nocturnal erections in 30% and definite vasculogenic contributions in 42%). Determining testosterone only in cases of low sexual desire or abnormal physical examination would have missed 40% of the cases with low testosterone, including 37% of those subsequently improved by androgen therapy. Prolactin exceeded 20 ng./ml. in 5 men and was normal in 2 at repeat determination. Only 1 prolactinoma was discovered. These data are lower than those we found during the last 2 decades (overall prolactin greater than 20 ng./ml. in 1.86% of 1,821 patients, prolactinomas in 7, 0.38%). Bromocriptine was definitely effective in cases with prolactin greater than 35 ng./ml. (8 of 12 compared to only 9 of 22 cases with prolactin between 20 and 35 ng./ml.). Testosterone was low in less than 50% of cases with prolactin greater than 35 ng./ml. CONCLUSIONS: Low prevalences and effects of low testosterone and high prolactin in erectile dysfunction cannot justify their routine determination. However, cost-effective screening strategies recommended so far missed 40 to 50% of cases improved with endocrine therapy and the pituitary tumors. We now advocate that before age 50 years testosterone be determined only in cases of low sexual desire and abnormal physical examination but that it be measured in all men older than 50 years. Prolactin should be determined only in cases of low sexual desire, gynecomastia and/or testosterone less than 4 ng./ml.", "entity": "Erectile Dysfunction", "aliases": "Dysfunction Erectile Impotence Male Sexual", "definition": "The inability in the male to have a PENILE ERECTION due to psychological or organ dysfunction.\n    ", "id": "MESH:D007172"}
{"mention": "Testosterone", "mention_text": "PURPOSE: We reviewed the results of serum testosterone and prolactin determination in 1,022 patients referred because of erectile dysfunction and compared the data with history, results of physical examination, other etiological investigations and effects of endocrine therapy to refine the rules of cost-effective endocrine screening and to pinpoint actual responsibility for hormonal abnormalities. MATERIALS AND METHODS: Testosterone and prolactin were determined by radioimmunoassay. Every patient was screened for testosterone and 451 were screened for prolactin on the basis of low sexual desire, gynecomastia or testosterone less than 4 ng./ml. Determination was repeated in case of abnormal first results. Prolactin results were compared with those of a previous personal cohort of 1,340 patients with erectile dysfunction and systematic prolactin determination. Main clinical criteria tested regarding efficiency in hormone determination were low sexual desire, small testes and gynecomastia. Endocrine therapy consisted of testosterone heptylate or human chorionic gonadotropin for hypogonadism and bromocriptine for hyperprolactinemia. RESULTS: Testosterone was less than 3 ng./ml. in 107 patients but normal in 40% at repeat determination. The prevalence of repeatedly low testosterone increased with age (4% before age 50 years and 9% 50 years or older). Two pituitary tumors were discovered after testosterone determination. Most of the other low testosterone levels seemed to result from nonorganic hypothalamic dysfunction because of normal serum luteinizing hormone and prolactin and to have only a small role in erectile dysfunction (definite improvement in only 16 of 44 [36%] after androgen therapy, normal morning or nocturnal erections in 30% and definite vasculogenic contributions in 42%). Determining testosterone only in cases of low sexual desire or abnormal physical examination would have missed 40% of the cases with low testosterone, including 37% of those subsequently improved by androgen therapy. Prolactin exceeded 20 ng./ml. in 5 men and was normal in 2 at repeat determination. Only 1 prolactinoma was discovered. These data are lower than those we found during the last 2 decades (overall prolactin greater than 20 ng./ml. in 1.86% of 1,821 patients, prolactinomas in 7, 0.38%). Bromocriptine was definitely effective in cases with prolactin greater than 35 ng./ml. (8 of 12 compared to only 9 of 22 cases with prolactin between 20 and 35 ng./ml.). Testosterone was low in less than 50% of cases with prolactin greater than 35 ng./ml. CONCLUSIONS: Low prevalences and effects of low testosterone and high prolactin in erectile dysfunction cannot justify their routine determination. However, cost-effective screening strategies recommended so far missed 40 to 50% of cases improved with endocrine therapy and the pituitary tumors. We now advocate that before age 50 years testosterone be determined only in cases of low sexual desire and abnormal physical examination but that it be measured in all men older than 50 years. Prolactin should be determined only in cases of low sexual desire, gynecomastia and/or testosterone less than 4 ng./ml.", "entity": "Testosterone", "aliases": "17 beta Hydroxy 4 Androsten 3 one 8 alpha 17-beta-Hydroxy-4-Androsten-3-one 17-beta-Hydroxy-8 alpha-4-Androsten-3-one Isotestosterone 8-Isotestosterone AndroGel Androderm Andropatch Androtop AstraZeneca Brand of Testosterone Auxilium Pharmaceuticals Inc. Bartor CEPA Dr. Kade Faulding Ferring GlaxoSmithKline Hauck Histerone Ortho Paladin Pasadena Schering SmithKline Beecham Solvay Sterotate Sustanon Testim Testoderm Testolin Testopel Sulfate Ulmer Unimed Watson", "definition": "A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.\n    ", "id": "MESH:D013739"}
{"mention": "low sexual desire", "mention_text": "PURPOSE: We reviewed the results of serum testosterone and prolactin determination in 1,022 patients referred because of erectile dysfunction and compared the data with history, results of physical examination, other etiological investigations and effects of endocrine therapy to refine the rules of cost-effective endocrine screening and to pinpoint actual responsibility for hormonal abnormalities. MATERIALS AND METHODS: Testosterone and prolactin were determined by radioimmunoassay. Every patient was screened for testosterone and 451 were screened for prolactin on the basis of low sexual desire, gynecomastia or testosterone less than 4 ng./ml. Determination was repeated in case of abnormal first results. Prolactin results were compared with those of a previous personal cohort of 1,340 patients with erectile dysfunction and systematic prolactin determination. Main clinical criteria tested regarding efficiency in hormone determination were low sexual desire, small testes and gynecomastia. Endocrine therapy consisted of testosterone heptylate or human chorionic gonadotropin for hypogonadism and bromocriptine for hyperprolactinemia. RESULTS: Testosterone was less than 3 ng./ml. in 107 patients but normal in 40% at repeat determination. The prevalence of repeatedly low testosterone increased with age (4% before age 50 years and 9% 50 years or older). Two pituitary tumors were discovered after testosterone determination. Most of the other low testosterone levels seemed to result from nonorganic hypothalamic dysfunction because of normal serum luteinizing hormone and prolactin and to have only a small role in erectile dysfunction (definite improvement in only 16 of 44 [36%] after androgen therapy, normal morning or nocturnal erections in 30% and definite vasculogenic contributions in 42%). Determining testosterone only in cases of low sexual desire or abnormal physical examination would have missed 40% of the cases with low testosterone, including 37% of those subsequently improved by androgen therapy. Prolactin exceeded 20 ng./ml. in 5 men and was normal in 2 at repeat determination. Only 1 prolactinoma was discovered. These data are lower than those we found during the last 2 decades (overall prolactin greater than 20 ng./ml. in 1.86% of 1,821 patients, prolactinomas in 7, 0.38%). Bromocriptine was definitely effective in cases with prolactin greater than 35 ng./ml. (8 of 12 compared to only 9 of 22 cases with prolactin between 20 and 35 ng./ml.). Testosterone was low in less than 50% of cases with prolactin greater than 35 ng./ml. CONCLUSIONS: Low prevalences and effects of low testosterone and high prolactin in erectile dysfunction cannot justify their routine determination. However, cost-effective screening strategies recommended so far missed 40 to 50% of cases improved with endocrine therapy and the pituitary tumors. We now advocate that before age 50 years testosterone be determined only in cases of low sexual desire and abnormal physical examination but that it be measured in all men older than 50 years. Prolactin should be determined only in cases of low sexual desire, gynecomastia and/or testosterone less than 4 ng./ml.", "entity": "Sexual Dysfunctions, Psychological", "aliases": "Arousal Disorders Sexual Aversion Disorder Psychosexual Orgasmic Dysfunction Psychological Dysfunctions Frigidity Hypoactive Desire", "definition": "Disturbances in sexual desire and the psychophysiologic changes that characterize the sexual response cycle and cause marked distress and interpersonal difficulty. (APA, DSM-IV, 1994)\n    ", "id": "MESH:D020018"}
{"mention": "gynecomastia", "mention_text": "PURPOSE: We reviewed the results of serum testosterone and prolactin determination in 1,022 patients referred because of erectile dysfunction and compared the data with history, results of physical examination, other etiological investigations and effects of endocrine therapy to refine the rules of cost-effective endocrine screening and to pinpoint actual responsibility for hormonal abnormalities. MATERIALS AND METHODS: Testosterone and prolactin were determined by radioimmunoassay. Every patient was screened for testosterone and 451 were screened for prolactin on the basis of low sexual desire, gynecomastia or testosterone less than 4 ng./ml. Determination was repeated in case of abnormal first results. Prolactin results were compared with those of a previous personal cohort of 1,340 patients with erectile dysfunction and systematic prolactin determination. Main clinical criteria tested regarding efficiency in hormone determination were low sexual desire, small testes and gynecomastia. Endocrine therapy consisted of testosterone heptylate or human chorionic gonadotropin for hypogonadism and bromocriptine for hyperprolactinemia. RESULTS: Testosterone was less than 3 ng./ml. in 107 patients but normal in 40% at repeat determination. The prevalence of repeatedly low testosterone increased with age (4% before age 50 years and 9% 50 years or older). Two pituitary tumors were discovered after testosterone determination. Most of the other low testosterone levels seemed to result from nonorganic hypothalamic dysfunction because of normal serum luteinizing hormone and prolactin and to have only a small role in erectile dysfunction (definite improvement in only 16 of 44 [36%] after androgen therapy, normal morning or nocturnal erections in 30% and definite vasculogenic contributions in 42%). Determining testosterone only in cases of low sexual desire or abnormal physical examination would have missed 40% of the cases with low testosterone, including 37% of those subsequently improved by androgen therapy. Prolactin exceeded 20 ng./ml. in 5 men and was normal in 2 at repeat determination. Only 1 prolactinoma was discovered. These data are lower than those we found during the last 2 decades (overall prolactin greater than 20 ng./ml. in 1.86% of 1,821 patients, prolactinomas in 7, 0.38%). Bromocriptine was definitely effective in cases with prolactin greater than 35 ng./ml. (8 of 12 compared to only 9 of 22 cases with prolactin between 20 and 35 ng./ml.). Testosterone was low in less than 50% of cases with prolactin greater than 35 ng./ml. CONCLUSIONS: Low prevalences and effects of low testosterone and high prolactin in erectile dysfunction cannot justify their routine determination. However, cost-effective screening strategies recommended so far missed 40 to 50% of cases improved with endocrine therapy and the pituitary tumors. We now advocate that before age 50 years testosterone be determined only in cases of low sexual desire and abnormal physical examination but that it be measured in all men older than 50 years. Prolactin should be determined only in cases of low sexual desire, gynecomastia and/or testosterone less than 4 ng./ml.", "entity": "Gynecomastia", "aliases": "Adolescent Gynecomastia Breast Enlargement Male Infant Newborn", "definition": "Enlargement of the BREAST in the males, caused by an excess of ESTROGENS. Physiological gynecomastia is normally observed in NEWBORNS; ADOLESCENT; and AGING males.\n    ", "id": "MESH:D006177"}
{"mention": "testosterone heptylate", "mention_text": "PURPOSE: We reviewed the results of serum testosterone and prolactin determination in 1,022 patients referred because of erectile dysfunction and compared the data with history, results of physical examination, other etiological investigations and effects of endocrine therapy to refine the rules of cost-effective endocrine screening and to pinpoint actual responsibility for hormonal abnormalities. MATERIALS AND METHODS: Testosterone and prolactin were determined by radioimmunoassay. Every patient was screened for testosterone and 451 were screened for prolactin on the basis of low sexual desire, gynecomastia or testosterone less than 4 ng./ml. Determination was repeated in case of abnormal first results. Prolactin results were compared with those of a previous personal cohort of 1,340 patients with erectile dysfunction and systematic prolactin determination. Main clinical criteria tested regarding efficiency in hormone determination were low sexual desire, small testes and gynecomastia. Endocrine therapy consisted of testosterone heptylate or human chorionic gonadotropin for hypogonadism and bromocriptine for hyperprolactinemia. RESULTS: Testosterone was less than 3 ng./ml. in 107 patients but normal in 40% at repeat determination. The prevalence of repeatedly low testosterone increased with age (4% before age 50 years and 9% 50 years or older). Two pituitary tumors were discovered after testosterone determination. Most of the other low testosterone levels seemed to result from nonorganic hypothalamic dysfunction because of normal serum luteinizing hormone and prolactin and to have only a small role in erectile dysfunction (definite improvement in only 16 of 44 [36%] after androgen therapy, normal morning or nocturnal erections in 30% and definite vasculogenic contributions in 42%). Determining testosterone only in cases of low sexual desire or abnormal physical examination would have missed 40% of the cases with low testosterone, including 37% of those subsequently improved by androgen therapy. Prolactin exceeded 20 ng./ml. in 5 men and was normal in 2 at repeat determination. Only 1 prolactinoma was discovered. These data are lower than those we found during the last 2 decades (overall prolactin greater than 20 ng./ml. in 1.86% of 1,821 patients, prolactinomas in 7, 0.38%). Bromocriptine was definitely effective in cases with prolactin greater than 35 ng./ml. (8 of 12 compared to only 9 of 22 cases with prolactin between 20 and 35 ng./ml.). Testosterone was low in less than 50% of cases with prolactin greater than 35 ng./ml. CONCLUSIONS: Low prevalences and effects of low testosterone and high prolactin in erectile dysfunction cannot justify their routine determination. However, cost-effective screening strategies recommended so far missed 40 to 50% of cases improved with endocrine therapy and the pituitary tumors. We now advocate that before age 50 years testosterone be determined only in cases of low sexual desire and abnormal physical examination but that it be measured in all men older than 50 years. Prolactin should be determined only in cases of low sexual desire, gynecomastia and/or testosterone less than 4 ng./ml.", "entity": "testosterone enanthate", "aliases": "Andropository BTG brand of testosterone enanthate Delatestryl Durathate Eifelfango Jenapharm Pasadena Primoteston Depot Roberts Rotexmedica Rugby Schering Testosteron Depot-Rotexmedica Testosteron-Depot Testrin P.A. Theramed Theramex heptanoate heptylate", "definition": "", "id": "MESH:C004648"}
{"mention": "hypogonadism", "mention_text": "PURPOSE: We reviewed the results of serum testosterone and prolactin determination in 1,022 patients referred because of erectile dysfunction and compared the data with history, results of physical examination, other etiological investigations and effects of endocrine therapy to refine the rules of cost-effective endocrine screening and to pinpoint actual responsibility for hormonal abnormalities. MATERIALS AND METHODS: Testosterone and prolactin were determined by radioimmunoassay. Every patient was screened for testosterone and 451 were screened for prolactin on the basis of low sexual desire, gynecomastia or testosterone less than 4 ng./ml. Determination was repeated in case of abnormal first results. Prolactin results were compared with those of a previous personal cohort of 1,340 patients with erectile dysfunction and systematic prolactin determination. Main clinical criteria tested regarding efficiency in hormone determination were low sexual desire, small testes and gynecomastia. Endocrine therapy consisted of testosterone heptylate or human chorionic gonadotropin for hypogonadism and bromocriptine for hyperprolactinemia. RESULTS: Testosterone was less than 3 ng./ml. in 107 patients but normal in 40% at repeat determination. The prevalence of repeatedly low testosterone increased with age (4% before age 50 years and 9% 50 years or older). Two pituitary tumors were discovered after testosterone determination. Most of the other low testosterone levels seemed to result from nonorganic hypothalamic dysfunction because of normal serum luteinizing hormone and prolactin and to have only a small role in erectile dysfunction (definite improvement in only 16 of 44 [36%] after androgen therapy, normal morning or nocturnal erections in 30% and definite vasculogenic contributions in 42%). Determining testosterone only in cases of low sexual desire or abnormal physical examination would have missed 40% of the cases with low testosterone, including 37% of those subsequently improved by androgen therapy. Prolactin exceeded 20 ng./ml. in 5 men and was normal in 2 at repeat determination. Only 1 prolactinoma was discovered. These data are lower than those we found during the last 2 decades (overall prolactin greater than 20 ng./ml. in 1.86% of 1,821 patients, prolactinomas in 7, 0.38%). Bromocriptine was definitely effective in cases with prolactin greater than 35 ng./ml. (8 of 12 compared to only 9 of 22 cases with prolactin between 20 and 35 ng./ml.). Testosterone was low in less than 50% of cases with prolactin greater than 35 ng./ml. CONCLUSIONS: Low prevalences and effects of low testosterone and high prolactin in erectile dysfunction cannot justify their routine determination. However, cost-effective screening strategies recommended so far missed 40 to 50% of cases improved with endocrine therapy and the pituitary tumors. We now advocate that before age 50 years testosterone be determined only in cases of low sexual desire and abnormal physical examination but that it be measured in all men older than 50 years. Prolactin should be determined only in cases of low sexual desire, gynecomastia and/or testosterone less than 4 ng./ml.", "entity": "Hypogonadism", "aliases": "Hypergonadotropic Hypogonadism Hypogonadotropic Isolated", "definition": "Condition resulting from deficient gonadal functions, such as GAMETOGENESIS and the production of GONADAL STEROID HORMONES. It is characterized by delay in GROWTH, germ cell maturation, and development of secondary sex characteristics. Hypogonadism can be due to a deficiency of GONADOTROPINS (hypogonadotropic hypogonadism) or due to primary gonadal failure (hypergonadotropic hypogonadism).\n    ", "id": "MESH:D007006"}
{"mention": "bromocriptine", "mention_text": "PURPOSE: We reviewed the results of serum testosterone and prolactin determination in 1,022 patients referred because of erectile dysfunction and compared the data with history, results of physical examination, other etiological investigations and effects of endocrine therapy to refine the rules of cost-effective endocrine screening and to pinpoint actual responsibility for hormonal abnormalities. MATERIALS AND METHODS: Testosterone and prolactin were determined by radioimmunoassay. Every patient was screened for testosterone and 451 were screened for prolactin on the basis of low sexual desire, gynecomastia or testosterone less than 4 ng./ml. Determination was repeated in case of abnormal first results. Prolactin results were compared with those of a previous personal cohort of 1,340 patients with erectile dysfunction and systematic prolactin determination. Main clinical criteria tested regarding efficiency in hormone determination were low sexual desire, small testes and gynecomastia. Endocrine therapy consisted of testosterone heptylate or human chorionic gonadotropin for hypogonadism and bromocriptine for hyperprolactinemia. RESULTS: Testosterone was less than 3 ng./ml. in 107 patients but normal in 40% at repeat determination. The prevalence of repeatedly low testosterone increased with age (4% before age 50 years and 9% 50 years or older). Two pituitary tumors were discovered after testosterone determination. Most of the other low testosterone levels seemed to result from nonorganic hypothalamic dysfunction because of normal serum luteinizing hormone and prolactin and to have only a small role in erectile dysfunction (definite improvement in only 16 of 44 [36%] after androgen therapy, normal morning or nocturnal erections in 30% and definite vasculogenic contributions in 42%). Determining testosterone only in cases of low sexual desire or abnormal physical examination would have missed 40% of the cases with low testosterone, including 37% of those subsequently improved by androgen therapy. Prolactin exceeded 20 ng./ml. in 5 men and was normal in 2 at repeat determination. Only 1 prolactinoma was discovered. These data are lower than those we found during the last 2 decades (overall prolactin greater than 20 ng./ml. in 1.86% of 1,821 patients, prolactinomas in 7, 0.38%). Bromocriptine was definitely effective in cases with prolactin greater than 35 ng./ml. (8 of 12 compared to only 9 of 22 cases with prolactin between 20 and 35 ng./ml.). Testosterone was low in less than 50% of cases with prolactin greater than 35 ng./ml. CONCLUSIONS: Low prevalences and effects of low testosterone and high prolactin in erectile dysfunction cannot justify their routine determination. However, cost-effective screening strategies recommended so far missed 40 to 50% of cases improved with endocrine therapy and the pituitary tumors. We now advocate that before age 50 years testosterone be determined only in cases of low sexual desire and abnormal physical examination but that it be measured in all men older than 50 years. Prolactin should be determined only in cases of low sexual desire, gynecomastia and/or testosterone less than 4 ng./ml.", "entity": "Bromocriptine", "aliases": "2 Bromo alpha ergocryptine ergokryptine Bromoergocryptine Mesylate Methanesulfonate Bromoergokryptine 2-Bromo-alpha-ergocryptine 2-Bromo-alpha-ergokryptine 2-Bromoergocryptine 2-Bromoergokryptine Bromocriptin Bromocriptine Bromocryptin CB 154 CB-154 CB154 Parlodel", "definition": "A semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion.\n    ", "id": "MESH:D001971"}
{"mention": "hyperprolactinemia", "mention_text": "PURPOSE: We reviewed the results of serum testosterone and prolactin determination in 1,022 patients referred because of erectile dysfunction and compared the data with history, results of physical examination, other etiological investigations and effects of endocrine therapy to refine the rules of cost-effective endocrine screening and to pinpoint actual responsibility for hormonal abnormalities. MATERIALS AND METHODS: Testosterone and prolactin were determined by radioimmunoassay. Every patient was screened for testosterone and 451 were screened for prolactin on the basis of low sexual desire, gynecomastia or testosterone less than 4 ng./ml. Determination was repeated in case of abnormal first results. Prolactin results were compared with those of a previous personal cohort of 1,340 patients with erectile dysfunction and systematic prolactin determination. Main clinical criteria tested regarding efficiency in hormone determination were low sexual desire, small testes and gynecomastia. Endocrine therapy consisted of testosterone heptylate or human chorionic gonadotropin for hypogonadism and bromocriptine for hyperprolactinemia. RESULTS: Testosterone was less than 3 ng./ml. in 107 patients but normal in 40% at repeat determination. The prevalence of repeatedly low testosterone increased with age (4% before age 50 years and 9% 50 years or older). Two pituitary tumors were discovered after testosterone determination. Most of the other low testosterone levels seemed to result from nonorganic hypothalamic dysfunction because of normal serum luteinizing hormone and prolactin and to have only a small role in erectile dysfunction (definite improvement in only 16 of 44 [36%] after androgen therapy, normal morning or nocturnal erections in 30% and definite vasculogenic contributions in 42%). Determining testosterone only in cases of low sexual desire or abnormal physical examination would have missed 40% of the cases with low testosterone, including 37% of those subsequently improved by androgen therapy. Prolactin exceeded 20 ng./ml. in 5 men and was normal in 2 at repeat determination. Only 1 prolactinoma was discovered. These data are lower than those we found during the last 2 decades (overall prolactin greater than 20 ng./ml. in 1.86% of 1,821 patients, prolactinomas in 7, 0.38%). Bromocriptine was definitely effective in cases with prolactin greater than 35 ng./ml. (8 of 12 compared to only 9 of 22 cases with prolactin between 20 and 35 ng./ml.). Testosterone was low in less than 50% of cases with prolactin greater than 35 ng./ml. CONCLUSIONS: Low prevalences and effects of low testosterone and high prolactin in erectile dysfunction cannot justify their routine determination. However, cost-effective screening strategies recommended so far missed 40 to 50% of cases improved with endocrine therapy and the pituitary tumors. We now advocate that before age 50 years testosterone be determined only in cases of low sexual desire and abnormal physical examination but that it be measured in all men older than 50 years. Prolactin should be determined only in cases of low sexual desire, gynecomastia and/or testosterone less than 4 ng./ml.", "entity": "Hyperprolactinemia", "aliases": "Hyperprolactinaemia Hyperprolactinemia Hyperprolactinemias Hypersecretion Syndrome Prolactin Inappropriate Secretion", "definition": "Increased levels of PROLACTIN in the BLOOD, which may be associated with AMENORRHEA and GALACTORRHEA. Relatively common etiologies include PROLACTINOMA, medication effect, KIDNEY FAILURE, granulomatous diseases of the PITUITARY GLAND, and disorders which interfere with the hypothalamic inhibition of prolactin release. Ectopic (non-pituitary) production of prolactin may also occur. (From Joynt, Clinical Neurology, 1992, Ch36, pp77-8)\n    ", "id": "MESH:D006966"}
{"mention": "pituitary tumors", "mention_text": "PURPOSE: We reviewed the results of serum testosterone and prolactin determination in 1,022 patients referred because of erectile dysfunction and compared the data with history, results of physical examination, other etiological investigations and effects of endocrine therapy to refine the rules of cost-effective endocrine screening and to pinpoint actual responsibility for hormonal abnormalities. MATERIALS AND METHODS: Testosterone and prolactin were determined by radioimmunoassay. Every patient was screened for testosterone and 451 were screened for prolactin on the basis of low sexual desire, gynecomastia or testosterone less than 4 ng./ml. Determination was repeated in case of abnormal first results. Prolactin results were compared with those of a previous personal cohort of 1,340 patients with erectile dysfunction and systematic prolactin determination. Main clinical criteria tested regarding efficiency in hormone determination were low sexual desire, small testes and gynecomastia. Endocrine therapy consisted of testosterone heptylate or human chorionic gonadotropin for hypogonadism and bromocriptine for hyperprolactinemia. RESULTS: Testosterone was less than 3 ng./ml. in 107 patients but normal in 40% at repeat determination. The prevalence of repeatedly low testosterone increased with age (4% before age 50 years and 9% 50 years or older). Two pituitary tumors were discovered after testosterone determination. Most of the other low testosterone levels seemed to result from nonorganic hypothalamic dysfunction because of normal serum luteinizing hormone and prolactin and to have only a small role in erectile dysfunction (definite improvement in only 16 of 44 [36%] after androgen therapy, normal morning or nocturnal erections in 30% and definite vasculogenic contributions in 42%). Determining testosterone only in cases of low sexual desire or abnormal physical examination would have missed 40% of the cases with low testosterone, including 37% of those subsequently improved by androgen therapy. Prolactin exceeded 20 ng./ml. in 5 men and was normal in 2 at repeat determination. Only 1 prolactinoma was discovered. These data are lower than those we found during the last 2 decades (overall prolactin greater than 20 ng./ml. in 1.86% of 1,821 patients, prolactinomas in 7, 0.38%). Bromocriptine was definitely effective in cases with prolactin greater than 35 ng./ml. (8 of 12 compared to only 9 of 22 cases with prolactin between 20 and 35 ng./ml.). Testosterone was low in less than 50% of cases with prolactin greater than 35 ng./ml. CONCLUSIONS: Low prevalences and effects of low testosterone and high prolactin in erectile dysfunction cannot justify their routine determination. However, cost-effective screening strategies recommended so far missed 40 to 50% of cases improved with endocrine therapy and the pituitary tumors. We now advocate that before age 50 years testosterone be determined only in cases of low sexual desire and abnormal physical examination but that it be measured in all men older than 50 years. Prolactin should be determined only in cases of low sexual desire, gynecomastia and/or testosterone less than 4 ng./ml.", "entity": "Pituitary Neoplasms", "aliases": "Adenoma Pituitary Adenomas Cancer of the Cancers Carcinoma Carcinomas Neoplasm Neoplasms Tumor Tumors", "definition": "Neoplasms which arise from or metastasize to the PITUITARY GLAND. The majority of pituitary neoplasms are adenomas, which are divided into non-secreting and secreting forms. Hormone producing forms are further classified by the type of hormone they secrete. Pituitary adenomas may also be characterized by their staining properties (see ADENOMA, BASOPHIL; ADENOMA, ACIDOPHIL; and ADENOMA, CHROMOPHOBE). Pituitary tumors may compress adjacent structures, including the HYPOTHALAMUS, several CRANIAL NERVES, and the OPTIC CHIASM. Chiasmal compression may result in bitemporal HEMIANOPSIA.\n    ", "id": "MESH:D010911"}
{"mention": "hypothalamic dysfunction", "mention_text": "PURPOSE: We reviewed the results of serum testosterone and prolactin determination in 1,022 patients referred because of erectile dysfunction and compared the data with history, results of physical examination, other etiological investigations and effects of endocrine therapy to refine the rules of cost-effective endocrine screening and to pinpoint actual responsibility for hormonal abnormalities. MATERIALS AND METHODS: Testosterone and prolactin were determined by radioimmunoassay. Every patient was screened for testosterone and 451 were screened for prolactin on the basis of low sexual desire, gynecomastia or testosterone less than 4 ng./ml. Determination was repeated in case of abnormal first results. Prolactin results were compared with those of a previous personal cohort of 1,340 patients with erectile dysfunction and systematic prolactin determination. Main clinical criteria tested regarding efficiency in hormone determination were low sexual desire, small testes and gynecomastia. Endocrine therapy consisted of testosterone heptylate or human chorionic gonadotropin for hypogonadism and bromocriptine for hyperprolactinemia. RESULTS: Testosterone was less than 3 ng./ml. in 107 patients but normal in 40% at repeat determination. The prevalence of repeatedly low testosterone increased with age (4% before age 50 years and 9% 50 years or older). Two pituitary tumors were discovered after testosterone determination. Most of the other low testosterone levels seemed to result from nonorganic hypothalamic dysfunction because of normal serum luteinizing hormone and prolactin and to have only a small role in erectile dysfunction (definite improvement in only 16 of 44 [36%] after androgen therapy, normal morning or nocturnal erections in 30% and definite vasculogenic contributions in 42%). Determining testosterone only in cases of low sexual desire or abnormal physical examination would have missed 40% of the cases with low testosterone, including 37% of those subsequently improved by androgen therapy. Prolactin exceeded 20 ng./ml. in 5 men and was normal in 2 at repeat determination. Only 1 prolactinoma was discovered. These data are lower than those we found during the last 2 decades (overall prolactin greater than 20 ng./ml. in 1.86% of 1,821 patients, prolactinomas in 7, 0.38%). Bromocriptine was definitely effective in cases with prolactin greater than 35 ng./ml. (8 of 12 compared to only 9 of 22 cases with prolactin between 20 and 35 ng./ml.). Testosterone was low in less than 50% of cases with prolactin greater than 35 ng./ml. CONCLUSIONS: Low prevalences and effects of low testosterone and high prolactin in erectile dysfunction cannot justify their routine determination. However, cost-effective screening strategies recommended so far missed 40 to 50% of cases improved with endocrine therapy and the pituitary tumors. We now advocate that before age 50 years testosterone be determined only in cases of low sexual desire and abnormal physical examination but that it be measured in all men older than 50 years. Prolactin should be determined only in cases of low sexual desire, gynecomastia and/or testosterone less than 4 ng./ml.", "entity": "Hypothalamic Diseases", "aliases": "Diencephalic Syndrome Pituitary Syndromes Disease Hypothalamic Diseases Disorder Hypothalamic-Adenohypophyseal Hypothalamic-Neurohypophyseal Disorders Dysfunction Dysinhibition Froehlich Froehlich's Froehlichs Adenohypophyseal Neurohypophyseal Overactivity Pseudopuberties Pseudopuberty", "definition": "Neoplastic, inflammatory, infectious, and other diseases of the hypothalamus. Clinical manifestations include appetite disorders; AUTONOMIC NERVOUS SYSTEM DISEASES; SLEEP DISORDERS; behavioral symptoms related to dysfunction of the LIMBIC SYSTEM; and neuroendocrine disorders.\n    ", "id": "MESH:D007027"}
{"mention": "prolactinoma", "mention_text": "PURPOSE: We reviewed the results of serum testosterone and prolactin determination in 1,022 patients referred because of erectile dysfunction and compared the data with history, results of physical examination, other etiological investigations and effects of endocrine therapy to refine the rules of cost-effective endocrine screening and to pinpoint actual responsibility for hormonal abnormalities. MATERIALS AND METHODS: Testosterone and prolactin were determined by radioimmunoassay. Every patient was screened for testosterone and 451 were screened for prolactin on the basis of low sexual desire, gynecomastia or testosterone less than 4 ng./ml. Determination was repeated in case of abnormal first results. Prolactin results were compared with those of a previous personal cohort of 1,340 patients with erectile dysfunction and systematic prolactin determination. Main clinical criteria tested regarding efficiency in hormone determination were low sexual desire, small testes and gynecomastia. Endocrine therapy consisted of testosterone heptylate or human chorionic gonadotropin for hypogonadism and bromocriptine for hyperprolactinemia. RESULTS: Testosterone was less than 3 ng./ml. in 107 patients but normal in 40% at repeat determination. The prevalence of repeatedly low testosterone increased with age (4% before age 50 years and 9% 50 years or older). Two pituitary tumors were discovered after testosterone determination. Most of the other low testosterone levels seemed to result from nonorganic hypothalamic dysfunction because of normal serum luteinizing hormone and prolactin and to have only a small role in erectile dysfunction (definite improvement in only 16 of 44 [36%] after androgen therapy, normal morning or nocturnal erections in 30% and definite vasculogenic contributions in 42%). Determining testosterone only in cases of low sexual desire or abnormal physical examination would have missed 40% of the cases with low testosterone, including 37% of those subsequently improved by androgen therapy. Prolactin exceeded 20 ng./ml. in 5 men and was normal in 2 at repeat determination. Only 1 prolactinoma was discovered. These data are lower than those we found during the last 2 decades (overall prolactin greater than 20 ng./ml. in 1.86% of 1,821 patients, prolactinomas in 7, 0.38%). Bromocriptine was definitely effective in cases with prolactin greater than 35 ng./ml. (8 of 12 compared to only 9 of 22 cases with prolactin between 20 and 35 ng./ml.). Testosterone was low in less than 50% of cases with prolactin greater than 35 ng./ml. CONCLUSIONS: Low prevalences and effects of low testosterone and high prolactin in erectile dysfunction cannot justify their routine determination. However, cost-effective screening strategies recommended so far missed 40 to 50% of cases improved with endocrine therapy and the pituitary tumors. We now advocate that before age 50 years testosterone be determined only in cases of low sexual desire and abnormal physical examination but that it be measured in all men older than 50 years. Prolactin should be determined only in cases of low sexual desire, gynecomastia and/or testosterone less than 4 ng./ml.", "entity": "Prolactinoma", "aliases": "Adenoma Lactotroph Prolactin-Secreting Pituitary Adenomas Macroprolactinoma Macroprolactinomas Microprolactinoma Microprolactinomas PRL Secreting PRL-Secreting Prolactin Prolactin-Producing Producing Prolactinoma Familial Prolactinomas", "definition": "A pituitary adenoma which secretes PROLACTIN, leading to HYPERPROLACTINEMIA. Clinical manifestations include AMENORRHEA; GALACTORRHEA; IMPOTENCE; HEADACHE; visual disturbances; and CEREBROSPINAL FLUID RHINORRHEA.\n    ", "id": "MESH:D015175"}
{"mention": "prolactinomas", "mention_text": "PURPOSE: We reviewed the results of serum testosterone and prolactin determination in 1,022 patients referred because of erectile dysfunction and compared the data with history, results of physical examination, other etiological investigations and effects of endocrine therapy to refine the rules of cost-effective endocrine screening and to pinpoint actual responsibility for hormonal abnormalities. MATERIALS AND METHODS: Testosterone and prolactin were determined by radioimmunoassay. Every patient was screened for testosterone and 451 were screened for prolactin on the basis of low sexual desire, gynecomastia or testosterone less than 4 ng./ml. Determination was repeated in case of abnormal first results. Prolactin results were compared with those of a previous personal cohort of 1,340 patients with erectile dysfunction and systematic prolactin determination. Main clinical criteria tested regarding efficiency in hormone determination were low sexual desire, small testes and gynecomastia. Endocrine therapy consisted of testosterone heptylate or human chorionic gonadotropin for hypogonadism and bromocriptine for hyperprolactinemia. RESULTS: Testosterone was less than 3 ng./ml. in 107 patients but normal in 40% at repeat determination. The prevalence of repeatedly low testosterone increased with age (4% before age 50 years and 9% 50 years or older). Two pituitary tumors were discovered after testosterone determination. Most of the other low testosterone levels seemed to result from nonorganic hypothalamic dysfunction because of normal serum luteinizing hormone and prolactin and to have only a small role in erectile dysfunction (definite improvement in only 16 of 44 [36%] after androgen therapy, normal morning or nocturnal erections in 30% and definite vasculogenic contributions in 42%). Determining testosterone only in cases of low sexual desire or abnormal physical examination would have missed 40% of the cases with low testosterone, including 37% of those subsequently improved by androgen therapy. Prolactin exceeded 20 ng./ml. in 5 men and was normal in 2 at repeat determination. Only 1 prolactinoma was discovered. These data are lower than those we found during the last 2 decades (overall prolactin greater than 20 ng./ml. in 1.86% of 1,821 patients, prolactinomas in 7, 0.38%). Bromocriptine was definitely effective in cases with prolactin greater than 35 ng./ml. (8 of 12 compared to only 9 of 22 cases with prolactin between 20 and 35 ng./ml.). Testosterone was low in less than 50% of cases with prolactin greater than 35 ng./ml. CONCLUSIONS: Low prevalences and effects of low testosterone and high prolactin in erectile dysfunction cannot justify their routine determination. However, cost-effective screening strategies recommended so far missed 40 to 50% of cases improved with endocrine therapy and the pituitary tumors. We now advocate that before age 50 years testosterone be determined only in cases of low sexual desire and abnormal physical examination but that it be measured in all men older than 50 years. Prolactin should be determined only in cases of low sexual desire, gynecomastia and/or testosterone less than 4 ng./ml.", "entity": "Prolactinoma", "aliases": "Adenoma Lactotroph Prolactin-Secreting Pituitary Adenomas Macroprolactinoma Macroprolactinomas Microprolactinoma Microprolactinomas PRL Secreting PRL-Secreting Prolactin Prolactin-Producing Producing Prolactinoma Familial Prolactinomas", "definition": "A pituitary adenoma which secretes PROLACTIN, leading to HYPERPROLACTINEMIA. Clinical manifestations include AMENORRHEA; GALACTORRHEA; IMPOTENCE; HEADACHE; visual disturbances; and CEREBROSPINAL FLUID RHINORRHEA.\n    ", "id": "MESH:D015175"}
{"mention": "Bromocriptine", "mention_text": "PURPOSE: We reviewed the results of serum testosterone and prolactin determination in 1,022 patients referred because of erectile dysfunction and compared the data with history, results of physical examination, other etiological investigations and effects of endocrine therapy to refine the rules of cost-effective endocrine screening and to pinpoint actual responsibility for hormonal abnormalities. MATERIALS AND METHODS: Testosterone and prolactin were determined by radioimmunoassay. Every patient was screened for testosterone and 451 were screened for prolactin on the basis of low sexual desire, gynecomastia or testosterone less than 4 ng./ml. Determination was repeated in case of abnormal first results. Prolactin results were compared with those of a previous personal cohort of 1,340 patients with erectile dysfunction and systematic prolactin determination. Main clinical criteria tested regarding efficiency in hormone determination were low sexual desire, small testes and gynecomastia. Endocrine therapy consisted of testosterone heptylate or human chorionic gonadotropin for hypogonadism and bromocriptine for hyperprolactinemia. RESULTS: Testosterone was less than 3 ng./ml. in 107 patients but normal in 40% at repeat determination. The prevalence of repeatedly low testosterone increased with age (4% before age 50 years and 9% 50 years or older). Two pituitary tumors were discovered after testosterone determination. Most of the other low testosterone levels seemed to result from nonorganic hypothalamic dysfunction because of normal serum luteinizing hormone and prolactin and to have only a small role in erectile dysfunction (definite improvement in only 16 of 44 [36%] after androgen therapy, normal morning or nocturnal erections in 30% and definite vasculogenic contributions in 42%). Determining testosterone only in cases of low sexual desire or abnormal physical examination would have missed 40% of the cases with low testosterone, including 37% of those subsequently improved by androgen therapy. Prolactin exceeded 20 ng./ml. in 5 men and was normal in 2 at repeat determination. Only 1 prolactinoma was discovered. These data are lower than those we found during the last 2 decades (overall prolactin greater than 20 ng./ml. in 1.86% of 1,821 patients, prolactinomas in 7, 0.38%). Bromocriptine was definitely effective in cases with prolactin greater than 35 ng./ml. (8 of 12 compared to only 9 of 22 cases with prolactin between 20 and 35 ng./ml.). Testosterone was low in less than 50% of cases with prolactin greater than 35 ng./ml. CONCLUSIONS: Low prevalences and effects of low testosterone and high prolactin in erectile dysfunction cannot justify their routine determination. However, cost-effective screening strategies recommended so far missed 40 to 50% of cases improved with endocrine therapy and the pituitary tumors. We now advocate that before age 50 years testosterone be determined only in cases of low sexual desire and abnormal physical examination but that it be measured in all men older than 50 years. Prolactin should be determined only in cases of low sexual desire, gynecomastia and/or testosterone less than 4 ng./ml.", "entity": "Bromocriptine", "aliases": "2 Bromo alpha ergocryptine ergokryptine Bromoergocryptine Mesylate Methanesulfonate Bromoergokryptine 2-Bromo-alpha-ergocryptine 2-Bromo-alpha-ergokryptine 2-Bromoergocryptine 2-Bromoergokryptine Bromocriptin Bromocriptine Bromocryptin CB 154 CB-154 CB154 Parlodel", "definition": "A semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion.\n    ", "id": "MESH:D001971"}
{"mention": "Thiopentone", "mention_text": "Thiopentone pretreatment for propofol injection pain in ambulatory patients.", "entity": "Thiopental", "aliases": "Abbott Brand of Thiopental Sodium Altana Pharma Bomathal Braun Merial Nesdonal Nycomed Penthiobarbital Pentothal Sodico Pharmtech Pisa Rhone Merieux Sodipental Thiomebumal Thionembutal Thiopentobarbital Thiopentone Tiobarbital Trapanal", "definition": "A barbiturate that is administered intravenously for the induction of general anesthesia or for the production of complete anesthesia of short duration.\n    ", "id": "MESH:D013874"}
{"mention": "propofol", "mention_text": "Thiopentone pretreatment for propofol injection pain in ambulatory patients.", "entity": "Propofol", "aliases": "2,6 Diisopropylphenol 2,6-Bis(1-methylethyl)phenol 2,6-Diisopropylphenol Abbott Brand of Propofol Alpha Aquafol Astra AstraZeneca Braun Curamed Diprivan Disoprivan Disoprofol Fresenius Kabi Fresofol ICI 35,868 35868 ICI-35,868 ICI-35868 ICI35,868 ICI35868 Ivofol Juste Parnell Pisa MCT Rovi Propofol-Lipuro Recofol Schering Zeneca", "definition": "An intravenous anesthetic agent which has the advantage of a very rapid onset after infusion or bolus injection plus a very short recovery period of a couple of minutes. (From Smith and Reynard, Textbook of Pharmacology, 1992, 1st ed, p206). Propofol has been used as ANTICONVULSANTS and ANTIEMETICS.\n    ", "id": "MESH:D015742"}
{"mention": "pain", "mention_text": "Thiopentone pretreatment for propofol injection pain in ambulatory patients.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "propofol", "mention_text": "This study investigated propofol injection pain in patients undergoing ambulatory anaesthesia. In a randomized, double-blind trial, 90 women were allocated to receive one of three treatments prior to induction of anaesthesia with propofol. Patients in Group C received 2 ml normal saline, Group L, 2 ml, lidocaine 2% (40 mg) and Group T, 2 ml thiopentone 2.5% (50 mg). Venous discomfort was assessed with a visual analogue scale (VAS) 5-15 sec after commencing propofol administration using an infusion pump (rate 1000 micrograms.kg-1.min-1). Loss of consciousness occurred in 60-90 sec. Visual analogue scores (mean +/- SD) during induction were lower in Groups L (3.3 +/- 2.5) and T (4.1 +/- 2.7) than in Group C (5.6 +/- 2.3); P = 0.0031. The incidence of venous discomfort was lower in Group L (76.6%; P < 0.05) than in Group C (100%) but not different from Group T (90%). The VAS scores for recall of pain in the recovery room were correlated with the VAS scores during induction (r = 0.7045; P < 0.0001). Recovery room discharge times were similar: C (75.9 +/- 19.4 min); L 73.6 +/- 21.6 min); T (77.1 +/- 18.9 min). Assessing their overall satisfaction, 89.7% would choose propofol anaesthesia again. We conclude that lidocaine reduces the incidence and severity of propofol injection pain in ambulatory patients whereas thiopentone only reduces its severity.", "entity": "Propofol", "aliases": "2,6 Diisopropylphenol 2,6-Bis(1-methylethyl)phenol 2,6-Diisopropylphenol Abbott Brand of Propofol Alpha Aquafol Astra AstraZeneca Braun Curamed Diprivan Disoprivan Disoprofol Fresenius Kabi Fresofol ICI 35,868 35868 ICI-35,868 ICI-35868 ICI35,868 ICI35868 Ivofol Juste Parnell Pisa MCT Rovi Propofol-Lipuro Recofol Schering Zeneca", "definition": "An intravenous anesthetic agent which has the advantage of a very rapid onset after infusion or bolus injection plus a very short recovery period of a couple of minutes. (From Smith and Reynard, Textbook of Pharmacology, 1992, 1st ed, p206). Propofol has been used as ANTICONVULSANTS and ANTIEMETICS.\n    ", "id": "MESH:D015742"}
{"mention": "pain", "mention_text": "This study investigated propofol injection pain in patients undergoing ambulatory anaesthesia. In a randomized, double-blind trial, 90 women were allocated to receive one of three treatments prior to induction of anaesthesia with propofol. Patients in Group C received 2 ml normal saline, Group L, 2 ml, lidocaine 2% (40 mg) and Group T, 2 ml thiopentone 2.5% (50 mg). Venous discomfort was assessed with a visual analogue scale (VAS) 5-15 sec after commencing propofol administration using an infusion pump (rate 1000 micrograms.kg-1.min-1). Loss of consciousness occurred in 60-90 sec. Visual analogue scores (mean +/- SD) during induction were lower in Groups L (3.3 +/- 2.5) and T (4.1 +/- 2.7) than in Group C (5.6 +/- 2.3); P = 0.0031. The incidence of venous discomfort was lower in Group L (76.6%; P < 0.05) than in Group C (100%) but not different from Group T (90%). The VAS scores for recall of pain in the recovery room were correlated with the VAS scores during induction (r = 0.7045; P < 0.0001). Recovery room discharge times were similar: C (75.9 +/- 19.4 min); L 73.6 +/- 21.6 min); T (77.1 +/- 18.9 min). Assessing their overall satisfaction, 89.7% would choose propofol anaesthesia again. We conclude that lidocaine reduces the incidence and severity of propofol injection pain in ambulatory patients whereas thiopentone only reduces its severity.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "lidocaine", "mention_text": "This study investigated propofol injection pain in patients undergoing ambulatory anaesthesia. In a randomized, double-blind trial, 90 women were allocated to receive one of three treatments prior to induction of anaesthesia with propofol. Patients in Group C received 2 ml normal saline, Group L, 2 ml, lidocaine 2% (40 mg) and Group T, 2 ml thiopentone 2.5% (50 mg). Venous discomfort was assessed with a visual analogue scale (VAS) 5-15 sec after commencing propofol administration using an infusion pump (rate 1000 micrograms.kg-1.min-1). Loss of consciousness occurred in 60-90 sec. Visual analogue scores (mean +/- SD) during induction were lower in Groups L (3.3 +/- 2.5) and T (4.1 +/- 2.7) than in Group C (5.6 +/- 2.3); P = 0.0031. The incidence of venous discomfort was lower in Group L (76.6%; P < 0.05) than in Group C (100%) but not different from Group T (90%). The VAS scores for recall of pain in the recovery room were correlated with the VAS scores during induction (r = 0.7045; P < 0.0001). Recovery room discharge times were similar: C (75.9 +/- 19.4 min); L 73.6 +/- 21.6 min); T (77.1 +/- 18.9 min). Assessing their overall satisfaction, 89.7% would choose propofol anaesthesia again. We conclude that lidocaine reduces the incidence and severity of propofol injection pain in ambulatory patients whereas thiopentone only reduces its severity.", "entity": "Lidocaine", "aliases": "2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide 2-2EtN-2MePhAcN Astrazeneca Brand of Lidocaine Dalcaine Jenapharm Lidocanine Hydrochloride Carbonate (2:1) Hydrocarbonate Monoacetate Monohydrochloride Monohydrate Sulfate (1:1) Lignocaine Novocol Octocaine Strathmann Xylesthesin Xylocaine Xylocitin Xyloneural", "definition": "A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.\n    ", "id": "MESH:D008012"}
{"mention": "thiopentone", "mention_text": "This study investigated propofol injection pain in patients undergoing ambulatory anaesthesia. In a randomized, double-blind trial, 90 women were allocated to receive one of three treatments prior to induction of anaesthesia with propofol. Patients in Group C received 2 ml normal saline, Group L, 2 ml, lidocaine 2% (40 mg) and Group T, 2 ml thiopentone 2.5% (50 mg). Venous discomfort was assessed with a visual analogue scale (VAS) 5-15 sec after commencing propofol administration using an infusion pump (rate 1000 micrograms.kg-1.min-1). Loss of consciousness occurred in 60-90 sec. Visual analogue scores (mean +/- SD) during induction were lower in Groups L (3.3 +/- 2.5) and T (4.1 +/- 2.7) than in Group C (5.6 +/- 2.3); P = 0.0031. The incidence of venous discomfort was lower in Group L (76.6%; P < 0.05) than in Group C (100%) but not different from Group T (90%). The VAS scores for recall of pain in the recovery room were correlated with the VAS scores during induction (r = 0.7045; P < 0.0001). Recovery room discharge times were similar: C (75.9 +/- 19.4 min); L 73.6 +/- 21.6 min); T (77.1 +/- 18.9 min). Assessing their overall satisfaction, 89.7% would choose propofol anaesthesia again. We conclude that lidocaine reduces the incidence and severity of propofol injection pain in ambulatory patients whereas thiopentone only reduces its severity.", "entity": "Thiopental", "aliases": "Abbott Brand of Thiopental Sodium Altana Pharma Bomathal Braun Merial Nesdonal Nycomed Penthiobarbital Pentothal Sodico Pharmtech Pisa Rhone Merieux Sodipental Thiomebumal Thionembutal Thiopentobarbital Thiopentone Tiobarbital Trapanal", "definition": "A barbiturate that is administered intravenously for the induction of general anesthesia or for the production of complete anesthesia of short duration.\n    ", "id": "MESH:D013874"}
{"mention": "Loss of consciousness", "mention_text": "This study investigated propofol injection pain in patients undergoing ambulatory anaesthesia. In a randomized, double-blind trial, 90 women were allocated to receive one of three treatments prior to induction of anaesthesia with propofol. Patients in Group C received 2 ml normal saline, Group L, 2 ml, lidocaine 2% (40 mg) and Group T, 2 ml thiopentone 2.5% (50 mg). Venous discomfort was assessed with a visual analogue scale (VAS) 5-15 sec after commencing propofol administration using an infusion pump (rate 1000 micrograms.kg-1.min-1). Loss of consciousness occurred in 60-90 sec. Visual analogue scores (mean +/- SD) during induction were lower in Groups L (3.3 +/- 2.5) and T (4.1 +/- 2.7) than in Group C (5.6 +/- 2.3); P = 0.0031. The incidence of venous discomfort was lower in Group L (76.6%; P < 0.05) than in Group C (100%) but not different from Group T (90%). The VAS scores for recall of pain in the recovery room were correlated with the VAS scores during induction (r = 0.7045; P < 0.0001). Recovery room discharge times were similar: C (75.9 +/- 19.4 min); L 73.6 +/- 21.6 min); T (77.1 +/- 18.9 min). Assessing their overall satisfaction, 89.7% would choose propofol anaesthesia again. We conclude that lidocaine reduces the incidence and severity of propofol injection pain in ambulatory patients whereas thiopentone only reduces its severity.", "entity": "Unconsciousness", "aliases": "Consciousness Loss of State Unconscious States Unconsciousness", "definition": "Loss of the ability to maintain awareness of self and environment combined with markedly reduced responsiveness to environmental stimuli. (From Adams et al., Principles of Neurology, 6th ed, pp344-5)\n    ", "id": "MESH:D014474"}
{"mention": "glycopyrrolate", "mention_text": "Comparison of i.v. glycopyrrolate and atropine in the prevention of bradycardia and arrhythmias following repeated doses of suxamethonium in children.", "entity": "Glycopyrrolate", "aliases": "Bromide Glycopyrronium Glycopyrrolate", "definition": "A muscarinic antagonist used as an antispasmodic, in some disorders of the gastrointestinal tract, and to reduce salivation with some anesthetics.\n    ", "id": "MESH:D006024"}
{"mention": "atropine", "mention_text": "Comparison of i.v. glycopyrrolate and atropine in the prevention of bradycardia and arrhythmias following repeated doses of suxamethonium in children.", "entity": "Atropine", "aliases": "Anhydrous Atropine Sulfate AtroPen Atropin Augenöl Chauvin Brand Winzer Atropinol of Survival Technology", "definition": "An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.\n    ", "id": "MESH:D001285"}
{"mention": "bradycardia", "mention_text": "Comparison of i.v. glycopyrrolate and atropine in the prevention of bradycardia and arrhythmias following repeated doses of suxamethonium in children.", "entity": "Bradycardia", "aliases": "Bradyarrhythmia Bradyarrhythmias Bradycardia Bradycardias", "definition": "Cardiac arrhythmias that are characterized by excessively slow HEART RATE, usually below 50 beats per minute in human adults. They can be classified broadly into SINOATRIAL NODE dysfunction and ATRIOVENTRICULAR BLOCK.\n    ", "id": "MESH:D001919"}
{"mention": "arrhythmias", "mention_text": "Comparison of i.v. glycopyrrolate and atropine in the prevention of bradycardia and arrhythmias following repeated doses of suxamethonium in children.", "entity": "Arrhythmias, Cardiac", "aliases": "Arrhythmia Cardiac Arrhythmias Arrythmia Dysrhythmia", "definition": "Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.\n    ", "id": "MESH:D001145"}
{"mention": "suxamethonium", "mention_text": "Comparison of i.v. glycopyrrolate and atropine in the prevention of bradycardia and arrhythmias following repeated doses of suxamethonium in children.", "entity": "Succinylcholine", "aliases": "Anectine Bromide Suxamethonium Celocurine Dibromide Succinylcholine Dichloride Diiodide Diperchlorate Ditilin Listenon Lysthenon Myorelaxin Quelicin Succicuran Chloride Di H2O Di-H2O Iodide Succinyldicholine", "definition": "A quaternary skeletal muscle relaxant usually used in the form of its bromide, chloride, or iodide. It is a depolarizing relaxant, acting in about 30 seconds and with a duration of effect averaging three to five minutes. Succinylcholine is used in surgical, anesthetic, and other procedures in which a brief period of muscle relaxation is called for.\n    ", "id": "MESH:D013390"}
{"mention": "glycopyrrolate", "mention_text": "The effectiveness of administration of glycopyrrolate 5 and 10 micrograms kg-1 and atropine 10 and 20 micrograms kg-1 i.v. immediately before the induction of anaesthesia, to prevent arrhythmia and bradycardia following repeated doses of suxamethonium in children, was studied. A control group was included for comparison with the lower dose range of glycopyrrolate and atropine. A frequency of bradycardia of 50% was noted in the control group, but this was not significantly different from the frequency with the active drugs. Bradycardia (defined as a decrease in heart rate to less than 50 beat min-1) was prevented when the larger dose of either active drug was used. It is recommended that either glycopyrrolate 10 micrograms kg-1 or atropine 20 micrograms kg-1 i.v. should immediately precede induction of anaesthesia, in children, if the repeated administration of suxamethonium is anticipated.", "entity": "Glycopyrrolate", "aliases": "Bromide Glycopyrronium Glycopyrrolate", "definition": "A muscarinic antagonist used as an antispasmodic, in some disorders of the gastrointestinal tract, and to reduce salivation with some anesthetics.\n    ", "id": "MESH:D006024"}
{"mention": "atropine", "mention_text": "The effectiveness of administration of glycopyrrolate 5 and 10 micrograms kg-1 and atropine 10 and 20 micrograms kg-1 i.v. immediately before the induction of anaesthesia, to prevent arrhythmia and bradycardia following repeated doses of suxamethonium in children, was studied. A control group was included for comparison with the lower dose range of glycopyrrolate and atropine. A frequency of bradycardia of 50% was noted in the control group, but this was not significantly different from the frequency with the active drugs. Bradycardia (defined as a decrease in heart rate to less than 50 beat min-1) was prevented when the larger dose of either active drug was used. It is recommended that either glycopyrrolate 10 micrograms kg-1 or atropine 20 micrograms kg-1 i.v. should immediately precede induction of anaesthesia, in children, if the repeated administration of suxamethonium is anticipated.", "entity": "Atropine", "aliases": "Anhydrous Atropine Sulfate AtroPen Atropin Augenöl Chauvin Brand Winzer Atropinol of Survival Technology", "definition": "An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.\n    ", "id": "MESH:D001285"}
{"mention": "arrhythmia", "mention_text": "The effectiveness of administration of glycopyrrolate 5 and 10 micrograms kg-1 and atropine 10 and 20 micrograms kg-1 i.v. immediately before the induction of anaesthesia, to prevent arrhythmia and bradycardia following repeated doses of suxamethonium in children, was studied. A control group was included for comparison with the lower dose range of glycopyrrolate and atropine. A frequency of bradycardia of 50% was noted in the control group, but this was not significantly different from the frequency with the active drugs. Bradycardia (defined as a decrease in heart rate to less than 50 beat min-1) was prevented when the larger dose of either active drug was used. It is recommended that either glycopyrrolate 10 micrograms kg-1 or atropine 20 micrograms kg-1 i.v. should immediately precede induction of anaesthesia, in children, if the repeated administration of suxamethonium is anticipated.", "entity": "Arrhythmias, Cardiac", "aliases": "Arrhythmia Cardiac Arrhythmias Arrythmia Dysrhythmia", "definition": "Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.\n    ", "id": "MESH:D001145"}
{"mention": "bradycardia", "mention_text": "The effectiveness of administration of glycopyrrolate 5 and 10 micrograms kg-1 and atropine 10 and 20 micrograms kg-1 i.v. immediately before the induction of anaesthesia, to prevent arrhythmia and bradycardia following repeated doses of suxamethonium in children, was studied. A control group was included for comparison with the lower dose range of glycopyrrolate and atropine. A frequency of bradycardia of 50% was noted in the control group, but this was not significantly different from the frequency with the active drugs. Bradycardia (defined as a decrease in heart rate to less than 50 beat min-1) was prevented when the larger dose of either active drug was used. It is recommended that either glycopyrrolate 10 micrograms kg-1 or atropine 20 micrograms kg-1 i.v. should immediately precede induction of anaesthesia, in children, if the repeated administration of suxamethonium is anticipated.", "entity": "Bradycardia", "aliases": "Bradyarrhythmia Bradyarrhythmias Bradycardia Bradycardias", "definition": "Cardiac arrhythmias that are characterized by excessively slow HEART RATE, usually below 50 beats per minute in human adults. They can be classified broadly into SINOATRIAL NODE dysfunction and ATRIOVENTRICULAR BLOCK.\n    ", "id": "MESH:D001919"}
{"mention": "suxamethonium", "mention_text": "The effectiveness of administration of glycopyrrolate 5 and 10 micrograms kg-1 and atropine 10 and 20 micrograms kg-1 i.v. immediately before the induction of anaesthesia, to prevent arrhythmia and bradycardia following repeated doses of suxamethonium in children, was studied. A control group was included for comparison with the lower dose range of glycopyrrolate and atropine. A frequency of bradycardia of 50% was noted in the control group, but this was not significantly different from the frequency with the active drugs. Bradycardia (defined as a decrease in heart rate to less than 50 beat min-1) was prevented when the larger dose of either active drug was used. It is recommended that either glycopyrrolate 10 micrograms kg-1 or atropine 20 micrograms kg-1 i.v. should immediately precede induction of anaesthesia, in children, if the repeated administration of suxamethonium is anticipated.", "entity": "Succinylcholine", "aliases": "Anectine Bromide Suxamethonium Celocurine Dibromide Succinylcholine Dichloride Diiodide Diperchlorate Ditilin Listenon Lysthenon Myorelaxin Quelicin Succicuran Chloride Di H2O Di-H2O Iodide Succinyldicholine", "definition": "A quaternary skeletal muscle relaxant usually used in the form of its bromide, chloride, or iodide. It is a depolarizing relaxant, acting in about 30 seconds and with a duration of effect averaging three to five minutes. Succinylcholine is used in surgical, anesthetic, and other procedures in which a brief period of muscle relaxation is called for.\n    ", "id": "MESH:D013390"}
{"mention": "Bradycardia", "mention_text": "The effectiveness of administration of glycopyrrolate 5 and 10 micrograms kg-1 and atropine 10 and 20 micrograms kg-1 i.v. immediately before the induction of anaesthesia, to prevent arrhythmia and bradycardia following repeated doses of suxamethonium in children, was studied. A control group was included for comparison with the lower dose range of glycopyrrolate and atropine. A frequency of bradycardia of 50% was noted in the control group, but this was not significantly different from the frequency with the active drugs. Bradycardia (defined as a decrease in heart rate to less than 50 beat min-1) was prevented when the larger dose of either active drug was used. It is recommended that either glycopyrrolate 10 micrograms kg-1 or atropine 20 micrograms kg-1 i.v. should immediately precede induction of anaesthesia, in children, if the repeated administration of suxamethonium is anticipated.", "entity": "Bradycardia", "aliases": "Bradyarrhythmia Bradyarrhythmias Bradycardia Bradycardias", "definition": "Cardiac arrhythmias that are characterized by excessively slow HEART RATE, usually below 50 beats per minute in human adults. They can be classified broadly into SINOATRIAL NODE dysfunction and ATRIOVENTRICULAR BLOCK.\n    ", "id": "MESH:D001919"}
{"mention": "caffeine", "mention_text": "Reduction in caffeine toxicity by acetaminophen.", "entity": "Caffeine", "aliases": "1,3,7-Trimethylxanthine Berlin-Chemie Brand of Caffeine Bristol-Myers Squibb Caffedrine Coffeinum N Purrum Dexitac Durvitan GlaxoSmithKline Merck dura No Doz Passauer Percoffedrinol Percutaféine Pierre Fabre Quick-Pep Republic Drug Seid Thompson 1 2 Vivarin", "definition": "A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling.\n    ", "id": "MESH:D002110"}
{"mention": "toxicity", "mention_text": "Reduction in caffeine toxicity by acetaminophen.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "acetaminophen", "mention_text": "Reduction in caffeine toxicity by acetaminophen.", "entity": "Acetaminophen", "aliases": "APAP Acamol Acephen Acetaco Acetamidophenol Acetaminophen Acetominophen Algotropyl Anacin 3 Anacin-3 Anacin3 Datril Hydroxyacetanilide N-(4-Hydroxyphenyl)acetanilide N-Acetyl-p-aminophenol Panadol Paracetamol Tylenol p-Acetamidophenol p-Hydroxyacetanilide", "definition": "Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.\n    ", "id": "MESH:D000082"}
{"mention": "caffeine", "mention_text": "A patient who allegedly consumed 100 tablets of an over-the-counter analgesic containing sodium acetylsalicylate, caffeine, and acetaminophen displayed no significant CNS stimulation despite the presence of 175 micrograms of caffeine per mL of serum. Because salicylates have been reported to augment the stimulatory effects of caffeine on the CNS, attention was focused on the possibility that the presence of acetaminophen (52 micrograms/mL) reduced the CNS toxicity of caffeine. Studies in DBA/2J mice showed that: 1) pretreatment with acetaminophen (100 mg/kg) increased the interval between the administration of caffeine (300 to 450 mg/kg IP) and the onset of fatal convulsions by a factor of about two; and 2) pretreatment with acetaminophen (75 mg/kg) reduced the incidence of audiogenic seizures produced in the presence of caffeine (12.5 to 75 mg/kg IP). The frequency of sound-induced seizures after 12.5 or 25 mg/kg caffeine was reduced from 50 to 5% by acetaminophen. In the absence of caffeine, acetaminophen (up to 300 mg/kg) did not modify the seizures induced by maximal electroshock and did not alter the convulsant dose of pentylenetetrezol in mice (tests performed by the Anticonvulsant Screening Project of NINCDS). Acetaminophen (up to 150 micrograms/mL) did not retard the incorporation of radioactive adenosine into ATP in slices of rat cerebral cortex. Thus the mechanism by which acetaminophen antagonizes the actions of caffeine in the CNS remains unknown.", "entity": "Caffeine", "aliases": "1,3,7-Trimethylxanthine Berlin-Chemie Brand of Caffeine Bristol-Myers Squibb Caffedrine Coffeinum N Purrum Dexitac Durvitan GlaxoSmithKline Merck dura No Doz Passauer Percoffedrinol Percutaféine Pierre Fabre Quick-Pep Republic Drug Seid Thompson 1 2 Vivarin", "definition": "A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling.\n    ", "id": "MESH:D002110"}
{"mention": "acetaminophen", "mention_text": "A patient who allegedly consumed 100 tablets of an over-the-counter analgesic containing sodium acetylsalicylate, caffeine, and acetaminophen displayed no significant CNS stimulation despite the presence of 175 micrograms of caffeine per mL of serum. Because salicylates have been reported to augment the stimulatory effects of caffeine on the CNS, attention was focused on the possibility that the presence of acetaminophen (52 micrograms/mL) reduced the CNS toxicity of caffeine. Studies in DBA/2J mice showed that: 1) pretreatment with acetaminophen (100 mg/kg) increased the interval between the administration of caffeine (300 to 450 mg/kg IP) and the onset of fatal convulsions by a factor of about two; and 2) pretreatment with acetaminophen (75 mg/kg) reduced the incidence of audiogenic seizures produced in the presence of caffeine (12.5 to 75 mg/kg IP). The frequency of sound-induced seizures after 12.5 or 25 mg/kg caffeine was reduced from 50 to 5% by acetaminophen. In the absence of caffeine, acetaminophen (up to 300 mg/kg) did not modify the seizures induced by maximal electroshock and did not alter the convulsant dose of pentylenetetrezol in mice (tests performed by the Anticonvulsant Screening Project of NINCDS). Acetaminophen (up to 150 micrograms/mL) did not retard the incorporation of radioactive adenosine into ATP in slices of rat cerebral cortex. Thus the mechanism by which acetaminophen antagonizes the actions of caffeine in the CNS remains unknown.", "entity": "Acetaminophen", "aliases": "APAP Acamol Acephen Acetaco Acetamidophenol Acetaminophen Acetominophen Algotropyl Anacin 3 Anacin-3 Anacin3 Datril Hydroxyacetanilide N-(4-Hydroxyphenyl)acetanilide N-Acetyl-p-aminophenol Panadol Paracetamol Tylenol p-Acetamidophenol p-Hydroxyacetanilide", "definition": "Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.\n    ", "id": "MESH:D000082"}
{"mention": "toxicity", "mention_text": "A patient who allegedly consumed 100 tablets of an over-the-counter analgesic containing sodium acetylsalicylate, caffeine, and acetaminophen displayed no significant CNS stimulation despite the presence of 175 micrograms of caffeine per mL of serum. Because salicylates have been reported to augment the stimulatory effects of caffeine on the CNS, attention was focused on the possibility that the presence of acetaminophen (52 micrograms/mL) reduced the CNS toxicity of caffeine. Studies in DBA/2J mice showed that: 1) pretreatment with acetaminophen (100 mg/kg) increased the interval between the administration of caffeine (300 to 450 mg/kg IP) and the onset of fatal convulsions by a factor of about two; and 2) pretreatment with acetaminophen (75 mg/kg) reduced the incidence of audiogenic seizures produced in the presence of caffeine (12.5 to 75 mg/kg IP). The frequency of sound-induced seizures after 12.5 or 25 mg/kg caffeine was reduced from 50 to 5% by acetaminophen. In the absence of caffeine, acetaminophen (up to 300 mg/kg) did not modify the seizures induced by maximal electroshock and did not alter the convulsant dose of pentylenetetrezol in mice (tests performed by the Anticonvulsant Screening Project of NINCDS). Acetaminophen (up to 150 micrograms/mL) did not retard the incorporation of radioactive adenosine into ATP in slices of rat cerebral cortex. Thus the mechanism by which acetaminophen antagonizes the actions of caffeine in the CNS remains unknown.", "entity": "Drug-Related Side Effects and Adverse Reactions", "aliases": "Adverse Drug Event Events Reaction Reactions Related Side Effects and Effect Toxicities Toxicity Drug-Related Drugs of", "definition": "Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.\n    ", "id": "MESH:D064420"}
{"mention": "convulsions", "mention_text": "A patient who allegedly consumed 100 tablets of an over-the-counter analgesic containing sodium acetylsalicylate, caffeine, and acetaminophen displayed no significant CNS stimulation despite the presence of 175 micrograms of caffeine per mL of serum. Because salicylates have been reported to augment the stimulatory effects of caffeine on the CNS, attention was focused on the possibility that the presence of acetaminophen (52 micrograms/mL) reduced the CNS toxicity of caffeine. Studies in DBA/2J mice showed that: 1) pretreatment with acetaminophen (100 mg/kg) increased the interval between the administration of caffeine (300 to 450 mg/kg IP) and the onset of fatal convulsions by a factor of about two; and 2) pretreatment with acetaminophen (75 mg/kg) reduced the incidence of audiogenic seizures produced in the presence of caffeine (12.5 to 75 mg/kg IP). The frequency of sound-induced seizures after 12.5 or 25 mg/kg caffeine was reduced from 50 to 5% by acetaminophen. In the absence of caffeine, acetaminophen (up to 300 mg/kg) did not modify the seizures induced by maximal electroshock and did not alter the convulsant dose of pentylenetetrezol in mice (tests performed by the Anticonvulsant Screening Project of NINCDS). Acetaminophen (up to 150 micrograms/mL) did not retard the incorporation of radioactive adenosine into ATP in slices of rat cerebral cortex. Thus the mechanism by which acetaminophen antagonizes the actions of caffeine in the CNS remains unknown.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "seizures", "mention_text": "A patient who allegedly consumed 100 tablets of an over-the-counter analgesic containing sodium acetylsalicylate, caffeine, and acetaminophen displayed no significant CNS stimulation despite the presence of 175 micrograms of caffeine per mL of serum. Because salicylates have been reported to augment the stimulatory effects of caffeine on the CNS, attention was focused on the possibility that the presence of acetaminophen (52 micrograms/mL) reduced the CNS toxicity of caffeine. Studies in DBA/2J mice showed that: 1) pretreatment with acetaminophen (100 mg/kg) increased the interval between the administration of caffeine (300 to 450 mg/kg IP) and the onset of fatal convulsions by a factor of about two; and 2) pretreatment with acetaminophen (75 mg/kg) reduced the incidence of audiogenic seizures produced in the presence of caffeine (12.5 to 75 mg/kg IP). The frequency of sound-induced seizures after 12.5 or 25 mg/kg caffeine was reduced from 50 to 5% by acetaminophen. In the absence of caffeine, acetaminophen (up to 300 mg/kg) did not modify the seizures induced by maximal electroshock and did not alter the convulsant dose of pentylenetetrezol in mice (tests performed by the Anticonvulsant Screening Project of NINCDS). Acetaminophen (up to 150 micrograms/mL) did not retard the incorporation of radioactive adenosine into ATP in slices of rat cerebral cortex. Thus the mechanism by which acetaminophen antagonizes the actions of caffeine in the CNS remains unknown.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "pentylenetetrezol", "mention_text": "A patient who allegedly consumed 100 tablets of an over-the-counter analgesic containing sodium acetylsalicylate, caffeine, and acetaminophen displayed no significant CNS stimulation despite the presence of 175 micrograms of caffeine per mL of serum. Because salicylates have been reported to augment the stimulatory effects of caffeine on the CNS, attention was focused on the possibility that the presence of acetaminophen (52 micrograms/mL) reduced the CNS toxicity of caffeine. Studies in DBA/2J mice showed that: 1) pretreatment with acetaminophen (100 mg/kg) increased the interval between the administration of caffeine (300 to 450 mg/kg IP) and the onset of fatal convulsions by a factor of about two; and 2) pretreatment with acetaminophen (75 mg/kg) reduced the incidence of audiogenic seizures produced in the presence of caffeine (12.5 to 75 mg/kg IP). The frequency of sound-induced seizures after 12.5 or 25 mg/kg caffeine was reduced from 50 to 5% by acetaminophen. In the absence of caffeine, acetaminophen (up to 300 mg/kg) did not modify the seizures induced by maximal electroshock and did not alter the convulsant dose of pentylenetetrezol in mice (tests performed by the Anticonvulsant Screening Project of NINCDS). Acetaminophen (up to 150 micrograms/mL) did not retard the incorporation of radioactive adenosine into ATP in slices of rat cerebral cortex. Thus the mechanism by which acetaminophen antagonizes the actions of caffeine in the CNS remains unknown.", "entity": "Pentylenetetrazole", "aliases": "Cardiazol Corasol Corazol Corazole Korazol Korazole Leptazole Metrazol Metrazole Pentamethylenetetrazole Pentazol Pentetrazole Pentylenetetrazol Pentylenetetrazole", "definition": "A pharmaceutical agent that displays activity as a central nervous system and respiratory stimulant. It is considered a non-competitive GAMMA-AMINOBUTYRIC ACID antagonist. Pentylenetetrazole has been used experimentally to study seizure phenomenon and to identify pharmaceuticals that may control seizure susceptibility.\n    ", "id": "MESH:D010433"}
{"mention": "Acetaminophen", "mention_text": "A patient who allegedly consumed 100 tablets of an over-the-counter analgesic containing sodium acetylsalicylate, caffeine, and acetaminophen displayed no significant CNS stimulation despite the presence of 175 micrograms of caffeine per mL of serum. Because salicylates have been reported to augment the stimulatory effects of caffeine on the CNS, attention was focused on the possibility that the presence of acetaminophen (52 micrograms/mL) reduced the CNS toxicity of caffeine. Studies in DBA/2J mice showed that: 1) pretreatment with acetaminophen (100 mg/kg) increased the interval between the administration of caffeine (300 to 450 mg/kg IP) and the onset of fatal convulsions by a factor of about two; and 2) pretreatment with acetaminophen (75 mg/kg) reduced the incidence of audiogenic seizures produced in the presence of caffeine (12.5 to 75 mg/kg IP). The frequency of sound-induced seizures after 12.5 or 25 mg/kg caffeine was reduced from 50 to 5% by acetaminophen. In the absence of caffeine, acetaminophen (up to 300 mg/kg) did not modify the seizures induced by maximal electroshock and did not alter the convulsant dose of pentylenetetrezol in mice (tests performed by the Anticonvulsant Screening Project of NINCDS). Acetaminophen (up to 150 micrograms/mL) did not retard the incorporation of radioactive adenosine into ATP in slices of rat cerebral cortex. Thus the mechanism by which acetaminophen antagonizes the actions of caffeine in the CNS remains unknown.", "entity": "Acetaminophen", "aliases": "APAP Acamol Acephen Acetaco Acetamidophenol Acetaminophen Acetominophen Algotropyl Anacin 3 Anacin-3 Anacin3 Datril Hydroxyacetanilide N-(4-Hydroxyphenyl)acetanilide N-Acetyl-p-aminophenol Panadol Paracetamol Tylenol p-Acetamidophenol p-Hydroxyacetanilide", "definition": "Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.\n    ", "id": "MESH:D000082"}
{"mention": "adenosine", "mention_text": "A patient who allegedly consumed 100 tablets of an over-the-counter analgesic containing sodium acetylsalicylate, caffeine, and acetaminophen displayed no significant CNS stimulation despite the presence of 175 micrograms of caffeine per mL of serum. Because salicylates have been reported to augment the stimulatory effects of caffeine on the CNS, attention was focused on the possibility that the presence of acetaminophen (52 micrograms/mL) reduced the CNS toxicity of caffeine. Studies in DBA/2J mice showed that: 1) pretreatment with acetaminophen (100 mg/kg) increased the interval between the administration of caffeine (300 to 450 mg/kg IP) and the onset of fatal convulsions by a factor of about two; and 2) pretreatment with acetaminophen (75 mg/kg) reduced the incidence of audiogenic seizures produced in the presence of caffeine (12.5 to 75 mg/kg IP). The frequency of sound-induced seizures after 12.5 or 25 mg/kg caffeine was reduced from 50 to 5% by acetaminophen. In the absence of caffeine, acetaminophen (up to 300 mg/kg) did not modify the seizures induced by maximal electroshock and did not alter the convulsant dose of pentylenetetrezol in mice (tests performed by the Anticonvulsant Screening Project of NINCDS). Acetaminophen (up to 150 micrograms/mL) did not retard the incorporation of radioactive adenosine into ATP in slices of rat cerebral cortex. Thus the mechanism by which acetaminophen antagonizes the actions of caffeine in the CNS remains unknown.", "entity": "Adenosine", "aliases": "Adenocard Adenoscan Adenosine", "definition": "A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.\n    ", "id": "MESH:D000241"}
{"mention": "ATP", "mention_text": "A patient who allegedly consumed 100 tablets of an over-the-counter analgesic containing sodium acetylsalicylate, caffeine, and acetaminophen displayed no significant CNS stimulation despite the presence of 175 micrograms of caffeine per mL of serum. Because salicylates have been reported to augment the stimulatory effects of caffeine on the CNS, attention was focused on the possibility that the presence of acetaminophen (52 micrograms/mL) reduced the CNS toxicity of caffeine. Studies in DBA/2J mice showed that: 1) pretreatment with acetaminophen (100 mg/kg) increased the interval between the administration of caffeine (300 to 450 mg/kg IP) and the onset of fatal convulsions by a factor of about two; and 2) pretreatment with acetaminophen (75 mg/kg) reduced the incidence of audiogenic seizures produced in the presence of caffeine (12.5 to 75 mg/kg IP). The frequency of sound-induced seizures after 12.5 or 25 mg/kg caffeine was reduced from 50 to 5% by acetaminophen. In the absence of caffeine, acetaminophen (up to 300 mg/kg) did not modify the seizures induced by maximal electroshock and did not alter the convulsant dose of pentylenetetrezol in mice (tests performed by the Anticonvulsant Screening Project of NINCDS). Acetaminophen (up to 150 micrograms/mL) did not retard the incorporation of radioactive adenosine into ATP in slices of rat cerebral cortex. Thus the mechanism by which acetaminophen antagonizes the actions of caffeine in the CNS remains unknown.", "entity": "Adenosine Triphosphate", "aliases": "ATP MgCl2 ATP-MgCl2 Adenosine Triphosphate Calcium Salt Chromium Ammonium Magnesium Chloride Manganese Adenylpyrophosphate Atriphos CaATP Cr(H2O)4 CrATP MgATP MnATP Striadyne", "definition": "An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.\n    ", "id": "MESH:D000255"}
{"mention": "Flestolol", "mention_text": "Flestolol: an ultra-short-acting beta-adrenergic blocking agent.", "entity": "flestolol", "aliases": "ACC 9089 ACC-9089 flestolol sulfate", "definition": "", "id": "MESH:C047847"}
{"mention": "Flestolol", "mention_text": "Flestolol (ACC-9089) is a nonselective, competitive, ultra-short-acting beta-adrenergic blocking agent, without any intrinsic sympathomimetic activity. Flestolol is metabolized by plasma esterases and has an elimination half-life of approximately 6.5 minutes. This agent was well tolerated in healthy volunteers at doses up to 100 micrograms/kg/min. In long-term infusion studies, flestolol was well tolerated at the effective beta-blocking dose (5 micrograms/kg/min) for up to seven days. Flestolol blood concentrations increased linearly with increasing dose and good correlation exists between blood concentrations of flestolol and beta-adrenergic blockade. Flestolol produced a dose-dependent attenuation of isoproterenol-induced tachycardia. Electrophysiologic and hemodynamic effects of flestolol are similar to those of other beta blockers. In contrast with other beta blockers, flestolol-induced effects reverse rapidly (within 30 minutes) following discontinuation because of its short half-life. Flestolol effectively reduced heart rate in patients with supraventricular tachyarrhythmia. In patients with unstable angina, flestolol infusion was found to be safe and effective in controlling chest pain. It is concluded that flestolol is a potent, well-tolerated, ultra-short-acting beta-adrenergic blocking agent. Use of flestolol in the critical care setting is currently undergoing investigation.", "entity": "flestolol", "aliases": "ACC 9089 ACC-9089 flestolol sulfate", "definition": "", "id": "MESH:C047847"}
{"mention": "ACC-9089", "mention_text": "Flestolol (ACC-9089) is a nonselective, competitive, ultra-short-acting beta-adrenergic blocking agent, without any intrinsic sympathomimetic activity. Flestolol is metabolized by plasma esterases and has an elimination half-life of approximately 6.5 minutes. This agent was well tolerated in healthy volunteers at doses up to 100 micrograms/kg/min. In long-term infusion studies, flestolol was well tolerated at the effective beta-blocking dose (5 micrograms/kg/min) for up to seven days. Flestolol blood concentrations increased linearly with increasing dose and good correlation exists between blood concentrations of flestolol and beta-adrenergic blockade. Flestolol produced a dose-dependent attenuation of isoproterenol-induced tachycardia. Electrophysiologic and hemodynamic effects of flestolol are similar to those of other beta blockers. In contrast with other beta blockers, flestolol-induced effects reverse rapidly (within 30 minutes) following discontinuation because of its short half-life. Flestolol effectively reduced heart rate in patients with supraventricular tachyarrhythmia. In patients with unstable angina, flestolol infusion was found to be safe and effective in controlling chest pain. It is concluded that flestolol is a potent, well-tolerated, ultra-short-acting beta-adrenergic blocking agent. Use of flestolol in the critical care setting is currently undergoing investigation.", "entity": "flestolol", "aliases": "ACC 9089 ACC-9089 flestolol sulfate", "definition": "", "id": "MESH:C047847"}
{"mention": "flestolol", "mention_text": "Flestolol (ACC-9089) is a nonselective, competitive, ultra-short-acting beta-adrenergic blocking agent, without any intrinsic sympathomimetic activity. Flestolol is metabolized by plasma esterases and has an elimination half-life of approximately 6.5 minutes. This agent was well tolerated in healthy volunteers at doses up to 100 micrograms/kg/min. In long-term infusion studies, flestolol was well tolerated at the effective beta-blocking dose (5 micrograms/kg/min) for up to seven days. Flestolol blood concentrations increased linearly with increasing dose and good correlation exists between blood concentrations of flestolol and beta-adrenergic blockade. Flestolol produced a dose-dependent attenuation of isoproterenol-induced tachycardia. Electrophysiologic and hemodynamic effects of flestolol are similar to those of other beta blockers. In contrast with other beta blockers, flestolol-induced effects reverse rapidly (within 30 minutes) following discontinuation because of its short half-life. Flestolol effectively reduced heart rate in patients with supraventricular tachyarrhythmia. In patients with unstable angina, flestolol infusion was found to be safe and effective in controlling chest pain. It is concluded that flestolol is a potent, well-tolerated, ultra-short-acting beta-adrenergic blocking agent. Use of flestolol in the critical care setting is currently undergoing investigation.", "entity": "flestolol", "aliases": "ACC 9089 ACC-9089 flestolol sulfate", "definition": "", "id": "MESH:C047847"}
{"mention": "isoproterenol", "mention_text": "Flestolol (ACC-9089) is a nonselective, competitive, ultra-short-acting beta-adrenergic blocking agent, without any intrinsic sympathomimetic activity. Flestolol is metabolized by plasma esterases and has an elimination half-life of approximately 6.5 minutes. This agent was well tolerated in healthy volunteers at doses up to 100 micrograms/kg/min. In long-term infusion studies, flestolol was well tolerated at the effective beta-blocking dose (5 micrograms/kg/min) for up to seven days. Flestolol blood concentrations increased linearly with increasing dose and good correlation exists between blood concentrations of flestolol and beta-adrenergic blockade. Flestolol produced a dose-dependent attenuation of isoproterenol-induced tachycardia. Electrophysiologic and hemodynamic effects of flestolol are similar to those of other beta blockers. In contrast with other beta blockers, flestolol-induced effects reverse rapidly (within 30 minutes) following discontinuation because of its short half-life. Flestolol effectively reduced heart rate in patients with supraventricular tachyarrhythmia. In patients with unstable angina, flestolol infusion was found to be safe and effective in controlling chest pain. It is concluded that flestolol is a potent, well-tolerated, ultra-short-acting beta-adrenergic blocking agent. Use of flestolol in the critical care setting is currently undergoing investigation.", "entity": "Isoproterenol", "aliases": "4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol Euspiran Hydrochloride Isoproterenol Isadrin Isadrine Isoprenaline Isopropyl Noradrenaline Isopropylarterenol Isopropylnoradrenaline Isopropylnorepinephrine Sulfate Isuprel Izadrin Norisodrine Novodrin", "definition": "Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.\n    ", "id": "MESH:D007545"}
{"mention": "tachycardia", "mention_text": "Flestolol (ACC-9089) is a nonselective, competitive, ultra-short-acting beta-adrenergic blocking agent, without any intrinsic sympathomimetic activity. Flestolol is metabolized by plasma esterases and has an elimination half-life of approximately 6.5 minutes. This agent was well tolerated in healthy volunteers at doses up to 100 micrograms/kg/min. In long-term infusion studies, flestolol was well tolerated at the effective beta-blocking dose (5 micrograms/kg/min) for up to seven days. Flestolol blood concentrations increased linearly with increasing dose and good correlation exists between blood concentrations of flestolol and beta-adrenergic blockade. Flestolol produced a dose-dependent attenuation of isoproterenol-induced tachycardia. Electrophysiologic and hemodynamic effects of flestolol are similar to those of other beta blockers. In contrast with other beta blockers, flestolol-induced effects reverse rapidly (within 30 minutes) following discontinuation because of its short half-life. Flestolol effectively reduced heart rate in patients with supraventricular tachyarrhythmia. In patients with unstable angina, flestolol infusion was found to be safe and effective in controlling chest pain. It is concluded that flestolol is a potent, well-tolerated, ultra-short-acting beta-adrenergic blocking agent. Use of flestolol in the critical care setting is currently undergoing investigation.", "entity": "Tachycardia", "aliases": "Tachyarrhythmia Tachyarrhythmias Tachycardia Tachycardias", "definition": "Abnormally rapid heartbeat, usually with a HEART RATE above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia.\n    ", "id": "MESH:D013610"}
{"mention": "supraventricular tachyarrhythmia", "mention_text": "Flestolol (ACC-9089) is a nonselective, competitive, ultra-short-acting beta-adrenergic blocking agent, without any intrinsic sympathomimetic activity. Flestolol is metabolized by plasma esterases and has an elimination half-life of approximately 6.5 minutes. This agent was well tolerated in healthy volunteers at doses up to 100 micrograms/kg/min. In long-term infusion studies, flestolol was well tolerated at the effective beta-blocking dose (5 micrograms/kg/min) for up to seven days. Flestolol blood concentrations increased linearly with increasing dose and good correlation exists between blood concentrations of flestolol and beta-adrenergic blockade. Flestolol produced a dose-dependent attenuation of isoproterenol-induced tachycardia. Electrophysiologic and hemodynamic effects of flestolol are similar to those of other beta blockers. In contrast with other beta blockers, flestolol-induced effects reverse rapidly (within 30 minutes) following discontinuation because of its short half-life. Flestolol effectively reduced heart rate in patients with supraventricular tachyarrhythmia. In patients with unstable angina, flestolol infusion was found to be safe and effective in controlling chest pain. It is concluded that flestolol is a potent, well-tolerated, ultra-short-acting beta-adrenergic blocking agent. Use of flestolol in the critical care setting is currently undergoing investigation.", "entity": "Tachycardia, Supraventricular", "aliases": "Supraventricular Tachycardia Tachycardias", "definition": "A generic expression for any tachycardia that originates above the BUNDLE OF HIS.\n    ", "id": "MESH:D013617"}
{"mention": "unstable angina", "mention_text": "Flestolol (ACC-9089) is a nonselective, competitive, ultra-short-acting beta-adrenergic blocking agent, without any intrinsic sympathomimetic activity. Flestolol is metabolized by plasma esterases and has an elimination half-life of approximately 6.5 minutes. This agent was well tolerated in healthy volunteers at doses up to 100 micrograms/kg/min. In long-term infusion studies, flestolol was well tolerated at the effective beta-blocking dose (5 micrograms/kg/min) for up to seven days. Flestolol blood concentrations increased linearly with increasing dose and good correlation exists between blood concentrations of flestolol and beta-adrenergic blockade. Flestolol produced a dose-dependent attenuation of isoproterenol-induced tachycardia. Electrophysiologic and hemodynamic effects of flestolol are similar to those of other beta blockers. In contrast with other beta blockers, flestolol-induced effects reverse rapidly (within 30 minutes) following discontinuation because of its short half-life. Flestolol effectively reduced heart rate in patients with supraventricular tachyarrhythmia. In patients with unstable angina, flestolol infusion was found to be safe and effective in controlling chest pain. It is concluded that flestolol is a potent, well-tolerated, ultra-short-acting beta-adrenergic blocking agent. Use of flestolol in the critical care setting is currently undergoing investigation.", "entity": "Angina, Unstable", "aliases": "Angina Pectori Unstable Pectoris at Rest Preinfarction Anginas Myocardial Syndrome Syndromes", "definition": "Precordial pain at rest, which may precede a MYOCARDIAL INFARCTION.\n    ", "id": "MESH:D000789"}
{"mention": "chest pain", "mention_text": "Flestolol (ACC-9089) is a nonselective, competitive, ultra-short-acting beta-adrenergic blocking agent, without any intrinsic sympathomimetic activity. Flestolol is metabolized by plasma esterases and has an elimination half-life of approximately 6.5 minutes. This agent was well tolerated in healthy volunteers at doses up to 100 micrograms/kg/min. In long-term infusion studies, flestolol was well tolerated at the effective beta-blocking dose (5 micrograms/kg/min) for up to seven days. Flestolol blood concentrations increased linearly with increasing dose and good correlation exists between blood concentrations of flestolol and beta-adrenergic blockade. Flestolol produced a dose-dependent attenuation of isoproterenol-induced tachycardia. Electrophysiologic and hemodynamic effects of flestolol are similar to those of other beta blockers. In contrast with other beta blockers, flestolol-induced effects reverse rapidly (within 30 minutes) following discontinuation because of its short half-life. Flestolol effectively reduced heart rate in patients with supraventricular tachyarrhythmia. In patients with unstable angina, flestolol infusion was found to be safe and effective in controlling chest pain. It is concluded that flestolol is a potent, well-tolerated, ultra-short-acting beta-adrenergic blocking agent. Use of flestolol in the critical care setting is currently undergoing investigation.", "entity": "Chest Pain", "aliases": "Chest Pain Pains", "definition": "Pressure, burning, or numbness in the chest.\n    ", "id": "MESH:D002637"}
{"mention": "calcium", "mention_text": "Adverse effect of the calcium channel blocker nitrendipine on nephrosclerosis in rats with renovascular hypertension.", "entity": "Calcium", "aliases": "Blood Coagulation Factor IV Calcium", "definition": "A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.\n    ", "id": "MESH:D002118"}
{"mention": "nitrendipine", "mention_text": "Adverse effect of the calcium channel blocker nitrendipine on nephrosclerosis in rats with renovascular hypertension.", "entity": "Nitrendipine", "aliases": "1A Brand of Nitrendipine Pharma Nitren AL Nitrendipin AbZ Nitre Aliud Almirall Alpharma Apogepha Atid Azupharma BC Balminil Basics Bay e 5009 Bayer Bayotensin Baypresol Baypress Bayvit Nitrendipino Biochemie Nitrendi Biomed Dexcel Docpharm Elan Elfar Gericin Heumann Hexal Jenapharm Juta Jutapress KSK Nitrend Lich Lichtenstein Lindo Lindopharm Merck dura Nidrel Niprina Puren Nitre-Puren NitrePuren Nitregamma acis Nitrendepat Nitrendidoc Nitrendimerck Stada beta ratiopharm Nitrendipin-ratiopharm Q", "definition": "A calcium channel blocker with marked vasodilator action. It is an effective antihypertensive agent and differs from other calcium channel blockers in that it does not reduce glomerular filtration rate and is mildly natriuretic, rather than sodium retentive.\n    ", "id": "MESH:D009568"}
{"mention": "nephrosclerosis", "mention_text": "Adverse effect of the calcium channel blocker nitrendipine on nephrosclerosis in rats with renovascular hypertension.", "entity": "Nephrosclerosis", "aliases": "Nephroscleroses Nephrosclerosis", "definition": "Hardening of the KIDNEY due to infiltration by fibrous connective tissue (FIBROSIS), usually caused by renovascular diseases or chronic HYPERTENSION. Nephrosclerosis leads to renal ISCHEMIA.\n    ", "id": "MESH:D009400"}
{"mention": "renovascular hypertension", "mention_text": "Adverse effect of the calcium channel blocker nitrendipine on nephrosclerosis in rats with renovascular hypertension.", "entity": "Hypertension, Renovascular", "aliases": "Goldblatt Hypertension Syndrome Renovascular", "definition": "Hypertension due to RENAL ARTERY OBSTRUCTION or compression.\n    ", "id": "MESH:D006978"}
{"mention": "calcium", "mention_text": "The effect of a 6-week treatment with the calcium channel blocker nitrendipine or the angiotensin converting enzyme inhibitor enalapril on blood pressure, albuminuria, renal hemodynamics, and morphology of the nonclipped kidney was studied in rats with two-kidney, one clip renovascular hypertension. Six weeks after clipping of one renal artery, hypertensive rats (178 +/- 4 mm Hg) were randomly assigned to three groups: untreated hypertensive controls (n = 8), enalapril-treated (n = 8), or nitrendipine-treated (n = 10). Sham-operated rats served as normotensive controls (128 +/- 3 mm Hg, n = 8). After 6 weeks of treatment, renal hemodynamics (glomerular filtration rate and renal plasma flow) were measured in the anesthetized rats. Renal tissue was obtained for determination of glomerular size and sclerosis. Enalapril but not nitrendipine reduced blood pressure significantly. After 6 weeks of therapy, glomerular filtration rate was not different among the studied groups. Renal plasma flow increased, but albumin excretion and glomerulosclerosis did not change after enalapril treatment. In contrast, in the nitrendipine-treated group albuminuria increased from 12.8 +/- 2 progressively to 163 +/- 55 compared with 19.2 +/- 9 mg/24 hr in the hypertensive controls. Furthermore, glomerulosclerosis index was significantly increased in the nitrendipine-treated group compared with the hypertensive controls (0.38 +/- 0.1 versus 0.13 +/- 0.04). In addition, glomerular size was higher in the nitrendipine-treated group (14.9 +/- 0.17 10(-3) mm2) but lower in the enalapril-treated group (11.5 +/- 0.15 10(-3) mm2) compared with the hypertensive controls (12.1 +/- 0.17 10(-3) mm2).(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Calcium", "aliases": "Blood Coagulation Factor IV Calcium", "definition": "A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.\n    ", "id": "MESH:D002118"}
{"mention": "nitrendipine", "mention_text": "The effect of a 6-week treatment with the calcium channel blocker nitrendipine or the angiotensin converting enzyme inhibitor enalapril on blood pressure, albuminuria, renal hemodynamics, and morphology of the nonclipped kidney was studied in rats with two-kidney, one clip renovascular hypertension. Six weeks after clipping of one renal artery, hypertensive rats (178 +/- 4 mm Hg) were randomly assigned to three groups: untreated hypertensive controls (n = 8), enalapril-treated (n = 8), or nitrendipine-treated (n = 10). Sham-operated rats served as normotensive controls (128 +/- 3 mm Hg, n = 8). After 6 weeks of treatment, renal hemodynamics (glomerular filtration rate and renal plasma flow) were measured in the anesthetized rats. Renal tissue was obtained for determination of glomerular size and sclerosis. Enalapril but not nitrendipine reduced blood pressure significantly. After 6 weeks of therapy, glomerular filtration rate was not different among the studied groups. Renal plasma flow increased, but albumin excretion and glomerulosclerosis did not change after enalapril treatment. In contrast, in the nitrendipine-treated group albuminuria increased from 12.8 +/- 2 progressively to 163 +/- 55 compared with 19.2 +/- 9 mg/24 hr in the hypertensive controls. Furthermore, glomerulosclerosis index was significantly increased in the nitrendipine-treated group compared with the hypertensive controls (0.38 +/- 0.1 versus 0.13 +/- 0.04). In addition, glomerular size was higher in the nitrendipine-treated group (14.9 +/- 0.17 10(-3) mm2) but lower in the enalapril-treated group (11.5 +/- 0.15 10(-3) mm2) compared with the hypertensive controls (12.1 +/- 0.17 10(-3) mm2).(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Nitrendipine", "aliases": "1A Brand of Nitrendipine Pharma Nitren AL Nitrendipin AbZ Nitre Aliud Almirall Alpharma Apogepha Atid Azupharma BC Balminil Basics Bay e 5009 Bayer Bayotensin Baypresol Baypress Bayvit Nitrendipino Biochemie Nitrendi Biomed Dexcel Docpharm Elan Elfar Gericin Heumann Hexal Jenapharm Juta Jutapress KSK Nitrend Lich Lichtenstein Lindo Lindopharm Merck dura Nidrel Niprina Puren Nitre-Puren NitrePuren Nitregamma acis Nitrendepat Nitrendidoc Nitrendimerck Stada beta ratiopharm Nitrendipin-ratiopharm Q", "definition": "A calcium channel blocker with marked vasodilator action. It is an effective antihypertensive agent and differs from other calcium channel blockers in that it does not reduce glomerular filtration rate and is mildly natriuretic, rather than sodium retentive.\n    ", "id": "MESH:D009568"}
{"mention": "angiotensin", "mention_text": "The effect of a 6-week treatment with the calcium channel blocker nitrendipine or the angiotensin converting enzyme inhibitor enalapril on blood pressure, albuminuria, renal hemodynamics, and morphology of the nonclipped kidney was studied in rats with two-kidney, one clip renovascular hypertension. Six weeks after clipping of one renal artery, hypertensive rats (178 +/- 4 mm Hg) were randomly assigned to three groups: untreated hypertensive controls (n = 8), enalapril-treated (n = 8), or nitrendipine-treated (n = 10). Sham-operated rats served as normotensive controls (128 +/- 3 mm Hg, n = 8). After 6 weeks of treatment, renal hemodynamics (glomerular filtration rate and renal plasma flow) were measured in the anesthetized rats. Renal tissue was obtained for determination of glomerular size and sclerosis. Enalapril but not nitrendipine reduced blood pressure significantly. After 6 weeks of therapy, glomerular filtration rate was not different among the studied groups. Renal plasma flow increased, but albumin excretion and glomerulosclerosis did not change after enalapril treatment. In contrast, in the nitrendipine-treated group albuminuria increased from 12.8 +/- 2 progressively to 163 +/- 55 compared with 19.2 +/- 9 mg/24 hr in the hypertensive controls. Furthermore, glomerulosclerosis index was significantly increased in the nitrendipine-treated group compared with the hypertensive controls (0.38 +/- 0.1 versus 0.13 +/- 0.04). In addition, glomerular size was higher in the nitrendipine-treated group (14.9 +/- 0.17 10(-3) mm2) but lower in the enalapril-treated group (11.5 +/- 0.15 10(-3) mm2) compared with the hypertensive controls (12.1 +/- 0.17 10(-3) mm2).(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Angiotensins", "aliases": "Angiotensin Angiotensins", "definition": "Oligopeptides which are important in the regulation of blood pressure (VASOCONSTRICTION) and fluid homeostasis via the RENIN-ANGIOTENSIN SYSTEM. These include angiotensins derived naturally from precursor ANGIOTENSINOGEN, and those synthesized.\n    ", "id": "MESH:D000809"}
{"mention": "enalapril", "mention_text": "The effect of a 6-week treatment with the calcium channel blocker nitrendipine or the angiotensin converting enzyme inhibitor enalapril on blood pressure, albuminuria, renal hemodynamics, and morphology of the nonclipped kidney was studied in rats with two-kidney, one clip renovascular hypertension. Six weeks after clipping of one renal artery, hypertensive rats (178 +/- 4 mm Hg) were randomly assigned to three groups: untreated hypertensive controls (n = 8), enalapril-treated (n = 8), or nitrendipine-treated (n = 10). Sham-operated rats served as normotensive controls (128 +/- 3 mm Hg, n = 8). After 6 weeks of treatment, renal hemodynamics (glomerular filtration rate and renal plasma flow) were measured in the anesthetized rats. Renal tissue was obtained for determination of glomerular size and sclerosis. Enalapril but not nitrendipine reduced blood pressure significantly. After 6 weeks of therapy, glomerular filtration rate was not different among the studied groups. Renal plasma flow increased, but albumin excretion and glomerulosclerosis did not change after enalapril treatment. In contrast, in the nitrendipine-treated group albuminuria increased from 12.8 +/- 2 progressively to 163 +/- 55 compared with 19.2 +/- 9 mg/24 hr in the hypertensive controls. Furthermore, glomerulosclerosis index was significantly increased in the nitrendipine-treated group compared with the hypertensive controls (0.38 +/- 0.1 versus 0.13 +/- 0.04). In addition, glomerular size was higher in the nitrendipine-treated group (14.9 +/- 0.17 10(-3) mm2) but lower in the enalapril-treated group (11.5 +/- 0.15 10(-3) mm2) compared with the hypertensive controls (12.1 +/- 0.17 10(-3) mm2).(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Enalapril", "aliases": "Enalapril Maleate MK 421 MK-421 MK421 Renitec Renitek", "definition": "One of the ANGIOTENSIN-CONVERTING ENZYME INHIBITORS that is used to treat hypertension.\n    ", "id": "MESH:D004656"}
{"mention": "albuminuria", "mention_text": "The effect of a 6-week treatment with the calcium channel blocker nitrendipine or the angiotensin converting enzyme inhibitor enalapril on blood pressure, albuminuria, renal hemodynamics, and morphology of the nonclipped kidney was studied in rats with two-kidney, one clip renovascular hypertension. Six weeks after clipping of one renal artery, hypertensive rats (178 +/- 4 mm Hg) were randomly assigned to three groups: untreated hypertensive controls (n = 8), enalapril-treated (n = 8), or nitrendipine-treated (n = 10). Sham-operated rats served as normotensive controls (128 +/- 3 mm Hg, n = 8). After 6 weeks of treatment, renal hemodynamics (glomerular filtration rate and renal plasma flow) were measured in the anesthetized rats. Renal tissue was obtained for determination of glomerular size and sclerosis. Enalapril but not nitrendipine reduced blood pressure significantly. After 6 weeks of therapy, glomerular filtration rate was not different among the studied groups. Renal plasma flow increased, but albumin excretion and glomerulosclerosis did not change after enalapril treatment. In contrast, in the nitrendipine-treated group albuminuria increased from 12.8 +/- 2 progressively to 163 +/- 55 compared with 19.2 +/- 9 mg/24 hr in the hypertensive controls. Furthermore, glomerulosclerosis index was significantly increased in the nitrendipine-treated group compared with the hypertensive controls (0.38 +/- 0.1 versus 0.13 +/- 0.04). In addition, glomerular size was higher in the nitrendipine-treated group (14.9 +/- 0.17 10(-3) mm2) but lower in the enalapril-treated group (11.5 +/- 0.15 10(-3) mm2) compared with the hypertensive controls (12.1 +/- 0.17 10(-3) mm2).(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Albuminuria", "aliases": "Albuminuria Albuminurias", "definition": "The presence of albumin in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D000419"}
{"mention": "renovascular hypertension", "mention_text": "The effect of a 6-week treatment with the calcium channel blocker nitrendipine or the angiotensin converting enzyme inhibitor enalapril on blood pressure, albuminuria, renal hemodynamics, and morphology of the nonclipped kidney was studied in rats with two-kidney, one clip renovascular hypertension. Six weeks after clipping of one renal artery, hypertensive rats (178 +/- 4 mm Hg) were randomly assigned to three groups: untreated hypertensive controls (n = 8), enalapril-treated (n = 8), or nitrendipine-treated (n = 10). Sham-operated rats served as normotensive controls (128 +/- 3 mm Hg, n = 8). After 6 weeks of treatment, renal hemodynamics (glomerular filtration rate and renal plasma flow) were measured in the anesthetized rats. Renal tissue was obtained for determination of glomerular size and sclerosis. Enalapril but not nitrendipine reduced blood pressure significantly. After 6 weeks of therapy, glomerular filtration rate was not different among the studied groups. Renal plasma flow increased, but albumin excretion and glomerulosclerosis did not change after enalapril treatment. In contrast, in the nitrendipine-treated group albuminuria increased from 12.8 +/- 2 progressively to 163 +/- 55 compared with 19.2 +/- 9 mg/24 hr in the hypertensive controls. Furthermore, glomerulosclerosis index was significantly increased in the nitrendipine-treated group compared with the hypertensive controls (0.38 +/- 0.1 versus 0.13 +/- 0.04). In addition, glomerular size was higher in the nitrendipine-treated group (14.9 +/- 0.17 10(-3) mm2) but lower in the enalapril-treated group (11.5 +/- 0.15 10(-3) mm2) compared with the hypertensive controls (12.1 +/- 0.17 10(-3) mm2).(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Hypertension, Renovascular", "aliases": "Goldblatt Hypertension Syndrome Renovascular", "definition": "Hypertension due to RENAL ARTERY OBSTRUCTION or compression.\n    ", "id": "MESH:D006978"}
{"mention": "hypertensive", "mention_text": "The effect of a 6-week treatment with the calcium channel blocker nitrendipine or the angiotensin converting enzyme inhibitor enalapril on blood pressure, albuminuria, renal hemodynamics, and morphology of the nonclipped kidney was studied in rats with two-kidney, one clip renovascular hypertension. Six weeks after clipping of one renal artery, hypertensive rats (178 +/- 4 mm Hg) were randomly assigned to three groups: untreated hypertensive controls (n = 8), enalapril-treated (n = 8), or nitrendipine-treated (n = 10). Sham-operated rats served as normotensive controls (128 +/- 3 mm Hg, n = 8). After 6 weeks of treatment, renal hemodynamics (glomerular filtration rate and renal plasma flow) were measured in the anesthetized rats. Renal tissue was obtained for determination of glomerular size and sclerosis. Enalapril but not nitrendipine reduced blood pressure significantly. After 6 weeks of therapy, glomerular filtration rate was not different among the studied groups. Renal plasma flow increased, but albumin excretion and glomerulosclerosis did not change after enalapril treatment. In contrast, in the nitrendipine-treated group albuminuria increased from 12.8 +/- 2 progressively to 163 +/- 55 compared with 19.2 +/- 9 mg/24 hr in the hypertensive controls. Furthermore, glomerulosclerosis index was significantly increased in the nitrendipine-treated group compared with the hypertensive controls (0.38 +/- 0.1 versus 0.13 +/- 0.04). In addition, glomerular size was higher in the nitrendipine-treated group (14.9 +/- 0.17 10(-3) mm2) but lower in the enalapril-treated group (11.5 +/- 0.15 10(-3) mm2) compared with the hypertensive controls (12.1 +/- 0.17 10(-3) mm2).(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "Enalapril", "mention_text": "The effect of a 6-week treatment with the calcium channel blocker nitrendipine or the angiotensin converting enzyme inhibitor enalapril on blood pressure, albuminuria, renal hemodynamics, and morphology of the nonclipped kidney was studied in rats with two-kidney, one clip renovascular hypertension. Six weeks after clipping of one renal artery, hypertensive rats (178 +/- 4 mm Hg) were randomly assigned to three groups: untreated hypertensive controls (n = 8), enalapril-treated (n = 8), or nitrendipine-treated (n = 10). Sham-operated rats served as normotensive controls (128 +/- 3 mm Hg, n = 8). After 6 weeks of treatment, renal hemodynamics (glomerular filtration rate and renal plasma flow) were measured in the anesthetized rats. Renal tissue was obtained for determination of glomerular size and sclerosis. Enalapril but not nitrendipine reduced blood pressure significantly. After 6 weeks of therapy, glomerular filtration rate was not different among the studied groups. Renal plasma flow increased, but albumin excretion and glomerulosclerosis did not change after enalapril treatment. In contrast, in the nitrendipine-treated group albuminuria increased from 12.8 +/- 2 progressively to 163 +/- 55 compared with 19.2 +/- 9 mg/24 hr in the hypertensive controls. Furthermore, glomerulosclerosis index was significantly increased in the nitrendipine-treated group compared with the hypertensive controls (0.38 +/- 0.1 versus 0.13 +/- 0.04). In addition, glomerular size was higher in the nitrendipine-treated group (14.9 +/- 0.17 10(-3) mm2) but lower in the enalapril-treated group (11.5 +/- 0.15 10(-3) mm2) compared with the hypertensive controls (12.1 +/- 0.17 10(-3) mm2).(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Enalapril", "aliases": "Enalapril Maleate MK 421 MK-421 MK421 Renitec Renitek", "definition": "One of the ANGIOTENSIN-CONVERTING ENZYME INHIBITORS that is used to treat hypertension.\n    ", "id": "MESH:D004656"}
{"mention": "glomerulosclerosis", "mention_text": "The effect of a 6-week treatment with the calcium channel blocker nitrendipine or the angiotensin converting enzyme inhibitor enalapril on blood pressure, albuminuria, renal hemodynamics, and morphology of the nonclipped kidney was studied in rats with two-kidney, one clip renovascular hypertension. Six weeks after clipping of one renal artery, hypertensive rats (178 +/- 4 mm Hg) were randomly assigned to three groups: untreated hypertensive controls (n = 8), enalapril-treated (n = 8), or nitrendipine-treated (n = 10). Sham-operated rats served as normotensive controls (128 +/- 3 mm Hg, n = 8). After 6 weeks of treatment, renal hemodynamics (glomerular filtration rate and renal plasma flow) were measured in the anesthetized rats. Renal tissue was obtained for determination of glomerular size and sclerosis. Enalapril but not nitrendipine reduced blood pressure significantly. After 6 weeks of therapy, glomerular filtration rate was not different among the studied groups. Renal plasma flow increased, but albumin excretion and glomerulosclerosis did not change after enalapril treatment. In contrast, in the nitrendipine-treated group albuminuria increased from 12.8 +/- 2 progressively to 163 +/- 55 compared with 19.2 +/- 9 mg/24 hr in the hypertensive controls. Furthermore, glomerulosclerosis index was significantly increased in the nitrendipine-treated group compared with the hypertensive controls (0.38 +/- 0.1 versus 0.13 +/- 0.04). In addition, glomerular size was higher in the nitrendipine-treated group (14.9 +/- 0.17 10(-3) mm2) but lower in the enalapril-treated group (11.5 +/- 0.15 10(-3) mm2) compared with the hypertensive controls (12.1 +/- 0.17 10(-3) mm2).(ABSTRACT TRUNCATED AT 250 WORDS)", "entity": "Glomerulonephritis", "aliases": "Bright Disease Glomerulonephritides Glomerulonephritis", "definition": "Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.\n    ", "id": "MESH:D005921"}
{"mention": "tinnitus", "mention_text": "Treatment of tinnitus by intratympanic instillation of lignocaine (lidocaine) 2 per cent through ventilation tubes.", "entity": "Tinnitus", "aliases": "Clicking Tinnitus Induced Noise Leudet Leudet's Objective Pulsatile Ringing Buzzing Ringing-Buzzing-Tinnitus Spontaneous Oto Acoustic Emission Oto-Acoustic Subjective Tensor Palatini Tympani of Vascular Origin Leudets", "definition": "A nonspecific symptom of hearing disorder characterized by the sensation of buzzing, ringing, clicking, pulsations, and other noises in the ear. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of COCHLEAR DISEASES; VESTIBULOCOCHLEAR NERVE DISEASES; INTRACRANIAL HYPERTENSION; CRANIOCEREBRAL TRAUMA; and other conditions.\n    ", "id": "MESH:D014012"}
{"mention": "lignocaine", "mention_text": "Treatment of tinnitus by intratympanic instillation of lignocaine (lidocaine) 2 per cent through ventilation tubes.", "entity": "Lidocaine", "aliases": "2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide 2-2EtN-2MePhAcN Astrazeneca Brand of Lidocaine Dalcaine Jenapharm Lidocanine Hydrochloride Carbonate (2:1) Hydrocarbonate Monoacetate Monohydrochloride Monohydrate Sulfate (1:1) Lignocaine Novocol Octocaine Strathmann Xylesthesin Xylocaine Xylocitin Xyloneural", "definition": "A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.\n    ", "id": "MESH:D008012"}
{"mention": "lidocaine", "mention_text": "Treatment of tinnitus by intratympanic instillation of lignocaine (lidocaine) 2 per cent through ventilation tubes.", "entity": "Lidocaine", "aliases": "2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide 2-2EtN-2MePhAcN Astrazeneca Brand of Lidocaine Dalcaine Jenapharm Lidocanine Hydrochloride Carbonate (2:1) Hydrocarbonate Monoacetate Monohydrochloride Monohydrate Sulfate (1:1) Lignocaine Novocol Octocaine Strathmann Xylesthesin Xylocaine Xylocitin Xyloneural", "definition": "A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.\n    ", "id": "MESH:D008012"}
{"mention": "Idiopathic subjective tinnitus", "mention_text": "Idiopathic subjective tinnitus (IST) is one of the most obscure otological pathologies. This paper presents the results of treating IST by intratympanic instillation of lignocaine (lidocaine) 2 per cent through a grommet, for five weekly courses. Fifty-two patients suffering from intractable tinnitus entered this therapeutic trial, but only nine finished all five courses. In one patient, the tinnitus was almost completely abolished, but in all the nine patients the decompensated tinnitus changed to a compensated one. We suggest this mode of treatment for patients that were previously treated by drugs, acupuncture and biofeedback, with disappointing results. Patients should be warned about the side effects of vertigo and vomiting, which subsides gradually with every new instillation, and that the tinnitus may not disappear but will be alleviated, enabling them to cope more easily with the disease and lead a more normal life.", "entity": "Tinnitus", "aliases": "Clicking Tinnitus Induced Noise Leudet Leudet's Objective Pulsatile Ringing Buzzing Ringing-Buzzing-Tinnitus Spontaneous Oto Acoustic Emission Oto-Acoustic Subjective Tensor Palatini Tympani of Vascular Origin Leudets", "definition": "A nonspecific symptom of hearing disorder characterized by the sensation of buzzing, ringing, clicking, pulsations, and other noises in the ear. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of COCHLEAR DISEASES; VESTIBULOCOCHLEAR NERVE DISEASES; INTRACRANIAL HYPERTENSION; CRANIOCEREBRAL TRAUMA; and other conditions.\n    ", "id": "MESH:D014012"}
{"mention": "IST", "mention_text": "Idiopathic subjective tinnitus (IST) is one of the most obscure otological pathologies. This paper presents the results of treating IST by intratympanic instillation of lignocaine (lidocaine) 2 per cent through a grommet, for five weekly courses. Fifty-two patients suffering from intractable tinnitus entered this therapeutic trial, but only nine finished all five courses. In one patient, the tinnitus was almost completely abolished, but in all the nine patients the decompensated tinnitus changed to a compensated one. We suggest this mode of treatment for patients that were previously treated by drugs, acupuncture and biofeedback, with disappointing results. Patients should be warned about the side effects of vertigo and vomiting, which subsides gradually with every new instillation, and that the tinnitus may not disappear but will be alleviated, enabling them to cope more easily with the disease and lead a more normal life.", "entity": "Tinnitus", "aliases": "Clicking Tinnitus Induced Noise Leudet Leudet's Objective Pulsatile Ringing Buzzing Ringing-Buzzing-Tinnitus Spontaneous Oto Acoustic Emission Oto-Acoustic Subjective Tensor Palatini Tympani of Vascular Origin Leudets", "definition": "A nonspecific symptom of hearing disorder characterized by the sensation of buzzing, ringing, clicking, pulsations, and other noises in the ear. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of COCHLEAR DISEASES; VESTIBULOCOCHLEAR NERVE DISEASES; INTRACRANIAL HYPERTENSION; CRANIOCEREBRAL TRAUMA; and other conditions.\n    ", "id": "MESH:D014012"}
{"mention": "lignocaine", "mention_text": "Idiopathic subjective tinnitus (IST) is one of the most obscure otological pathologies. This paper presents the results of treating IST by intratympanic instillation of lignocaine (lidocaine) 2 per cent through a grommet, for five weekly courses. Fifty-two patients suffering from intractable tinnitus entered this therapeutic trial, but only nine finished all five courses. In one patient, the tinnitus was almost completely abolished, but in all the nine patients the decompensated tinnitus changed to a compensated one. We suggest this mode of treatment for patients that were previously treated by drugs, acupuncture and biofeedback, with disappointing results. Patients should be warned about the side effects of vertigo and vomiting, which subsides gradually with every new instillation, and that the tinnitus may not disappear but will be alleviated, enabling them to cope more easily with the disease and lead a more normal life.", "entity": "Lidocaine", "aliases": "2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide 2-2EtN-2MePhAcN Astrazeneca Brand of Lidocaine Dalcaine Jenapharm Lidocanine Hydrochloride Carbonate (2:1) Hydrocarbonate Monoacetate Monohydrochloride Monohydrate Sulfate (1:1) Lignocaine Novocol Octocaine Strathmann Xylesthesin Xylocaine Xylocitin Xyloneural", "definition": "A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.\n    ", "id": "MESH:D008012"}
{"mention": "lidocaine", "mention_text": "Idiopathic subjective tinnitus (IST) is one of the most obscure otological pathologies. This paper presents the results of treating IST by intratympanic instillation of lignocaine (lidocaine) 2 per cent through a grommet, for five weekly courses. Fifty-two patients suffering from intractable tinnitus entered this therapeutic trial, but only nine finished all five courses. In one patient, the tinnitus was almost completely abolished, but in all the nine patients the decompensated tinnitus changed to a compensated one. We suggest this mode of treatment for patients that were previously treated by drugs, acupuncture and biofeedback, with disappointing results. Patients should be warned about the side effects of vertigo and vomiting, which subsides gradually with every new instillation, and that the tinnitus may not disappear but will be alleviated, enabling them to cope more easily with the disease and lead a more normal life.", "entity": "Lidocaine", "aliases": "2-(Diethylamino)-N-(2,6-Dimethylphenyl)Acetamide 2-2EtN-2MePhAcN Astrazeneca Brand of Lidocaine Dalcaine Jenapharm Lidocanine Hydrochloride Carbonate (2:1) Hydrocarbonate Monoacetate Monohydrochloride Monohydrate Sulfate (1:1) Lignocaine Novocol Octocaine Strathmann Xylesthesin Xylocaine Xylocitin Xyloneural", "definition": "A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.\n    ", "id": "MESH:D008012"}
{"mention": "tinnitus", "mention_text": "Idiopathic subjective tinnitus (IST) is one of the most obscure otological pathologies. This paper presents the results of treating IST by intratympanic instillation of lignocaine (lidocaine) 2 per cent through a grommet, for five weekly courses. Fifty-two patients suffering from intractable tinnitus entered this therapeutic trial, but only nine finished all five courses. In one patient, the tinnitus was almost completely abolished, but in all the nine patients the decompensated tinnitus changed to a compensated one. We suggest this mode of treatment for patients that were previously treated by drugs, acupuncture and biofeedback, with disappointing results. Patients should be warned about the side effects of vertigo and vomiting, which subsides gradually with every new instillation, and that the tinnitus may not disappear but will be alleviated, enabling them to cope more easily with the disease and lead a more normal life.", "entity": "Tinnitus", "aliases": "Clicking Tinnitus Induced Noise Leudet Leudet's Objective Pulsatile Ringing Buzzing Ringing-Buzzing-Tinnitus Spontaneous Oto Acoustic Emission Oto-Acoustic Subjective Tensor Palatini Tympani of Vascular Origin Leudets", "definition": "A nonspecific symptom of hearing disorder characterized by the sensation of buzzing, ringing, clicking, pulsations, and other noises in the ear. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of COCHLEAR DISEASES; VESTIBULOCOCHLEAR NERVE DISEASES; INTRACRANIAL HYPERTENSION; CRANIOCEREBRAL TRAUMA; and other conditions.\n    ", "id": "MESH:D014012"}
{"mention": "vertigo", "mention_text": "Idiopathic subjective tinnitus (IST) is one of the most obscure otological pathologies. This paper presents the results of treating IST by intratympanic instillation of lignocaine (lidocaine) 2 per cent through a grommet, for five weekly courses. Fifty-two patients suffering from intractable tinnitus entered this therapeutic trial, but only nine finished all five courses. In one patient, the tinnitus was almost completely abolished, but in all the nine patients the decompensated tinnitus changed to a compensated one. We suggest this mode of treatment for patients that were previously treated by drugs, acupuncture and biofeedback, with disappointing results. Patients should be warned about the side effects of vertigo and vomiting, which subsides gradually with every new instillation, and that the tinnitus may not disappear but will be alleviated, enabling them to cope more easily with the disease and lead a more normal life.", "entity": "Vertigo", "aliases": "Brain Stem Vertigo Vertigos Brainstem CNS Origin Central Nervous System Constant Essential Intermittant Paroxysmal Peripheral Positional Sensation Spinning Sensations Subjective", "definition": "An illusion of movement, either of the external world revolving around the individual or of the individual revolving in space. Vertigo may be associated with disorders of the inner ear (EAR, INNER); VESTIBULAR NERVE; BRAINSTEM; or CEREBRAL CORTEX. Lesions in the TEMPORAL LOBE and PARIETAL LOBE may be associated with FOCAL SEIZURES that may feature vertigo as an ictal manifestation. (From Adams et al., Principles of Neurology, 6th ed, pp300-1)\n    ", "id": "MESH:D014717"}
{"mention": "vomiting", "mention_text": "Idiopathic subjective tinnitus (IST) is one of the most obscure otological pathologies. This paper presents the results of treating IST by intratympanic instillation of lignocaine (lidocaine) 2 per cent through a grommet, for five weekly courses. Fifty-two patients suffering from intractable tinnitus entered this therapeutic trial, but only nine finished all five courses. In one patient, the tinnitus was almost completely abolished, but in all the nine patients the decompensated tinnitus changed to a compensated one. We suggest this mode of treatment for patients that were previously treated by drugs, acupuncture and biofeedback, with disappointing results. Patients should be warned about the side effects of vertigo and vomiting, which subsides gradually with every new instillation, and that the tinnitus may not disappear but will be alleviated, enabling them to cope more easily with the disease and lead a more normal life.", "entity": "Vomiting", "aliases": "Emesis Vomiting", "definition": "The forcible expulsion of the contents of the STOMACH through the MOUTH.\n    ", "id": "MESH:D014839"}
{"mention": "Perhexiline maleate", "mention_text": "Perhexiline maleate and peripheral neuropathy.", "entity": "perhexiline maleate", "aliases": "perhexiline maleate", "definition": "", "id": "MESH:C023470"}
{"mention": "peripheral neuropathy", "mention_text": "Perhexiline maleate and peripheral neuropathy.", "entity": "Peripheral Nervous System Diseases", "aliases": "Nerve Disease Peripheral Diseases Neuropathy PNS (Peripheral Nervous System) System Disorders Neuropathies", "definition": "Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.\n    ", "id": "MESH:D010523"}
{"mention": "Peripheral neuropathy", "mention_text": "Peripheral neuropathy has been noted as a complication of therapy with perhexiline maleate, a drug widely used in France (and in clinical trials in the United States) for the prophylactic treatment of angina pectoris. In 24 patients with this complication, the marked slowing of motor nerve conduction velocity and the electromyographic changes imply mainly a demyelinating disorder. Improvement was noted with cessation of therapy. In a few cases the presence of active denervation signified a poor prognosis, with only slight improvement. The underlying mechanism causing the neuropathy is not yet fully known, although some evidence indicates that it may be a lipid storage process.", "entity": "Peripheral Nervous System Diseases", "aliases": "Nerve Disease Peripheral Diseases Neuropathy PNS (Peripheral Nervous System) System Disorders Neuropathies", "definition": "Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.\n    ", "id": "MESH:D010523"}
{"mention": "perhexiline maleate", "mention_text": "Peripheral neuropathy has been noted as a complication of therapy with perhexiline maleate, a drug widely used in France (and in clinical trials in the United States) for the prophylactic treatment of angina pectoris. In 24 patients with this complication, the marked slowing of motor nerve conduction velocity and the electromyographic changes imply mainly a demyelinating disorder. Improvement was noted with cessation of therapy. In a few cases the presence of active denervation signified a poor prognosis, with only slight improvement. The underlying mechanism causing the neuropathy is not yet fully known, although some evidence indicates that it may be a lipid storage process.", "entity": "perhexiline maleate", "aliases": "perhexiline maleate", "definition": "", "id": "MESH:C023470"}
{"mention": "angina pectoris", "mention_text": "Peripheral neuropathy has been noted as a complication of therapy with perhexiline maleate, a drug widely used in France (and in clinical trials in the United States) for the prophylactic treatment of angina pectoris. In 24 patients with this complication, the marked slowing of motor nerve conduction velocity and the electromyographic changes imply mainly a demyelinating disorder. Improvement was noted with cessation of therapy. In a few cases the presence of active denervation signified a poor prognosis, with only slight improvement. The underlying mechanism causing the neuropathy is not yet fully known, although some evidence indicates that it may be a lipid storage process.", "entity": "Angina Pectoris", "aliases": "Angina Pectoris Angor Stenocardia Stenocardias", "definition": "The symptom of paroxysmal pain consequent to MYOCARDIAL ISCHEMIA usually of distinctive character, location and radiation. It is thought to be provoked by a transient stressful situation during which the oxygen requirements of the MYOCARDIUM exceed that supplied by the CORONARY CIRCULATION.\n    ", "id": "MESH:D000787"}
{"mention": "demyelinating disorder", "mention_text": "Peripheral neuropathy has been noted as a complication of therapy with perhexiline maleate, a drug widely used in France (and in clinical trials in the United States) for the prophylactic treatment of angina pectoris. In 24 patients with this complication, the marked slowing of motor nerve conduction velocity and the electromyographic changes imply mainly a demyelinating disorder. Improvement was noted with cessation of therapy. In a few cases the presence of active denervation signified a poor prognosis, with only slight improvement. The underlying mechanism causing the neuropathy is not yet fully known, although some evidence indicates that it may be a lipid storage process.", "entity": "Demyelinating Diseases", "aliases": "Clinically Isolated CNS Demyelinating Syndrome Disease Diseases Disorder Disorders Demyelination Demyelinations", "definition": "Diseases characterized by loss or dysfunction of myelin in the central or peripheral nervous system.\n    ", "id": "MESH:D003711"}
{"mention": "neuropathy", "mention_text": "Peripheral neuropathy has been noted as a complication of therapy with perhexiline maleate, a drug widely used in France (and in clinical trials in the United States) for the prophylactic treatment of angina pectoris. In 24 patients with this complication, the marked slowing of motor nerve conduction velocity and the electromyographic changes imply mainly a demyelinating disorder. Improvement was noted with cessation of therapy. In a few cases the presence of active denervation signified a poor prognosis, with only slight improvement. The underlying mechanism causing the neuropathy is not yet fully known, although some evidence indicates that it may be a lipid storage process.", "entity": "Nervous System Diseases", "aliases": "Disease Nervous System Diseases Disorder Neurologic Neurological Disorders", "definition": "Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.\n    ", "id": "MESH:D009422"}
{"mention": "morphine", "mention_text": "Effect of humoral modulators of morphine-induced increase in locomotor activity of mice.", "entity": "Morphine", "aliases": "Chloride Morphine Contin MS Duramorph Morphia Sulfate (2:1) Anhydrous Pentahydrate Oramorph SR SDZ 202 250 202-250 202250 SDZ202 SDZ202-250 SDZ202250", "definition": "The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.\n    ", "id": "MESH:D009020"}
{"mention": "increase in locomotor activity", "mention_text": "Effect of humoral modulators of morphine-induced increase in locomotor activity of mice.", "entity": "Hyperkinesis", "aliases": "Generalized Hyperkinesia Hyperkinesias Hyperactivity Motor Hyperkinesis Hyperkinetic Movement Movements", "definition": "Excessive movement of muscles of the body as a whole, which may be associated with organic or psychological disorders.\n    ", "id": "MESH:D006948"}
{"mention": "morphine", "mention_text": "The effect of humoral modulators on the morphine-induced increase in locomotor activity of mice was studied. The subcutaneous administration of 10 mg/kg of morphine-HC1 produced a marked increase in locomotor activity in mice. The morphine-induced hyperactivity was potentiated by scopolamine and attenuated by physostigmine. In contrast, both methscopolamine and neostigmine, which do not penetrate the blood-brain barrier, had no effect on the hyperactivity produced by morphine. Pretreatment of mice with alpha-methyltyrosine (20 mg/kg i.p., one hour), an inhibitor of tyrosine hydroxylase, significantly decreased the activity-increasing effects of morphine. On the other hand, pretreatment with p-chlorophenylalamine (3 X 320 mg/kg i.p., 24 hr), a serotonin depletor, caused no significant change in the hyperactivity. The study suggests that the activity-increasing effects of morphine are mediated by the release of catecholamines from adrenergic neurons in the brain. And the results are consistent with the hypothesis that morphine acts by retarding the release of acetylcholine at some central cholinergic synapses. It is also suggested from collected evidence that the activity-increasing effects of morphine in mice are mediated by mechanisms different from those which mediate the activity-increasing effects of morphine in rats.", "entity": "Morphine", "aliases": "Chloride Morphine Contin MS Duramorph Morphia Sulfate (2:1) Anhydrous Pentahydrate Oramorph SR SDZ 202 250 202-250 202250 SDZ202 SDZ202-250 SDZ202250", "definition": "The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.\n    ", "id": "MESH:D009020"}
{"mention": "increase in locomotor activity", "mention_text": "The effect of humoral modulators on the morphine-induced increase in locomotor activity of mice was studied. The subcutaneous administration of 10 mg/kg of morphine-HC1 produced a marked increase in locomotor activity in mice. The morphine-induced hyperactivity was potentiated by scopolamine and attenuated by physostigmine. In contrast, both methscopolamine and neostigmine, which do not penetrate the blood-brain barrier, had no effect on the hyperactivity produced by morphine. Pretreatment of mice with alpha-methyltyrosine (20 mg/kg i.p., one hour), an inhibitor of tyrosine hydroxylase, significantly decreased the activity-increasing effects of morphine. On the other hand, pretreatment with p-chlorophenylalamine (3 X 320 mg/kg i.p., 24 hr), a serotonin depletor, caused no significant change in the hyperactivity. The study suggests that the activity-increasing effects of morphine are mediated by the release of catecholamines from adrenergic neurons in the brain. And the results are consistent with the hypothesis that morphine acts by retarding the release of acetylcholine at some central cholinergic synapses. It is also suggested from collected evidence that the activity-increasing effects of morphine in mice are mediated by mechanisms different from those which mediate the activity-increasing effects of morphine in rats.", "entity": "Hyperkinesis", "aliases": "Generalized Hyperkinesia Hyperkinesias Hyperactivity Motor Hyperkinesis Hyperkinetic Movement Movements", "definition": "Excessive movement of muscles of the body as a whole, which may be associated with organic or psychological disorders.\n    ", "id": "MESH:D006948"}
{"mention": "hyperactivity", "mention_text": "The effect of humoral modulators on the morphine-induced increase in locomotor activity of mice was studied. The subcutaneous administration of 10 mg/kg of morphine-HC1 produced a marked increase in locomotor activity in mice. The morphine-induced hyperactivity was potentiated by scopolamine and attenuated by physostigmine. In contrast, both methscopolamine and neostigmine, which do not penetrate the blood-brain barrier, had no effect on the hyperactivity produced by morphine. Pretreatment of mice with alpha-methyltyrosine (20 mg/kg i.p., one hour), an inhibitor of tyrosine hydroxylase, significantly decreased the activity-increasing effects of morphine. On the other hand, pretreatment with p-chlorophenylalamine (3 X 320 mg/kg i.p., 24 hr), a serotonin depletor, caused no significant change in the hyperactivity. The study suggests that the activity-increasing effects of morphine are mediated by the release of catecholamines from adrenergic neurons in the brain. And the results are consistent with the hypothesis that morphine acts by retarding the release of acetylcholine at some central cholinergic synapses. It is also suggested from collected evidence that the activity-increasing effects of morphine in mice are mediated by mechanisms different from those which mediate the activity-increasing effects of morphine in rats.", "entity": "Hyperkinesis", "aliases": "Generalized Hyperkinesia Hyperkinesias Hyperactivity Motor Hyperkinesis Hyperkinetic Movement Movements", "definition": "Excessive movement of muscles of the body as a whole, which may be associated with organic or psychological disorders.\n    ", "id": "MESH:D006948"}
{"mention": "scopolamine", "mention_text": "The effect of humoral modulators on the morphine-induced increase in locomotor activity of mice was studied. The subcutaneous administration of 10 mg/kg of morphine-HC1 produced a marked increase in locomotor activity in mice. The morphine-induced hyperactivity was potentiated by scopolamine and attenuated by physostigmine. In contrast, both methscopolamine and neostigmine, which do not penetrate the blood-brain barrier, had no effect on the hyperactivity produced by morphine. Pretreatment of mice with alpha-methyltyrosine (20 mg/kg i.p., one hour), an inhibitor of tyrosine hydroxylase, significantly decreased the activity-increasing effects of morphine. On the other hand, pretreatment with p-chlorophenylalamine (3 X 320 mg/kg i.p., 24 hr), a serotonin depletor, caused no significant change in the hyperactivity. The study suggests that the activity-increasing effects of morphine are mediated by the release of catecholamines from adrenergic neurons in the brain. And the results are consistent with the hypothesis that morphine acts by retarding the release of acetylcholine at some central cholinergic synapses. It is also suggested from collected evidence that the activity-increasing effects of morphine in mice are mediated by mechanisms different from those which mediate the activity-increasing effects of morphine in rats.", "entity": "Scopolamine Hydrobromide", "aliases": "Alcon Brand of Scopolamine Hydrobromide Boro Scopol Boro-Scopol BoroScopol Bull Cooper Hamilton Hope Hyoscine Inibisa Isopto Kwells Novartis Consumer Health Renaudin Roche Scoburen Scopace Scopoderm TTS Transderm Scop V Transderm-V Travacalm HO Vorigeno Winzer Borate", "definition": "An alkaloid from SOLANACEAE, especially DATURA and SCOPOLIA. Scopolamine and its quaternary derivatives act as antimuscarinics like ATROPINE, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in URINARY INCONTINENCE, in MOTION SICKNESS, as an antispasmodic, and as a mydriatic and cycloplegic.\n    ", "id": "MESH:D012601"}
{"mention": "physostigmine", "mention_text": "The effect of humoral modulators on the morphine-induced increase in locomotor activity of mice was studied. The subcutaneous administration of 10 mg/kg of morphine-HC1 produced a marked increase in locomotor activity in mice. The morphine-induced hyperactivity was potentiated by scopolamine and attenuated by physostigmine. In contrast, both methscopolamine and neostigmine, which do not penetrate the blood-brain barrier, had no effect on the hyperactivity produced by morphine. Pretreatment of mice with alpha-methyltyrosine (20 mg/kg i.p., one hour), an inhibitor of tyrosine hydroxylase, significantly decreased the activity-increasing effects of morphine. On the other hand, pretreatment with p-chlorophenylalamine (3 X 320 mg/kg i.p., 24 hr), a serotonin depletor, caused no significant change in the hyperactivity. The study suggests that the activity-increasing effects of morphine are mediated by the release of catecholamines from adrenergic neurons in the brain. And the results are consistent with the hypothesis that morphine acts by retarding the release of acetylcholine at some central cholinergic synapses. It is also suggested from collected evidence that the activity-increasing effects of morphine in mice are mediated by mechanisms different from those which mediate the activity-increasing effects of morphine in rats.", "entity": "Physostigmine", "aliases": "Eserine Physostigmine", "definition": "A cholinesterase inhibitor that is rapidly absorbed through membranes. It can be applied topically to the conjunctiva. It also can cross the blood-brain barrier and is used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity.\n    ", "id": "MESH:D010830"}
{"mention": "methscopolamine", "mention_text": "The effect of humoral modulators on the morphine-induced increase in locomotor activity of mice was studied. The subcutaneous administration of 10 mg/kg of morphine-HC1 produced a marked increase in locomotor activity in mice. The morphine-induced hyperactivity was potentiated by scopolamine and attenuated by physostigmine. In contrast, both methscopolamine and neostigmine, which do not penetrate the blood-brain barrier, had no effect on the hyperactivity produced by morphine. Pretreatment of mice with alpha-methyltyrosine (20 mg/kg i.p., one hour), an inhibitor of tyrosine hydroxylase, significantly decreased the activity-increasing effects of morphine. On the other hand, pretreatment with p-chlorophenylalamine (3 X 320 mg/kg i.p., 24 hr), a serotonin depletor, caused no significant change in the hyperactivity. The study suggests that the activity-increasing effects of morphine are mediated by the release of catecholamines from adrenergic neurons in the brain. And the results are consistent with the hypothesis that morphine acts by retarding the release of acetylcholine at some central cholinergic synapses. It is also suggested from collected evidence that the activity-increasing effects of morphine in mice are mediated by mechanisms different from those which mediate the activity-increasing effects of morphine in rats.", "entity": "N-Methylscopolamine", "aliases": "Bromide N-Methylscopolamine DD 234 DD-234 DD234 Hyoscine Methiodide Methobromide Iodide Methscopolamine Methylbromide Scopolamine Methylchloride Methylscopolamine Nitrate Methylscopolammonium Methylsulfate N-Methylscine N Methylscine Skopyl Ulix", "definition": "A muscarinic antagonist used to study binding characteristics of muscarinic cholinergic receptors.\n    ", "id": "MESH:D019832"}
{"mention": "neostigmine", "mention_text": "The effect of humoral modulators on the morphine-induced increase in locomotor activity of mice was studied. The subcutaneous administration of 10 mg/kg of morphine-HC1 produced a marked increase in locomotor activity in mice. The morphine-induced hyperactivity was potentiated by scopolamine and attenuated by physostigmine. In contrast, both methscopolamine and neostigmine, which do not penetrate the blood-brain barrier, had no effect on the hyperactivity produced by morphine. Pretreatment of mice with alpha-methyltyrosine (20 mg/kg i.p., one hour), an inhibitor of tyrosine hydroxylase, significantly decreased the activity-increasing effects of morphine. On the other hand, pretreatment with p-chlorophenylalamine (3 X 320 mg/kg i.p., 24 hr), a serotonin depletor, caused no significant change in the hyperactivity. The study suggests that the activity-increasing effects of morphine are mediated by the release of catecholamines from adrenergic neurons in the brain. And the results are consistent with the hypothesis that morphine acts by retarding the release of acetylcholine at some central cholinergic synapses. It is also suggested from collected evidence that the activity-increasing effects of morphine in mice are mediated by mechanisms different from those which mediate the activity-increasing effects of morphine in rats.", "entity": "Neostigmine", "aliases": "Bromide Neostigmine Methylsulfate Polstigmine Proserine Prostigmin Prostigmine Prozerin Synstigmin Syntostigmine", "definition": "A cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine. Neostigmine, unlike PHYSOSTIGMINE, does not cross the blood-brain barrier.\n    ", "id": "MESH:D009388"}
{"mention": "alpha-methyltyrosine", "mention_text": "The effect of humoral modulators on the morphine-induced increase in locomotor activity of mice was studied. The subcutaneous administration of 10 mg/kg of morphine-HC1 produced a marked increase in locomotor activity in mice. The morphine-induced hyperactivity was potentiated by scopolamine and attenuated by physostigmine. In contrast, both methscopolamine and neostigmine, which do not penetrate the blood-brain barrier, had no effect on the hyperactivity produced by morphine. Pretreatment of mice with alpha-methyltyrosine (20 mg/kg i.p., one hour), an inhibitor of tyrosine hydroxylase, significantly decreased the activity-increasing effects of morphine. On the other hand, pretreatment with p-chlorophenylalamine (3 X 320 mg/kg i.p., 24 hr), a serotonin depletor, caused no significant change in the hyperactivity. The study suggests that the activity-increasing effects of morphine are mediated by the release of catecholamines from adrenergic neurons in the brain. And the results are consistent with the hypothesis that morphine acts by retarding the release of acetylcholine at some central cholinergic synapses. It is also suggested from collected evidence that the activity-increasing effects of morphine in mice are mediated by mechanisms different from those which mediate the activity-increasing effects of morphine in rats.", "entity": "alpha-Methyltyrosine", "aliases": "DL-Tyrosine alpha-methyl- Demser Hydrochloride alpha-Methyltyrosine Merck Brand of Metyrosine Sharp & Dohme Metirosine Racemetirosine alpha MPT Methyl p tyrosine para Methyltyrosine alpha-MPT alpha-Methyl-p-tyrosine alpha-Methyl-para-tyrosine (+,-)-Isomer (D,L)-Isomer (L)-Isomer", "definition": "An inhibitor of the enzyme TYROSINE 3-MONOOXYGENASE, and consequently of the synthesis of catecholamines. It is used to control the symptoms of excessive sympathetic stimulation in patients with PHEOCHROMOCYTOMA. (Martindale, The Extra Pharmacopoeia, 30th ed)\n    ", "id": "MESH:D019805"}
{"mention": "tyrosine", "mention_text": "The effect of humoral modulators on the morphine-induced increase in locomotor activity of mice was studied. The subcutaneous administration of 10 mg/kg of morphine-HC1 produced a marked increase in locomotor activity in mice. The morphine-induced hyperactivity was potentiated by scopolamine and attenuated by physostigmine. In contrast, both methscopolamine and neostigmine, which do not penetrate the blood-brain barrier, had no effect on the hyperactivity produced by morphine. Pretreatment of mice with alpha-methyltyrosine (20 mg/kg i.p., one hour), an inhibitor of tyrosine hydroxylase, significantly decreased the activity-increasing effects of morphine. On the other hand, pretreatment with p-chlorophenylalamine (3 X 320 mg/kg i.p., 24 hr), a serotonin depletor, caused no significant change in the hyperactivity. The study suggests that the activity-increasing effects of morphine are mediated by the release of catecholamines from adrenergic neurons in the brain. And the results are consistent with the hypothesis that morphine acts by retarding the release of acetylcholine at some central cholinergic synapses. It is also suggested from collected evidence that the activity-increasing effects of morphine in mice are mediated by mechanisms different from those which mediate the activity-increasing effects of morphine in rats.", "entity": "Tyrosine", "aliases": "L Tyrosine L-Tyrosine isomer L-isomer para para-Tyrosine", "definition": "A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.\n    ", "id": "MESH:D014443"}
{"mention": "p-chlorophenylalamine", "mention_text": "The effect of humoral modulators on the morphine-induced increase in locomotor activity of mice was studied. The subcutaneous administration of 10 mg/kg of morphine-HC1 produced a marked increase in locomotor activity in mice. The morphine-induced hyperactivity was potentiated by scopolamine and attenuated by physostigmine. In contrast, both methscopolamine and neostigmine, which do not penetrate the blood-brain barrier, had no effect on the hyperactivity produced by morphine. Pretreatment of mice with alpha-methyltyrosine (20 mg/kg i.p., one hour), an inhibitor of tyrosine hydroxylase, significantly decreased the activity-increasing effects of morphine. On the other hand, pretreatment with p-chlorophenylalamine (3 X 320 mg/kg i.p., 24 hr), a serotonin depletor, caused no significant change in the hyperactivity. The study suggests that the activity-increasing effects of morphine are mediated by the release of catecholamines from adrenergic neurons in the brain. And the results are consistent with the hypothesis that morphine acts by retarding the release of acetylcholine at some central cholinergic synapses. It is also suggested from collected evidence that the activity-increasing effects of morphine in mice are mediated by mechanisms different from those which mediate the activity-increasing effects of morphine in rats.", "entity": "Fenclonine", "aliases": "CP-10,188 DL-3-(4-Chlorophenyl)alanine Fenclonin Fenclonine (L)-Isomer Hydrobromide Hydrochloride (D)-Isomer p-Chlorophenylalanine para Chlorophenylalanine para-Chlorophenylalanine", "definition": "A selective and irreversible inhibitor of tryptophan hydroxylase, a rate-limiting enzyme in the biosynthesis of serotonin (5-HYDROXYTRYPTAMINE). Fenclonine acts pharmacologically to deplete endogenous levels of serotonin.\n    ", "id": "MESH:D010134"}
{"mention": "serotonin", "mention_text": "The effect of humoral modulators on the morphine-induced increase in locomotor activity of mice was studied. The subcutaneous administration of 10 mg/kg of morphine-HC1 produced a marked increase in locomotor activity in mice. The morphine-induced hyperactivity was potentiated by scopolamine and attenuated by physostigmine. In contrast, both methscopolamine and neostigmine, which do not penetrate the blood-brain barrier, had no effect on the hyperactivity produced by morphine. Pretreatment of mice with alpha-methyltyrosine (20 mg/kg i.p., one hour), an inhibitor of tyrosine hydroxylase, significantly decreased the activity-increasing effects of morphine. On the other hand, pretreatment with p-chlorophenylalamine (3 X 320 mg/kg i.p., 24 hr), a serotonin depletor, caused no significant change in the hyperactivity. The study suggests that the activity-increasing effects of morphine are mediated by the release of catecholamines from adrenergic neurons in the brain. And the results are consistent with the hypothesis that morphine acts by retarding the release of acetylcholine at some central cholinergic synapses. It is also suggested from collected evidence that the activity-increasing effects of morphine in mice are mediated by mechanisms different from those which mediate the activity-increasing effects of morphine in rats.", "entity": "Serotonin", "aliases": "3-(2-Aminoethyl)-1H-indol-5-ol 5 Hydroxytryptamine 5-HT 5-Hydroxytryptamine Enteramine Hippophaine Serotonin", "definition": "A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.\n    ", "id": "MESH:D012701"}
{"mention": "catecholamines", "mention_text": "The effect of humoral modulators on the morphine-induced increase in locomotor activity of mice was studied. The subcutaneous administration of 10 mg/kg of morphine-HC1 produced a marked increase in locomotor activity in mice. The morphine-induced hyperactivity was potentiated by scopolamine and attenuated by physostigmine. In contrast, both methscopolamine and neostigmine, which do not penetrate the blood-brain barrier, had no effect on the hyperactivity produced by morphine. Pretreatment of mice with alpha-methyltyrosine (20 mg/kg i.p., one hour), an inhibitor of tyrosine hydroxylase, significantly decreased the activity-increasing effects of morphine. On the other hand, pretreatment with p-chlorophenylalamine (3 X 320 mg/kg i.p., 24 hr), a serotonin depletor, caused no significant change in the hyperactivity. The study suggests that the activity-increasing effects of morphine are mediated by the release of catecholamines from adrenergic neurons in the brain. And the results are consistent with the hypothesis that morphine acts by retarding the release of acetylcholine at some central cholinergic synapses. It is also suggested from collected evidence that the activity-increasing effects of morphine in mice are mediated by mechanisms different from those which mediate the activity-increasing effects of morphine in rats.", "entity": "Catecholamines", "aliases": "Catecholamines Sympathins", "definition": "A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine.\n    ", "id": "MESH:D002395"}
{"mention": "acetylcholine", "mention_text": "The effect of humoral modulators on the morphine-induced increase in locomotor activity of mice was studied. The subcutaneous administration of 10 mg/kg of morphine-HC1 produced a marked increase in locomotor activity in mice. The morphine-induced hyperactivity was potentiated by scopolamine and attenuated by physostigmine. In contrast, both methscopolamine and neostigmine, which do not penetrate the blood-brain barrier, had no effect on the hyperactivity produced by morphine. Pretreatment of mice with alpha-methyltyrosine (20 mg/kg i.p., one hour), an inhibitor of tyrosine hydroxylase, significantly decreased the activity-increasing effects of morphine. On the other hand, pretreatment with p-chlorophenylalamine (3 X 320 mg/kg i.p., 24 hr), a serotonin depletor, caused no significant change in the hyperactivity. The study suggests that the activity-increasing effects of morphine are mediated by the release of catecholamines from adrenergic neurons in the brain. And the results are consistent with the hypothesis that morphine acts by retarding the release of acetylcholine at some central cholinergic synapses. It is also suggested from collected evidence that the activity-increasing effects of morphine in mice are mediated by mechanisms different from those which mediate the activity-increasing effects of morphine in rats.", "entity": "Acetylcholine", "aliases": "2-(Acetyloxy)-N,N,N-trimethylethanaminium Acetilcolina Cusi Acetylcholine Bromide Chloride Fluoride Hydroxide Iodide L Tartrate L-Tartrate Perchlorate Picrate (1:1) Sulfate Alcon Brand of Bournonville Bromoacetylcholine Chloroacetylcholine Ciba Vision Iolab Miochol", "definition": "A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.\n    ", "id": "MESH:D000109"}
{"mention": "FK 506", "mention_text": "Mechanisms of FK 506-induced hypertension in the rat.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "hypertension", "mention_text": "Mechanisms of FK 506-induced hypertension in the rat.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "Tacrolimus", "mention_text": "-Tacrolimus (FK 506) is a powerful, widely used immunosuppressant. The clinical utility of FK 506 is complicated by substantial hypertension and nephrotoxicity. To clarify the mechanisms of FK 506-induced hypertension, we studied the chronic effects of FK 506 on the synthesis of endothelin-1 (ET-1), the expression of mRNA of ET-1 and endothelin-converting enzyme-1 (ECE-1), the endothelial nitric oxide synthase (eNOS) activity, and the expression of mRNA of eNOS and C-type natriuretic peptide (CNP) in rat blood vessels. In addition, the effect of the specific endothelin type A receptor antagonist FR 139317 on FK 506-induced hypertension in rats was studied. FK 506, 5 mg. kg-1. d-1 given for 4 weeks, elevated blood pressure from 102+/-13 to 152+/-15 mm Hg and increased the synthesis of ET-1 and the levels of ET-1 mRNA in the mesenteric artery (240% and 230%, respectively). Little change was observed in the expression of ECE-1 mRNA and CNP mRNA. FK 506 decreased eNOS activity and the levels of eNOS mRNA in the aorta (48% and 55%, respectively). The administration of FR 139317 (10 mg. kg-1. d-1) prevented FK 506-induced hypertension in rats. These results indicate that FK 506 may increase blood pressure not only by increasing ET-1 production but also by decreasing NO synthesis in the vasculature.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "FK 506", "mention_text": "-Tacrolimus (FK 506) is a powerful, widely used immunosuppressant. The clinical utility of FK 506 is complicated by substantial hypertension and nephrotoxicity. To clarify the mechanisms of FK 506-induced hypertension, we studied the chronic effects of FK 506 on the synthesis of endothelin-1 (ET-1), the expression of mRNA of ET-1 and endothelin-converting enzyme-1 (ECE-1), the endothelial nitric oxide synthase (eNOS) activity, and the expression of mRNA of eNOS and C-type natriuretic peptide (CNP) in rat blood vessels. In addition, the effect of the specific endothelin type A receptor antagonist FR 139317 on FK 506-induced hypertension in rats was studied. FK 506, 5 mg. kg-1. d-1 given for 4 weeks, elevated blood pressure from 102+/-13 to 152+/-15 mm Hg and increased the synthesis of ET-1 and the levels of ET-1 mRNA in the mesenteric artery (240% and 230%, respectively). Little change was observed in the expression of ECE-1 mRNA and CNP mRNA. FK 506 decreased eNOS activity and the levels of eNOS mRNA in the aorta (48% and 55%, respectively). The administration of FR 139317 (10 mg. kg-1. d-1) prevented FK 506-induced hypertension in rats. These results indicate that FK 506 may increase blood pressure not only by increasing ET-1 production but also by decreasing NO synthesis in the vasculature.", "entity": "Tacrolimus", "aliases": "Anhydrous Tacrolimus Cilag Brand of FK 506 FK-506 FK506 FR 900506 FR-900506 FR900506 Fujisawa Janssen Prograf Prograft", "definition": "A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.\n    ", "id": "MESH:D016559"}
{"mention": "hypertension", "mention_text": "-Tacrolimus (FK 506) is a powerful, widely used immunosuppressant. The clinical utility of FK 506 is complicated by substantial hypertension and nephrotoxicity. To clarify the mechanisms of FK 506-induced hypertension, we studied the chronic effects of FK 506 on the synthesis of endothelin-1 (ET-1), the expression of mRNA of ET-1 and endothelin-converting enzyme-1 (ECE-1), the endothelial nitric oxide synthase (eNOS) activity, and the expression of mRNA of eNOS and C-type natriuretic peptide (CNP) in rat blood vessels. In addition, the effect of the specific endothelin type A receptor antagonist FR 139317 on FK 506-induced hypertension in rats was studied. FK 506, 5 mg. kg-1. d-1 given for 4 weeks, elevated blood pressure from 102+/-13 to 152+/-15 mm Hg and increased the synthesis of ET-1 and the levels of ET-1 mRNA in the mesenteric artery (240% and 230%, respectively). Little change was observed in the expression of ECE-1 mRNA and CNP mRNA. FK 506 decreased eNOS activity and the levels of eNOS mRNA in the aorta (48% and 55%, respectively). The administration of FR 139317 (10 mg. kg-1. d-1) prevented FK 506-induced hypertension in rats. These results indicate that FK 506 may increase blood pressure not only by increasing ET-1 production but also by decreasing NO synthesis in the vasculature.", "entity": "Hypertension", "aliases": "Blood Pressure High Pressures Hypertension", "definition": "Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.\n    ", "id": "MESH:D006973"}
{"mention": "nephrotoxicity", "mention_text": "-Tacrolimus (FK 506) is a powerful, widely used immunosuppressant. The clinical utility of FK 506 is complicated by substantial hypertension and nephrotoxicity. To clarify the mechanisms of FK 506-induced hypertension, we studied the chronic effects of FK 506 on the synthesis of endothelin-1 (ET-1), the expression of mRNA of ET-1 and endothelin-converting enzyme-1 (ECE-1), the endothelial nitric oxide synthase (eNOS) activity, and the expression of mRNA of eNOS and C-type natriuretic peptide (CNP) in rat blood vessels. In addition, the effect of the specific endothelin type A receptor antagonist FR 139317 on FK 506-induced hypertension in rats was studied. FK 506, 5 mg. kg-1. d-1 given for 4 weeks, elevated blood pressure from 102+/-13 to 152+/-15 mm Hg and increased the synthesis of ET-1 and the levels of ET-1 mRNA in the mesenteric artery (240% and 230%, respectively). Little change was observed in the expression of ECE-1 mRNA and CNP mRNA. FK 506 decreased eNOS activity and the levels of eNOS mRNA in the aorta (48% and 55%, respectively). The administration of FR 139317 (10 mg. kg-1. d-1) prevented FK 506-induced hypertension in rats. These results indicate that FK 506 may increase blood pressure not only by increasing ET-1 production but also by decreasing NO synthesis in the vasculature.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "nitric oxide", "mention_text": "-Tacrolimus (FK 506) is a powerful, widely used immunosuppressant. The clinical utility of FK 506 is complicated by substantial hypertension and nephrotoxicity. To clarify the mechanisms of FK 506-induced hypertension, we studied the chronic effects of FK 506 on the synthesis of endothelin-1 (ET-1), the expression of mRNA of ET-1 and endothelin-converting enzyme-1 (ECE-1), the endothelial nitric oxide synthase (eNOS) activity, and the expression of mRNA of eNOS and C-type natriuretic peptide (CNP) in rat blood vessels. In addition, the effect of the specific endothelin type A receptor antagonist FR 139317 on FK 506-induced hypertension in rats was studied. FK 506, 5 mg. kg-1. d-1 given for 4 weeks, elevated blood pressure from 102+/-13 to 152+/-15 mm Hg and increased the synthesis of ET-1 and the levels of ET-1 mRNA in the mesenteric artery (240% and 230%, respectively). Little change was observed in the expression of ECE-1 mRNA and CNP mRNA. FK 506 decreased eNOS activity and the levels of eNOS mRNA in the aorta (48% and 55%, respectively). The administration of FR 139317 (10 mg. kg-1. d-1) prevented FK 506-induced hypertension in rats. These results indicate that FK 506 may increase blood pressure not only by increasing ET-1 production but also by decreasing NO synthesis in the vasculature.", "entity": "Nitric Oxide", "aliases": "Endogenous Nitrate Vasodilator Endothelium-Derived Nitric Oxide Mononitrogen Monoxide Nitrogen Endothelium Derived", "definition": "A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.\n    ", "id": "MESH:D009569"}
{"mention": "FR 139317", "mention_text": "-Tacrolimus (FK 506) is a powerful, widely used immunosuppressant. The clinical utility of FK 506 is complicated by substantial hypertension and nephrotoxicity. To clarify the mechanisms of FK 506-induced hypertension, we studied the chronic effects of FK 506 on the synthesis of endothelin-1 (ET-1), the expression of mRNA of ET-1 and endothelin-converting enzyme-1 (ECE-1), the endothelial nitric oxide synthase (eNOS) activity, and the expression of mRNA of eNOS and C-type natriuretic peptide (CNP) in rat blood vessels. In addition, the effect of the specific endothelin type A receptor antagonist FR 139317 on FK 506-induced hypertension in rats was studied. FK 506, 5 mg. kg-1. d-1 given for 4 weeks, elevated blood pressure from 102+/-13 to 152+/-15 mm Hg and increased the synthesis of ET-1 and the levels of ET-1 mRNA in the mesenteric artery (240% and 230%, respectively). Little change was observed in the expression of ECE-1 mRNA and CNP mRNA. FK 506 decreased eNOS activity and the levels of eNOS mRNA in the aorta (48% and 55%, respectively). The administration of FR 139317 (10 mg. kg-1. d-1) prevented FK 506-induced hypertension in rats. These results indicate that FK 506 may increase blood pressure not only by increasing ET-1 production but also by decreasing NO synthesis in the vasculature.", "entity": "FR 139317", "aliases": "2-((1-(hexahydro-1H-azepinyl)carbonyl)amino-4-methylpentanoyl)-3-(-(1-methyl-1H-indolyl)propionyl)amino-3-(2-pyridyl)propionic acid FR 139317 FR-139317 FR139317", "definition": "", "id": "MESH:C079574"}
{"mention": "NO", "mention_text": "-Tacrolimus (FK 506) is a powerful, widely used immunosuppressant. The clinical utility of FK 506 is complicated by substantial hypertension and nephrotoxicity. To clarify the mechanisms of FK 506-induced hypertension, we studied the chronic effects of FK 506 on the synthesis of endothelin-1 (ET-1), the expression of mRNA of ET-1 and endothelin-converting enzyme-1 (ECE-1), the endothelial nitric oxide synthase (eNOS) activity, and the expression of mRNA of eNOS and C-type natriuretic peptide (CNP) in rat blood vessels. In addition, the effect of the specific endothelin type A receptor antagonist FR 139317 on FK 506-induced hypertension in rats was studied. FK 506, 5 mg. kg-1. d-1 given for 4 weeks, elevated blood pressure from 102+/-13 to 152+/-15 mm Hg and increased the synthesis of ET-1 and the levels of ET-1 mRNA in the mesenteric artery (240% and 230%, respectively). Little change was observed in the expression of ECE-1 mRNA and CNP mRNA. FK 506 decreased eNOS activity and the levels of eNOS mRNA in the aorta (48% and 55%, respectively). The administration of FR 139317 (10 mg. kg-1. d-1) prevented FK 506-induced hypertension in rats. These results indicate that FK 506 may increase blood pressure not only by increasing ET-1 production but also by decreasing NO synthesis in the vasculature.", "entity": "Nitric Oxide", "aliases": "Endogenous Nitrate Vasodilator Endothelium-Derived Nitric Oxide Mononitrogen Monoxide Nitrogen Endothelium Derived", "definition": "A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.\n    ", "id": "MESH:D009569"}
{"mention": "Suxamethonium", "mention_text": "Suxamethonium induced prolonged apnea in a patient receiving electroconvulsive therapy.", "entity": "Succinylcholine", "aliases": "Anectine Bromide Suxamethonium Celocurine Dibromide Succinylcholine Dichloride Diiodide Diperchlorate Ditilin Listenon Lysthenon Myorelaxin Quelicin Succicuran Chloride Di H2O Di-H2O Iodide Succinyldicholine", "definition": "A quaternary skeletal muscle relaxant usually used in the form of its bromide, chloride, or iodide. It is a depolarizing relaxant, acting in about 30 seconds and with a duration of effect averaging three to five minutes. Succinylcholine is used in surgical, anesthetic, and other procedures in which a brief period of muscle relaxation is called for.\n    ", "id": "MESH:D013390"}
{"mention": "apnea", "mention_text": "Suxamethonium induced prolonged apnea in a patient receiving electroconvulsive therapy.", "entity": "Apnea", "aliases": "Apnea Apneas", "definition": "A transient absence of spontaneous respiration.\n    ", "id": "MESH:D001049"}
{"mention": "Suxamethonium", "mention_text": "Suxamethonium causes prolonged apnea in patients in whom pseudocholinesterase enzyme gets deactivated by organophosphorus (OP) poisons. Here, we present a similar incident in a severely depressed patient who received electroconvulsive therapy (ECT). Prolonged apnea in our case ensued because the information about suicidal attempt by OP compound was concealed from the treating team.", "entity": "Succinylcholine", "aliases": "Anectine Bromide Suxamethonium Celocurine Dibromide Succinylcholine Dichloride Diiodide Diperchlorate Ditilin Listenon Lysthenon Myorelaxin Quelicin Succicuran Chloride Di H2O Di-H2O Iodide Succinyldicholine", "definition": "A quaternary skeletal muscle relaxant usually used in the form of its bromide, chloride, or iodide. It is a depolarizing relaxant, acting in about 30 seconds and with a duration of effect averaging three to five minutes. Succinylcholine is used in surgical, anesthetic, and other procedures in which a brief period of muscle relaxation is called for.\n    ", "id": "MESH:D013390"}
{"mention": "apnea", "mention_text": "Suxamethonium causes prolonged apnea in patients in whom pseudocholinesterase enzyme gets deactivated by organophosphorus (OP) poisons. Here, we present a similar incident in a severely depressed patient who received electroconvulsive therapy (ECT). Prolonged apnea in our case ensued because the information about suicidal attempt by OP compound was concealed from the treating team.", "entity": "Apnea", "aliases": "Apnea Apneas", "definition": "A transient absence of spontaneous respiration.\n    ", "id": "MESH:D001049"}
{"mention": "organophosphorus (OP) poisons", "mention_text": "Suxamethonium causes prolonged apnea in patients in whom pseudocholinesterase enzyme gets deactivated by organophosphorus (OP) poisons. Here, we present a similar incident in a severely depressed patient who received electroconvulsive therapy (ECT). Prolonged apnea in our case ensued because the information about suicidal attempt by OP compound was concealed from the treating team.", "entity": "Organophosphorus Compounds", "aliases": "Compounds Organophosphorus Organopyrophosphorus", "definition": "Organic compounds that contain phosphorus as an integral part of the molecule. Included under this heading is broad array of synthetic compounds that are used as PESTICIDES and DRUGS.\n    ", "id": "MESH:D009943"}
{"mention": "depressed", "mention_text": "Suxamethonium causes prolonged apnea in patients in whom pseudocholinesterase enzyme gets deactivated by organophosphorus (OP) poisons. Here, we present a similar incident in a severely depressed patient who received electroconvulsive therapy (ECT). Prolonged apnea in our case ensued because the information about suicidal attempt by OP compound was concealed from the treating team.", "entity": "Depressive Disorder", "aliases": "Depression Endogenous Neurotic Unipolar Depressions Depressive Disorder Disorders Neuroses Neurosis Syndrome Syndromes Melancholia Melancholias", "definition": "An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.\n    ", "id": "MESH:D003866"}
{"mention": "OP compound", "mention_text": "Suxamethonium causes prolonged apnea in patients in whom pseudocholinesterase enzyme gets deactivated by organophosphorus (OP) poisons. Here, we present a similar incident in a severely depressed patient who received electroconvulsive therapy (ECT). Prolonged apnea in our case ensued because the information about suicidal attempt by OP compound was concealed from the treating team.", "entity": "Organophosphorus Compounds", "aliases": "Compounds Organophosphorus Organopyrophosphorus", "definition": "Organic compounds that contain phosphorus as an integral part of the molecule. Included under this heading is broad array of synthetic compounds that are used as PESTICIDES and DRUGS.\n    ", "id": "MESH:D009943"}
{"mention": "bupropion", "mention_text": "The effects of the adjunctive bupropion on male sexual dysfunction induced by a selective serotonin reuptake inhibitor: a double-blind placebo-controlled and randomized study.", "entity": "Bupropion", "aliases": "(+-)-1-(3-Chlorophenyl)-2-((1,1-dimethylethyl)amino)-1-propanone Amfebutamone Bupropion Hydrochloride (+-)-Isomer Esteve Brand of Glaxo Wellcome 1 2 3 GlaxoSmithKline Quomen Wellbutrin Zyban (Anti-Smoking) Zyntabac", "definition": "A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment.\n    ", "id": "MESH:D016642"}
{"mention": "sexual dysfunction", "mention_text": "The effects of the adjunctive bupropion on male sexual dysfunction induced by a selective serotonin reuptake inhibitor: a double-blind placebo-controlled and randomized study.", "entity": "Sexual Dysfunction, Physiological", "aliases": "Physiological Sexual Disorder Disorders Dysfunction Dysfunctions Sex", "definition": "Physiological disturbances in normal sexual performance in either the male or the female.\n    ", "id": "MESH:D012735"}
{"mention": "selective serotonin reuptake inhibitor", "mention_text": "The effects of the adjunctive bupropion on male sexual dysfunction induced by a selective serotonin reuptake inhibitor: a double-blind placebo-controlled and randomized study.", "entity": "Serotonin Uptake Inhibitors", "aliases": "5 HT Uptake Inhibitors Hydroxytryptamine 5-HT 5-Hydroxytryptamine Serotonin Reuptake Selective", "definition": "Compounds that specifically inhibit the reuptake of serotonin in the brain.\n    ", "id": "MESH:D017367"}
{"mention": "bupropion", "mention_text": "OBJECTIVE: To determine the safety and efficacy of adjunctive bupropion sustained-release (SR) on male sexual dysfunction (SD) induced by a selective serotonin reuptake inhibitor (SSRI), as SD is a common side-effect of SSRIs and the most effective treatments have yet to be determined. PATIENTS AND METHODS: The randomized sample consisted of 234 euthymic men who were receiving some type of SSRI. The men were randomly assigned to bupropion SR (150 mg twice daily, 117) or placebo (twice daily, 117) for 12 weeks. Efficacy was evaluated using the Clinical Global Impression-Sexual Function (CGI-SF; the primary outcome measure), the International Index of Erectile Function (IIEF), Arizona Sexual Experience Scale (ASEX), and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) (secondary outcome measures). Participants were followed biweekly during study period. RESULTS: After 12 weeks of treatment, the mean (sd) scores for CGI-SF were significantly lower, i.e. better, in patients on bupropion SR, at 2.4 (1.2), than in the placebo group, at 3.9 (1.1) (P= 0.01). Men who received bupropion had a significant increase in the total IIEF score (54.4% vs 1.2%; P= 0.003), and in the five different domains of the IIEF. Total ASEX scores were significantly lower, i.e. better, among men who received bupropion than placebo, at 15.5 (4.3) vs 21.5 (4.7) (P= 0.002). The EDITS scores were 67.4 (10.2) for the bupropion and 36.3 (11.7) for the placebo group (P= 0.001). The ASEX score and CGI-SF score were correlated (P= 0.003). In linear regression analyses the CGI-SF score was not affected significantly by the duration of SD, type of SSRI used and age. CONCLUSIONS: Bupropion is an effective treatment for male SD induced by SSRIs. These results provide empirical support for conducting a further study of bupropion.", "entity": "Bupropion", "aliases": "(+-)-1-(3-Chlorophenyl)-2-((1,1-dimethylethyl)amino)-1-propanone Amfebutamone Bupropion Hydrochloride (+-)-Isomer Esteve Brand of Glaxo Wellcome 1 2 3 GlaxoSmithKline Quomen Wellbutrin Zyban (Anti-Smoking) Zyntabac", "definition": "A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment.\n    ", "id": "MESH:D016642"}
{"mention": "sexual dysfunction", "mention_text": "OBJECTIVE: To determine the safety and efficacy of adjunctive bupropion sustained-release (SR) on male sexual dysfunction (SD) induced by a selective serotonin reuptake inhibitor (SSRI), as SD is a common side-effect of SSRIs and the most effective treatments have yet to be determined. PATIENTS AND METHODS: The randomized sample consisted of 234 euthymic men who were receiving some type of SSRI. The men were randomly assigned to bupropion SR (150 mg twice daily, 117) or placebo (twice daily, 117) for 12 weeks. Efficacy was evaluated using the Clinical Global Impression-Sexual Function (CGI-SF; the primary outcome measure), the International Index of Erectile Function (IIEF), Arizona Sexual Experience Scale (ASEX), and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) (secondary outcome measures). Participants were followed biweekly during study period. RESULTS: After 12 weeks of treatment, the mean (sd) scores for CGI-SF were significantly lower, i.e. better, in patients on bupropion SR, at 2.4 (1.2), than in the placebo group, at 3.9 (1.1) (P= 0.01). Men who received bupropion had a significant increase in the total IIEF score (54.4% vs 1.2%; P= 0.003), and in the five different domains of the IIEF. Total ASEX scores were significantly lower, i.e. better, among men who received bupropion than placebo, at 15.5 (4.3) vs 21.5 (4.7) (P= 0.002). The EDITS scores were 67.4 (10.2) for the bupropion and 36.3 (11.7) for the placebo group (P= 0.001). The ASEX score and CGI-SF score were correlated (P= 0.003). In linear regression analyses the CGI-SF score was not affected significantly by the duration of SD, type of SSRI used and age. CONCLUSIONS: Bupropion is an effective treatment for male SD induced by SSRIs. These results provide empirical support for conducting a further study of bupropion.", "entity": "Sexual Dysfunction, Physiological", "aliases": "Physiological Sexual Disorder Disorders Dysfunction Dysfunctions Sex", "definition": "Physiological disturbances in normal sexual performance in either the male or the female.\n    ", "id": "MESH:D012735"}
{"mention": "SD", "mention_text": "OBJECTIVE: To determine the safety and efficacy of adjunctive bupropion sustained-release (SR) on male sexual dysfunction (SD) induced by a selective serotonin reuptake inhibitor (SSRI), as SD is a common side-effect of SSRIs and the most effective treatments have yet to be determined. PATIENTS AND METHODS: The randomized sample consisted of 234 euthymic men who were receiving some type of SSRI. The men were randomly assigned to bupropion SR (150 mg twice daily, 117) or placebo (twice daily, 117) for 12 weeks. Efficacy was evaluated using the Clinical Global Impression-Sexual Function (CGI-SF; the primary outcome measure), the International Index of Erectile Function (IIEF), Arizona Sexual Experience Scale (ASEX), and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) (secondary outcome measures). Participants were followed biweekly during study period. RESULTS: After 12 weeks of treatment, the mean (sd) scores for CGI-SF were significantly lower, i.e. better, in patients on bupropion SR, at 2.4 (1.2), than in the placebo group, at 3.9 (1.1) (P= 0.01). Men who received bupropion had a significant increase in the total IIEF score (54.4% vs 1.2%; P= 0.003), and in the five different domains of the IIEF. Total ASEX scores were significantly lower, i.e. better, among men who received bupropion than placebo, at 15.5 (4.3) vs 21.5 (4.7) (P= 0.002). The EDITS scores were 67.4 (10.2) for the bupropion and 36.3 (11.7) for the placebo group (P= 0.001). The ASEX score and CGI-SF score were correlated (P= 0.003). In linear regression analyses the CGI-SF score was not affected significantly by the duration of SD, type of SSRI used and age. CONCLUSIONS: Bupropion is an effective treatment for male SD induced by SSRIs. These results provide empirical support for conducting a further study of bupropion.", "entity": "Sexual Dysfunction, Physiological", "aliases": "Physiological Sexual Disorder Disorders Dysfunction Dysfunctions Sex", "definition": "Physiological disturbances in normal sexual performance in either the male or the female.\n    ", "id": "MESH:D012735"}
{"mention": "selective serotonin reuptake inhibitor", "mention_text": "OBJECTIVE: To determine the safety and efficacy of adjunctive bupropion sustained-release (SR) on male sexual dysfunction (SD) induced by a selective serotonin reuptake inhibitor (SSRI), as SD is a common side-effect of SSRIs and the most effective treatments have yet to be determined. PATIENTS AND METHODS: The randomized sample consisted of 234 euthymic men who were receiving some type of SSRI. The men were randomly assigned to bupropion SR (150 mg twice daily, 117) or placebo (twice daily, 117) for 12 weeks. Efficacy was evaluated using the Clinical Global Impression-Sexual Function (CGI-SF; the primary outcome measure), the International Index of Erectile Function (IIEF), Arizona Sexual Experience Scale (ASEX), and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) (secondary outcome measures). Participants were followed biweekly during study period. RESULTS: After 12 weeks of treatment, the mean (sd) scores for CGI-SF were significantly lower, i.e. better, in patients on bupropion SR, at 2.4 (1.2), than in the placebo group, at 3.9 (1.1) (P= 0.01). Men who received bupropion had a significant increase in the total IIEF score (54.4% vs 1.2%; P= 0.003), and in the five different domains of the IIEF. Total ASEX scores were significantly lower, i.e. better, among men who received bupropion than placebo, at 15.5 (4.3) vs 21.5 (4.7) (P= 0.002). The EDITS scores were 67.4 (10.2) for the bupropion and 36.3 (11.7) for the placebo group (P= 0.001). The ASEX score and CGI-SF score were correlated (P= 0.003). In linear regression analyses the CGI-SF score was not affected significantly by the duration of SD, type of SSRI used and age. CONCLUSIONS: Bupropion is an effective treatment for male SD induced by SSRIs. These results provide empirical support for conducting a further study of bupropion.", "entity": "Serotonin Uptake Inhibitors", "aliases": "5 HT Uptake Inhibitors Hydroxytryptamine 5-HT 5-Hydroxytryptamine Serotonin Reuptake Selective", "definition": "Compounds that specifically inhibit the reuptake of serotonin in the brain.\n    ", "id": "MESH:D017367"}
{"mention": "SSRI", "mention_text": "OBJECTIVE: To determine the safety and efficacy of adjunctive bupropion sustained-release (SR) on male sexual dysfunction (SD) induced by a selective serotonin reuptake inhibitor (SSRI), as SD is a common side-effect of SSRIs and the most effective treatments have yet to be determined. PATIENTS AND METHODS: The randomized sample consisted of 234 euthymic men who were receiving some type of SSRI. The men were randomly assigned to bupropion SR (150 mg twice daily, 117) or placebo (twice daily, 117) for 12 weeks. Efficacy was evaluated using the Clinical Global Impression-Sexual Function (CGI-SF; the primary outcome measure), the International Index of Erectile Function (IIEF), Arizona Sexual Experience Scale (ASEX), and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) (secondary outcome measures). Participants were followed biweekly during study period. RESULTS: After 12 weeks of treatment, the mean (sd) scores for CGI-SF were significantly lower, i.e. better, in patients on bupropion SR, at 2.4 (1.2), than in the placebo group, at 3.9 (1.1) (P= 0.01). Men who received bupropion had a significant increase in the total IIEF score (54.4% vs 1.2%; P= 0.003), and in the five different domains of the IIEF. Total ASEX scores were significantly lower, i.e. better, among men who received bupropion than placebo, at 15.5 (4.3) vs 21.5 (4.7) (P= 0.002). The EDITS scores were 67.4 (10.2) for the bupropion and 36.3 (11.7) for the placebo group (P= 0.001). The ASEX score and CGI-SF score were correlated (P= 0.003). In linear regression analyses the CGI-SF score was not affected significantly by the duration of SD, type of SSRI used and age. CONCLUSIONS: Bupropion is an effective treatment for male SD induced by SSRIs. These results provide empirical support for conducting a further study of bupropion.", "entity": "Serotonin Uptake Inhibitors", "aliases": "5 HT Uptake Inhibitors Hydroxytryptamine 5-HT 5-Hydroxytryptamine Serotonin Reuptake Selective", "definition": "Compounds that specifically inhibit the reuptake of serotonin in the brain.\n    ", "id": "MESH:D017367"}
{"mention": "SSRIs", "mention_text": "OBJECTIVE: To determine the safety and efficacy of adjunctive bupropion sustained-release (SR) on male sexual dysfunction (SD) induced by a selective serotonin reuptake inhibitor (SSRI), as SD is a common side-effect of SSRIs and the most effective treatments have yet to be determined. PATIENTS AND METHODS: The randomized sample consisted of 234 euthymic men who were receiving some type of SSRI. The men were randomly assigned to bupropion SR (150 mg twice daily, 117) or placebo (twice daily, 117) for 12 weeks. Efficacy was evaluated using the Clinical Global Impression-Sexual Function (CGI-SF; the primary outcome measure), the International Index of Erectile Function (IIEF), Arizona Sexual Experience Scale (ASEX), and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) (secondary outcome measures). Participants were followed biweekly during study period. RESULTS: After 12 weeks of treatment, the mean (sd) scores for CGI-SF were significantly lower, i.e. better, in patients on bupropion SR, at 2.4 (1.2), than in the placebo group, at 3.9 (1.1) (P= 0.01). Men who received bupropion had a significant increase in the total IIEF score (54.4% vs 1.2%; P= 0.003), and in the five different domains of the IIEF. Total ASEX scores were significantly lower, i.e. better, among men who received bupropion than placebo, at 15.5 (4.3) vs 21.5 (4.7) (P= 0.002). The EDITS scores were 67.4 (10.2) for the bupropion and 36.3 (11.7) for the placebo group (P= 0.001). The ASEX score and CGI-SF score were correlated (P= 0.003). In linear regression analyses the CGI-SF score was not affected significantly by the duration of SD, type of SSRI used and age. CONCLUSIONS: Bupropion is an effective treatment for male SD induced by SSRIs. These results provide empirical support for conducting a further study of bupropion.", "entity": "Serotonin Uptake Inhibitors", "aliases": "5 HT Uptake Inhibitors Hydroxytryptamine 5-HT 5-Hydroxytryptamine Serotonin Reuptake Selective", "definition": "Compounds that specifically inhibit the reuptake of serotonin in the brain.\n    ", "id": "MESH:D017367"}
{"mention": "Erectile Dysfunction", "mention_text": "OBJECTIVE: To determine the safety and efficacy of adjunctive bupropion sustained-release (SR) on male sexual dysfunction (SD) induced by a selective serotonin reuptake inhibitor (SSRI), as SD is a common side-effect of SSRIs and the most effective treatments have yet to be determined. PATIENTS AND METHODS: The randomized sample consisted of 234 euthymic men who were receiving some type of SSRI. The men were randomly assigned to bupropion SR (150 mg twice daily, 117) or placebo (twice daily, 117) for 12 weeks. Efficacy was evaluated using the Clinical Global Impression-Sexual Function (CGI-SF; the primary outcome measure), the International Index of Erectile Function (IIEF), Arizona Sexual Experience Scale (ASEX), and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) (secondary outcome measures). Participants were followed biweekly during study period. RESULTS: After 12 weeks of treatment, the mean (sd) scores for CGI-SF were significantly lower, i.e. better, in patients on bupropion SR, at 2.4 (1.2), than in the placebo group, at 3.9 (1.1) (P= 0.01). Men who received bupropion had a significant increase in the total IIEF score (54.4% vs 1.2%; P= 0.003), and in the five different domains of the IIEF. Total ASEX scores were significantly lower, i.e. better, among men who received bupropion than placebo, at 15.5 (4.3) vs 21.5 (4.7) (P= 0.002). The EDITS scores were 67.4 (10.2) for the bupropion and 36.3 (11.7) for the placebo group (P= 0.001). The ASEX score and CGI-SF score were correlated (P= 0.003). In linear regression analyses the CGI-SF score was not affected significantly by the duration of SD, type of SSRI used and age. CONCLUSIONS: Bupropion is an effective treatment for male SD induced by SSRIs. These results provide empirical support for conducting a further study of bupropion.", "entity": "Erectile Dysfunction", "aliases": "Dysfunction Erectile Impotence Male Sexual", "definition": "The inability in the male to have a PENILE ERECTION due to psychological or organ dysfunction.\n    ", "id": "MESH:D007172"}
{"mention": "Bupropion", "mention_text": "OBJECTIVE: To determine the safety and efficacy of adjunctive bupropion sustained-release (SR) on male sexual dysfunction (SD) induced by a selective serotonin reuptake inhibitor (SSRI), as SD is a common side-effect of SSRIs and the most effective treatments have yet to be determined. PATIENTS AND METHODS: The randomized sample consisted of 234 euthymic men who were receiving some type of SSRI. The men were randomly assigned to bupropion SR (150 mg twice daily, 117) or placebo (twice daily, 117) for 12 weeks. Efficacy was evaluated using the Clinical Global Impression-Sexual Function (CGI-SF; the primary outcome measure), the International Index of Erectile Function (IIEF), Arizona Sexual Experience Scale (ASEX), and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) (secondary outcome measures). Participants were followed biweekly during study period. RESULTS: After 12 weeks of treatment, the mean (sd) scores for CGI-SF were significantly lower, i.e. better, in patients on bupropion SR, at 2.4 (1.2), than in the placebo group, at 3.9 (1.1) (P= 0.01). Men who received bupropion had a significant increase in the total IIEF score (54.4% vs 1.2%; P= 0.003), and in the five different domains of the IIEF. Total ASEX scores were significantly lower, i.e. better, among men who received bupropion than placebo, at 15.5 (4.3) vs 21.5 (4.7) (P= 0.002). The EDITS scores were 67.4 (10.2) for the bupropion and 36.3 (11.7) for the placebo group (P= 0.001). The ASEX score and CGI-SF score were correlated (P= 0.003). In linear regression analyses the CGI-SF score was not affected significantly by the duration of SD, type of SSRI used and age. CONCLUSIONS: Bupropion is an effective treatment for male SD induced by SSRIs. These results provide empirical support for conducting a further study of bupropion.", "entity": "Bupropion", "aliases": "(+-)-1-(3-Chlorophenyl)-2-((1,1-dimethylethyl)amino)-1-propanone Amfebutamone Bupropion Hydrochloride (+-)-Isomer Esteve Brand of Glaxo Wellcome 1 2 3 GlaxoSmithKline Quomen Wellbutrin Zyban (Anti-Smoking) Zyntabac", "definition": "A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment.\n    ", "id": "MESH:D016642"}
{"mention": "Lamivudine", "mention_text": "Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis-B surface antigen (HBSAG) seropositive cancer patients undergoing cytotoxic chemotherapy.", "entity": "Lamivudine", "aliases": "2',3' Dideoxy 3' thiacytidine 2',3'-Dideoxy-3'-thiacytidine 3TC BCH 189 BCH-189 BCH189 Epivir GR-109714X GR109714X Lamivudine (2S-cis)-Isomer", "definition": "A reverse transcriptase inhibitor and ZALCITABINE analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease.\n    ", "id": "MESH:D019259"}
{"mention": "hepatitis B", "mention_text": "Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis-B surface antigen (HBSAG) seropositive cancer patients undergoing cytotoxic chemotherapy.", "entity": "Hepatitis B", "aliases": "Hepatitis B", "definition": "INFLAMMATION of the LIVER in humans caused by a member of the ORTHOHEPADNAVIRUS genus, HEPATITIS B VIRUS. It is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact.\n    ", "id": "MESH:D006509"}
{"mention": "hepatitis-B surface antigen", "mention_text": "Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis-B surface antigen (HBSAG) seropositive cancer patients undergoing cytotoxic chemotherapy.", "entity": "Hepatitis B Surface Antigens", "aliases": "Antigen Australia HBsAg Hepatitis B Surface Antigens", "definition": "Those hepatitis B antigens found on the surface of the Dane particle and on the 20 nm spherical and tubular particles. Several subspecificities of the surface antigen are known. These were formerly called the Australia antigen.\n    ", "id": "MESH:D006514"}
{"mention": "HBSAG", "mention_text": "Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis-B surface antigen (HBSAG) seropositive cancer patients undergoing cytotoxic chemotherapy.", "entity": "Hepatitis B Surface Antigens", "aliases": "Antigen Australia HBsAg Hepatitis B Surface Antigens", "definition": "Those hepatitis B antigens found on the surface of the Dane particle and on the 20 nm spherical and tubular particles. Several subspecificities of the surface antigen are known. These were formerly called the Australia antigen.\n    ", "id": "MESH:D006514"}
{"mention": "cancer", "mention_text": "Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis-B surface antigen (HBSAG) seropositive cancer patients undergoing cytotoxic chemotherapy.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "Hepatitis B", "mention_text": "Hepatitis B virus (HBV) is one of the major causes of chronic liver disease worldwide. Cancer patients who are chronic carriers of HBV have a higher hepatic complication rate while receiving cytotoxic chemotherapy (CT) and this has mainly been attributed to HBV reactivation. In this study, cancer patients who have solid and hematological malignancies with chronic HBV infection received the antiviral agent lamivudine prior and during CT compared with historical control group who did not receive lamivudine. The objectives were to assess the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity and mortality during CT. Two groups were compared in this study. The prophylactic lamivudin group consisted of 37 patients who received prophylactic lamivudine treatment. The historical controls consisted of 50 consecutive patients who underwent CT without prophylactic lamivudine. They were followed up during and for 8 weeks after CT. The outcomes were compared for both groups. Of our control group (n= 50), 21 patients (42%) were established hepatitis. Twelve (24%) of them were evaluated as severe hepatitis. In the prophylactic lamivudine group severe hepatitis were observed only in 1 patient (2.7%) of 37 patients (p < 0.006). Comparison of the mean ALT values revealed significantly higher mean alanine aminotransferase (ALT) values in the control group than the prophylactic lamivudine group; 154:64 (p < 0.32). Our study suggests that prophylactic lamivudine significantly decreases the incidence of HBV reactivation and overall morbidity in cancer patients during and after immunosuppressive therapy. Further studies are needed to determine the most appropriate nucleoside or nucleotide analogue for antiviral prophylaxis during CT and the optimal duration of administration after completion of CT.", "entity": "Hepatitis B", "aliases": "Hepatitis B", "definition": "INFLAMMATION of the LIVER in humans caused by a member of the ORTHOHEPADNAVIRUS genus, HEPATITIS B VIRUS. It is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact.\n    ", "id": "MESH:D006509"}
{"mention": "liver disease", "mention_text": "Hepatitis B virus (HBV) is one of the major causes of chronic liver disease worldwide. Cancer patients who are chronic carriers of HBV have a higher hepatic complication rate while receiving cytotoxic chemotherapy (CT) and this has mainly been attributed to HBV reactivation. In this study, cancer patients who have solid and hematological malignancies with chronic HBV infection received the antiviral agent lamivudine prior and during CT compared with historical control group who did not receive lamivudine. The objectives were to assess the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity and mortality during CT. Two groups were compared in this study. The prophylactic lamivudin group consisted of 37 patients who received prophylactic lamivudine treatment. The historical controls consisted of 50 consecutive patients who underwent CT without prophylactic lamivudine. They were followed up during and for 8 weeks after CT. The outcomes were compared for both groups. Of our control group (n= 50), 21 patients (42%) were established hepatitis. Twelve (24%) of them were evaluated as severe hepatitis. In the prophylactic lamivudine group severe hepatitis were observed only in 1 patient (2.7%) of 37 patients (p < 0.006). Comparison of the mean ALT values revealed significantly higher mean alanine aminotransferase (ALT) values in the control group than the prophylactic lamivudine group; 154:64 (p < 0.32). Our study suggests that prophylactic lamivudine significantly decreases the incidence of HBV reactivation and overall morbidity in cancer patients during and after immunosuppressive therapy. Further studies are needed to determine the most appropriate nucleoside or nucleotide analogue for antiviral prophylaxis during CT and the optimal duration of administration after completion of CT.", "entity": "Liver Diseases", "aliases": "Disease Liver Diseases Dysfunction Dysfunctions", "definition": "Pathological processes of the LIVER.\n    ", "id": "MESH:D008107"}
{"mention": "Cancer", "mention_text": "Hepatitis B virus (HBV) is one of the major causes of chronic liver disease worldwide. Cancer patients who are chronic carriers of HBV have a higher hepatic complication rate while receiving cytotoxic chemotherapy (CT) and this has mainly been attributed to HBV reactivation. In this study, cancer patients who have solid and hematological malignancies with chronic HBV infection received the antiviral agent lamivudine prior and during CT compared with historical control group who did not receive lamivudine. The objectives were to assess the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity and mortality during CT. Two groups were compared in this study. The prophylactic lamivudin group consisted of 37 patients who received prophylactic lamivudine treatment. The historical controls consisted of 50 consecutive patients who underwent CT without prophylactic lamivudine. They were followed up during and for 8 weeks after CT. The outcomes were compared for both groups. Of our control group (n= 50), 21 patients (42%) were established hepatitis. Twelve (24%) of them were evaluated as severe hepatitis. In the prophylactic lamivudine group severe hepatitis were observed only in 1 patient (2.7%) of 37 patients (p < 0.006). Comparison of the mean ALT values revealed significantly higher mean alanine aminotransferase (ALT) values in the control group than the prophylactic lamivudine group; 154:64 (p < 0.32). Our study suggests that prophylactic lamivudine significantly decreases the incidence of HBV reactivation and overall morbidity in cancer patients during and after immunosuppressive therapy. Further studies are needed to determine the most appropriate nucleoside or nucleotide analogue for antiviral prophylaxis during CT and the optimal duration of administration after completion of CT.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "hepatic complication", "mention_text": "Hepatitis B virus (HBV) is one of the major causes of chronic liver disease worldwide. Cancer patients who are chronic carriers of HBV have a higher hepatic complication rate while receiving cytotoxic chemotherapy (CT) and this has mainly been attributed to HBV reactivation. In this study, cancer patients who have solid and hematological malignancies with chronic HBV infection received the antiviral agent lamivudine prior and during CT compared with historical control group who did not receive lamivudine. The objectives were to assess the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity and mortality during CT. Two groups were compared in this study. The prophylactic lamivudin group consisted of 37 patients who received prophylactic lamivudine treatment. The historical controls consisted of 50 consecutive patients who underwent CT without prophylactic lamivudine. They were followed up during and for 8 weeks after CT. The outcomes were compared for both groups. Of our control group (n= 50), 21 patients (42%) were established hepatitis. Twelve (24%) of them were evaluated as severe hepatitis. In the prophylactic lamivudine group severe hepatitis were observed only in 1 patient (2.7%) of 37 patients (p < 0.006). Comparison of the mean ALT values revealed significantly higher mean alanine aminotransferase (ALT) values in the control group than the prophylactic lamivudine group; 154:64 (p < 0.32). Our study suggests that prophylactic lamivudine significantly decreases the incidence of HBV reactivation and overall morbidity in cancer patients during and after immunosuppressive therapy. Further studies are needed to determine the most appropriate nucleoside or nucleotide analogue for antiviral prophylaxis during CT and the optimal duration of administration after completion of CT.", "entity": "Liver Diseases", "aliases": "Disease Liver Diseases Dysfunction Dysfunctions", "definition": "Pathological processes of the LIVER.\n    ", "id": "MESH:D008107"}
{"mention": "cancer", "mention_text": "Hepatitis B virus (HBV) is one of the major causes of chronic liver disease worldwide. Cancer patients who are chronic carriers of HBV have a higher hepatic complication rate while receiving cytotoxic chemotherapy (CT) and this has mainly been attributed to HBV reactivation. In this study, cancer patients who have solid and hematological malignancies with chronic HBV infection received the antiviral agent lamivudine prior and during CT compared with historical control group who did not receive lamivudine. The objectives were to assess the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity and mortality during CT. Two groups were compared in this study. The prophylactic lamivudin group consisted of 37 patients who received prophylactic lamivudine treatment. The historical controls consisted of 50 consecutive patients who underwent CT without prophylactic lamivudine. They were followed up during and for 8 weeks after CT. The outcomes were compared for both groups. Of our control group (n= 50), 21 patients (42%) were established hepatitis. Twelve (24%) of them were evaluated as severe hepatitis. In the prophylactic lamivudine group severe hepatitis were observed only in 1 patient (2.7%) of 37 patients (p < 0.006). Comparison of the mean ALT values revealed significantly higher mean alanine aminotransferase (ALT) values in the control group than the prophylactic lamivudine group; 154:64 (p < 0.32). Our study suggests that prophylactic lamivudine significantly decreases the incidence of HBV reactivation and overall morbidity in cancer patients during and after immunosuppressive therapy. Further studies are needed to determine the most appropriate nucleoside or nucleotide analogue for antiviral prophylaxis during CT and the optimal duration of administration after completion of CT.", "entity": "Neoplasms", "aliases": "Benign Neoplasm Neoplasms Cancer Cancers Neoplasia Tumor Tumors", "definition": "New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.\n    ", "id": "MESH:D009369"}
{"mention": "hematological malignancies", "mention_text": "Hepatitis B virus (HBV) is one of the major causes of chronic liver disease worldwide. Cancer patients who are chronic carriers of HBV have a higher hepatic complication rate while receiving cytotoxic chemotherapy (CT) and this has mainly been attributed to HBV reactivation. In this study, cancer patients who have solid and hematological malignancies with chronic HBV infection received the antiviral agent lamivudine prior and during CT compared with historical control group who did not receive lamivudine. The objectives were to assess the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity and mortality during CT. Two groups were compared in this study. The prophylactic lamivudin group consisted of 37 patients who received prophylactic lamivudine treatment. The historical controls consisted of 50 consecutive patients who underwent CT without prophylactic lamivudine. They were followed up during and for 8 weeks after CT. The outcomes were compared for both groups. Of our control group (n= 50), 21 patients (42%) were established hepatitis. Twelve (24%) of them were evaluated as severe hepatitis. In the prophylactic lamivudine group severe hepatitis were observed only in 1 patient (2.7%) of 37 patients (p < 0.006). Comparison of the mean ALT values revealed significantly higher mean alanine aminotransferase (ALT) values in the control group than the prophylactic lamivudine group; 154:64 (p < 0.32). Our study suggests that prophylactic lamivudine significantly decreases the incidence of HBV reactivation and overall morbidity in cancer patients during and after immunosuppressive therapy. Further studies are needed to determine the most appropriate nucleoside or nucleotide analogue for antiviral prophylaxis during CT and the optimal duration of administration after completion of CT.", "entity": "Hematologic Neoplasms", "aliases": "Hematologic Malignancies Malignancy Neoplasm Neoplasms Hematological Hematopoietic", "definition": "Neoplasms located in the blood and blood-forming tissue (the bone marrow and lymphatic tissue). The commonest forms are the various types of LEUKEMIA, of LYMPHOMA, and of the progressive, life-threatening forms of the MYELODYSPLASTIC SYNDROMES.\n    ", "id": "MESH:D019337"}
{"mention": "HBV infection", "mention_text": "Hepatitis B virus (HBV) is one of the major causes of chronic liver disease worldwide. Cancer patients who are chronic carriers of HBV have a higher hepatic complication rate while receiving cytotoxic chemotherapy (CT) and this has mainly been attributed to HBV reactivation. In this study, cancer patients who have solid and hematological malignancies with chronic HBV infection received the antiviral agent lamivudine prior and during CT compared with historical control group who did not receive lamivudine. The objectives were to assess the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity and mortality during CT. Two groups were compared in this study. The prophylactic lamivudin group consisted of 37 patients who received prophylactic lamivudine treatment. The historical controls consisted of 50 consecutive patients who underwent CT without prophylactic lamivudine. They were followed up during and for 8 weeks after CT. The outcomes were compared for both groups. Of our control group (n= 50), 21 patients (42%) were established hepatitis. Twelve (24%) of them were evaluated as severe hepatitis. In the prophylactic lamivudine group severe hepatitis were observed only in 1 patient (2.7%) of 37 patients (p < 0.006). Comparison of the mean ALT values revealed significantly higher mean alanine aminotransferase (ALT) values in the control group than the prophylactic lamivudine group; 154:64 (p < 0.32). Our study suggests that prophylactic lamivudine significantly decreases the incidence of HBV reactivation and overall morbidity in cancer patients during and after immunosuppressive therapy. Further studies are needed to determine the most appropriate nucleoside or nucleotide analogue for antiviral prophylaxis during CT and the optimal duration of administration after completion of CT.", "entity": "Hepatitis B", "aliases": "Hepatitis B", "definition": "INFLAMMATION of the LIVER in humans caused by a member of the ORTHOHEPADNAVIRUS genus, HEPATITIS B VIRUS. It is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact.\n    ", "id": "MESH:D006509"}
{"mention": "lamivudine", "mention_text": "Hepatitis B virus (HBV) is one of the major causes of chronic liver disease worldwide. Cancer patients who are chronic carriers of HBV have a higher hepatic complication rate while receiving cytotoxic chemotherapy (CT) and this has mainly been attributed to HBV reactivation. In this study, cancer patients who have solid and hematological malignancies with chronic HBV infection received the antiviral agent lamivudine prior and during CT compared with historical control group who did not receive lamivudine. The objectives were to assess the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity and mortality during CT. Two groups were compared in this study. The prophylactic lamivudin group consisted of 37 patients who received prophylactic lamivudine treatment. The historical controls consisted of 50 consecutive patients who underwent CT without prophylactic lamivudine. They were followed up during and for 8 weeks after CT. The outcomes were compared for both groups. Of our control group (n= 50), 21 patients (42%) were established hepatitis. Twelve (24%) of them were evaluated as severe hepatitis. In the prophylactic lamivudine group severe hepatitis were observed only in 1 patient (2.7%) of 37 patients (p < 0.006). Comparison of the mean ALT values revealed significantly higher mean alanine aminotransferase (ALT) values in the control group than the prophylactic lamivudine group; 154:64 (p < 0.32). Our study suggests that prophylactic lamivudine significantly decreases the incidence of HBV reactivation and overall morbidity in cancer patients during and after immunosuppressive therapy. Further studies are needed to determine the most appropriate nucleoside or nucleotide analogue for antiviral prophylaxis during CT and the optimal duration of administration after completion of CT.", "entity": "Lamivudine", "aliases": "2',3' Dideoxy 3' thiacytidine 2',3'-Dideoxy-3'-thiacytidine 3TC BCH 189 BCH-189 BCH189 Epivir GR-109714X GR109714X Lamivudine (2S-cis)-Isomer", "definition": "A reverse transcriptase inhibitor and ZALCITABINE analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease.\n    ", "id": "MESH:D019259"}
{"mention": "lamivudin", "mention_text": "Hepatitis B virus (HBV) is one of the major causes of chronic liver disease worldwide. Cancer patients who are chronic carriers of HBV have a higher hepatic complication rate while receiving cytotoxic chemotherapy (CT) and this has mainly been attributed to HBV reactivation. In this study, cancer patients who have solid and hematological malignancies with chronic HBV infection received the antiviral agent lamivudine prior and during CT compared with historical control group who did not receive lamivudine. The objectives were to assess the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity and mortality during CT. Two groups were compared in this study. The prophylactic lamivudin group consisted of 37 patients who received prophylactic lamivudine treatment. The historical controls consisted of 50 consecutive patients who underwent CT without prophylactic lamivudine. They were followed up during and for 8 weeks after CT. The outcomes were compared for both groups. Of our control group (n= 50), 21 patients (42%) were established hepatitis. Twelve (24%) of them were evaluated as severe hepatitis. In the prophylactic lamivudine group severe hepatitis were observed only in 1 patient (2.7%) of 37 patients (p < 0.006). Comparison of the mean ALT values revealed significantly higher mean alanine aminotransferase (ALT) values in the control group than the prophylactic lamivudine group; 154:64 (p < 0.32). Our study suggests that prophylactic lamivudine significantly decreases the incidence of HBV reactivation and overall morbidity in cancer patients during and after immunosuppressive therapy. Further studies are needed to determine the most appropriate nucleoside or nucleotide analogue for antiviral prophylaxis during CT and the optimal duration of administration after completion of CT.", "entity": "Lamivudine", "aliases": "2',3' Dideoxy 3' thiacytidine 2',3'-Dideoxy-3'-thiacytidine 3TC BCH 189 BCH-189 BCH189 Epivir GR-109714X GR109714X Lamivudine (2S-cis)-Isomer", "definition": "A reverse transcriptase inhibitor and ZALCITABINE analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease.\n    ", "id": "MESH:D019259"}
{"mention": "hepatitis", "mention_text": "Hepatitis B virus (HBV) is one of the major causes of chronic liver disease worldwide. Cancer patients who are chronic carriers of HBV have a higher hepatic complication rate while receiving cytotoxic chemotherapy (CT) and this has mainly been attributed to HBV reactivation. In this study, cancer patients who have solid and hematological malignancies with chronic HBV infection received the antiviral agent lamivudine prior and during CT compared with historical control group who did not receive lamivudine. The objectives were to assess the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity and mortality during CT. Two groups were compared in this study. The prophylactic lamivudin group consisted of 37 patients who received prophylactic lamivudine treatment. The historical controls consisted of 50 consecutive patients who underwent CT without prophylactic lamivudine. They were followed up during and for 8 weeks after CT. The outcomes were compared for both groups. Of our control group (n= 50), 21 patients (42%) were established hepatitis. Twelve (24%) of them were evaluated as severe hepatitis. In the prophylactic lamivudine group severe hepatitis were observed only in 1 patient (2.7%) of 37 patients (p < 0.006). Comparison of the mean ALT values revealed significantly higher mean alanine aminotransferase (ALT) values in the control group than the prophylactic lamivudine group; 154:64 (p < 0.32). Our study suggests that prophylactic lamivudine significantly decreases the incidence of HBV reactivation and overall morbidity in cancer patients during and after immunosuppressive therapy. Further studies are needed to determine the most appropriate nucleoside or nucleotide analogue for antiviral prophylaxis during CT and the optimal duration of administration after completion of CT.", "entity": "Drug-Induced Liver Injury", "aliases": "Acute Liver Injury Drug Induced Drug-Induced Disease Diseases Hepatitides Hepatitis Injuries Toxic", "definition": "A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.\n    ", "id": "MESH:D056486"}
{"mention": "alanine", "mention_text": "Hepatitis B virus (HBV) is one of the major causes of chronic liver disease worldwide. Cancer patients who are chronic carriers of HBV have a higher hepatic complication rate while receiving cytotoxic chemotherapy (CT) and this has mainly been attributed to HBV reactivation. In this study, cancer patients who have solid and hematological malignancies with chronic HBV infection received the antiviral agent lamivudine prior and during CT compared with historical control group who did not receive lamivudine. The objectives were to assess the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity and mortality during CT. Two groups were compared in this study. The prophylactic lamivudin group consisted of 37 patients who received prophylactic lamivudine treatment. The historical controls consisted of 50 consecutive patients who underwent CT without prophylactic lamivudine. They were followed up during and for 8 weeks after CT. The outcomes were compared for both groups. Of our control group (n= 50), 21 patients (42%) were established hepatitis. Twelve (24%) of them were evaluated as severe hepatitis. In the prophylactic lamivudine group severe hepatitis were observed only in 1 patient (2.7%) of 37 patients (p < 0.006). Comparison of the mean ALT values revealed significantly higher mean alanine aminotransferase (ALT) values in the control group than the prophylactic lamivudine group; 154:64 (p < 0.32). Our study suggests that prophylactic lamivudine significantly decreases the incidence of HBV reactivation and overall morbidity in cancer patients during and after immunosuppressive therapy. Further studies are needed to determine the most appropriate nucleoside or nucleotide analogue for antiviral prophylaxis during CT and the optimal duration of administration after completion of CT.", "entity": "Alanine", "aliases": "Abufène Alanine Doms-Adrian Brand L Isomer L-Isomer Doms Adrian of L-Alanine", "definition": "A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases IMMUNITY, and provides energy for muscle tissue, BRAIN, and the CENTRAL NERVOUS SYSTEM.\n    ", "id": "MESH:D000409"}
{"mention": "nucleoside", "mention_text": "Hepatitis B virus (HBV) is one of the major causes of chronic liver disease worldwide. Cancer patients who are chronic carriers of HBV have a higher hepatic complication rate while receiving cytotoxic chemotherapy (CT) and this has mainly been attributed to HBV reactivation. In this study, cancer patients who have solid and hematological malignancies with chronic HBV infection received the antiviral agent lamivudine prior and during CT compared with historical control group who did not receive lamivudine. The objectives were to assess the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity and mortality during CT. Two groups were compared in this study. The prophylactic lamivudin group consisted of 37 patients who received prophylactic lamivudine treatment. The historical controls consisted of 50 consecutive patients who underwent CT without prophylactic lamivudine. They were followed up during and for 8 weeks after CT. The outcomes were compared for both groups. Of our control group (n= 50), 21 patients (42%) were established hepatitis. Twelve (24%) of them were evaluated as severe hepatitis. In the prophylactic lamivudine group severe hepatitis were observed only in 1 patient (2.7%) of 37 patients (p < 0.006). Comparison of the mean ALT values revealed significantly higher mean alanine aminotransferase (ALT) values in the control group than the prophylactic lamivudine group; 154:64 (p < 0.32). Our study suggests that prophylactic lamivudine significantly decreases the incidence of HBV reactivation and overall morbidity in cancer patients during and after immunosuppressive therapy. Further studies are needed to determine the most appropriate nucleoside or nucleotide analogue for antiviral prophylaxis during CT and the optimal duration of administration after completion of CT.", "entity": "Nucleosides", "aliases": "Nucleosides", "definition": "Purine or pyrimidine bases attached to a ribose or deoxyribose. (From King & Stansfield, A Dictionary of Genetics, 4th ed)\n    ", "id": "MESH:D009705"}
{"mention": "nucleotide", "mention_text": "Hepatitis B virus (HBV) is one of the major causes of chronic liver disease worldwide. Cancer patients who are chronic carriers of HBV have a higher hepatic complication rate while receiving cytotoxic chemotherapy (CT) and this has mainly been attributed to HBV reactivation. In this study, cancer patients who have solid and hematological malignancies with chronic HBV infection received the antiviral agent lamivudine prior and during CT compared with historical control group who did not receive lamivudine. The objectives were to assess the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity and mortality during CT. Two groups were compared in this study. The prophylactic lamivudin group consisted of 37 patients who received prophylactic lamivudine treatment. The historical controls consisted of 50 consecutive patients who underwent CT without prophylactic lamivudine. They were followed up during and for 8 weeks after CT. The outcomes were compared for both groups. Of our control group (n= 50), 21 patients (42%) were established hepatitis. Twelve (24%) of them were evaluated as severe hepatitis. In the prophylactic lamivudine group severe hepatitis were observed only in 1 patient (2.7%) of 37 patients (p < 0.006). Comparison of the mean ALT values revealed significantly higher mean alanine aminotransferase (ALT) values in the control group than the prophylactic lamivudine group; 154:64 (p < 0.32). Our study suggests that prophylactic lamivudine significantly decreases the incidence of HBV reactivation and overall morbidity in cancer patients during and after immunosuppressive therapy. Further studies are needed to determine the most appropriate nucleoside or nucleotide analogue for antiviral prophylaxis during CT and the optimal duration of administration after completion of CT.", "entity": "Nucleotides", "aliases": "Nucleotides", "definition": "The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)\n    ", "id": "MESH:D009711"}
{"mention": "Ginsenoside Rg1", "mention_text": "Ginsenoside Rg1 restores the impairment of learning induced by chronic morphine administration in rats.", "entity": "ginsenoside Rg1", "aliases": "ginsenoside Rg1 ginsenoside-Rg(1) panaxoside sanchinoside C(1) C1", "definition": "", "id": "MESH:C035054"}
{"mention": "impairment of learning", "mention_text": "Ginsenoside Rg1 restores the impairment of learning induced by chronic morphine administration in rats.", "entity": "Learning Disorders", "aliases": "Academic Disorder Developmental Disorders Adult Learning of Scholastic Skills Disabilities Disability Disturbance Disturbances Development", "definition": "Conditions characterized by a significant discrepancy between an individual's perceived level of intellect and their ability to acquire new language and other cognitive skills. These disorders may result from organic or psychological conditions. Relatively common subtypes include DYSLEXIA, dyscalculia, and dysgraphia.\n    ", "id": "MESH:D007859"}
{"mention": "morphine", "mention_text": "Ginsenoside Rg1 restores the impairment of learning induced by chronic morphine administration in rats.", "entity": "Morphine", "aliases": "Chloride Morphine Contin MS Duramorph Morphia Sulfate (2:1) Anhydrous Pentahydrate Oramorph SR SDZ 202 250 202-250 202250 SDZ202 SDZ202-250 SDZ202250", "definition": "The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.\n    ", "id": "MESH:D009020"}
{"mention": "Rg1", "mention_text": "Rg1, as a ginsenoside extracted from Panax ginseng, could ameliorate spatial learning impairment. Previous studies have demonstrated that Rg1 might be a useful agent for the prevention and treatment of the adverse effects of morphine. The aim of this study was to investigate the effect of Rg1 on learning impairment by chronic morphine administration and the mechanism responsible for this effect. Male rats were subcutaneously injected with morphine (10 mg/kg) twice a day at 12 hour intervals for 10 days, and Rg1 (30 mg/kg) was intraperitoneally injected 2 hours after the second injection of morphine once a day for 10 days. Spatial learning capacity was assessed in the Morris water maze. The results showed that rats treated with Morphine/Rg1 decreased escape latency and increased the time spent in platform quadrant and entering frequency. By implantation of electrodes and electrophysiological recording in vivo, the results showed that Rg1 restored the long-term potentiation (LTP) impaired by morphine in both freely moving and anaesthetised rats. The electrophysiological recording in vitro showed that Rg1 restored the LTP in slices from the rats treated with morphine, but not changed LTP in the slices from normal saline- or morphine/Rg1-treated rats; this restoration could be inhibited by N-methyl-D-aspartate (NMDA) receptor antagonist MK801. We conclude that Rg1 may significantly improve the spatial learning capacity impaired by chonic morphine administration and restore the morphine-inhibited LTP. This effect is NMDA receptor dependent.", "entity": "ginsenoside Rg1", "aliases": "ginsenoside Rg1 ginsenoside-Rg(1) panaxoside sanchinoside C(1) C1", "definition": "", "id": "MESH:C035054"}
{"mention": "ginsenoside", "mention_text": "Rg1, as a ginsenoside extracted from Panax ginseng, could ameliorate spatial learning impairment. Previous studies have demonstrated that Rg1 might be a useful agent for the prevention and treatment of the adverse effects of morphine. The aim of this study was to investigate the effect of Rg1 on learning impairment by chronic morphine administration and the mechanism responsible for this effect. Male rats were subcutaneously injected with morphine (10 mg/kg) twice a day at 12 hour intervals for 10 days, and Rg1 (30 mg/kg) was intraperitoneally injected 2 hours after the second injection of morphine once a day for 10 days. Spatial learning capacity was assessed in the Morris water maze. The results showed that rats treated with Morphine/Rg1 decreased escape latency and increased the time spent in platform quadrant and entering frequency. By implantation of electrodes and electrophysiological recording in vivo, the results showed that Rg1 restored the long-term potentiation (LTP) impaired by morphine in both freely moving and anaesthetised rats. The electrophysiological recording in vitro showed that Rg1 restored the LTP in slices from the rats treated with morphine, but not changed LTP in the slices from normal saline- or morphine/Rg1-treated rats; this restoration could be inhibited by N-methyl-D-aspartate (NMDA) receptor antagonist MK801. We conclude that Rg1 may significantly improve the spatial learning capacity impaired by chonic morphine administration and restore the morphine-inhibited LTP. This effect is NMDA receptor dependent.", "entity": "Ginsenosides", "aliases": "Ginsenosides Panaxosides Sanchinosides", "definition": "Dammarane type triterpene saponins based mainly on the aglycones, protopanaxadiol and protopanaxatriol.\n    ", "id": "MESH:D036145"}
{"mention": "learning impairment", "mention_text": "Rg1, as a ginsenoside extracted from Panax ginseng, could ameliorate spatial learning impairment. Previous studies have demonstrated that Rg1 might be a useful agent for the prevention and treatment of the adverse effects of morphine. The aim of this study was to investigate the effect of Rg1 on learning impairment by chronic morphine administration and the mechanism responsible for this effect. Male rats were subcutaneously injected with morphine (10 mg/kg) twice a day at 12 hour intervals for 10 days, and Rg1 (30 mg/kg) was intraperitoneally injected 2 hours after the second injection of morphine once a day for 10 days. Spatial learning capacity was assessed in the Morris water maze. The results showed that rats treated with Morphine/Rg1 decreased escape latency and increased the time spent in platform quadrant and entering frequency. By implantation of electrodes and electrophysiological recording in vivo, the results showed that Rg1 restored the long-term potentiation (LTP) impaired by morphine in both freely moving and anaesthetised rats. The electrophysiological recording in vitro showed that Rg1 restored the LTP in slices from the rats treated with morphine, but not changed LTP in the slices from normal saline- or morphine/Rg1-treated rats; this restoration could be inhibited by N-methyl-D-aspartate (NMDA) receptor antagonist MK801. We conclude that Rg1 may significantly improve the spatial learning capacity impaired by chonic morphine administration and restore the morphine-inhibited LTP. This effect is NMDA receptor dependent.", "entity": "Learning Disorders", "aliases": "Academic Disorder Developmental Disorders Adult Learning of Scholastic Skills Disabilities Disability Disturbance Disturbances Development", "definition": "Conditions characterized by a significant discrepancy between an individual's perceived level of intellect and their ability to acquire new language and other cognitive skills. These disorders may result from organic or psychological conditions. Relatively common subtypes include DYSLEXIA, dyscalculia, and dysgraphia.\n    ", "id": "MESH:D007859"}
{"mention": "morphine", "mention_text": "Rg1, as a ginsenoside extracted from Panax ginseng, could ameliorate spatial learning impairment. Previous studies have demonstrated that Rg1 might be a useful agent for the prevention and treatment of the adverse effects of morphine. The aim of this study was to investigate the effect of Rg1 on learning impairment by chronic morphine administration and the mechanism responsible for this effect. Male rats were subcutaneously injected with morphine (10 mg/kg) twice a day at 12 hour intervals for 10 days, and Rg1 (30 mg/kg) was intraperitoneally injected 2 hours after the second injection of morphine once a day for 10 days. Spatial learning capacity was assessed in the Morris water maze. The results showed that rats treated with Morphine/Rg1 decreased escape latency and increased the time spent in platform quadrant and entering frequency. By implantation of electrodes and electrophysiological recording in vivo, the results showed that Rg1 restored the long-term potentiation (LTP) impaired by morphine in both freely moving and anaesthetised rats. The electrophysiological recording in vitro showed that Rg1 restored the LTP in slices from the rats treated with morphine, but not changed LTP in the slices from normal saline- or morphine/Rg1-treated rats; this restoration could be inhibited by N-methyl-D-aspartate (NMDA) receptor antagonist MK801. We conclude that Rg1 may significantly improve the spatial learning capacity impaired by chonic morphine administration and restore the morphine-inhibited LTP. This effect is NMDA receptor dependent.", "entity": "Morphine", "aliases": "Chloride Morphine Contin MS Duramorph Morphia Sulfate (2:1) Anhydrous Pentahydrate Oramorph SR SDZ 202 250 202-250 202250 SDZ202 SDZ202-250 SDZ202250", "definition": "The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.\n    ", "id": "MESH:D009020"}
{"mention": "Morphine", "mention_text": "Rg1, as a ginsenoside extracted from Panax ginseng, could ameliorate spatial learning impairment. Previous studies have demonstrated that Rg1 might be a useful agent for the prevention and treatment of the adverse effects of morphine. The aim of this study was to investigate the effect of Rg1 on learning impairment by chronic morphine administration and the mechanism responsible for this effect. Male rats were subcutaneously injected with morphine (10 mg/kg) twice a day at 12 hour intervals for 10 days, and Rg1 (30 mg/kg) was intraperitoneally injected 2 hours after the second injection of morphine once a day for 10 days. Spatial learning capacity was assessed in the Morris water maze. The results showed that rats treated with Morphine/Rg1 decreased escape latency and increased the time spent in platform quadrant and entering frequency. By implantation of electrodes and electrophysiological recording in vivo, the results showed that Rg1 restored the long-term potentiation (LTP) impaired by morphine in both freely moving and anaesthetised rats. The electrophysiological recording in vitro showed that Rg1 restored the LTP in slices from the rats treated with morphine, but not changed LTP in the slices from normal saline- or morphine/Rg1-treated rats; this restoration could be inhibited by N-methyl-D-aspartate (NMDA) receptor antagonist MK801. We conclude that Rg1 may significantly improve the spatial learning capacity impaired by chonic morphine administration and restore the morphine-inhibited LTP. This effect is NMDA receptor dependent.", "entity": "Morphine", "aliases": "Chloride Morphine Contin MS Duramorph Morphia Sulfate (2:1) Anhydrous Pentahydrate Oramorph SR SDZ 202 250 202-250 202250 SDZ202 SDZ202-250 SDZ202250", "definition": "The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.\n    ", "id": "MESH:D009020"}
{"mention": "N-methyl-D-aspartate", "mention_text": "Rg1, as a ginsenoside extracted from Panax ginseng, could ameliorate spatial learning impairment. Previous studies have demonstrated that Rg1 might be a useful agent for the prevention and treatment of the adverse effects of morphine. The aim of this study was to investigate the effect of Rg1 on learning impairment by chronic morphine administration and the mechanism responsible for this effect. Male rats were subcutaneously injected with morphine (10 mg/kg) twice a day at 12 hour intervals for 10 days, and Rg1 (30 mg/kg) was intraperitoneally injected 2 hours after the second injection of morphine once a day for 10 days. Spatial learning capacity was assessed in the Morris water maze. The results showed that rats treated with Morphine/Rg1 decreased escape latency and increased the time spent in platform quadrant and entering frequency. By implantation of electrodes and electrophysiological recording in vivo, the results showed that Rg1 restored the long-term potentiation (LTP) impaired by morphine in both freely moving and anaesthetised rats. The electrophysiological recording in vitro showed that Rg1 restored the LTP in slices from the rats treated with morphine, but not changed LTP in the slices from normal saline- or morphine/Rg1-treated rats; this restoration could be inhibited by N-methyl-D-aspartate (NMDA) receptor antagonist MK801. We conclude that Rg1 may significantly improve the spatial learning capacity impaired by chonic morphine administration and restore the morphine-inhibited LTP. This effect is NMDA receptor dependent.", "entity": "N-Methylaspartate", "aliases": "Acid N-Methyl-D-aspartic N Methyl D aspartate aspartic Methylaspartate N-Methyl-D-aspartate N-Methylaspartate NMDA", "definition": "An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).\n    ", "id": "MESH:D016202"}
{"mention": "NMDA", "mention_text": "Rg1, as a ginsenoside extracted from Panax ginseng, could ameliorate spatial learning impairment. Previous studies have demonstrated that Rg1 might be a useful agent for the prevention and treatment of the adverse effects of morphine. The aim of this study was to investigate the effect of Rg1 on learning impairment by chronic morphine administration and the mechanism responsible for this effect. Male rats were subcutaneously injected with morphine (10 mg/kg) twice a day at 12 hour intervals for 10 days, and Rg1 (30 mg/kg) was intraperitoneally injected 2 hours after the second injection of morphine once a day for 10 days. Spatial learning capacity was assessed in the Morris water maze. The results showed that rats treated with Morphine/Rg1 decreased escape latency and increased the time spent in platform quadrant and entering frequency. By implantation of electrodes and electrophysiological recording in vivo, the results showed that Rg1 restored the long-term potentiation (LTP) impaired by morphine in both freely moving and anaesthetised rats. The electrophysiological recording in vitro showed that Rg1 restored the LTP in slices from the rats treated with morphine, but not changed LTP in the slices from normal saline- or morphine/Rg1-treated rats; this restoration could be inhibited by N-methyl-D-aspartate (NMDA) receptor antagonist MK801. We conclude that Rg1 may significantly improve the spatial learning capacity impaired by chonic morphine administration and restore the morphine-inhibited LTP. This effect is NMDA receptor dependent.", "entity": "N-Methylaspartate", "aliases": "Acid N-Methyl-D-aspartic N Methyl D aspartate aspartic Methylaspartate N-Methyl-D-aspartate N-Methylaspartate NMDA", "definition": "An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).\n    ", "id": "MESH:D016202"}
{"mention": "MK801", "mention_text": "Rg1, as a ginsenoside extracted from Panax ginseng, could ameliorate spatial learning impairment. Previous studies have demonstrated that Rg1 might be a useful agent for the prevention and treatment of the adverse effects of morphine. The aim of this study was to investigate the effect of Rg1 on learning impairment by chronic morphine administration and the mechanism responsible for this effect. Male rats were subcutaneously injected with morphine (10 mg/kg) twice a day at 12 hour intervals for 10 days, and Rg1 (30 mg/kg) was intraperitoneally injected 2 hours after the second injection of morphine once a day for 10 days. Spatial learning capacity was assessed in the Morris water maze. The results showed that rats treated with Morphine/Rg1 decreased escape latency and increased the time spent in platform quadrant and entering frequency. By implantation of electrodes and electrophysiological recording in vivo, the results showed that Rg1 restored the long-term potentiation (LTP) impaired by morphine in both freely moving and anaesthetised rats. The electrophysiological recording in vitro showed that Rg1 restored the LTP in slices from the rats treated with morphine, but not changed LTP in the slices from normal saline- or morphine/Rg1-treated rats; this restoration could be inhibited by N-methyl-D-aspartate (NMDA) receptor antagonist MK801. We conclude that Rg1 may significantly improve the spatial learning capacity impaired by chonic morphine administration and restore the morphine-inhibited LTP. This effect is NMDA receptor dependent.", "entity": "Dizocilpine Maleate", "aliases": "Dizocilpine Maleate MK 801 MK-801 MK801", "definition": "A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects.\n    ", "id": "MESH:D016291"}
{"mention": "heparin", "mention_text": "A study on the effect of the duration of subcutaneous heparin injection on bruising and pain.", "entity": "Heparin", "aliases": "Heparin Sodium Unfractionated Heparinic Acid Liquaemin alpha alpha-Heparin", "definition": "A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.\n    ", "id": "MESH:D006493"}
{"mention": "bruising", "mention_text": "A study on the effect of the duration of subcutaneous heparin injection on bruising and pain.", "entity": "Contusions", "aliases": "Bruise Bruises Contusion Contusions", "definition": "Injuries resulting in hemorrhage, usually manifested in the skin.\n    ", "id": "MESH:D003288"}
{"mention": "pain", "mention_text": "A study on the effect of the duration of subcutaneous heparin injection on bruising and pain.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "bruising", "mention_text": "AIM: This study was carried out to determine the effect of injection duration on bruising and pain following the administration of the subcutaneous injection of heparin. BACKGROUND: Although different methods to prevent bruising and pain following the subcutaneous injection of heparin have been widely studied and described, the effect of injection duration on the occurrence of bruising and pain is little documented. DESIGN: This study was designed as within-subject, quasi-experimental research. METHOD: The sample for the study consisted of 50 patients to whom subcutaneous heparin was administered. Heparin was injected over 10 seconds on the right abdominal site and 30 seconds on the left abdominal site. Injections areas were assessed for the presence of bruising at 48 and 72 hours after each injection. Dimensions of the bruising on the heparin applied areas were measured using transparent millimetric measuring paper. The visual analog scale (VAS) was used to measure pain intensity and a stop-watch was used to time the pain period. Data were analysed using chi-square test, Mann-Whitney U, Wilcoxon signed ranks tests and correlation. RESULTS: The percentage of bruising occurrence was 64% with the injection of 10 seconds duration and 42% in the 30-second injection. It was determined that the size of the bruising was smaller in the 30-second injection. Pain intensity and pain period were statistically significantly lower for the 30-second injection than for the 10-second injection. CONCLUSIONS: It was determined that injection duration had an effect on bruising and pain following the subcutaneous administration of heparin. This study should be repeated on a larger sample. RELEVANCE TO CLINICAL PRACTICE: When administering subcutaneous heparin injections, it is important to extend the duration of the injection.", "entity": "Contusions", "aliases": "Bruise Bruises Contusion Contusions", "definition": "Injuries resulting in hemorrhage, usually manifested in the skin.\n    ", "id": "MESH:D003288"}
{"mention": "pain", "mention_text": "AIM: This study was carried out to determine the effect of injection duration on bruising and pain following the administration of the subcutaneous injection of heparin. BACKGROUND: Although different methods to prevent bruising and pain following the subcutaneous injection of heparin have been widely studied and described, the effect of injection duration on the occurrence of bruising and pain is little documented. DESIGN: This study was designed as within-subject, quasi-experimental research. METHOD: The sample for the study consisted of 50 patients to whom subcutaneous heparin was administered. Heparin was injected over 10 seconds on the right abdominal site and 30 seconds on the left abdominal site. Injections areas were assessed for the presence of bruising at 48 and 72 hours after each injection. Dimensions of the bruising on the heparin applied areas were measured using transparent millimetric measuring paper. The visual analog scale (VAS) was used to measure pain intensity and a stop-watch was used to time the pain period. Data were analysed using chi-square test, Mann-Whitney U, Wilcoxon signed ranks tests and correlation. RESULTS: The percentage of bruising occurrence was 64% with the injection of 10 seconds duration and 42% in the 30-second injection. It was determined that the size of the bruising was smaller in the 30-second injection. Pain intensity and pain period were statistically significantly lower for the 30-second injection than for the 10-second injection. CONCLUSIONS: It was determined that injection duration had an effect on bruising and pain following the subcutaneous administration of heparin. This study should be repeated on a larger sample. RELEVANCE TO CLINICAL PRACTICE: When administering subcutaneous heparin injections, it is important to extend the duration of the injection.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "heparin", "mention_text": "AIM: This study was carried out to determine the effect of injection duration on bruising and pain following the administration of the subcutaneous injection of heparin. BACKGROUND: Although different methods to prevent bruising and pain following the subcutaneous injection of heparin have been widely studied and described, the effect of injection duration on the occurrence of bruising and pain is little documented. DESIGN: This study was designed as within-subject, quasi-experimental research. METHOD: The sample for the study consisted of 50 patients to whom subcutaneous heparin was administered. Heparin was injected over 10 seconds on the right abdominal site and 30 seconds on the left abdominal site. Injections areas were assessed for the presence of bruising at 48 and 72 hours after each injection. Dimensions of the bruising on the heparin applied areas were measured using transparent millimetric measuring paper. The visual analog scale (VAS) was used to measure pain intensity and a stop-watch was used to time the pain period. Data were analysed using chi-square test, Mann-Whitney U, Wilcoxon signed ranks tests and correlation. RESULTS: The percentage of bruising occurrence was 64% with the injection of 10 seconds duration and 42% in the 30-second injection. It was determined that the size of the bruising was smaller in the 30-second injection. Pain intensity and pain period were statistically significantly lower for the 30-second injection than for the 10-second injection. CONCLUSIONS: It was determined that injection duration had an effect on bruising and pain following the subcutaneous administration of heparin. This study should be repeated on a larger sample. RELEVANCE TO CLINICAL PRACTICE: When administering subcutaneous heparin injections, it is important to extend the duration of the injection.", "entity": "Heparin", "aliases": "Heparin Sodium Unfractionated Heparinic Acid Liquaemin alpha alpha-Heparin", "definition": "A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.\n    ", "id": "MESH:D006493"}
{"mention": "Heparin", "mention_text": "AIM: This study was carried out to determine the effect of injection duration on bruising and pain following the administration of the subcutaneous injection of heparin. BACKGROUND: Although different methods to prevent bruising and pain following the subcutaneous injection of heparin have been widely studied and described, the effect of injection duration on the occurrence of bruising and pain is little documented. DESIGN: This study was designed as within-subject, quasi-experimental research. METHOD: The sample for the study consisted of 50 patients to whom subcutaneous heparin was administered. Heparin was injected over 10 seconds on the right abdominal site and 30 seconds on the left abdominal site. Injections areas were assessed for the presence of bruising at 48 and 72 hours after each injection. Dimensions of the bruising on the heparin applied areas were measured using transparent millimetric measuring paper. The visual analog scale (VAS) was used to measure pain intensity and a stop-watch was used to time the pain period. Data were analysed using chi-square test, Mann-Whitney U, Wilcoxon signed ranks tests and correlation. RESULTS: The percentage of bruising occurrence was 64% with the injection of 10 seconds duration and 42% in the 30-second injection. It was determined that the size of the bruising was smaller in the 30-second injection. Pain intensity and pain period were statistically significantly lower for the 30-second injection than for the 10-second injection. CONCLUSIONS: It was determined that injection duration had an effect on bruising and pain following the subcutaneous administration of heparin. This study should be repeated on a larger sample. RELEVANCE TO CLINICAL PRACTICE: When administering subcutaneous heparin injections, it is important to extend the duration of the injection.", "entity": "Heparin", "aliases": "Heparin Sodium Unfractionated Heparinic Acid Liquaemin alpha alpha-Heparin", "definition": "A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.\n    ", "id": "MESH:D006493"}
{"mention": "Pain", "mention_text": "AIM: This study was carried out to determine the effect of injection duration on bruising and pain following the administration of the subcutaneous injection of heparin. BACKGROUND: Although different methods to prevent bruising and pain following the subcutaneous injection of heparin have been widely studied and described, the effect of injection duration on the occurrence of bruising and pain is little documented. DESIGN: This study was designed as within-subject, quasi-experimental research. METHOD: The sample for the study consisted of 50 patients to whom subcutaneous heparin was administered. Heparin was injected over 10 seconds on the right abdominal site and 30 seconds on the left abdominal site. Injections areas were assessed for the presence of bruising at 48 and 72 hours after each injection. Dimensions of the bruising on the heparin applied areas were measured using transparent millimetric measuring paper. The visual analog scale (VAS) was used to measure pain intensity and a stop-watch was used to time the pain period. Data were analysed using chi-square test, Mann-Whitney U, Wilcoxon signed ranks tests and correlation. RESULTS: The percentage of bruising occurrence was 64% with the injection of 10 seconds duration and 42% in the 30-second injection. It was determined that the size of the bruising was smaller in the 30-second injection. Pain intensity and pain period were statistically significantly lower for the 30-second injection than for the 10-second injection. CONCLUSIONS: It was determined that injection duration had an effect on bruising and pain following the subcutaneous administration of heparin. This study should be repeated on a larger sample. RELEVANCE TO CLINICAL PRACTICE: When administering subcutaneous heparin injections, it is important to extend the duration of the injection.", "entity": "Pain", "aliases": "Ache Aches Burning Pain Pains Crushing Migratory Radiating Splitting Physical Suffering Sufferings", "definition": "An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.\n    ", "id": "MESH:D010146"}
{"mention": "reserpine", "mention_text": "Acute reserpine and subchronic haloperidol treatments change synaptosomal brain glutamate uptake and elicit orofacial dyskinesia in rats.", "entity": "Reserpine", "aliases": "Raunervil Raupasil Rausedil Rausedyl Reserpine Serpasil Serpivite V Serp V-Serp Vangarde Brand of Vitarine", "definition": "An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use.\n    ", "id": "MESH:D012110"}
{"mention": "haloperidol", "mention_text": "Acute reserpine and subchronic haloperidol treatments change synaptosomal brain glutamate uptake and elicit orofacial dyskinesia in rats.", "entity": "Haloperidol", "aliases": "Haldol Haloperidol", "definition": "A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)\n    ", "id": "MESH:D006220"}
{"mention": "glutamate", "mention_text": "Acute reserpine and subchronic haloperidol treatments change synaptosomal brain glutamate uptake and elicit orofacial dyskinesia in rats.", "entity": "Glutamic Acid", "aliases": "Aluminum L Glutamate L-Glutamate D D-Glutamate Potassium Glutamic Acid (D)-Isomer L-Glutamic", "definition": "A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.\n    ", "id": "MESH:D018698"}
{"mention": "orofacial dyskinesia", "mention_text": "Acute reserpine and subchronic haloperidol treatments change synaptosomal brain glutamate uptake and elicit orofacial dyskinesia in rats.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "Reserpine", "mention_text": "Reserpine- and haloperidol-induced orofacial dyskinesia are putative animal models of tardive dyskinesia (TD) whose pathophysiology has been related to free radical generation and oxidative stress. In the present study, the authors induced orofacial dyskinesia by acute reserpine and subchronic haloperidol administration to rats. Reserpine injection (one dose of 1 mg/kg s.c.) every other day for 3 days caused a significant increase in vacuous chewing, tongue protrusion and duration of facial twitching, compared to the control. Haloperidol administration (one dose of 12 mg/kg once a week s.c.) for 4 weeks caused an increase in vacuous chewing, tongue protrusion and duration of facial twitching observed in four weekly evaluations. After the treatments and behavioral observation, glutamate uptake by segments of the brain was analyzed. A decreased glutamate uptake was observed in the subcortical parts of animals treated with reserpine and haloperidol, compared to the control. Importantly, a decrease in glutamate uptake correlates negatively with an increase in the incidence of orofacial diskinesia. These results indicate that early changes in glutamate transport may be related to the development of vacuous chewing movements in rats.", "entity": "Reserpine", "aliases": "Raunervil Raupasil Rausedil Rausedyl Reserpine Serpasil Serpivite V Serp V-Serp Vangarde Brand of Vitarine", "definition": "An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use.\n    ", "id": "MESH:D012110"}
{"mention": "haloperidol", "mention_text": "Reserpine- and haloperidol-induced orofacial dyskinesia are putative animal models of tardive dyskinesia (TD) whose pathophysiology has been related to free radical generation and oxidative stress. In the present study, the authors induced orofacial dyskinesia by acute reserpine and subchronic haloperidol administration to rats. Reserpine injection (one dose of 1 mg/kg s.c.) every other day for 3 days caused a significant increase in vacuous chewing, tongue protrusion and duration of facial twitching, compared to the control. Haloperidol administration (one dose of 12 mg/kg once a week s.c.) for 4 weeks caused an increase in vacuous chewing, tongue protrusion and duration of facial twitching observed in four weekly evaluations. After the treatments and behavioral observation, glutamate uptake by segments of the brain was analyzed. A decreased glutamate uptake was observed in the subcortical parts of animals treated with reserpine and haloperidol, compared to the control. Importantly, a decrease in glutamate uptake correlates negatively with an increase in the incidence of orofacial diskinesia. These results indicate that early changes in glutamate transport may be related to the development of vacuous chewing movements in rats.", "entity": "Haloperidol", "aliases": "Haldol Haloperidol", "definition": "A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)\n    ", "id": "MESH:D006220"}
{"mention": "orofacial dyskinesia", "mention_text": "Reserpine- and haloperidol-induced orofacial dyskinesia are putative animal models of tardive dyskinesia (TD) whose pathophysiology has been related to free radical generation and oxidative stress. In the present study, the authors induced orofacial dyskinesia by acute reserpine and subchronic haloperidol administration to rats. Reserpine injection (one dose of 1 mg/kg s.c.) every other day for 3 days caused a significant increase in vacuous chewing, tongue protrusion and duration of facial twitching, compared to the control. Haloperidol administration (one dose of 12 mg/kg once a week s.c.) for 4 weeks caused an increase in vacuous chewing, tongue protrusion and duration of facial twitching observed in four weekly evaluations. After the treatments and behavioral observation, glutamate uptake by segments of the brain was analyzed. A decreased glutamate uptake was observed in the subcortical parts of animals treated with reserpine and haloperidol, compared to the control. Importantly, a decrease in glutamate uptake correlates negatively with an increase in the incidence of orofacial diskinesia. These results indicate that early changes in glutamate transport may be related to the development of vacuous chewing movements in rats.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "tardive dyskinesia", "mention_text": "Reserpine- and haloperidol-induced orofacial dyskinesia are putative animal models of tardive dyskinesia (TD) whose pathophysiology has been related to free radical generation and oxidative stress. In the present study, the authors induced orofacial dyskinesia by acute reserpine and subchronic haloperidol administration to rats. Reserpine injection (one dose of 1 mg/kg s.c.) every other day for 3 days caused a significant increase in vacuous chewing, tongue protrusion and duration of facial twitching, compared to the control. Haloperidol administration (one dose of 12 mg/kg once a week s.c.) for 4 weeks caused an increase in vacuous chewing, tongue protrusion and duration of facial twitching observed in four weekly evaluations. After the treatments and behavioral observation, glutamate uptake by segments of the brain was analyzed. A decreased glutamate uptake was observed in the subcortical parts of animals treated with reserpine and haloperidol, compared to the control. Importantly, a decrease in glutamate uptake correlates negatively with an increase in the incidence of orofacial diskinesia. These results indicate that early changes in glutamate transport may be related to the development of vacuous chewing movements in rats.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "TD", "mention_text": "Reserpine- and haloperidol-induced orofacial dyskinesia are putative animal models of tardive dyskinesia (TD) whose pathophysiology has been related to free radical generation and oxidative stress. In the present study, the authors induced orofacial dyskinesia by acute reserpine and subchronic haloperidol administration to rats. Reserpine injection (one dose of 1 mg/kg s.c.) every other day for 3 days caused a significant increase in vacuous chewing, tongue protrusion and duration of facial twitching, compared to the control. Haloperidol administration (one dose of 12 mg/kg once a week s.c.) for 4 weeks caused an increase in vacuous chewing, tongue protrusion and duration of facial twitching observed in four weekly evaluations. After the treatments and behavioral observation, glutamate uptake by segments of the brain was analyzed. A decreased glutamate uptake was observed in the subcortical parts of animals treated with reserpine and haloperidol, compared to the control. Importantly, a decrease in glutamate uptake correlates negatively with an increase in the incidence of orofacial diskinesia. These results indicate that early changes in glutamate transport may be related to the development of vacuous chewing movements in rats.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "reserpine", "mention_text": "Reserpine- and haloperidol-induced orofacial dyskinesia are putative animal models of tardive dyskinesia (TD) whose pathophysiology has been related to free radical generation and oxidative stress. In the present study, the authors induced orofacial dyskinesia by acute reserpine and subchronic haloperidol administration to rats. Reserpine injection (one dose of 1 mg/kg s.c.) every other day for 3 days caused a significant increase in vacuous chewing, tongue protrusion and duration of facial twitching, compared to the control. Haloperidol administration (one dose of 12 mg/kg once a week s.c.) for 4 weeks caused an increase in vacuous chewing, tongue protrusion and duration of facial twitching observed in four weekly evaluations. After the treatments and behavioral observation, glutamate uptake by segments of the brain was analyzed. A decreased glutamate uptake was observed in the subcortical parts of animals treated with reserpine and haloperidol, compared to the control. Importantly, a decrease in glutamate uptake correlates negatively with an increase in the incidence of orofacial diskinesia. These results indicate that early changes in glutamate transport may be related to the development of vacuous chewing movements in rats.", "entity": "Reserpine", "aliases": "Raunervil Raupasil Rausedil Rausedyl Reserpine Serpasil Serpivite V Serp V-Serp Vangarde Brand of Vitarine", "definition": "An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use.\n    ", "id": "MESH:D012110"}
{"mention": "Haloperidol", "mention_text": "Reserpine- and haloperidol-induced orofacial dyskinesia are putative animal models of tardive dyskinesia (TD) whose pathophysiology has been related to free radical generation and oxidative stress. In the present study, the authors induced orofacial dyskinesia by acute reserpine and subchronic haloperidol administration to rats. Reserpine injection (one dose of 1 mg/kg s.c.) every other day for 3 days caused a significant increase in vacuous chewing, tongue protrusion and duration of facial twitching, compared to the control. Haloperidol administration (one dose of 12 mg/kg once a week s.c.) for 4 weeks caused an increase in vacuous chewing, tongue protrusion and duration of facial twitching observed in four weekly evaluations. After the treatments and behavioral observation, glutamate uptake by segments of the brain was analyzed. A decreased glutamate uptake was observed in the subcortical parts of animals treated with reserpine and haloperidol, compared to the control. Importantly, a decrease in glutamate uptake correlates negatively with an increase in the incidence of orofacial diskinesia. These results indicate that early changes in glutamate transport may be related to the development of vacuous chewing movements in rats.", "entity": "Haloperidol", "aliases": "Haldol Haloperidol", "definition": "A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)\n    ", "id": "MESH:D006220"}
{"mention": "glutamate", "mention_text": "Reserpine- and haloperidol-induced orofacial dyskinesia are putative animal models of tardive dyskinesia (TD) whose pathophysiology has been related to free radical generation and oxidative stress. In the present study, the authors induced orofacial dyskinesia by acute reserpine and subchronic haloperidol administration to rats. Reserpine injection (one dose of 1 mg/kg s.c.) every other day for 3 days caused a significant increase in vacuous chewing, tongue protrusion and duration of facial twitching, compared to the control. Haloperidol administration (one dose of 12 mg/kg once a week s.c.) for 4 weeks caused an increase in vacuous chewing, tongue protrusion and duration of facial twitching observed in four weekly evaluations. After the treatments and behavioral observation, glutamate uptake by segments of the brain was analyzed. A decreased glutamate uptake was observed in the subcortical parts of animals treated with reserpine and haloperidol, compared to the control. Importantly, a decrease in glutamate uptake correlates negatively with an increase in the incidence of orofacial diskinesia. These results indicate that early changes in glutamate transport may be related to the development of vacuous chewing movements in rats.", "entity": "Glutamic Acid", "aliases": "Aluminum L Glutamate L-Glutamate D D-Glutamate Potassium Glutamic Acid (D)-Isomer L-Glutamic", "definition": "A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.\n    ", "id": "MESH:D018698"}
{"mention": "orofacial diskinesia", "mention_text": "Reserpine- and haloperidol-induced orofacial dyskinesia are putative animal models of tardive dyskinesia (TD) whose pathophysiology has been related to free radical generation and oxidative stress. In the present study, the authors induced orofacial dyskinesia by acute reserpine and subchronic haloperidol administration to rats. Reserpine injection (one dose of 1 mg/kg s.c.) every other day for 3 days caused a significant increase in vacuous chewing, tongue protrusion and duration of facial twitching, compared to the control. Haloperidol administration (one dose of 12 mg/kg once a week s.c.) for 4 weeks caused an increase in vacuous chewing, tongue protrusion and duration of facial twitching observed in four weekly evaluations. After the treatments and behavioral observation, glutamate uptake by segments of the brain was analyzed. A decreased glutamate uptake was observed in the subcortical parts of animals treated with reserpine and haloperidol, compared to the control. Importantly, a decrease in glutamate uptake correlates negatively with an increase in the incidence of orofacial diskinesia. These results indicate that early changes in glutamate transport may be related to the development of vacuous chewing movements in rats.", "entity": "Dyskinesia, Drug-Induced", "aliases": "Drug-Induced Dyskinesia Dyskinesias Drug Induced Medication Medication-Induced", "definition": "Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)\n    ", "id": "MESH:D004409"}
{"mention": "Acute psychosis", "mention_text": "Acute psychosis due to treatment with phenytoin in a nonepileptic patient.", "entity": "Psychoses, Substance-Induced", "aliases": "Drug Psychoses Substance Induced Substance-Induced Toxic", "definition": "Psychotic organic mental disorders resulting from the toxic effect of drugs and chemicals or other harmful substance.\n    ", "id": "MESH:D011605"}
{"mention": "phenytoin", "mention_text": "Acute psychosis due to treatment with phenytoin in a nonepileptic patient.", "entity": "Phenytoin", "aliases": "5,5-Diphenylhydantoin Antisacer Difenin Dihydan Dilantin Diphenylhydantoin Diphenylhydantoinate Sodium Epamin Epanutin Fenitoin Hydantol Park Davis brand of Phenytoin Pfizer Brand Phizer", "definition": "An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs.\n    ", "id": "MESH:D010672"}
{"mention": "psychosis", "mention_text": "The development of psychosis related to antiepileptic drug treatment is usually attributed to the interaction between the epileptic brain substratum and the antiepileptic drugs. The case of a nonepileptic patient who developed psychosis following phenytoin treatment for trigeminal neuralgia is described. This case suggests that the psychotic symptoms that occur following phenytoin treatment in some epileptic patients may be the direct result of medication, unrelated to seizures.", "entity": "Psychoses, Substance-Induced", "aliases": "Drug Psychoses Substance Induced Substance-Induced Toxic", "definition": "Psychotic organic mental disorders resulting from the toxic effect of drugs and chemicals or other harmful substance.\n    ", "id": "MESH:D011605"}
{"mention": "epileptic", "mention_text": "The development of psychosis related to antiepileptic drug treatment is usually attributed to the interaction between the epileptic brain substratum and the antiepileptic drugs. The case of a nonepileptic patient who developed psychosis following phenytoin treatment for trigeminal neuralgia is described. This case suggests that the psychotic symptoms that occur following phenytoin treatment in some epileptic patients may be the direct result of medication, unrelated to seizures.", "entity": "Epilepsy", "aliases": "Aura Auras Awakening Epilepsy Cryptogenic Epilepsies Epileptic Seizure Seizures Disorder Disorders Single", "definition": "A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313)\n    ", "id": "MESH:D004827"}
{"mention": "phenytoin", "mention_text": "The development of psychosis related to antiepileptic drug treatment is usually attributed to the interaction between the epileptic brain substratum and the antiepileptic drugs. The case of a nonepileptic patient who developed psychosis following phenytoin treatment for trigeminal neuralgia is described. This case suggests that the psychotic symptoms that occur following phenytoin treatment in some epileptic patients may be the direct result of medication, unrelated to seizures.", "entity": "Phenytoin", "aliases": "5,5-Diphenylhydantoin Antisacer Difenin Dihydan Dilantin Diphenylhydantoin Diphenylhydantoinate Sodium Epamin Epanutin Fenitoin Hydantol Park Davis brand of Phenytoin Pfizer Brand Phizer", "definition": "An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs.\n    ", "id": "MESH:D010672"}
{"mention": "trigeminal neuralgia", "mention_text": "The development of psychosis related to antiepileptic drug treatment is usually attributed to the interaction between the epileptic brain substratum and the antiepileptic drugs. The case of a nonepileptic patient who developed psychosis following phenytoin treatment for trigeminal neuralgia is described. This case suggests that the psychotic symptoms that occur following phenytoin treatment in some epileptic patients may be the direct result of medication, unrelated to seizures.", "entity": "Trigeminal Neuralgia", "aliases": "Disease Fothergill Epileptiform Neuralgia Neuralgias Idiopathic Trigeminal Secondary Trifacial Tic Douloureux", "definition": "A syndrome characterized by recurrent episodes of excruciating pain lasting several seconds or longer in the sensory distribution of the TRIGEMINAL NERVE. Pain may be initiated by stimulation of trigger points on the face, lips, or gums or by movement of facial muscles or chewing. Associated conditions include MULTIPLE SCLEROSIS, vascular anomalies, ANEURYSMS, and neoplasms. (Adams et al., Principles of Neurology, 6th ed, p187)\n    ", "id": "MESH:D014277"}
{"mention": "psychotic symptoms", "mention_text": "The development of psychosis related to antiepileptic drug treatment is usually attributed to the interaction between the epileptic brain substratum and the antiepileptic drugs. The case of a nonepileptic patient who developed psychosis following phenytoin treatment for trigeminal neuralgia is described. This case suggests that the psychotic symptoms that occur following phenytoin treatment in some epileptic patients may be the direct result of medication, unrelated to seizures.", "entity": "Psychoses, Substance-Induced", "aliases": "Drug Psychoses Substance Induced Substance-Induced Toxic", "definition": "Psychotic organic mental disorders resulting from the toxic effect of drugs and chemicals or other harmful substance.\n    ", "id": "MESH:D011605"}
{"mention": "seizures", "mention_text": "The development of psychosis related to antiepileptic drug treatment is usually attributed to the interaction between the epileptic brain substratum and the antiepileptic drugs. The case of a nonepileptic patient who developed psychosis following phenytoin treatment for trigeminal neuralgia is described. This case suggests that the psychotic symptoms that occur following phenytoin treatment in some epileptic patients may be the direct result of medication, unrelated to seizures.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "gum Arabic", "mention_text": "The effect of treatment with gum Arabic on gentamicin nephrotoxicity in rats: a preliminary study.", "entity": "Gum Arabic", "aliases": "Acacia Gum Arabic", "definition": "Powdered exudate from various Acacia species, especially A. senegal (Leguminosae). It forms mucilage or syrup in water. Gum arabic is used as a suspending agent, excipient, and emulsifier in foods and pharmaceuticals.\n    ", "id": "MESH:D006170"}
{"mention": "gentamicin", "mention_text": "The effect of treatment with gum Arabic on gentamicin nephrotoxicity in rats: a preliminary study.", "entity": "Gentamicins", "aliases": "G Myticin G-Myticin GMyticin Garamycin Gentacycol Gentamicin Sulfate (USP) Gentamicins Gentamycin Gentamycins Gentavet Genticin", "definition": "A complex of closely related aminoglycosides obtained from MICROMONOSPORA purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit PROTEIN BIOSYNTHESIS.\n    ", "id": "MESH:D005839"}
{"mention": "nephrotoxicity", "mention_text": "The effect of treatment with gum Arabic on gentamicin nephrotoxicity in rats: a preliminary study.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "gum Arabic", "mention_text": "In the present work we assessed the effect of treatment of rats with gum Arabic on acute renal failure induced by gentamicin (GM) nephrotoxicity. Rats were treated with the vehicle (2 mL/kg of distilled water and 5% w/v cellulose, 10 days), gum Arabic (2 mL/kg of a 10% w/v aqueous suspension of gum Arabic powder, orally for 10 days), or gum Arabic concomitantly with GM (80mg/kg/day intramuscularly, during the last six days of the treatment period). Nephrotoxicity was assessed by measuring the concentrations of creatinine and urea in the plasma and reduced glutathione (GSH) in the kidney cortex, and by light microscopic examination of kidney sections. The results indicated that concomitant treatment with gum Arabic and GM significantly increased creatinine and urea by about 183 and 239%, respectively (compared to 432 and 346%, respectively, in rats treated with cellulose and GM), and decreased that of cortical GSH by 21% (compared to 27% in the cellulose plus GM group) The GM-induced proximal tubular necrosis appeared to be slightly less severe in rats given GM together with gum Arabic than in those given GM and cellulose. It could be inferred that gum Arabic treatment has induced a modest amelioration of some of the histological and biochemical indices of GM nephrotoxicity. Further work is warranted on the effect of the treatments on renal functional aspects in models of chronic renal failure, and on the mechanism(s) involved.", "entity": "Gum Arabic", "aliases": "Acacia Gum Arabic", "definition": "Powdered exudate from various Acacia species, especially A. senegal (Leguminosae). It forms mucilage or syrup in water. Gum arabic is used as a suspending agent, excipient, and emulsifier in foods and pharmaceuticals.\n    ", "id": "MESH:D006170"}
{"mention": "acute renal failure", "mention_text": "In the present work we assessed the effect of treatment of rats with gum Arabic on acute renal failure induced by gentamicin (GM) nephrotoxicity. Rats were treated with the vehicle (2 mL/kg of distilled water and 5% w/v cellulose, 10 days), gum Arabic (2 mL/kg of a 10% w/v aqueous suspension of gum Arabic powder, orally for 10 days), or gum Arabic concomitantly with GM (80mg/kg/day intramuscularly, during the last six days of the treatment period). Nephrotoxicity was assessed by measuring the concentrations of creatinine and urea in the plasma and reduced glutathione (GSH) in the kidney cortex, and by light microscopic examination of kidney sections. The results indicated that concomitant treatment with gum Arabic and GM significantly increased creatinine and urea by about 183 and 239%, respectively (compared to 432 and 346%, respectively, in rats treated with cellulose and GM), and decreased that of cortical GSH by 21% (compared to 27% in the cellulose plus GM group) The GM-induced proximal tubular necrosis appeared to be slightly less severe in rats given GM together with gum Arabic than in those given GM and cellulose. It could be inferred that gum Arabic treatment has induced a modest amelioration of some of the histological and biochemical indices of GM nephrotoxicity. Further work is warranted on the effect of the treatments on renal functional aspects in models of chronic renal failure, and on the mechanism(s) involved.", "entity": "Acute Kidney Injury", "aliases": "Acute Kidney Failure Failures Injuries Injury Insufficiencies Insufficiency Renal", "definition": "Abrupt reduction in kidney function. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions.\n    ", "id": "MESH:D058186"}
{"mention": "gentamicin", "mention_text": "In the present work we assessed the effect of treatment of rats with gum Arabic on acute renal failure induced by gentamicin (GM) nephrotoxicity. Rats were treated with the vehicle (2 mL/kg of distilled water and 5% w/v cellulose, 10 days), gum Arabic (2 mL/kg of a 10% w/v aqueous suspension of gum Arabic powder, orally for 10 days), or gum Arabic concomitantly with GM (80mg/kg/day intramuscularly, during the last six days of the treatment period). Nephrotoxicity was assessed by measuring the concentrations of creatinine and urea in the plasma and reduced glutathione (GSH) in the kidney cortex, and by light microscopic examination of kidney sections. The results indicated that concomitant treatment with gum Arabic and GM significantly increased creatinine and urea by about 183 and 239%, respectively (compared to 432 and 346%, respectively, in rats treated with cellulose and GM), and decreased that of cortical GSH by 21% (compared to 27% in the cellulose plus GM group) The GM-induced proximal tubular necrosis appeared to be slightly less severe in rats given GM together with gum Arabic than in those given GM and cellulose. It could be inferred that gum Arabic treatment has induced a modest amelioration of some of the histological and biochemical indices of GM nephrotoxicity. Further work is warranted on the effect of the treatments on renal functional aspects in models of chronic renal failure, and on the mechanism(s) involved.", "entity": "Gentamicins", "aliases": "G Myticin G-Myticin GMyticin Garamycin Gentacycol Gentamicin Sulfate (USP) Gentamicins Gentamycin Gentamycins Gentavet Genticin", "definition": "A complex of closely related aminoglycosides obtained from MICROMONOSPORA purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit PROTEIN BIOSYNTHESIS.\n    ", "id": "MESH:D005839"}
{"mention": "GM", "mention_text": "In the present work we assessed the effect of treatment of rats with gum Arabic on acute renal failure induced by gentamicin (GM) nephrotoxicity. Rats were treated with the vehicle (2 mL/kg of distilled water and 5% w/v cellulose, 10 days), gum Arabic (2 mL/kg of a 10% w/v aqueous suspension of gum Arabic powder, orally for 10 days), or gum Arabic concomitantly with GM (80mg/kg/day intramuscularly, during the last six days of the treatment period). Nephrotoxicity was assessed by measuring the concentrations of creatinine and urea in the plasma and reduced glutathione (GSH) in the kidney cortex, and by light microscopic examination of kidney sections. The results indicated that concomitant treatment with gum Arabic and GM significantly increased creatinine and urea by about 183 and 239%, respectively (compared to 432 and 346%, respectively, in rats treated with cellulose and GM), and decreased that of cortical GSH by 21% (compared to 27% in the cellulose plus GM group) The GM-induced proximal tubular necrosis appeared to be slightly less severe in rats given GM together with gum Arabic than in those given GM and cellulose. It could be inferred that gum Arabic treatment has induced a modest amelioration of some of the histological and biochemical indices of GM nephrotoxicity. Further work is warranted on the effect of the treatments on renal functional aspects in models of chronic renal failure, and on the mechanism(s) involved.", "entity": "Gentamicins", "aliases": "G Myticin G-Myticin GMyticin Garamycin Gentacycol Gentamicin Sulfate (USP) Gentamicins Gentamycin Gentamycins Gentavet Genticin", "definition": "A complex of closely related aminoglycosides obtained from MICROMONOSPORA purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit PROTEIN BIOSYNTHESIS.\n    ", "id": "MESH:D005839"}
{"mention": "nephrotoxicity", "mention_text": "In the present work we assessed the effect of treatment of rats with gum Arabic on acute renal failure induced by gentamicin (GM) nephrotoxicity. Rats were treated with the vehicle (2 mL/kg of distilled water and 5% w/v cellulose, 10 days), gum Arabic (2 mL/kg of a 10% w/v aqueous suspension of gum Arabic powder, orally for 10 days), or gum Arabic concomitantly with GM (80mg/kg/day intramuscularly, during the last six days of the treatment period). Nephrotoxicity was assessed by measuring the concentrations of creatinine and urea in the plasma and reduced glutathione (GSH) in the kidney cortex, and by light microscopic examination of kidney sections. The results indicated that concomitant treatment with gum Arabic and GM significantly increased creatinine and urea by about 183 and 239%, respectively (compared to 432 and 346%, respectively, in rats treated with cellulose and GM), and decreased that of cortical GSH by 21% (compared to 27% in the cellulose plus GM group) The GM-induced proximal tubular necrosis appeared to be slightly less severe in rats given GM together with gum Arabic than in those given GM and cellulose. It could be inferred that gum Arabic treatment has induced a modest amelioration of some of the histological and biochemical indices of GM nephrotoxicity. Further work is warranted on the effect of the treatments on renal functional aspects in models of chronic renal failure, and on the mechanism(s) involved.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "Nephrotoxicity", "mention_text": "In the present work we assessed the effect of treatment of rats with gum Arabic on acute renal failure induced by gentamicin (GM) nephrotoxicity. Rats were treated with the vehicle (2 mL/kg of distilled water and 5% w/v cellulose, 10 days), gum Arabic (2 mL/kg of a 10% w/v aqueous suspension of gum Arabic powder, orally for 10 days), or gum Arabic concomitantly with GM (80mg/kg/day intramuscularly, during the last six days of the treatment period). Nephrotoxicity was assessed by measuring the concentrations of creatinine and urea in the plasma and reduced glutathione (GSH) in the kidney cortex, and by light microscopic examination of kidney sections. The results indicated that concomitant treatment with gum Arabic and GM significantly increased creatinine and urea by about 183 and 239%, respectively (compared to 432 and 346%, respectively, in rats treated with cellulose and GM), and decreased that of cortical GSH by 21% (compared to 27% in the cellulose plus GM group) The GM-induced proximal tubular necrosis appeared to be slightly less severe in rats given GM together with gum Arabic than in those given GM and cellulose. It could be inferred that gum Arabic treatment has induced a modest amelioration of some of the histological and biochemical indices of GM nephrotoxicity. Further work is warranted on the effect of the treatments on renal functional aspects in models of chronic renal failure, and on the mechanism(s) involved.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "creatinine", "mention_text": "In the present work we assessed the effect of treatment of rats with gum Arabic on acute renal failure induced by gentamicin (GM) nephrotoxicity. Rats were treated with the vehicle (2 mL/kg of distilled water and 5% w/v cellulose, 10 days), gum Arabic (2 mL/kg of a 10% w/v aqueous suspension of gum Arabic powder, orally for 10 days), or gum Arabic concomitantly with GM (80mg/kg/day intramuscularly, during the last six days of the treatment period). Nephrotoxicity was assessed by measuring the concentrations of creatinine and urea in the plasma and reduced glutathione (GSH) in the kidney cortex, and by light microscopic examination of kidney sections. The results indicated that concomitant treatment with gum Arabic and GM significantly increased creatinine and urea by about 183 and 239%, respectively (compared to 432 and 346%, respectively, in rats treated with cellulose and GM), and decreased that of cortical GSH by 21% (compared to 27% in the cellulose plus GM group) The GM-induced proximal tubular necrosis appeared to be slightly less severe in rats given GM together with gum Arabic than in those given GM and cellulose. It could be inferred that gum Arabic treatment has induced a modest amelioration of some of the histological and biochemical indices of GM nephrotoxicity. Further work is warranted on the effect of the treatments on renal functional aspects in models of chronic renal failure, and on the mechanism(s) involved.", "entity": "Creatinine", "aliases": "Creatinine Sulfate Salt Krebiozen", "definition": "", "id": "MESH:D003404"}
{"mention": "urea", "mention_text": "In the present work we assessed the effect of treatment of rats with gum Arabic on acute renal failure induced by gentamicin (GM) nephrotoxicity. Rats were treated with the vehicle (2 mL/kg of distilled water and 5% w/v cellulose, 10 days), gum Arabic (2 mL/kg of a 10% w/v aqueous suspension of gum Arabic powder, orally for 10 days), or gum Arabic concomitantly with GM (80mg/kg/day intramuscularly, during the last six days of the treatment period). Nephrotoxicity was assessed by measuring the concentrations of creatinine and urea in the plasma and reduced glutathione (GSH) in the kidney cortex, and by light microscopic examination of kidney sections. The results indicated that concomitant treatment with gum Arabic and GM significantly increased creatinine and urea by about 183 and 239%, respectively (compared to 432 and 346%, respectively, in rats treated with cellulose and GM), and decreased that of cortical GSH by 21% (compared to 27% in the cellulose plus GM group) The GM-induced proximal tubular necrosis appeared to be slightly less severe in rats given GM together with gum Arabic than in those given GM and cellulose. It could be inferred that gum Arabic treatment has induced a modest amelioration of some of the histological and biochemical indices of GM nephrotoxicity. Further work is warranted on the effect of the treatments on renal functional aspects in models of chronic renal failure, and on the mechanism(s) involved.", "entity": "Urea", "aliases": "Basodexan Carbamide Carmol Urea", "definition": "A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids.\n    ", "id": "MESH:D014508"}
{"mention": "glutathione", "mention_text": "In the present work we assessed the effect of treatment of rats with gum Arabic on acute renal failure induced by gentamicin (GM) nephrotoxicity. Rats were treated with the vehicle (2 mL/kg of distilled water and 5% w/v cellulose, 10 days), gum Arabic (2 mL/kg of a 10% w/v aqueous suspension of gum Arabic powder, orally for 10 days), or gum Arabic concomitantly with GM (80mg/kg/day intramuscularly, during the last six days of the treatment period). Nephrotoxicity was assessed by measuring the concentrations of creatinine and urea in the plasma and reduced glutathione (GSH) in the kidney cortex, and by light microscopic examination of kidney sections. The results indicated that concomitant treatment with gum Arabic and GM significantly increased creatinine and urea by about 183 and 239%, respectively (compared to 432 and 346%, respectively, in rats treated with cellulose and GM), and decreased that of cortical GSH by 21% (compared to 27% in the cellulose plus GM group) The GM-induced proximal tubular necrosis appeared to be slightly less severe in rats given GM together with gum Arabic than in those given GM and cellulose. It could be inferred that gum Arabic treatment has induced a modest amelioration of some of the histological and biochemical indices of GM nephrotoxicity. Further work is warranted on the effect of the treatments on renal functional aspects in models of chronic renal failure, and on the mechanism(s) involved.", "entity": "Glutathione", "aliases": "Glutathione Reduced gamma L Glu L Cys Gly Glutamyl Cysteinylglycine gamma-L-Glu-L-Cys-Gly gamma-L-Glutamyl-L-Cysteinylglycine", "definition": "A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.\n    ", "id": "MESH:D005978"}
{"mention": "GSH", "mention_text": "In the present work we assessed the effect of treatment of rats with gum Arabic on acute renal failure induced by gentamicin (GM) nephrotoxicity. Rats were treated with the vehicle (2 mL/kg of distilled water and 5% w/v cellulose, 10 days), gum Arabic (2 mL/kg of a 10% w/v aqueous suspension of gum Arabic powder, orally for 10 days), or gum Arabic concomitantly with GM (80mg/kg/day intramuscularly, during the last six days of the treatment period). Nephrotoxicity was assessed by measuring the concentrations of creatinine and urea in the plasma and reduced glutathione (GSH) in the kidney cortex, and by light microscopic examination of kidney sections. The results indicated that concomitant treatment with gum Arabic and GM significantly increased creatinine and urea by about 183 and 239%, respectively (compared to 432 and 346%, respectively, in rats treated with cellulose and GM), and decreased that of cortical GSH by 21% (compared to 27% in the cellulose plus GM group) The GM-induced proximal tubular necrosis appeared to be slightly less severe in rats given GM together with gum Arabic than in those given GM and cellulose. It could be inferred that gum Arabic treatment has induced a modest amelioration of some of the histological and biochemical indices of GM nephrotoxicity. Further work is warranted on the effect of the treatments on renal functional aspects in models of chronic renal failure, and on the mechanism(s) involved.", "entity": "Glutathione", "aliases": "Glutathione Reduced gamma L Glu L Cys Gly Glutamyl Cysteinylglycine gamma-L-Glu-L-Cys-Gly gamma-L-Glutamyl-L-Cysteinylglycine", "definition": "A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.\n    ", "id": "MESH:D005978"}
{"mention": "tubular necrosis", "mention_text": "In the present work we assessed the effect of treatment of rats with gum Arabic on acute renal failure induced by gentamicin (GM) nephrotoxicity. Rats were treated with the vehicle (2 mL/kg of distilled water and 5% w/v cellulose, 10 days), gum Arabic (2 mL/kg of a 10% w/v aqueous suspension of gum Arabic powder, orally for 10 days), or gum Arabic concomitantly with GM (80mg/kg/day intramuscularly, during the last six days of the treatment period). Nephrotoxicity was assessed by measuring the concentrations of creatinine and urea in the plasma and reduced glutathione (GSH) in the kidney cortex, and by light microscopic examination of kidney sections. The results indicated that concomitant treatment with gum Arabic and GM significantly increased creatinine and urea by about 183 and 239%, respectively (compared to 432 and 346%, respectively, in rats treated with cellulose and GM), and decreased that of cortical GSH by 21% (compared to 27% in the cellulose plus GM group) The GM-induced proximal tubular necrosis appeared to be slightly less severe in rats given GM together with gum Arabic than in those given GM and cellulose. It could be inferred that gum Arabic treatment has induced a modest amelioration of some of the histological and biochemical indices of GM nephrotoxicity. Further work is warranted on the effect of the treatments on renal functional aspects in models of chronic renal failure, and on the mechanism(s) involved.", "entity": "Kidney Tubular Necrosis, Acute", "aliases": "Acute Kidney Tubular Necrosis Lower Nephron Nephroses Nephrosis", "definition": "Acute kidney failure resulting from destruction of EPITHELIAL CELLS of the KIDNEY TUBULES. It is commonly attributed to exposure to toxic agents or renal ISCHEMIA following severe TRAUMA.\n    ", "id": "MESH:D007683"}
{"mention": "chronic renal failure", "mention_text": "In the present work we assessed the effect of treatment of rats with gum Arabic on acute renal failure induced by gentamicin (GM) nephrotoxicity. Rats were treated with the vehicle (2 mL/kg of distilled water and 5% w/v cellulose, 10 days), gum Arabic (2 mL/kg of a 10% w/v aqueous suspension of gum Arabic powder, orally for 10 days), or gum Arabic concomitantly with GM (80mg/kg/day intramuscularly, during the last six days of the treatment period). Nephrotoxicity was assessed by measuring the concentrations of creatinine and urea in the plasma and reduced glutathione (GSH) in the kidney cortex, and by light microscopic examination of kidney sections. The results indicated that concomitant treatment with gum Arabic and GM significantly increased creatinine and urea by about 183 and 239%, respectively (compared to 432 and 346%, respectively, in rats treated with cellulose and GM), and decreased that of cortical GSH by 21% (compared to 27% in the cellulose plus GM group) The GM-induced proximal tubular necrosis appeared to be slightly less severe in rats given GM together with gum Arabic than in those given GM and cellulose. It could be inferred that gum Arabic treatment has induced a modest amelioration of some of the histological and biochemical indices of GM nephrotoxicity. Further work is warranted on the effect of the treatments on renal functional aspects in models of chronic renal failure, and on the mechanism(s) involved.", "entity": "Kidney Failure, Chronic", "aliases": "Chronic Kidney Failure Renal Disease End-Stage ESRD End Stage", "definition": "The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.\n    ", "id": "MESH:D007676"}
{"mention": "Visual hallucinations", "mention_text": "Visual hallucinations associated with zonisamide.", "entity": "Hallucinations", "aliases": "Auditory Hallucination Verbal Hallucinations Body Sensation Dissociative Elementary Gustatory of Hypnagogic Hypnapompic Kinesthetic Mood Congruent Incongruent Olfactory Organic Reflex Sensory Somatic Tactile Visual Formed People Internal Unformed", "definition": "Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with MENTAL DISORDERS.\n    ", "id": "MESH:D006212"}
{"mention": "zonisamide", "mention_text": "Visual hallucinations associated with zonisamide.", "entity": "zonisamide", "aliases": "1,2-benzisoxazole-3-methanesulfonamide 3-sulfamoylmethyl-1,2-benzisoxazole AD 810 AD-810 CI 912 CI-912 Elan brand of zonisamide Zonegran monosodium", "definition": "", "id": "MESH:C022189"}
{"mention": "Zonisamide", "mention_text": "Zonisamide is a broad-spectrum antiepileptic drug used to treat various types of seizures. Although visual hallucinations have not been reported as an adverse effect of this agent, we describe three patients who experienced complex visual hallucinations and altered mental status after zonisamide treatment was begun or its dosage increased. All three had been diagnosed earlier with epilepsy, and their electroencephalogram (EEG) findings were abnormal. During monitoring, visual hallucinations did not correlate with EEG readings, nor did video recording capture any of the described events. None of the patients had experienced visual hallucinations before this event. The only recent change in their treatment was the introduction or increased dosage of zonisamide. With either discontinuation or decreased dosage of the drug the symptoms disappeared and did not recur. Further observations and reports will help clarify this adverse effect. Until then, clinicians need to be aware of this possible complication associated with zonisamide.", "entity": "zonisamide", "aliases": "1,2-benzisoxazole-3-methanesulfonamide 3-sulfamoylmethyl-1,2-benzisoxazole AD 810 AD-810 CI 912 CI-912 Elan brand of zonisamide Zonegran monosodium", "definition": "", "id": "MESH:C022189"}
{"mention": "seizures", "mention_text": "Zonisamide is a broad-spectrum antiepileptic drug used to treat various types of seizures. Although visual hallucinations have not been reported as an adverse effect of this agent, we describe three patients who experienced complex visual hallucinations and altered mental status after zonisamide treatment was begun or its dosage increased. All three had been diagnosed earlier with epilepsy, and their electroencephalogram (EEG) findings were abnormal. During monitoring, visual hallucinations did not correlate with EEG readings, nor did video recording capture any of the described events. None of the patients had experienced visual hallucinations before this event. The only recent change in their treatment was the introduction or increased dosage of zonisamide. With either discontinuation or decreased dosage of the drug the symptoms disappeared and did not recur. Further observations and reports will help clarify this adverse effect. Until then, clinicians need to be aware of this possible complication associated with zonisamide.", "entity": "Seizures", "aliases": "Auditory Seizure Seizures Clonic Convulsion Non Epileptic Non-Epileptic Convulsions Convulsive Focal Generalized Gustatory Jacksonian Motor Olfactory Sensory Somatosensory Tonic Tonic-Clonic Vertiginous Vestibular Visual", "definition": "Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\"\n    ", "id": "MESH:D012640"}
{"mention": "visual hallucinations", "mention_text": "Zonisamide is a broad-spectrum antiepileptic drug used to treat various types of seizures. Although visual hallucinations have not been reported as an adverse effect of this agent, we describe three patients who experienced complex visual hallucinations and altered mental status after zonisamide treatment was begun or its dosage increased. All three had been diagnosed earlier with epilepsy, and their electroencephalogram (EEG) findings were abnormal. During monitoring, visual hallucinations did not correlate with EEG readings, nor did video recording capture any of the described events. None of the patients had experienced visual hallucinations before this event. The only recent change in their treatment was the introduction or increased dosage of zonisamide. With either discontinuation or decreased dosage of the drug the symptoms disappeared and did not recur. Further observations and reports will help clarify this adverse effect. Until then, clinicians need to be aware of this possible complication associated with zonisamide.", "entity": "Hallucinations", "aliases": "Auditory Hallucination Verbal Hallucinations Body Sensation Dissociative Elementary Gustatory of Hypnagogic Hypnapompic Kinesthetic Mood Congruent Incongruent Olfactory Organic Reflex Sensory Somatic Tactile Visual Formed People Internal Unformed", "definition": "Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with MENTAL DISORDERS.\n    ", "id": "MESH:D006212"}
{"mention": "zonisamide", "mention_text": "Zonisamide is a broad-spectrum antiepileptic drug used to treat various types of seizures. Although visual hallucinations have not been reported as an adverse effect of this agent, we describe three patients who experienced complex visual hallucinations and altered mental status after zonisamide treatment was begun or its dosage increased. All three had been diagnosed earlier with epilepsy, and their electroencephalogram (EEG) findings were abnormal. During monitoring, visual hallucinations did not correlate with EEG readings, nor did video recording capture any of the described events. None of the patients had experienced visual hallucinations before this event. The only recent change in their treatment was the introduction or increased dosage of zonisamide. With either discontinuation or decreased dosage of the drug the symptoms disappeared and did not recur. Further observations and reports will help clarify this adverse effect. Until then, clinicians need to be aware of this possible complication associated with zonisamide.", "entity": "zonisamide", "aliases": "1,2-benzisoxazole-3-methanesulfonamide 3-sulfamoylmethyl-1,2-benzisoxazole AD 810 AD-810 CI 912 CI-912 Elan brand of zonisamide Zonegran monosodium", "definition": "", "id": "MESH:C022189"}
{"mention": "epilepsy", "mention_text": "Zonisamide is a broad-spectrum antiepileptic drug used to treat various types of seizures. Although visual hallucinations have not been reported as an adverse effect of this agent, we describe three patients who experienced complex visual hallucinations and altered mental status after zonisamide treatment was begun or its dosage increased. All three had been diagnosed earlier with epilepsy, and their electroencephalogram (EEG) findings were abnormal. During monitoring, visual hallucinations did not correlate with EEG readings, nor did video recording capture any of the described events. None of the patients had experienced visual hallucinations before this event. The only recent change in their treatment was the introduction or increased dosage of zonisamide. With either discontinuation or decreased dosage of the drug the symptoms disappeared and did not recur. Further observations and reports will help clarify this adverse effect. Until then, clinicians need to be aware of this possible complication associated with zonisamide.", "entity": "Epilepsy", "aliases": "Aura Auras Awakening Epilepsy Cryptogenic Epilepsies Epileptic Seizure Seizures Disorder Disorders Single", "definition": "A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313)\n    ", "id": "MESH:D004827"}
{"mention": "tyrosine", "mention_text": "GLEPP1 receptor tyrosine phosphatase (Ptpro) in rat PAN nephrosis. A marker of acute podocyte injury.", "entity": "Tyrosine", "aliases": "L Tyrosine L-Tyrosine isomer L-isomer para para-Tyrosine", "definition": "A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.\n    ", "id": "MESH:D014443"}
{"mention": "PAN", "mention_text": "GLEPP1 receptor tyrosine phosphatase (Ptpro) in rat PAN nephrosis. A marker of acute podocyte injury.", "entity": "Puromycin Aminonucleoside", "aliases": "3' Amino 3' deoxy N,N dimethyladenosine 3'-Amino-3'-deoxy-N,N-dimethyladenosine Aminonucleoside Puromycin", "definition": "PUROMYCIN derivative that lacks the methoxyphenylalanyl group on the amine of the sugar ring. It is an antibiotic with antineoplastic properties and can cause nephrosis.\n    ", "id": "MESH:D011692"}
{"mention": "nephrosis", "mention_text": "GLEPP1 receptor tyrosine phosphatase (Ptpro) in rat PAN nephrosis. A marker of acute podocyte injury.", "entity": "Nephrosis", "aliases": "Nephroses Nephrosis", "definition": "Pathological processes of the KIDNEY without inflammatory or neoplastic components. Nephrosis may be a primary disorder or secondary complication of other diseases. It is characterized by the NEPHROTIC SYNDROME indicating the presence of PROTEINURIA and HYPOALBUMINEMIA with accompanying EDEMA.\n    ", "id": "MESH:D009401"}
{"mention": "tyrosine", "mention_text": "Glomerular epithelial protein 1 (GLEPP1) is a podocyte receptor membrane protein tyrosine phosphatase located on the apical cell membrane of visceral glomerular epithelial cell and foot processes. This receptor plays a role in regulating the structure and function of podocyte foot process. To better understand the utility of GLEPP1 as a marker of glomerular injury, the amount and distribution of GLEPP1 protein and mRNA were examined by immunohistochemistry, Western blot and RNase protection assay in a model of podocyte injury in the rat. Puromycin aminonucleoside nephrosis was induced by single intraperitoneal injection of puromycin aminonucleoside (PAN, 20 mg/100g BW). Tissues were analyzed at 0, 5, 7, 11, 21, 45, 80 and 126 days after PAN injection so as to include both the acute phase of proteinuria associated with foot process effacement (days 5-11) and the chronic phase of proteinuria associated with glomerulosclerosis (days 45-126). At day 5, GLEPP1 protein and mRNA were reduced from the normal range (265.2 +/- 79.6 x 10(6) moles/glomerulus and 100%) to 15% of normal (41.8 +/- 4.8 x 10(6) moles/glomerulus, p < 0.005). This occurred in association with an increase in urinary protein content from 1.8 +/- 1 to 99.0 +/- 61 mg/day (p < 0.001). In contrast, podocalyxin did not change significantly at this time. By day 11, GLEPP1 protein and mRNA had begun to return towards baseline. By day 45-126, at a time when glomerular scarring was present, GLEPP1 was absent from glomerulosclerotic areas although the total glomerular content of GLEPP1 was not different from normal. We conclude that GLEPP1 expression, unlike podocalyxin, reflects podocyte injury induced by PAN. GLEPP1 expression may be a useful marker of podocyte injury.", "entity": "Tyrosine", "aliases": "L Tyrosine L-Tyrosine isomer L-isomer para para-Tyrosine", "definition": "A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.\n    ", "id": "MESH:D014443"}
{"mention": "glomerular injury", "mention_text": "Glomerular epithelial protein 1 (GLEPP1) is a podocyte receptor membrane protein tyrosine phosphatase located on the apical cell membrane of visceral glomerular epithelial cell and foot processes. This receptor plays a role in regulating the structure and function of podocyte foot process. To better understand the utility of GLEPP1 as a marker of glomerular injury, the amount and distribution of GLEPP1 protein and mRNA were examined by immunohistochemistry, Western blot and RNase protection assay in a model of podocyte injury in the rat. Puromycin aminonucleoside nephrosis was induced by single intraperitoneal injection of puromycin aminonucleoside (PAN, 20 mg/100g BW). Tissues were analyzed at 0, 5, 7, 11, 21, 45, 80 and 126 days after PAN injection so as to include both the acute phase of proteinuria associated with foot process effacement (days 5-11) and the chronic phase of proteinuria associated with glomerulosclerosis (days 45-126). At day 5, GLEPP1 protein and mRNA were reduced from the normal range (265.2 +/- 79.6 x 10(6) moles/glomerulus and 100%) to 15% of normal (41.8 +/- 4.8 x 10(6) moles/glomerulus, p < 0.005). This occurred in association with an increase in urinary protein content from 1.8 +/- 1 to 99.0 +/- 61 mg/day (p < 0.001). In contrast, podocalyxin did not change significantly at this time. By day 11, GLEPP1 protein and mRNA had begun to return towards baseline. By day 45-126, at a time when glomerular scarring was present, GLEPP1 was absent from glomerulosclerotic areas although the total glomerular content of GLEPP1 was not different from normal. We conclude that GLEPP1 expression, unlike podocalyxin, reflects podocyte injury induced by PAN. GLEPP1 expression may be a useful marker of podocyte injury.", "entity": "Kidney Diseases", "aliases": "Disease Kidney Diseases", "definition": "Pathological processes of the KIDNEY or its component tissues.\n    ", "id": "MESH:D007674"}
{"mention": "Puromycin aminonucleoside", "mention_text": "Glomerular epithelial protein 1 (GLEPP1) is a podocyte receptor membrane protein tyrosine phosphatase located on the apical cell membrane of visceral glomerular epithelial cell and foot processes. This receptor plays a role in regulating the structure and function of podocyte foot process. To better understand the utility of GLEPP1 as a marker of glomerular injury, the amount and distribution of GLEPP1 protein and mRNA were examined by immunohistochemistry, Western blot and RNase protection assay in a model of podocyte injury in the rat. Puromycin aminonucleoside nephrosis was induced by single intraperitoneal injection of puromycin aminonucleoside (PAN, 20 mg/100g BW). Tissues were analyzed at 0, 5, 7, 11, 21, 45, 80 and 126 days after PAN injection so as to include both the acute phase of proteinuria associated with foot process effacement (days 5-11) and the chronic phase of proteinuria associated with glomerulosclerosis (days 45-126). At day 5, GLEPP1 protein and mRNA were reduced from the normal range (265.2 +/- 79.6 x 10(6) moles/glomerulus and 100%) to 15% of normal (41.8 +/- 4.8 x 10(6) moles/glomerulus, p < 0.005). This occurred in association with an increase in urinary protein content from 1.8 +/- 1 to 99.0 +/- 61 mg/day (p < 0.001). In contrast, podocalyxin did not change significantly at this time. By day 11, GLEPP1 protein and mRNA had begun to return towards baseline. By day 45-126, at a time when glomerular scarring was present, GLEPP1 was absent from glomerulosclerotic areas although the total glomerular content of GLEPP1 was not different from normal. We conclude that GLEPP1 expression, unlike podocalyxin, reflects podocyte injury induced by PAN. GLEPP1 expression may be a useful marker of podocyte injury.", "entity": "Puromycin Aminonucleoside", "aliases": "3' Amino 3' deoxy N,N dimethyladenosine 3'-Amino-3'-deoxy-N,N-dimethyladenosine Aminonucleoside Puromycin", "definition": "PUROMYCIN derivative that lacks the methoxyphenylalanyl group on the amine of the sugar ring. It is an antibiotic with antineoplastic properties and can cause nephrosis.\n    ", "id": "MESH:D011692"}
{"mention": "nephrosis", "mention_text": "Glomerular epithelial protein 1 (GLEPP1) is a podocyte receptor membrane protein tyrosine phosphatase located on the apical cell membrane of visceral glomerular epithelial cell and foot processes. This receptor plays a role in regulating the structure and function of podocyte foot process. To better understand the utility of GLEPP1 as a marker of glomerular injury, the amount and distribution of GLEPP1 protein and mRNA were examined by immunohistochemistry, Western blot and RNase protection assay in a model of podocyte injury in the rat. Puromycin aminonucleoside nephrosis was induced by single intraperitoneal injection of puromycin aminonucleoside (PAN, 20 mg/100g BW). Tissues were analyzed at 0, 5, 7, 11, 21, 45, 80 and 126 days after PAN injection so as to include both the acute phase of proteinuria associated with foot process effacement (days 5-11) and the chronic phase of proteinuria associated with glomerulosclerosis (days 45-126). At day 5, GLEPP1 protein and mRNA were reduced from the normal range (265.2 +/- 79.6 x 10(6) moles/glomerulus and 100%) to 15% of normal (41.8 +/- 4.8 x 10(6) moles/glomerulus, p < 0.005). This occurred in association with an increase in urinary protein content from 1.8 +/- 1 to 99.0 +/- 61 mg/day (p < 0.001). In contrast, podocalyxin did not change significantly at this time. By day 11, GLEPP1 protein and mRNA had begun to return towards baseline. By day 45-126, at a time when glomerular scarring was present, GLEPP1 was absent from glomerulosclerotic areas although the total glomerular content of GLEPP1 was not different from normal. We conclude that GLEPP1 expression, unlike podocalyxin, reflects podocyte injury induced by PAN. GLEPP1 expression may be a useful marker of podocyte injury.", "entity": "Nephrosis", "aliases": "Nephroses Nephrosis", "definition": "Pathological processes of the KIDNEY without inflammatory or neoplastic components. Nephrosis may be a primary disorder or secondary complication of other diseases. It is characterized by the NEPHROTIC SYNDROME indicating the presence of PROTEINURIA and HYPOALBUMINEMIA with accompanying EDEMA.\n    ", "id": "MESH:D009401"}
{"mention": "puromycin aminonucleoside", "mention_text": "Glomerular epithelial protein 1 (GLEPP1) is a podocyte receptor membrane protein tyrosine phosphatase located on the apical cell membrane of visceral glomerular epithelial cell and foot processes. This receptor plays a role in regulating the structure and function of podocyte foot process. To better understand the utility of GLEPP1 as a marker of glomerular injury, the amount and distribution of GLEPP1 protein and mRNA were examined by immunohistochemistry, Western blot and RNase protection assay in a model of podocyte injury in the rat. Puromycin aminonucleoside nephrosis was induced by single intraperitoneal injection of puromycin aminonucleoside (PAN, 20 mg/100g BW). Tissues were analyzed at 0, 5, 7, 11, 21, 45, 80 and 126 days after PAN injection so as to include both the acute phase of proteinuria associated with foot process effacement (days 5-11) and the chronic phase of proteinuria associated with glomerulosclerosis (days 45-126). At day 5, GLEPP1 protein and mRNA were reduced from the normal range (265.2 +/- 79.6 x 10(6) moles/glomerulus and 100%) to 15% of normal (41.8 +/- 4.8 x 10(6) moles/glomerulus, p < 0.005). This occurred in association with an increase in urinary protein content from 1.8 +/- 1 to 99.0 +/- 61 mg/day (p < 0.001). In contrast, podocalyxin did not change significantly at this time. By day 11, GLEPP1 protein and mRNA had begun to return towards baseline. By day 45-126, at a time when glomerular scarring was present, GLEPP1 was absent from glomerulosclerotic areas although the total glomerular content of GLEPP1 was not different from normal. We conclude that GLEPP1 expression, unlike podocalyxin, reflects podocyte injury induced by PAN. GLEPP1 expression may be a useful marker of podocyte injury.", "entity": "Puromycin Aminonucleoside", "aliases": "3' Amino 3' deoxy N,N dimethyladenosine 3'-Amino-3'-deoxy-N,N-dimethyladenosine Aminonucleoside Puromycin", "definition": "PUROMYCIN derivative that lacks the methoxyphenylalanyl group on the amine of the sugar ring. It is an antibiotic with antineoplastic properties and can cause nephrosis.\n    ", "id": "MESH:D011692"}
{"mention": "PAN", "mention_text": "Glomerular epithelial protein 1 (GLEPP1) is a podocyte receptor membrane protein tyrosine phosphatase located on the apical cell membrane of visceral glomerular epithelial cell and foot processes. This receptor plays a role in regulating the structure and function of podocyte foot process. To better understand the utility of GLEPP1 as a marker of glomerular injury, the amount and distribution of GLEPP1 protein and mRNA were examined by immunohistochemistry, Western blot and RNase protection assay in a model of podocyte injury in the rat. Puromycin aminonucleoside nephrosis was induced by single intraperitoneal injection of puromycin aminonucleoside (PAN, 20 mg/100g BW). Tissues were analyzed at 0, 5, 7, 11, 21, 45, 80 and 126 days after PAN injection so as to include both the acute phase of proteinuria associated with foot process effacement (days 5-11) and the chronic phase of proteinuria associated with glomerulosclerosis (days 45-126). At day 5, GLEPP1 protein and mRNA were reduced from the normal range (265.2 +/- 79.6 x 10(6) moles/glomerulus and 100%) to 15% of normal (41.8 +/- 4.8 x 10(6) moles/glomerulus, p < 0.005). This occurred in association with an increase in urinary protein content from 1.8 +/- 1 to 99.0 +/- 61 mg/day (p < 0.001). In contrast, podocalyxin did not change significantly at this time. By day 11, GLEPP1 protein and mRNA had begun to return towards baseline. By day 45-126, at a time when glomerular scarring was present, GLEPP1 was absent from glomerulosclerotic areas although the total glomerular content of GLEPP1 was not different from normal. We conclude that GLEPP1 expression, unlike podocalyxin, reflects podocyte injury induced by PAN. GLEPP1 expression may be a useful marker of podocyte injury.", "entity": "Puromycin Aminonucleoside", "aliases": "3' Amino 3' deoxy N,N dimethyladenosine 3'-Amino-3'-deoxy-N,N-dimethyladenosine Aminonucleoside Puromycin", "definition": "PUROMYCIN derivative that lacks the methoxyphenylalanyl group on the amine of the sugar ring. It is an antibiotic with antineoplastic properties and can cause nephrosis.\n    ", "id": "MESH:D011692"}
{"mention": "proteinuria", "mention_text": "Glomerular epithelial protein 1 (GLEPP1) is a podocyte receptor membrane protein tyrosine phosphatase located on the apical cell membrane of visceral glomerular epithelial cell and foot processes. This receptor plays a role in regulating the structure and function of podocyte foot process. To better understand the utility of GLEPP1 as a marker of glomerular injury, the amount and distribution of GLEPP1 protein and mRNA were examined by immunohistochemistry, Western blot and RNase protection assay in a model of podocyte injury in the rat. Puromycin aminonucleoside nephrosis was induced by single intraperitoneal injection of puromycin aminonucleoside (PAN, 20 mg/100g BW). Tissues were analyzed at 0, 5, 7, 11, 21, 45, 80 and 126 days after PAN injection so as to include both the acute phase of proteinuria associated with foot process effacement (days 5-11) and the chronic phase of proteinuria associated with glomerulosclerosis (days 45-126). At day 5, GLEPP1 protein and mRNA were reduced from the normal range (265.2 +/- 79.6 x 10(6) moles/glomerulus and 100%) to 15% of normal (41.8 +/- 4.8 x 10(6) moles/glomerulus, p < 0.005). This occurred in association with an increase in urinary protein content from 1.8 +/- 1 to 99.0 +/- 61 mg/day (p < 0.001). In contrast, podocalyxin did not change significantly at this time. By day 11, GLEPP1 protein and mRNA had begun to return towards baseline. By day 45-126, at a time when glomerular scarring was present, GLEPP1 was absent from glomerulosclerotic areas although the total glomerular content of GLEPP1 was not different from normal. We conclude that GLEPP1 expression, unlike podocalyxin, reflects podocyte injury induced by PAN. GLEPP1 expression may be a useful marker of podocyte injury.", "entity": "Proteinuria", "aliases": "Proteinuria Proteinurias", "definition": "The presence of proteins in the urine, an indicator of KIDNEY DISEASES.\n    ", "id": "MESH:D011507"}
{"mention": "glomerulosclerosis", "mention_text": "Glomerular epithelial protein 1 (GLEPP1) is a podocyte receptor membrane protein tyrosine phosphatase located on the apical cell membrane of visceral glomerular epithelial cell and foot processes. This receptor plays a role in regulating the structure and function of podocyte foot process. To better understand the utility of GLEPP1 as a marker of glomerular injury, the amount and distribution of GLEPP1 protein and mRNA were examined by immunohistochemistry, Western blot and RNase protection assay in a model of podocyte injury in the rat. Puromycin aminonucleoside nephrosis was induced by single intraperitoneal injection of puromycin aminonucleoside (PAN, 20 mg/100g BW). Tissues were analyzed at 0, 5, 7, 11, 21, 45, 80 and 126 days after PAN injection so as to include both the acute phase of proteinuria associated with foot process effacement (days 5-11) and the chronic phase of proteinuria associated with glomerulosclerosis (days 45-126). At day 5, GLEPP1 protein and mRNA were reduced from the normal range (265.2 +/- 79.6 x 10(6) moles/glomerulus and 100%) to 15% of normal (41.8 +/- 4.8 x 10(6) moles/glomerulus, p < 0.005). This occurred in association with an increase in urinary protein content from 1.8 +/- 1 to 99.0 +/- 61 mg/day (p < 0.001). In contrast, podocalyxin did not change significantly at this time. By day 11, GLEPP1 protein and mRNA had begun to return towards baseline. By day 45-126, at a time when glomerular scarring was present, GLEPP1 was absent from glomerulosclerotic areas although the total glomerular content of GLEPP1 was not different from normal. We conclude that GLEPP1 expression, unlike podocalyxin, reflects podocyte injury induced by PAN. GLEPP1 expression may be a useful marker of podocyte injury.", "entity": "Glomerulonephritis", "aliases": "Bright Disease Glomerulonephritides Glomerulonephritis", "definition": "Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.\n    ", "id": "MESH:D005921"}
{"mention": "Ticlopidine", "mention_text": "Ticlopidine-induced aplastic anemia: report of three Chinese patients and review of the literature.", "entity": "Ticlopidine", "aliases": "53 32C 53-32C 5332C Almirall Brand of Ticlopidine Hydrochloride Roche Ticlid Ticlodix Ticlodone Vitoria", "definition": "An effective inhibitor of platelet aggregation commonly used in the placement of STENTS in CORONARY ARTERIES.\n    ", "id": "MESH:D013988"}
{"mention": "aplastic anemia", "mention_text": "Ticlopidine-induced aplastic anemia: report of three Chinese patients and review of the literature.", "entity": "Anemia, Aplastic", "aliases": "Anemia Aplastic Hypoplastic Anemias", "definition": "A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements.\n    ", "id": "MESH:D000741"}
{"mention": "ticlopidine", "mention_text": "In this study, three Chinese patients with ticlopidine-induced aplastic anemia were reported and another 13 patients in the English literature were reviewed. We attempted to find underlying similarities, evaluate the risk factors, and identify appropriate treatment for this complication. All but one of the patients were over 60 years old, and the 6 who died were all older than 65. Therefore, old age may be a risk factor for developing this complication. Agranulocytosis occurred 3-20 weeks after initiation of ticlopidine, so frequent examination of white cell count during treatment is recommended. There seemed to be no direct correlation between the dose or duration used and the severity of bone marrow suppression. Treatment for ticlopidine-induced aplastic anemia with colony-stimulating factors seemed to have little effect. The fact that 5 of the 6 patients who received concurrent calcium channel blockers died, should alert clinicians to be more cautious when using these two drugs simultaneously.", "entity": "Ticlopidine", "aliases": "53 32C 53-32C 5332C Almirall Brand of Ticlopidine Hydrochloride Roche Ticlid Ticlodix Ticlodone Vitoria", "definition": "An effective inhibitor of platelet aggregation commonly used in the placement of STENTS in CORONARY ARTERIES.\n    ", "id": "MESH:D013988"}
{"mention": "aplastic anemia", "mention_text": "In this study, three Chinese patients with ticlopidine-induced aplastic anemia were reported and another 13 patients in the English literature were reviewed. We attempted to find underlying similarities, evaluate the risk factors, and identify appropriate treatment for this complication. All but one of the patients were over 60 years old, and the 6 who died were all older than 65. Therefore, old age may be a risk factor for developing this complication. Agranulocytosis occurred 3-20 weeks after initiation of ticlopidine, so frequent examination of white cell count during treatment is recommended. There seemed to be no direct correlation between the dose or duration used and the severity of bone marrow suppression. Treatment for ticlopidine-induced aplastic anemia with colony-stimulating factors seemed to have little effect. The fact that 5 of the 6 patients who received concurrent calcium channel blockers died, should alert clinicians to be more cautious when using these two drugs simultaneously.", "entity": "Anemia, Aplastic", "aliases": "Anemia Aplastic Hypoplastic Anemias", "definition": "A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements.\n    ", "id": "MESH:D000741"}
{"mention": "Agranulocytosis", "mention_text": "In this study, three Chinese patients with ticlopidine-induced aplastic anemia were reported and another 13 patients in the English literature were reviewed. We attempted to find underlying similarities, evaluate the risk factors, and identify appropriate treatment for this complication. All but one of the patients were over 60 years old, and the 6 who died were all older than 65. Therefore, old age may be a risk factor for developing this complication. Agranulocytosis occurred 3-20 weeks after initiation of ticlopidine, so frequent examination of white cell count during treatment is recommended. There seemed to be no direct correlation between the dose or duration used and the severity of bone marrow suppression. Treatment for ticlopidine-induced aplastic anemia with colony-stimulating factors seemed to have little effect. The fact that 5 of the 6 patients who received concurrent calcium channel blockers died, should alert clinicians to be more cautious when using these two drugs simultaneously.", "entity": "Agranulocytosis", "aliases": "Agranulocytoses Agranulocytosis Granulocytopenia Granulocytopenias", "definition": "A decrease in the number of GRANULOCYTES; (BASOPHILS; EOSINOPHILS; and NEUTROPHILS).\n    ", "id": "MESH:D000380"}
{"mention": "bone marrow suppression", "mention_text": "In this study, three Chinese patients with ticlopidine-induced aplastic anemia were reported and another 13 patients in the English literature were reviewed. We attempted to find underlying similarities, evaluate the risk factors, and identify appropriate treatment for this complication. All but one of the patients were over 60 years old, and the 6 who died were all older than 65. Therefore, old age may be a risk factor for developing this complication. Agranulocytosis occurred 3-20 weeks after initiation of ticlopidine, so frequent examination of white cell count during treatment is recommended. There seemed to be no direct correlation between the dose or duration used and the severity of bone marrow suppression. Treatment for ticlopidine-induced aplastic anemia with colony-stimulating factors seemed to have little effect. The fact that 5 of the 6 patients who received concurrent calcium channel blockers died, should alert clinicians to be more cautious when using these two drugs simultaneously.", "entity": "Bone Marrow Diseases", "aliases": "Bone Marrow Disease Diseases", "definition": "", "id": "MESH:D001855"}
{"mention": "calcium", "mention_text": "In this study, three Chinese patients with ticlopidine-induced aplastic anemia were reported and another 13 patients in the English literature were reviewed. We attempted to find underlying similarities, evaluate the risk factors, and identify appropriate treatment for this complication. All but one of the patients were over 60 years old, and the 6 who died were all older than 65. Therefore, old age may be a risk factor for developing this complication. Agranulocytosis occurred 3-20 weeks after initiation of ticlopidine, so frequent examination of white cell count during treatment is recommended. There seemed to be no direct correlation between the dose or duration used and the severity of bone marrow suppression. Treatment for ticlopidine-induced aplastic anemia with colony-stimulating factors seemed to have little effect. The fact that 5 of the 6 patients who received concurrent calcium channel blockers died, should alert clinicians to be more cautious when using these two drugs simultaneously.", "entity": "Calcium", "aliases": "Blood Coagulation Factor IV Calcium", "definition": "A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.\n    ", "id": "MESH:D002118"}
{"mention": "morphine", "mention_text": "Facilitation of memory retrieval by pre-test morphine and its state dependency in the step-through type passive avoidance learning test in mice.", "entity": "Morphine", "aliases": "Chloride Morphine Contin MS Duramorph Morphia Sulfate (2:1) Anhydrous Pentahydrate Oramorph SR SDZ 202 250 202-250 202250 SDZ202 SDZ202-250 SDZ202250", "definition": "The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.\n    ", "id": "MESH:D009020"}
{"mention": "Amnesia", "mention_text": "Amnesia produced by scopolamine and cycloheximide were reversed by morphine given 30 min before the test trial (pre-test), and pre-test morphine also facilitated the memory retrieval in the animals administered naloxone during the training trial. Similarly, pre-test scopolamine partially reversed the scopolamine-induced amnesia, but not significantly; and pre-test cycloheximide failed to reverse the cycloheximide-induced amnesia. These results suggest that the facilitation of memory retrieval by pre-test morphine might be the direct action of morphine rather than a state dependent effect.", "entity": "Amnesia", "aliases": "Amnesia Memory Loss Dissociative Global Hysterical Tactile Temporary Amnesia-Memory Losses Amnesias Amnestic State States", "definition": "Pathologic partial or complete loss of the ability to recall past experiences (AMNESIA, RETROGRADE) or to form new memories (AMNESIA, ANTEROGRADE). This condition may be of organic or psychologic origin. Organic forms of amnesia are usually associated with dysfunction of the DIENCEPHALON or HIPPOCAMPUS. (From Adams et al., Principles of Neurology, 6th ed, pp426-7)\n    ", "id": "MESH:D000647"}
{"mention": "scopolamine", "mention_text": "Amnesia produced by scopolamine and cycloheximide were reversed by morphine given 30 min before the test trial (pre-test), and pre-test morphine also facilitated the memory retrieval in the animals administered naloxone during the training trial. Similarly, pre-test scopolamine partially reversed the scopolamine-induced amnesia, but not significantly; and pre-test cycloheximide failed to reverse the cycloheximide-induced amnesia. These results suggest that the facilitation of memory retrieval by pre-test morphine might be the direct action of morphine rather than a state dependent effect.", "entity": "Scopolamine Hydrobromide", "aliases": "Alcon Brand of Scopolamine Hydrobromide Boro Scopol Boro-Scopol BoroScopol Bull Cooper Hamilton Hope Hyoscine Inibisa Isopto Kwells Novartis Consumer Health Renaudin Roche Scoburen Scopace Scopoderm TTS Transderm Scop V Transderm-V Travacalm HO Vorigeno Winzer Borate", "definition": "An alkaloid from SOLANACEAE, especially DATURA and SCOPOLIA. Scopolamine and its quaternary derivatives act as antimuscarinics like ATROPINE, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in URINARY INCONTINENCE, in MOTION SICKNESS, as an antispasmodic, and as a mydriatic and cycloplegic.\n    ", "id": "MESH:D012601"}
{"mention": "cycloheximide", "mention_text": "Amnesia produced by scopolamine and cycloheximide were reversed by morphine given 30 min before the test trial (pre-test), and pre-test morphine also facilitated the memory retrieval in the animals administered naloxone during the training trial. Similarly, pre-test scopolamine partially reversed the scopolamine-induced amnesia, but not significantly; and pre-test cycloheximide failed to reverse the cycloheximide-induced amnesia. These results suggest that the facilitation of memory retrieval by pre-test morphine might be the direct action of morphine rather than a state dependent effect.", "entity": "Cycloheximide", "aliases": "Actidione Cicloheximide Cycloheximide", "definition": "Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.\n    ", "id": "MESH:D003513"}
{"mention": "morphine", "mention_text": "Amnesia produced by scopolamine and cycloheximide were reversed by morphine given 30 min before the test trial (pre-test), and pre-test morphine also facilitated the memory retrieval in the animals administered naloxone during the training trial. Similarly, pre-test scopolamine partially reversed the scopolamine-induced amnesia, but not significantly; and pre-test cycloheximide failed to reverse the cycloheximide-induced amnesia. These results suggest that the facilitation of memory retrieval by pre-test morphine might be the direct action of morphine rather than a state dependent effect.", "entity": "Morphine", "aliases": "Chloride Morphine Contin MS Duramorph Morphia Sulfate (2:1) Anhydrous Pentahydrate Oramorph SR SDZ 202 250 202-250 202250 SDZ202 SDZ202-250 SDZ202250", "definition": "The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.\n    ", "id": "MESH:D009020"}
{"mention": "naloxone", "mention_text": "Amnesia produced by scopolamine and cycloheximide were reversed by morphine given 30 min before the test trial (pre-test), and pre-test morphine also facilitated the memory retrieval in the animals administered naloxone during the training trial. Similarly, pre-test scopolamine partially reversed the scopolamine-induced amnesia, but not significantly; and pre-test cycloheximide failed to reverse the cycloheximide-induced amnesia. These results suggest that the facilitation of memory retrieval by pre-test morphine might be the direct action of morphine rather than a state dependent effect.", "entity": "Naloxone", "aliases": "Abello Brand of Naloxone Hydrochloride Boots Bristol Myers Squibb Bristol-Myers Curamed Naloxon Dihydride Endo Hydrobromide Lamepro MRZ 2593 Br 2593-Br 2593Br MRZ-2593 MRZ2593 Nalone ratiopharm Naloxon-ratiopharm (5 beta,9 alpha,13 alpha,14 alpha)-Isomer Naloxonratiopharm Narcan Narcanti SERB United Drug", "definition": "A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.\n    ", "id": "MESH:D009270"}
{"mention": "amnesia", "mention_text": "Amnesia produced by scopolamine and cycloheximide were reversed by morphine given 30 min before the test trial (pre-test), and pre-test morphine also facilitated the memory retrieval in the animals administered naloxone during the training trial. Similarly, pre-test scopolamine partially reversed the scopolamine-induced amnesia, but not significantly; and pre-test cycloheximide failed to reverse the cycloheximide-induced amnesia. These results suggest that the facilitation of memory retrieval by pre-test morphine might be the direct action of morphine rather than a state dependent effect.", "entity": "Amnesia", "aliases": "Amnesia Memory Loss Dissociative Global Hysterical Tactile Temporary Amnesia-Memory Losses Amnesias Amnestic State States", "definition": "Pathologic partial or complete loss of the ability to recall past experiences (AMNESIA, RETROGRADE) or to form new memories (AMNESIA, ANTEROGRADE). This condition may be of organic or psychologic origin. Organic forms of amnesia are usually associated with dysfunction of the DIENCEPHALON or HIPPOCAMPUS. (From Adams et al., Principles of Neurology, 6th ed, pp426-7)\n    ", "id": "MESH:D000647"}
{"mention": "Apomorphine", "mention_text": "These studies were conducted to examine the differential response to a drug challenge under varied experimental test conditions routinely employed to study drug-induced behavioral and neurophysiological responses in rodents. Apomorphine, a nonselective dopamine agonist, was selected due to its biphasic behavioral effects, its ability to induce hypothermia, and to produce distinct changes to dopamine turnover in the rodent brain. From such experiments there is evidence that characterization and detection of apomorphine-induced activity in rodents critically depends upon the test conditions employed. In rats, detection of apomorphine-induced hyperactivity was facilitated by a period of acclimatization to the test conditions. Moreover, test conditions can impact upon other physiological responses to apomorphine such as drug-induced hypothermia. In mice, apomorphine produced qualitatively different responses under novel conditions when compared to those behaviors elicited in the home test cage. Drug-induced gross activity counts were increased in the novel exploratory box only, while measures of stereotypic behavior were similar in both. By contrast, apomorphine-induced locomotion was more prominent in the novel exploratory box. Dopamine turnover ratios (DOPAC:DA and HVA:DA) were found to be lower in those animals exposed to the exploratory box when compared to their home cage counterparts. However, apomorphine-induced reductions in striatal dopamine turnover were detected in both novel and home cage environments. The implications of these findings are discussed with particular emphasis upon conducting psychopharmacological challenge tests in rodents.", "entity": "Apomorphine", "aliases": "Aguettant Brand of Apomorphine Hydrochloride Anhydrous Apokinon Apomorphin Teclapharm Apomorphin-Teclapharm ApomorphinTeclapharm Chloride Hemihydrate Britaject Britannia", "definition": "A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use.\n    ", "id": "MESH:D001058"}
{"mention": "dopamine agonist", "mention_text": "These studies were conducted to examine the differential response to a drug challenge under varied experimental test conditions routinely employed to study drug-induced behavioral and neurophysiological responses in rodents. Apomorphine, a nonselective dopamine agonist, was selected due to its biphasic behavioral effects, its ability to induce hypothermia, and to produce distinct changes to dopamine turnover in the rodent brain. From such experiments there is evidence that characterization and detection of apomorphine-induced activity in rodents critically depends upon the test conditions employed. In rats, detection of apomorphine-induced hyperactivity was facilitated by a period of acclimatization to the test conditions. Moreover, test conditions can impact upon other physiological responses to apomorphine such as drug-induced hypothermia. In mice, apomorphine produced qualitatively different responses under novel conditions when compared to those behaviors elicited in the home test cage. Drug-induced gross activity counts were increased in the novel exploratory box only, while measures of stereotypic behavior were similar in both. By contrast, apomorphine-induced locomotion was more prominent in the novel exploratory box. Dopamine turnover ratios (DOPAC:DA and HVA:DA) were found to be lower in those animals exposed to the exploratory box when compared to their home cage counterparts. However, apomorphine-induced reductions in striatal dopamine turnover were detected in both novel and home cage environments. The implications of these findings are discussed with particular emphasis upon conducting psychopharmacological challenge tests in rodents.", "entity": "Dopamine Agonists", "aliases": "Agonist Dopamine Receptor Dopaminergic Agonists", "definition": "Drugs that bind to and activate dopamine receptors.\n    ", "id": "MESH:D018491"}
{"mention": "hypothermia", "mention_text": "These studies were conducted to examine the differential response to a drug challenge under varied experimental test conditions routinely employed to study drug-induced behavioral and neurophysiological responses in rodents. Apomorphine, a nonselective dopamine agonist, was selected due to its biphasic behavioral effects, its ability to induce hypothermia, and to produce distinct changes to dopamine turnover in the rodent brain. From such experiments there is evidence that characterization and detection of apomorphine-induced activity in rodents critically depends upon the test conditions employed. In rats, detection of apomorphine-induced hyperactivity was facilitated by a period of acclimatization to the test conditions. Moreover, test conditions can impact upon other physiological responses to apomorphine such as drug-induced hypothermia. In mice, apomorphine produced qualitatively different responses under novel conditions when compared to those behaviors elicited in the home test cage. Drug-induced gross activity counts were increased in the novel exploratory box only, while measures of stereotypic behavior were similar in both. By contrast, apomorphine-induced locomotion was more prominent in the novel exploratory box. Dopamine turnover ratios (DOPAC:DA and HVA:DA) were found to be lower in those animals exposed to the exploratory box when compared to their home cage counterparts. However, apomorphine-induced reductions in striatal dopamine turnover were detected in both novel and home cage environments. The implications of these findings are discussed with particular emphasis upon conducting psychopharmacological challenge tests in rodents.", "entity": "Hypothermia", "aliases": "Accidental Hypothermia Hypothermias", "definition": "Lower than normal body temperature, especially in warm-blooded animals.\n    ", "id": "MESH:D007035"}
{"mention": "dopamine", "mention_text": "These studies were conducted to examine the differential response to a drug challenge under varied experimental test conditions routinely employed to study drug-induced behavioral and neurophysiological responses in rodents. Apomorphine, a nonselective dopamine agonist, was selected due to its biphasic behavioral effects, its ability to induce hypothermia, and to produce distinct changes to dopamine turnover in the rodent brain. From such experiments there is evidence that characterization and detection of apomorphine-induced activity in rodents critically depends upon the test conditions employed. In rats, detection of apomorphine-induced hyperactivity was facilitated by a period of acclimatization to the test conditions. Moreover, test conditions can impact upon other physiological responses to apomorphine such as drug-induced hypothermia. In mice, apomorphine produced qualitatively different responses under novel conditions when compared to those behaviors elicited in the home test cage. Drug-induced gross activity counts were increased in the novel exploratory box only, while measures of stereotypic behavior were similar in both. By contrast, apomorphine-induced locomotion was more prominent in the novel exploratory box. Dopamine turnover ratios (DOPAC:DA and HVA:DA) were found to be lower in those animals exposed to the exploratory box when compared to their home cage counterparts. However, apomorphine-induced reductions in striatal dopamine turnover were detected in both novel and home cage environments. The implications of these findings are discussed with particular emphasis upon conducting psychopharmacological challenge tests in rodents.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "apomorphine", "mention_text": "These studies were conducted to examine the differential response to a drug challenge under varied experimental test conditions routinely employed to study drug-induced behavioral and neurophysiological responses in rodents. Apomorphine, a nonselective dopamine agonist, was selected due to its biphasic behavioral effects, its ability to induce hypothermia, and to produce distinct changes to dopamine turnover in the rodent brain. From such experiments there is evidence that characterization and detection of apomorphine-induced activity in rodents critically depends upon the test conditions employed. In rats, detection of apomorphine-induced hyperactivity was facilitated by a period of acclimatization to the test conditions. Moreover, test conditions can impact upon other physiological responses to apomorphine such as drug-induced hypothermia. In mice, apomorphine produced qualitatively different responses under novel conditions when compared to those behaviors elicited in the home test cage. Drug-induced gross activity counts were increased in the novel exploratory box only, while measures of stereotypic behavior were similar in both. By contrast, apomorphine-induced locomotion was more prominent in the novel exploratory box. Dopamine turnover ratios (DOPAC:DA and HVA:DA) were found to be lower in those animals exposed to the exploratory box when compared to their home cage counterparts. However, apomorphine-induced reductions in striatal dopamine turnover were detected in both novel and home cage environments. The implications of these findings are discussed with particular emphasis upon conducting psychopharmacological challenge tests in rodents.", "entity": "Apomorphine", "aliases": "Aguettant Brand of Apomorphine Hydrochloride Anhydrous Apokinon Apomorphin Teclapharm Apomorphin-Teclapharm ApomorphinTeclapharm Chloride Hemihydrate Britaject Britannia", "definition": "A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use.\n    ", "id": "MESH:D001058"}
{"mention": "hyperactivity", "mention_text": "These studies were conducted to examine the differential response to a drug challenge under varied experimental test conditions routinely employed to study drug-induced behavioral and neurophysiological responses in rodents. Apomorphine, a nonselective dopamine agonist, was selected due to its biphasic behavioral effects, its ability to induce hypothermia, and to produce distinct changes to dopamine turnover in the rodent brain. From such experiments there is evidence that characterization and detection of apomorphine-induced activity in rodents critically depends upon the test conditions employed. In rats, detection of apomorphine-induced hyperactivity was facilitated by a period of acclimatization to the test conditions. Moreover, test conditions can impact upon other physiological responses to apomorphine such as drug-induced hypothermia. In mice, apomorphine produced qualitatively different responses under novel conditions when compared to those behaviors elicited in the home test cage. Drug-induced gross activity counts were increased in the novel exploratory box only, while measures of stereotypic behavior were similar in both. By contrast, apomorphine-induced locomotion was more prominent in the novel exploratory box. Dopamine turnover ratios (DOPAC:DA and HVA:DA) were found to be lower in those animals exposed to the exploratory box when compared to their home cage counterparts. However, apomorphine-induced reductions in striatal dopamine turnover were detected in both novel and home cage environments. The implications of these findings are discussed with particular emphasis upon conducting psychopharmacological challenge tests in rodents.", "entity": "Hyperkinesis", "aliases": "Generalized Hyperkinesia Hyperkinesias Hyperactivity Motor Hyperkinesis Hyperkinetic Movement Movements", "definition": "Excessive movement of muscles of the body as a whole, which may be associated with organic or psychological disorders.\n    ", "id": "MESH:D006948"}
{"mention": "Dopamine", "mention_text": "These studies were conducted to examine the differential response to a drug challenge under varied experimental test conditions routinely employed to study drug-induced behavioral and neurophysiological responses in rodents. Apomorphine, a nonselective dopamine agonist, was selected due to its biphasic behavioral effects, its ability to induce hypothermia, and to produce distinct changes to dopamine turnover in the rodent brain. From such experiments there is evidence that characterization and detection of apomorphine-induced activity in rodents critically depends upon the test conditions employed. In rats, detection of apomorphine-induced hyperactivity was facilitated by a period of acclimatization to the test conditions. Moreover, test conditions can impact upon other physiological responses to apomorphine such as drug-induced hypothermia. In mice, apomorphine produced qualitatively different responses under novel conditions when compared to those behaviors elicited in the home test cage. Drug-induced gross activity counts were increased in the novel exploratory box only, while measures of stereotypic behavior were similar in both. By contrast, apomorphine-induced locomotion was more prominent in the novel exploratory box. Dopamine turnover ratios (DOPAC:DA and HVA:DA) were found to be lower in those animals exposed to the exploratory box when compared to their home cage counterparts. However, apomorphine-induced reductions in striatal dopamine turnover were detected in both novel and home cage environments. The implications of these findings are discussed with particular emphasis upon conducting psychopharmacological challenge tests in rodents.", "entity": "Dopamine", "aliases": "3,4 Dihydroxyphenethylamine 3,4-Dihydroxyphenethylamine 4-(2-Aminoethyl)-1,2-benzenediol Dopamine Hydrochloride Hydroxytyramine Intropin", "definition": "One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.\n    ", "id": "MESH:D004298"}
{"mention": "DOPAC", "mention_text": "These studies were conducted to examine the differential response to a drug challenge under varied experimental test conditions routinely employed to study drug-induced behavioral and neurophysiological responses in rodents. Apomorphine, a nonselective dopamine agonist, was selected due to its biphasic behavioral effects, its ability to induce hypothermia, and to produce distinct changes to dopamine turnover in the rodent brain. From such experiments there is evidence that characterization and detection of apomorphine-induced activity in rodents critically depends upon the test conditions employed. In rats, detection of apomorphine-induced hyperactivity was facilitated by a period of acclimatization to the test conditions. Moreover, test conditions can impact upon other physiological responses to apomorphine such as drug-induced hypothermia. In mice, apomorphine produced qualitatively different responses under novel conditions when compared to those behaviors elicited in the home test cage. Drug-induced gross activity counts were increased in the novel exploratory box only, while measures of stereotypic behavior were similar in both. By contrast, apomorphine-induced locomotion was more prominent in the novel exploratory box. Dopamine turnover ratios (DOPAC:DA and HVA:DA) were found to be lower in those animals exposed to the exploratory box when compared to their home cage counterparts. However, apomorphine-induced reductions in striatal dopamine turnover were detected in both novel and home cage environments. The implications of these findings are discussed with particular emphasis upon conducting psychopharmacological challenge tests in rodents.", "entity": "3,4-Dihydroxyphenylacetic Acid", "aliases": "3,4 Dihydroxyphenylacetic Acid 3,4-Dihydroxyphenylacetic Monosodium Salt DOPAC Homoprotocatechuic", "definition": "A deaminated metabolite of LEVODOPA.\n    ", "id": "MESH:D015102"}
{"mention": "DA", "mention_text": "These studies were conducted to examine the differential response to a drug challenge under varied experimental test conditions routinely employed to study drug-induced behavioral and neurophysiological responses in rodents. Apomorphine, a nonselective dopamine agonist, was selected due to its biphasic behavioral effects, its ability to induce hypothermia, and to produce distinct changes to dopamine turnover in the rodent brain. From such experiments there is evidence that characterization and detection of apomorphine-induced activity in rodents critically depends upon the test conditions employed. In rats, detection of apomorphine-induced hyperactivity was facilitated by a period of acclimatization to the test conditions. Moreover, test conditions can impact upon other physiological responses to apomorphine such as drug-induced hypothermia. In mice, apomorphine produced qualitatively different responses under novel conditions when compared to those behaviors elicited in the home test cage. Drug-induced gross activity counts were increased in the novel exploratory box only, while measures of stereotypic behavior were similar in both. By contrast, apomorphine-induced locomotion was more prominent in the novel exploratory box. Dopamine turnover ratios (DOPAC:DA and HVA:DA) were found to be lower in those animals exposed to the exploratory box when compared to their home cage counterparts. However, apomorphine-induced reductions in striatal dopamine turnover were detected in both novel and home cage environments. The implications of these findings are discussed with particular emphasis upon conducting psychopharmacological challenge tests in rodents.", "entity": "Dopamine Agonists", "aliases": "Agonist Dopamine Receptor Dopaminergic Agonists", "definition": "Drugs that bind to and activate dopamine receptors.\n    ", "id": "MESH:D018491"}
{"mention": "HVA", "mention_text": "These studies were conducted to examine the differential response to a drug challenge under varied experimental test conditions routinely employed to study drug-induced behavioral and neurophysiological responses in rodents. Apomorphine, a nonselective dopamine agonist, was selected due to its biphasic behavioral effects, its ability to induce hypothermia, and to produce distinct changes to dopamine turnover in the rodent brain. From such experiments there is evidence that characterization and detection of apomorphine-induced activity in rodents critically depends upon the test conditions employed. In rats, detection of apomorphine-induced hyperactivity was facilitated by a period of acclimatization to the test conditions. Moreover, test conditions can impact upon other physiological responses to apomorphine such as drug-induced hypothermia. In mice, apomorphine produced qualitatively different responses under novel conditions when compared to those behaviors elicited in the home test cage. Drug-induced gross activity counts were increased in the novel exploratory box only, while measures of stereotypic behavior were similar in both. By contrast, apomorphine-induced locomotion was more prominent in the novel exploratory box. Dopamine turnover ratios (DOPAC:DA and HVA:DA) were found to be lower in those animals exposed to the exploratory box when compared to their home cage counterparts. However, apomorphine-induced reductions in striatal dopamine turnover were detected in both novel and home cage environments. The implications of these findings are discussed with particular emphasis upon conducting psychopharmacological challenge tests in rodents.", "entity": "Homovanillic Acid", "aliases": "3 Methoxy 4 Hydroxyphenylacetic Acid 3-Methoxy-4-Hydroxyphenylacetic Hydroxy Methoxyphenylacetic 4-Hydroxy-3-Methoxyphenylacetic Homovanillic", "definition": "", "id": "MESH:D006719"}